What to think if the results of the National Institutes of Health randomized trial of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus control measures are negative (and other advice to young epidemiologists): a review and an au revoir.

The incidence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) infections continues to rise in National Nosocomial Infections Surveillance system hospitals, and these pathogens are reportedly causing more than 100,000 infections and many deaths each year in US healthcare facilities. This has led some to insist that control measures are now urgently needed, but several recent articles have suggested that isolation of patients does not work, is not needed, or is unsafe, or that a single cluster-randomized trial could be used to decide such matters. At least 101 studies have reported controlling MRSA infection and 38 have reported controlling VRE infection by means of active detection by surveillance culture and use of isolation for all colonized patients in healthcare settings where the pathogens are epidemic or endemic, in academic and nonacademic hospitals, and in acute care, intensive care, and long-term care settings. MRSA colonization and infection have been controlled to exceedingly low levels in multiple nations and in the state of Western Australia for decades by use of active detection and isolation. Studies suggesting problems with using such data to control MRSA colonization and infection have their own problems, which are discussed. Randomized trials are epidemiologic tools that can sometimes provide erroneous results, and they have not been considered necessary for studying isolation before it is used to control other important infections, such as tuberculosis, smallpox, and severe acute respiratory syndrome. No single epidemiologic study should be considered definitive. One should always weigh all available evidence. Infection with antibiotic-resistant pathogens such as MRSA and VRE is controllable to a low level by active detection and isolation of colonized and infected patients. Effective measures should be used to minimize the morbidity and mortality attributable to these largely preventable infections.

What proportion of hospital patients colonized with methicillin-resistant Staphylococcus aureus are identified by clinical microbiological cultures?

BACKGROUND: Most hospitals in the United States do not perform active surveillance cultures and, thus, rely on clinical microbiological cultures (CMCs) to identify patients colonized with methicillin-resistant Staphylococcus aureus (MRSA). We sought to determine what proportion of patients who are colonized with MRSA at admission are identified by CMCs during hospitalization. METHODS: From February 1998 through November 2002, patients found to be colonized with MRSA at admission by use of active surveillance cultures were identified. The proportion of colonized patients who had a CMC that was positive for MRSA, the number of CMCs performed and their type (ie, according to the anatomical site from which specimens were obtained for culture), and the number and type of CMCs that were positive for MRSA were calculated. RESULTS: Four hundred thirty-seven patients were found to be colonized with MRSA at admission, and 98 of 1,238 CMCs (7.9%; 95% confidence interval, 6.5%-9.6%) performed for 66 of these patients (15%; 95% confidence interval, 11.9%-18.8%) were positive for MRSA. The number of nonisolated days that would have occurred by relying on CMCs to identify MRSA-colonized patients was 3,247 (mean, 7.4 days per patient). Among the anatomical sites from which specimens were obtained for CMC, wounds demonstrated the highest sensitivity (30.2%) for identifying MRSA-colonized patients. CONCLUSIONS: CMCs failed to identify 85% of MRSA-colonized patients, because, in part, CMCs identified only a small proportion of colonized patients. Because many studies have shown a decrease in the transmission of MRSA from colonized patients for whom contact precautions, rather than standard precautions, are used, the findings of this study suggest that failure to identify colonized patients and to use contact precautions may be an important reason for the increasing rate of nosocomial MRSA infection in hospitals in the United States.

Cognitive effects of diarrhea, malnutrition, and Entamoeba histolytica infection on school age children in Dhaka, Bangladesh.

Cognitive function was assessed in 191 Bangladeshi children 6-9 years of age using verbal and nonverbal tests. These scores were added to a health surveillance database that was compiled over the four previous years that includes incidence of diarrhea and Entamoeba histolytica infection and nutritional status. The associations of diarrhea, malnutrition, and social factors with cognitive scores were analyzed statistically, and associations between diarrhea and test scores were controlled for the influence of social factors. Cognitive scores were negatively associated with stunting during school age, as well as the height-for-age and weight-for-age scores at study enrollment. Incidence of diarrhea was associated with nonverbal test scores before, but not after, controlling for socioeconomic factors. Generally E. histolytica infection was not found to independently influence scores, except that E. histolytica-associated dysentery was associated with lower test scores while dysentery of any etiology was not. Thus, malnutrition during the school age years, but not diarrhea or E. histolytica infection, was associated with a lower level of cognitive functioning. This suggested that intervention during school age years may be able to mitigate the cognitive deficiencies associated with malnutrition.

