David H. Culver

Nosocomial infections in medical intensive care units in the United States

OBJECTIVE To describe the epidemiology of nosocomial infections in medical intensive care units (ICUs) in the United States. DESIGN Analysis of ICU surveillance data collected through the National Nosocomial Infections Surveillance (NNIS) System between 1992 and 1997. SETTING Medical ICUs in the United States. PATIENTS A total of 181,993 patients. MEASUREMENTS AND MAIN RESULTS Nosocomial infections were analyzed by infection site and pathogen distribution. Urinary tract infections were most frequent (31%), followed by pneumonia (27%) and primary bloodstream infections (19%). Eighty-seven percent of primary bloodstream infections were associated with central lines, 86% of nosocomial pneumonia was associated with mechanical ventilation, and 95% of urinary tract infections were associated with urinary catheters. Coagulase-negative staphylococci (36%) were the most common bloodstream infection isolates, followed by enterococci (16%) and Staphylococcus aureus (13%). Twelve percent of bloodstream isolates were fungi. The most frequent isolates from pneumonia were Gram-negative aerobic organisms (64%). Pseudomonas aeruginosa (21%) was the most frequently isolated of these. S. aureus (20%) was isolated with similar frequency. Candida albicans was the most common single pathogen isolated from urine and made up just over half of the fungal isolates. Fungal urinary infections were associated with asymptomatic funguria rather than symptomatic urinary tract infections (p < .0001). Certain pathogens were associated with device use: coagulase-negative staphylococci with central lines, P. aeruginosa and Acinetobacter species with ventilators, and fungal infections with urinary catheters. Patient nosocomial infection rates for the major sites correlated strongly with device use. Device exposure was controlled for by calculating device-associated infection rates for bloodstream infections, pneumonia, and urinary tract infections by dividing the number of device-associated infections by the number of days of device use. There was no association between these device-associated infection rates and number of hospital beds, number of ICU beds, or length of stay. There is a considerable variation within the distribution of each of these infection rates. CONCLUSIONS The distribution of sites of infection in medical ICUs differed from that previously reported in NNIS ICU surveillance studies, largely as a result of anticipated low rates of surgical site infections. Primary bloodstream infections, pneumonia, and urinary tract infections associated with invasive devices made up the great majority of nosocomial infections. Coagulase-negative staphylococci were more frequently associated with primary bloodstream infections than reported from NNIS ICUs of all types in the 1980s, and enterococci were a more frequent isolate from bloodstream infections than S. aureus. Fungal urinary tract infections, often asymptomatic and associated with catheter use, were considerably more frequent than previously reported. Invasive device-associated infections were associated with specific pathogens. Although device-associated site-specific infection rates are currently our most useful rates for performing comparisons between ICUs, the considerable variation in these rates between ICUs indicates the need for further risk adjustment.

A case-control study of HIV seroconversion in health care workers after percutaneous exposure

BACKGROUND The average risk of human immunodeficiency virus (HIV) infection after percutaneous exposure to HIV-infected blood is 0.3 percent, but the factors that influence this risk are not well understood. METHODS We conducted a case-control study of health care workers with occupational, percutaneous exposure to HIV-infected blood. The case patients were those who became seropositive after exposure to HIV, as reported by national surveillance systems in France, Italy, the United Kingdom, and the United States. The controls were health care workers in a prospective surveillance project who were exposed to HIV but did not seroconvert. RESULTS Logistic-regression analysis based on 33 case patients and 665 controls showed that significant risk factors for seroconversion were deep injury (odds ratio= 15; 95 percent confidence interval, 6.0 to 41), injury with a device that was visibly contaminated with the source patients blood (odds ratio= 6.2; 95 percent confidence interval, 2.2 to 21), a procedure involving a needle placed in the source patients artery or vein (odds ratio=4.3; 95 percent confidence interval, 1.7 to 12), and exposure to a source patient who died of the acquired immunodeficiency syndrome within two months afterward (odds ratio=5.6; 95 percent confidence interval, 2.0 to 16). The case patients were significantly less likely than the controls to have taken zidovudine after the exposure (odds ratio=0.19; 95 percent confidence interval, 0.06 to 0.52). CONCLUSIONS The risk of HIV infection after percutaneous exposure increases with a larger volume of blood and, probably, a higher titer of HIV in the source patients blood. Postexposure prophylaxis with zidovudine appears to be protective.Background The average risk of human immunodeficiency virus (HIV) infection after percutaneous exposure to HIV-infected blood is 0.3 percent, but the factors that influence this risk are not well understood. Methods We conducted a case–control study of health care workers with occupational, percutaneous exposure to HIV-infected blood. The case patients were those who became seropositive after exposure to HIV, as reported by national surveillance systems in France, Italy, the United Kingdom, and the United States. The controls were health care workers in a prospective surveillance project who were exposed to HIV but did not seroconvert. Results Logistic-regression analysis based on 33 case patients and 665 controls showed that significant risk factors for seroconversion were deep injury (odds ratio = 15; 95 percent confidence interval, 6.0 to 41), injury with a device that was visibly contaminated with the source patients blood (odds ratio = 6.2; 95 percent confidence interval, 2.2 to 21), a procedure inv...

