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Antibiotic prophylaxis for cirrhotic patients with upper
gastrointestinal bleeding (Review)
Chavez-Tapia NC, Barrientos-Gutierrez T, Tellez-Avila FI, Soares-Weiser K, Uribe M
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2010, Issue 9
http://www.thecochranelibrary.com
Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
T A B L E O F C O N T E N T S
1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Figure 4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Figure 5. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
13DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
14AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
14ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
15REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
18CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
38DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 1 Mortality. . . . . . . . . 39
Analysis 1.2. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 2 Mortality from bacterial infections. 40
Analysis 1.3. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 3 Bacterial infections. . . . . . 41
Analysis 1.4. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 4 Bacteremia. . . . . . . . 42
Analysis 1.5. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 5 Pneumonia. . . . . . . . 43
Analysis 1.6. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 6 Spontaneous bacterial peritonitis. 44
Analysis 1.7. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 7 Urinary tract infections. . . . 45
Analysis 1.8. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 8 Other infections. . . . . . . 46
Analysis 1.9. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 9 Drop outs before end of study. . 47
Analysis 1.10. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 10 Mortality according to trial sample
size. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
Analysis 1.11. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 11 Bacterial infections according to trial
sample size. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Analysis 1.12. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 12 Mortality sensitivity analysis worst-
best case. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
Analysis 1.13. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 13 Mortality sensitivity analysis best-
worst case. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Analysis 1.14. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 14 Mortality from bacterial infections
sensitivity analysis worst-best case. . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Analysis 1.15. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 15 Mortality from bacterial infections
sensitivity analysis best-worst case. . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
Analysis 1.16. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 16 Bacterial infections sensitivity
analysis worst-best case. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
Analysis 1.17. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 17 Bacterial infections sensitivity
analysis best-worst case. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Analysis 1.18. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 18 Mortality according to the antibiotic
used. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Analysis 1.19. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 19 Mortality from bacterial infections
according to the antibiotic used. . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Analysis 1.20. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 20 Bacterial infections according to the
antibiotic used. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
Analysis 1.21. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 21 Rebleeding. . . . . . . 60
Analysis 1.22. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 22 Early rebleeding (up to 7 days). 61
iAntibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.23. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 23 Days of hospitalisation. . . 62
62ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
64APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
66WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
66HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
66CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
66DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
67SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
67DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .
67INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
iiAntibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Review]
Antibiotic prophylaxis for cirrhotic patients with uppergastrointestinal bleeding
Norberto C Chavez-Tapia1, Tonatiuh Barrientos-Gutierrez2 , Felix I Tellez-Avila3, Karla Soares-Weiser4, Misael Uribe3
1Medica Sur Clinic & Foundation, Mexico City, Mexico. 2Tobacco Research Department, National Institute of Public Health, Mexico
City, Mexico. 3Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City,
Mexico. 4Enhance Reviews Ltd, London, UK
Contact address: Norberto C Chavez-Tapia, Medica Sur Clinic & Foundation, Puente de Piedra 150, Mexico City, 14050, Mexico.
Editorial group: Cochrane Hepato-Biliary Group.
Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 9, 2010.
Review content assessed as up-to-date: 29 June 2010.
Citation: Chavez-Tapia NC, Barrientos-Gutierrez T, Tellez-Avila FI, Soares-Weiser K, Uribe M. Antibiotic prophylaxis for cirrhotic
patients with upper gastrointestinal bleeding. Cochrane Database of Systematic Reviews 2010, Issue 9. Art. No.: CD002907. DOI:
10.1002/14651858.CD002907.pub2.
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
A B S T R A C T
Background
Bacterial infections are a frequent complication in patients with cirrhosis and upper gastrointestinal bleeding. Antibiotic prophylaxis
seems to decrease the incidence of bacterial infections. Oral antibiotics, active against enteric bacteria, have been commonly used
as antibiotic prophylaxis in patients with cirrhosis and upper gastrointestinal bleeding. This is an update of a Cochrane review first
published in 2002.
Objectives
To assess the benefits and harms of antibiotic prophylaxis in cirrhotic patients with upper gastrointestinal bleeding.
Search methods
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL)
in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index EXPANDED until June 2010. In addition, we handsearched
the references of all identified studies.
Selection criteria
Randomised clinical trials comparing different types of antibiotic prophylaxis with no intervention, placebo, or another antibiotic to
prevent bacterial infections in cirrhotic patients with upper gastrointestinal bleeding.
Data collection and analysis
Three authors independently assessed trial quality, risk of bias, and extracted data. We contacted study authors for additional information.
Association measures were relative risk (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes.
1Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Main results
Twelve trials (1241 patients) evaluated antibiotic prophylaxis compared with placebo or no antibiotic prophylaxis. All trials were at risk
of bias. Antibiotic prophylaxis compared with no intervention or placebo was associated with beneficial effects on mortality (RR 0.79,
95% CI 0.63 to 0.98), mortality from bacterial infections (RR 0.43, 95% CI 0.19 to 0.97), bacterial infections (RR 0.36, 95% CI
0.27 to 0.49), rebleeding (RR 0.53, 95% CI 0.38 to 0.74), days of hospitalisation (MD -1.91, 95% CI -3.80 to -0.02), bacteraemia
(RR 0.25, 95% CI 0.15 to 0.40), pneumonia (RR 0.45, 95% CI 0.27 to 0.75), spontaneous bacterial peritonitis (RR 0.29, 95% CI
0.15 to 0.57), and urinary tract infections (RR 0.23, 95% CI 0.12 to 0.41). No serious adverse events were reported. The trials showed
no significant heterogeneity of effects. Another five trials (650 patients) compared different antibiotic regimens. Data could not be
combined as each trial used different antibiotic regimen. None of the examined antibiotic regimen was superior to the control regimen
regarding mortality or bacterial infections.
Authors’ conclusions
Prophylactic antibiotic use in patients with cirrhosis and upper gastrointestinal bleeding significantly reduced bacterial infections, and
seems to have reduced all-cause mortality, bacterial infection mortality, rebleeding events, and hospitalisation length. These benefits
were observed independently of the type of antibiotic used; thus, no specific antibiotic can be preferred. Therefore, antibiotic selection
should be made considering local conditions such as bacterial resistance profile and treatment cost.
P L A I N L A N G U A G E S U M M A R Y
Antibiotic prophylaxis for prevention of bacterial infections and death in cirrhotic patients with upper gastrointestinal bleeding
Patients with liver cirrhosis have an impaired immune response. Often, liver cirrhosis patients experience complications from portal
hypertension, such as gastroesophageal varices. These varices can bleed, increasing the risk of infection and death in a short period
of time, despite proper endoscopic management. Patients who develop bacterial infections during hospitalisation for gastroesophageal
haemorrhage are at increased risk of dying. Twelve trials (1241 patients) assessing several antibiotic prophylaxis regimens versus no
intervention or placebo were analysed, showing that antibiotic prophylaxis successfully reduced the incidence of bacterial infections.
Antibiotic prophylaxis was also associated with a reduction in mortality, mortality from bacterial infections, rebleeding rate, and days
of hospitalisation. The prophylactic treatment was not associated with important adverse effects. Five trials (650 patients) assessed one
antibiotic regimen compared with another. All antibiotic regimens provided similar benefits and none seemed superior. Thus, to this
point there is no evidence to recommend one specific antibiotic regimen over the other. All trials analysed were subject to bias; thus,
results should be interpreted carefully.
B A C K G R O U N D
Description of the condition
Chronic liver diseases are characterised by important changes on
hepatic physiology with portal hypertension being their haemo-
dynamic expression. The presence of clinically significant portal
hypertension (portal pressure gradient ≥10 mmHg) promotes the
formation of collateral portosystemic circulation, portal hyperten-
sive gastropathy, gastric varices, and oesophageal varices (Bosch
2009).
Bleeding, secondary to oesophageal or gastro-oesophageal varices,
is observed in up to 30% of the patients with liver cirrhosis dur-
ing the course of their illness, recurring in 70% of the patients
and being fatal in 20% (NIEC 1988). The highest mortality peak
is observed during the first six weeks after the bleeding episode
(Burroughs 2009). Hepatic functional status (assessed by Child-
Pugh score), renal dysfunction (assessed by creatinine serum lev-
els), and bacterial infections are the most important mortality risk
factors (Augustin 2009). Consequently, guidelines for treatment
of patients suffering variceal gastrointestinal bleeding include vol-
ume expansion, haemorrhage control, use of vasoconstrictors, and
short-term antibiotic prophylaxis (Garcia-Tsao 2009).
2Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Description of the intervention
The prophylactic use of oral or intravenous antibiotics has been
recommended in several consensus guidelines. The recommended
drugs are mainly oral quinolones (norfloxacin 400 mg b.i.d for
7 days) or intravenous cephalosporins (ceftriaxone 1 g/day for
7 days) (Garcia-Tsao 2009). However, other groups of antibi-
otics have been assessed such as beta-lactams or aminoglycosides
(Bernard 1999).
How the intervention might work
Cirrhosis is characterised by cellular and humoral immune dys-
function as well as increased bacterial translocation from the gut
into the bloodstream, facilitating the development of infections
(Chavez-Tapia 2007). The most common bacterial infections are
caused by gram-negative bacteria, producing spontaneous bacte-
rial peritonitis (25%), urinary tract infections (20%), pneumonia
(15%), and bacteraemia (12%) (Fernandez 2002). Considering
the increased mortality associated with infections, the vulnerabil-
ity of the immune system and the bacteriological profile, the use
of antibiotics is recommended.
Why it is important to do this review
Prophylactic use of antibiotics during an episode of upper gas-
trointestinal bleeding in cirrhotic patients is considered standard
of care. However, differences in the antibiotics used, schedules of
administration, duration of therapy, and changes in the bacterio-
logical profile across clinical trials make the evaluation of this in-
tervention difficult. This review systematically assesses these issues
and updates the information from a previous published review
(Soares-Weiser 2002).
O B J E C T I V E S
• To assess the benefits and harms of antibiotic prophylaxis in
cirrhotic patients with upper gastrointestinal bleeding.
Specifically this review was designed to:
• Compare the all-cause mortality and infection mortality
between cirrhotic patients with gastrointestinal bleeding
receiving antibiotic prophylaxis or no intervention/placebo.
• Compare the proportion of bacterial infections in patients
with gastrointestinal bleeding receiving antibiotic prophylaxis
versus no intervention/placebo.
• Determine the most effective antibiotic regimen.
M E T H O D S
Criteria for considering studies for this review
Types of studies
Randomised clinical trials comparing different types of antibiotic
therapy against no intervention, or placebo, or another antibi-
otic, in the prophylaxis of bacterial infections in cirrhotic patients
with upper gastrointestinal bleeding were identified. Trials were
included irrespective of publication status, language, or blinding.
Types of participants
Adult patients with cirrhosis and upper gastrointestinal bleeding
were included, regardless of the aetiology of cirrhosis or severity
of the disease.
Types of interventions
The following interventions, used alone or in combination, and
regardless of the mode of administration (intravenous or oral),
were considered.
• Aminoglycosides (eg, gentamicin, neomycin, tobramycin);
• Amoxicillin with or without clavulanic acid;
• Cephalosporins (eg, cefotaxime, ceftriaxone, ceftazidime,
cefonicid);
• Quinolones (eg, ciprofloxacin, ofloxacin, norfloxacin);
• Trimethoprim/sulphamethoxazole;
• Non-absorbable antibiotics (eg, colistin, nystatin);
• Other antibiotics.
Control groups received no intervention, placebo, or any antibi-
otic.
Types of outcome measures
Primary outcome measures:
• Number of deaths;
• Number of patients that developed bacterial infections
(bacteraemia, pneumonia, urinary tract infection, spontaneous
bacterial peritonitis, and/or other bacterial infections);
• Quality of life score (measured by any scale) between
groups;
• Adverse events (ICH-GCP 1997):
i) Any serious adverse events that were fatal, life-
threatening, or requiring inpatient hospitalisation or
prolongation of existing hospitalisation;
ii) Any adverse events that resulted in significant
disability or incapacity;
3Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
iii) Any important medical events that might not be
immediately life-threatening or resulted in death or
hospitalisation, but might jeopardise the patient or required
intervention to prevent one of the above outcomes;
iv) Any adverse events that required discontinuation of
medication.
Secondary outcome measures:
• Number of patients who developed bacterial infections after
an invasive procedure to stop upper gastrointestinal bleeding;
• Number of patients who developed superinfection or
antibiotic resistance in at least one of the follow-up cultures;
• Number of patients who developed rebleeding during the
follow-up (overall rebleeding rate and up to seven days rate);
• Number of patients who dropped out from the trial after
randomisation;
• Cost of different types of antibiotics used for prophylaxis;
• Number of days of hospitalisation.
Search methods for identification of studies
Electronic searches
Relevant randomised trials were identified by searching TheCochrane Hepato-Biliary Group Controlled Trials Register (Gluud
2010), the Cochrane Central Register of Controlled Trials (CEN-TRAL) (Issue 2, 2010) in The Cochrane Library, MEDLINE (1950
to 21 June 2010), EMBASE (1980 to 21 June 2010), and ScienceCitation Index EXPANDED (1945 to 21 June 2010) (Royle 2003).
Search strategies and time span of the searches are given in
Appendix 1.
Searching other resources
The references of all identified studies were inspected for more
trials. Additionally, the first or corresponding author of each in-
cluded trial, as well as researchers active in the field, were contacted
for information regarding unpublished trials and complementary
information on their own trial.
References from an existing review on this topic (Bernard 1999)
were also checked for any missing trials.
Data collection and analysis
Selection of studies
Three authors (NC, FT, TB) independently inspected each iden-
tified reference and applied the inclusion criteria. For potentially
relevant articles, or in cases of disagreement between the three re-
viewers, the full text article was obtained and inspected indepen-
dently. If resolving disagreement by discussion was not possible,
the article was added to those ’awaiting assessment’ and the au-
thors of the original study were contacted for clarification. In the
event of no reply from the authors within three months, a fourth
reviewer (MU or KSW) reviewed the article to solve the disagree-
ment. Justification for study exclusion was documented.
Data extraction and management
Two authors (NC and TB) independently extracted the data from
the included trials. In case of disagreement between the two au-
thors, a third author (FT) extracted the data. The data extraction
was discussed, decisions documented, and, when necessary, the
authors of the original studies were contacted for clarification. Jus-
tification for study exclusion was documented. Trials were identi-
fied with the last name of the first author and the year in which
the trial was first published, and ordered chronologically.
The following data were extracted, verified, and recorded:
Characteristics of trials
• Date, location, and setting of trial;
• Publication status;
• Case definitions used (clinical, serological, bacteriological);
• Sponsor of trial (known or unknown; industry or not
industry).
Characteristics of participants
• Number of participants in each group;
• Age, sex, nationality;
• Severity of liver disease and cirrhosis according to the
aetiology of liver disease, regardless of the criteria used.
Characteristics of interventions
• Type of antibiotic, dose, mode of administration, schedule,
length of follow-up (in months).
• Number of days that antibiotic prophylaxis was provided.
Characteristics of outcome measures
Whenever possible, the number of events previously listed under
Types of outcome measures were recorded in each group of the
randomised trials.
Assessment of risk of bias in included studies
Two authors (NC and TB) independently assessed bias risk of
the trials, without masking the trial names. For this purpose, in-
structions given in the Cochrane Handbook for Systematic Reviews
4Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
of Interventions (Higgins 2009) and the Cochrane Hepato-BiliaryGroup Module (Gluud 2010) were followed. The risk of overesti-
mation of intervention effects in randomised trials due to inad-
equate methodological quality (Schulz 1995; Moher 1998; Jüni
2001; Kjaergard 2001; Wood 2008) was assessed using the do-
mains below. Whenever information was not available in the pub-
lished trial, authors were contacted directly.
Sequence generation
• Low risk of bias, if the allocation sequence was generated by
a computer or random number table. Drawing of lots, tossing of
a coin, shuffling of cards, or throwing dice were also considered
as adequate if a person who was not otherwise involved in the
recruitment of participants performed the procedure.
• Unclear, if the trial was described as randomised, but the
method used for the allocation sequence generation was not
described or insufficient to permit judgement.
• High risk of bias, if a system involving dates, names, or
admittance numbers were used for the allocation of patients.
