REVIEW ARTICLE Phcw"""XOECOf'>OI'I>a 7 (2l. 1 2~14(I. 1m l ' lO-l~'()l~ISOI> !£I/O

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Epidemiology, Therapy and Costs of Nosocomial Infection Rnmon Gdfvez-Vargas,1,2 Aurora Bileno-Cavanillas l and Miguel Garda-Martfn 1

Department of Preventive Medicine and Public Hea lth, School of Medicine, University of Granada, Granada, Spain

2 Service of Preventive Medicine, University Hospital of Granada, Granada, Spain

Contents SUmmary 1 Descriptive Epidemiology

128 129 130 130 132 133 133 133 133 134 135 135 136

2. Causes of Nosocomial Infection 2.1 Infecting Organisms 2.2 Host Factors

3. Treatment of Nosocomial Infection 3.1 Aseptic Techniques. 3.2 Surveillance 3.3 Phormacological Approaches

4. The Cost of Nosocomial Infections . 4.1 Direct Costs .:1 ,2 Indirect Costs

5, Conclusions .

Summary In t he current climate of cost containment a nd quality control, nosocomial infection is a worrisome adverse evcnt in hospital care. Hospitaliscd paticnts rcquire care for increasingly scvere illncsses. and are therefore morc susceptible to infection. especially by opponunistic micro-organisms. It is thus nccessary to accurately assess and adjust for the severity of the underlying illness in studies of risk factors involved in nosocomial infections.

The appearance of new diagnostic and therapeutic tcch niques providcs novcl opponunities for infection control and rcpresents a constant challenge to hospital systems. The continuous selection of resistant flora, together with the identifica­tion of new pathogens, call s for a reconsiderat ion of hospital policies regarding the dispensation of antibiotics.

Epidemiological surveillance continucs to be the most imponant aspect of attempts to monitor in fection control programmes, and to identify changes in risk factors that may increase the infection rate. Among the major challenges now facing the infection control practitioner is the use of nosocomial infection ratcs as an indicator of quality of care. Awareness of infection statistics would servc as a stimulus to the prevention and control of infection, bUI would be uselcss if not accompanied by adequate systems to guarantce the comparability of data from different studies and centres. Su itably sensi ti ve and specific surveillance systcms

Nosocomial Infection 129

should be developed, and the use of site-specific and procedure-specific infection rates adjusted for the patient's intrinsic risk should be encouraged.

Nosocomial infection can be defined as a set of clinical manifestations caused by a micro-organism acquired through exposure to the hospilal env iron­ment. ll ) This defin ition includes any infection that appears in hospitalised palients, unless the infec­tion was in the incubation phase at the time of ad­mission,l2·31 and infections acqu ired by hospital staff in the course of their work. Nosocomial infec­tions also include those manifested after the patient has been discharged. Although incidence statistics do not usually take these cases into account, they arc becoming more common because of the increasing use of outpatient surgical procedures and the ten­dency to reduce the length of inpatient slays.l4-71

One of the most worrisome obstacles to the study o f nosocomial infection is the lack of a pre­cise definition of the term. These in fections include a wide range of disease processes that occasionally have no features in common, from skin infections to pneumonia or septicaemia. The epidemiological study, survei llance and control of hospi tal infec­tions wou ld benefit from a precise definition such as those proposed by the Centers for Disease Con­trol (CDC).I8.91 Ihe Study on the Efficacy of Nos­ocomial Infection Control (SEN IC project),II01 or the hospital acquired infections Steering Group,!11l all of which classi fy infections on the basis of their anatomical location. Table I shows the definitions of surgical wound infection proposed by the CDC.!91

Currently, there is increasing interest in nosoco­mial infect ion. The adverse effects of hospital-ac­quired infection may be estimated in terms of mor­bidity, mortality and economic consequences. The direct costs of nosocomial infection are defined as the specific costs incurred in treating the infection , which can be measured by quantifyi ng the increase in length of hospital stay, and the additional inves­ti gations, consumables and drugs required. Indirect and intangible costs are incurred because of mor­tality excess, absence from work and personal pai n.

