www.thelancet.com/infection Published online February 4, 2016 http://dx.doi.org/10.1016/S1473-3099(16)00017-7 1 Articles Lancet Infect Dis 2016 Published Online February 4, 2016 http://dx.doi.org/10.1016/ S1473-3099(16)00017-7 See Online/Comment http://dx.doi.org/10.1016/ S1473-3099(16)00068-2 A&L Clinical Research, Miami, FL, USA (C M Barrera MD); Instituto Medico Platense, La Plata, Argentina (A Mykietiuk MD); Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Ruse, Bulgaria (H Metev MD); Dr Victor Babes Clinical Hospital for Infectious Diseases and Pneumophthisiology, Craiova, Romania (M F Nitu MD); Delta County Medical Center, Houston, TX, USA (N Karimjee MD); Centro Medico, Buenos Aires, Argentina (P A Doreski MD); World Wide Clinical Trials, Benoni, South Africa (I Mitha MD); St Pantelimon Emergency Clinical Hospital, Bucharest, Romania (Prof C M Tanaseanu MD); Hospital Vernaza, Guayaquil, Ecuador (J M Molina MD); Medsantrud City Clinical Hospital #23, Moscow, Russia (Y Antonovsky MD); Park Medical Center, Witbank, South Africa (D J Van Rensburg MD); Department of Emergency Medicine and School of Public Health, University of Alberta, Edmonton, AB, Canada (Prof B H Rowe MD); JM Research, Houston, TX, USA (J Flores-Figueroa MD); Good Doctor Specialist Outpatient Clinics, Cracow, Poland (B Rewerska MD); Cempra Pharmaceuticals, Chapel Hill, NC, USA (K Clark RN, K Keedy PhD, A Sheets PhD, Efficacy and safety of oral solithromycin versus oral moxifloxacin for treatment of community-acquired bacterial pneumonia: a global, double-blind, multicentre, randomised, active-controlled, non-inferiority trial (SOLITAIRE-ORAL) Carlos M Barrera, Analia Mykietiuk, Hristo Metev, Mimi Floarea Nitu, Najumuddin Karimjee, Pablo Alexis Doreski, Ismail Mitha, Cristina Mihaela Tanaseanu, Joseph McDermott Molina, Yuri Antonovsky, Dirkie Johanna Van Rensburg, Brian H Rowe, Jose Flores-Figueroa, Barbara Rewerska, Kay Clark, Kara Keedy, Amanda Sheets, Drusilla Scott, Gary Horwith, Anita F Das, Brian Jamieson, Prabhavathi Fernandes, David Oldach, for the SOLITAIRE-ORAL Pneumonia Team Summary Background Community-acquired bacterial pneumonia (CABP) is a leading cause of morbidity and mortality, and treatment recommendations, each with specific limitations, vary globally. We aimed to compare the efficacy and safety of solithromycin, a novel macrolide, with moxifloxacin for treatment of CABP. Methods We did this global, double-blind, double-dummy, randomised, active-controlled, non-inferiority trial at 114 centres in North America, Latin America, Europe, and South Africa. Patients (aged ≥18 years) with clinically and radiographically confirmed pneumonia of Pneumonia Outcomes Research Team (PORT) risk class II, III, or IV were randomly assigned (1:1), via an internet-based central block randomisation procedure (block size of four), to receive either oral solithromycin (800 mg on day 1, 400 mg on days 2–5, placebo on days 6–7) or oral moxifloxacin (400 mg on days 1–7). Randomisation was stratified by geographical region, PORT risk class (II vs III or IV), and medical history of asthma or chronic obstructive pulmonary disease. The study sponsor, investigators, staff, and patients were masked to group allocation. The primary outcome was early clinical response, defined as an improvement in at least two of four symptoms (cough, chest pain, sputum production, dyspnoea) with no worsening in any symptom at 72 h after the first dose of study drug, with a 10% non-inferiority margin. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT-01756339. Findings Between Jan 3, 2013, and Sept 24, 2014, we randomly assigned 860 patients to receive solithromycin (n=426) or moxifloxacin (n=434). Patients were followed up to days 28–35 after first dose. Solithromycin was non-inferior to moxifloxacin in achievement of early clinical response: 333 (78·2%) patients had an early clinical response in the solithromycin group versus 338 (77·9%) patients in the moxifloxacin group (difference 0·29, 95% CI –5·5 to 6·1). Both drugs had a similar safety profile. 43 (10%) of 155 treatment-emergent adverse events in the solithromycin group and 54 (13%) of 154 such events in the moxifloxacin group were deemed to be related to study drug. The most common adverse events, mostly of mild severity, were gastrointestinal disorders, including diarrhoea (18 [4%] patients in the solithromycin group vs 28 [6%] patients in the moxifloxacin group), nausea (15 [4%] vs 17 [4%] patients) and vomiting (ten [2%] patients in each group); and nervous system disorders, including headache (19 [4%] vs 11 [3%] patients) and dizziness (nine [2%] vs seven [2%] patients). Interpretation Oral solithromycin was non-inferior to oral moxifloxacin for treatment of patients with CABP, showing the potential to restore macrolide monotherapy for this indication. Funding Cempra. Introduction Community-acquired bacterial pneumonia (CABP) is a leading cause of morbidity and mortality. 1 Various pathogens cause the disease, including readily isolated bacteria historically sensitive to β-lactam antibiotics (eg, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Klebsiella pneumoniae) and the more difficult to culture atypical pathogens (eg, Legionella pneumophila and Mycoplasma pneumoniae). S pneumoniae is the most commonly identified bacterial pathogen. 2–6 Recommendations for treatment of CABP vary globally. For outpatient treatment, European guidelines recommend amoxicillin or tetracycline as monotherapy, 7 whereas for patients admitted to hospital with non-severe CABP, treatment with a β-lactam (with or without addition of a macrolide) or a respiratory fluoroquinolone is recommended. By contrast, treatment guidelines from the American Thoracic Society and the Infectious Diseases Society of America (ATS–IDSA) 8 recommend empirical outpatient treatment with a macrolide or doxycycline, unless clinically significant comorbidities