Diarrheal Disease in the Hospitalized PatientAuthor(s): Peter H. GilliganSource: Infection Control, Vol. 7, No. 12 (Dec., 1986), pp. 607-609Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiologyof AmericaStable URL: http://www.jstor.org/stable/30143887 .

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Cost Contoinment in nfection Control Dr. Gilligan's review of diarrhea is particularly worthwhile

because it focuses on the diagnosis and cost-effective manage- ment of nosocomial diarrhea. Isolated cases of diarrhea, clusters

Edited by Peter A. Gross, MD

of cases, and cases in AIDS patients each present a unique range of etiologic agents and therefore, a unique method for diagnostic evaluation.

Diarrheal Disease in the Hospitalized Patient Peter H. Gilligan, PhD

In the past 15 years, our knowledge of the pathogenesis and etiologic agents of diarrheal disease has expanded rapidly. No longer is it scientifically appropriate or cost effective for the laboratory simply to culture a stool for Salmonella and Shigella and to do a wet mount for amebae. Today we have a plethora of agents including, but not limited to, Campylobacter, Yersinia, Clostridium difficile, Escherichia coli, Aeromonas, Plesiomonas, vibrios, rotavirus, Norwalk agent, Giardia, and Cryptosporidium, which have all been suggested to be agents of diarrheal disease. Given such a wide range of possibilities, what approaches should be taken to determine the etiologic agent of diar- rheal disease in the hospitalized patient in an era of cost containment?

In this paper I will discuss three aspects of this prob- lem. They will be: 1) the most frequent causes and diag- nosis of nosocomial diarrhea in adults and children; 2) food-borne outbreaks of diarrheal disease in hospitalized patients; and 3) the special diagnostic problem presented by chronic diarrhea in AIDS patients.

For patients who develop diarrheal disease while hospi- talized, two organisms, C difficile and rotavirus, are proba- bly the most common. In a study of unselected, primarily adult patients with diarrhea, we found C difficile to be the most common etiologic agent recovered.' Several stud- ies2,3 have shown rotavirus to be the most frequent cause

From the Clinical Microbiology-Immunology Laboratories, North Carolina Memorial Hospital and Departments of Microbiology & Immunology and Medi- cine, School of Medicine, University of North Carolina.

Address reprint requests to Peter H. Gilligan, PhD, Department of Micro- biology & Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC 27514.

of diarrhea in young children. The magnitude of nosocomial diarrhea caused by these organisms is unknown, mainly because accurate diagnostic tests for detection of these organisms are only now becoming widely available.

The diagnosis of C difficile should be considered in all individuals older than 2 years who are receiving or have recently received antimicrobial or anti-cancer chemother- apy and develop diarrhea. Both antimicrobial and anti- cancer chemotherapy have been shown to be important predisposing factors for disease caused by this organism.4 Most of these individuals will be hospitalized. The diag- nosis of C difficile disease is difficult to make in children less than 2 years old because many asymptomatic children in this age group can harbor this organism and the toxin(s) it makes.5 Limited data concerning the attack rate of C difficile in hospitalized patients indicate that this organism is an important cause of nosocomial infection.

In a retrospective survey performed over a 13-month period of patients with diarrheal disease in seven hospitals in the Philadelphia metropolitan area,6 a composite C difficile attack rate of 0.9 per 1000 discharges and 1.8 per 1000 discharges was found at three university and four community teaching hospitals, respectively. The attack rate at the individual institutions varied from 0.3 per 1000 discharges to 3 per 1000 discharges. Diagnosis of C difficile was accomplished by cytotoxin detection using tissue culture assay. Greater than 95% of the patients from whom clinical information was available were receiving or had recently received antimicrobials.

The pathogenicity of C difficile is due to its ability to produce two protein exotoxins, one that has primarily cytotoxic activity and the other having enterotoxic activity.7 The diagnosis of C difficile disease is best accom-

INFECTION CONTROL 1986/Vol. 7, No. 12 607

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plished by detecting toxin directly in feces. The gold standard for detecting toxin is a tissue culture cytotoxicity assay.8 Other techniques, including enzyme immunosor- bent assay (EIA),9 counterimmunoelectrophoresis (CIE),1' and latex agglutination" have been proposed to

supplant this technique. However, EIA reagents are not commercially available, CIE lacks sensitivity and speci- ficity, and the latex agglutination test which is commer-

cially available is currently clouded in controversy.12 Culture is not a useful alternative to toxin detection for

definitive diagnosis of this disease because asymptomatic individuals who have received antimicrobials can be culture positive but toxin negative.'3 Culture, however, may be a useful tool in assessing the efficacy of treatment and the probability of relapse since it has been shown that C difficile persists in individuals who relapse after discon- tinuation of appropriate therapy.14

Nosocomial spread of C difficile is well documented.'5 The ability of this strict anaerobe to persist in the hospital is due to its ability to produce spores. Studies have shown that the spores can persist in the environment for up to 5 months.16 In addition, these spores are often resistant to

many commonly used disinfectants. This suggests that

patients suspected of having C difficile infection should be

placed on enteric precautions. When patients proven to have C difficile disease vacate their rooms, the room should be thoroughly cleaned to insure that the new occupant is not exposed to this organism.

