Katie E. Barber

Therapeutic options for vancomycin-resistant enterococcal bacteremia

Enterococcal infections are relatively common among hospitalized patients, likely because these organisms are commensals of human gastrointestinal and genitourinary tracts. With widespread usage of glycopeptides in both humans and livestock, vancomycin-resistant enterococci (VRE) quickly emerged. Bloodstream infections caused by these isolates are of significant concern with limited bactericidal options for treatment. Presently, daptomycin and linezolid serve as the mainstays of therapy, although resistance to both agents has been documented. Newer antimicrobials, specifically lipoglycopeptides and oxazolidinones, have been developed with in vitro activity against these organisms. However, no clinical data are available with their usage for VRE infections, let alone those in the bloodstream. This review focuses on the epidemiology, current and potential future therapeutic options for the treatment of VRE bacteremia.

Elbasvir/Grazoprevir: A Review of the Latest Agent in the Fight against Hepatitis C

Hepatitis C virus (HCV) is estimated to affect up to 150 million people worldwide. Despite worldwide prevalence, treatment modalities prior to 2011 remained suboptimal, with low virologic response rates and intolerable side effect profiles. Fortunately, the landscape of treatment for chronic hepatitis C has rapidly evolved since the introduction of HCV NS3/4 protease inhibitors in 2011. Elbasvir, a NS5A inhibitor, combined with grazoprevir, a NS3/4A protease inhibitor, is the latest FDA-approved therapy for patients with genotype 1 or 4 chronic hepatitis C, with or without compensated cirrhosis. This review will focus on the current literature and clinical evidence supporting elbasvir/grazoprevir as first-line therapy in patients with genotypes 1 and 4 chronic hepatitis C.

Comparison of susceptibility patterns using commercially available susceptibility testing methods performed on prevalent Candida spp.

The rising rates of invasive fungal infections caused by non-albicans Candida and the increasing emergence of antifungal resistance complicate the management of invasive candidiasis. Accurate and timely antifungal susceptibility testing is critical to targeting antifungal therapy. The purpose of this study was to compare commercially available susceptibility testing methods using prospectively collected Candida isolates. Susceptibility testing was performed on 74 Candida isolates collected from July 2014 to March 2015 using broth microdilution according to the Clinical and Laboratory Standards Institute method, Etest, Vitek 2 (YS-05) and Sensititre. Essential agreement and categorical agreement (CA) were assessed using the reference method. Of the 34 total blood isolates collected, Candida albicans comprised only 38 % (13) of the Candida spp. with Candidaglabrata being nearly as prevalent (29 %, 10). CA using Etest was 86 % for fluconazole, 72 % for caspofungin, 98 % for micafungin and 97 % for anidulafungin. Vitek 2 CA was 90 % for fluconazole and 98 % for caspofungin. Sensititre CA was 93 % for fluconazole, 98 % for caspofungin, 98 % for micafungin and 100 % for anidulafungin. Although our study tested a small population of Candida isolates, our results were variable by method. When implementing antifungal susceptibility testing, clinicians should be aware of the strengths and limitations of each testing method.

Mechanisms of fosfomycin resistance in carbapenem-resistant Enterobacter sp.

We report on fosfomycin susceptibility and mechanisms of resistance in clinical strains of blaKPC-positive Enterobacter sp. (n = 19). A total of 14 strains (74%) were susceptible to fosfomycin; 8 strains (42%) were positive for fosA and no strains were positive for FosA3 or FosC2. FosA presence does not appear to correlate with susceptibility.

