Combination Regimens for Treatment of Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections.

Previous studies reported decreased mortality in patients with carbapenemase-producing Klebsiella pneumoniae bloodstream infections (BSIs) treated with combination therapy but included carbapenem-susceptible and -intermediate isolates, as per revised CLSI breakpoints. Here, we assessed outcomes in patients with BSIs caused by phenotypically carbapenem-resistant K. pneumoniae (CRKP) according to the number of in vitro active agents received and whether an extended-spectrum beta-lactam (BL) antibiotic, including meropenem, or an extended-spectrum cephalosporin was administered. We retrospectively reviewed CRKP BSIs at two New York City hospitals from 2006 to 2013, where all isolates had meropenem or imipenem MICs of ≥4 µg/ml. Univariate and multivariable models were created to identify factors associated with mortality. Of 141 CRKP BSI episodes, 23% were treated with a single active agent (SAA), 26% were treated with an SAA plus BL, 28% were treated with multiple active agents (MAA), and 23% were treated with MAA plus BL. Ninety percent of isolates had meropenem MICs of ≥16 µg/ml. Thirty-day mortality was 33% overall and did not significantly differ across the four treatment groups in a multivariable model (P = 0.4); mortality was significantly associated with a Pitt bacteremia score of ≥4 (odds ratio [OR], 7.7; 95% confidence interval [CI], 3.2 to 18.1; P = 0.1), and immunosuppression was protective (OR, 0.4; 95% CI, 0.2 to 1.0; P = 0.04). Individual treatment characteristics were also not significantly associated with outcome, including use of SAAs versus MAA (26% versus 38%, P = 0.1) or BL versus no BL (26% versus 39%, P = 0.1). In summary, in patients with CRKP BSIs caused by isolates with high carbapenem MICs, the role of combination therapy remains unclear, highlighting the need for prospective studies to identify optimal treatment regimens.

Epidemiology and outcomes of carbapenem-resistant Klebsiella pneumoniae bacteriuria in kidney transplant recipients.

BACKGROUND: Little is known about the epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteriuria following kidney transplantation. We determined the incidence of post-transplant CRKP bacteriuria in adults who underwent kidney transplant from 2007 to 2010 at 2 New York City centers. METHODS: We conducted a case-control study to identify factors associated with CRKP bacteriuria compared with carbapenem-susceptible K. pneumoniae (CSKP) bacteriuria, assessed whether CRKP bacteriuria was associated with mortality or graft failure, and compared outcomes of treated episodes of CRKP and CSKP bacteriuria. RESULTS: Of 1852 transplants, 20 (1.1%) patients developed CRKP bacteriuria. Factors associated with CRKP bacteriuria included receipt of multiple organs (odds ratio [OR] 4.7, 95% confidence interval [CI] 1.1-20.4), deceased-donor allograft (OR 5.9, 95% CI 1.3-26.8), transplant admission length of stay (OR 1.1 per day, 95% CI 1.0-1.1), pre-transplant CRKP infection or colonization (OR 18.3, 95% CI 2.0-170.5), diabetes mellitus (OR 2.8, 95% CI 1.0-7.8), and receipt of antimicrobials other than trimethoprim-sulfamethoxazole (OR 4.3, 95% CI 1.6-11.2). CONCLUSION: Compared to CSKP bacteriuria, CRKP bacteriuria was associated with increased mortality (30% vs. 10%, P = 0.03) but not graft failure. Treated episodes of CRKP bacteriuria were less likely to achieve microbiologic clearance (83% vs. 97%; P = 0.05) and more likely to recur within 3 months (50% vs. 22%, P = 0.02) than CSKP episodes. CRKP bacteriuria after kidney transplant is associated with mortality and antimicrobial failure after treatment.

Multicenter study of epidemiological cutoff values and detection of resistance in Candida spp. to anidulafungin, caspofungin, and micafungin using the Sensititre YeastOne colorimetric method.