Allocation concealment
• Low risk of bias, if the allocation of patients involved a
central independent unit, on-site locked computer, identically
appearing numbered drug bottles or containers prepared by an
independent pharmacist or investigator, or sealed envelopes.
• Unclear, if the trial was described as randomised, but the
method used to conceal the allocation was not described or
insufficient to permit judgement.
• High risk of bias, if the allocation sequence was known to
the investigators who assigned participants or if the study was
quasi-randomised.
Blinding
• Low risk of bias, if the trial was described as double blind
and the method of blinding involved identical placebo or active
drugs.
• Unclear, if the trial was described as double blind, but the
method of blinding was not described.
• High risk of bias, if the trial was not double blind.
Incomplete outcome data
• Low risk of bias, if there were no post-randomisation drop-
outs or withdrawals.
• Unclear, if it is not clear whether there are any drop-outs or
withdrawals or if the reasons for these drop-outs are not clear.
• High risk of bias, if the reasons for missing data are likely to
be related to true outcomes.
Selective outcome reporting
• Low risk of bias, considering that most of the included
trials were made before of the obligatory registration on
randomised controlled trials databases, and the pre-specified
outcomes are not available. The following outcomes were
considered fundamental as outcome to avoid selective reporting;
a) mortality, b) response rate, and c) adverse events.
• Unclear, there is insufficient information to assess whether
the magnitude and direction of the observed effect is related to
selective outcome reporting.
• High risk of bias, not all of the trial’s pre-specified primary
outcomes have been reported or similar.
Other sources of bias
• Low risk of bias, the trial appears to be free of other sources
of bias, considering; a) baseline imbalance, b) source of funding,
c) early stopping, and d) interim analysis.
• Unclear, there is insufficient information to assess whether
other sources of bias are present.
• High risk of bias, it is likely that potential sources of bias.
Following the definitions of the above domains, an included trial
was judged as a trial with a low risk of bias when the risk of bias
was evaluated as ’low’ in all domains. If the risk of bias was judged
as ’uncertain’ or ’high’, then the trial was judged as having ’high
risk of bias’.
Furthermore, we registered whether or not the randomised clini-
cal trials had used ’intention-to-treat’ analysis (Gluud 2001), the
length of follow-up, and sample size calculation. Any disagreement
was resolved by discussion and settled by a third author (FT). We
contacted the trial author for clarification as necessary.
Measures of treatment effect
Dichotomous data were analysed calculating the relative risk (RR)
for each trial, expressing the uncertainty with 95% confidence
intervals (CI). Continuous data were analysed calculating mean
differences between groups of each trial and its 95% CI. Compar-
isons were made between trials evaluating antibiotic prophylaxis
against no intervention or placebo, and trials comparing different
antibiotic regimens.
Assessment of heterogeneity
We checked the heterogeneity of effects across trials by visual in-
spection of the forest plots and Chi2 and I2 tests for heterogeneity
(Higgins 2009). Statistical heterogeneity was defined as a P value
≤ 0.10 (Chi2) or I2 > 25%. When heterogeneity existed, subgroup
analyses were performed in order to assess the impact of potential
sources of heterogeneity over the main results.
5Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Assessment of reporting biases
A funnel plot estimating the precision of trials (plot of logarithm
of the RR against the sample size) was examined in order to esti-
mate potential asymmetry. In addition, the standard normal devi-
ate (SND), defined as the RR divided by its standard error, was re-
gressed against the estimate’s precision (regression equation: SND
= a + b x precision) in order to facilitate the prediction of poten-
tial heterogeneity or data irregularities in the meta-analyses (Egger
1997). In this equation, the SND reflects the degree of funnel
plot asymmetry as measured by the intercept from the regression
analysis.
Data synthesis
For the statistical analyses, we used RevMan Analyses (RevMan
2010). Dichotomous data were synthesised poling the RR and
95% CI from all trials to estimate the global effect of the interven-
tion. Continous data were synthesised pooling mean differences
and 95% CI from each trial to calculate the average mean differ-
ence.
In order to compare the RR from different antibiotic groups and
detect differences among the antibiotics tested versus no inter-
vention or placebo, a test for interaction was calculated (Altman
2003).
Sensitivity analysis
We analysed data using both fixed-effect and random-effects mod-
els. When both models produced similar estimates, the fixed-effect
result was reported; otherwise, we reported the results from both
analyses. Outcomes were analysed as reported in the trial, that is,
either per protocol or as intention-to-treat analysis. In order to ex-
amine the influence of drop-outs, we performed both worst-best-
case (assigning bad outcomes to all of the missing experimental
group patients and good outcomes to all of the missing control
group patients) and best-worst-case (assigning good outcomes to
all of the missing experimental group patients and bad outcomes
to all of the missing control group patients) analyses.
To assess the reliability of the meta-analyses on mortality, mortal-
ity from bacterial infections, and bacterial infections, the required
information size (RIS) was calculated by trial sequential analysis
(TSA). We respectively assumed an average event proportion of
22%, 5%, and 36% in the control group of the three meta-anal-
yses; a 20% relative risk reduction of the experimental interven-
tion, and statistical error levels of 5% alpha and 20% beta (80%
power). Whenever the cumulative information size in the meta-
analysis was smaller than the RIS, the threshold to maintain statis-
tical significance was calculated with the O’Brien-Fleming bound-
aries (Brok 2008; Wetterslev 2008; Thorlund 2009).
R E S U L T S
Description of studies
See: Characteristics of included studies; Characteristics of excluded
studies.
Results of the search
Forty-one relevant references were initially identified and screened
for retrieval. Subsequently, reviews (fourteen references), com-
ments and editorials (four references) were excluded. Twenty-six
studies were considered suitable to be included, but nine studies
were excluded because they were not randomised trials (six stud-
ies), did not include patients with upper gastrointestinal bleeding
(two studies), or did not include any of the outcomes assessed in
this review (one study) (See ’Excluded studies’ for additional in-
formation). Finally, seventeen trials (twenty-one references) were
included for analyses (see ’Included studies’ for additional infor-
mation).
Included studies
Seventeen trials evaluating th effectiveness of antibiotic prophy-
laxis against bacterial infections in 1891 patients were included
in this review (Rimola 1985; Soriano 1992; Rolando 1993; Blaise
1994; Selby 1994; Pauwels 1996; Zacharof 1997; Hsieh 1998;
Sabat 1998; Spanish Group 1998; Gulberg 1999; Hong 2002;
Lin 2002; Hou 2004; Lata 2005; Fernandez 2006; Jun 2006),
in twelve trials (fourteen references) comparison with no inter-
vention or placebo was conducted (Rimola 1985; Soriano 1992;
Rolando 1993; Blaise 1994; Selby 1994; Pauwels 1996; Zacharof
1997; Hsieh 1998; Hong 2002; Lin 2002; Hou 2004; Jun 2006).
Five trials (eight references) were head-to-head antibiotic com-
parisons (Sabat 1998; Spanish Group 1998; Gulberg 1999; Lata
2005; Fernandez 2006).
Most trials were retrieved as complete manuscript and two trials as
abstracts (Spanish Group 1998; Zacharof 1997). The only non-
English article was written in Korean (Hong 2002).
Trials were conducted in Australia (Selby 1994), Czech Repub-
lic (Lata 2005), France (Blaise 1994; Pauwels 1996), Germany
(Gulberg 1999), Greece (Zacharof 1997), Korea (Hong 2002;
Jun 2006), Spain (Rimola 1985; Soriano 1992; Sabat 1998;
Spanish Group 1998; Fernandez 2006), Taiwan (Hsieh 1998; Lin
2002; Hou 2004), and the United Kingdom (Rolando 1993) (see
’Characteristics of included studies’ for details).
The source of the haemorrhage was gastroesophageal varices in six
trials (Rolando 1993; Blaise 1994; Hong 2002; Hou 2004; Lata
2005; Jun 2006), mixed (variceal and non-variceal gastrointestinal
haemorrhage) in seven trials (Rimola 1985; Soriano 1992; Pauwels
1996; Hsieh 1998; Sabat 1998; Lin 2002; Fernandez 2006), and
not specified in four trials (Selby 1994; Zacharof 1997; Spanish
Group 1998; Gulberg 1999).
While all trials assessed the use of antibiotic prophylaxis, the pri-
mary outcome differed between them. The most common was
6Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
prevention of bacterial infections in fourteen trials (Rimola 1985;
Soriano 1992; Rolando 1993; Blaise 1994; Selby 1994; Pauwels
1996; Zacharof 1997; Hsieh 1998; Sabat 1998; Spanish Group
1998; Gulberg 1999; Hong 2002; Lin 2002; Fernandez 2006),
rebleeding rate in two trials (Hou 2004; Jun 2006), and early and
late mortality in one trial (Lata 2005).
All trials were performed on hospitalised patients, but four specif-
ically described critical care settings (Rimola 1985; Blaise 1994;
Pauwels 1996; Lata 2005). Eleven trials reported the Child-Pugh
score as a categorical variable, from them nine included patients
with Child-Pugh score A/B/C (overall distribution 17/51/32%,
respectively), two trials reported only patients with Child Pugh
score B/C. Diagnostic and management of the gastrointestinal
haemorrhage was done by endoscopy.
The antibiotics compared versus no intervention or placebo were:
quinolones (five trials), quinolones plus beta-lactams (two trials),
cephalosporins (three trials), carbapenems (one trial) and non-
absorbable antibiotics (one trial) (Table 1).
The head-to-head antibiotic comparisons were explored in five
trials (Table 2), as follows: combination of antibiotics versus a
single antibiotic (Sabat 1998), two antibiotics from the same group
(Spanish Group 1998; Gulberg 1999), and different groups of
antibiotics in each intervention group (Lata 2005; Fernandez
2006).
Excluded studies
Nine studies were excluded from this review. The main reason was
the retrospective or non-interventional study design, one study
used inadequate allocation concealment (Henrion 1992); another
trial did not measure any of the outcomes analysed in this review
(Pulanic 1989); two studies were excluded because the patients did
not have upper gastrointestinal haemorrhage (Gines 1990; Novella
1997).
Risk of bias in included studies
See Figure 1 and Figure 2 for more information. None of the trials
was of low risk of bias.
7Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Figure 1. Risk of bias summary: review authors’ judgements about each risk of bias item for each included
study.
8Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Figure 2. Risk of bias graph: review authors’ judgements about each risk of bias item presented as
percentages across all included studies.
Allocation
Allocation sequence was generated by random table number or
software in eleven trials (Rimola 1985; Soriano 1992; Rolando
1993; Selby 1994; Pauwels 1996; Zacharof 1997; Sabat 1998;
Hou 2004; Lata 2005; Fernandez 2006; Jun 2006). In six trials
no clear information about the sequence generation was reported
and authors did not provide further information, being classified
as unclear. The allocation concealment information was properly
indicated in only one trial (Jun 2006), was clarified by direct com-
munication in four trials (Rimola 1985; Rolando 1993; Zacharof
1997; Fernandez 2006), and was unclear in twelve trials. Consider-
ing both sequence generation process and allocation concealment,
only five trials were classified as having low risk of bias (Rimola
1985; Rolando 1993; Selby 1994; Zacharof 1997; Jun 2006).
Blinding
The risk of bias was high or unclear in all trials included in this
review. Only one trial used placebo (Hsieh 1998), but blinding
procedures were not reported. Most trials were designed to com-
pare antibiotic prophylaxis versus no intervention, complicating
the blinding process. The Cochrane Handbook for Systematic Re-views or Interventions (Higgins 2009) allows considering a trial
with a low risk of bias if the outcome is not directly affected by
the lack of blinding. Thus, when mortality was the outcome, the
trials were considered to be at low risk of bias. Mortality secondary
to infections and overall infections as the outcomes could have
been affected by the lack of blinding, therefore, considering these
outcomes, all trials were considered at high risk of bias.
Incomplete outcome data
Common exclusion criteria from the trials included bacterial in-
fections at admission, positivity of biological cultures during fol-
low-up and death, or surgery during the first twelve to twenty-
four hours. The trial by Rimola 1985 was considered at high risk
of bias because patients excluded were not balanced across groups;
similarly, Jun 2006 reported a higher proportion of missing out-
comes in the non-prophylaxis group.
Selective reporting
9Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Except for the trials reported only in abstract form (Zacharof 1997;
Spanish Group 1998), all the trials reported at least the primary
outcome in their methods.
Other potential sources of bias
Lack of sample size calculation was the most frequently observed
source of other bias. Sample size calculation was described in four
trials (Sabat 1998; Hou 2004; Fernandez 2006; Jun 2006).
Intention-to-treat analysis was performed in one trial (Hsieh
1998). There was a clear rule to exclude some patients from the
analysis in certain trials (Blaise 1994; Lin 2002; Fernandez 2006),
without considering the intention-to-treat analysis (Higgins
2009).
Three other trials could have been subjected to other forms of
bias. In Rimola 1985, the antibiotic used was changed over the
course of the trial; Gulberg 1999 used surrogates for infection in
several analysis; and Sabat 1998 stopped the trial prematurely due
to differences in economical outcomes.
Effects of interventions
Mortality
Twelve trials reported overall mortality in 1241 patients. No sig-
nificant heterogeneity of effects was observed and a slight asym-
metry towards the left side of the funnel plot suggested a potential
overestimation of effects from small sized trials. The effect of an-
tibiotic prophylaxis on overall mortality was significant (RR 0.79,
95% CI 0.79 to 0.98).
To explore the impact of dropouts on mortality, best-worst-case
and worst-best-case analyses were performed (worst-best-case anal-
ysis RR 1.45, 95% CI 1.04 to 2.02; best-worst-case analysis RR
0.48, 95% CI 0.38 to 0.60).
The TSA showed a trend towards beneficial effects of the interven-
tion to reduce mortality, but the cumulative Z-score did not cross
the O’Brien-Fleming boundaries (Figure 3); therefore, no clear
conclusion can be drawn and more trials are needed to confirm
the result of this outcome.
Figure 3. O’Brien-Fleming monitoring boundaries for assessing statistical significance for overall mortality.
The solid blue curve presents the cumulative meta-analysis test-score and the inward sloping red curves
present the adjusted threshold for statistical significance - the two-sided O’Brien-Fleming boundaries.
10Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Mortality from bacterial infections
Six trials reported mortality from bacterial infections, compar-
ing prophylaxis with no intervention or placebo (Rimola 1985;
Soriano 1992; Pauwels 1996; Lin 2002; Hou 2004; Jun 2006).
Antibiotic prophylaxis was associated with a significant decrease
in mortality from bacterial infections (RR 0.43, 95% CI 0.19 to
0.97).
The sensitivity analysis showed this estimation could have been
biased by differential drop-out rates (worst-best-case analysis RR
3.30, 95% CI 1.43 to 7.62; best-worst-case analysis RR 0.14, 95%
CI 0.06 to 0.31).
The TSA demonstrated that the few number of trials included
in the analysis were not enough to conclude a beneficial effect of
prophylaxis over mortality from bacterial infections (Figure 4).
Figure 4. O’Brien-Fleming monitoring boundaries for assessing statistical significance for mortality from
bacterial infections. The solid blue curve presents the cumulative meta-analysis test-score and the inward
sloping red curves present the adjusted threshold for statistical significance - the two-sided O’Brien-Fleming
boundaries.
11Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Bacterial infections
All trials comparing antibiotic prophylaxis versus no intervention
or placebo reported incidence of bacterial infections. For this re-
view, only confirmed bacterial infections were considered. A to-
tal of 1241 patients were included in the trials, showing antibi-
otic prophylaxis to be significantly beneficial to reduce bacterial
infections (RR 0.36, 95% CI 0.27 to 0.49). Heterogeneity of ef-
fects across trials was significant. However, all estimators remained
statistically significant independently of the type of analyses used
(random or fixed-effects), strengthening the evidence for the pro-
posed effect.
Bacterial infections were not affected by the sensitivity analysis
(worst-best-case analysis RR 0.77, 95% CI 0.63 to 0.93; best-
worst-case analysis RR 0.26, 95% CI 0.26 to 0.43), and also the
TSA showed significant benefit of antibiotic prophylaxis over no
intervention or placebo (Figure 5).
Figure 5. O’Brien-Fleming monitoring boundaries for assessing statistical significance for bacterial
infections. The solid blue curve presents the cumulative meta-analysis test-score and the inward sloping red
curves present the adjusted threshold for statistical significance - the two-sided O’Brien-Fleming boundaries.