Rotavirus is the other organism of primary concern as a cause of nosocomial diarrhea. This organism causes dis- ease primarily in children less than 2 years of age and is a

leading cause of morbidity and mortality in the develop- ing world.'7

Rotaviral infection is often referred to as "winter vomit-

ing disease," which aptly describes two important features of this disease. First, the disease occurs primarily in the winter months in temperate climate zones. Second, one of the most important clinical signs of this disease is vomit-

ing. This sign is present in approximately 60% of patients, whereas diarrhea is seen in approximately 70%.18,19 Vomiting contributes to development of dehydration in these patients, which often results in their hospitalization. The epidemiology of rotavirus may be somewhat unusual for a diarrheal disease pathogen in that not only can it be

spread by the fecal-oral route, but there is some evidence to suggest it may also be spread by the respiratory route.20 If this is true, exposure of uninfected to infected children, especially in crowded wards and nurseries, may result in

rapid spread of the virus. Therefore, techniques are nec- essary to rapidly diagnose this infection so that infection control measures can be taken to prevent its spread.

Rotavirus was first identified by electron microscopy, and this technique remains the most accurate for detect- ing the virus. However, both EIA and latex agglutination tests are commercially available for rotavirus and, although slightly less sensitive and specific than EM,21 both are much more practical, less time consuming, and less expensive.

Latex agglutination has the advantage over EIA of much greater rapidity and ease of performance. As long as it is done early in the disease course when virus excre-

tion is high,22 latex agglutination's sensitivity is similar to EIA. The latex test, which takes approximately 10 minutes to perform, would be a useful screening test, allowing the cohorting of children who were excreting virus. This is a reasonable approach since a significant number of pedi- atric hospital admissions in the winter months are a result of rotavirus disease.19,20 Cohorting of excreters should restrict the spread of rotavirus in the pediatric setting.

Organisms such as Salmonella, Shigella, Campylobacter and Yersinia will rarely be recovered from patients with nosocomial diarrhea. In general, cultures for these organisms should not be performed on feces from these

patients. The most important exception to this is when outbreaks of food-borne diarrhea occur. The infection control officer plays a pivotal role in the recognition and containment of these outbreaks. Early recognition of such outbreaks is critical to their control, since it enhances the likelihood of identifying the source of disease and pre- venting its further distribution. It also allows the institu- tion of infection control measures so that secondary cases of the disease can be prevented.

Determination of the etiologic agent can be greatly enhanced by determining the incubation period of the disease. A short incubation period (ie, less than 12 hours) suggests a toxin induced disease with Staphylococcus aureus, Bacillus cereus, or Clostridium perfringens. It is more useful to try to attempt to isolate organisms causing food- borne disease from implicated foods rather than from the

patient, especially when S aureus and C perfringens (organ- isms which are usually considered normal enteric flora) may be the etiologic agent. Patients who have longer incubation times (>12 hours) are more likely to have food

poisoning due to Salmonella, Shigella, Campylobacter, enteropathogenic E coli, or Yersinia enterocolitica. These

organisms are of concern because of their morbidity and

mortality in debilitated patients. Of special note are out- breaks characterized by patients having bloody diarrhea. In this situation, cytotoxin-producing E coli should be sought because of their association with food-borne hem-

orrhagic colitis.23 Because detection of this organism can be difficult, assistance from the state health laboratory should be solicited. Although food-borne outbreaks in

hospitals are relatively uncommon, their identification and control is dependent on early detection by the infec- tion control practitioner.

AIDS patients with chronic diarrhea present an ever

increasing challenge to both infection control practi- tioners and clinical microbiologists. The determination of an etiologic agent of chronic diarrhea in these patients is important since diarrhea can be life-threatening and recurrent bacteremia secondary to bacterial diarrhea, especially with Salmonella, occurs much more frequently in this population.24 Cryptosporidium is a parasite that appears to be a frequent cause of diarrhea in AIDS patients. The diagnosis of this disease may be difficult to make unless special techniques are used to concentrate the parasite and visualize it.25 In addition, these patients are often chronically treated with antimicrobials, and so the diagnosis of C difficile in these patients should always be considered. Because HTLV-III/LAV infects the nerv- ous system, patients with AIDS can become incontinent,

608 Cost Containment in Infection Control/Gilligan

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further complicating their care and control of the agents with which they may be infected.

The key to laboratory diagnosis of diarrheal disease in the hospitalized patient is the physician's understanding of the pathogenesis and epidemiology of the different etiological agents of diarrhea. He/she must also be aware that specific techniques and media are required for the detection of different enteric pathogens. The clinical microbiology laboratory must have the flexibility to allow screening for individual enteric pathogens such as C difficile or rotavirus when clinically indicated. This will reduce costs for both the patient and the laboratory. Clos- tridium difficile in older children and adults and rotavirus in young children will be the agents most commonly causing nosocomial diarrhea. Tests to detect these organ- isms should be done first, and only when this testing is negative should other agents be considered. If the patients are receiving antimicrobials, the likelihood of detecting other agents in non-outbreak situations will be very low and may not be warranted. Control of food-borne outbreaks of diarrheal disease is dependent upon sur- veillance, which should result in their prompt recogni- tion. Finally, chronic diarrhea in AIDS patients requires that the full resources of the clinical microbiology labora- tory be used to establish the etiology of disease.

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