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Table I. Diagnostic criteria for surgical i,.,fection (adapted from Gamer et atl~~

Superficial

All criteria must be present Manifestation wfthin 30 days of operation, no Pfosthesis implanted:

minimal purulent drainage from incision srte or drain located above fascial layer

m inimal cellu litis

no systemic findings of infection

no sinus tract

infection can be managed at bedside or in office

infection does rlO1 prolong hospitalisation, increase activity services, delay retum to usual activities or resuH in readmission to hosp4tal or death

Inclslonal

Anyone crrterio<l can be pres9J'\\. Manrtestation wrthin 30 days of operation. no prosthesis impla,.,ted:

moderate or extensive purulenl drainage from incision or dra in

Iocaled above fascial layer

moderate or exlensive cellulitis

partial wound dehiscence as a resu~ of infection (or necessary opening 01 wound by surgeons to ma,.,age infectiOl1) w~hout disruption of fascial approx imation

systemic findings of infection

hospital readmission for management of infection

infection management prolongs hospital isation or increases acuity of care

surgeon or consuhing ptlysician diagnosis

OptH"atlve site infec1lon AI1y one criterion can be presef1\. Manifestation w~hin 30 days of operation or w~hin 1 year ij Pfosthesis impla,.,ted·

puru lent drainage from beneath fasci.allayer

extension 01 incisional infection beyond operative site (mediastin~is, periton~is, osteomyelitis. cellulit is. abscess. necrotising fasci~is. etc.) or ,.,ew infection arising within the operative area ('leaki"'g· anastomosis. cholangitis. f istula. empyema. etc.)

complete wound de!1iscence includ ing fascia as a resuH of i,.,fection (or complete ope,.,ing of wound necessary to manage infection)

sinus tract extending beneath fascia

surgeon or consu"ing physicia,., diagnosis

infection resuhing i,., death

1. Descriptive Epidemiology

Because of its frequency, nosocomial infection is a significant factor in heahhcare efforts. Differ-

PhormocoEconomics 7 (2) 1995

130 Ga/wz-Vargas ct 01/.

Table II. Overall and sile-specific infection rates by service (no. 01 nosocom~1 inleelions per 100 discharges) .. _ Overall Bloodstream Surgical wound Urinary tract Pneumonia Reference rate" infection infection infection

SENIC universeb ,., 0.3 " 2' 06 " Medicine 3.' 0.3 >'7 0.6 " Ger.era l surgery 6.' OA >.9 >., ... " Surgical leu 61.6 7.' 9.> 15.1 7.8 34

Medical leu 35.7 ,. 23 99 99 34 a The overall rate may not equal the sum of the rates for ind ividual inleelion s~es because the numbers 0 1 patients ditter between medical

wards. For example, higher infection rates in ICUs have little inrluence on the overal l rate because leu pa~ents constitute a small percentage of all hospitalised patients.

b 6449 acute care US hospitals_

Abbrevialions: leU" intensive care un~: SENIC "Study on the Efficacy 01 Nosooomialiniection Control.{10!

en! studies have placed the incidence risk of noso­comial infection aI between 4 and 9 cases per 100 discharges[12.J51 and the prevalence rate at 6 to 15 cases per 100 inpatients.116.21] The actual fig ures may beeven higher, given the likelihood that banal infections, especially those caused by viruses, are under -reported.122]

The incidence risk increases with the length of hospital stay,123-251 and differs cons iderably de­pending on the characteri stics of the patients them­selves and the type of care provided .126-301 The in­fect ion rate al so varies markedly between different types of fac ilities and different wards within hos­pitals, and is much greater in intensive care wards than in other areas.126.31-351

Any assessment of the frequency of nosocomial infection should take into account the influence of intrinsic ri sk,127.28.32,36-381 the procedure used,123.29.30.39) the criteria used to define nosoco­mial infection,11 2, 14.40) the surveillance system used to identify casesI3.5.41.451 and the freq uency measures used. 146-50J Recent proposals suggest us­ing the rates of hospital infection as an indicator of the quality of healthcare.l 51 .521 This measure would require researchers to standardise the meth­ods used t o determine the freque ncy of nosocomial infection, develop indicators of the risk of infec­tion, and establish acceptable basal rates of infec­tion that do not imply any deterioration in the qual­ity of healthcare.

