Maury Ellis Mulligan

Nosocomial Acquisition of Clostridium difficile Infection

We studied the acquisition and transmission of Clostridium difficile infection prospectively on a general medical ward by serially culturing rectal-swab specimens from 428 patients admitted over an 11-month period. Immunoblot typing was used to differentiate individual strains of C. difficile. Seven percent of the patients (29) had positive cultures at admission. Eighty-three (21 percent) of the 399 patients with negative cultures acquired C. difficile during their hospitalizations. Of these patients, 52 (63 percent) remained asymptomatic and 31 (37 percent) had diarrhea; none had colitis. Patient-to-patient transmission of C. difficile was evidenced by time-space clustering of incident cases with identical immunoblot types and by significantly more frequent and earlier acquisition of C. difficile among patients exposed to roommates with positive cultures. Of the hospital personnel caring for patients with positive cultures, 59 percent (20) had positive cultures for C. difficile from their hands. The hospital rooms occupied by symptomatic patients (49 percent) as well as those occupied by asymptomatic patients (29 percent) were frequently contaminated. Eighty-two percent of the infected cohort still had positive cultures at hospital discharge, and such patients were significantly more likely to be discharged to a long-term care facility. We conclude that nosocomial C. difficile infection, which was associated with diarrhea in about one third of cases, is frequently transmitted among hospitalized patients and that the organism is often present on the hands of hospital personnel caring for such patients. Effective preventive measures are needed to reduce nosocomial acquisition of C. difficile.

Methicillin-resistant Staphylococcus aureus: A consensus review of the microbiology, pathogenesis, and epidemiology with implications for prevention and management

Methicillin-resistant Staphylococcus aureus (MRSA) has become a major nosocomial pathogen in community hospitals, long-term-care facilities, and tertiary care hospitals. The basic mechanism of resistance is alteration in penicillin-binding proteins of the organism. Methods for isolation by culture and typing of the organism are reviewed. MRSA colonization precedes infection. A major reservoir is the anterior nares. MRSA is usually introduced into an institution by a colonized or infected patient or health care worker. The principal mode of transmission is via the transiently colonized hands of hospital personnel. Indications for antibiotic therapy for eradication of colonization and treatment of infection are reviewed. Infection control guidelines and discharge policy are presented in detail for acute-care hospitals, intensive care and burn units, outpatient settings, and long-term-care facilities. Recommendations for handling an outbreak, surveillance, and culturing of patients are presented based on the known epidemiology.

CLOSTRIDIUM DIFFICILE-ASSOCIATED DIARRHEA AND COLITIS

OBJECTIVES To review and summarize the status of diagnosis, epidemiology, infection control, and treatment of Clostridium difficile-associated disease (CDAD). DIAGNOSIS A case definition of CDAD should include the presence of symptoms (usually diarrhea) and at least one of the following positive tests: endoscopy revealing pseudomembranes, stool cytotoxicity test for toxin B, stool enzyme immunoassay for toxin A or B, or stool culture for C difficile (preferably with confirmation of organism toxicity if a direct stool toxin test is negative or not done). Testing of asymptomatic patients, including those who are asymptomatic after treatment, is not recommended other than for epidemiologic purposes. Lower gastrointestinal endoscopy is the only diagnostic test for pseudomembranous colitis, but it is expensive, invasive, and insensitive (51% to 55%) for the diagnosis of CDAD. Stool culture is the most sensitive laboratory test currently in clinical use, but it is not as specific as the cell cytotoxicity assay. EPIDEMIOLOGY C difficile is the most frequently identified cause of nosocomial diarrhea. The majority of C difficile infections are acquired nosocomially, and most patients remain asymptomatic following acquisition. Antimicrobial exposure is the greatest risk factor for patients, especially clindamycin, cephalosporins, and penicillins, although virtually every antimicrobial has been implicated. Cases of CDAD unassociated with prior antimicrobial or antineoplastic use are very rare. Hands of personnel, as well as a variety of environmental sites within institutions, have been found to be contaminated with C difficile, which can persist as spores for many months. Contaminated commodes, bathing tubs, and electronic thermometers have been implicated as sources of C difficile. Symptomatic and asymptomatic infected patients are the major reservoirs and sources for environmental contamination. Both genotypic and phenotypic typing systems for C difficile are available and have enhanced epidemiologic investigation greatly. INFECTION CONTROL Successful infection control measures designed to prevent horizontal transmission include the use of gloves in handling body substances and replacement of electronic thermometers with disposable devices. Isolation, cohorting, handwashing, environmental disinfection, and treatment of asymptomatic carriers are recommended practices for which convincing data of efficacy are not available. The most successful control measure directed at reduction in symptomatic disease has been antimicrobial restriction. TREATMENT Treatment of symptomatic (but not asymptomatic) patients with metronidazole or vancomycin for 10 days is effective; metronidazole may be preferred to reduce risk of vancomycin resistance among other organisms in hospitals. Recurrence of symptoms occurs in 7% to 20% of patients and is due to both relapse and reinfection. Over 90% of first recurrences can be treated successfully in the same manner as initial cases. Combination treatment with vancomycin plus rifampin or the addition orally of the yeast Saccharomyces boulardii to vancomycin or metronidazole treatment has been shown to prevent subsequent diarrhea in patients with recurrent disease.