Neither breakpoints (BPs) nor epidemiological cutoff values (ECVs) have been established for Candida spp. with anidulafungin, caspofungin, and micafungin when using the Sensititre YeastOne (SYO) broth dilution colorimetric method. In addition, reference caspofungin MICs have so far proven to be unreliable. Candida species wild-type (WT) MIC distributions (for microorganisms in a species/drug combination with no detectable phenotypic resistance) were established for 6,007 Candida albicans, 186 C. dubliniensis, 3,188 C. glabrata complex, 119 C. guilliermondii, 493 C. krusei, 205 C. lusitaniae, 3,136 C. parapsilosis complex, and 1,016 C. tropicalis isolates. SYO MIC data gathered from 38 laboratories in Australia, Canada, Europe, Mexico, New Zealand, South Africa, and the United States were pooled to statistically define SYO ECVs. ECVs for anidulafungin, caspofungin, and micafungin encompassing ≥97.5% of the statistically modeled population were, respectively, 0.12, 0.25, and 0.06 µg/ml for C. albicans, 0.12, 0.25, and 0.03 µg/ml for C. glabrata complex, 4, 2, and 4 µg/ml for C. parapsilosis complex, 0.5, 0.25, and 0.06 µg/ml for C. tropicalis, 0.25, 1, and 0.25 µg/ml for C. krusei, 0.25, 1, and 0.12 µg/ml for C. lusitaniae, 4, 2, and 2 µg/ml for C. guilliermondii, and 0.25, 0.25, and 0.12 µg/ml for C. dubliniensis. Species-specific SYO ECVs for anidulafungin, caspofungin, and micafungin correctly classified 72 (88.9%), 74 (91.4%), 76 (93.8%), respectively, of 81 Candida isolates with identified fks mutations. SYO ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin, micafungin, and especially caspofungin, since testing the susceptibilities of Candida spp. to caspofungin by reference methodologies is not recommended.

Risk factors associated with Clostridium difficile infection after kidney and pancreas transplantation.

BACKGROUND: Clostridium difficile infection (CDI) is a common cause of nosocomial antibiotic-associated diarrhea with an increased incidence reported in solid organ transplant recipients. We sought to determine if kidney and/or pancreas transplant recipients possess unique risk factors for CDI. METHODS: Between January 2009 and February 2011, 942 kidney and 56 pancreas transplants were performed at the 2 centers. Of these, 28 recipients (kidney, n = 24; pancreas, n = 4) developed CDI. Cases were matched to controls (n = 56) in a 1:2 ratio. RESULTS: Those with CDI were mostly male patients (82% vs. 48%, P = 0.003), deceased-donor organ recipients (86% vs. 64%, P = 0.045), more likely to have leukopenia (18% vs. 4%, P = 0.038), and had undergone a gastrointestinal procedure within 3 months preceding CDI diagnosis (18% vs. 4%, P = 0.038). Cases had higher cumulative and restricted antimicrobial exposure in days (37 ± 79 vs. 8 ± 12, P = 0.009 and 27 ± 69 vs. 7 ± 10, P = 0.032). Cephalosporin use was more common among cases (43% vs. 16%, P = 0.008). CONCLUSION: Careful antimicrobial selection and assurance of optimal treatment duration in the kidney and pancreas transplant population is prudent. Clinicians should have a heightened awareness of CDI risk particularly during periods of leukopenia and in the setting of gastrointestinal procedures.

Vancomycin-resistant Enterococcus faecium meningitis successfully managed with linezolid: case report and review of the literature.

Enterococci cause serious illness in immunocompromised patients and severely ill, hospitalized patients. Resistance to vancomycin has increased in frequency during the past few years. Limited therapeutic options are available for vancomycin-resistant enterococcal infections and the optimum therapy has not been established. We report a case of nosocomial vancomycin-resistant Enterococcus faecium meningitis in the setting of hyperinfection with Strongyloides stercoralis that was successfully treated with linezolid. We also review the previously reported cases of vancomycin-resistant E. faecium meningitis.

Delayed-onset ticlopidine-induced cholestatic jaundice.

An 86-year-old man experienced a rash approximately 2 weeks after starting ticlopidine therapy, necessitating discontinuation of the drug. About 1 month later, despite discontinuation, he developed jaundice and liver test abnormalities. These resolved gradually over the next few months. Based on case reports and the drug's pharmacokinetic profile, a high index of suspicion for ticlopidine-induced jaundice is prudent in patients with recent exposure to the agent who have evidence of liver damage.