Table II summarises info rmation from several sources regarding the frequency of infec tion in dif-

ferent sites. In general, uri nary tract and surgical wound infections are the most common. al though the distribution in different sites as well as the fre­quency vary depending on the hospital service in­volved. For example, respiratory tract infecti ons are more widespread in intensive care units, whereas skin infections predom inate in burn un its.

2. Causes of Nosocomial Infection

Nosocomial infection is the result of interaction between a micro-organism (or other infectious agent) and the host within a speci fi c environ ment: the hospital. Several factors can affect the outcome of the interaction. Endogenous (i.e. origi nating in the patient) and exogenous (determined by the hos­pital environment) facto rs can polentiate the palho­genicity of the agent, ordimi ni sh the host's defence mechanisms.

2.1 Infecting Organisms

Nosocomial infecti on can be caused not only by habitual pathogens, but a lso by opportunistic mi ­cro-organisms considered to have little pathogen ic potenti al, especially in severely ill patients. The most problematic micro-organi sms arc those gen­erally ubiquitous and resistant to external condi­tions, and that read il y become res istant to antibiot­ics.(53.541 In fact, selective pressure exerted by antibiotics is an important determinant of nosoco­mial infection, as illustrated by the evolu tion of pathogenic micro-organisms durin g the past 40 years. The introduction of penicilli n, although il

Nosocomial Infection

won an initial victory by drastically reducing the mortality associated with hospital infections, si­multaneously favoured the evolution of the first resistant strains. Staphylococcal infections reached epidem ic proportions in the late 1950s and early 1960s.(551 The successive introduct ion of new ant ibiotics all but elimi naled Gram-positive cocci, which nonetheless gave way to Gram-negative rods, especiall y enterobacteria and pseudomon­ads. 156,57]

Recent years have seen a tendency towards in­creasingly frequent infections caused by Gram­positive cocci and species of Candida fu ngi, al­though pseudomonads and enterobacteria continue to be major causes of nosocomial infection.f53.58-621 Data from the National Nosocomial Infect ion Study (NNIS) for the period between 1986 and 1989 give the causes of 85% of all reponed infec­tions; of these, 85% were due to aerobic bacteria, 5% to anaerobic bacteria, 9% to fu ngi, and the re­maining I % to viruses, protozoa and parasites.(OOl

\31

As table III shows, the frequency with which different micro-organisms are isolated varies with the infection site. Escherichia coli, which predom­inated in urinary tract infections and was also com­mon in other sites, was the most frequently isolated pathogen in all types of infection regardless of the site of infection. Staphylococclls al/rellS, com­monly isolated in all sites except the urinary tract. was next in order of freq uency, fo ll owed by en­terococci, pseudomonads and coagulase-negative staphy lococci. The increasing frequency of these latter micro-organisms is thought to be attributable to their role in bacteraemias.l 601

Nosocomial infections may be exogenous or en­dogenous on the basis of the source of the causlil micro-organism. More than 80% of all infections are of endogenous origin, i.e. caused by micro-or­gan isms that had previously colonised the pa­tient. (63-65 j Afteradmission, all patients are rapidl y colonised by hospital micro-organisms, wh ich be­come part of the patient 's commensal flora, In the

nble III , Frequency (%) of organism responsible for nosocomial infections according to major sile. Data from the National Nosocomial Surveillance System 1986-198g10501

Organism

Bloodstream Coagulase-negative staphylococci

Staphylococcus aureus

Enterococci

Candida spp.

Escherichia coli

Enterobacter spp.

Klebsiella pneumoniae

Pseudomonas aeruginosa Streptococci

Proteus mirabilis

Pneumonia P aerug;nosa S. 8ureus

Enterobacter spp. K. pneumoniae

E. coli

Candida spp.

