WEYHN YHLN Cirrhosis Guidance. Management of Spontaneous Bacterial Peritonitis

7/23/2019 WEYHN YHLN Cirrhosis Guidance. Management of Spontaneous Bacterial Peritonitis

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Diagnosis and Management of Spontaneous Bacterial Peritonitis

This guidance is based on LTHT guidelines for the management of Spontaneous Bacterial Peritonitis

and was proposed and accepted by the network in 2010. It is intended for the guidance of hospital

departments.

Summary/Quick reference guide

Diagnosis

History

The most common symptoms and signs of SBP are: fevers, increased confusion, diffuse abdominalpain and vomiting.

Determine previous history of liver disease and previous episodes of SBP.

Examination.

The most common signs in patients with SBP are pyrexia, confusion, ileus and other features of asystemic inflammatory response or severe sepsis, measure MEWS score.

SBP may be suspected on clinical grounds but confirmation and classification is a laboratory

diagnosis.

Investigations

A routine diagnostic paracentesis should be performed PRIOR to starting antimicrobial therapy within6 hours in all patients:

With a clinical suspicion of SBP

With cirrhosis and ascites on hospital admission,

on the development of ascites,

suffering gastrointestinal haemorrhage

with cirrhosis on the development of any local (abdominal pain, reduced motility) or systemicsymptoms (fever, sepsis) or signs (encephalopathy, renal impairment).

Test Tube Department

White cell count (WCC) anddifferential

EDTA tube Haematology

Culture & susceptibility.Universal container &blood culture bottles

Microbiology

Protein, albumin, LDH, pH(amylase)

Li-Hep Yellow tube oruniversal container

Biochemistry

Cytology Universal container Pathology

Table 1. Ascitic fluid tests required.

Diagnosis and Management of Spontaneous BacterialPeritonitis


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Consider ascitic fluid neutrophil count 250/mm3(or 0.25 x10

9/l) diagnostic for SBP in an appropriate

clinical situation.

When culture unexpectedly yields an organism known to cause SBP in a patient without clinical signsof infection or with a low ascitic WCC, repeat ascitic tap.

When an ascitic culture yield a potential contaminant (e.g. coagulase-negative staphylococcus or

diphtheroid) repeat the ascitic tap.If mixed organisms are seen on Gram-stain or cultured(particularly anaerobes and Candidaspecies). Consider a surgical cause or sampling from gut lumen.

Consider secondary bacterial peritonitis if ascitic fluid neutrophil count is climbing despite 48 hours ofantibiotics.

Paracentesis may be repeated after 48 hours of treatment to assess the response to antibiotics.

Non-antimicrobial management

Urgent radiology (US/S if serum creatinine > 150 mmol/l, CT if normal renal function) and surgical

review is mandatory for secondary SBP.Early recognition and treatment of SBP is essential to preserve renal function. If creatinine raisedsend urine sodium. Urine sodium < 20 mmol/ suggests HRS.

If hypovolaemic give 1.5mg/kg body weight of albumin within 6 hours of the first antibiotic dose.

Day 3If hypovolaemic repeat human albumin dose of 1mg/kg.

After day 3- Consider large volume paracentesis e.g. if diaphragmatic splinting or variceal

haemorrhageseek expert help.

Antimicrobial treatment

The literature supports the use of 3rd generation cephalosporins but many trusts around the regionhave limited the use of these antibiotics. For the guidance of the region, LTHT is recommendingpiperacillin/tazobactam 4.5g 8-hourly iv. However, network members are advised to discuss this withtheir microbiology departments to ensure it fits with infection prevention and control policies locally.

If genuine penicillin allergy LTHT is recommending vancomycin 1g 12-hourly iv plus aztreonam

1g 8-hourly iv OR tigecycline 100mg loading followed by 50mg 12-hourly*. *Child Pugh C liverdisease reduce to 25mg 12-hourly iv.However, network members are advised to discuss thiswith their microbiology departments to ensure it fits with infection prevention and control

policies locally.

