Gregory A. Eschenauer

Carbapenem-resistant Klebsiella pneumoniae bacteremia: factors correlated with clinical and microbiologic outcomes.

We undertook a retrospective cohort study describing general outcomes and specific factors associated with positive outcomes in bacteremia due to carbapenem-resistant Klebsiella pneumoniae (CRKP). Forty-eight patients were included, of which 42% died at 30 days. Forty-two percent of patients were in septic shock at the time of the first positive blood culture, and 42% were recipients of solid organ transplants. Lack of microbiologic eradication at 7 days was independently associated with 30-day mortality. Adjunctive procedures performed for source control and microbiologic eradication at 7 days were associated with a favorable clinical response at 7 days. Time to initiation and receipt at any time of antimicrobials with in vitro activity against CRKP were not associated with improved survival. Breakthrough bacteremia occurred in 8 cases, all in patients receiving tigecycline. Our data suggest that severity of illness, rapid microbiologic eradication, and source control are crucial factors in the outcomes of patients with CRKP bacteremia.

Epidemiology, Clinical Characteristics and Outcomes of Extensively Drug-Resistant Acinetobacter baumannii Infections among Solid Organ Transplant Recipients

Background Extensively drug-resistant Acinetobacter baumannii (XDR-Ab) has emerged as a major nosocomial pathogen, but optimal treatment regimens are unknown. Although solid organ transplant (SOT) recipients are particularly susceptible to XDR-Ab infections, studies in this population are limited. Our objectives were to determine the epidemiology, clinical characteristics and outcomes of XDR-Ab infections among SOT patients. Methods A retrospective study of SOT recipients at our center who were colonized or infected with XDR-Ab between November 2006 and December 2011 was conducted. Among infected patients, the primary outcome was survival at 28 days. Secondary outcomes included survival at 90 days and clinical success at 28 days, and XDR-Ab infection recurrence. Results XDR-Ab was isolated from 69 SOT patients, of whom 41% (28) and 59% (41) were colonized and infected, respectively. Infections were significantly more common among cardiothoracic than abdominal transplant recipients (p = 0.0004). Ninety-eight percent (40/41) of patients had respiratory tract infections, most commonly ventilator-associated pneumonia (VAP; 88% [36/41]). Survival rates at 28 and 90 days were 54% (22/41) and 46% (19/41), respectively. Treatment with a colistin-carbapenem regimen was an independent predictor of 28-day survival (p = 0.01; odds ratio = 7.88 [95% CI: 1.60–38.76]). Clinical success at 28 days was achieved in 49% (18/37) of patients who received antimicrobial therapy, but 44% (8/18) of successes were associated with infection recurrence within 3 months. Colistin resistance emerged in 18% (2/11) and 100% (3/3) of patients treated with colistin-carbapenem and colistin-tigecycline, respectively (p = 0.03). Conclusions XDR-Ab causes VAP and other respiratory infections following SOT that are associated with significant recurrence and mortality rates. Cardiothoracic transplant recipients are at greatest risk. Results from this retrospective study suggest that colistin-carbapenem combinations may result in improved clinical responses and survival compared to other regimens and may also limit the emergence of colistin resistance.

Antifungal prophylaxis in liver transplant recipients

Although the overall incidence of fungal infections in liver transplant recipients has declined, these infections still contribute significantly to the morbidity and mortality of patients with risk factors for infection. Although antifungal prophylaxis has been widely studied and practiced, no consensus exists on which patients should receive prophylaxis, with which agent, and for what duration. Numerous studies have attempted to ascertain independent risk factors for invasive fungal infections in liver transplant patients, and these data, in addition to clinical trials, identify several patient groups at exceedingly high risk of fungal infection. These include retransplant patients, patients with renal failure requiring hemodialysis or renal replacement therapy, and those requiring reoperations after transplant. Because the majority of infections occur in the first month after transplantation, prophylaxis should be continued for 4‐6 weeks. However, local epidemiology and research should guide decisions regarding choice of agent as well as overall development of interinstitutional guidelines, because the incidence and spectrum of infection may differ dramatically among institutions. Liver Transpl 15:842–858, 2009.