The Search for a Better Treatment for Recurrent Clostridium difficile Disease: Use of High-Dose Vancomycin Combined with Saccharomyces boulardii

Recurrent Clostridium difficile disease (CDD) is a difficult clinical problem because antibiotic therapy often does not prevent further recurrences. In a previous study, the biotherapeutic agent Saccharomyces boulardii was used in combination with standard antibiotics and was found to be effective in reducing subsequent recurrences of CDD. In an effort to further refine a standard regimen, we tested patients receiving a regimen of a standard antibiotic for 10 days and then added either S. boulardii (1 g/day for 28 days) or placebo. A significant decrease in recurrences was observed only in patients treated with high-dose vancomycin (2 g/day) and S. boulardii (16.7%), compared with those who received high-dose vancomycin and placebo (50%; P=.05). No serious adverse reactions were observed in these patients. Comparison of data from this trial with data from previous studies indicates that recurrent CDD may respond to a short course of high-dose vancomycin or to longer courses of low-dose vancomycin when either is combined with S. boulardii.

Contamination of a hospital environment byClostridium difficile

Clostridium difficile was recovered from a variety of environmental sites in three hospital rooms occupied by a patient who had colitis due to this organism.C. difficile was detected for 40 days after the patient was moved from one of these rooms. These findings suggest that the contaminated hospital environment may be a clinically significant reservoir forC. difficile and that this organism may be a nosocomial pathogen. Isolation of patients and adequate decontamination of rooms may be needed to minimize risk to other patients.

EPIDEMIOLOGIC AND CLINICAL UTILITY OF TYPING SYSTEMS FOR DIFFERENTIATING AMONG STRAINS OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS

Typing systems for differentiating among strains of methicillin-resistant Staphylococcus aureus (MRSA) can be valuable tools for the epidemiologist and the clinician. Specific criteria for evaluating such systems are typeability, reproducibility, and discriminatory power. An ideal typing system also would be rapid, inexpensive, technically simple, and readily available. Systems based on the detection of phenotypic variations include antimicrobial susceptibility testing, bacteriophage typing, multilocus enzyme electrophoresis, and electrophoretic methods such as protein electrophoresis and immunoblotting. Systems that directly detect genotypic variations include plasmid profile analysis, restriction enzyme analysis of plasmid DNA, restriction enzyme analysis of chromosomal DNA, Southern blot analysis of specific restriction fragment length polymorphisms, and pulse field gel electrophoresis. In general, the more widely available typing systems based on phenotypic assays and plasmid analysis have limitations in typeability and/or discriminatory power. The chromosomal DNA-based techniques, although promising, are unproven approaches still under active investigation.

Epidemiologic typing systems

Microbial strain typing is a useful adjunct to clinical epidemiology. Phenotypic typing systems examine expressed characteristics, whereas genotypic systems, including recent PCR-based systems, examine chromosomal or plasmid DNA. Typing systems have evaluated bacteria, fungi, and viruses successfully. The criteria used to assess the utility of each system include typeability, reproducibility, and discriminatory power.

In vitro activities of 17 antimicrobial agents against the formate/fumarate-requiring, anaerobic gram-negative bacilli

The in vitro activities of 17 antimicrobial agents were evaluated against 46 clinical isolates of formate/fumarate-requiring anaerobic gram-negative bacilli. Strains of Bacteroides ureolyticus (23) were almost uniformly susceptible to the tested antimicrobials, whereas strains of Bacteroides gracilis (18) showed some striking resistance with penicillin active against only 67%, the cephalosporins active against 67%-89%, and clindamycin active against 67%. Although few strains of Wolinella species/C. concisus (5) were available for testing, these isolates tended to be more resistant than B. ureolyticus but less resistant than B. gracilis.

In vitro activity of novobiocin and rifampin alone and in combination against oxacillin-resistant Staphylococcus aureus

Rifampin and novobiocin both have excellent activity against oxacillin-resistant Staphylococcus aureus, but their single use may be associated with the development of resistance. To help predict their clinical value in our institution, 60 recent clinical isolates of oxacillin-resistant S. aureus were studied for in vitro susceptibility to the two agents. Ten isolates with increased MICs to both agents or to rifampin alone were also studied by modified checkerboard and kill-curve methods. Indifference was consistently demonstrated by the checkerboard method and generally found in kill-curve studies. Prevention of development of resistance was demonstrated with the antimicrobial combinations for some isolates. Isolates with increased MICs for the two agents fell into two distinctive groups, with prevention of the development of rifampin resistance occurring in one group but not in the other, suggesting that different strains of oxacillin-resistant S. aureus may have different capacities for development of rifampin resistance.

Immunoblot Characterization of Porphyromonas Species from Infected Dog and Cat Bite Wounds in Humans

Immunoblot Characterization of Porphyromonas Species from Infected Dog and Cat Bite Wounds in Humans. M. E. MULLIGAN, D. M. CITRON, R. Y. Y. KWOK, AND E. J. C. GOLDSTEIN. From the Veterans Affairs Medical Center, Long Beach, Long Beach; the University of California, Irvine, College of Medicine, Irvine; the R. M. Alden Research Laboratory, Santa Monica; and the UCLA School of Medicine, Los Angeles, California