Bacteremia was reported in nine trials with a significant risk re-
duction in patients under antibiotic prophylaxis (RR 0.25, 95%
CI 0.15 to 0.40). Similarly, other infectious outcomes were signif-
icantly reduced with the use of antibiotic prophylaxis: pneumonia
in nine trials (RR 0.45, 95% CI 0.27 to 0.75), spontaneous bac-
terial peritonitis in eight trials (RR 0.29, 95% CI 0.15 to 0.57),
and urinary tract infections in nine trials (RR 0.23, 95% CI 0.12
to 0.41).
12Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Drop-outs and sensitivity analysis
There was no significant difference in drop-out rates across eight
trials reporting this outcome (RR 1.07, 95% CI 0.76 to 1.51).
We analysed overall mortality and bacterial infections stratifying
by sample size (larger than 100 versus smaller than 101 patients),
RR were homogeneous across strata.
Adverse events
No significant adverse events were reported.
Quality of life
No information regarding this outcome was reported in the trials.
Antibiotic regimens
Although a beneficial effect of antibiotic prophylaxis was observed
when pooling all trials, stratifying by group of antibiotic diluted
the effect and no beneficial effects on mortality or mortality from
bacterial infections was observed.
Regarding bacterial infections, all the antibiotics showed a risk
reduction, the beneficial effect seemed to be higher in trials us-
ing cephalosporins (RR 0.16, 95% CI 0.05 to 0.48), followed by
quinolones (RR 0.27, 95% CI 0.18 to 0.39), quinolones plus beta-
lactams (RR 0.38, 95% CI 0.23 to 0.62), and other antibiotics
(RR 0.57, 95%CI 0.41 to 0.81). However, the test for interac-
tion demonstrated that only the group of ’other antibiotics’ signif-
icantly differed from all other drugs (quinolones versus other an-
tibiotics P value = 0.004, and cephalosporins versus other antibi-
otics P value 0.03). No significant difference between quinolones
and cephalosporins was observed (Table 3).
Rebleeding
In three trials (Hong 2002; Hou 2004; Jun 2006) rebleeding was
reported. A significant reduction was observed among patients
under antibiotic prophylaxis in overall rebleeding (RR 0.53, 95%
CI 0.38 to 0.74), and rebleeding after up to seven days of follow-
up (RR 0.24, 95% CI 0.12 to 0.50).
Days of hospitalisation
Seven trials reported hospitalisation length of stay, two trials during
intensive care hospitalisation only (Blaise 1994; Pauwels 1996),
and five trials during full-length of hospitalisation (Soriano 1992;
Hsieh 1998; Hong 2002; Lin 2002; Jun 2006). The overall effect
of the intervention was not significant (MD -0.79 days, 95% CI
-1.84 to 0.26) - however, this estimate is highly influenced by the
intensive care hospitalisation trials. When full-length hospitalisa-
tion trials were considered alone, a beneficial effect from the inter-
vention was observed (MD -1.91 days, 95% CI -3.80 to -0.02).
Antibiotic regimens versus other antibiotic regimens
Five trials compared different antibiotic regimens. No significant
differences between regimens were observed for the outcomes un-
der study. See Table 4 for more information.
D I S C U S S I O N
Summary of main results
This systematic review is an update of a previous systematic review
and meta-analysis published in 2002 (Soares-Weiser 2002). From
that date, new trials supporting the use of antibiotic prophylaxis on
cirrhotic patients with upper gastrointestinal haemorrhage became
available. Six new trials - four comparing antibiotics against no-
intervention, and two comparing different antibiotic regimens -
were included in this update.
The most clinically relevant outcomes assessed in this review were
mortality, mortality from bacterial infections, bacterial infections,
and rebleeding. The inclusion of new trials did not modify a previ-
ously observed beneficial effect of antibiotic prophylaxis on mor-
tality and bacterial infections. Rebleedingwas included as a new
secondary outcome as it is an important outcome in clinical prac-
tice. We observed a statistically significant beneficial effect of the
intervention on rebleeding. However, studies assessing rebleeding
are still scarce and our presented results are based on only three
trials. To confirm this observation, more data are required. In this
updated review, antibiotic prophylaxis reduced the hospitalisation
length of stay, but not the time in critical care.
The effects observed were more robust for prevention of bacterial
infections, which remained significant after sensitivity analysis and
TSA. This could be explained by the fact that all the trials included
were designed and powered to evaluate this outcome.
The evolution of the intervention goes from non-absorbable an-
tibiotics (one trial), to quinolones (five trials), and to more recent
cephalosporins (three trials), but there is no solid evidence to pre-
fer one antibiotic regimen over the other. This was also observed
in trials exploring several antibiotic regimens simultaneously. Use
of quinolones was first explored by Soriano 1992 and quinolones
have been broadly used since then, despite rising concerns of a po-
tential reduction of their effects due to bacterial resistance. How-
ever, considering that bacterial resistance pattern vary by location,
use of quinolones for antibiotic prophylaxis will have to be assessed
in specific local settings.
Overall completeness and applicability ofevidence
The current evidence to support antibiotic prophylaxis is based
on twelve randomised trials, and, except for America and Africa,
the intervention has been assessed in heterogeneous populations,
13Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
providing external validity to this review. This review aimed to
evaluate the effects of antibiotic prophylaxis on bacterial infections
and mortality, and although a beneficial effect was observed, cau-
tion should be exerted when interpreting mortality results, since
all included trials were not specifically designed to evaluate this
outcome. Moreover, the significance of the observation could not
be confirmed in trial sequential analysis (Wetterslev 2008; Brok
2008; Thorlund 2009).
Several issues were not answered in this review. Adverse events,
quality of life, and the economic impact of the intervention were
not explored in the trials included, remaining important areas of
uncertainty and requiring further data to establish an evidence-
based conclusion.
Quality of the evidence
This review included 1891 cirrhotic patients with upper gastroin-
testinal bleeding; 1241 of them participated in randomised tri-
als comparing antibiotic prophylaxis versus no intervention or
placebo, and the remaining 650 participants in trials compar-
ing different antibiotic prophylactic regimens. All trials presented
methodological weaknesses and should be considered at risk of
bias. Lack of blinding and lack of proper sample size calculations
were the most common sources of bias. Although less subjective
outcomes were considered in this review (mortality, mortality from
bacterial infections, confirmed bacterial infections, and rebleed-
ing) the influence of these sources of bias cannot be determined
precisely.
Potential biases in the review process
All trials included in this review presented incomplete data to
adequately assess their methodological strength and usefulness.
Several attempts were made to contact original authors, but only
in few cases an answer was obtained.
Agreements and disagreements with otherstudies or reviews
The current treatment guidelines consider antibiotic prophylaxis
as standard of care (Garcia-Tsao 2007; Bosch 2008; Garcia-Tsao
2009) based on the beneficial effects reported on mortality. How-
ever, this effect is less well-supported compared to the effect of
prophylaxis to prevent bacterial infections. The information pro-
vided in this review will help the practitioner to weight the most
important effects from antibiotic prophylaxis.
A U T H O R S ’ C O N C L U S I O N S
Implications for practice
The use of prophylactic antibiotics in patients with cirrhosis and
upper gastrointestinal bleeding significantly reduce bacterial infec-
tions and seems to reduce all-cause mortality, bacterial infection
mortality, incidence of rebleeding events, and length of hospitali-
sation. These benefits were observed indistinctly of the antibiotic
assessed. No specific antibiotic regimen can be recommended over
another.Thus, antibiotic selection should be made considering lo-
cal conditions such as bacterial resistance profile and treatment
cost.
Implications for research
The sensitivity analysis and the TSA, in addition to the meta-anal-
ysis, demonstrate the robustness of data regarding antibiotic pro-
phylaxis to prevent bacterial infections. However, data are not as
conclusive concerning the other outcomes. Considering the ben-
efits of antibiotic prophylaxis for bacterial infection prevention it
will seem unwise to further conduct trials with placebo or no in-
tervention as comparators, although specific conditions in clinical
settings could justify their conduct.
The information regarding the benefits and harms from different
antibiotic regimens is still scarce. Critical information such as the
differential impact of each regimen over quality of life or their
pharmaco-economical advantages are still unclear and require fur-
ther investigation.
Future research must include adequate sample size calculations and
proper blinding processes. Additionaly, information about other
significant outcomes, particularly adverse events, should also be
considered in the future. Finally, trials should follow the recom-
mended guidelines for the reporting of clinical trials (CONSORT
- Consolidated Standards of Reporting Trials: www.consort-state-
ment.org).
A C K N O W L E D G E M E N T S
We thank Dimitrinka Nikolova and Christian Gluud of The
Cochrane Hepato-Biliary Group for ongoing support for this re-
view.
Thanks to J. Fernandez, P. Gines, A. Rimola, N. Rolando, and
A. Zacharof, who kindly supplied additional information on their
own trials.
We would like thank M Brezis, R Tur-Kaspa, and L Leibovici who
participated in the previous version of this review (Soares-Weiser
2002). Their work was supported by the Tel Aviv University,
Hadassah University Hospital - Mount Scopus, and Rabin Medi-
cal Center - Beilinson Campus, (Israel). The Danish Medical Re-
search Council’s Grant on Getting Research into Practice (GRIP),
Copenhagen Hospital Corporation’s Research Grant on Getting
14Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Research into Practice (GRIP), and The 1991 Pharmacy Founda-
tion (Denmark
Peer Reviewers: Wolfgang Fleig, Germany; Gennaro D’Amico,
Italy.
Contact Editor: Christian Gluud, Denmark.
R E F E R E N C E S
References to studies included in this review
Blaise 1994 {published data only}
Blaise M, Pateron D, Trinchet JC, Levacher S, Beaugrand
M, Pourriat JL. Systemic antibiotic therapy prevents
bacterial infection in cirrhotic patients with gastrointestinal
hemorrhage. Hepatology 1994;20(1 Pt 1):34–8.
[MEDLINE: 94292124]
Fernandez 2006 {published data only}
Fernandez J, Ruiz del Arbol L, Gomez C, Durandez R,
Serradilla R, Guarner C, et al.Norfloxacin vs ceftriaxone
in the prophylaxis of infections in patients with advanced
cirrhosis and hemorrhage. Gastroenterology 2006;131(4):
1049-56; quiz 1285.
Gulberg 1999 {published data only}
Gulberg V, Deibert P, Ochs A, Rossle M, Gerbes AL.
Prevention of infectious complications after transjugular
intrahepatic portosystemic shunt (TIPS) in patients with
cirrhosis of the liver with a single dose of ceftriaxone
(AASLD Abstract). Hepatology 1997;26(4):518A.∗ Gulberg V, Deibert P, Ochs A, Rossle M, Gerbes AL.
Prevention of infectious complications after transjugular
intrahepatic portosystemic shunt in cirrhotic patients with a
single dose of ceftriaxone. Hepato-Gastroenterology 1999;46
(26):1126–30. [MEDLINE: 99298817]
Hong 2002 {published data only}
Hong SN, Kim BJ, Lee SY, Lee CY, Ryu MK, Choi MS, et
al.[Prospective randomized trial of intravenous ciprofloxacin
for prevention of bacterial infection in cirrhotic patients
with esophageal variceal bleeding]. Taehan Kan Hakhoe Chi2002;8(3):288–96.
Hou 2004 {published data only}
Hou MC, Lin HC, Liu TT, Kuo BI, Lee FY, Chang FY, et
al.Antibiotic prophylaxis after endoscopic therapy prevents
rebleeding in acute variceal hemorrhage: a randomized trial.
Hepatology 2004;39(3):746–53.
Hsieh 1998 {published data only}
Hsieh W, Lin H, Hwang S, Hou M, Lee F, Chang F, et al.The
effect of ciprofloxacin in the prevention of bacterial infection
in patients with cirrhosis after upper gastrointestinal
bleeding. American Journal of Gastroenterology 1998;93(6):
962–6. [MEDLINE: 98309244]
Jun 2006 {published data only}
Jun CH, Park CH, Lee WS, Joo YE, Kim HS, Choi
SK, et al.Antibiotic prophylaxis using third generation
cephalosporins can reduce the risk of early rebleeding in
the first acute gastroesophageal variceal hemorrhage: a
prospective randomized study. Journal of Korean Medical
Science 2006;21(5):883–90.
Lata 2005 {published data only}
Lata J, Jurankova J, Husova L, Senkyrik M, Dite P, Dastych
M, et al.Variceal bleeding in portal hypertension: bacterial
infection and comparison of efficacy of intravenous and
per-oral application of antibiotics - a randomized trial.
European Journal of Gastroenterology & Hepatology 2005;17
(10):1105–10.
Lin 2002 {published data only}
Lin YT, Lo GH, Lai KH, Chen TA, Lin WJ. Prophylactic
antibiotics in cirrhotics with upper gastrointestinal
hemorrhage: a prospective, controlled trial. Zhonghua YiXue Za Zhi (Taipei) 2002;65(8):365–71.
Pauwels 1996 {published data only}
Pauwels A, Mostefa Kara N, Debenes B, Degoutte E, Levy
VG. Systemic antibiotic prophylaxis after gastrointestinal
hemorrhage in cirrhotic patients with a high risk of
infection. Hepatology 1996;24(4):802–6. [MEDLINE:
97007920]
Rimola 1985 {published and unpublished data}
Rimola A, Bory F, Teres J, Perez-Ayuso R, Arroyo V, Rodes
J. Oral, nonabsorbable antibiotics prevent infection in
cirrhotics with gastrointestinal hemorrhage. Hepatology1985;5(3):463–7. [MEDLINE: 85205789]
Rolando 1993 {published and unpublished data}
Rolando N, Gimson A, Philpott-Howard J, Sahathevan
M, Casewell M, Fagan E, et al.Infectious sequelae after
endoscopic sclerotherapy of oesophageal varices: role of
antibiotic prophylaxis. Journal of Hepatology 1993;18(3):
290–4. [MEDLINE: 94044619]
Sabat 1998 {published data only}
Sabat M, Kolle L, Ortiz J, Pamplona J, Novella MT,
Villanueva C, et al.Parental antibiotic prophylaxis in
cirrhotic patients with gastrointestinal bleeding (AASLD
abstract). Hepatology 1996;24(4 Pt 2):448A.∗ Sabat M, Kolle L, Soriano G, Ortiz J, Pamplona J,
Novella MT, et al.Parenteral antibiotic prophylaxis of
bacterial infections does not improve cost-efficacy of oral
norfloxacin in cirrhotic patients with gastrointestinal
bleeding. American Journal of Gastroenterology 1998;93(12):
2457–62. [MEDLINE: 99075752]
15Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Selby 1994 {published data only}
Selby WS, Norton ID, Pokorny CS, Benn RA. Bacteremia
and bacterascites after endoscopic sclerotherapy for
bleeding esophageal varices and prevention by intravenous
cefotaxime: a randomized trial. Gastrointestinal Endoscopy
1994;40(6):680–4. [MEDLINE: 95163822]
Soriano 1992 {published data only}∗ Soriano G, Guarner C, Tomas A, Villanueva C, Torras X,
Gonzalez D, et al.Norfloxacin prevents bacterial infection in
cirrhotics with gastrointestinal hemorrhage (see comments).
Gastroenterology 1992;103(4):1267–72.
Soriano G, Guarner G, Tena F, Villanueva C, Fabrega E,
Gonzalez D, et al.Prophylaxis of infections with norfloxacin
in cirrhotic patients with gastrointestinal bleeding (EASL
abstract). Journal of Hepatology 1990;11(Suppl 2):S56.
[MEDLINE: 99075752]
Spanish Group 1998 {published data only}
Spanish Group for the Study of Bacterial Infections in
Cirrhosis. Norfloxacin versus ofloxacin in the prophylaxis
of infection in cirrhotic patients with gastrointestinal
hemorrhage. Journal of Hepatology 1998;28(Suppl 1):80.
Zacharof 1997 {published and unpublished data}
Zacharof A, Petrogiannopoulos C, Flevaris C, Deliousis A,
Poulikakos J. Ciprofloxacin prevents bacterial infection in
cirrhotics with gastrointestinal hemorrhage (EASL abstract).
Journal of Hepatology 1997;26(Suppl 1):12.∗ Zacharof A, Petrogiannopoulos C, Soutos D, Katsaros D,
Zacharof H. Bacterial infection is prevented by ciprofloxacin
in cirrhotics with gastrointestinal hemorrhage (Abstract).
Gut 1997;41(Suppl 3):A189.
