The Evolving Role of Antifungal Susceptibility Testing

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98278/1/phar1233.pd

Azithromycin‐Warfarin Interaction: Are We Fishing with a Red Herring?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90099/1/phco.25.4.630.61028.pd

Macrolide‐resistant Mycoplasma pneumoniae pneumonia in transplantation: Increasingly typical?

Mycoplasma pneumoniae is one of the most common bacterial causes of pneumonia. Macrolide‐resistant M pneumoniae (MRMP) was documented in 7.5% of isolates in the United States. Resistance portends poor outcomes to macrolide therapy, yet patients respond well to fluoroquinolones or tetracyclines such as minocycline. However, MRMP may be under‐appreciated because M pneumoniae generally causes relatively mild infections in non‐immunosuppressed adults that may resolve without effective therapy and because microbiological confirmation and susceptibility are not routinely performed. We report two cases of pneumonia due to MRMP in kidney transplant recipients. Both patients required hospital admission, worsened on macrolide therapy, and rapidly defervesced on doxycycline or levofloxacin. In one case, M pneumoniae was only identified by multiplex respiratory pathogen panel analysis of BAL fluid. Macrolide resistance was confirmed in both cases by real‐time PCR and point mutations associated with macrolide resistance were identified. M pneumoniae was isolated from both cases, and molecular genotyping revealed the same genotype. In conclusion, clinicians should be aware of the potential for macrolide resistance in M pneumoniae, and may consider non‐macrolide‐based therapy for confirmed or non‐responding infections in patients who are immunocompromised or hospitalized.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163484/2/tid13318.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163484/1/tid13318_am.pd

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

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

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. © 2009 AASLD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63531/1/21826_ftp.pd

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

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 ($2,226 versus$2,410 versus $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

Epidemiology, clinical characteristics and outcomes of extensively drug-resistant Acinetobacter baumannii infections among solid organ transplant recipients.

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.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.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).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