Background. Colistin, originally abandoned due to high rates of nephrotoxicity, has been recently reintroduced due to activity against carbapenem-resistant Gram-negative organisms. Recent literature, largely obtained from outside the United States, suggests a lower rate of nephrotoxicity than historically reported. Methods. A retrospective cohort of all patients who received colistin for ≥48 hours at the Detroit Medical Center over a 5-year period was performed to determine the rate of colistin-associated nephrotoxicity as defined by the RIFLE criteria. Results. Fifty-four (43%) patients in the cohort developed nephrotoxicity. Patients who experienced nephrotoxicity after colistin administration were in the Risk (13%), Injury (17%), or Failure (13%) categories per RIFLE criteria. Patients who developed nephrotoxicity received significantly higher mean doses than those who did not (5.48 mg/kg per day vs 3.95 mg/kg per day; P < .001), and the toxicity occurred in a dose-dependent fashion. Independent predictors for nephrotoxicity were a colistin dose of ≥5.0 mg/kg per day of ideal body weight (odds ratio [OR], 23.41; 95% confidence interval [CI], 5.3–103.55), receipt of concomitant rifampin (OR, 3.81; 95% CI, 1.42–10.2), and coadministration of ≥3 concomitant nephrotoxins (OR, 6.80; 95% CI, 1.42–32.49). Conclusions. In this retrospective cohort, nephrotoxicity (as defined by RIFLE criteria) occurred among 43% of treated patients in a dose-dependent manner. Higher colistin doses, similar to those commonly used in the United States, led to a relatively high rate of nephrotoxicity. These data raise important questions regarding the safe use of colistin in the treatment of multidrug-resistant pathogens.

Carbapenem-resistant Klebsiella pneumoniae has spread worldwide and throughout the United States. Colistin is used extensively to treat infections with this organism. We describe a cluster of colistin-resistant, carbapenem-resistant K. pneumoniae infection cases involving three institutions in Detroit, MI. A cluster of five cases of colistin-resistant, carbapenem-resistant K. pneumoniae was identified at Detroit Medical Center (DMC) from 27 July to 22 August 2009. Epidemiologic data were collected, and transmission opportunities were analyzed. Isolates were genotyped by using pulsed-field gel electrophoresis and repetitive extragenic palindromic PCR. Data regarding the use of colistin were obtained from pharmacy records. The index case of colistin-resistant, carbapenem-resistant K. pneumoniae was followed 20 days later by four additional cases occurring in a 6-day interval. All of the patients, at some point, had stayed at one particular institution. The mean number of opportunities for transmission between patients was 2.3 ± 0.5, and each patient had at least one opportunity for transmission with one of the other patients. Compared to 60 colistin-susceptible, carbapenem-resistant K. pneumoniae controls isolated in the previous year at DMC, case patients were significantly older ( P = 0.05) and the carbapenem-resistant K. pneumoniae organisms isolated from them displayed much higher MICs to imipenem ( P < 0.001). Colistin use was not enhanced in the months preceding the outbreak. Genotyping revealed two closely related clones. This report of a colistin-resistant, carbapenem-resistant K. pneumoniae outbreak is strongly linked to patient-to-patient transmission. Controlling the spread and novel emergence of bacteria with this phenotype is of paramount importance.

Drug-resistant Acinetobacter species are problematic in tertiary-care hospitals. We describe the epidemiology, resistance patterns, and outcomes of older adults with Acinetobacter infection in community hospitals. We queried the microbiology databases of the Oakwood Healthcare System (4 hospitals with 632, 259, 199, and 168 beds) for clinical Acinetobacter cultures obtained in 2003-2008. Patients aged 60 years who were admitted from home or nursing homes were included. We recorded the initial Acinetobacter isolate and susceptibility to 8 antibiotics. Cultures obtained 48 h after hospitalization were categorized as "nosocomial." Administrative databases provided patients' origins (home or nursing home) and discharge destinations (home, nursing home, long-term acute-care facility, another hospital, or hospice care or death). During the 6-year period, 560 community-dwelling (mean age +/- standard deviation, 74 +/- 8.6 years) and 280 nursing home-dwelling (78 +/- 9.1 years) patients had Acinetobacter isolated. During this period, Acinetobacter prevalence increased 25% (P<.001, by trend test). In comparison of 2003 with 2008, Acinetobacter resistance to imipenem and ampicillin/sulbactam increased (from 1.8% to 33.1%; P<.001), as did "panresistance" (ie, resistance to all 8 antibiotics; increase from 0.0% to 13.6%; P<.001). Although resistance was stable in community-acquired isolates (resistance to approximately 4.2 antibiotics), resistance increased among nursing home-acquired and nosocomial-acquired isolates (from 4.5 to 5.7 and from 5.0 to 6.0 antibiotics, respectively; P<.01). At discharge, only 25% of community-dwelling and 50% of nursing home-dwelling patients returned to their place of origin; the remainder required higher levels of care or died. After adjustment for age, length of stay, and origin, resistance to each additional antibiotic predicted a >20% increased risk for discharge to higher levels of care or death (odds ratio, 1.23; 95% confidence interval, 1.11-1.36). The prevalence and resistance of Acinetobacter species are increasing in the community. Patients with resistant isolates are selectively discharged to nursing homes and long-term acute-care facilities, introducing resistance to new facilities.