References to studies excluded from this review
Gines 1990 {published and unpublished data}
Gines P, Rimola A, Planas R, Vargas V, Forne M, Miranda
ML, et al.Norfloxacin prevents spontaneous bacterial
peritonitis (SBP) in cirrhosis. Final results of a multicenter
double-blind placebo controlled study (EASL abstract).
Journal of Hepatology 1990;11(Suppl2):S26.
Gines P, Rimola A, Planas R, Vargas V, Llach J, Salmeron
JM, et al.Norfloxacin for prophylaxis of spontaneous
bacterial peritonitis (SBP) in cirrhosis: results of a double-
blind, placebo-controlled trial (AASLD Annual Meeting).
Hepatology 1989;10(4):587.∗ Gines P, Rimola A, Planas R, Vargas V, Marco F, Almela M,
et al.Norfloxacin prevents spontaneous bacterial peritonitis
recurrence in cirrhosis: results of a double-blind, placebo-
controlled trial. Hepatology 1990;12:716–24. [MEDLINE:
91007687]
Goulis 1998 {published data only}
Goulis J, Armonis A, Patch D, Sabin C, Greenslade
L, Burroughs AK. Bacterial infection is independently
associated with failure to control bleeding in cirrhotic
patients with gastrointestinal hemorrhage. Hepatology 1998;
27(5):1207–12.
Henrion 1992 {published data only}
Henrion J, Schapira M, Derue G, Heller FR. Prevention of
bacterial infection using selective intestinal decontamination
in patients with cirrhosis admitted to intensive care.
Controlled study in 120 patients [Prevention de l’infection
bacterienne par decontamination intestinale selective chez
des patients cirrhotiques admis en soins intensifs Etude
controlee chez 120 malades]. Acta Gastroenterologica Belgica1992;55(4):333–40. [MEDLINE: 93097875]
Husova 2005 {published data only}
Husova L, Lata J, Husa P, Senkyrik M, Jurankova J, Dite
P. Bacterial infection and acute bleeding from upper
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Bernard B, Grange JD, Khac EN, Amiot X, Opolon P,
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References to other published versions of this review
Soares-Weiser 2002
Soares-Weiser K, Brezis M, Tur-Kaspa R, Leibovici
L. Antibiotic prophylaxis for cirrhotic patients with
gastrointestinal bleeding. Cochrane Database ofSystematic Reviews 2002, Issue 2. [DOI: 10.1002/
14651858.CD002907]∗ Indicates the major publication for the study
18Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
C H A R A C T E R I S T I C S O F S T U D I E S
Characteristics of included studies [ordered by study ID]
Blaise 1994
Methods Data collection: 09/1990 to 01/1992.
Exclusion from analysis: patients with no oesophageal varices or infected.
Follow-up period: 14 days.
Participants France
Hospitalised cirrhotic patients with upper gastrointestinal haemorrhage, without infec-
tion, or treatment with antibiotics in the previous two weeks.
Etiology of bleeding: oesophageal varices.
Initial infection assessment: chest X-ray, blood count, urine/sputum/blood/ascites cul-
ture.
Endoscopy scheduled within 12 h after enrolment.
Sclerotherapy performed together with endoscopy to stop bleeding.
Child-Pugh class A/B/C: 0/20/7.
Interventions Experimental: intravenous + oral ofloxacin, 400 mg/day, 10 days; amoxicillin + clavulanic
acid (bolus, 1g) before each endoscopy procedure
Control: no antibiotic prophylaxis.
Outcomes Prevent bacterial infections.
Notes Authors were contacted for the first version of this review.
Risk of bias
Item Authors’ judgement Description
Adequate sequence generation? Unclear No information provided.
Allocation concealment? Unclear No information provided.
Blinding?
All outcomes
No Not a blinded trial.
Incomplete outcome data addressed?
All outcomes
Yes Missing data are balanced in number across
the intervention groups
Free of selective reporting? Yes The report include all the expected out-
comes.
Free of other bias? Yes The trial appears to be free of other sources
of bias.
Intention to treat analysis? No The excluded participants are balanced and
with a justifiable reason
19Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Blaise 1994 (Continued)
Sample calculation? No No sample calculation was done.
Fernandez 2006
Methods Data collection 02/2000 to 04/2004.
Exclusion from analysis: occult infection (positive blood cultures obtained prior to ran-
domisation) and less than two signs of liver failure (Norfloxacin group 6/63; Ceftriaxone
group 7/61).
Follow-up period: 10 days.
Participants Spain
Multicenter trial on hospitalised patients in patients with cirrhosis and upper gastroin-
testinal haemorrhage
Etiology of bleeding: portal hypertension related in 77% of participants
Initial infection assessment: blood cultures, ascitic fluid polymorphonuclear count, urine
sediment and culture, chest X-ray
Emergency endoscopy within 24 h after onset of the haemorrhage, plus somatostatin or
terlipressin on portal hypertension related haemorrhage
Sclerotherapy or banding was performed to stop bleeding.
Chil-Pugh class A/B/C: 0/52/59.
Interventions Experimental: intravenous ceftriaxone 1g per day for 7 days.
Control: oral norfloxacin 400 mg b.i.d. for 7 days.
Outcomes Prevention of bacterial infections.
Notes The authors were contacted via e-mail and response was received (28-June-2010)
Risk of bias
Item Authors’ judgement Description
Adequate sequence generation? Yes The sequence was generated using a ran-
dom number software.
Allocation concealment? Unclear No information provided.
Blinding?
All outcomes
No Not a blinded trial.
Incomplete outcome data addressed?
All outcomes
Yes Missing data are balanced in number across
the intervention groups
Free of selective reporting? Yes The report include all the expected out-
comes.
Free of other bias? Yes The trial appears to be free of other sources
of bias.
20Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Fernandez 2006 (Continued)
Intention to treat analysis? No The excluded participants are balanced and
with a justifiable reason
Sample calculation? Yes The sample was calculated considering the
expected incidence of proved and possible
infections
Gulberg 1999
Methods Date of collection: no information provided.
Exclusion from analysis: no information provided.
Follow-up period: 7 days.
Participants Germany
Cirrhotic patients with upper gastrointestinal haemorrhage, without infection, or treat-
ment with antibiotics in the previous week, who underwent TIPS.
Etiology of bleeding: no information provided.
Initial infection assessment: fever, white blood cells, C-reactive protein
Child-Pugh class A/B/C: 29/39/14.
Interventions Experimental: intravenous ceftriaxone, 1g, single dose before TIPS
Control: intravenous ceftriaxone, 2g, single dose before TIPS
Outcomes Bacterial infection after TIPS procedure.
Notes Authors were contacted for the first version of this review.
Risk of bias
Item Authors’ judgement Description
Adequate sequence generation? Unclear No information provided.
Allocation concealment? Unclear No information provided.
Blinding?
All outcomes
No Not a blinded trial.
Incomplete outcome data addressed?
All outcomes
Yes No missing outcome data.
Free of selective reporting? Yes The report include all the expected out-
comes.
Free of other bias? No The report support the intervention effects
on surrogates of infection
21Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Gulberg 1999 (Continued)
Intention to treat analysis? Unclear No information provided.
Sample calculation? No No sample calculation procedure.
Hong 2002
Methods Data collection: 12/1998 to 9/2001.
Exclusion from analysis: death or surgery within 24 h.
Follow-up period: 30 days.
Participants Korea
Hospitalised cirrhotic patients with oesophageal variceal bleeding, without infection or
previous use of antibiotics
Initial infection assessment: physical examination, white blood cells count, liver function
test, ascitic fluid analysis and culture
All patients were enrolled after emergency endoscopic oesophageal variceal ligation
Child-Pugh class: 8.8 ± 1.6 vs 9.1 ± 1.4.
Interventions Experimental: intravenous ciprofloxacin 200 mg b.i.d. for 3 days
Control: no antibiotic prophylaxis.
Outcomes Prevention of bacterial infections.
Notes The authors were contacted via e-mail and no response was received (23-June-2010)
Risk of bias
Item Authors’ judgement Description
Adequate sequence generation? Unclear No information provided.
Allocation concealment? Unclear No information provided.
Blinding?
All outcomes
No Not a blinded trial.
Incomplete outcome data addressed?
All outcomes
Unclear No information provided.
Free of selective reporting? Yes The report include all the expected out-
comes.
Free of other bias? Unclear No information provided.
Intention to treat analysis? Unclear No information provided.
Sample calculation? Unclear No information provided.
22Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Hou 2004
Methods Data collection: 01/2001 to 02/2003.
Exclusion from analysis: positive initial bacteriological sample.
Follow-up period: until death or 3 months.
Participants Taiwan
Hospitalised patients with endoscopy-proven gastroesophageal variceal bleeding without
signs of infection
Etiology of bleeding: endoscopy-proven gastroesophageal variceal bleeding
Endoscopic procedure was completed within 24 h of admission or bleeding onset
Endoscopic variceal ligation or sclerotherapy was preceded by vasoactive agent or balloon
tamponade
Child-Pugh class (A/B/C): 20/64/27.
Interventions Experimental: intravenous ofloxacin 200 mg b.i.d. for 2 days followed by oral ofloxacin
200 mg b.i.d. for 5 days
Control: no antibiotic prophylaxis.
Outcomes Rebleeding rate.
Notes The authors were contacted via e-mail and no response was received (23-June-2010)
Risk of bias
Item Authors’ judgement Description
Adequate sequence generation? Yes The sequence was generated using a ran-
dom number software.
Allocation concealment? Unclear No information provided.
Blinding?
All outcomes
No Not a blinded trial.
Incomplete outcome data addressed?
All outcomes
Yes Missing data are balanced in number across
the intervention groups
Free of selective reporting? Yes The report include all the expected out-
comes.
Free of other bias? Yes The trial appears to be free of other sources
of bias.
Intention to treat analysis? No The exclusion of the patients was not based
on an exclusion rule
Sample calculation? Yes The sample was calculated considering the
expected rebleeding rate
23Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Hsieh 1998
Methods Data collection: 07/95 to 07/96.
Exclusion from analysis: no information.
Follow-up period: 30 days.
Participants Taiwan
Hospitalised cirrhotic patients with upper gastrointestinal haemorrhage, without infec-
tion, or treatment with antibiotics in the previous two weeks.
Etiology of bleeding: oesophageal or gastric varices, peptic ulcers, others.
Initial infection assessment: chest X-ray, blood count, urine/blood/ascites culture.
Source of bleeding determined by endoscopy scheduled within 24 h after enrolment.
Sclerotherapy, or band ligation performed within 48 h after enrolment.
Child-Pugh class A/B/C: 11/64/45.
Interventions Experimental: oral ciprofloxacin, 1 g/day, 7 days.
Control: placebo.
Outcomes Prevention of bacterial infections.
Notes Authors were contacted for the first version of this review.
Risk of bias
Item Authors’ judgement Description
Adequate sequence generation? Unclear No information provided.
Allocation concealment? Unclear No information provided.
Blinding?
All outcomes
Unclear No information provided.
Incomplete outcome data addressed?
All outcomes
Yes No missing outcome data.
Free of selective reporting? Yes The report include all the expected out-
comes.
Free of other bias? Yes The trial appears to be free of other sources
of bias.
Intention to treat analysis? Yes All randomised participants were included
in the analysis.
Sample calculation? No No sample calculation procedure.
24Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Jun 2006
Methods Data collection: 01/2010 to 12/2004.
Exclusion from the analysis: past history of previous gastroesophageal variceal bleeding,
or surgical or endoscopic treatment of gastroesophageal varices; or antibiotics use in the
previous two weeks; or terminal illness (or non hepatic malignancy); or other causes of
gastrointestinal bleeding.
Follow-up period: 22 ± 14 months.
Participants Korea
Hospitalised cirrhotic patients with endoscopy-proven bleeding from oesophageal or
gastric varices, with no signs of infection at admission
Etiology of the bleeding: oesophageal or gastric varices.
Initial infection assessment: complete blood cell count, chest X-ray, urine analysis and
culture, blood culture, and ascitic fluid neutrophil count with culture
Endoscopy procedure was performed within 12h of admission to emergency room
Before endoscopy octreotide was used, followed by endoscopic treatment (variceal liga-
tion or sclerotherapy)
Child-Pugh class A/B/C: 8.7 ± 1.9 and 8.3 ± 2.1.
Interventions Experimental: intravenous cefotaxime 2 g t.i.d for 7 days.
Control: no antibiotic prophylaxis.
Outcomes Rebleeding rate.
Notes The authors were contacted via e-mail and no response was received (23-June-2010)
Risk of bias
Item Authors’ judgement Description
Adequate sequence generation? Yes The sequence was generated using a table
of random numbers.
Allocation concealment? Yes The concealment was done using num-
bered envelopes.
Blinding?
All outcomes
No Not a blinded trial.
Incomplete outcome data addressed?
All outcomes
No The proportion of missing outcomes is
higher in the no prophylaxis group
Free of selective reporting? Yes The report include all the expected out-
comes.
Free of other bias? Yes The trial appears to be free of other sources
of bias.
Intention to treat analysis? No The exclusion of the patients was not based
on an exclusion rule
25Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Jun 2006 (Continued)
Sample calculation? Yes The sample was calculated considering the
expected rebleeding rate
Lata 2005
Methods Data collection: 05/2001 to 11/2003.
Exclusion from analysis: Past history of previous variceal bleeding within 3 months
Follow-up period: 42 days.
Participants Czech Republic.
Hospitalised (intensive care unit) patients with endoscopy proven oesophageal varices
Etiology of bleeding: oesophageal varices.
Initial infection assessment: aerobic blood culture, anaerobic blood culture, perianal
smear, urine examination, throat smear, ascites examination (>250 neutrophils/mL)
The endoscopic treatment was performed within 3 h after admission to intensive care
unit and was preceded by the administration of terlipressin
Schlerotherapy performed together with endoscopy to stop bleeding
Child-Pugh class A/B/C: 4/19/23.
Interventions Experimental:intravenous ampicillin/sulbactam 1.5 g b.i.d. for 7 days
Control: oral or through nasogastric tube norfloxacin 400 mg b.i.d. for 7 days
Outcomes Early and late mortality.
Notes The authors were contacted via e-mail and no response was received (23-June-2010)
Risk of bias
Item Authors’ judgement Description
Adequate sequence generation? Yes The sequence was generated using a system
of accidental numbers
Allocation concealment? Unclear No information provided.
Blinding?
All outcomes
No Not a blinded trial.
Incomplete outcome data addressed?
All outcomes
Yes No missing outcome data.
Free of selective reporting? Yes The report include all the expected out-
comes.
Free of other bias? Yes The trial appears to be free of other sources
of bias.
Intention to treat analysis? Unclear No information provided.
26Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Lata 2005 (Continued)
Sample calculation? No No sample calculation procedure.
Lin 2002
Methods Data collection: 7/1999 to 8/2000.
Exclusion from analysis: life expectancy less than 7 days, fever or infection on entry,
positive bacterial culture on entry, and previous use of antibiotics within 2 weeks prior
to admission.
Initial infection assessment: blood culture, urine culture cell, chest X-ray, sputum culture,
and ascitic fluid culture.
Follow-up period: 7 days.
Participants Taiwan
Hospitalised cirrhotic patients with endoscopy proven upper gastrointestinal bleeding,
without infection or previous use of antibiotics
Endoscopy was performed 12 h within of hospitalisation.
The haemostatic procedure include band ligation plus somastotatin, sandostatin or terli-
pressin (variceal bleeding) or endoscopic injection of water or diluted epinephrine (pep-
tic ulcer bleeding)
Child-Pugh class A/B/C: 27/50/20.
Interventions Experimental: intravenous cefazolin 1 g tid during 3 days and then shift to oral cephalexin
500 mg qid for 4 days
Control: no antibiotic prophylaxis.
Outcomes Prevention of bacterial infections.
Notes The authors were contacted via e-mail and no response was received (23-June-2010)
Risk of bias
Item Authors’ judgement Description
Adequate sequence generation? Unclear No information provided.
Allocation concealment? Unclear No information provided.
Blinding?
All outcomes
No Not a blinded trial.
Incomplete outcome data addressed?
All outcomes
Yes Missing data are balanced in number across
the intervention groups
Free of selective reporting? Yes The report include all the expected out-
comes.
Free of other bias? Yes The trial appears to be free of other sources
of bias.
27Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Lin 2002 (Continued)
Intention to treat analysis? No The exclusion of the patients was based an
exclusion rule.
