Ceftriaxone as an Alternative Therapy for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia after Initial Clearance of Bloodstream Infection.

INTRODUCTION: Staphylococcus spp. represent the leading cause of hospital-acquired infections and second-most frequent pathogen in bloodstream infections. Methicillin-susceptible S. aureus (MSSA) comprise approximately half of all S. aureus isolates. Standard-of-care therapies (SOCTs) display high treatment success but require frequent dosing, are problematic in penicillin allergic patients, and are nephrotoxic. Ceftriaxone may represent an alternative treatment option. METHODS: Adult patients hospitalized from January 2015 through June 2016 with positive MSSA blood cultures and treated with SOCT or ceftriaxone for ≥48 hours were included. Exclusion criteria were receipt of vancomycin or concomitant systemic antimicrobials with activity against MSSA, polymicrobial infections, and pregnant patients. Additional data collected included demographics, source/site of infection, and treatment. The primary endpoint was clinical cure (normalization of white blood cell count and temperature within 7 days and clearance of bloodstream within 7 days). Readmission within 60 days, length of stay, and discharge disposition were collected. RESULTS: A total of 43 patients were included: 23 receiving SOCT and 20 receiving ceftriaxone group. Sixteen patients received SOCT prior to ceftriaxone while 4 patients were initiated on ceftriaxone. Clinical cure was observed in 18/23 (78%) and 10/20 (50%), respectively (P=0.052). Clinical failure was driven by leukocytosis despite clearance of their bloodstream infection in 3/23 (13%) SOCT group compared to 8/20 (40%) in the ceftriaxone group (P=0.043). Six patients (SOCT: 2, ceftriaxone: 4; p=0.669) had infection-related readmissions, and 1 death per group was observed. CONCLUSION: Ceftriaxone poses a reasonable alternative to consider for MSSA bacteremia when cost and feasibility are concerns for outpatient parenteral therapy after initial clearance of bloodstream infections.

Trends in and Predictors of Carbapenem Consumption across North American Hospitals: Results from a Multicenter Survey by the MAD-ID Research Network.

We sought to define trends in and predictors of carbapenem consumption across community, teaching, and university-affiliated hospitals in the United States and Canada. We conducted a retrospective multicenter survey of carbapenem and broad-spectrum noncarbapenem beta-lactam consumption between January 2011 and December 2013. Consumption was tabulated as defined daily doses (DDD) or as days of therapy (DOT) per 1,000 patient days (PD). Multivariate mixed-effects models were explored, and final model goodness of fit was assessed by regressions of observed versus predicted values and residual distributions. A total of 20 acute-care hospitals responded. The centers treated adult patients (n = 19/20) and pediatric/neonatal patients (n = 17/20). The majority of the centers were nonprofit (n = 17/20) and not affiliated with medical/teaching institutions (n = 11/20). The median (interquartile range [IQR]) carbapenem consumption rates were 38.8 (17.4 to 95.7) DDD/1,000 PD and 29.7 (19.2 to 40.1) DOT/1,000 PD overall. Carbapenem consumption was well described by a multivariate linear mixed-effects model (fixed effects, R2 = 0.792; fixed plus random effects, R2 = 0.974). Carbapenem consumption increased by 1.91-fold/quarter from 48.6 DDD/1,000 PD (P = 0.004) and by 0.056-fold/quarter from 45.7 DOT/1,000 PD (P = 0.93) over the study period. Noncarbapenem consumption was independently related to increasing carbapenem consumption (beta = 0.31 for increasing noncarbapenem beta-lactam consumption; P < 0.001). Regular antibiogram publication and promotion of conversion from intravenous (i.v.) to oral (p.o.) administration independently affected carbapenem consumption rates. In the final model, 58.5% of the observed variance in consumption was attributable to between-hospital differences. Rates of carbapenem consumption across 20 North American hospitals differed greatly, and the observed differences were correlated with hospital-specific demographics. Additional studies focusing on the drivers of hospital-specific carbapenem consumption are needed to determine whether these rates are justifiable.