Discuss ongoing treatment with microbiology.

For directed therapy regimens, duration of treatment, switch to oral agent(s) see full guideline


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Full guideline

Full guideline

Aims

To improve the diagnosis and management of spontaneous bacterial peritonitis.

Objectives

To provide evidence-based recommendations for the diagnosis and appropriate investigation of spontaneousbacterial peritonitis (SBP).

To provide evidence-based recommendations for appropriate empirical or directed antimicrobial therapy ofSBP.

To standardise non-antimicrobial management of SBP.

To recommend appropriate dose, route of administration and duration of antimicrobial agents.

To advise in the event of antimicrobial allergy.

To set-out criteria for referral to specialists.

Background (there will be a direct link to this section on LHP)

Spontaneous bacterial peritonitis (SBP) is the infection of ascitic fluid in the absence of any intra-abdominal,surgically treatable source of infection (Conn et al., 1971) and in the absence of medical devices such as

ventriculoperitoneal shunts or continuous ambulatory peritoneal dialysis catheters.

SBP is therefore sometimes referred to as primary bacterial peritonitis but the term SBP is used throughoutthis guideline.

SBP can occur at any age but this guideline concerns adults, in whom cirrhosis is the most commonpredisposing condition.

Current British Society of Gastroenterology (BSG) guidelines on the management of ascites in cirrhosis

highlight the effect of early diagnosis and prompt treatment of SBP with a reduction of in-hospital mortalityfrom 90% to less than 20% (Garcia-Tsao 2001).

Classification

Bacterial infection of ascitic fluid can be classified in the table below based on (Koulaouzidids, 2007).


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Category Ascitic fluid analysis Comment

PMN250/mm3

Culture results

Spontaneous bacterialperitonitis (SBP)

+ Single organism No known or suspectedintra-abdominal surgical

source of the infectionCulture-negative neutrocyticascites

+ negative May represent theexpected 20% failure rateof culture. Treated as SBP

Monomicrobrial non-neurocytic bacterascites

- Single organism Possible contaminant orlow-grade infection,managed according tosymptoms

Polymicrobrial bacterascites - multiple This usually indicatesinadvertent perforation ofthe bowel wall by theparacentesis needle.

Secondary bacterialperitonitis

+ Multipleorganisms

differentiated from SBP bythe presence of a known orsuspected intra-abdominalsurgical source of theinfection e.g. perforatedviscus

Table 2. Classification of ascetic fluid infection.

Alternative causes of neutrocytic ascites should be considered: Peritoneal tumour deposits

Pancreatitis

TB

Connective tissue disease

Haemorrhage into ascitic fluid.

Incidence

The reported incidence in patients with ascites varies from 7 to 30% per annum (Rimola et al., 2000,Sherlock 2002, Soares-Weiser et al., 2005, Wong 2005). Patients with cirrhosis can also develop similarspontaneous infection of the pleural fluid (Arroyo et al., 2000). SBP occurs primarily in patients with pre-existing ascites in the setting of cirrhosis. It is less common in those with sub-acute liver disease e.g.alcoholic hepatitis.

Risk factors for developing SBP include:

Prior episode of SBP(two-thirds develop a recurrence within a year)

GI bleeding (variceal haemorrhage)

Ascitic total protein < 1.0 g/dl


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Child-Pugh score (Arroyo et al., 2000).

20% of patients with cirrhosis who have a variceal haemorrhage develop SBP at the time of admission and50% of these develop SBP during the admission. Infections are associated with higher rates of rebleedingand a higher mortality (Garcia-Tsao 2004).