Major trends in the microbial etiology of nosocomial infection

To determine trends in the microbial etiology of nosocomial infections in the 1980s, surveillance data on the microbiology of documented nosocomial infection reported to the National Nosocomial Infections Surveillance System and from the University of Michigan Hospital were analyzed. Antimicrobial susceptibility data on selected pathogens from both sources were also reviewed. Overall, Escherichia coli decreased from 23% of infections in 1980 to 16% in 1986-1989, Klebsiella pneumoniae dropped from 7% to 5%, whereas coagulase negative staphylococci increased from 4% to 9% and Candida albicans increased from 2% to 5%. Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacter species and enterococci had minor increases, but antimicrobial resistant strains for these pathogens as well as coagulase-negative staphylococci were seen more frequently. In contrast to the 1970s, major shifts in the etiology of nosocomial infection have occurred in the decade of the 1980s. Taken as a whole, the shifts are away from more easily treated pathogens toward more resistant pathogens with fewer options for therapy. These shifts underscore the continued need for prevention and control to accompany new developments in therapy.

Nosocomial Infections in Combined Medical-Surgical Intensive Care Units in the United States

OBJECTIVE To describe the epidemiology of nosocomial infections in combined medical-surgical (MS) intensive care units (ICUs) participating in the National Nosocomial Infection Surveillance (NNIS) System. DESIGN Analysis of surveillance data on 498,998 patients with 1,554,070 patient-days, collected between 1992 and 1998 from 205 MS ICUs following the NNIS Intensive Care Unit protocol, representing 152 participating NNIS hospitals in the United States. RESULTS Infections at three major sites represented 68% of all reported infections (nosocomial pneumonia, 31%; urinary tract infections (UTIs), 23%; and primary bloodstream infections (BSIs), 14%: 83% of episodes of nosocomial pneumonia were associated with mechanical ventilation, 97% of UTIs occurred in catheterized patients, and 87% of primary BSIs in patients with a central line. In patients with primary BSIs, coagulase-negative staphylococci (39%) were the most common pathogens reported; Staphylococcus aureus (12%) was as frequently reported as enterococci (11%). Coagulase-negative staphylococcal BSIs were increasingly reported over the 6 years, but no increase was seen in candidemia or enterococcal bacteremia. In patients with pneumonia, S. aureus (17%) was the most frequently reported isolate. Of reported isolates, 59% were gram-negative bacilli. In patients with UTIs, Escherichia coli (19%) was the most frequently reported isolate. Of reported isolates, 31% were fungi. In patients with surgical-site infections, Enterococcus (17%) was the single most frequently reported pathogen. Device-associated nosocomial infection rates for BSIs, pneumonia, and UTIs did not correlate with length of ICU stay, hospital bed size, number of beds in the ICU, or season. Combined MS ICUs in major teaching hospitals had higher device-associated infection rates compared to all other hospitals with combined medical-surgical units. CONCLUSIONS Nosocomial infections in MS ICUs at the most frequent infection sites (bloodstream, urinary, and respiratory tract) almost always were associated with use of an invasive device. Device-associated infection rates were the best available comparative rates between combined MS ICUs, but the distribution of device-associated rates should be stratified by a hospitals major teaching affiliation status.

