The VPT combination was associated with both an increased AKI risk and a more rapid onset of AKI compared to the VC combination.

Despite their common use as an empirical combination therapy for the better part of a decade, there has been a recent association between combination therapy with vancomycin and piperacillin-tazobactam and high rates of acute kidney injury (AKI). The reasons for this increased association are unclear, and this analysis was designed to investigate the association. Retrospective cohort and case-control studies were performed. The primary objective was to assess if there is an association between extendedinfusion piperacillin-tazobactam in combination with vancomycin and development of AKI. The secondary objectives were to identify risk factors for AKI in patients on the combination, regardless of infusion strategy, and to evaluate the impact of AKI on clinical outcomes. T he combination of vancomycin and piperacillin-tazobactam is a commonly prescribed empirical therapy for patients with health care-associated infections, as it provides coverage against both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (1). There have been recent reports of relatively high rates of acute kidney injury (AKI), in the range of 15 to 35%, for patients receiving a combination of vancomycin and piperacillin-tazobactam (2-5), which are higher than those reported for patients receiving vancomycin alone (2, 5) and for patients receiving vancomycin and cefepime concomitantly (3). Although vancomycin has long been recognized as a nephrotoxic agent, and piperacillin-tazobactam has been associated with interstitial nephritis, the combination of these agents has been routinely used for many years; however, reports of increased AKI risk have only recently emerged (2-5).The reason for the high rates of AKI in patients receiving vancomycin and piperacillin-tazobactam is unclear, as is the reason for the recent increase in the frequency of reports regarding an association between patients receiving this combination and AKI. Some have hypothesized that the recently reported increased risk is related to more-aggressive vancomycin dosing based on the recently published vancomycin consensus guidelines (6).In addition to the changes in vancomycin dosing, there has also been increased interest in implementing extended-duration infusions of piperacillin-tazobactam in an attempt to optimize the time that free concentrations of the drug are above the MIC of target pathogens, as this is the pharmacokinetic/pharmacodynamic predictor of efficacy. Evidence has been mounting that extended infusion of piperacillin-tazobactam can improve outcomes in patients with invasive infections (7).In 2013, there was an anecdotal increase in cases of AKI among patients receiving vancomycin at the Detroit Medical Center (DMC), Detroit, MI. This perceived increase coincided temporally with a switch of the preferred antipseudomonal agent from cefepime to piperacillin-tazobactam, as well as the implementation of extended-infusion (3-h) administration of all antipseudomonal ␤-lactams (previously administered via standard intermit-

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We studied the clinical and economic impact of a protocol encouraging the use of fidaxomicin as a first-line drug for treatment of Clostridium difficile infection (CDI) in patients hospitalized during a 2-year period. This study evaluated patients who received oral vancomycin or fidaxomicin for the treatment of CDI during a 2-year period. All included patients were eligible for administration of fidaxomicin via a protocol that encouraged its use for selected patients. The primary clinical endpoint was 90-day readmission with a diagnosis of CDI. Hospital charges and insurance reimbursements for readmissions were calculated along with the cost of CDI therapy to estimate the financial impact of the choice of therapy. Recurrences were seen in 10/49 (20.4%) fidaxomicin patients and 19/46 (41.3%) vancomycin patients (P ‫؍‬ 0.027). In a multivariate analysis that included determinations of severity of CDI, serum creatinine increases, and concomitant antibiotic use, only fidaxomicin was significantly as- C lostridium difficile infection (CDI) has been increasing in both severity and incidence (1, 2). In 2011, it was associated with an estimated 29,000 deaths in the United States alone (1). The current mainstays of therapy, metronidazole and oral vancomycin, have been used in CDI therapy for over 30 years with very little drug resistance seen (3). Current guidelines for the treatment of CDI recommend metronidazole for mild to moderate infection and vancomycin for severe infection or recurrent episodes (3, 4). Recent data have challenged the positioning of these drugs for CDI therapy, as oral vancomycin was superior to metronidazole in a study comparing the two drugs and tolevamer, a toxin-binding agent that did not fair well in the study (5).Recently, fidaxomicin, a nonabsorbed macrolide antibiotic, was studied for the treatment of CDI and was found to be superior to oral vancomycin for the prevention of recurrences of CDI (6, 7). Cost concerns and a lack of updated guidelines for CDI may have prevented uptake of fidaxomicin by hospital and managedcare formularies, decreasing its utilization. However, CDI treatment is itself expensive, and if the use of fidaxomicin could prevent readmissions, it is possible that the increased clinical benefits would correlate with decreased costs. To achieve these ends, we instituted a guideline that recommended fidaxomicin as a firstline agent for treatment of many patients with CDI. This study evaluated the outcomes, costs, and costs avoided associated with the use of vancomycin and fidaxomicin after the implementation of this policy. MATERIALS AND METHODSThis was a single-center retrospective study of adult patients who received oral vancomycin or fidaxomicin for CDI treatment from January 2012 to January 2014. A protocol was established encouraging fidaxomicin use for selected patients (Fig. 1). All patients included in this study were eligible for fidaxomicin therapy by the terms of the protocol. The dose recommended by the protocol was 200 mg administered orally twice daily.Inclusi...

