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Tristan O’Driscoll,1 Christopher W Crank2 1Department of Pharmacy Practice, Chicago College of Pharmacy, Downers Grove, IL, USA; 2Pharmacy Services, Rush-Copley Medical Center, Aurora, IL, USA Abstract: Since its discovery in England and France in 1986, vancomycin-resistant Enterococcus has increasingly become a major nosocomial pathogen worldwide. Enterococci are prolific colonizers, with tremendous genome plasticity and a propensity for persistence in hospital environments, allowing for increased transmission and the dissemination of resistance elements. Infections typically present in immunosuppressed patients who have received multiple courses of antibiotics in the past. Virulence is variable, and typical clinical manifestations include bacteremia, endocarditis, intra-abdominal and pelvic infections, urinary tract infections, skin and skin structure infections, and, rarely, central nervous system infections. As enterococci are common colonizers, careful consideration is needed before initiating targeted therapy, and source control is first priority. Current treatment options including linezolid, daptomycin, quinupristin/dalfopristin, and tigecycline have shown favorable activity against various vancomycin-resistant Enterococcus infections, but there is a lack of randomized controlled trials assessing their efficacy. Clearer distinctions in preferred therapies can be made based on adverse effects, drug interactions, and pharmacokinetic profiles. Although combination therapies and newer agents such as tedizolid, telavancin, dalbavancin, and oritavancin hold promise for the future treatment of vancomycin-resistant Enterococcus infections, further studies are needed to assess their possible clinical impact, especially in the treatment of serious infections. Keywords: Gram-positive, Enterococcus faecalis, Enterococcus faecium, VRE, antibiotic resistance, multidrug resistance

Clinical preference for a semisynthetic penicillin (oxacillin or nafcillin) over cefazolin for deep-seated methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI) perseveres despite limited data to support this approach. A retrospective cohort study of patients treated for MSSA BSI with either oxacillin or cefazolin was performed across two medical centers in Chicago, IL. The outcome measures included documented in-hospital treatment failure, all-cause in-hospital mortality, duration of MSSA BSI, and incidence of documented adverse events. Of 161 patients with MSSA BSI, 103 (64%) received cefazolin, and 58 (36%) received oxacillin. The identified sources of BSI were central line (37.9%), osteoarticular (18%), and skin and soft tissue (17.4%). Patients with endocarditis (29/52 [44.2%]) and other deep-seated infections (23/52 [55.8%]) were classified under the subset of deep-seated infections (52/161 [32.3%]). Multivariate models found deep-seated infection (adjusted odds ratio [aOR], 4.52; 95% confidence interval [CI], 1.23 to 16.6; P = 0.023), metastatic disease (aOR, 4.21; 95% CI, 1.13 to 15.7; P = 0.033), and intensive care unit (ICU) onset of infection (aOR, 4.80; 95% CI, 1.26 to 18.4; P = 0.022) to be independent risk factors for in-hospital treatment failure. Treatment group was not an independent predictor of failure (aOR, 3.76; 95% CI, 0.98 to 14.4; P = 0.053). The rates of treatment failure were similar among cefazolin-treated (5/32 [15.6%]) and oxacillin-treated (4/20 [20.0%]) patients (P = 0.72) in the subset of deep-seated infections. Mortality was observed in 1 (1%) and 3 (5.2%) cases of cefazolin- and oxacillin-treated patients, respectively (P = 0.13). Cefazolin was not associated with higher rates of treatment failure and appears to be an effective alternative to oxacillin for treatment of deep-seated MSSA BSI., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Since its discovery in England and France in 1986, vancomycin-resistant Enterococcus has increasingly become a major nosocomial pathogen worldwide. Enterococci are prolific colonizers, with tremendous genome plasticity and a propensity for persistence in hospital environments, allowing for increased transmission and the dissemination of resistance elements. Infections typically present in immunosuppressed patients who have received multiple courses of antibiotics in the past. Virulence is variable, and typical clinical manifestations include bacteremia, endocarditis, intra-abdominal and pelvic infections, urinary tract infections, skin and skin structure infections, and, rarely, central nervous system infections. As enterococci are common colonizers, careful consideration is needed before initiating targeted therapy, and source control is first priority. Current treatment options including linezolid, daptomycin, quinupristin/dalfopristin, and tigecycline have shown favorable activity against various vancomycin-resistant Enterococcus infections, but there is a lack of randomized controlled trials assessing their efficacy. Clearer distinctions in preferred therapies can be made based on adverse effects, drug interactions, and pharmacokinetic profiles. Although combination therapies and newer agents such as tedizolid, telavancin, dalbavancin, and oritavancin hold promise for the future treatment of vancomycin-resistant Enterococcus infections, further studies are needed to assess their possible clinical impact, especially in the treatment of serious infections.

Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-resistant enterococci (VRE) are limited. Prior data suggest that daptomycin at >6 mg/kg of body weight/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (>6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two hundred forty-five patients were evaluated. Enterococcus faecium was identified in 175 (71%), followed by Enterococcus faecalis in 49 (20%) and Enterococcus spp. in 21 (9%); overall, 204 (83%) isolates were VRE. Enterococcal infections included bacteremia (173, 71%) and intra-abdominal (35, 14%) and bone and joint (25, 10%) infections. The median dosage and duration of HD-daptomycin were 8.2 mg/kg/day (interquartile range [IQR], 7.7 to 9.7) and 10 days (IQR, 6 to 15), respectively. The overall clinical success rate was 89% (193/218), and microbiological eradication was observed in 93% (177/191) of patients. The median time to clearance of blood cultures on HD-daptomycin was 3 days (IQR, 2 to 5). The 30-day all-cause mortality rate was 27%, and 5 (2%) patients developed daptomycin-nonsusceptible enterococcal strains while on HD-daptomycin. Seven patients (3%) had creatine phosphokinase (CPK) elevation, yet no HD-daptomycin regimen was discontinued due to an elevated CPK and all patients were asymptomatic. Overall, there was a high frequency of clinical success and microbiological eradication in patients treated with HD-daptomycin for enterococcal infections, even in patients with complicated and difficult-to-treat infections. No adverse event-related discontinuation of HD-daptomycin was noted. HD-daptomycin may be an option for the treatment of enterococcal infections.

Hepatic and renal functions are important considerations when selecting antifungal therapy. This investigation of liposomal amphotericin B (L-AMB) was conducted to determine the incidence and factors associated with the development of hepatotoxicity and nephrotoxicity. A retrospective chart review was conducted of 100 consecutive patients receiving L-AMB at doses of 1, 3, and 5 mg/kg. Hepatotoxicity was defined as an increase of bilirubin greater than 1.5 mg/dl or AST and ALT greater than three times the normal range. Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dl or an increase of 50% from baseline. Patients were included if they were 18 years of age or older. Patients were excluded if they had developed hepatic or renal dysfunction prior to L-AMB administration. Seventy-five patients were included based upon the predefined inclusion/exclusion criteria. Twenty-one percent (16/75) developed hepatotoxicity based upon the predefined criteria. There were no additive correlates for this adverse effect. Overall, 56% (42/75) of patients developed nephrotoxicity. Seventy-four percent (31/42) were exposed to IV contrast, and 90% (38/42) were receiving nephrotoxins concurrently. Age, cumulative dose, concomitant nephrotoxins, and IV contrast exposure were associated with increased nephrotoxicity (p<0.001). The development of hepatotoxicity was observed; however, no correlates (age, dose escalation, or cumulative dose) were significantly associated with its occurrence. Overall nephrotoxicity with L-AMB was common and often multifactorial. Lipid amphotericin B products are associated with lower rates of nephrotoxicity than conventional amphotericin; however, in this analysis, L-AMB was associated with a high incidence of nephrotoxicity., (© American College of Medical Toxicology 2010)