National nosocomial infections surveillance system (NNIS): Description of surveillance methods

The National Nosocomial Infections Surveillance System (NNIS) is an ongoing collaborative surveillance system sponsored by the Centers for Disease Control (CDC) to obtain national data on nosocomial infections. The CDC uses the data that are reported voluntarily by participating hospitals to estimate the magnitude of the nosocomial infection problem in the United States and to monitor trends in infections and risk factors. Hospitals collect data by prospectively monitoring specific groups of patients for infections with the use of protocols called surveillance components. The surveillance components used by the NNIS are hospitalwide, intensive care unit, high-risk nursery, and surgical patient. Detailed information including demographic characteristics, infections and related risk factors, pathogens and their antimicrobial susceptibilities, and outcome, is collected on each infected patient. Data on risk factors in the population of patients being monitored are also collected; these permit the calculation of risk-specific rates. An infection risk index, which includes the traditional wound class, is being evaluated as a predictor of the likelihood that an infection will develop after an operation. A major goal of the NNIS is to use surveillance data to develop and evaluate strategies to prevent and control nosocomial infections. The data collected with the use of the surveillance components permit the calculation of risk-specific infection rates, which can be used by individual hospitals as well as national health-care planners to set priorities for their infection control programs and to evaluate the effectiveness of their efforts. The NNIS will continue to evolve in finding more effective and efficient ways to assess the influence of patient risk and changes in the financing of health care on the infection rate.

METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS IN U.S. HOSPITALS, 1975-1991

OBJECTIVES Analyze changes that have occurred among U.S. hospitals over a 17-year period, 1975 through 1991, in the percentage of Staphylococcus aureus resistant to beta-lactam antibiotics and associated with nosocomial infections. DESIGN Retrospective review. The percentage of methicillin-resistant S aureus (MRSA) was defined as the number of S aureus isolates resistant to either methicillin, oxacillin, or nafcillin divided by the total number of S aureus isolates for which methicillin, oxacillin, or nafcillin susceptibility test results were reported to the National Nosocomial Infections Surveillance (NNIS) System. SETTING NNIS System hospitals. RESULTS Of the 66,132 S aureus isolates that were tested for susceptibility to methicillin, oxacillin, or nafcillin during 1975 through 1991, 6,986 (11%) were resistant to methicillin, oxacillin, or nafcillin. The percentage MRSA among all hospitals rose from 2.4% in 1975 to 29% in 1991, but the rate of increase differed significantly among 3 bed-size categories: < 200 beds, 200 to 499 beds, and > or = 500 beds. In 1991, for hospitals with < 200 beds, 14.9% of S aureus isolates were MRSA; for hospitals with 200 to 499 beds, 20.3% were MRSA; and for hospitals with > or = 500 beds, 38.3% were MRSA. The percentage MRSA in each of the bed-size categories rose above 5% at different times: in 1983, for hospitals with > or = 500 beds; in 1985, for hospitals with 200 to 499 beds; and in 1987, for hospitals with < 200 beds. CONCLUSIONS This study suggests that hospitals of all sizes are facing the problem of MRSA, the problem appears to be increasing regardless of hospital size, and control measures advocated for MRSA appear to require re-evaluation. Further study of MRSA in hospitals would benefit our understanding of this costly pathogen.

Nosocomial Infections in Pediatric Intensive Care Units in the United States

Objectives. To describe the epidemiology of nosocomial infections in pediatric intensive care units (ICUs) in the United States. Background. Patient and ICU characteristics in pediatric ICUs suggest the pattern of nosocomial infections experienced may differ from that seen in adult ICUs. Methods. Data were collected between January 1992 and December 1997 from 61 pediatric ICUs in the United States using the standard surveillance protocols and nosocomial infection site definitions of the National Nosocomial Infections Surveillance Systems ICU surveillance component. Results. Data on 110 709 patients with 6290 nosocomial infections were analyzed. Primary bloodstream infections (28%), pneumonia (21%), and urinary tract infections (15%) were most frequent and were almost always associated with use of an invasive device. Primary bloodstream infections and surgical site infections were reported more frequently in infants aged 2 months or less as compared with older children. Urinary tract infections were reported more frequently in children >5 years old compared with younger children. Coagulase-negative staphylococci (38%) were the most common bloodstream isolates, and aerobic Gram-negative bacilli were reported in 25% of primary bloodstream infections. Pseudomonas aeruginosa (22%) was the most common species reported from pneumonia and Escherichia coli (19%), from urinary tract infections. Enterobacter spp. were isolated with increasing frequency from pneumonia and were the most common Gram-negative isolates from bloodstream infections. Device-associated infection rates for bloodstream infections, pneumonia, and urinary tract infections did not correlate with length of stay, the number of hospital beds, or season. Conclusions. In pediatric ICUs, bloodstream infections were the most common nosocomial infection. The distribution of infection sites and pathogens differed with age and from that reported from adult ICUs. Device-associated infection rates were the best rates currently available for comparisons between units, because they were not associated with length of stay, the number of beds in the hospital, or season.