Sample calculation? No No sample calculation procedure.
Pauwels 1996
Methods Data collection: 12/89 to 03/92.
Exclusion from analysis: infection on admission, undergoing surgery within 24 hs after
admission, or death in the first 12 h.
Follow-up period: up to 10 days after stopping bleeding (four weeks)
Participants France
Hospitalised cirrhotic patients with upper gastrointestinal haemorrhage, without infec-
tion, or treatment with antibiotics in the previous week.
Etiology of bleeding: oesophageal or gastric varices, gastric or duodenal ulceration, and
others
Initial infection assessment: chest X-ray, white blood cell count, urine/blood/ascites
culture.
Source of bleeding determined by endoscopy scheduled within 12 hs after enrolment.
Emergency sclerotherapy performed for patients bleeding from varices.
Child-Pugh class A/B/C: 16/54/49.
Interventions Experimental (Group III): intravenous + oral ciprofloxacin 400mg per day, amoxicillin-
clavulanic acid 3g per day, until three days after cessation of haemorrhage
Control (Group I and II): no antibiotic prophylaxis.
Outcomes Prevention of bacterial infections.
Notes Two group of patients received no intervention and were combined for the purpose of
this review
Authors were contacted for the first version of this review.
Risk of bias
Item Authors’ judgement Description
Adequate sequence generation? Yes The sequence was generated using a table
of random numbers.
Allocation concealment? Unclear No information provided.
Blinding?
All outcomes
No Not a blinded trial.
Incomplete outcome data addressed?
All outcomes
Yes Missing data are balanced in number across
the intervention groups
28Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Pauwels 1996 (Continued)
Free of selective reporting? Yes The report include all the expected out-
comes.
Free of other bias? Yes The trial appears to be free of other sources
of bias.
Intention to treat analysis? No The exclusion of the patients was based on
an exclusion rule
Sample calculation? No No sample calculation procedure.
Rimola 1985
Methods Data collection: no information provided.
Exclusion from analysis: underwent surgery, or died within 24 hs after admission.
Follow-up period: up to 10 days after stopping bleeding (four weeks)
Participants Spain
Hospitalised cirrhotic patients with upper gastrointestinal haemorrhage, without infec-
tion, or treatment with antibiotics in the previous two weeks.
Etiology of bleeding: oesophageal varices (128 patients), gastric haemorrhage ( 10 pa-
tients), peptic ulcers (8 patients).
Initial infection assessment: chest X-ray, white blood cell count, urine/blood/ascites
culture.
Source of bleeding determined by endoscopy scheduled within 24 hs after enrolment.
Emergency sclerotherapy performed for patients bleeding from varices.
Child-Pugh class A/B/C: not reported.
Interventions Experimental (non-absorbable antibiotics):
Group Ia - oral gentamicin (200mg) + vancomycin (500 mg) + nystatin (10ˆ6 UI) every
six hs, until two days after cessation of haemorrhage.
Group Ib - neomycin (1 gm) + colistin (1.5 x 10ˆ6 UI) + nystatin (10ˆ6 UI) every six
hs, until two days after cessation of haemorrhage
Control (Group II): no antibiotic prophylaxis.
Outcomes Prevent bacterial infections.
Notes The antibiotic therapy regimen was modified after inclusion of the first 40 patients in
the experimental group because of budget constraints.
The two group of patients treated with antibiotics were combined for the purpose of
this review
Authors were contacted for the first version of this review, and additional information
was received
Risk of bias
Item Authors’ judgement Description
29Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Rimola 1985 (Continued)
Adequate sequence generation? Yes The sequence was generated using random
number table.
Allocation concealment? Yes Adequate, this item keeps as the first review.
Blinding?
All outcomes
No Not a blinded trial.
Incomplete outcome data addressed?
All outcomes
No The proportion of missing outcomes is not
balanced among the groups
Free of selective reporting? Yes The report include all the expected out-
comes.
Free of other bias? No The antibiotic therapy regimen was modi-
fied after inclusion of the first 40 patients
in the experimental group because of bud-
get constraints
Intention to treat analysis? No The exclusion of the patients was based on
an exclusion rule
Sample calculation? No No sample calculation procedure.
Rolando 1993
Methods Data collection: no information provided.
Exclusion from analysis: bleeding not related to variceal bleeding.
Follow-up period: 7 days.
Participants UK
Hospitalised cirrhotic patients with upper gastrointestinal haemorrhage and high risk of
infection, without infection, or treatment with antibiotics in the previous two weeks.
Etiology of bleeding: all patients had oesophageal varices.
Endoscopic sclerotherapy was performed after randomisation.
Initial infection assessment: chest X-ray, white blood cell count, urine/blood/ascites
culture.
Child-Pugh class A/B/C: not reported.
Interventions Experimental: intravenous imipenem + cilastin, 500 mg before and after the sclerotherapy
Control: intravenous dextrose-saline solution.
Outcomes Prevent bacterial infections.
Notes Authors were contacted for the first version of this review, and additional information
was received
Risk of bias
30Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Rolando 1993 (Continued)
Item Authors’ judgement Description
Adequate sequence generation? Yes The sequence was generated using a com-
puter-based table of random numbers
Allocation concealment? Yes Patients assigned sequentially, sealed
opaque envelopes used
Blinding?
All outcomes
No Not a blinded trial.
Incomplete outcome data addressed?
All outcomes
Yes Reassons for missing data are based on the
violation of the protocol
Free of selective reporting? Yes The report include all the expected out-
comes.
Free of other bias? Unclear The trial appears to be free of other sources
of bias.
Intention to treat analysis? No The exclusion of the patients was based on
an exclusion rule
Sample calculation? No No sample calculation procedure.
Sabat 1998
Methods Data collection: 06/93 to 06/95.
Exclusion from analysis: occult infection, or underwent surgery, or died within 24 hs
after admission.
Follow-up period: up to three weeks.
Participants Spain
Hospitalised cirrhotic patients with upper gastrointestinal haemorrhage and high risk of
infection, without infection, or treatment with antibiotics in the previous two weeks.
Etiology of bleeding: no information.
Initial infection assessment: chest X-ray, white blood cell count, urine/blood/ascites
culture.
Source of bleeding determined by endoscopy scheduled within four hs after enrolment.
Emergency sclerotherapy performed for patients bleeding from varices.
Child-Pugh class A/B/C: 4/31/11.
Interventions Experimental: oral norfloxacin 800 mg/day, during seven days plus intravenous ceftri-
axone 2g/day the first three days
Control: oral norfloxacin 800 mg/day, seven days.
Outcomes Prevent bacterial infections.
31Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Sabat 1998 (Continued)
Notes The initial sample size was calculated to be 152 patients. An interim analysis was done
after 1/3 of patients were included, a statistical significant result was found and the trial
was stopped
Authors were contacted for the first version of this review.
Risk of bias
Item Authors’ judgement Description
Adequate sequence generation? Unclear No information provided.
Allocation concealment? Unclear No information provided.
Blinding?
All outcomes
No Not a blinded trial.
Incomplete outcome data addressed?
All outcomes
Yes Reassons for missing data are based on the
violation of the protocol
Free of selective reporting? Yes The report include all the expected out-
comes.
Free of other bias? No The trials was stopped due to economical
differences and not due to primary out-
come differences
Intention to treat analysis? No The exclusion of the patients was based on
an exclusion rule
Sample calculation? Unclear The was calculated considering the primary
outcome, but the trial was stopped consid-
ering differences in secondary outcomes
Selby 1994
Methods Data collection: 08/89 to 12/91.
Exclusion from analysis: no information provided.
Follow-up period: up to 24 hs.
Participants Australia
Hospitalised cirrhotic patients with upper gastrointestinal haemorrhage and high risk of
infection, without infection, or treatment with antibiotics in the previous two weeks.
Etiology of bleeding: no information provided.
All patients underwent emergency section of sclerotherapy, followed by further sections
in weekly intervals.
Initial infection assessment: chest X-ray, white blood cell count, urine/blood/ascites
culture.
Child-Pugh class A/B/C: 8/18/13.
32Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Selby 1994 (Continued)
Interventions Experimental: intravenous cefotaxime, 1 g immediately before sclerotherapy
Control: no antibiotic prophylaxis.
Outcomes Prevent bacterial infections.
Notes Authors were contacted for the first version of this review.
Risk of bias
Item Authors’ judgement Description
Adequate sequence generation? Yes The sequence was generated using a table
of random numbers.
Allocation concealment? Yes The treatment was contained in sealed en-
velopes.
Blinding?
All outcomes
No Not a blinded trial.
Incomplete outcome data addressed?
All outcomes
Yes Reassons for missing data are based on the
violation of the protocol
Free of selective reporting? Yes The report include all the expected out-
comes.
Free of other bias? Unclear The trial appears to be free of other sources
of bias.
Intention to treat analysis? No The exclusion of the patients was based on
an exclusion rule
Sample calculation? No No sample calculation procedure.
Soriano 1992
Methods Data collection: 08/89 to 06/91.
Exclusion from analysis: underwent surgery, or died within 24 hs after admission.
Follow-up period: up to four weeks.
Participants Spain
Hospitalised cirrhotic patients with upper gastrointestinal haemorrhage, without infec-
tion or treatment with antibiotics in the previous two weeks.
Etiology of bleeding: oesophageal varices, gastric haemorrhage, peptic ulcers, and others.
Initial infection assessment: chest X-ray, white blood cell count, urine/blood/ascites
culture.
Source of bleeding determined by endoscopy scheduled within four hs after enrolment.
Emergency sclerotherapy performed for patients bleeding from varices.
33Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Soriano 1992 (Continued)
Child-Pugh class A/B/C: 40/55/24.
Interventions Experimental: oral norfloxacin 800 mg/day during seven days.
Control: no antibiotic prophylaxis.
Outcomes Prevent bacterial infection.
Notes Authors were contacted for the first version of this review.
Risk of bias
Item Authors’ judgement Description
Adequate sequence generation? Yes The sequence was generated using a table
of random numbers.
Allocation concealment? Unclear No information provided.
Blinding?
All outcomes
No Not a blinded trial.
Incomplete outcome data addressed?
All outcomes
Yes Reassons for missing data are based on the
violation of the protocol and are balanced
across the groups
Free of selective reporting? Yes The report include all the expected out-
comes.
Free of other bias? Yes The trial appears to be free of other sources
of bias.
Intention to treat analysis? No The exclusion of the patients was based on
an exclusion rule
Sample calculation? No No sample calculation procedure.
Spanish Group 1998
Methods Data collection: no information provided.
Exclusion from analysis: no information provided.
Follow-up period: first 10 days of the bleeding episode.
Participants Spain
Cirrhotic patients with upper gastrointestinal haemorrhage.
Etiology of bleeding: no information provided.
Initial infection assessment: no information provided.
Source of bleeding determined by: no information.
Child-Pugh class A/B/C: no information provided.
34Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Spanish Group 1998 (Continued)
Interventions Experimental: oral norfloxacin, 800 mg/day, five days.
Control: oral ofloxacin, 400 mg/day, five days.
Outcomes Prevent bacterial infections.
Notes Data extracted from an abstract, no publication available.
Authors were contacted for the first version of this review, and additional information
was received
Risk of bias
Item Authors’ judgement Description
Adequate sequence generation? Unclear No information provided.
Allocation concealment? Unclear No information provided.
Blinding?
All outcomes
Unclear No information provided.
Incomplete outcome data addressed?
All outcomes
Unclear Insufficient information to permit judge-
ment.
Free of selective reporting? Unclear Insufficient information to permit judge-
ment.
Free of other bias? Unclear Insufficient information to permit judge-
ment.
Intention to treat analysis? Unclear No information provided.
Sample calculation? Unclear No information provided.
Zacharof 1997
Methods Data collection: no information provided.
Exclusion from analysis: no information provided.
Follow-up period: no information provided.
Participants Greece
Hospitalised cirrhotic patients with upper gastrointestinal haemorrhage.
Etiology of bleeding: no information provided.
Source of bleeding determined by emergency endoscopy.
Child-Pugh class A/B/C: not information provided.
Interventions Experimental: oral ciprofloxacin 500 mg/day during seven days
Control: no antibiotic prophylaxis.
35Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Zacharof 1997 (Continued)
Outcomes Prevent bacterial infections.
Notes Data extracted from an abstract, and confirmed by the authors
Authors were contacted for the first version of this review, and additional information
was received
Risk of bias
Item Authors’ judgement Description
Adequate sequence generation? Yes The sequence was generated using a table
of random numbers.
Allocation concealment? Yes Sequentially administered by a pharmacist
not involved in the trial
Blinding?
All outcomes
No Not a blinded trial.
Incomplete outcome data addressed?
All outcomes
Yes The report include all the expected out-
comes.
Free of selective reporting? Unclear Insufficient information to permit judge-
ment.
Free of other bias? Unclear Insufficient information to permit judge-
ment.
Intention to treat analysis? Unclear No information provided.
Sample calculation? Unclear No information provided.
b.i.d. = twice (two times) a day.
hs = hours.
Characteristics of excluded studies [ordered by study ID]
Study Reason for exclusion
Gines 1990 Spain
Randomised clinical trial.
Through communication with the first author it was clarified that the patients did not have upper gastrointestinal
bleeding
36Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)
Goulis 1998 UK
Observational study. Not a randomised trial.
Henrion 1992 Belgium
Controlled clinical study.
Inadequate allocation concealment, alternate method.
Husova 2005 Czech Republic
Observational study. Not a randomised trial.
Novella 1997 Spain
Randomised clinical trial.
Through communication with the first author it was clarified that the patients did not have upper gastrointestinal
bleeding
Pohl 2004 Germany
Retrospective cohort study.
Pulanic 1989 Yugoslavia
Randomised clinical trial.
No clinical outcomes, only laboratory variables after antibiotic prophylaxis
Wilbur 2005 Canada
Retrospective cohort study.
Zhao 2002 China
Not a randomised trial.
RCT - randomised clinical trial.
CCT - controlled clinical trial.
37Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
D A T A A N D A N A L Y S E S
Comparison 1. Antibiotics versus no intervention/placebo
Outcome or subgroup titleNo. of
studies
No. of
participants Statistical method Effect size
1 Mortality 12 1241 Risk Ratio (M-H, Fixed, 95% CI) 0.79 [0.63, 0.98]
2 Mortality from bacterial
infections
6 761 Risk Ratio (M-H, Fixed, 95% CI) 0.43 [0.19, 0.97]
3 Bacterial infections 12 1241 Risk Ratio (M-H, Random, 95% CI) 0.36 [0.27, 0.49]
4 Bacteremia 9 987 Risk Ratio (M-H, Fixed, 95% CI) 0.25 [0.15, 0.40]
5 Pneumonia 9 1041 Risk Ratio (M-H, Fixed, 95% CI) 0.45 [0.27, 0.75]
6 Spontaneous bacterial peritonitis 8 890 Risk Ratio (M-H, Fixed, 95% CI) 0.29 [0.15, 0.57]
7 Urinary tract infections 9 1098 Risk Ratio (M-H, Fixed, 95% CI) 0.23 [0.13, 0.41]
8 Other infections 3 257 Risk Ratio (M-H, Fixed, 95% CI) 0.43 [0.12, 1.56]
9 Drop outs before end of study 8 919 Risk Ratio (M-H, Fixed, 95% CI) 1.07 [0.76, 1.51]
10 Mortality according to trial
sample size
12 1241 Risk Ratio (M-H, Fixed, 95% CI) 0.79 [0.63, 0.98]
10.1 Sample size smaller than
101 patients
5 340 Risk Ratio (M-H, Fixed, 95% CI) 0.71 [0.44, 1.15]
10.2 Sample size larger than
100 patients
7 901 Risk Ratio (M-H, Fixed, 95% CI) 0.81 [0.63, 1.03]
11 Bacterial infections according
to trial sample size
12 1241 Risk Ratio (M-H, Fixed, 95% CI) 0.37 [0.30, 0.46]
11.1 Sample size smaller than
101 patients
5 340 Risk Ratio (M-H, Fixed, 95% CI) 0.42 [0.29, 0.62]
11.2 Sample size larger than
100 patients
7 901 Risk Ratio (M-H, Fixed, 95% CI) 0.35 [0.27, 0.46]
12 Mortality sensitivity analysis
worst-best case
8 978 Risk Ratio (M-H, Random, 95% CI) 1.45 [1.04, 2.02]
13 Mortality sensitivity analysis
best-worst case
8 969 Risk Ratio (M-H, Fixed, 95% CI) 0.48 [0.38, 0.60]
14 Mortality from bacterial
infections sensitivity analysis
worst-best case
5 708 Risk Ratio (M-H, Random, 95% CI) 3.30 [1.43, 7.62]
15 Mortality from bacterial
infections sensitivity analysis
best-worst case
5 699 Risk Ratio (M-H, Fixed, 95% CI) 0.14 [0.06, 0.31]
16 Bacterial infections sensitivity
analysis worst-best case
8 978 Risk Ratio (M-H, Fixed, 95% CI) 0.77 [0.63, 0.93]
17 Bacterial infections sensitivity
analysis best-worst case
8 969 Risk Ratio (M-H, Random, 95% CI) 0.26 [0.16, 0.43]
18 Mortality according to the
antibiotic used
12 1241 Risk Ratio (M-H, Fixed, 95% CI) 0.79 [0.63, 0.98]
18.1 Quinolones 5 473 Risk Ratio (M-H, Fixed, 95% CI) 0.88 [0.61, 1.27]
18.2 Quinolones +
beta-lactams
2 264 Risk Ratio (M-H, Fixed, 95% CI) 0.74 [0.42, 1.31]
18.3 Cephalosporins 3 255 Risk Ratio (M-H, Fixed, 95% CI) 0.72 [0.46, 1.11]
38Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
18.4 Other antibiotics 2 249 Risk Ratio (M-H, Fixed, 95% CI) 0.76 [0.50, 1.17]
19 Mortality from bacterial
infections according to the
antibiotic used
6 761 Risk Ratio (M-H, Fixed, 95% CI) 0.43 [0.19, 0.97]
19.1 Quinolones 2 248 Risk Ratio (M-H, Fixed, 95% CI) 0.76 [0.18, 3.34]
19.2 Quinolones + beta
lactam
1 147 Risk Ratio (M-H, Fixed, 95% CI) 0.67 [0.08, 5.80]
19.3 Cephalosporins 2 217 Risk Ratio (M-H, Fixed, 95% CI) 0.44 [0.10, 1.95]
19.4 Others 1 149 Risk Ratio (M-H, Fixed, 95% CI) 0.14 [0.02, 1.15]
20 Bacterial infections according
to the antibiotic used
12 1241 Risk Ratio (M-H, Fixed, 95% CI) 0.36 [0.29, 0.45]
20.1 Quinolones 5 473 Risk Ratio (M-H, Fixed, 95% CI) 0.27 [0.18, 0.39]
20.2 Quinolones +
beta-lactams
2 264 Risk Ratio (M-H, Fixed, 95% CI) 0.38 [0.23, 0.62]
20.3 Cephalosporins 3 255 Risk Ratio (M-H, Fixed, 95% CI) 0.16 [0.05, 0.48]
20.4 Others 2 249 Risk Ratio (M-H, Fixed, 95% CI) 0.57 [0.41, 0.81]
21 Rebleeding 3 280 Risk Ratio (M-H, Fixed, 95% CI) 0.53 [0.38, 0.74]
22 Early rebleeding (up to 7 days) 3 280 Risk Ratio (M-H, Fixed, 95% CI) 0.24 [0.12, 0.50]
23 Days of hospitalisation 7 769 Mean Difference (IV, Random, 95% CI) -0.79 [-1.84, 0.26]
23.1 Intensive care unit 2 264 Mean Difference (IV, Random, 95% CI) -0.27 [-1.55, 1.00]
23.2 Full-lenght 5 505 Mean Difference (IV, Random, 95% CI) -1.91 [-3.80, -0.02]
Analysis 1.1. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 1 Mortality.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 1 Mortality
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Rimola 1985 18/74 23/75 16.3 % 0.79 [ 0.47, 1.34 ]
Soriano 1992 4/64 7/64 5.0 % 0.57 [ 0.18, 1.86 ]
Rolando 1993 10/50 14/50 10.0 % 0.71 [ 0.35, 1.45 ]
Blaise 1994 11/58 16/59 11.3 % 0.70 [ 0.36, 1.38 ]
Selby 1994 2/19 5/19 3.6 % 0.40 [ 0.09, 1.81 ]
Pauwels 1996 4/40 13/107 5.1 % 0.82 [ 0.29, 2.38 ]
Zacharof 1997 8/35 8/30 6.2 % 0.86 [ 0.37, 2.01 ]
Hsieh 1998 13/60 18/60 12.9 % 0.72 [ 0.39, 1.34 ]
Hong 2002 1/20 1/20 0.7 % 1.00 [ 0.07, 14.90 ]
0.01 0.1 1 10 100
Favours antibiotic Favours control
(Continued . . . )
39Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(. . . Continued)Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Lin 2002 2/47 3/50 2.1 % 0.71 [ 0.12, 4.06 ]
Hou 2004 16/59 13/61 9.1 % 1.27 [ 0.67, 2.41 ]
Jun 2006 20/62 24/58 17.7 % 0.78 [ 0.49, 1.25 ]
Total (95% CI) 588 653 100.0 % 0.79 [ 0.63, 0.98 ]
Total events: 109 (Antibiotic), 145 (Control)
Heterogeneity: Chi2 = 3.58, df = 11 (P = 0.98); I2 =0.0%
Test for overall effect: Z = 2.16 (P = 0.031)
0.01 0.1 1 10 100
Favours antibiotic Favours control
Analysis 1.2. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 2 Mortality from bacterial
infections.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 2 Mortality from bacterial infections
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Rimola 1985 1/74 7/75 37.3 % 0.14 [ 0.02, 1.15 ]
Soriano 1992 1/64 2/64 10.7 % 0.50 [ 0.05, 5.38 ]
Pauwels 1996 1/40 4/107 11.7 % 0.67 [ 0.08, 5.80 ]
Lin 2002 0/47 2/50 13.0 % 0.21 [ 0.01, 4.31 ]
Hou 2004 2/59 2/61 10.6 % 1.03 [ 0.15, 7.10 ]
Jun 2006 2/62 3/58 16.6 % 0.62 [ 0.11, 3.60 ]
Total (95% CI) 346 415 100.0 % 0.43 [ 0.19, 0.97 ]
Total events: 7 (Antibiotic), 20 (Control)
Heterogeneity: Chi2 = 2.43, df = 5 (P = 0.79); I2 =0.0%
Test for overall effect: Z = 2.02 (P = 0.043)
0.01 0.1 1 10 100
Favours antibiotic Favours control
40Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.3. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 3 Bacterial infections.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 3 Bacterial infections
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N
M-H,Random,95%
CI
M-H,Random,95%
CI
Rimola 1985 16/74 32/75 15.9 % 0.51 [ 0.31, 0.84 ]
Soriano 1992 12/64 28/64 14.0 % 0.43 [ 0.24, 0.77 ]
Rolando 1993 17/50 26/50 17.0 % 0.65 [ 0.41, 1.05 ]
Selby 1994 1/19 6/19 2.1 % 0.17 [ 0.02, 1.26 ]
Blaise 1994 9/58 30/59 12.3 % 0.31 [ 0.16, 0.59 ]
Pauwels 1996 6/40 32/107 9.6 % 0.50 [ 0.23, 1.11 ]
Zacharof 1997 4/35 16/30 7.1 % 0.21 [ 0.08, 0.57 ]
Hsieh 1998 6/60 27/60 9.4 % 0.22 [ 0.10, 0.50 ]
Lin 2002 0/47 6/50 1.1 % 0.08 [ 0.00, 1.41 ]
Hong 2002 2/20 9/20 4.0 % 0.22 [ 0.05, 0.90 ]
Hou 2004 2/59 16/61 3.9 % 0.13 [ 0.03, 0.54 ]
Jun 2006 2/62 9/58 3.6 % 0.21 [ 0.05, 0.92 ]
Total (95% CI) 588 653 100.0 % 0.36 [ 0.27, 0.49 ]
Total events: 77 (Antibiotic), 237 (Control)
Heterogeneity: Tau2 = 0.08; Chi2 = 16.30, df = 11 (P = 0.13); I2 =33%
Test for overall effect: Z = 6.64 (P < 0.00001)
0.01 0.1 1 10 100
Favours antibiotic Favours control
41Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.4. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 4 Bacteremia.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 4 Bacteremia
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Soriano 1992 0/64 6/64 8.5 % 0.08 [ 0.00, 1.34 ]
Rolando 1993 5/50 10/50 13.1 % 0.50 [ 0.18, 1.36 ]
Selby 1994 1/19 6/19 7.9 % 0.17 [ 0.02, 1.26 ]
Blaise 1994 6/58 17/59 22.1 % 0.36 [ 0.15, 0.85 ]
Pauwels 1996 2/40 16/107 11.4 % 0.33 [ 0.08, 1.39 ]
Hsieh 1998 0/60 14/60 19.0 % 0.03 [ 0.00, 0.57 ]
Lin 2002 0/47 4/50 5.7 % 0.12 [ 0.01, 2.13 ]
Hou 2004 0/59 7/61 9.7 % 0.07 [ 0.00, 1.18 ]
Jun 2006 2/62 2/58 2.7 % 0.94 [ 0.14, 6.43 ]
Total (95% CI) 459 528 100.0 % 0.25 [ 0.15, 0.40 ]
Total events: 16 (Antibiotic), 82 (Control)
Heterogeneity: Chi2 = 8.35, df = 8 (P = 0.40); I2 =4%
Test for overall effect: Z = 5.57 (P < 0.00001)
0.01 0.1 1 10 100
Favours antibiotic Favours control
42Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.5. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 5 Pneumonia.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 5 Pneumonia
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Rimola 1985 2/74 4/75 8.9 % 0.51 [ 0.10, 2.68 ]
Soriano 1992 4/64 4/64 8.9 % 1.00 [ 0.26, 3.83 ]
Rolando 1993 8/50 7/50 15.6 % 1.14 [ 0.45, 2.91 ]
Blaise 1994 2/58 18/59 39.8 % 0.11 [ 0.03, 0.47 ]
Pauwels 1996 0/40 4/107 5.5 % 0.29 [ 0.02, 5.32 ]
Hsieh 1998 2/60 3/60 6.7 % 0.67 [ 0.12, 3.85 ]
Hong 2002 0/20 2/20 5.6 % 0.20 [ 0.01, 3.92 ]
Hou 2004 0/59 2/61 5.5 % 0.21 [ 0.01, 4.22 ]
Jun 2006 0/62 1/58 3.5 % 0.31 [ 0.01, 7.51 ]
Total (95% CI) 487 554 100.0 % 0.45 [ 0.27, 0.75 ]
Total events: 18 (Antibiotic), 45 (Control)
Heterogeneity: Chi2 = 9.70, df = 8 (P = 0.29); I2 =18%
Test for overall effect: Z = 3.05 (P = 0.0023)
0.01 0.1 1 10 100
Favours antibiotic Favours control
43Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.6. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 6 Spontaneous bacterial
peritonitis.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 6 Spontaneous bacterial peritonitis
Study or subgroup Antibiotic Control Risk Ratio Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Soriano 1992 2/64 4/64 0.50 [ 0.09, 2.63 ]
Rolando 1993 1/50 6/50 0.17 [ 0.02, 1.33 ]
Blaise 1994 3/58 7/59 0.44 [ 0.12, 1.60 ]
Selby 1994 0/19 0/19 0.0 [ 0.0, 0.0 ]
Pauwels 1996 1/40 11/107 0.24 [ 0.03, 1.82 ]
Hsieh 1998 2/60 8/60 0.25 [ 0.06, 1.13 ]
Hou 2004 1/59 2/61 0.52 [ 0.05, 5.55 ]
Jun 2006 0/62 4/58 0.10 [ 0.01, 1.89 ]
Total (95% CI) 412 478 0.29 [ 0.15, 0.57 ]
Total events: 10 (Antibiotic), 42 (Control)
Heterogeneity: Chi2 = 1.82, df = 6 (P = 0.94); I2 =0.0%
Test for overall effect: Z = 3.59 (P = 0.00033)
0.01 0.1 1 10 100
Favours antibiotic Favours control
44Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.7. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 7 Urinary tract infections.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 7 Urinary tract infections
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Rimola 1985 3/74 9/75 15.5 % 0.34 [ 0.10, 1.20 ]
Soriano 1992 0/64 11/64 19.9 % 0.04 [ 0.00, 0.72 ]
Rolando 1993 3/50 6/50 10.4 % 0.50 [ 0.13, 1.89 ]
Blaise 1994 1/58 10/59 17.2 % 0.10 [ 0.01, 0.77 ]
Pauwels 1996 0/40 4/107 4.3 % 0.29 [ 0.02, 5.32 ]
Hsieh 1998 3/60 11/60 19.0 % 0.27 [ 0.08, 0.93 ]
Lin 2002 0/47 1/50 2.5 % 0.35 [ 0.01, 8.48 ]
Hou 2004 1/59 5/61 8.5 % 0.21 [ 0.02, 1.72 ]
Jun 2006 0/62 1/58 2.7 % 0.31 [ 0.01, 7.51 ]
Total (95% CI) 514 584 100.0 % 0.23 [ 0.13, 0.41 ]
Total events: 11 (Antibiotic), 58 (Control)
Heterogeneity: Chi2 = 3.86, df = 8 (P = 0.87); I2 =0.0%
Test for overall effect: Z = 4.91 (P < 0.00001)
0.01 0.1 1 10 100
Favours antibiotic Favours control
45Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.8. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 8 Other infections.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 8 Other infections
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Lin 2002 0/47 1/50 20.8 % 0.35 [ 0.01, 8.48 ]
Hong 2002 2/20 4/20 57.1 % 0.50 [ 0.10, 2.43 ]
Jun 2006 0/62 1/58 22.1 % 0.31 [ 0.01, 7.51 ]
Total (95% CI) 129 128 100.0 % 0.43 [ 0.12, 1.56 ]
Total events: 2 (Antibiotic), 6 (Control)
Heterogeneity: Chi2 = 0.09, df = 2 (P = 0.96); I2 =0.0%
Test for overall effect: Z = 1.29 (P = 0.20)
Test for subgroup differences: Not applicable
0.01 0.1 1 10 100
Favours experimental Favours control
46Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.9. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 9 Drop outs before end of
study.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 9 Drop outs before end of study
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Rimola 1985 6/74 3/75 5.7 % 2.03 [ 0.53, 7.80 ]
Soriano 1992 4/64 5/64 9.6 % 0.80 [ 0.23, 2.84 ]
Rolando 1993 3/50 0/50 1.0 % 7.00 [ 0.37, 132.10 ]
Selby 1994 0/19 1/19 2.9 % 0.33 [ 0.01, 7.70 ]
Blaise 1994 12/58 14/59 26.7 % 0.87 [ 0.44, 1.72 ]
Pauwels 1996 10/40 18/107 18.9 % 1.49 [ 0.75, 2.94 ]
Hou 2004 9/59 7/61 13.3 % 1.33 [ 0.53, 3.34 ]
Jun 2006 6/62 11/58 21.9 % 0.51 [ 0.20, 1.29 ]
Total (95% CI) 426 493 100.0 % 1.07 [ 0.76, 1.51 ]
Total events: 50 (Antibiotic), 59 (Control)
Heterogeneity: Chi2 = 7.06, df = 7 (P = 0.42); I2 =1%
Test for overall effect: Z = 0.40 (P = 0.69)
0.01 0.1 1 10 100
Favours antibiotic Favours control
47Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.10. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 10 Mortality according
to trial sample size.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 10 Mortality according to trial sample size
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
1 Sample size smaller than 101 patients
Rolando 1993 10/50 14/50 10.0 % 0.71 [ 0.35, 1.45 ]
Selby 1994 2/19 5/19 3.6 % 0.40 [ 0.09, 1.81 ]
Zacharof 1997 8/35 8/30 6.2 % 0.86 [ 0.37, 2.01 ]
Hong 2002 1/20 1/20 0.7 % 1.00 [ 0.07, 14.90 ]
Lin 2002 2/47 3/50 2.1 % 0.71 [ 0.12, 4.06 ]
Subtotal (95% CI) 171 169 22.5 % 0.71 [ 0.44, 1.15 ]
Total events: 23 (Antibiotic), 31 (Control)
Heterogeneity: Chi2 = 0.80, df = 4 (P = 0.94); I2 =0.0%
Test for overall effect: Z = 1.38 (P = 0.17)
2 Sample size larger than 100 patients
Rimola 1985 18/74 23/75 16.3 % 0.79 [ 0.47, 1.34 ]
Soriano 1992 4/64 7/64 5.0 % 0.57 [ 0.18, 1.86 ]
Blaise 1994 11/58 16/59 11.3 % 0.70 [ 0.36, 1.38 ]
Pauwels 1996 4/40 13/107 5.1 % 0.82 [ 0.29, 2.38 ]
Hsieh 1998 13/60 18/60 12.9 % 0.72 [ 0.39, 1.34 ]
Hou 2004 16/59 13/61 9.1 % 1.27 [ 0.67, 2.41 ]
Jun 2006 20/62 24/58 17.7 % 0.78 [ 0.49, 1.25 ]
Subtotal (95% CI) 417 484 77.5 % 0.81 [ 0.63, 1.03 ]
Total events: 86 (Antibiotic), 114 (Control)
Heterogeneity: Chi2 = 2.61, df = 6 (P = 0.86); I2 =0.0%
Test for overall effect: Z = 1.71 (P = 0.087)
Total (95% CI) 588 653 100.0 % 0.79 [ 0.63, 0.98 ]
Total events: 109 (Antibiotic), 145 (Control)
Heterogeneity: Chi2 = 3.58, df = 11 (P = 0.98); I2 =0.0%
Test for overall effect: Z = 2.16 (P = 0.031)
0.01 0.1 1 10 100
Favours antibiotic Favours control
48Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.11. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 11 Bacterial infections
according to trial sample size.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 11 Bacterial infections according to trial sample size