Objective.: To determine whether increases in contact isolation precautions are associated with decreased adherence to isolation practices among healthcare workers (HCWs).Design.: Prospective cohort study from February 2009 to October 2009.Setting.: Eleven teaching hospitals.Participants.: HCWs.Methods.: One thousand thirteen observations conducted on HCWs. Additional data included the number of persons in isolation, types of HCWs, and hospital-specific contact precaution practices. Main outcome measures included compliance with individual components of contact isolation precautions (hand hygiene before and after patient encounter, donning of gown and glove upon entering a patient room, and doffing upon exiting) and overall compliance (all 5 measures together) during varying burdens of isolation.Results.: Compliance with hand hygiene was as follows: prior to donning gowns/gloves, 37.2%; gowning, 74.3%; gloving, 80.1%; doffing of gowns/gloves, 80.1%; after gown/glove removal, 61%. Compliance with all components was 28.9%. As the burden of isolation increased (20% or less to greater than 60%), a decrease in compliance with hand hygiene (43.6%—4.9%) and with all 5 components (31.5%—6.5%) was observed. In multivariable analysis, there was an increase in noncompliance with all 5 components of the contact isolation precautions bundle (odds ratio [OR], 6.6 [95% confidence interval (CI), 1.15-37.44];P= .03) and in noncompliance with hand hygiene prior to donning gowns and gloves (OR, 10.1 [95% CI, 1.84—55.54];P= .008) associated with increasing burden of isolation.Conclusions.: As the proportion of patients in contact isolation increases, compliance with contact isolation precautions decreases. Placing 40% of patients under contact precautions represents a tipping point for noncompliance with contact isolation precautions measures.

Background.: Carbapenem-resistant Enterobacteriaceae (CRE) are rapidly emerging worldwide. Control group selection is critically important when analyzing predictors of antimicrobial resistance. Focusing on modifiable risk factors can optimize prevention and resource expenditures. To identify specific predictors of CRE, patients with CRE were compared with 3 control groups: (1) patients with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, (2) patients with non-ESBL-containing Enterobacteriaceae, and (3) uninfected controls.Design.: Matched multivariable analyses.Patients and Setting.: Patients possessing CRE that were isolated at Detroit Medical Center from September 1, 2008, to August 31, 2009.Methods.: Patients were matched (1:1 ratio) to the 3 sets of controls. Matching parameters included (1) bacteria type, (2) hospital/ facility, (3) unit/clinic, (4) calendar year, and (5) time at risk (ie, from admission to culture). Matched multivariable analyses were conducted between uninfected controls and patients with CRE, ESBL, and non-ESBL Enterobacteriaceae. Models were also designed comparing patients with CRE to patients with ESBL, patients with non-ESBL Enterobacteriaceae, and all 3 non-CRE groups combined.Results.: Ninety-one unique patients with CRE were identified, and 6 matched models were constructed. Recent (less than 3 months) exposure to antibiotics was the only parameter that was consistently associated with CRE, regardless of the group to which CRE was compared, and was not independently associated with isolation of ESBL or non-ESBL Enterobacteriaceae.Conclusions.: Exposure to antibiotics within 3 months was an independent predictor that characterized patients with CRE isolation. As a result, antimicrobial stewardship efforts need to become a major focus of preventive Interventions. Regulatory focus regarding appropriate antimicrobial use might decrease the detrimental effects of antibiotic misuse and spread of CRE.

Extended-spectrum-β-lactamase (ESBL)-producing pathogens are associated with extensive morbidity and mortality and rising health care costs. Scant data exist on the impact of antimicrobial therapy on clinical outcomes in patients with ESBL bloodstream infections (BSI), and no large studies have examined the impact of cefepime therapy. A retrospective 3-year study was performed at the Detroit Medical Center on adult patients with BSI due to ESBL-producing Klebsiella pneumoniae or Escherichia coli . Data were collected from the medical records of study patients at five hospitals between January 2005 and December 2007. Multivariate analysis was performed using logistic regression. One hundred forty-five patients with BSI due to ESBL-producing pathogens, including K. pneumoniae (83%) and E. coli (16.5%), were studied. The mean age of the patients was 66 years. Fifty-one percent of the patients were female, and 79.3% were African-American. Fifty-three patients (37%) died in the hospital, and 92 survived to discharge. In bivariate analysis, the variables associated with mortality ( P < 0.05) were presence of a rapidly fatal condition at the time of admission, use of gentamicin as a consolidative therapeutic agent, and presence of one or more of the following prior to culture date: mechanical ventilation, stay in the intensive care unit (ICU), and presence of a central venous catheter. In multivariate analysis, the predictors of in-hospital mortality included stay in the intensive care unit (odds ratio [OR], 2.17; 95% confidence interval [CI], 0.98 to 4.78), presence of a central-line catheter prior to positive culture (OR, 2.33; 95% CI, 0.77 to 7.03), presence of a rapidly fatal condition at the time of admission (OR, 5.13; 95% CI, 2.13 to 12.39), and recent prior hospitalization (OR, 1.92; 95% CI, 0.83 to 4.09). When carbapenems were added as empirical therapy to the predictor model, there was a trend between empirical carbapenem therapy and decreased mortality (OR, 0.61; 95% CI, 0.26 to 1.50). When added to the model, receipt of empirical cefepime alone ( n = 43) was associated with increased mortality, although this association did not reach statistical significance (OR, 1.66; 95% CI, 0.71 to 3.87). The median length of hospital stay was shorter for patients receiving empirical cefepime than for those receiving empirical or consolidated carbapenem therapy. In multivariate analysis, empirical therapy with cefepime for BSI due to an ESBL-producing pathogen was associated with a trend toward an increased mortality risk and empirical carbapenem therapy was associated with a trend toward decreased mortality risk.