Candida auris is a recently discovered, rapidly emerging fungal pathogen. Infections due to C. auris are hospital-acquired, multidrug resistant and associated with high mortality. Areas covered: This review highlights epidemiology, pathogenesis, microbiological characteristics, clinical presentation, diagnostic challenges and treatment options of C. auris infections. Infection prevention measures to prevent spread of C. auris and special measures during an outbreak situation have also been reviewed. Expert commentary: Rapid emergence of hospital onset C. auris is worrisome. Early diagnosis of C. auris is essential for better outcomes and the implementation of infection prevention measures. Lack of widespread awareness, absence of general availability of diagnostic testing methods, and limited options for treatment of C. auris infections make it a difficult-to-treat pathogen. Further studies are needed for better understanding of this emerging pathogen.

Clostridium difficile infection (CDI) is the most common health care-acquired infection associated with high hospital expenditures. The incidence of subsequent recurrent CDI increases with prior episodes of CDI, 15%–35% risk after primary CDI to 35%–65% risk after the first recurrent episode. Recurrent CDI is one of the most challenging and a very difficult to treat infections. Standard guidelines provide recommendations on treatment of primary CDI. However, treatment choices for recurrent CDI are limited. Recent research studies have focused on the discovery of newer alternatives for prevention of recurrent CDI targeting prime virulence factors involved in C. difficile pathogenesis. Bezlotoxumab is a human monoclonal antibody directed against C. difficile toxin B. Multiple in vitro and in vivo animal studies have demonstrated direct binding of bezlotoxumab to C. difficile toxin B preventing intestinal epithelial damage and colitis. Furthermore, this monoclonal antibody mediates early reconstitution of gut microbiota preventing risk of recurrent CDI. Randomized placebo-controlled trials showed concomitant administration of a single intravenous dose of 10 mg/kg of bezlotoxumab, in patients on standard-of-care therapy for CDI, had no substantial effect on clinical cure rates but significantly reduced the incidence of recurrent CDI (~40%). It shows efficacy against multiple strains, including the epidemic BI/NAP1/027 strain. Bezlotoxumab is a US Food and Drug administration-approved, safe and well-tolerated drug with low risk of serious adverse events and drug–drug interactions. Bezlotoxumab has emerged as a novel dynamic adjunctive therapy for prevention of recurrent CDI. Further studies on real-world experience with bezlotoxumab and its impact in reducing rates of recurrent CDI are needed.

There is ongoing debate regarding the role of aerosols in the transmission of SARS-CoV2 in the health care environment. Here, we report a case in which multiple operating room health care providers were exposed to a patient with asymptomatic SARS-CoV2 infection during a prolonged orthopedic surgical intervention and had no evidence of COVID-19 during the 14-day post-exposure period.

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