Surgical Site Infection (SSI) Rates in the United States, 1992–1998: The National Nosocomial Infections Surveillance System Basic SSI Risk Index

By use of the National Nosocomial Infections Surveillance (NNIS) Systems surgical patient surveillance component protocol, the NNIS basic risk index was examined to predict the risk of a surgical site infection (SSI). The NNIS basic SSI risk index is composed of the following criteria: American Society of Anesthesiologists score of 3, 4, or 5; wound class; and duration of surgery. The effect when a laparoscope was used was also determined. Overall, for 34 of the 44 NNIS procedure categories, SSI rates increased significantly (P< .05) with the number of risk factors present. With regard to cholecystectomy and colon surgery, the SSI rate was significantly lower when the procedure was done laparoscopically within each risk index category. With regard to appendectomy and gastric surgery, use of a laparoscope affected SSI rates only when no other risk factors were present. The NNIS basic SSI index is useful for risk adjustment for a wide variety of procedures. For 4 operations, the use of a laparoscope lowered SSI risk, requiring modification of the NNIS basic SSI risk index.

Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda.

BACKGROUND Prophylaxis with co-trimoxazole (trimethoprim-sulphamethoxazole) is recommended for people with HIV infection or AIDS but is rarely used in Africa. We assessed the effect of such prophylaxis on morbidity, mortality, CD4-cell count, and viral load among people with HIV infection living in rural Uganda, an area with high rates of bacterial resistance to co-trimoxazole. METHODS Between April, 2001, and March, 2003, we enrolled, and followed up with weekly home visits, 509 individuals with HIV-1 infection and their 1522 HIV-negative household members. After 5 months of follow-up, HIV-positive participants were offered daily co-trimoxazole prophylaxis (800 mg trimethoprim, 160 mg sulphamethoxazole) and followed up for a further 1.5 years. We assessed rates of malaria, diarrhoea, hospital admission, and death. FINDINGS Co-trimoxazole was well tolerated with rare (<2% per person-year) adverse reactions. Even though rates of resistance in diarrhoeal pathogens were high (76%), co-trimoxazole prophylaxis was associated with a 46% reduction in mortality (hazard ratio 0.54 [95% CI 0.35-0.84], p=0.006) and lower rates of malaria (multivariate incidence rate ratio 0.28 [0.19-0.40], p<0.0001), diarrhoea (0.65 [0.53-0.81], p<0.0001), and hospital admission (0.69 [0.48-0.98], p=0.04). The annual rate of decline in CD4-cell count was less during prophylaxis than before (77 vs 203 cells per microL, p<0.0001), and the annual rate of increase in viral load was lower (0.08 vs 0.90 log(10) copies per mL, p=0.01). INTERPRETATION Daily co-trimoxazole prophylaxis was associated with reduced morbidity and mortality and had beneficial effects on CD4-cell count and viral load. Co-trimoxazole prophylaxis is a readily available, effective intervention for people with HIV infection in Africa.

