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Importance New antibacterials are needed to treat community-acquired bacterial pneumonia (CABP) because of growing antibacterial resistance and safety concerns with standard care. Objective To evaluate the efficacy and adverse events of a 5-day oral lefamulin regimen in patients with CABP. Design, Setting, and Participants A phase 3, noninferiority randomized clinical trial conducted at 99 sites in 19 countries that included adults aged 18 years or older with a Pneumonia Outcomes Research Team (PORT) risk class of II, III, or IV; radiographically documented pneumonia; acute illness; 3 or more CABP symptoms; and 2 or more vital sign abnormalities. The first patient visit was on August 30, 2016, and patients were followed up for 30 days; the final follow-up visit was on January 2, 2018. Interventions Patients were randomized 1:1 to receive oral lefamulin (600 mg every 12 hours for 5 days; n = 370) or moxifloxacin (400 mg every 24 hours for 7 days; n = 368). Main Outcomes and Measures The US Food and Drug Administration (FDA) primary end point was early clinical response at 96 hours (within a 24-hour window) after the first dose of either study drug in the intent-to-treat (ITT) population (all randomized patients). Responders were defined as alive, showing improvement in 2 or more of the 4 CABP symptoms, having no worsening of any CABP symptoms, and not receiving any nonstudy antibacterial drug for current CABP episode. The European Medicines Agency coprimary end points (FDA secondary end points) were investigator assessment of clinical response at test of cure (5-10 days after last dose) in the modified ITT population and in the clinically evaluable population. The noninferiority margin was 10% for early clinical response and investigator assessment of clinical response. Results Among 738 randomized patients (mean age, 57.5 years; 351 women [47.6%]; 360 had a PORT risk class of III or IV [48.8%]), 707 (95.8%) completed the trial. Early clinical response rates were 90.8% with lefamulin and 90.8% with moxifloxacin (difference, 0.1% [1-sided 97.5% CI, –4.4% to ∞]). Rates of investigator assessment of clinical response success were 87.5% with lefamulin and 89.1% with moxifloxacin in the modified ITT population (difference, –1.6% [1-sided 97.5% CI, –6.3% to ∞]) and 89.7% and 93.6%, respectively, in the clinically evaluable population (difference, –3.9% [1-sided 97.5% CI, –8.2% to ∞]) at test of cure. The most frequently reported treatment-emergent adverse events were gastrointestinal (diarrhea: 45/368 [12.2%] in lefamulin group and 4/368 [1.1%] in moxifloxacin group; nausea: 19/368 [5.2%] in lefamulin group and 7/368 [1.9%] in moxifloxacin group). Conclusions and Relevance Among patients with CABP, 5-day oral lefamulin was noninferior to 7-day oral moxifloxacin with respect to early clinical response at 96 hours after first dose. Trial Registrations ClinicalTrials.gov Identifier:NCT02813694; European Clinical Trials Identifier:2015-004782-92

Although liberalization of donor criteria could expand the donor pool, the use of certain "marginal donors," such as those who are hepatitis C virus (HCV) positive, is controversial. Little is known about the effect of donor HCV positivity on survival in cardiac transplantation.To examine the association between donor HCV positivity and survival among heart transplant recipients and to determine the effects of recipient age and recipient HCV status on this association.A multicenter cohort study was performed using the US Scientific Registry of Transplant Recipients. Adult heart transplant patients who received their transplants between April 1, 1994, and July 31, 2003, were eligible for inclusion.All-cause mortality.Of 10 915 patients meeting entry criteria, 261 received an HCV-positive donor heart. Mortality was higher among recipients of HCV-positive donor hearts at 1 year (16.9% vs 8.2%; P.001), 5 years (41.8% vs 18.5%; P.001), and 10 years (50.6% vs 24.3%; P.001). Using Kaplan-Meier methods, 1-, 5-, and 10-year survival rates were 83%, 53%, and 25%, and 92%, 77%, and 53% for recipients of HCV-positive and HCV-negative donor hearts, respectively (P.001, log-rank test). Recipients of HCV-positive donor hearts were more likely to die of liver disease and coronary vasculopathy. After propensity matching, the overall hazard ratio (HR) associated with receipt of an HCV-positive donor heart was 2.10 (95% confidence interval [CI], 1.60-2.75). Stratified analyses showed that HRs did not vary by recipient HCV status or by recipient age (for recipients aged 18-39 years: HR, 1.75 [95% CI, 0.70-4.40]; for recipients aged 40-59 years: HR, 2.23 [95% CI, 1.42-3.52]; and for recipients aged 60 years and older: HR, 2.07 [95% CI, 1.32-3.27]; overall P value for interaction,.10).Receipt of a heart from an HCV-positive donor is associated with decreased survival in heart transplant recipients. This association appears to be independent of recipient HCV status and age. Preferential allocation of HCV-positive donors to HCV-positive recipients and/or older recipients is not warranted.