Serratia marcescens

P. mirabilis

Enterococci

Streptococci

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Frequency

28

" 8

8

6

5 , , ,

" " " , 6

5 , 3 ,

Organism

Surgical wound infections S. aureus

Emerooocci

Coagulase-negative staphylococci

E.coIi

P. aeruginosa

Enlerobar:tfN spp. P. mirabilis

K. pneumoniae

Streptococci

Candida albicans

Urinary tract infection E. coli

Enterococx:i

S. auf6US

P 8eruginosa

CaneJida spp.

EnlerobactfN spp. K. pneumoniae

P. mirabilis

Coagulase-negative staphylococci

Cilrobacter spp.

Frequency

n

" " " 8

8 , , , ,

" " n

" , 6

6

5 , ,

PhcurnocoEcOl""lOfY"»cs 7 (2) 1<1%

next stage, the host is infected not by his or her origi nal flora, but by colonising micro-organisms that characterise the hospital environment.[66.67) Exogenous infections, on the other hand, are much less frequen t, and most of the causa) agents are transmiued by direct contact (mainly via the hands),135.68.70) whi le transmi ssion via contami­nated objects plays a relatively minor role. It is nevertheless true that nearly half of all nosocomial infections are related to invas ive diagnostic or therapeutic devices, such as uri nary and intravas­cular catheters and mechanical ventilators, among others.17 ]J

2.2 Host Factors

2.2.1 Endogenous Facfors Endogenous or intrinsic host-dependent factors

such as age, sex, nutri tional Slatus, immune status, clinical status and severity of the u nderlying dis­ease(27,3 t.39.72-77) influence the inherent risk of in­fect ion, but can be modified onl y slightly, if at all. Such factors determine the proportion of risk pres­ent in a given patient al the moment of hospital admission, and have become one of the major in­fluences of infection r ates.J39.78 ] Increased life ex­pectancy, particularly that achieved b y prolonging life in chronically or terminally ill patients, has led to an overall increase in host susceptibility. Hos­pital ised patients are becoming o lder and sicker, and hence more susceptible.fI5 ,79l

The importance of a patient 's immune status is obvious, and this factor has become especially rel­evant with in the context of the AIDS epidemic. Moreover, it appears evident that a patient with chronic bronchitis, in w hom the defence mecha­nisms in the respiratory mucosa are markedly de­teriorated, is at much greater risk than a patient admitted for correction of a hernia. Understand­ably, an intensive care unit occupied by coronary patients will have much lower infection rates than a medical-surgical uni t.[26,32-35l

In addition to the underlying disease, the sever­ity of the disease, i.e. the patient's degree of phys­iological deterioration, infl uences the likelihood of nosocomial infection.[78l T his is an area of re-

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search that has received increasing attention in re­cent years. The severi ty of the patient's disease needs to be laken into account in comparisons of infec tion rales between diffe rent hospitals, or re­lated to different procedures,115,79l as these factors have been shown to mod ify the risk of infection.

Several objective measures have been proposed as indicators of disease severity,[26.38,801 incl uding the Therapeutic In tensity Score System,l8 1l the Acute Physiologic and Chronic Health Evaluation system[82l and the Index ofComorbidity.[83] These indicators, for the most part, are di rectly correlated with the risk of death, and have also been shown to be related to the chance of nosocomial infec­tion.l26l The risk of in fection increases with sever­ity of the illness up to a threshold value, then sta­bil ises or declines. The change in the direction of this association resu lts from increased mortality during the first hours of hosp italisation in patients in whom the severity of ill ness surpasses a certain threshold .1 33.84,85]

A patient 's intrinsic risk has been considered the equivalent of the severity of his or her underlying disease. Most recent studies emphasise the need to develop overa ll indicators of intri nsic risk, al­though the most notable progress in this area has been limited 10 studies of surgical wound infec­tion)37,381 A suitable indicator of risk should ide­ally be developed with the help of multivariate analysis, and efforls shou ld be made to include all those variables that contribute 10 intrinsic risk.! 371 Such an indicator should:

• weight the specific imparlance of each risk factor • establish the intrinsic likelihood of an individ­

ual lO have an infection

• permit comparisons of specific infection rates per risk category, and

• control fo r confou nding factors. 1861

2.2.2 Extrinsic Focfors Extrinsic risk factors (table IV) are those that

increase the chances of contact between an infec­tious agent and a host, facil itate invasion of host tissues, potentiate infectiousness, pathogenicity or

I'hormocoEconorrics 7 (2) 1m

Nosocomial Infection

virulence of the i nfectious agent, or dim inish the hosl's defences.!87 )

All invasive procedures the patient undergoes can be considered eX lrinsic ri sk fac tors, from placement of a urinary catheter for cystoscopy to surgery, although the aetiological importance of each procedure varies depending on the infec tion site, how the instruments are handled by hospi tal staff, and the duration of exposure to different pro­cedures.130,71.88·101 I Other extrinsic risk factors are treatments. whether indicated or not, which modify the patient's intrinsic susceptibility to in­fection. Antibiotics. transfusions of blood or blood-derived products, and immunosuppressive agents such as corticosteroids and cytostatics can be included in this category.l91,102. 1051

In vas ive proced ures, which are assoc iated with at least 50% of all nosocom ial infec­tions,f30.71.88.106) and therefore are poten ti ally important factors in its prevention, are t he most accurate predictors of infection risk. Despite the connection between invasive procedures and nos­ocomial infection. their role has most often been studied in epidemic outbreaks, whereas their rela­tionship with endemic rates of nosocomial infec­tion remains obscure.

The scarcity of reliable information can be traced to the lack of an adequate database; because the number of patients who have undergone inva­sive procedures is not known, the corresponding procedure-specific infection rates cannot be esti­mated.123.301 In addition, each patient usually

Table IV. Extrinsic risk factors for nosocomial infection

Physical environment of the hospital

Hospital staff

Medicat-surgical instruments intravascular device urinary catheter tracheal intubation assisted respiration

Therapeutic interventions antibiotics immunosuppresive agents blood and blood.oorived products rad iotherapy surgery

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133

undergoes more than one procedure, and more se­riously ill patients are more likely to have been subjected to more procedures, making it difficul t to determine the aetiological role and the att ribut­able proportion of each to extrinsic risk.130.71. ]071

3. Treatment of Nosocomiallnlection

3. J Aseptic Techniques

The control of nosocomial infections was first undertaken in the mid-nineteenth century. In 1847, Semmelweis showed that puerperal infecti on de­creased when medical students washed their hands before they anended women during and after child­birth, and was thus the fi rs t to successfully treat this entity.l108j These results supported the trans­missible nature of nosocomial infect ion, a notion that was later reinforced by others such as Simp­son, Holmes and Lister, who helped lay the foun­dation fo r surgical asepsis and antisepsis.ll0S1

A clean environment, steri lisation of all mate­rial that penetrates the skin or makes contact with Ihe mucosa, and strict asepsis during any invasive procedure are now considered essential. Of all these measures, the most important is hand wash­ing (including when gloves are worn) before and afler contact with each patient.

3.2 Surveillance

From a different stand-poin!. the surveillance and control of nosocomial infection have been shown to reduce its incidence by 32%.1 !091 Meas­ures such as the communication of in fection rates to surgeons have brought about addit ional reduc­tions .llIOI Surveillance of nosocomia l infections now constitutes the main approach tocontrol;! 111-1131 its effectiveness is based on the timely idcntifi(~a­tion of changes in risk fac tors for infection, the development of preventive and control measures suggested by analyses of epidemiological d;lta, and the evaluation of control measures adopted.

