Risk factors for community-associated Staphylococcus aureus infections: results from parallel studies including methicillin-resistant and methicillin-sensitive S. aureus compared to uninfected controls.

Despite the increasing burden of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, the risk factors are not well understood. We conducted a hypothesis-generating study using three parallel case-control studies to identify risk factors for CA-MRSA and community-associated methicillin-susceptible S. aureus (CA-MSSA) infections. In the multivariate model, antimicrobial use in the 1-6 months prior to culture was associated with CA-MRSA infection compared to CA-MSSA [adjusted odds ratio (aOR) 1·7, P=0·07] cases. Antimicrobial use 1-6 months prior to culture (aOR 1·8, P=0·04), history of boils (aOR 1·6, P=0·03), and having a household member who was a smoker (aOR 1·3, P=0·05) were associated with CA-MRSA compared to uninfected community controls. The finding of an increased risk of CA-MRSA infection associated with prior antimicrobial use highlights the importance of careful antimicrobial stewardship.

Nosocomial acquisition of Pseudomonas aeruginosa resistant to both ciprofloxacin and imipenem: a risk factor and laboratory analysis.

In vitro, ciprofloxacin can select for dual resistance to fluoroquinolones and imipenem in Pseudomonas aeruginosa via a mutation in the regulatory gene, mexT, which downregulates OprD and upregulates MexEF-OprN. We performed a nested case-control study of patients in two medical intensive care units participating in an observational cohort study. Patients colonized or infected with P. aeruginosa resistant to both ciprofloxacin and imipenem (cases) were compared to controls. The presence of OprD and OprN from cases was evaluated by Western blot. In total, 44 cases were compared to 132 controls. Imipenem exposure [adjusted odds ratio (AOR) = 11.4, p = 0.044] was significantly associated with case status, but fluoroquinolone use was not (AOR = 1.0, p = 0.998). Neither OprD nor OprN were detected in any isolate. Fluoroquinolone use was not a risk factor for acquisitions of dually resistant P. aeruginosa. The absence of OprN in these isolates suggests that dual resistance is not due to mexT mutations.

Impact of early central venous catheter removal on outcome in patients with candidaemia.

Removal of central venous catheters (CVCs) from candidaemic patients is considered the reference standard of care, although this practice is not always possible. The impact of prompt catheter removal on outcome was investigated by analysing data from an active population-based surveillance study in Barcelona, Spain. Patients with candidaemia and a CVC were identified between January 2002 and December 2003. Cases with CVC removal within 2 days were classified as having early CVC removal. Outcome, defined as in-hospital mortality 2-30 days after diagnosis of candidaemia, was determined among hospitalised adults using univariate, Kaplan-Meier and multivariate logistic regression analysis. Outpatients, paediatric patients and those who died or were discharged within 2 days were excluded. The study identified 265 patients with candidaemia and a CVC. Median time from diagnosis of candidaemia to catheter removal was 1 day (range 0-29 days). Overall, 172 patients met the criteria for inclusion in the outcome study. Patients with early CVC removal differed significantly from those with delayed CVC removal. According to univariate, Kaplan-Meier and multivariate analysis, the marker most predictive of in-hospital mortality among candidaemic patients with CVCs was severity of illness. These data suggest that timing of CVC removal may best be determined after carefully considering the risks and benefits to individual patients.

Incidence of invasive aspergillosis following hematopoietic stem cell and solid organ transplantation: interim results of a prospective multicenter surveillance program.