Surveillance of HIV Infection and Zidovudine Use among Health Care Workers after Occupational Exposure to HIV-Infected Blood

Health care workers are at risk for human immunodeficiency virus (HIV) infection after an occupational exposure to blood, certain other body fluids, and tissue from an HIV-infected patient [1, 2]. Zidovudine has been used after exposure to reduce this risk, despite the lack of data on efficacy and limited data on toxicity when used for this purpose [3-5]. In 1983, the Centers for Disease Control and Prevention (CDC) began a national voluntary surveillance project to estimate the risk for HIV transmission after a single exposure to HIV-infected blood [6]. In October 1988, the project was expanded to collect information describing the use of postexposure zidovudine among enrolled workers. In this update of the ongoing surveillance project, we focus on the patterns of use and associated toxicity of postexposure zidovudine use among enrolled workers and report the failure of zidovudine to prevent HIV infection in one worker. Methods CDC Surveillance Project The surveillance project has been described previously [6, 7]. In brief, workers in a group of participating health care institutions throughout the United States are voluntarily enrolled by cooperating investigators after an exposure to blood from a patient with documented HIV infection as a result of percutaneous injury (for example, a needlestick or a cut from a sharp object), contamination of mucous membranes, or contamination of nonintact skin. (Extensive or prolonged blood contact with intact skin may constitute an occupational exposure [4], but workers with intact skin exposures are not enrolled in this project.) Epidemiologic information and a blood specimen for HIV serologic testing are collected by the cooperating investigator at a baseline visit within 1 month after exposure and at follow-up visits 6 weeks, 3 months, 6 months, and 1 year after exposure. At enrollment, workers complete and mail directly to the CDC an anonymous questionnaire that includes information on nonoccupational risk factors for HIV infection. Workers who seroconvert are interviewed in person by an investigator using a standard CDC protocol for the interview of persons with no identified risk. Human immunodeficiency virus serologic testing is done either at the CDC or at the cooperating institutions laboratory, with all positive results confirmed at the CDC. Use of Postexposure Zidovudine In October 1988, the surveillance project was expanded to collect additional information on the postexposure use and toxicity of antiviral agents, such as zidovudine. A standardized protocol for offering or using postexposure zidovudine was not provided by the CDC; in accordance with the Public Health Service statement [4], individual cooperating investigators and exposed workers determined whether postexposure zidovudine would be used, and, among those using zidovudine, the dosage and duration of prophylaxis. Adverse Events At the 6-week follow-up visit, the cooperating investigators were asked to record reported symptoms on a standardized checklist provided by the CDC, as well as the zidovudine regimen, if used. In this surveillance project, a standard protocol for laboratory testing for adverse effects (for example, anemia) of zidovudine was not provided by the CDC; such tests were done at the discretion of the cooperating investigator, who recorded the test date and any results outside the testing laboratorys normal range. Statistical Analysis Data were analyzed using PRODAS (Conceptual Software, Houston, Texas), Epi-Info (CDC, Atlanta, Georgia), and the Statistical Analysis System (SAS Institute, Inc., Cary, North Carolina). The upper bounds of the 95% CI were calculated using the binomial distribution. Because of missing data, totals for specific analyses may not equal the total number of enrolled workers. Results From August 1983 through June 1992, 1245 workers from 312 institutions were enrolled and tested for HIV antibody at baseline and at least 180 days after exposure. These workers comprised nurses (64%), physicians and dentists (12%), phlebotomists (8%), laboratory workers (6%), medical students (2%), housekeepers (1%), and other workers (such as technicians and physician and nursing assistants) (8%). Exposures to HIV-infected Blood and Risk for HIV Infection A total of 1245 workers were enrolled and tested for HIV antibody at baseline and at least 180 days after exposure. These workers had been exposed to blood from source patients who had AIDS as defined by the CDC surveillance case definition in use at the time of enrollment, (1012 [81%] exposures) [8], who were HIV-antibody positive and symptomatic but who did not have AIDS (68 [5%] exposures), or were HIV-antibody positive and asymptomatic (165 [13%] exposures). Exposure types were percutaneous injury (1103; 89%) and blood contact with mucous membranes (67; 5%) or nonintact skin (75; 6%). The 1103 percutaneous injuries were caused by syringe needles (375; 