3.3 Pharmacological Approaches

Despi te the importance of disinfection, ster­ilisation and surveillance, treatment of nosocomial

PhormocoEcOflO<T'oics 7 (2) 1995

134

infect ion usua ll y means pharmacologica l treat­ment with antibiot ics. These drugs account for slight ly over 25% of a hospital's pharmaceutical expenses, and the proportion may be on the in ­crease. The prevalence of antibiotic treatment in differe nt hospitals ranges from 23.5%11141 to 38%,1115) and can surpass 50% in intensive care services.1201 In general, approx imately one-thi rd of all hospitalised palients receive ant ibiotics at some time du ring their stay; l] 16) of this proportion, 70% are given these drugs for therapeutic indications. and the remaining 30% for prophy laxis. 1117 )

However, as many as 50% of antibiotic courses may be superfluous.11 ]8 ) Dunagan Cl al.I 1191 esti­mated that 22% of all treatment days were inappro­priate. The percentage of hospital patients who re­ceive at least one antibiotic increased from 22% in 1978 to 44% in 1992; this was parall eled by a rise in the mean number of differe nt antibiotics pre­scribed from 1.8 to 2. 1.[1201

A detail ed examination of the treatment for di f­fe rent types of nosocomial infecti ons is beyond the scope of this review. In general , factors that should be kept in mind when managing nosocomial infec­tions are the anatomical site, suspected or docu­me nted cause (and resu lt s o f antim icrobial sen ­si tiv ity tests), the resistance patterns prevalent in a given hospital , and espec ially patient charac­teri stics.

3.3.' Chemoprophylaxis Chemoprophy laxi s is another aspect of a nt ibi­

otic manage ment o f nosocom ial infection. In clean-contami nated surgery, clean operations in­volving foreign materials and in contami nated sur­gery, chemoprophylax is has been wide ly accepted as an effecti ve measure against nosocomial infec­tion.[ 121-1231 The theoretical basis for prophylactic trealment is that il maintains high enough plasma antibiotic levels duri ng the operation to keep the microbial load that reaches the surgical fie ld within nonin fecti ve limits.

A review by Ehren kranzl1241 emphasised that the effectiveness of intraoperative prophylaxis has been convincingly shown, and the optimal duration of the perioperative period during which prophy-

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lax is should be given has been deli mited. Prolong­ing the administration of anti biotics for longer than necessary was not only shown to be ineffect ive, but was also found to involve risks and to increase costs. The most common errors were delaying chemoprophylaxis or extending it unduly. Excel­lent publi shed reviews have provided a set of ru les for the appropriate selection and use of antibiotics as prophylaxis against surgical wound infec­tion .1125-1301

The effectiveness of chemoprophylaxi s in sur­gical patients has been attributed to coverage dur­ing a clearly de lim ited and usually brief period. Extension of the philosophy of chemoprophylaxis to other invasive procedures, such a s the placement o f a uri nary catheter or tracheal intubation. must nonethe less be weighed against longer exposure and treatment periods, which increase the chances that resistant micro-organi sms will be selected and favou red.

Because of this drawback. there is still contro­versy regardi ng the effective ness of se lective di­gesti ve decontam ination in preventi ng respiratory infect ions of endogenous origin in intubated pa­tients. II3I-1341 Initi al enth usiasm for this measu re was fo llowed by the reali sation that although the incidence of lower respiratory tract infecti on de­creased . mortality due to nosocom ial in fection re­mained unchanged. I135.136l At the First European

Consensus Confere nce in Inten sive Care Medic ine, it was concluded that although selecti ve digestive decontamination was potentially useful in prevent­ing nosocomial pneumonia in patients with severe injuries, its eventual effect on bacterial resistance in patients needi ng long stays in the intensive care unit should be carefully evaluated. I 1371

4. The Cost of Nosocomial Infections

The mean cost of nosocomial infect ions varies depending on the predominant types of infection in each hospital and thc cost of healthcare in a givcn setti ng.

PhormocoEconomics 7 (2) 1995

Nosocomial Infection

4.1 Direct Costs

In the UK, nosocomial infections were respon­sible for more than 950 000 days of hospitali sation in 1986, representing an estimated cost of £ III million.[138) In the US, each infection led toa mean of 4 days of hospi tali sation. with a cost of $US 1833 at 1985 values.l 1391 Projection of these figures for the entire country yie lded a total of 8 700 000 days of hospital care, at a cost of$US4.5 bi11ion.154l In the former Federal Republic of Ger­many, nosocomial infections were estimated to cost between DM500 and DM 1000 million annu­ally at 1984 values.1140l A Spanish study reported that these infections led to a mean adjusted prolon ­gation of 9.9 days in intensive care.114t I At 1993 values, this represents a cost of Pta I 551 833 (ap­proximately $US II 000) per infection .