The incidence of invasive aspergillosis was estimated among 4621 hematopoietic stem cell transplants (HSCT) and 4110 solid organ transplants (SOT) at 19 sites dispersed throughout the United States, during a 22 month period from 1 March 2001 through 31 December 2002. Cases were identified using the consensus definitions for proven and probable infection developed by the Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group of the National Institute of Allergy and Infectious Diseases. The cumulative incidence (CI) of aspergillosis was calculated for the first episode of the infection that occurred within the specified time period after transplantation. To obtain an aggregate CI for each type of transplant, data from participating sites were weighted according to the proportion of transplants followed-up for specified time periods (four and 12 months for HSCT; six and 12 months for SOT). The aggregate CI of aspergillosis at 12 months was 0.5% after autologous HSCT, 2.3% after allogeneic HSCT from an HLA-matched related donor, 3.2% after transplantation from an HLA-mismatched related donor, and 3.9% after transplantation from an unrelated donor. The aggregate CI at 12 months was similar following myeloablative or non-myeloablative conditioning before allogeneic HSCT (3.1 vs. 3.3%). After HSCT, mortality at 3 months following diagnosis of aspergillosis ranged from 53.8% of autologous transplants to 84.6% of unrelated-donor transplants. The aggregate CI of aspergillosis at 12 months was 2.4% after lung transplantation, 0.8% after heart transplantation, 0.3% after liver transplantation, and 0.1% after kidney transplantation. After SOT, mortality at three months after diagnosis of aspergillosis ranged from 20% for lung transplants to 66.7% for heart and kidney transplants. The Aspergillus spp. associated with infections after HSCT included A. fumigatus (56%), A. flavus (18.7%), A. terreus (16%), A. niger (8%), and A. versicolor (1.3%). Those associated with infections after SOT included A. fumigatus (76.4%), A. flavus (11.8%), and A. terreus (11.8%). In conclusion, we found that invasive aspergillosis is an uncommon complication of HSCT and SOT, but one that continues to be associated with poor outcomes. Our CI figures are lower compared to those of previous reports. The reasons for this are unclear, but may be related to changes in transplantation practices, diagnostic methods, and supportive care.

The effect of renal dysfunction on antimicrobial use measurements.

The defined daily dose, a popular measurement of antimicrobial use, may underestimate the use of antimicrobials that are dose-adjusted in patients with renal insufficiency. To evaluate the effect of renal dysfunction on these measures, we performed a retrospective cohort study that involved patients receiving ceftriaxone, levofloxacin, or vancomycin, with use of defined daily doses and 2 methods based on therapy duration--stop-start days (i.e., entire therapy duration) and transaction days (i.e., unique therapeutic days). The vancomycin use rate for patients with renal insufficiency was 36% lower than that of patients with normal renal function for defined daily doses, and it was 23% lower for transaction days; for levofloxacin, there was a 27% rate reduction for the defined daily dose. No significant reduction was noted when the stop-start day method was used. Compared with the defined daily dose method, measures of therapy duration are less affected by renal function and may improve comparisons between populations.

Secular trend of hospital-acquired candidemia among intensive care unit patients in the United States during 1989-1999.

We describe the annual incidence of primary bloodstream infection (BSI) associated with Candida albicans and common non-albicans species of Candida among patients in intensive care units that participated in the National Nosocomial Infections Surveillance system from 1 January 1989 through 31 December 1999. During the study period, there was a significant decrease in the incidence of C. albicans BSI (P<.001) and a significant increase in the incidence of Candida glabrata BSI (P=.05).

Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States.

From October 4 to November 2, 2001, the first 10 confirmed cases of inhalational anthrax caused by intentional release of Bacillus anthracis were identified in the United States. Epidemiologic investigation indicated that the outbreak, in the District of Columbia, Florida, New Jersey, and New York, resulted from intentional delivery of B. anthracis spores through mailed letters or packages. We describe the clinical presentation and course of these cases of bioterrorism-related inhalational anthrax. The median age of patients was 56 years (range 43 to 73 years), 70% were male, and except for one, all were known or believed to have processed, handled, or received letters containing B. anthracis spores. The median incubation period from the time of exposure to onset of symptoms, when known (n=6), was 4 days (range 4 to 6 days). Symptoms at initial presentation included fever or chills (n=10), sweats (n=7), fatigue or malaise (n=10), minimal or nonproductive cough (n=9), dyspnea (n=8), and nausea or vomiting (n=9). The median white blood cell count was 9.8 X 10(3)/mm(3) (range 7.5 to 13.3), often with increased neutrophils and band forms. Nine patients had elevated serum transaminase levels, and six were hypoxic. All 10 patients had abnormal chest X-rays; abnormalities included infiltrates (n=7), pleural effusion (n=8), and mediastinal widening (seven patients). Computed tomography of the chest was performed on eight patients, and mediastinal lymphadenopathy was present in seven. With multidrug antibiotic regimens and supportive care, survival of patients (60%) was markedly higher (<15%) than previously reported.

