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This randomized, double-blind, noninferiority study was designed to demonstrate that a single 2.0-g oral dose of a novel microsphere formulation of azithromycin was at least as effective as 7 days of levofloxacin, 500 mg/day, in the treatment of adult patients with mild to moderate community-acquired pneumonia (Fine classes I, II, and III). In total, 427 subjects were randomly assigned to receive either a single 2.0-g dose of azithromycin microspheres (n ‫؍‬ 213) or a 7-day regimen of levofloxacin (n ‫؍‬ 214). At baseline, 219 of 423 (51.8%) treated subjects had at least one pathogen identified by culture, PCR, or serology. The primary end point was the clinical response (cure or failure) in the "clinical per protocol" population at test of cure (days 13 to 24). Clinical cure rates were 89.7% (156 of 174) for azithromycin microspheres and 93.7% (177 of 189) for levofloxacin (treatment difference, ؊4.0%; 95% confidence interval, ؊9.7%, 1.7%). Bacteriologic success at test of cure in the "bacteriologic per protocol" population was 90.7% (97 of 107) for azithromycin microspheres and 92.3% (120 of 130) for levofloxacin (treatment difference, ؊1.7%; 95% confidence interval, ؊8.8%, 5.5%). Both treatment regimens were well tolerated; the incidence of treatment-related adverse events was 19.9% and 12.3% for azithromycin and levofloxacin, respectively. A single 2.0-g dose of azithromycin microspheres was at least as effective as a 7-day course of levofloxacin in the treatment of mild to moderate community-acquired pneumonia in adult outpatients.

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Background SUL-DUR is a β-lactam/β-lactamase inhibitor combination in development for the treatment of ABC, which is a cause of severe infections with substantial mortality. ATTACK evaluated the efficacy and safety of SUL-DUR versus colistin (COL) in patients with serious ABC infections. Methods Part A was a randomized, blinded non-inferiority study (SUL-DUR versus COL) in ABC pneumonia or bacteremia; Part B was an open label study (SUL-DUR only) that enrolled patients with ABC infections who did not tolerate COL or whose pathogens were resistant to COL (COL-R). All subjects received imipenem/cilastatin as background therapy. Primary endpoint included 28-day all-cause mortality (ACM) in Part A patients with carbapenem-resistant ABC at baseline (CRABC m-MITT). Clinical and microbiologic outcomes were measured at the End of Therapy (EOT), Test of Cure (TOC) and Late Follow-up (LFU) visits in CRABC m-MITT patients. In this study, COL-R was defined as MIC ≥ 4 µg/ml and SUL-DUR-non-susceptible (NS) was defined as MIC ≥ 8 µg/ml. Results SUL-DUR was non-inferior to COL in 28-day ACM; 19.0% SUL-DUR versus 32.3% in the COL group (Table 1). SUL-DUR therapy resulted in statistically significant higher clinical cures at EOT and TOC. Similarly, a significant treatment difference in microbiological favorable assessment was observed at EOT and TOC (24.4% and 26.3%, respectively, in Part A). Similar mortality differences were observed in subgroups including infection type, severity of illness, mechanical ventilation, and duration of stay of at least 5 days in the ICU prior to starting study treatment (Table 2). All 149 baseline ABC isolates from CRABC m-MITT patients were multi-drug resistant; the SUL-DUR MIC50/90 was 2/4 µg/ml (range of 0.25 – 8 µg/ml). At baseline 33% of ABC infections were polymicrobial. Conclusion In ATTACK, patients treated with SUL-DUR had lower mortality, higher clinical cure rates and significantly greater microbiologically favorable outcomes than those treated with COL. The correlation between clinical and microbiologic outcomes provides additional evidence that, if approved, SUL-DUR could be an important therapeutic option for Acinetobacter infections including carbapenem-resistant and multidrug-resistant strains. Disclosures David Altarac, MD, MPA, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds Alita Miller, PhD, Entasis Therapeutics: Employee Sarah McLeod, PhD, Entasis Therapeutics: Employee Adam B. Shapiro, Ph.D, Entasis Therapeutics: Employee|Entasis Therapeutics: Stocks/Bonds Khurram Rana, PharmD, Entasis Therapeutics: Employee|Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds Drew Lewis, MD, MTM&H, Entasis Therapeutics: employee|Entasis Therapeutics: employee|Entasis Therapeutics: Stocks/Bonds|Entasis Therapeutics: Stocks/Bonds Gabrielle Poirier, BS, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds Daria Chabas, BS, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds.

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