Pathogenesis

Bacterial seeding of ascitic fluid is the common denominator of ascitic fluid infections. However the route ofbacterial entry is controversial. Two theories of the initial step in pathogenesis are proposed, the first beingthe currently favoured model:

Translocation. Bacterial translocation is the passage of bacteria from the gut lumen into mesenteric lymph

nodes and thereafter into the blood stream and other extra-intestinal sites (Guarner 2005). Translocation ispromoted by abnormal gut flora, mucosal oedema and altered gut permeability. Bacterial overgrowth inassociation with impairment of the intestinal barrier, alterations of local immune defences, slow motility of the

bowel, and reduced opsonic activity may precede the episodes of bacterial translocation (Cirera et al., 2001,Guarner 2005). Interestingly the gut microflora of animals with cirrhosis contains an increased proportion ofGram-negative bacteria (Guarner et al., 1997). Furthermore Frances et al.(2004) described bacterial DNA in30% of peritoneal macrophages isolated from patients with cirrhosis and ascites. These macrophagesexhibited an activated phenotype.

Haematogenous. 50% of episodes of SBP are accompanied by bacteraemia (Friedman et al., 2004). The

organism is identical to that cultured from ascitic fluid and can sometimes be isolated from urine or sputum.This suggests haematogenous seeding of the ascitic fluid might be the initial key step in pathogenesis.

Microbiology

The microorganisms isolated from patients with SBP are most commonly members of the normal microbialflora of the gastrointestinal tract including Escherichia coli(70%), Klebsiellaspecies (10%), Proteusspecies(4%), Enterococcus faecalis(4%), Pseudomonas species (2%) and others (6%) (Arroyo et al., 2000). Beta-haemolytic streptococci and Streptococcus pneumoniaeare also an important cause in a small number ofpatients.

The cultures results of all ascetic fluid samples that grew a single organism in Leeds during the 3 years 2006-2008 are shown in Figure 1. The raw data are presented without an assessment of clinical significance, thelarge number of coagulase negative staphylococci (CNS) cultured suggests a high rate of samplecontamination with skin flora.


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37

3

4

9

1

15231

41

21

1

11

22

2

1

1 911

CNS

Staph aureus

MRSA

Enterococcus

Gamella

Lactococcus

Streptococcus sp

Streptococcus pneumoniae

Corynebacterium

Anaerobe

Propionibacterium

Actinomyces

ASB

Strep pyogenes

Candida

"Coliform"

Escherichia

Enterobacter

Serratia

Citrobacter

Klebsiella

Pseudomonas

Achromobacter

Figure 1. Results of ascitic fluid cultures that grew a single organism from samples sent January 2006-December 2008. 1875 samples were sent. CNS=coagulase negative staphylococci.

Prognosis

Mortality for an episode of SBP remains high at 20 to 40%. Patients with cirrhosis who survive an episode ofSBP have a 40 to 70% chance of recurrence within 12 months (Wong et al., 2005). Patients who recover

from an episode of SBP should be considered as potential candidates for liver transplantation (Rimola et al.,2000). Guidance on prevention of subsequent episodes of SBP will be provided in LTHT prophylaxisguideline (link) currently under development. The environment in which a patient acquires SBP (nosocomialor community) does not appear to affect either the short or long term survival (Song et al., 2006).


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Clinical diagnosis (there will be a direct link to this section on LHP)

History

The most common symptoms and signs in patients with SBP are: fevers, increased confusion, diffuseabdominal pain and vomiting.

Determine previous history of liver disease and previous episodes of SBP.

Examination.

The most common signs in patients with SBP are pyrexia, confusion, ileus and other features of a systemicinflammatory response or severe sepsis.

Symptoms &signs

SBP

(%)

Bacterascites

(%)

CNNA

(%)

Secondaryperitonitis (%)

Fever 68 57 50 33

Abdominal pain 49 32 72 67

Tenderness 39 32 44 59

Rebound 10 5 0 17

Encephalopathy 54 50 61 33

Table 3. Adapted from Sleisengers & Fordtrans Gastrointestinal & Liver Disease, 7thEd, Elsevier.