Vancomycin-intermediate Staphylococcus aureus in a home health-care patient.

In June 2000, vancomycin-intermediate Staphylococcus aureus (VISA) was isolated from a 27-year-old home health-care patient following a complicated cholecystectomy. Two VISA strains were identified with identical MICs to all antimicrobials tested except oxacillin and with closely related pulsed-field gel electrophoresis types. The patient was treated successfully with antimicrobial therapy, biliary drainage, and reconstruction. Standard precautions in the home health setting appear successful in preventing transmission.

The effect of vancomycin and third-generation cephalosporins on prevalence of vancomycin-resistant enterococci in 126 U.S. adult intensive care units.

BACKGROUND: Patient-specific risk factors for acquisition of vancomycin-resistant enterococci (VRE) among hospitalized patients are becoming well defined. However, few studies have reported data on the institutional risk factors, including rates of antimicrobial use, that predict rates of VRE. Identifying modifiable institutional factors can advance quality-improvement efforts to minimize hospital-acquired infections with VRE. OBJECTIVE: To determine the independent importance of any association between antimicrobial use and risk factors for nosocomial infection on rates of VRE in intensive care units (ICUs). DESIGN: Prospective ecologic study. SETTING: 126 adult ICUs from 60 U.S. hospitals from January 1996 through July 1999. PATIENTS: All patients admitted to participating ICUs. MEASUREMENTS: Monthly use of antimicrobial agents (defined daily doses per 1000 patient-days), nosocomial infection rates, and susceptibilities of all tested enterococci isolated from clinical cultures. RESULTS: Prevalence of VRE (median, 10%; range, 0% to 59%) varied by type of ICU and by teaching status and size of the hospital. Prevalence of VRE was strongly associated with VRE prevalence among inpatient non-ICU areas and outpatient areas in the hospital, ventilator-days per 1000 patient-days, and rate of parenteral vancomycin use. In a weighted linear regression model controlling for type of ICU and rates of VRE among non-ICU inpatient areas, rates of vancomycin use (P < 0.001) and third-generation cephalosporin use (P = 0.02) were independently associated with VRE prevalence. CONCLUSIONS: Higher rates of vancomycin or third-generation cephalosporin use were associated with increased prevalence of VRE, independent of other ICU characteristics and the endemic VRE prevalence elsewhere in the hospital. Decreasing the use rates of these antimicrobial agents could reduce rates of VRE in ICUs.

Antimicrobial resistance prevalence rates in hospital antibiograms reflect prevalence rates among pathogens associated with hospital-acquired infections.

To determine whether routine antibiograms (summaries reporting resistance of all tested isolates) reflect resistance rates among pathogens associated with hospital-acquired infections, we compared data collected from 2 different surveillance components in the same 166 intensive care units (ICUs). ICUs reported data during the same months to both the infection-based surveillance and the laboratory-based surveillance. Paired comparisons of the percentage of isolates resistant were made between systems within each ICU. No significant differences existed (P>.05) between the percentage of isolates resistant from the infection-based system and laboratory-based system for all antimicrobial-resistant organisms studied, except methicillin resistance in Staphylococcus species. The mean difference in percentage resistance was higher from the infection-based system than the laboratory-based system for S. aureus (mean difference, +8%, P<.001) and coagulase-negative staphylococci (mean difference, +9%, P<.001). Overall, hospital antibiograms reflected susceptibility patterns among isolates associated with hospital-acquired infections. Hospital antibiograms may underestimate the relative frequency of methicillin resistance among Staphylococcus species when associated with hospital-acquired infections.