Lefamulin: Review of a Promising Novel Pleuromutilin Antibiotic.

The emergence and spread of antimicrobial resistance have led to a global public health emergency requiring development of new antimicrobial classes. Lefamulin (formally BC-3781) is a novel pleuromutilin antibiotic currently undergoing Food and Drug Administration review for community-acquired bacterial pneumonia (CABP) as intravenous (IV) and oral (PO) formulations. Although pleuromutilin antibiotics were first developed in the 1950s, lefamulin is the first to be used for systemic treatment of bacterial infections in humans. Lefamulin exhibits a unique mechanism of action through inhibition of protein synthesis by binding to the peptidyl transferase center of the 50S bacterial ribosome, thus preventing the binding of transfer RNA for peptide transfer. Lefamulin displays activity against gram-positive and atypical organisms associated with CABP (i.e., Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydophila pneumoniae), with an expanded gram-positive spectrum including Staphylococcus aureus (i.e., methicillin-resistant, vancomycin-intermediate, and heterogeneous strains) and vancomycin-resistant Enterococcus faecium. Lefamulin was also shown to retain activity against multidrug-resistant Neisseria gonorrhoeae and Mycoplasma genitalium. Lefamulin exhibits time-dependent killing, and the pharmacodynamic target best associated with antibacterial activity is ƒAUC0-24 /MIC (minimum inhibitory concentration [MIC]). Preclinical and phase II trials indicate that lefamulin concentrates in lung tissue are well tolerated at an IV dose of 150 mg twice/day over 1 hour or a PO dose of 600 mg twice/day, and preliminary phase III data suggest similar efficacy when compared with moxifloxacin with or without linezolid in CABP. Documented resistance and cross-resistance with other gram-positive antibacterials remains low. Additional published in vitro, in vivo, and preclinical trial data suggest further exploration of lefamulin in various infectious disease states (e.g., acute bacterial skin and skin structure infections, and sexually transmitted infections). This review discusses the pertinent bacterial spectrum of activity, preclinical and ongoing clinical data, and potential roles in therapy for lefamulin.

Effect of elevated imipenem/cilastatin minimum inhibitory concentrations on patient outcomes in Gram-negative bloodstream infections.

OBJECTIVES: Carbapenem minimum inhibitory concentration (MICs) are known to predict outcomes for patients with Gram-negative bacteraemia. However, limited data exist on how MICs influence such outcomes when organisms are classified as carbapenem-resistant. The purpose of this study was to evaluate the effect of increasing imipenem/cilastatin MICs on mortality in patients with Gram-negative bloodstream infection (BSI). METHODS: Patients with an imipenem/cilastatin-resistant (MIC>4mg/L) monomicrobial Gram-negative BSI were eligible for inclusion in the study and were assessed for baseline characteristics, organ function, microbiological data, timing and type of therapeutic treatment, and in-hospital mortality. RESULTS: A total of 62 patients with imipenem/cilastatin-resistant bacterial isolates (MIC>4mg/L) were retrospectively studied. Time to event analyses found no difference between patients who received carbapenem therapy and those who did not (P=0.10). After adjustment, patients receiving directed therapy were less likely to die (adjusted hazard ratio=0.35, 95% confidence interval 0.15-0.83; P<0.01), whereas higher modified Acute Physiology and Chronic Health Evaluation (APACHE) II score and days to positive culture were associated with non-survival. CONCLUSION: This study did not demonstrate a relationship between receipt of a carbapenem and mortality in patients with carbapenem-resistant Gram-negative BSI.

Ablative therapies of the breast.

Minimally invasive ablative therapy techniques are being used in research protocols to treat benign and malignant tumors of the breast in select patient populations. These techniques offer the advantages of an outpatient setting, decreased pain, and improved cosmesis. These therapies, including radiofrequency ablation, cryotherapy, interstitial laser therapy, high-intensity focused ultrasonography, and focused microwave thermotherapy, are reviewed in this article.