Many of the features of liver failure make the recognition of sepsis difficult. For example, the reducedperipheral neutrophil count due to hypersplenism, elevated basal heart rate and relative hypotension due tothe hyperdynamic circulation and basal hyperventilation due to encephalopathy (Wong et al., 2005). A highindex of suspicion must be maintained. [Evidence level C]

SBP may be suspected on clinical grounds but confirmation and classification is a laboratory diagnosis (seeinvestigations below).

(Initial) Investigations (there will be a direct link to this section on LHP)

SBP can only be diagnosed by examining a sample of ascitic fluid. Abdominal paracentesis (ascitic tap) issafe (Runyon 1986, Lin et al., 2005).

Recommendation: A routine diagnostic paracentesis should be performed PRIOR to starting antimicrobialtherapy within 6 hours in all patients:

with a clinical suspicion of SBP

with cirrhosis and ascites on hospital admission,

on the development of ascites,

suffering gastrointestinal haemorrhage

with cirrhosis on the development of any local (abdominal pain, reduced motility) or systemic


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symptoms (fever, sepsis) or signs (encephalopathy, renal impairment)[Evidence level C] Rimola et al.(2000)and the International Ascites Club.

A number of ascitic fluid parameters have been evaluated for the diagnosis of SBP. The highest accuracy fora diagnosis of SBP can be made from a pH 7.34 or a blood-ascitic fluid gradient 0.10 in combination withan ascitic fluid neutrophil count > 500/mm3(Stassen et al., 1986). An ascitic fluid neutrophil count 250/mm3is consistent with a diagnosis of SBP (Garcia-Tsao 1992, Arroyo et al., 2000). The total white cell

count can also be used to diagnose SBP. Runyon et al. (2006) suggest a WCC > 500mm3is diagnostic,irrespective of the differential. The ascitic cell count and differential is performed by automated techniques inthe laboratory.

Recommendation: Samples of ascitic fluid should be routinely sent to haematology for a differential white cellcount [Evidence level B].

Recommendation: an ascitic fluid neutrophil count 250/mm3(or 0.25 x109/l) should be considereddiagnostic for SBP in an appropriate clinical situation. [Evidence level B]

Leukocyte esterase reagent strips have a high sensitivity (64 to 100%) and specificity (92.5 to 100%) in thedetection of an elevated ascitic fluid neutrophil count (Castelote et al., 2002, Sapey et al., 2005). Althoughthese are cheap, rapid and readily available on wards (urine dipsticks) microscopy is an absolute requirementso bedside testing will not alter management and is not therefore recommended.

Recommendation: use of Leukocyte esterase reagent strips is not recommended for the diagnosis of SBP.[Evidence level D]

The yield of ascitic fluid culture can be increased from ~45% to more than 80% by inoculating ascitic f luidsamples into blood culture bottles (Bobadilla et al., 1989). At least 10ml of fluid is required.

Recommendation: 10ml ascitic fluid should be inoculated directly into both an aerobic and anaerobic bloodculture bottle according to Standard operating procedure.[Evidence level D]

Recommendation: When an ascitic culture unexpectedly yields an organism known to cause SBP in apatient without clinical signs of infection or with a low ascitic WCC the ascitic tap must be repeated toreassess the neutrophil count and re-culture (Rimola et al., 2000). [Evidence level C]

Recommendation: When an ascitic culture yield a potential contaminant (e.g. coagulase-negativestaphylococcus or diphtheroid the ascitic tap should be repeated to reassess the neutrophil count and re-culture (Rimola et al., 2000). [Evidence level C]

Recommendation: If mixed organisms are seen on Gram-stain or cultured(particularly anaerobes andCandidaspecies). Consider a surgical cause or sampling from gut lumen. [Evidence level C]

Recommendation: consider secondary bacterial peritonitis if ascitic fluid neutrophil count is climbing despite

48 hours of antibiotics. [Evidence level C]

Paracentesis may be repeated after 48 hours of treatment to assess the response to antibiotics. [Evidence level


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D]

Non-Antimicrobial Treatment (there will be a direct link to this section on LHP)

Secondary bacteria peritonitis is suggested by an ascitic fluid neutrophil count 250/mm3 and multiple gutorganisms on Gram-stain and culture.