Community-acquired methicillin-resistant Staphylococcus aureus: a meta-analysis of prevalence and risk factors.

Reports suggest that carriage of methicillin-resistant Staphylococcus aureus (MRSA) among persons without health care-associated risks has increased. A meta-analysis of studies reporting the prevalence of community-acquired MRSA (CA-MRSA) among MRSA isolates from hospitalized patients or the prevalence of MRSA colonization among community members was conducted. The CA-MRSA prevalence among hospital MRSA was 30.2% in 27 retrospective studies and 37.3% in 5 prospective studies; 85% of all patients with CA-MRSA had > or =1 health care-associated risk. The pooled MRSA colonization rate among community members was 1.3% (95% confidence interval [CI], 1.04%-1.53%), but there was significant heterogeneity among study populations. Community members from whom samples were obtained in health care facilities were more likely to be carrying MRSA than were community members from whom samples were obtained outside of the health care setting (relative risk, 2.35; 95% CI, 1.56-3.53). Among studies that excluded persons with health care contacts, the MRSA prevalence was 0.2%. Moreover, most persons with CA-MRSA had > or =1 health care-associated risk, which suggests that the prevalence of MRSA among persons without risks remains low (< or =0.24%). Effective control of dissemination of MRSA throughout the community likely will require effective control of nosocomial MRSA transmission.

Control of endemic vancomycin-resistant Enterococcus among inpatients at a university hospital.

We sought to determine the ability of surveillance cultures and isolation of vancomycin-resistant Enterococcus (VRE)-colonized patients to control nosocomial VRE infection and colonization during a 5-year period (November 1994 through October 1999). During this period, VRE colonization was limited to 0.82% of admissions. The incidence of VRE infection was 0.12 cases per 1000 patient-days (attack rate, 0.07%). Colonized patients were first identified by surveillance (95%) or routine clinical cultures (5%); 14% of colonized patients had a positive clinical culture a median of 15 days after a positive surveillance culture. Ten percent of colonized patients were identified by surveillance at the time of transfer from another health care facility. Identification of these colonized patients was associated with reduction from a peak incidence rate of 2.07% to a rate of 1.25% and stabilization at this lower level. The use of surveillance cultures to identify and isolate patients with asymptomatic colonization can provide sustained control of the spread of VRE within a health care facility.

Influenza in the acute hospital setting.

Influenza poses special hazards inside healthcare facilities and can cause explosive outbreaks of illness. Healthcare workers are at risk of acquiring influenza and thus serve as an important reservoir for patients under their care. Annual influenza immunisation of high-risk persons and their contacts, including healthcare workers, is the primary means of preventing nosocomial influenza. Despite influenza vaccine effectiveness, it is substantially underused by healthcare providers. Influenza can be diagnosed by culturing the virus from respiratory secretions and by rapid antigen detection kits; recognition of a nosocomial outbreak is important in order to employ infection-control efforts. Optimal control of influenza in the acute-care setting should focus upon reducing potential influenza reservoirs in the hospital, including: isolating patients with suspected or documented influenza, sending home healthcare providers or staff who exhibit typical symptoms of influenza, and discouraging persons with febrile respiratory illness from visiting the hospital during a known influenza outbreak in the community. (Note: influenza and other respiratory viruses can cause non-febrile illness but are still transmissible.) The antiviral M2 protein inhibitors (amantadine, rimantadine) and neuraminidase inhibitors (zanamivir, oseltamivir) have proven efficacy in treating and preventing influenza illness; however, their role in the prevention and control of influenza in the acute hospital setting remains to be more fully studied.

Outcomes associated with vancomycin-resistant enterococci: a meta-analysis.