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
1 Sample size smaller than 101 patients
Rolando 1993 17/50 26/50 11.8 % 0.65 [ 0.41, 1.05 ]
Selby 1994 1/19 6/19 2.7 % 0.17 [ 0.02, 1.26 ]
Zacharof 1997 4/35 16/30 7.8 % 0.21 [ 0.08, 0.57 ]
Hong 2002 2/20 9/20 4.1 % 0.22 [ 0.05, 0.90 ]
Lin 2002 2/47 3/50 1.3 % 0.71 [ 0.12, 4.06 ]
Subtotal (95% CI) 171 169 27.8 % 0.42 [ 0.29, 0.62 ]
Total events: 26 (Antibiotic), 60 (Control)
Heterogeneity: Chi2 = 7.15, df = 4 (P = 0.13); I2 =44%
Test for overall effect: Z = 4.37 (P = 0.000012)
2 Sample size larger than 100 patients
Rimola 1985 16/74 32/75 14.4 % 0.51 [ 0.31, 0.84 ]
Soriano 1992 12/64 28/64 12.7 % 0.43 [ 0.24, 0.77 ]
Blaise 1994 9/58 30/59 13.5 % 0.31 [ 0.16, 0.59 ]
Pauwels 1996 6/40 32/107 7.9 % 0.50 [ 0.23, 1.11 ]
Hsieh 1998 6/60 27/60 12.3 % 0.22 [ 0.10, 0.50 ]
Hou 2004 2/59 16/61 7.1 % 0.13 [ 0.03, 0.54 ]
Jun 2006 2/62 9/58 4.2 % 0.21 [ 0.05, 0.92 ]
Subtotal (95% CI) 417 484 72.2 % 0.35 [ 0.27, 0.46 ]
Total events: 53 (Antibiotic), 174 (Control)
Heterogeneity: Chi2 = 7.00, df = 6 (P = 0.32); I2 =14%
Test for overall effect: Z = 7.49 (P < 0.00001)
Total (95% CI) 588 653 100.0 % 0.37 [ 0.30, 0.46 ]
Total events: 79 (Antibiotic), 234 (Control)
Heterogeneity: Chi2 = 15.28, df = 11 (P = 0.17); I2 =28%
Test for overall effect: Z = 8.68 (P < 0.00001)
0.01 0.1 1 10 100
Favours antibiotic Favours control
49Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.12. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 12 Mortality sensitivity
analysis worst-best case.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 12 Mortality sensitivity analysis worst-best case
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N
M-H,Random,95%
CI
M-H,Random,95%
CI
Rimola 1985 24/74 23/78 16.4 % 1.10 [ 0.68, 1.77 ]
Soriano 1992 8/64 7/69 8.1 % 1.23 [ 0.47, 3.20 ]
Rolando 1993 13/50 14/50 12.7 % 0.93 [ 0.49, 1.77 ]
Blaise 1994 23/58 16/73 15.0 % 1.81 [ 1.06, 3.10 ]
Selby 1994 2/19 5/20 4.0 % 0.42 [ 0.09, 1.92 ]
Pauwels 1996 14/40 13/125 12.4 % 3.37 [ 1.73, 6.55 ]
Hou 2004 25/59 13/68 14.2 % 2.22 [ 1.25, 3.93 ]
Jun 2006 26/62 24/69 17.3 % 1.21 [ 0.78, 1.86 ]
Total (95% CI) 426 552 100.0 % 1.45 [ 1.04, 2.02 ]
Total events: 135 (Antibiotic), 115 (Control)
Heterogeneity: Tau2 = 0.12; Chi2 = 15.40, df = 7 (P = 0.03); I2 =55%
Test for overall effect: Z = 2.20 (P = 0.028)
0.01 0.1 1 10 100
Favours antibiotic Favours control
50Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.13. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 13 Mortality sensitivity
analysis best-worst case.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 13 Mortality sensitivity analysis best-worst case
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Rimola 1985 18/80 26/75 15.7 % 0.65 [ 0.39, 1.08 ]
Soriano 1992 4/68 12/64 7.2 % 0.31 [ 0.11, 0.92 ]
Rolando 1993 10/53 14/50 8.4 % 0.67 [ 0.33, 1.38 ]
Blaise 1994 11/70 30/59 19.1 % 0.31 [ 0.17, 0.56 ]
Selby 1994 2/19 6/19 3.5 % 0.33 [ 0.08, 1.45 ]
Pauwels 1996 4/50 31/107 11.6 % 0.28 [ 0.10, 0.74 ]
Hou 2004 16/68 20/61 12.3 % 0.72 [ 0.41, 1.26 ]
Jun 2006 20/68 35/58 22.1 % 0.49 [ 0.32, 0.74 ]
Total (95% CI) 476 493 100.0 % 0.48 [ 0.38, 0.60 ]
Total events: 85 (Antibiotic), 174 (Control)
Heterogeneity: Chi2 = 8.31, df = 7 (P = 0.31); I2 =16%
Test for overall effect: Z = 6.33 (P < 0.00001)
0.01 0.1 1 10 100
Favours antibiotic Favours control
51Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.14. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 14 Mortality from
bacterial infections sensitivity analysis worst-best case.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 14 Mortality from bacterial infections sensitivity analysis worst-best case
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N
M-H,Random,95%
CI
M-H,Random,95%
CI
Rimola 1985 7/74 7/78 24.3 % 1.05 [ 0.39, 2.86 ]
Soriano 1992 5/64 2/69 15.7 % 2.70 [ 0.54, 13.41 ]
Pauwels 1996 11/40 4/125 22.8 % 8.59 [ 2.90, 25.50 ]
Hou 2004 11/59 2/68 17.3 % 6.34 [ 1.46, 27.45 ]
Jun 2006 8/62 3/69 19.8 % 2.97 [ 0.82, 10.69 ]
Total (95% CI) 299 409 100.0 % 3.30 [ 1.43, 7.62 ]
Total events: 42 (Antibiotic), 18 (Control)
Heterogeneity: Tau2 = 0.49; Chi2 = 8.82, df = 4 (P = 0.07); I2 =55%
Test for overall effect: Z = 2.80 (P = 0.0050)
0.01 0.1 1 10 100
Favours antibiotic Favours control
52Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.15. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 15 Mortality from
bacterial infections sensitivity analysis best-worst case.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 15 Mortality from bacterial infections sensitivity analysis best-worst case
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Rimola 1985 1/80 13/75 26.9 % 0.07 [ 0.01, 0.54 ]
Soriano 1992 1/68 6/64 12.4 % 0.16 [ 0.02, 1.27 ]
Pauwels 1996 1/50 14/107 17.9 % 0.15 [ 0.02, 1.13 ]
Hou 2004 2/68 11/61 23.3 % 0.16 [ 0.04, 0.71 ]
Jun 2006 2/68 9/58 19.5 % 0.19 [ 0.04, 0.84 ]
Total (95% CI) 334 365 100.0 % 0.14 [ 0.06, 0.31 ]
Total events: 7 (Antibiotic), 53 (Control)
Heterogeneity: Chi2 = 0.63, df = 4 (P = 0.96); I2 =0.0%
Test for overall effect: Z = 4.91 (P < 0.00001)
0.01 0.1 1 10 100
Favours antibiotic Favours control
53Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.16. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 16 Bacterial infections
sensitivity analysis worst-best case.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 16 Bacterial infections sensitivity analysis worst-best case
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Rimola 1985 22/74 32/78 20.0 % 0.72 [ 0.47, 1.13 ]
Soriano 1992 16/64 28/69 17.3 % 0.62 [ 0.37, 1.03 ]
Rolando 1993 20/50 26/50 16.7 % 0.77 [ 0.50, 1.18 ]
Blaise 1994 21/58 30/73 17.1 % 0.88 [ 0.57, 1.37 ]
Selby 1994 1/19 6/20 3.8 % 0.18 [ 0.02, 1.32 ]
Pauwels 1996 10/40 32/125 10.0 % 0.98 [ 0.53, 1.81 ]
Hou 2004 11/59 16/68 9.6 % 0.79 [ 0.40, 1.57 ]
Jun 2006 8/62 9/69 5.5 % 0.99 [ 0.41, 2.41 ]
Total (95% CI) 426 552 100.0 % 0.77 [ 0.63, 0.93 ]
Total events: 109 (Antibiotic), 179 (Control)
Heterogeneity: Chi2 = 4.12, df = 7 (P = 0.77); I2 =0.0%
Test for overall effect: Z = 2.65 (P = 0.0080)
0.01 0.1 1 10 100
Favours antibiotic Favours control
54Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.17. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 17 Bacterial infections
sensitivity analysis best-worst case.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 17 Bacterial infections sensitivity analysis best-worst case
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N
M-H,Random,95%
CI
M-H,Random,95%
CI
Rimola 1985 16/80 34/75 17.1 % 0.44 [ 0.27, 0.73 ]
Soriano 1992 12/68 33/64 16.3 % 0.34 [ 0.19, 0.60 ]
Rolando 1993 17/53 26/50 17.5 % 0.62 [ 0.38, 0.99 ]
Blaise 1994 9/70 44/59 15.5 % 0.17 [ 0.09, 0.32 ]
Selby 1994 1/19 7/19 4.7 % 0.14 [ 0.02, 1.05 ]
Pauwels 1996 6/50 50/107 13.7 % 0.26 [ 0.12, 0.56 ]
Hou 2004 2/68 23/61 7.7 % 0.08 [ 0.02, 0.32 ]
Jun 2006 2/68 20/58 7.6 % 0.09 [ 0.02, 0.35 ]
Total (95% CI) 476 493 100.0 % 0.26 [ 0.16, 0.43 ]
Total events: 65 (Antibiotic), 237 (Control)
Heterogeneity: Tau2 = 0.30; Chi2 = 22.67, df = 7 (P = 0.002); I2 =69%
Test for overall effect: Z = 5.34 (P < 0.00001)
0.01 0.1 1 10 100
Favours antibiotic Favours control
55Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.18. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 18 Mortality according
to the antibiotic used.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 18 Mortality according to the antibiotic used
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
1 Quinolones
Soriano 1992 4/64 7/64 5.0 % 0.57 [ 0.18, 1.86 ]
Zacharof 1997 8/35 8/30 6.2 % 0.86 [ 0.37, 2.01 ]
Hsieh 1998 13/60 18/60 12.9 % 0.72 [ 0.39, 1.34 ]
Hong 2002 1/20 1/20 0.7 % 1.00 [ 0.07, 14.90 ]
Hou 2004 16/59 13/61 9.1 % 1.27 [ 0.67, 2.41 ]
Subtotal (95% CI) 238 235 33.9 % 0.88 [ 0.61, 1.27 ]
Total events: 42 (Antibiotic), 47 (Control)
Heterogeneity: Chi2 = 2.20, df = 4 (P = 0.70); I2 =0.0%
Test for overall effect: Z = 0.69 (P = 0.49)
2 Quinolones + beta-lactams
Blaise 1994 11/58 16/59 11.3 % 0.70 [ 0.36, 1.38 ]
Pauwels 1996 4/40 13/107 5.1 % 0.82 [ 0.29, 2.38 ]
Subtotal (95% CI) 98 166 16.4 % 0.74 [ 0.42, 1.31 ]
Total events: 15 (Antibiotic), 29 (Control)
Heterogeneity: Chi2 = 0.06, df = 1 (P = 0.80); I2 =0.0%
Test for overall effect: Z = 1.04 (P = 0.30)
3 Cephalosporins
Selby 1994 2/19 5/19 3.6 % 0.40 [ 0.09, 1.81 ]
Lin 2002 2/47 3/50 2.1 % 0.71 [ 0.12, 4.06 ]
Jun 2006 20/62 24/58 17.7 % 0.78 [ 0.49, 1.25 ]
Subtotal (95% CI) 128 127 23.4 % 0.72 [ 0.46, 1.11 ]
Total events: 24 (Antibiotic), 32 (Control)
Heterogeneity: Chi2 = 0.70, df = 2 (P = 0.71); I2 =0.0%
Test for overall effect: Z = 1.49 (P = 0.14)
4 Other antibiotics
Rimola 1985 18/74 23/75 16.3 % 0.79 [ 0.47, 1.34 ]
Rolando 1993 10/50 14/50 10.0 % 0.71 [ 0.35, 1.45 ]
Subtotal (95% CI) 124 125 26.3 % 0.76 [ 0.50, 1.17 ]
Total events: 28 (Antibiotic), 37 (Control)
0.01 0.1 1 10 100
Favours antibiotic Favours control
(Continued . . . )
56Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(. . . Continued)Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Heterogeneity: Chi2 = 0.05, df = 1 (P = 0.82); I2 =0.0%
Test for overall effect: Z = 1.25 (P = 0.21)
Total (95% CI) 588 653 100.0 % 0.79 [ 0.63, 0.98 ]
Total events: 109 (Antibiotic), 145 (Control)
Heterogeneity: Chi2 = 3.58, df = 11 (P = 0.98); I2 =0.0%
Test for overall effect: Z = 2.16 (P = 0.031)
0.01 0.1 1 10 100
Favours antibiotic Favours control
Analysis 1.19. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 19 Mortality from
bacterial infections according to the antibiotic used.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 19 Mortality from bacterial infections according to the antibiotic used
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
1 Quinolones
Soriano 1992 1/64 2/64 10.7 % 0.50 [ 0.05, 5.38 ]
Hou 2004 2/59 2/61 10.6 % 1.03 [ 0.15, 7.10 ]
Subtotal (95% CI) 123 125 21.3 % 0.76 [ 0.18, 3.34 ]
Total events: 3 (Antibiotic), 4 (Control)
Heterogeneity: Chi2 = 0.22, df = 1 (P = 0.64); I2 =0.0%
Test for overall effect: Z = 0.36 (P = 0.72)
2 Quinolones + beta lactam
Pauwels 1996 1/40 4/107 11.7 % 0.67 [ 0.08, 5.80 ]
Subtotal (95% CI) 40 107 11.7 % 0.67 [ 0.08, 5.80 ]
Total events: 1 (Antibiotic), 4 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 0.36 (P = 0.72)
3 Cephalosporins
Lin 2002 0/47 2/50 13.0 % 0.21 [ 0.01, 4.31 ]
Jun 2006 2/62 3/58 16.6 % 0.62 [ 0.11, 3.60 ]
0.01 0.1 1 10 100
Favours antibiotic Favours control
(Continued . . . )
57Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(. . . Continued)Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Subtotal (95% CI) 109 108 29.7 % 0.44 [ 0.10, 1.95 ]
Total events: 2 (Antibiotic), 5 (Control)
Heterogeneity: Chi2 = 0.37, df = 1 (P = 0.54); I2 =0.0%
Test for overall effect: Z = 1.08 (P = 0.28)
4 Others
Rimola 1985 1/74 7/75 37.3 % 0.14 [ 0.02, 1.15 ]
Subtotal (95% CI) 74 75 37.3 % 0.14 [ 0.02, 1.15 ]
Total events: 1 (Antibiotic), 7 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 1.83 (P = 0.067)
Total (95% CI) 346 415 100.0 % 0.43 [ 0.19, 0.97 ]
Total events: 7 (Antibiotic), 20 (Control)
Heterogeneity: Chi2 = 2.43, df = 5 (P = 0.79); I2 =0.0%
Test for overall effect: Z = 2.02 (P = 0.043)
Test for subgroup differences: Chi2 = 0.0, df = 3 (P = 0.0), I2 =0.0%
0.01 0.1 1 10 100
Favours antibiotic Favours control
58Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.20. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 20 Bacterial infections
according to the antibiotic used.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 20 Bacterial infections according to the antibiotic used
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
1 Quinolones
Soriano 1992 12/64 28/64 12.5 % 0.43 [ 0.24, 0.77 ]
Zacharof 1997 4/35 16/30 7.7 % 0.21 [ 0.08, 0.57 ]
Hsieh 1998 6/60 27/60 12.1 % 0.22 [ 0.10, 0.50 ]
Hong 2002 2/20 9/20 4.0 % 0.22 [ 0.05, 0.90 ]
Hou 2004 2/59 16/61 7.0 % 0.13 [ 0.03, 0.54 ]
Subtotal (95% CI) 238 235 43.4 % 0.27 [ 0.18, 0.39 ]
Total events: 26 (Antibiotic), 96 (Control)
Heterogeneity: Chi2 = 4.02, df = 4 (P = 0.40); I2 =1%
Test for overall effect: Z = 6.65 (P < 0.00001)
2 Quinolones + beta-lactams
Blaise 1994 9/58 30/59 13.3 % 0.31 [ 0.16, 0.59 ]
Pauwels 1996 6/40 32/107 7.8 % 0.50 [ 0.23, 1.11 ]
Subtotal (95% CI) 98 166 21.1 % 0.38 [ 0.23, 0.62 ]
Total events: 15 (Antibiotic), 62 (Control)
Heterogeneity: Chi2 = 0.90, df = 1 (P = 0.34); I2 =0.0%
Test for overall effect: Z = 3.82 (P = 0.00013)
3 Cephalosporins
Selby 1994 1/19 6/19 2.7 % 0.17 [ 0.02, 1.26 ]
Lin 2002 0/47 6/50 2.8 % 0.08 [ 0.00, 1.41 ]
Jun 2006 2/62 9/58 4.2 % 0.21 [ 0.05, 0.92 ]
Subtotal (95% CI) 128 127 9.7 % 0.16 [ 0.05, 0.48 ]
Total events: 3 (Antibiotic), 21 (Control)
Heterogeneity: Chi2 = 0.33, df = 2 (P = 0.85); I2 =0.0%
Test for overall effect: Z = 3.26 (P = 0.0011)
4 Others
Rimola 1985 16/74 32/75 14.2 % 0.51 [ 0.31, 0.84 ]
Rolando 1993 17/50 26/50 11.6 % 0.65 [ 0.41, 1.05 ]
Subtotal (95% CI) 124 125 25.9 % 0.57 [ 0.41, 0.81 ]
Total events: 33 (Antibiotic), 58 (Control)
0.01 0.1 1 10 100
Favours antibiotic Favours control
(Continued . . . )
59Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(. . . Continued)Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Heterogeneity: Chi2 = 0.53, df = 1 (P = 0.47); I2 =0.0%
Test for overall effect: Z = 3.16 (P = 0.0016)
Total (95% CI) 588 653 100.0 % 0.36 [ 0.29, 0.45 ]
Total events: 77 (Antibiotic), 237 (Control)
Heterogeneity: Chi2 = 16.30, df = 11 (P = 0.13); I2 =33%
Test for overall effect: Z = 8.92 (P < 0.00001)
Test for subgroup differences: Chi2 = 0.0, df = 3 (P = 0.0), I2 =0.0%
0.01 0.1 1 10 100
Favours antibiotic Favours control
Analysis 1.21. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 21 Rebleeding.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 21 Rebleeding
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Hong 2002 1/20 0/20 0.8 % 3.00 [ 0.13, 69.52 ]
Hou 2004 12/59 27/61 41.3 % 0.46 [ 0.26, 0.82 ]
Jun 2006 21/62 36/58 57.9 % 0.55 [ 0.37, 0.82 ]
Total (95% CI) 141 139 100.0 % 0.53 [ 0.38, 0.74 ]
Total events: 34 (Antibiotic), 63 (Control)
Heterogeneity: Chi2 = 1.42, df = 2 (P = 0.49); I2 =0.0%
Test for overall effect: Z = 3.78 (P = 0.00016)
Test for subgroup differences: Not applicable
0.01 0.1 1 10 100
Favours antibiotic Favours control
60Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.22. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 22 Early rebleeding (up
to 7 days).