Secondary bacteria peritonitis is suggested from the ascitic fluid analysis by:

Total protein > 1.0g/dl

Glucose < 50mg/dl (2.78 mmol/l)

Raised LDH (Rimola et al., 2000, Wong et al., 2005).

Recommendation: Urgent radiology (US/S if serum creatinine > 150 mmol/l, CT if normal renal function) and

surgical review is mandatory for secondary bacterial peritonitis. [Evidence level B]

Patients with SBP are at risk of hepatorenal syndrome (HRS). Bacteria and their endotoxins trigger asystemic inflammatory response with vasodilatation, hypotension and a hyperdynamic circulation. Thedevelopment of renal impairment in SBP carries a poor prognosis (Ruiz-del-Arbo et al., 2003).

Recommendation: Early recognition and treatment of SBP is essential to preserve renal function. IfCreatinine raised send urine sodium. Urine sodium < 20 mmol/ suggests HRS.

Sort et al. (1999) described the use of human albumin solution as a plasma expander in SBP. The use ofalbumin improved the mortality rate in SBP from 29 to 10%. The study had no control plasma expander.However albumin may play an additional role to simple plasma expansion: It may bind endotoxin, improveopsonisation within ascitic fluid and stabilise the vascular endothelium.

Recommendation: If the patient is hypovolaemic consider the administration of 1.5mg/kg body weight ofalbumin within 6 hours of the first antibiotic dose. A repeat dose of 1mg/kg may be given on day 3. [Evidencelevel B]

The role of large volume paracentesis in SBP is unclear. Ruiz-del-Arbol et al. (2003) described a higher

incidence of renal impairment and hyponatraemia following paracentesis. However this was not statisticallysignificant. Anecdotal evidence suggests that ascites rapidly reaccumulates during SBP makingparacentesis during acute infection worthless. More clinical data is required.

Recommendation: routine use of large volume paracentesis is not recommended for the treatment of SBP.[Evidence level B] Paracentesis may still have a role if diaphragmatic splinting or variceal haemorrhageseekexpert help.

Empirical antimicrobial treatment (there will be a direct link to this section on LHP)

The initial decision to treat suspected ascitic fluid infection is based on an elevated fluid neutrophil count


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and/or the clinical setting. A high index of suspicion is essential. CNNA and SBP have comparable mortalityrates so similar management is warranted.

LTHT is recommending empirical regimen for SBP with pipercillin/tazobactam 4.5g 8-hourly iv. However, dueto the introduction of local antibiotic policies, departments around the region are advised to reach localagreement with their microbiology departments. If there is genuine penicillin allergy LTHT is recommendingvancomycin 1g 12-hourly iv plus aztreonam 1g 8-hourly iv OR tigecycline 100mg iv loading followed by 50mg

12-hourly iv*. Similarly, due to the introduction of local antibiotic policies, departments around the region areadvised to reach local agreement with their microbiology departments. (Evidence level D, the use ofcephalosporins is evidenced in the literature).

*Tigecycline requires dosage adjustment in Child Pugh C liver disease to 25mg 12-hourly iv.

Justification/Evidence review.

Empirical antimicrobial therapy should be started early after appropriate sampling and have activity againstcoliforms such as Escherichia coliand Klebsiellaspecies, and Gram positives such as Enterococcus faecalis

and streptococci. Nephrotoxic antimicrobials should be avoided if at all possible. The choice of antimicrobialtherapy must take into consideration the increasing frequency of hospital acquired infections, for example, arecent audit at Leeds Teaching Hospitals NHS Trust has identified that patients with liver failure are atincreased risk of Clostridium difficileinfection.