BACKGROUND: Because patients with vancomycin-resistant Enterococcus bacteremia (VREB) usually have a higher severity of illness, it has been unclear whether VREB is worse than vancomycin-susceptible Enterococcus bacteremia (VSEB). METHODS: Data on morbidity and case fatality rates and costs were pooled from studies comparing VREB and VSEB, identified by Medline January 1986 to April 2002) and meeting abstracts. Heterogeneity across studies was assessed with contingency table chi-square. Multivariate analyses (MVAs) controlling for other predictors were evaluated. RESULTS: Thirteen studies compared case-fatality rates of VREB and VSEB. VREB case fatality was significantly higher (48.9% vs 19%; RR, 2.57; CI95, 2.27 to 2.91; attributable mortality = 30%). Five studies compared VREB with VSEB when bacteremia was the direct cause of death; VREB case fatality was significantly higher (39.1% vs 21.8%; RR, 1.79; CI95, 1.28 to 2.5; attributable mortality = 17%). Four MVAs found significant increases in case-fatality rates (OR, 2.10 to 4.0), 3 showed trends toward increase (OR, 1.74 to 3.34 with wide confidence intervals), and 3 with low statistical power found no difference. VREB recurred in 16.9% versus 3.7% with VSEB (P < .0001). Three studies reported significant increases in LOS, costs, or both with VREB. CONCLUSION: Most studies have had inadequate sample size, inadequate adjustment for other predictors of adverse outcomes, or both, but available data suggest that VREB is associated with higher recurrence, mortality, and excess costs than VSEB including multiple studies adjusting for severity of illness.

Failure to develop vancomycin-resistant Enterococcus with oral vancomycin treatment of Clostridium difficile.

OBJECTIVE: Oral vancomycin therapy has been a risk factor for turning culture positive for vancomycin-resistant Enterococcus (VRE). VRE colonization status was reviewed for all patients who received oral vancomycin and underwent prospective cultures. METHODS: Data were extracted from the medical records of all patients receiving oral vancomycin between August 1995 and February 2001 regarding history, hospital course, and perirectal VRE cultures. Hospital policy required contact isolation for patients receiving oral vancomycin until colonization with VRE was excluded. RESULTS: Twenty-six courses of oral vancomycin were given to 22 patients. VRE colonization status after completion of therapy was evaluated for 23 courses in 20 (91%) of these patients. None of these patients became VRE culture positive during a median follow-up of 18 days (range, 9 to 39 days), with a median duration of treatment of 10 days (range, 3 to 58 days), and with a median total dose of 6,500 mg (range, 1,250 to 29,000 mg). All patients received other antibiotics within 30 days prior to therapy with oral vancomycin, during therapy with oral vancomycin, or both; 95% had received anti-anaerobic therapy and 35% had received parenteral vancomycin. CONCLUSIONS: Even when other risk factors were present, no patient receiving oral vancomycin at our facility subsequently became culture positive for VRE. This suggests that oral vancomycin therapy or other antibiotic use, including anti-anaerobic therapy, may not be a significant independent risk factor for turning culture positive for VRE among patients not previously exposed to the microbe.

Isoniazid-resistant cavitary tuberculosis in a physician following isoniazid prophylaxis.

Single-drug prophylaxis is recommended after tuberculin skin test conversion, but not when there is active disease on chest radiograph because resistance develops frequently. Isoniazid-resistant tuberculosis developed in a physician receiving prophylaxis despite "faint left upper lobe soft tissue density" on chest radiograph. Ignoring active disease on chest x-ray renders this strategy counterproductive and cost ineffective.

Preventing nosocomial influenza by improving the vaccine acceptance rate of clinicians.

