Teena Chopra

Incidence of and Risk Factors for Colistin-Associated Nephrotoxicity in a Large Academic Health System

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.

Outbreak of Colistin-Resistant, Carbapenem-Resistant Klebsiella pneumoniae in Metropolitan Detroit, Michigan

ABSTRACT 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.

Recent Exposure to Antimicrobials and Carbapenem-Resistant Enterobacteriaceae: The Role of Antimicrobial Stewardship

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.

Impact of Cefepime Therapy on Mortality among Patients with Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase-Producing Klebsiella pneumoniae and Escherichia coli

ABSTRACT 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.

Recent epidemiology of Clostridium difficile infection during hematopoietic stem cell transplantation

Chopra T, Chandrasekar P, Salimnia H, Heilbrun LK, Smith D, Alangaden GJ. Recent epidemiology of Clostridium difficile infection during hematopoietic stem cell transplantation.
Clin Transplant 2011: 25: E82–E87.

Contact Precautions: More Is Not Necessarily Better

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.

Clostridium difficile infection in cancer patients and hematopoietic stem cell transplant recipients

Clostridium difficile has become the most common bacterial cause of nosocomial diarrhea. High rates of C. difficile infection (CDI) coupled with increasing morbidity and mortality attributed to CDI have sparked a renewed interest in this disease. Emergence of hypervirulent strains, rising rates of severe and recurrent infection and associated infection control challenges, and diagnostic and therapeutic dilemmas are major issues in the non-oncology population. Scant data on CDI exist in the cancer/transplant population. The purpose of this article is to describe the epidemiology, pathogenesis and management of CDI in patients receiving cancer chemotherapeutic agents, and in hematopoietic stem cell transplant recipients.

Outcomes and genetic relatedness of carbapenem-resistant enterobacteriaceae at Detroit medical center.

BACKGROUND Carbapenem-resistant Enterobacteriaceae (CRE) are rapidly emerging in hospitals in the United States and are posing a significant threat. To better understand the transmission dynamics and the acquisition of resistant strains, a thorough analysis of epidemiologic and molecular characteristics was performed. METHODS CRE isolated at Detroit Medical Center were analyzed from September 2008 to September 2009. bla(KPC) genes were investigated by polymerase chain reaction (PCR), and repetitive extragenic palindromic PCR (rep-PCR) was used to determine genetic similarity among strains. Epidemiologic and outcomes analyses were performed. RESULTS Ninety-two unique patient CRE isolates were recovered. Sixty-eight strains (74%) were Klebsiella pneumoniae, 7 were Klebsiella oxytoca, 15 were Enterobacter species, and 2 were Escherichia coli. Fifteen isolates (16%) were resistant to colistin, 14 (16%) were resistant to tigecycline, and 2 were resistant to all antimicrobials tested. The mean ± standard deviation age of patients was 63 ± 2 years. Sixty patients (68%) were admitted to the hospital from long-term care facilities. Only 70% of patients received effective antimicrobial therapy when infection was suspected, with a mean time to appropriate therapy of 120 ± 23 hours following sample culturing. The mean length of hospitalization after sample culturing was 18.6 ± 2.5 days. Of 57 inpatients, 18 (32%) died in the hospital. Independent predictors for mortality were intensive care unit stay (odds ratio [OR], 15.8; P = .003) and co-colonization with CRE and either Acinetobacter baumannii or Pseudomonas aeruginosa (OR, 17.2; P = .006). Among K. pneumoniae CRE, rep-PCR revealed 2 genetically related strains that comprised 70% and 20% of isolates, respectively. CONCLUSIONS In this large U.S. cohort of patients with CRE infection, which reflects the modern continuum of medical care, co-colonization with CRE and A. baumannii or P. aeruginosa was associated with increased mortality. Two predominant clones of K. pneumoniae accounted for the majority of cases of CRE infection.

Trends in antimicrobial resistance of Acinetobacter baumannii isolates from a metropolitan Detroit health system.

ABSTRACT A phenotypic and genotypic analysis of Acinetobacter baumannii was conducted from 2003 to 2008 in Detroit, MI. The incidence of A. baumannii increased from 1.7 to 3.7/1,000 patient days during the study period. Susceptibility to ampicillin-sulbactam and imipenem decreased from ∼90% to ∼40%. Genotyping revealed polyclonality, suggesting either emergence of multiple resistant strains or spread of a common genetic element. The sharp rise mandates major multidisciplinary interventions to optimize management of this multidrug-resistant pathogen.

Retrospective evaluation of colistin versus tigecycline for the treatment of Acinetobacter baumannii and/or carbapenem-resistant Enterobacteriaceae infections

BACKGROUND Therapeutic options are limited for infections because of Acinetobacter baumannii and carbapenem-resistant Enterobacteriaceae (CRE). Study aim was to compare the efficacy of colistin to tigecycline for the treatment of these types of infections. METHODS A retrospective study was conducted at the Detroit Medical Center. Adult patients with infections because of A baumannii or CRE in 2009 who received ≥2 doses of colistin or tigecycline were studied. Risk factors, outcomes, and costs were analyzed. RESULTS There were 82 patients with infections because of A baumannii, 12 with CRE, and 12 with A baumannii and CRE coinfection. Seventy-one patients received colistin, 16 received tigecycline, and 19 received both colistin and tigecycline. Seven isolates were nonsusceptible to colistin and 79 to tigecycline. Patients receiving colistin alone or in combination were more likely to die during their hospitalization than patients receiving only tigecycline (P = .002). However, patients receiving colistin had higher severity of acute illness and had notable delays in initiation of effective antimicrobial therapy (P < .001). CONCLUSION Compared with patients who received tigecycline alone, patients who received colistin alone or in combination had a higher severity of acute illness indices and delays in initiation of effective therapy. This increased severity of illness contributed to the increased rate of mortality among patients treated with colistin for A baumannii or CRE infections.