The use of antibiotics for SBP in patients with cirrhosis has been described in the Cochrane Database ofSystematic Reviews (2009). Thirteen studies were included in this review. No meta-analysis was performedsince each trial compared different antibiotics in their experimental and control groups. These trials looked atthe following antibiotics: intravenous (iv)/oral (po) ciprofloxacin, iv ceftazidime, iv cefotaxime, iv amikcacin, ivcefotaxime, iv ampicillin-tobramycin, iv/po moxifloxacin, iv/po co-amoxiclav, oral cefixime and oral ofloxacin.The most commonly used antibiotics were 3rd generation cephalosporins although these did not demonstratesuperior efficacy over other antibiotics.

Up to 10% of infections are caused by Gram-positive cocci (particularly Enterococcus species). Ampicillin-tobramycin and co-amoxiclav have been used with the assumption that they would provide adequate Gram-positive cover.

The Cochrane review made no firm conclusions from the randomised controlled trials. Although thirdgeneration cephalosporins have been established as the standard treatment of SBP in many centres, currentconcerns about Clostridium difficileinfection, selection of extended-spectrum beta-lactamase (ESBL)producing coliforms and adequacy of spectrum have raised questions about the wisdom of this approach.

The final recommendation were influenced by local epidemiology and resistance patterns which are shown inFigures 1 and 2.


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0

10

20

30

40

50

60

70

80

AMO CIP CXM COT PTA GEN

Figure 2. Showing the percentage of Gram negative ascitic fluid isolates resistance to various antimicrobials.AMO, amoxicillin; CIP, ciprofloxacin; CXM, cefuroxime; COT, cotrimoxazole; PTA, piperacillin/tazobactam;GEN, gentamicin.

Piperacillin/tazobactam was chosen in order to provide appropriate antimicrobial cover (including enterococci,streptococci, and resistant gram-negative including Pseudomonas species) and to avoid the use ofcephalosporins, quinolones (whose activity can no longer be relied upon for empirical treatment) andgentamicin (to reduce the risk of toxicity). Vancomycin and aztreonam in combination provides a similarspectrum of activity. Tigecycline has an appropriate spectrum of activity (active against Staphylococusaureus, enterococci and many Gram negatives but not Pseudomonas). Tigecycline is licensed for use inintrabdominal infections but data specific for spontaneous bacterial peritonitis are lacking.

N.B. Coamoxiclav susceptibility was not been routinely tested in the laboratory during the review period sodata are not available. Cefuroxime can be used as a reasonable marker of co-amoxiclav susceptibility. Thisantimicrobial is less broad spectrum than pipercillin/tazobactam against Gram-negatives and lacksantipseudomonal activity.

Directed therapy

If ascitic fluid culture results are positive then antimicrobials should be changed to optimise effectiveness andreduce adverse effects - this will usually be the most narrow spectrum effective agent available.

Directed therapy should be determined on a case by case basis with discussion with microbiology if required.

Oral switch

There is some evidence to support a switch from intravenous to oral antibiotics early in patients who show animprovement after a short iv course. Oral therapy alone may be possible from the start of treatment in those withoutsystemic inflammatory response or renal failure. Oral ciprofloxacin/ofloxacin, co-amoxiclav, and oral 3rd generation

cephalosporins demonstrated non-inferiority when compared to iv therapies. Oral ofloxacin was compared with ivcefotaxime in 123 patient with uncomplicated SBP (no encephalopathy, renal failure, vomiting, ileus, shock or GIhaemorrhage) - no difference in the number of deaths, resolution of SBP or presence of adverse effects was seen. Two


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3r

generation cephalosporins were compared in 38 patients - oral cefixime vs iv ceftriaxone, but no significantdifferences were found for any of the outcomes provided. No difference in effectiveness or mortality was demonstratedwhen oral ciprofloxacin was compared to iv ciprofloxacin in 80 cirrhotic patients with SBP.