OBJECTIVES: To assess the effects of interventions to prevent transmission of influenza and to increase employee compliance with influenza vaccination. DESIGN: The change in the proportion of hospitalized patients with laboratory-confirmed nosocomial influenza was observed over time and assessed using chi-square for trend analysis. The association between nosocomial influenza in patients and healthcare worker (HCW) compliance with vaccine was assessed by logistic regression. SETTING: A 600-bed, tertiary-care academic hospital. METHODS: After an outbreak of influenza A at this hospital in 1988, a mobile cart program was instituted with increased efforts to motivate employees to be vaccinated and furloughed when ill as well as new measures to prevent nosocomial spread. RESULTS: HCW vaccination rates increased from 4% in 1987-1988 to 67% in 1999-2000 (P < .0001). Proportions of nosocomially acquired influenza cases among employees or patients both declined significantly (P < .0001). Logistic regression analysis revealed a significant inverse association between HCW compliance with vaccination and the rate of nosocomial influenza among patients (P < .001). CONCLUSION: A mobile cart vaccination program and an increased emphasis on HCWs to receive the vaccine were associated with a significant increase in vaccine acceptance and a significant decrease in the rate of nosocomial influenza among patients.

Ultraviolet light disinfection of hospital water for preventing nosocomial Legionella infection: a 13-year follow-up.

BACKGROUND AND OBJECTIVE: CDC has estimated that 23% of Legionella infections are nosocomial. When a new hospital was being constructed and a substantial increase in transplantation was anticipated, an ultraviolet light apparatus was installed in the water main of the new building because 27% of water samples from taps in the old hospital contained Legionella. This study reports the rate of nosocomial Legionella infection and water contamination since opening the new hospital. METHODS: Charts of all patients with positive Legionella cultures, direct immunofluorescent antibody (DFA), or urine antigen between April 1989 and November 2001 were reviewed. Frequencies of DFAs and urine antigens were obtained from the laboratory. RESULTS: None of the 930 cultures of hospital water have been positive since moving into the new building. Fifty-three (0.02%) of 219,521 patients had a positive Legionella test; 41 had pneumonia (40 community acquired). One definite L. pneumophila pneumonia confirmed by culture and DFA in August 1994 was nosocomial (0.0005%) by dates. This patient was transferred after prolonged hospitalization in another country, was transplanted 11 days after admission, and developed symptoms 5 days after liver transplant. However, tap water from the patient's room did not grow Legionella. Seventeen (2.5%) of 670 urine antigens were positive for Legionella (none nosocomial). Thirty-three (1.2%) of 2,671 DFAs were positive, including 7 patients (21%) without evidence of pneumonia and 6 (18%) who had an alternative diagnosis. CONCLUSION: Ultraviolet light usage was associated with negative water cultures and lack of clearly documented nosocomial Legionella infection for 13 years at this hospital.

Duration of colonization with vancomycin-resistant Enterococcus.

OBJECTIVE: To determine the duration of colonization with vancomycin-resistant Enterococcus (VRE) and the adequacy of 3 consecutive negative cultures to determine clearance. DESIGN: Retrospective cohort study. SETTING: A university hospital. POPULATION: Patients identified by perirectal cultures as VRE carriers who had follow-up cultures. METHODS: Follow-up perirectal cultures were collected in inpatient and outpatient settings, at least 1 week apart, when patients were not receiving antibiotics with activity against VRE. The likelihood of culture positivity was analyzed given prior culture results and time from the initial positive culture. RESULTS: A total of 116 patients colonized with VRE had 423 follow-up cultures, a mean of 204 days (range, 4 to 709 days) after their initial isolate. The first follow-up culture, collected a mean of 125 days after the initial positive isolate, was negative in 64%. After 1 negative follow-up culture, the next one was negative in 92% of the patients. After 2 negative cultures, 95% remained culture-negative. After 3 sequential negative cultures, 35 (95%) of 37 patients remained culture-negative. As the interval between the initial and the follow-up isolates increased, the probability that a subsequent culture would be positive decreased (P < .001, chi square for trend). Prolonged hospitalization, intensive care, and antibiotic use each decreased the likelihood of clearing VRE. CONCLUSION: These data support the Centers for Disease Control and Prevention criterion of 3 sequential negative cultures, at least 1 week apart, to remove patients from VRE isolation. Nevertheless, this may reflect a decrease in the quantity of VRE to an undetectable level and these patients should be observed for relapse, especially when re-treated with antibiotics.