34%), intravenous needles (343; 31%), suture needles (41; 4%), and other needles (228; 21%); scalpels (41; 4%); lancets (27; 2%); and other sharp objects (48; 4%). Among 1103 workers with percutaneous injuries who were HIV seronegative at baseline, 4 (0.36%; upper limit CI, 0.83%) seroconverted to HIV. Among workers with percutaneous injury, the seroconversion rate after exposure to blood from source patients with AIDS was 0.44% (4 of 899; upper limit CI, 1.01%); the seroconversion rate was not statistically different after exposure to blood from source patients who were HIV-antibody positive and symptomatic but who were without AIDS (0 of 57, P > 0.2) or source patients who were HIV-antibody positive and asymptomatic (0 of 147, P > 0.2). No seroconversions occurred among workers with blood exposure of mucous membranes (67 workers; upper limit CI, 4.31%) or skin (75 workers; upper limit CI, 3.87%). An additional 497 workers enrolled in the early 1980s, before HIV-antibody testing was available, were tested for HIV antibody at least 180 days after exposure but not at baseline. One of these workers was HIV-antibody positive when first tested 10 months after exposure [7]. At that time, a sex partner of this worker was also tested and found to be HIV seropositive; the dates of HIV infection for this worker and partner are unknown. Including these 497 workers, the HIV seroprevalence rate was 0.32% (5 of 1532; upper limit CI, 0.68%) after percutaneous exposure, 0% (0 of 100; upper limit CI, 2.9%) after mucous membrane exposure, and 0% (0 of 110; upper limit CI, 2.7%) after skin exposure to HIV-infected blood. Of the four workers enrolled in this project who have seroconverted after exposure to HIV, three have been previously described [6, 7]. The fourth worker, a female laboratory worker, was injured in 1992 by a 21-gauge syringe needle after doing a phlebotomy on a patient who was known to have AIDS. The worker reported no behavioral risk factors for HIV infection, except for having had sexual contact with a person at risk for HIV infection more than 1 year before her injury. The worker began taking zidovudine 2 hours after the injury, in a dose of 100 mg, five times a day, for the first day and then 200 mg, five times per day, for 16 additional days (Table 1, report 5). The worker discontinued use of zidovudine after 17 days because of nausea, fatigue, and myalgia. Thirty-eight days after exposure, the worker developed fever, malaise, fatigue, nausea, arthralgia, myalgia, and rash. Serologic test results for HIV were negative for specimens of the workers blood collected on the day of the injury and 6 weeks afterward, were indeterminate by enzyme immunoassay and positive by Western blot 3 months after injury, and were positive by both enzyme immunoassay and Western blot 4 months after injury. The source patient was not known to have received zidovudine before the needlestick incident. Table 1. Reported Instances of Failure of Postexposure Zidovudine To Prevent HIV Infection in Health Care Workers after Percutaneous Exposure to HIV-infected Blood To determine whether the worker was infected with zidovudine-resistant virus, peripheral blood mononuclear cells were collected from the worker and the source patient 3 months and 8 months after exposure, respectively. At the Walter Reed Army Institute of Research (Washington, D.C.), cells from the worker were positive for HIV-1 using the polymerase chain reaction (PCR), but efforts to isolate the virus for phenotypic zidovudine-susceptibility testing were not successful. Nested PCR to detect mutations in the HIV reverse transcriptase at amino acid position 215 associated with zidovudine resistance did not show alterations at that site in peripheral blood mononuclear cells from either worker or source patient [9] (D. Mayers. Personal communication). At the CDC, direct sequencing of the HIV-1 reverse-transcriptase gene (amplified by PCR from the workers peripheral blood mononuclear cells [10]) showed no mutations at position 215 or at the four other amino acid positions (positions 41, 67, 70, and 219) known to be associated with zidovudine resistance [11, 12] (data not shown). Use of Postexposure Zidovudine From October 1988 to June 1992, the period when use of zidovudine was studied, 848 workers were enrolled. Postexposure zidovudine was used by 265 (31%) of these workers. Of 200 cooperating investigators who enrolled workers during this period, 110 (55%) reported that at least one worker used zidovudine. Zidovudine was prescribed in doses ranging from 200 to 1800 mg/d (median, 1000 mg/d) and for periods of 1 to 180 days (median, 42 days). The interval from exposure to first dose of zidovudine ranged from less than 5 minutes to 17 days (median, 4 hours). No clinically significant changes in prescribed regimens of zidovudine were seen during the study period (data not shown). The proportion of enrolled workers using zidovudine increased from 5% in the fourth quarter of 1988 to 50% in the third quarter of 1990 and has been stable subseq