Recommendation: Switch to oral antimicrobials should be considered when patients are clinically improving,afebrile and inflammatory markers falling. [Evidence level C]

If patients have been commenced on piperacillin tazobactam then oral co-amoxiclav 625mg 8-hourly isappropriate for oral switch unless culture results indicate otherwise. [Evidence level B]

Duration of therapy

In most studies the length of treatment was based on disappearance of symptoms and signs. One studydemonstrated no difference in either mortality or resolution of SBP with 5 or 10 days treatment withintravenous cefotaxime.

Recommendation: To reduce adverse events including selection for resistant bacteria five days should be thestandard duration, extended up to 10 days if clinical response is slow. [Evidence level B]

Provenance: Author name (s) and address (es)

Dr Jason Jennings, Consultant Gastroenterologist, Leeds Teaching Hospitals

Dr Jonathan Sandoe, Consultant Microbiologist, Leeds Teaching Hospitals

Dr Mervyn Davies, Consultant Hepatologist, Leeds Teaching Hospitals

Mr Dan Greer Pharmacist, Lead GI Pharmacist, Leeds Teaching Hospitals

Miss Faye Coxen, Liver Unit, Leeds Teaching Hospitals

Clinical condition- SBP

Target patient groupall adult patients with SBP

Target professional group (clinical competence) all healthcare professional caring for patientswith SBP.

Evidence Bases: References

Arroyo V et al. Spontaneous Bacterial Peritonitis, Eds. OGrady and Lakes comprehensive clinicalhepatology, 1stEd. Barcelona: Mosby, 2000:7.10-7.14.

Bobadilla et al. Improved method for bacteriological diagnosis of spontaneous bacterial peritonitis. J ClinMicrobiol1989; 27:2145-7.

Campillo B et al. Epidemiology of severe hospital-acquired infections in patients with liver cirrhosis: effect oflong term administration of norfloxacin. Clin Infect Dis1998; 26:1066-70.

Castelote J et al. Rapid diagnosis of SBP by the use of reagent strips. Hepatology2002; 37:893-6.

Cirera I et al. Bacterial translocation of enteric organisms in patients with cirrhosis. J Hepatol 2001; 34:32-7.

Conn H, Fessel J. Spontaneous bacterial peritonitis in cirrhosis: variations on a theme. Medicine1971;


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50:161-97.

Fernandez J et al. Bacterial infections in cirrhosis: Epidemiological changes with invasive procedures andnorfloxacin prophylaxis. Hepatology 2002; 35:140-8.

Fernandez J et al. Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advancedcirrhosis and haemorrhage. Gastroenterology2006. 131(4): 1049-56.

Frances R et al. Bacterial DNA activates cell mediated immune response and nitric oxide overproduction in

peritoneal macrophages from patients with cirrhosis and ascites. Gut 2004; 53:860-4.Friedman LS, Keeffe EB. Handbook of Liver Disease. 2nd Ed. Elsevier Inc 2004.

Garcia-Tsao G. Spontaneous bacterial peritonitis. Gastroenterol Clin N Am1992; 21:257-75.

Garcia-Tsao G. Current management of the complications of cirrhosis and portal hypertension: varicealhaemorrhage, ascites and spontaneous bacterial peritonitis. Gastroenterology 2001; 120:726-48.

Garcia-Tsao G. Spontaneous Bacterial Peritonitis: a historical perspective. J Hepatol2004; 41: 522-7.

Gines P, Rimola A, Planas R, et al. Norfloxacin prevents spontaneous bacterial peritonitis recurrence incirrhosis: results of a double-blind, placebo-controlled trial. Hepatology 1990; 12:71624.