Cost-effectiveness of perirectal surveillance cultures for controlling vancomycin-resistant Enterococcus.

BACKGROUND: Several hospitals opting not to use active surveillance cultures to identify carriers of vancomycin-resistant Enterococcus (VRE) have reported that adoption of other parts of the Centers for Disease Control and Prevention guideline for controlling VRE has had little to no impact. Because use of surveillance cultures and contact isolation controlled a large outbreak at this hospital, their costs were estimated for comparison with the excess costs of VRE bacteremias occurring at a higher rate at a hospital not employing these measures. SETTING: Two university hospitals. METHODS: Inpatients deemed high risk for VRE acquisition at this hospital underwent weekly perirectal surveillance cultures. Estimated costs of cultures and resulting isolation during a 2-year period were compared with the estimated excess costs of more frequent VRE bacteremias at another hospital of similar size and complexity not using surveillance cultures to control spread throughout the hospital. RESULTS: Of 54,052 patients admitted, 10,400 had perirectal swabs taken. Cultures and isolation cost an estimated $253,099. VRE culture positivity was limited to 193 (0.38%) and VRE bacteremia to 1 (0.002%) as compared with 29 bacteremias at the comparison hospital. The estimated attributable cost of VRE bacteremia at the comparison hospital of $761,320 exceeded the cost of the control program at this hospital by threefold. CONCLUSIONS: The excess costs of VRE bacteremia may justify the costs of preventive measures. The costs of VRE infections at other body sites, of deaths from untreatable infections, and of dissemination of genes for vancomycin resistance also help to justify the costs of implementing an effective control program.

Low rate of false-positive results with use of a rapid HIV test.

BACKGROUND: Occupational exposure to human immunodeficiency virus (HIV) is an important threat to healthcare workers. Centers for Disease Control and Prevention guidelines recommend prompt institution of prophylaxis. This requires (1) immediate prophylaxis after exposure, pending test results that may take more than 24 hours in many hospitals; or (2) performance of a rapid test. The Single Use Diagnostic System (SUDS) HIV-1 Test is used to screen rapidly for antibodies to HIV type 1 in plasma or serum, with a reported sensitivity of more than 99.9%. We used this test from January 1999 until September 2000, when it was withdrawn from the market following reports claiming a high rate of false-positive results. METHODS: We reviewed the results of postexposure HIV testing during 21 months. RESULTS: A total of 884 SUDS tests were performed on source patients after occupational exposures (883 negative results, 1 reactive result). The results of repeat SUDS testing on the reactive specimen were also reactive, but the results of enzyme immunoassay and Western blot testing were negative. A new specimen from the same patient showed a negative result on SUDS testing. This suggested a specificity of 99.9%. In the 4 months after SUDS testing was suspended, there was 1 false-positive result on enzyme immunoassay for 1 of 132 source patients (presumed specificity, 99.2%). CONCLUSION: Use of the SUDS test facilitated rapid and accurate evaluation of source specimens, obviating unnecessary prophylaxis.

Spread of methicillin-resistant Staphylococcus aureus (MRSA) among household contacts of individuals with nosocomially acquired MRSA.

OBJECTIVE: To determine the frequency with which methicillin-resistant Staphylococcus aureus (MRSA) is spread from colonized or infected patients to their household and community contacts. DESIGN: Retrospective cohort study. SETTING: University hospital. PARTICIPANTS: Household and community contacts of MRSA-colonized or -infected patients for whom MRSA screening cultures were performed. RESULTS: MRSA was isolated from 25 (14.5%) of 172 individuals. Among the contacts of index patients who had at least one MRSA-colonized contact, those with close contact to the index patient were 7.5 times more likely to be colonized (53% vs 7%; 95% confidence interval, 1.1 to 50.3; P = .002). An analysis of antimicrobial susceptibility and DNA fingerprint patterns suggested person-to-person spread. CONCLUSIONS: MRSA colonization occurs frequently among household and community contacts of patients with nosocomially acquired MRSA, suggesting that transmission of nosocomially acquired MRSA outside of the healthcare setting may be a substantial source of MRSA colonization and infection in the community.