Increasing prevalence of antimicrobial resistance in intensive care units.

The unique nature of the intensive care unit (ICU) environment makes this part of the hospital a focus for the emergence and spread of many antimicrobial-resistant pathogens. There are ample opportunities for the cross-transmission of resistant bacteria from patient to patient, and patients are commonly exposed to broad-spectrum antimicrobial agents. Rates of resistance have increased for most pathogens associated with hospital-acquired infections among ICU patients, and rates are almost universally higher among ICU patients than non-ICU patients. Likewise, ICU patients hospitalized longer (i.e., >7 days) are two- to three-fold more likely to be infected with a pathogen possessing an antimicrobial-resistant phenotype of concern. However, there are many opportunities to prevent the emergence and spread of these resistant pathogens through improved use of established infection control measures (patient isolation, handwashing, glove use, and appropriate gown use) and implementation of a systematic review of antimicrobial use. (Crit Care Med 2001; 29[Suppl.]: N64-N68)

Vancomycin-intermediate and -resistant Staphylococcus aureus: what the infectious disease specialist needs to know.

Ever since the first strain of Staphylococcus aureus with reduced susceptibility to vancomycin and teicoplanin was reported from Japan, there has been a lot of confusion regarding the laboratory and clinical approach to patients with infections due to S. aureus with reduced susceptibility to vancomycin. To date, 6 clinical infections with vancomycin-intermediate S. aureus (VISA) have been reported in the United States. Intermediate resistance appears to develop from preexisting strains of methicillin-resistant S. aureus in the presence of vancomycin, and all but 1 infection occurred in patients with exposure to dialysis for renal insufficiency. Detection of VISA is difficult in the laboratory, and special inquiries about susceptibility testing methods may be needed. These VISA-infected patients had underlying illnesses, and their infections did not appear to respond well to conventional treatment. Prevention strategies have been outlined. Without continued vigilance in enforcing infection-control measures, improved use of antimicrobials, and coordination of efforts among public health authorities, increasing levels of vancomycin resistance in S. aureus are likely to be encountered.

Ability of laboratories to detect emerging antimicrobial resistance in nosocomial pathogens: a survey of project ICARE laboratories.

A proficiency testing project was conducted among 48 microbiology laboratories participating in Project ICARE (Intensive Care Antimicrobial Resistance Epidemiology). All laboratories correctly identified the Staphylococcus aureus challenge strain as oxacillin- resistant and an Enterococcus faecium strain as vancomycin-resistant. Thirty-one (97%) of 32 laboratories correctly reported the Streptococcus pneumoniae strain as erythromycin-resistant. All laboratories testing the Pseudomonas aeruginosa strain against ciprofloxacin or ofloxacin correctly reported the organism as resistant. Of 40 laboratories, 30 (75%) correctly reported resistant MICs or zone sizes for the imipenem- and meropenem-resistant Serratia marcescens. For the extended-spectrum beta-lactamase (ESBL)-producing strain of Klebsiella pneumoniae, 18 (42%) of 43 laboratories testing ceftazidime correctly reported ceftazidime MICs in the resistant range. These results suggest that current testing generally produces accurate results, although some laboratories have difficulty detecting resistance to carbapenems and extended-spectrum cephalosporins. This highlights the need for monitoring how well susceptibility test systems in clinical laboratories detect emerging resistance.

Practices to improve antimicrobial use at 47 US hospitals: the status of the 1997 SHEA/IDSA position paper recommendations. Society for Healthcare Epidemiology of America/Infectious Diseases Society of America.