Real-World Experience with Echinocandin MICs against Candida Species in a Multicenter Study of Hospitals That Routinely Perform Susceptibility Testing of Bloodstream Isolates

ABSTRACT Reference broth microdilution methods of Candida echinocandin susceptibility testing are limited by interlaboratory variability in caspofungin MICs. Recently revised Clinical and Laboratory Standards Institute (CLSI) breakpoint MICs for echinocandin nonsusceptibility may not be valid for commercial tests employed in hospital laboratories. Indeed, there are limited echinocandin susceptibility testing data from hospital laboratories. We conducted a multicenter retrospective study of 9 U.S., Australian, and New Zealand hospitals that routinely tested Candida bloodstream isolates for echinocandin susceptibility from 2005 to 2013. Eight hospitals used Sensititre YeastOne assays. The Candida spp. were C. albicans (n = 1,067), C. glabrata (n = 911), C. parapsilosis (n = 476), C. tropicalis (n = 185), C. krusei (n = 104), and others (n = 154). Resistance and intermediate rates were ≤1.4% and ≤3%, respectively, for each echinocandin against C. albicans, C. parapsilosis, and C. tropicalis. Resistance rates among C. glabrata and C. krusei isolates were ≤7.5% and ≤5.6%, respectively. Caspofungin intermediate rates among C. glabrata and C. krusei isolates were 17.8% and 46.5%, respectively, compared to ≤4.3% and ≤4.4% for other echinocandins. Using CLSI breakpoints, 18% and 19% of C. glabrata isolates were anidulafungin susceptible/caspofungin nonsusceptible and micafungin susceptible/caspofungin nonsusceptible, respectively; similar discrepancies were observed for 38% and 39% of C. krusei isolates. If only YeastOne data were considered, interhospital modal MIC variability was low (within 2 doubling dilutions for each agent). In conclusion, YeastOne assays employed in hospitals may reduce the interlaboratory variability in caspofungin MICs against Candida species that are observed between reference laboratories using CLSI broth microdilution methods. The significance of classifying isolates as caspofungin intermediate and anidulafungin/micafungin susceptible will require clarification in future studies.

To Test or Not To Test: a Cost Minimization Analysis of Susceptibility Testing for Patients with Documented Candida glabrata Fungemias

ABSTRACT This cost minimization analysis investigated the financial impact of the treatment of fungemias due to Candida glabrata from a hospital perspective using three competing alternatives: (i) performing in-house susceptibility testing on all C. glabrata isolates and changing patients to less expensive fluconazole therapy for isolates that test susceptible; (ii) susceptibility testing at outside laboratories with delayed deescalation to fluconazole if isolates test susceptible; and (iii) no routine susceptibility testing with full echinocandin treatment course. Sensitivity analyses and Monte Carlo simulation enhanced the robustness of the model through variation of all assumptions and costs. In the base case, the use of in-house testing displayed a cost advantage over the options of send-out testing and no susceptibility testing (

Multicenter Study of Epidemiological Cutoff Values and Detection of Resistance in Candida spp. to Anidulafungin, Caspofungin, and Micafungin Using the Sensititre YeastOne Colorimetric Method

2,226 versus

Fluconazole versus an echinocandin for Candida glabrata fungaemia: a retrospective cohort study

2,410 versus

Evolving role of early antifungals in the adult intensive care unit.

3,136, respectively). Sensitivity analyses determined that the cost of echinocandin therapy and the turnaround time for send-out testing had the potential to impact the base case model. The decision model indicated that in-house susceptibility testing of C. glabrata isolates should result in lower overall treatment costs in patients with documented C. glabrata fungemias.

Targeted Versus Universal Antifungal Prophylaxis Among Liver Transplant Recipients

ABSTRACT 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.

Doripenem MICs and ompK36 Porin Genotypes of Sequence Type 258, KPC-Producing Klebsiella pneumoniae May Predict Responses to Carbapenem-Colistin Combination Therapy among Patients with Bacteremia

OBJECTIVES We studied whether fluconazole or echinocandin treatment of Candida glabrata fungaemia results in superior outcomes. METHODS A multicentre, retrospective study was performed with 224 adult patients who received ≥ 5 days of therapy with either fluconazole or an echinocandin as their first antifungal treatment after collection of a blood culture that grew C. glabrata. The primary outcome was day 14 complete response. RESULTS Patients in the echinocandin group were generally more ill, both at baseline and at the time of the index culture. Day 14 complete response was obtained in 58/127 (46%) and 50/97 (52%) of the fluconazole and echinocandin patients, respectively (P=0.383). Logistic regression found intensive care unit admission to be associated with failure [OR 0.456 (0.217-0.957), P=0.038] and echinocandin therapy to be associated with day 14 complete response [OR 2.305 (1.124-4.727), P=0.023]. Twenty-eight day survival was similar between the fluconazole and echinocandin groups and logistic regression did not reveal antifungal therapy choice to be independently predictive of mortality. For patients treated with fluconazole, a dose:MIC ratio >12.5 (when compared with a ratio ≤ 12.5) was associated with a significantly higher day 14 complete response [4/20 (20%) ≤ 12.5 versus 50/102 (49%) >12.5, P=0.025]. CONCLUSIONS Severity of illness and choice of antifungal predict response in patients with C. glabrata fungaemia. Antifungal choice, however, does not influence mortality. In addition, new CLSI C. glabrata fluconazole susceptibility breakpoints are predictive of response when fluconazole is dosed appropriately.