Ashish Bhargava

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.

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.

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.

Satraplatin: leading the new generation of oral platinum agents

Background: In recent years, JM-216/satraplatin (GPC Biotech, Inc.) has emerged as a novel oral platinum analogue with a better toxicity profile than cisplatin. Since satraplatin is more hydrophobic than cisplatin or oxaliplatin, it appears to demonstrate efficacy in cisplatin-resistant cell lines. The preclinical and clinical evaluation of satraplatin stimulated this review of the pharmacology and clinical trial data of this agent. Methods: A literature review was conducted in the MEDLINE database from 1985 to present using the keywords ‘satraplatin’ or ‘JM-216’. The abstracts regarding satraplatin reported at the 2007 – 2009 American Society of Clinical Oncology meetings were also reviewed. Results/conclusion: Satraplatin has a favorable toxicity profile, and appears to have clinical activity against a variety of malignancies such as breast, prostate and lung cancer. The oral route of administration and the intermittent schedule makes it very convenient for clinical use. Despite this, a FDA-approved indication has not yet been achieved. The only Phase III trial with satraplatin was conducted in pretreated metastatic castrate-resistant prostate cancer (CRPC), revealing an improvement in progression-free survival but no overall survival benefit. Future development would have to include designing trials in docetaxel-refractory metastatic CRPC, or in other malignancies where cisplatin is of benefit.

Risk factors for colonization due to carbapenem-resistant Enterobacteriaceae among patients exposed to long-term acute care and acute care facilities.

BACKGROUND This study aimed to identify risk factors associated with carbapenem-resistant Enterobacteriaceae (CRE) colonization among patients screened with rectal cultures upon admission to a hospital or long-term acute care (LTAC) center and to compare risk factors among patients who were screen positive for CRE at the time of hospital admission with those screen positive prior to LTAC admission. METHODS A retrospective nested matched case-control study was conducted from June 2009 to December 2011. Patients with recent LTAC exposure were screened for CRE carriage at the time of hospital admission, and patients admitted to a regional LTAC facility were screened prior to LTAC admission. Cases were patients with a positive CRE screening culture, and controls (matched in a 3∶1 ratio to cases) were patients with negative screening cultures. RESULTS Nine hundred five cultures were performed on 679 patients. Forty-eight (7.1%) cases were matched to 144 controls. One hundred fifty-eight patients were screened upon hospital admission and 521 prior to LTAC admission. Independent predictors for CRE colonization included Charlsons score greater than 3 (odds ratio [OR], 4.85 [95% confidence interval (CI), 1.64-14.41]), immunosuppression (OR, 3.92 [95% CI, 1.08-1.28]), presence of indwelling devices (OR, 5.21 [95% CI, 1.09-2.96]), and prior antimicrobial exposures (OR, 3.89 [95% CI, 0.71-21.47]). Risk factors among patients screened upon hospital admission were similar to the entire cohort. Among patients screened prior to LTAC admission, the characteristics of the CRE-colonized and noncolonized patients were similar. CONCLUSIONS These results can be used to identify patients at increased risk for CRE colonization and to help target active surveillance programs in healthcare settings.

Epidemiology and Risk Factors for Isolation of Escherichia coli Producing CTX-M-Type Extended-Spectrum β-Lactamase in a Large U.S. Medical Center

ABSTRACT A case-case-control study was conducted to identify independent risk factors for recovery of Escherichia coli strains producing CTX-M-type extended-spectrum β-lactamases (CTX-M E. coli) within a large Southeastern Michigan medical center. Unique cases with isolation of ESBL-producing E. coli from February 2010 through July 2011 were analyzed by PCR for blaCTX-M, blaTEM, and blaSHV genes. Patients with CTX-M E. coli were compared to patients with E. coli strains not producing CTX-M-type ESBLs (non-CTX-M E. coli) and uninfected controls. Of 575 patients with ESBL-producing E. coli, 491 (85.4%) isolates contained a CTX-M ESBL gene. A total of 319 (84.6%) patients with CTX-M E. coli (282 [74.8%] CTX-M-15 type) were compared to 58 (15.4%) non-CTX-M E. coli patients and to uninfected controls. Independent risk factors for CTX-M E. coli isolation compared to non-CTX-M E. coli included male gender, impaired consciousness, H2 blocker use, immunosuppression, and exposure to penicillins and/or trimethoprim-sulfamethoxazole. Compared to uninfected controls, independent risk factors for isolation of CTX-M E. coli included presence of a urinary catheter, previous urinary tract infection, exposure to oxyimino-cephalosporins, dependent functional status, non-home residence, and multiple comorbid conditions. Within 48 h of admission, community-acquired CTX-M E. coli (n = 51 [16%]) and non-CTX-M E coli (n = 11 [19%]) strains were isolated from patients with no recent health care contacts. CTX-M E. coli strains were more resistant to multiple antibiotics than non-CTX-M E. coli strains. CTX-M-encoding genes, especially blaCTX-M-15 type, represented the most common ESBL determinants from ESBL-producing E. coli, the majority of which were present upon admission. Septic patients with risk factors for isolation of CTX-M E. coli should be empirically treated with appropriate agents. Regional infection control efforts and judicious antibiotic use are needed to control the spread of these organisms.