The figures for all of these stud ies represent the direct costs! 142[ associated with prolonged hospital stays and the increased needs for diagnostic and therapeutic services,!14},144) and do not include healthcare costs outside the hospital . Because the cost of hospitalisation and treatment differ widely between countries and hospi tals, it is difficu lt 10 use these data to calculate the theoretical costs in­volved for a g iven centre. The methods used to ide ntify costs attributed directly to nosocomial in fections are more informati ve for this pur­pose.l145.151l

Subjecti ve methods used 10 estimate hospital stays att ributable to nosocomial infections have in­volved the observation of infected patients and the review of patient records. I 152] The validity and re­liability of these methods are open to doubt, and they generally tend to underestimate the cost of nosocomial infection.1147J Part of the problem stems from the practice of considering only those days beyond the projected discharge date as a pro­longation of hospital stay, a measure that would be valid only if the infection were manifested on the discharge date. When nosocomial infection ap­pears before the date of discharge, thi s date is then postponed precisely because of the infection.l t49 [ In addit ion, infected patients are usually among the more seriously iII,I141.!47. 1521 and are likely to re-

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135

main hospitalised for longer; this complicates the subjective assessment of hospital days attributable excl usively to the infection.l 152 ) An additional fac­tor is that the development of a nosocomial infec­tion can lead to further compli cations such as su­ture dehiscence and renal insuffic iency, which also prolong the hospital stay and increase costs.

A more widely used and objecti ve alternative is 10 observe patients with and without nosocomial infecti on.11471 and compare the length of stay in the 2 groups. The choice of the control group deter­mines the validi ty of such studies, as the distribu­tion of variables that can influence the risk of in­fec tion and the length of stay must be sim ilar in both groups,! 1451 Paired case-control studies selcct one or more noninfected control patients per in­fected patient , matching them for fac tors that might have affected the length of stay, then calcu­late the difference in cost per each case-control pair. The sum of the differences for all infected patients is then taken to represent the difference in cost attributable to nosocomial infection.1147J

The results of such st udies arc strongly condi ­ti oned by the choice of pairi ng variables, which should ideally be limited to those that con found the resu its.l145,1471 The closer the pairing, the lower the estimated stay attributable to infection. Consid­ering nosocomial infect ion as a single emily can lead to serious errors in the estimate, as the infec­tion site can markedly influence the cost. As table V shows. pneumonias were associated with higher costs, fo llowed by septicaemias and surgical wound infections,l 541 Indeed, different causal agents may be associated with different wsts in the same anatomical site.

4.2 Indirect Costs

Nosocomial infection also generates indirect costs (such as reduced productivity) as a resull of morbidity and mortality associated with infec­tion.l33.34.86,140) The intangible costs associated with the pain, suffe ri ng and anxiety experienced by patients and thei r relatives arc difficu lt to calculate, Although nosocomial infections have been shown to increase work absenteeism,l153) most studies

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T.ble V. Estimated e~l ,a days. extra eharoes and deaths atlributable to nosocomial infections in US hospitals (adapted from Martone at 81.1501~

Infection Average eidra lime in AVllrage eidra charges Deaths directly caused Deaths to which hospital per infection per infection by inlect~ns infection COI11nOOied (days) (1992 SUS)

Surgical wound Infection 7.3 3152 0." 1.91

Pneumonia 5.9 S683 3.12 10.13

septicaemia 7.' "" 4 .37 8.59 Urirwy tract Infection 10 680 0.10 0.72 -- ., 1617 0.80 2."

All ail'" ' .0 "00 0.90 2.70 a The data lor all tiles do not correspond to the arithmetic means 01 the data lor individual sites because of the ddlefllOce in incidence

between ditlerent infection types. For example. urinary tract infections ale more common than septicaemia or pneumonia.

consider only costs assoc iated with mortality at­tributed to the infcction,l154 ) despite the difficulty of establishing an unequivocal link between mor­tality and a specific emity. in thi s case nosocomial infection.