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 22 Early rebleeding (up to 7 days)
Study or subgroup Antibiotic Control Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Hong 2002 1/20 0/20 1.4 % 3.00 [ 0.13, 69.52 ]
Hou 2004 4/59 19/61 53.9 % 0.22 [ 0.08, 0.60 ]
Jun 2006 3/62 15/58 44.7 % 0.19 [ 0.06, 0.61 ]
Total (95% CI) 141 139 100.0 % 0.24 [ 0.12, 0.50 ]
Total events: 8 (Antibiotic), 34 (Control)
Heterogeneity: Chi2 = 2.69, df = 2 (P = 0.26); I2 =26%
Test for overall effect: Z = 3.88 (P = 0.00011)
0.01 0.1 1 10 100
Favours antibiotic Favours control
61Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.23. Comparison 1 Antibiotics versus no intervention/placebo, Outcome 23 Days of
hospitalisation.
Review: Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding
Comparison: 1 Antibiotics versus no intervention/placebo
Outcome: 23 Days of hospitalisation
Study or subgroup Antibiotic ControlMean
Difference WeightMean
Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
1 Intensive care unit
Blaise 1994 58 7.1 (2) 59 6.7 (1.2) 32.7 % 0.40 [ -0.20, 1.00 ]
Pauwels 1996 40 6.5 (0.9) 107 7.4 (1.1) 35.2 % -0.90 [ -1.25, -0.55 ]
Subtotal (95% CI) 98 166 67.9 % -0.27 [ -1.55, 1.00 ]
Heterogeneity: Tau2 = 0.78; Chi2 = 13.53, df = 1 (P = 0.00024); I2 =93%
Test for overall effect: Z = 0.42 (P = 0.67)
2 Full-lenght
Soriano 1992 64 13.5 (9.2) 64 14.4 (10.9) 7.2 % -0.90 [ -4.39, 2.59 ]
Hsieh 1998 60 19 (12) 60 26 (18) 3.3 % -7.00 [ -12.47, -1.53 ]
Hong 2002 20 13.4 (9.6) 20 20.4 (23.7) 0.9 % -7.00 [ -18.21, 4.21 ]
Lin 2002 47 10.2 (2.4) 50 11.4 (7.8) 13.5 % -1.20 [ -3.47, 1.07 ]
Jun 2006 62 13.6 (9.7) 58 14.8 (10) 7.1 % -1.20 [ -4.73, 2.33 ]
Subtotal (95% CI) 253 252 32.1 % -1.91 [ -3.80, -0.02 ]
Heterogeneity: Tau2 = 0.90; Chi2 = 4.92, df = 4 (P = 0.30); I2 =19%
Test for overall effect: Z = 1.98 (P = 0.047)
Total (95% CI) 351 418 100.0 % -0.79 [ -1.84, 0.26 ]
Heterogeneity: Tau2 = 0.78; Chi2 = 20.47, df = 6 (P = 0.002); I2 =71%
Test for overall effect: Z = 1.48 (P = 0.14)
-10 -5 0 5 10
Favours antibiotic Favours control
A D D I T I O N A L T A B L E S
Table 1. Group of antibiotics compared versus no intervention or placebo
Group of antibiotics Reference
Quinolones Soriano 1992; Zacharof 1997; Hsieh 1998; Hong 2002; Hou 2004
Quinolones plus beta-lactams Blaise 1994; Pauwels 1996
Cephalosporins Selby 1994; Lin 2002; Jun 2006
62Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 1. Group of antibiotics compared versus no intervention or placebo (Continued)
Carbapenems Rolando 1993
Non absorbable Rimola 1985
Table 2. Trials comparing different antibiotic regimens
Reference Intervention 1 Intervention 2
Sabat 1998 Quinolone Quinolone plus cephalosporin
Spanish Group 1998 Quinolone (Norfloxacin) Quinolone (Ofloxacin)
Gulberg 1999 Cephalosporin low dose Cephalosporin high dose
Lata 2005 Quinolone beta-lactams
Fernandez 2006 Quinolone Cephalosporin
Table 3. Test of interaction for antibiotic regimens (assessing bacterial infections)
Antibiotic regimen 1 Antibiotic regimen 1 P-value
Cephalosporins Quinolones 0.39
Cephalosporins Quinolones + beta-lactams 0.17
Cephalosporins Other antibiotics 0.03
Quinolones Quinolones + beta-lactams 0.29
Quinolones Other antibiotics 0.004
Quinolones + beta-lactams Other antibiotics 0.19
Table 4. Data on trials comparing two different regimens of antibiotic prophylaxis
Trial ID Outcome Experimental (n/
N)
Control (n/N) Relative Risk 95% CI
Sabat 1998 Mortality Norfloxacin + ceftri-
axone (1/24)
Norfloxacin (2/22) 0.46 0.04 to 4.71
Sabat 1998 Bacterial infections Norfloxacin + ceftri-
axone (3/24)
Norfloxacin (4/22) 0.69 0.17 to 2.73
63Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 4. Data on trials comparing two different regimens of antibiotic prophylaxis (Continued)
Sabat 1998 Cost Norfloxacin + ceftri-
axone - US $99.3 to
220.1
Norfloxacin - US
$1.9 to 745.5
- -
Sabat 1998 Drop-outs Norfloxacin + ceftri-
axone (4/28)
Norfloxacin (6/28) 0.67 0.21 to 2.11
Gulberg 1999 Mortality Ceftriaxone 1g (0/
40)
Ceftriaxone 2g (0/
42)
Risk difference: 0.
00
-0.05 to 0.05
Gulberg 1999 Bacterial infections Ceftriaxone 1g (1/
40)
Ceftriaxone 2g (1/
42)
1.05 0.11 to 9.80
Spanish Group
1998
Bacterial infections
(proven)
Norfloxacin 800mg
(26/183)
Ofloxacin 400mg
(27/182)
0.96 0.58 to 1.58
Spanish Group
1998
Bacterial infections
(suspected)
Norfloxacin 800mg
(51/183)
Ofloxacin 400mg
(53/182)
0.96 0.69 to 1.32
Lata 2005 Mortality Ampicillin and sul-
bactam 3g (12/21)
Norfloxacin 800 mg
(7/25)
2.04 0.98 to 4.23
Fernandez 2006 Mortality Ceftriaxone 1g (8/
54)
Norfloxacin 800 mg
(6/57)
1.41 0.52 to 3.79
Fernandez 2006 Mortality from bac-
terial infections
Ceftriaxone 1g (1/
54)
Norfloxacin 800 mg
(1/57)
1.06 0.07 to 16.46
Fernandez 2006 Bacterial infections Ceftriaxone 1g (6/
54)
Norfloxacin 800 mg
(5/57)
1.27 0.41 to 3.94
A P P E N D I C E S
Appendix 1. Search Strategies
Database Time span Search strategy
The Cochrane Hepato-Biliary Group Con-
trolled Trials Register
June 2010 (antibiotic* OR antibacteri*) AND (bleed* OR hemorr* or
haemorr*) AND cirrho*
64Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)
Cochrane Central Register of Controlled
Trials (CENTRAL) in The Cochrane Li-
brary
Issue 2, 2010 #1 MeSH Descriptor antibiotic-prophylaxis explode all trees in
MeSH products
#2 antibiotic* in All Fields in all products
#3 antibacteri* NEAR prophyl* in All Fields in all products
#4 (#1 OR #2 OR #3)
#5 MeSH descriptor Gastrointestinal Hemorrhage explode all trees
in MeSH products
#6 bleed* in All Fields in all products
#7 haemorr* in All Fields in all products
#8 hemorr* in All Fields in all products
#9 (#5 OR #6 OR #7 OR #8)
#10 MeSH Descriptor Liver Cirrhosis explode all tress in MeSH
products
#11 cirrho* in All Fields in all products
#12 (#10 OR #11)
#13 (#4 AND #9 AND #12)
MEDLINE (Ovid SP) 1950 to June 2010 #1 explode antibiotic-prophylaxis /All subheadings
#2 antibiotic* prophyl*
#3 antibiotic* pre
*#4 #1 or #2 or #3
#5 explode liver-cirrhosis /All subheadings
#6 liver cirrho*
#7 hepatic cirrho*
#8 liver fibro*
#9 #5 or #6 or #7 or #8
#10 explode gastrointestinal-hemorrhage /All subheadings
#11 gastr* hemorrhage
#12 gastr* haemorrhage
#13 gastr* bleeding
#14 #10 or #11 or #12 or #13
#15 random* or blind* or placebo* or meta-analysis
#16 #4 and #9 and #14 and #15
EMBASE (Ovid SP) 1980 to June 2010 #1 explode “antibiotic-prophylaxis”/all subheadings
#2 antibiotic*
#3 antibacteri* prophy*
#4 #1 or #2 or #3
#5 explode “gastrointestinal-hemorrhage”/all subheadings
#6 hemorr*
#7 haemorr*
#8 bleed*
#9 #5 or #6 or #7 or #8
#10 explode “liver-cirrhosis”/all subheadings
#11 cirrho*
#12 #10 or #11
#13 #4 and #9 and #12
#14 random* or blind* or placebo* or meta-analysis
#13 #13 and #14
65Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)
Science Citation Index EXPANDED
(http://apps.isiknowledge.com)
1945 to June 2010 #1 TS=(antibiotic* OR antibacteri* prophyl*)
#2 TS=(bleed* or hemorr* or haemorr*)
#3 TS=(cirrho*)
#4 #3 AND #2 AND #1
#5 TS=(random* or blind* or placebo* or meta-analysis)
#6 #5 AND #4
W H A T ’ S N E W
Last assessed as up-to-date: 29 June 2010.
Date Event Description
4 August 2010 New citation required but conclusions have not changed Six new trials were added to the review.
29 June 2010 New search has been performed This review was updated: the list of authors was changed,
six new trials were included, the Background section was
changed, the Methods section was modified according
the Cochrane Handbook for Systematic Reviews of In-
terventions (Higgins 2009), the discussion was modified.
The primary outcomes were arranged to include quality
of life and adverse events as primary outcomes in con-
cordance with the Cochrane Handbook for Systematic
Reviews of Interventions (Higgins 2009).
H I S T O R Y
Protocol first published: Issue 1, 2001
Review first published: Issue 2, 2002
C O N T R I B U T I O N S O F A U T H O R S
Norberto C. Chavez-Tapia: update co-ordination, data collection, data management, data interpretation, and review writing.
Tonatiuh Barrientos-Gutierrez: data collection, data management, data analysis, and review writing.
Felix I Tellez-Avila: data analysis and interpretation.
Karla Soares-Weiser: conception and co-ordination of the previous version of this review, provided general advice on this updated
review.
Misael Uribe: data interpretation, provided general advice on the review, and secured funding for the review.
66Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
D E C L A R A T I O N S O F I N T E R E S T
None known.
S O U R C E S O F S U P P O R T
Internal sources
• Medica Sur Clinic & Foundation, Mexico.
External sources
• No sources of support supplied
D I F F E R E N C E S B E T W E E N P R O T O C O L A N D R E V I E W
During the update process, the condition assessed changed from gastrointestinal bleeding to upper gastrointestinal bleeding. Rebleeding
was included as a secondary outcome, and quality of life and adverse events were included as primary outcomes.
Test of interaction and TSA were included.
I N D E X T E R M S
Medical Subject Headings (MeSH)
∗Antibiotic Prophylaxis; Bacterial Infections [mortality; ∗prevention & control]; Gastrointestinal Hemorrhage [∗complications; mor-
tality]; Liver Cirrhosis [∗complications; mortality]; Prognosis; Randomized Controlled Trials as Topic
MeSH check words
Humans
67Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.