Extended-Spectrum β-Lactamase Producers Reported as Susceptible to Piperacillin-Tazobactam, Cefepime, and Cefuroxime in the Era of Lowered Breakpoints and No Confirmatory Tests

Cefepime, and Cefuroxime in the Era of Lowered Breakpoints and No Confirmatory Tests Author(s): Dror Marchaim, MD; Bharath Sunkara, MD; Paul R. Lephart, PhD; Uma Mahesh Gudur, MBBS; Ashish Bhargava, MD; Ryan P. Mynatt, PharmD; Jing J. Zhao, PharmD; Suchitha Bheemreddy, MD; Kayoko Hayakawa, MD, PhD; Teena Chopra, MD; Sorabh Dhar, MD; Keith S. Kaye, MD, MPH Source: Infection Control and Hospital Epidemiology, Vol. 33, No. 8 (August 2012), pp. 853-855 Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiology of America Stable URL: http://www.jstor.org/stable/10.1086/666632 . Accessed: 26/07/2013 10:59

Rhodococcus equi venous catheter infection: a case report and review of the literature

IntroductionRhodococcus equi is an animal pathogen that was initially isolated from horses and is being increasingly reported as a cause of infection in humans with impaired cellular immunity. However, this pathogen is underestimated as a challenging antagonist and is frequently considered to be a mere contaminant despite the potential for life-threatening infections. Most case reports have occurred in immunocompromised patients who have received organ transplants (for example kidney, heart, bone marrow) or those with human immunodeficiency virus infection. Infections often manifest as pulmonary involvement or soft tissue abscesses. Bacteremia related to R. equi infections of tunneled central venous catheters has rarely been described.Case presentationWe report the case of a 63-year-old non-transplant recipient, non-HIV infected Caucasian woman with endometrial carcinoma who developed recurrent bloodstream infections and septic shock due to R. equi and ultimately required the removal of her port catheter, a subcutaneous implantable central venous catheter. We also review the medical literature related to human infections with R. equi.ConclusionR. equi should be considered a serious pathogen, not a contaminant, particularly in an immunocompromised patient who presents with a central venous catheter-related bloodstream infection. Counseling patients with central venous catheters who participate in activities involving exposure to domesticated animals is recommended.

Candida kefyr endocarditis in a patient with hypertrophic obstructive cardiomyopathy.

We report an uncommon but emerging fungal pathogen, Candida kefyr, as a causative agent of infective endocarditis in a patient with a known history of hypertrophic obstructive cardiomyopathy. A 74-year-old woman with diabetes type II, hypertrophic obstructive cardiomyopathy, presented with gross hematuria and abdominal pain. Computed tomography scan revealed a hemorrhagic mass in the superior pole of the right kidney, with a thrombus extending from the ureter to the bladder. She underwent cryotherapy of the renal mass, together with retrograde ureteral stent placement, developed hypotension and respiratory distress, spiked high-grade fever, and had a new pansystolic murmur over the mitral and aortic areas. Urine and blood culture grew C. kefyr. Transthoracic echocardiogram revealed large mitral valve vegetation with moderate regurgitation. Micafungin was started, patient responded, and fungemia cleared. Repeat echocardiogram showed small vegetation, preserved leaflet mobility and mild regurgitation. Patient received 10 days of micafungin, followed by 6 weeks of fluconazole.