Guarner C et al. Intestinal bacterial overgrowth and bacterial translocation in an experimental model of

cirrhosis in rats. J Hepatol1997; 26:1372-8.Guarner C et al. Bacterial translocation and its consequences in patients with cirrhosis. Eur J GastroenterolHepatol 2005; 17:27-31.

Jalan R, Hayes P. UK guidelines on the management of variceal haemorrhage in cirrhotic patients. BritishSociety of Gastroenterology 2000.

Lin Y et al. Prophylactic antibiotics with upper gastrointestinal haemorrhage: a prospective, controlled trial.Chinese Medical Journal2002; 65(8): 365-371.

Lin C et al. Pre-procedure coagulation tests are unnecessary before abdominal paracentesis in emergencydepartments. Hepatology2005; 41:402-3.

Moore K, Aithal G. Guidelines on the management of ascites in cirrhosis. Gut2006; 55; 1-12.

Rimola A et al. Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensusdocument. J Hepatol2000; 32:142-53.

Rolachon A, Cordier L, Bacq Y, et al. Ciprofloxacin and long-term prevention of spontaneous bacterialperitonitis: results of a prospective controlled trial. Hepatology1995; 22:11714.

Ruiz-del-Arbo L et al. Cardiovascular, renal and hepatic haemodynamic derangement in cirrhotic patientswith spontaneous peritonitis. Hepatology2003; 38:1210-8.

Runyon B. Paracentesis of ascitic fluid: a safe procedure. Arch Intern Med1986; 146:2259-61.

Runyon B. Ascites and spontaneous bacterial peritonitis. In: Feldman M et al. Sleisenger and Fordransgastrointestinal and liver disease, 8thEd. Philadelphia: Saunders 2006:1935-64.

Sapey T et al. Rapid diagnosis of spontaneous bacterial peritonitis with leukocyte esterase reagent strips inan European and in an American centre. J Gastroenterol Hepatol2005; 20:187-92.

Sherlock S, Dooley J. Spontaneous Bacterial Peritonitis. In: Sherlock and Dooleys diseases of the liver andbiliary system, 11thEd. Oxford: Blackwell, 2002:132-4.

Singh N et al.Trimethoprim-Sulfamethoxazole for the prevention of Spontaneous Bacterial peritonitis incirrhosis. Annals of Internal medicine1995; 122: 595-598.

Sleisengers & Fordtrans Gastrointestinal & Liver Disease, 7thEd, Elsevier Inc.

Soares-Weiser K, Brezis M, Tur-Kaspa R, Leibovici L. Antibiotic prophylaxis for cirrhotic patients withgastrointestinal bleeding. TheCochrane Collaboration2005; 1:1-34.

SongJ et al. Prognostic significance of infection acquisition sites in spontaneous bacterial peritonitis:nosocomial vs. community acquired. J Korean Med Sci2006; 21:666-71.

Sort P et al. Effects of intravenous albumin on renal impairment and mortality in patients with cirrhosis and


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SBP. N Engl J Med1999; 341:403-9.

Stassen W et al. Immediate diagnostic criteria for bacterial infection of ascitic fluidevaluation of ascitic fluidpolymorphonuclear leukocyte count, pH, and lactate concentration, alone and in combination.Gastroenterology1986; 90:1247-54.

Wong F et al. Sepsis in cirrhosis: report on the 7thmeeting of the International Ascites Club. Gut 2005;54:718-25.

Evidence levels:

A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs

B. Robust experimental or observational studies

C. Expert consensus.

D. Leeds consensus. (where no national guidance exists or there is wide disagreement with a level Crecommendation or where national guidance documents contradict each other)

Guideline Provenance:

As detailed above. Reviewed and accepted at network meeting April 2010. Adopted initially as WYHN

guidance, the WEYHN and YHLN guidance with name changes in 2010 and 2012 respectively.Review date October 2013.

Documents

WEYHN YHLN Cirrhosis Guidance. Management of Spontaneous Bacterial Peritonitis