OBJECTIVE: To determine the status of programs to improve antimicrobial prescribing at select US hospitals. DESIGN: Cross-sectional survey. PARTICIPANTS AND SETTING: Pharmacy and infection control staff at all 47 hospitals participating in phase 3 of Project Intensive Care Antimicrobial Resistance Epidemiology. RESULTS: All 47 hospitals had some programs to improve antimicrobial use, but the practices reported varied considerably. All used a formulary, and 43 (91%) used it in conjunction with at least one of the other three antimicrobial-use policies evaluated: stop orders, restriction, and criteria-based clinical practice guidelines (CPGs). CPGs were reported most commonly (70%), followed by stop orders (60%) and restriction policies (40%). Although consultation with an infectious disease physician (70%) or pharmacist (66%) was commonly used to influence initial antimicrobial choice, few (40%) reported a system to measure compliance with these consultations. CONCLUSIONS: In most hospitals surveyed, practices to improve antimicrobial use, although present, were inadequate based on recommendations in a Society for Healthcare Epidemiology of America and Infectious Disease Society of America joint position paper. There is room to improve antimicrobial-use stewardship at US hospitals.

The influence of the composition of the nursing staff on primary bloodstream infection rates in a surgical intensive care unit.

OBJECTIVES: To determine the risk factors for acquisition of nosocomial primary bloodstream infections (BSIs), including the effect of nursing-staff levels, in surgical intensive care unit (SICU) patients. DESIGN: A nested case-control study. SETTING: A 20-bed SICU in a 1,000-bed inner-city public hospital. PATIENTS: 28 patients with BSI (case-patients) were compared to 99 randomly selected patients (controls) hospitalized > or =3 days in the same unit. RESULTS: Case- and control-patients were similar in age, severity of illness, and type of central venous catheter (CVC) used. Case-patients were significantly more likely than controls to be hospitalized during a 5-month period that had lower regular-nurse-to-patient and higher pool-nurse-to-patient ratios than during an 8-month reference period; to be in the SICU for a longer period of time; to be mechanically ventilated longer; to receive more antimicrobials and total parenteral nutrition; to have more CVC days; or to die. Case-patients had significantly lower regular-nurse-to-patient and higher pool-nurse-to-patient ratios for the 3 days before BSI than controls. In multivariate analyses, admission during a period of higher pool-nurse-to-patient ratio (odds ratio [OR]=3.8), total parenteral nutrition (OR=1.3), and CVC days (OR=1.1) remained independent BSI risk factors. CONCLUSIONS: Our data suggest that, in addition to other factors, nurse staffing composition (ie, pool-nurse-to-patient ratio) may be related to primary BSI risk. Patterns in intensive care unit nurse staffing should be monitored to assess their impact on nosocomial infection rates. This may be particularly important in an era of cost containment and healthcare reform.

Glycopeptide-intermediate Staphylococcus aureus: evaluation of a novel screening method and results of a survey of selected U.S. hospitals.

Isolates of Staphylococcus aureus with decreased susceptibilities to glycopeptide antimicrobial agents, such as vancomycin and teicoplanin, have emerged in the United States and elsewhere. Commercially prepared brain heart infusion agar (BHIA) supplemented with 6 microg of vancomycin per ml was shown in a previous study to detect glycopeptide-intermediate S. aureus (GISA) with high sensitivity and specificity; however, this medium, when prepared in-house, occasionally showed growth of vancomycin-susceptible control organisms. This limitation could significantly impact laboratories that prepare media in-house, particularly if they wished to conduct large surveillance studies for GISA. Therefore, a pilot study to detect GISA was performed with vancomycin-containing Mueller-Hinton agar (MHA) prepared in-house in place of commercially prepared BHIA. MHA was selected for this study because this medium is widely available and well standardized. The results of the pilot study showed that supplementation of MHA with 5 microg of vancomycin per ml was both a sensitive and a specific method for screening for GISA isolates. This method was used to screen for GISA among 630 clinical isolates of methicillin-resistant S. aureus collected during 1997 from 33 U.S. hospitals. Although 14 S. aureus isolates grew on the screening agar, all were vancomycin susceptible (MICs were

Surveillance of antimicrobial use and antimicrobial resistance in United States hospitals: project ICARE phase 2. Project Intensive Care Antimicrobial Resistance Epidemiology (ICARE) hospitals.