Data provided by the NNJS indicate that 0 .9% of pat ients wi th nosocomial infect ion die as a direct result , and that the infection contribu tes to death in an additional 2.7% (table V). In the US, these fig­ures translate to 19000 deaths annually, traceable directl y to nosocomial infec tion, and 58000 deaths in which the infection is a contributing fac tor.[54[ When evidence of nosocomial in fect ion is sought from data on hospital mortality, the fi gures are even more imposing; one-third of all intrahospi tal deaths are thought to be related to hospital infec­tions. In a study of 88 patients who died with hos­pital infections, Gross et aLl 1551 concluded that in­fect ion was unrelated to death in only 36; it was the direct cause of the death of 22 pat ient s, and was a major contribut ing fac tor in another 30.

The impact of nosocomial in fec tion on mortal­ity is influenced by many factors, most notably in­fection site. the hospital service in wh ich the pa­tient is admi tted, the aetiological agents invo lved and the severity o f the underly in g di sease (see section 2).m.34.S4.861 A study by Gross and Van Antwerpcn,l841 as well as other reports, found that the nosocom ial infections most commonly associ­ated with increased risk of death were those located in the lower respiratory tract and bacteraemias. Wenzel[ 1561 estimated the mortality attributable to

bacteraemias at 6 to 48%, dependi ng on the patho­gens responsible for causing the infection . A sllLdy by Rodriguez et al .[ 1571 found that among patients who died of nosocomial infection, the most com­mon infection site was the lower respiratory tract (1 3% of all deaths). followed by primary bacter­aemia (4.3%) and urinary tract in fect ion (3%). In a cohort of patie nts admitted to an intensive care ser­vice at the University of Granada Hospi tal the ovcr­all risk of death in patient s with nosocomial infec­tion wa s 2.5 times g reater than in hospitali sed patients without nosocomial infection (28.0% V.f

11 .3%).1861 The strongest association between nos­ocomial infection and mortali ty was found in young patients admitted for less serious ill nesses, i.e. those who wou ld ini tially be assumed to have a better prognosis.l l58)

5. Conclusions

We arc convi nced that nosocomial infection s can be effecti vely managed; indeed. the SEN IC project showed that 30% of all nosocomial infec­lions can actually be prevented. In fection rates, if used as indicators o f Ihe quali ty of healthcarc, can serve as an incent ive fo r the control o f n osocomial infections. Clearly, contro l measures should be im­pl emented from a mu ltidisc iplinary appro;lch. Clinical pharmacists should be e ncouraged to play an act ive role in developing measures to control hospital in fections, because of the elevated propor­tion of pharmaceutical costs represented by antibi · otic treatment, and the effects of antibiotic treat-

Phoo"ocoEOOI'OOIY'ia 1 (2) 1m

Nosocomial Infection

ment on the evolution of agents that cause nosoco­mial infecti ons.

Di viding the costs attributable to an infect ion comrol program me by the anticipllted benefits de­rived from preventi ng infections, a cost-benefit ra­tio for the programme is obtained. At a preventive efficacy of 20%. the costs wou ld outweigh the ben­efits by 30%. However. a t preventive effi cacies of 50 and 80%. the costs would constitute only 5 1 % and 32% o f the benefits. respecti vely.l lS41 As pari of the planning of the SENIC project. Haley] 1471

performed a cost-benefit analysis. At a preventi ve effi cacy of 6%, the cost of the programme wou ld be exactly balanced by the benefit s obllI ined through infections avened. At highcr preventi ve efficacy rates. there would be a net benefi t.

Acknowledgements

We [hank. M s Karen Shashok. for [ransla[ing [he original manuscript into English.

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Correspondence and reprints: Dr Ramon Gillvez-Varsas, Departamento de Medicina Prevcntiva y Salud rublic~, Facultad de Medicina, Universidad de Granada, Avcnida de Madrid 11, 18012 Granada, Spain.

Phormocofconorni<;$ 7 (2) 1905