Successful Treatment of Necrotizing Fasciitis and Streptococcal Toxic Shock Syndrome with the Addition of Linezolid

Necrotizing fasciitis is a deep-seated subcutaneous tissue infection that is commonly associated with streptococcal toxic shock syndrome (TSS). Surgical debridement plus penicillin and clindamycin are the current standard of care. We report a case of necrotizing fasciitis and streptococcal TSS where linezolid was added after a failure to improve with standard therapy. Briefly after isolation of Streptococcus pyogenes from tissue cultures, the patient underwent two surgical debridement procedures and was changed to standard of care therapy. While the patient was hemodynamically stable, the patients wounds, leukocytosis, and thrombocytopenia all progressively worsened. After initiation of linezolid, the patient slowly improved clinically. The present report is the first to highlight the role of linezolid in streptococcal necrotizing fasciitis and TSS not improving with standard therapy.

Ceftaroline for the treatment of methicillin-resistant Staphylococcus aureus bacteremia

PURPOSE The utility of ceftaroline for the treatment of methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) is reviewed. SUMMARY Ceftaroline was originally approved for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSIs) but recently received an additional approval for the treatment of S. aureus bacteremia (SAB) associated with ABSSSIs. Ceftaroline has demonstrated efficacy for the treatment of MRSAB, including isolates with elevated minimum inhibitory concentrations to conventional therapy when used alone or in combination with other agents. In multiple studies, ceftaroline has displayed rapid bloodstream eradication, even in the setting of refractory MRSAB or infective endocarditis. The clinical resolution of MRSAB or SAB in patients who received ceftaroline ranged from 31.0% to 83.3%; studies used varying definitions for clinical resolution and included differing proportions of patients with endocarditis. The use of ceftaroline in treatment-refractory patients and assorted populations makes absolute effectiveness difficult to determine. Ceftaroline has been shown to be effective in patients who have not responded to other agents for MRSAB, making it an attractive option for such patients. Although the approved dosing regimen for ceftaroline fosamil is 600 mg every 12 hours for patients with normal renal function for the treatment of ABSSSIs and CABP, there is some debate about whether more frequent doses (i.e., every 8 hours) are needed for MRSAB. CONCLUSION Ceftaroline has been used to successfully treat SAB, including endocarditis. Therapy with ceftaroline may be considered when antibiotic resistance or previous treatment failure precludes the use of first-line agents.

Intravenous Vancomycin Dosing in the Elderly: A Focus on Clinical Issues and Practical Application

The elderly population can be divided into three distinct age groups: 65–74 years (young-old), 75–84 years (middle-old), and 85+ years (old-old). Despite evidence of a shift in leading causes for mortality in the elderly from infectious diseases to chronic conditions, infections are still a serious cause of death in this population. These patients are at increased risk due to weakened immune systems, an increased prevalence of underlying comorbidities, and decreased physiologic reserves to fight infection. Additionally, elderly patients, especially adults in institutional settings, are at an increased risk of colonization and subsequent infection with methicillin-resistant Staphylococcus aureus at a rate that is five times higher than in younger individuals, causing an increase in empiric and definitive vancomycin use. Elderly patients have unique characteristics that make dosing vancomycin a challenge for clinicians, such as increased volume of distribution and decreased renal function. Using the best available evidence, it is recommended to initiate lower empiric maintenance doses and monitor vancomycin serum concentrations earlier than steady state to accurately calculate drug elimination and make appropriate dose adjustments.

Impact of piperacillin-tazobactam shortage on meropenem use: implications for antimicrobial stewardship programs

Drug shortages pose a clear detriment to antimicrobial stewardship (AS) efforts. Our objective was to evaluate the effect of a piperacillin-tazobactam shortage on meropenem use, related costs, and associated changes in AS activity. A quasi-experimental quality improvement review compared adult patients receiving meropenem ≥72h three months pre-shortage and three months during the shortage. 320 patients were included (pre-shortage: 103; shortage: 217). Baseline characteristics were similar, but the length of stay was slightly longer in pre-shortage [19 (11-32) days] versus shortage [16 (11-32) days] (p=0.094). In pre-shortage and shortage, median days of therapy and estimated meropenem cost were 7 (5-11) and 7 (5-10) and

Impact of an antifungal stewardship intervention on optimization of candidemia management

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Omadacycline Enters the Ring: A New Antimicrobial Contender

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