SHEA guideline for preventing nosocomial transmission of multidrug-resistant strains of Staphylococcus aureus and enterococcus.

BACKGROUND: Infection control programs were created three decades ago to control antibiotic-resistant healthcare-associated infections, but there has been little evidence of control in most facilities. After long, steady increases of MRSA and VRE infections in NNIS System hospitals, the Society for Healthcare Epidemiology of America (SHEA) Board of Directors made reducing antibiotic-resistant infections a strategic SHEA goal in January 2000. After 2 more years without improvement, a SHEA task force was appointed to draft this evidence-based guideline on preventing nosocomial transmission of such pathogens, focusing on the two considered most out of control: MRSA and VRE. METHODS: Medline searches were conducted spanning 1966 to 2002. Pertinent abstracts of unpublished studies providing sufficient data were included. RESULTS: Frequent antibiotic therapy in healthcare settings provides a selective advantage for resistant flora, but patients with MRSA or VRE usually acquire it via spread. The CDC has long-recommended contact precautions for patients colonized or infected with such pathogens. Most facilities have required this as policy, but have not actively identified colonized patients with surveillance cultures, leaving most colonized patients undetected and unisolated. Many studies have shown control of endemic and/or epidemic MRSA and VRE infections using surveillance cultures and contact precautions, demonstrating consistency of evidence, high strength of association, reversibility, a dose gradient, and specificity for control with this approach. Adjunctive control measures are also discussed. CONCLUSION: Active surveillance cultures are essential to identify the reservoir for spread of MRSA and VRE infections and make control possible using the CDC's long-recommended contact precautions.

Epidemiologic and clinical characteristics of acute diarrhea with emphasis on Entamoeba histolytica infections in preschool children in an urban slum of Dhaka, Bangladesh.

The epidemiology, clinical features, nutritional status, and causative agents of diarrhea were studied in 289 Bangladeshi children (147 boys and 142 girls) 2-5 years old. The use of improved diagnostic tests for amebiasis enabled for the first time analysis of the contribution of Entamoeba histolytica to total diarrheal illness in this community setting. The average incidence rate of diarrhea was 1.8/child-year, and the average number of diarrheal days was 3.7 days/child-year over an average observation period of 2.8 years/child. Seventy-five percent of the diarrheal episodes were < or = 2 days in duration. Persistent diarrhea was relatively uncommon (0.2% of the children) and chronic diarrhea was observed in only one episode. Compared with malnourished and/or stunted children, better-nourished children experienced significantly fewer diarrheal episodes. The diarrheal incidence rate for children with blood group A was significantly less that that of the children with blood groups O and AB. The most frequent bacterial enteropathogens isolated from diarrheal stool specimens were enterotoxigenic Escherichia coli (9%) and Aeromonas species (9%), followed by Plesimonas shigelloides (4%) and Shigella flexneri (3.8%). Rotavirus was the most common viral agent isolated from diarrheal stool samples (5%). Giardia lamblia, Cryptosporidium parvum, and E. histolytica were identified in 11%, 8.4%, and 8%, respectively, of the diarrheal stool specimens. Dysentery was observed in 7.7% of all diarrheal episodes. The most common pathogens isolated from dysenteric stool were S. flexneri (11.6%), Aeromonas sp. (10%), E. histolytica (8.7%), Campylobacter jejunii (5.8%), P. shigelloides (4.3%), and A. caviae (4.3%). The overall incidence rate of E. histolytica-associated diarrhea was 0.08/child-year. Visible blood and hemoccult test-detected blood loss was found in 7% and 25%, respectively, of cases of E. histolytica-associated diarrhea. Children who had recovered from a diarrheal episode with E. histolytica, but not E. dispar, had half the chance of developing subsequent E. histolytica-associated diarrhea, consistent with the development of species-specific acquired immunity. In conclusion, the use of modern diagnostic tests demonstrated that E. histolytica contributed to overall morbidity from diarrheal illness. Understanding the etiology, frequency, and consequences of acute diarrhea in children from a developing country should aid in the design of interventions to improve child health.