The search for the means to understand and control the emergence and spread of antimicrobial resistance has become a public health priority. Project ICARE (Intensive Care Antimicrobial Resistance Epidemiology) has established laboratory-based surveillance for antimicrobial resistance and antimicrobial use at a subset of hospitals participating in the National Nosocomial Infection Surveillance system. These data illustrate that for most antimicrobial-resistant organisms studied, rates of resistance were highest in the intensive care unit (ICU) areas and lowest in the outpatient areas. A notable exception was ciprofloxacin- or ofloxacin-resistant Pseudomonas aeruginosa, for which resistance rates were highest in the outpatient areas. For most of the antimicrobial agents associated with this resistance, the rate of use was highest in the ICU areas, in parallel to the pattern seen for resistance. These comparative data on use and resistance among similar areas (i.e., ICU or other inpatient areas) can be used as a benchmark by participating hospitals to focus their efforts at addressing antimicrobial resistance.

Determinants of vancomycin use in adult intensive care units in 41 United States hospitals.

We analyzed data from a prospective observational cohort study that included 108 adult intensive care units (ICUs) in 41 United States hospitals. Use of vancomycin (defined daily doses per 1,000 patient-days), nosocomial infection rates, and proportion of all Staphylococcus aureus isolates resistant to methicillin (MRSA rate) were recorded from January 1996 through November 1997. The median rate of vancomycin use was lowest in coronary care ICUs and highest in general surgical ICUs. Prior approval before use of vancomycin was required in only 26 (24%) of the 108 ICUs. In a multivariate linear regression model, rates of MRSA, central line-associated bloodstream infection, and the type of ICU were independent predictors of vancomycin use. None of the vancomycin control practices was associated with lower rates of vancomycin use; however, it is important to recognize that this database was not designed to measure rates of inappropriate use. Vancomycin use is heavily determined by rates of endemic MRSA and central line-associated bloodstream infection. Efforts to reduce these rates through infection control activities should be included in hospitals' efforts to reduce vancomycin use.

Antimicrobial resistance in intensive care units.

The unique nature of the intensive care unit (ICU) environment makes this part of the hospital a focus for the emergence and spread of many antimicrobial-resistant pathogens. There are ample opportunities for the cross-transmission of resistant bacteria from patient to patient, and patients are commonly exposed to broad-spectrum antimicrobial agents. Rates of resistance have increased for most pathogens associated with nosocomial infections among ICU patients, and rates are almost universally higher among ICU patients compared with non-ICU patients. There are many opportunities, however, to prevent the emergence and spread of these resistant pathogens through improved use of established infection control measures (i.e., patient isolation, hand washing, glove use, and appropriate gown use), and implementation of a systematic review of antimicrobial use.

Risk factors for early recurrent Clostridium difficile-associated diarrhea.

Recurrence is a common sequela of Clostridium difficile-associated diarrhea (CDD) and may increase morbidity, costs, and treatment-related antimicrobial resistance. Because recurrent CDD (RCDD) frequently occurs very soon after an initial episode, our goal was to determine the risk factors for early RCDD (occurring < or = 45 days after the initial episode). We conducted a case-control study, comparing 13 patients with early RCDD (case patients) with 46 patients who had only one CDD episode (control patients) at Centre Hospitalier Angrignon (Québec) during January 1993 through November 1994. Risk factors for early RCDD included a history of chronic renal insufficiency, a white blood cell count of > or = 15 x 10(3)/mm3, and community-acquired diarrhea with the first CDD episode. For seven of eight case patients, C. difficile strains from the first and second CDD episodes were identical, suggesting that relapse is more common than reinfection. These results suggest that treatments should be directed at preventing relapses in patients at high risk for early RCDD.