Etiology and efficacy of anti-microbial treatment for community-acquired pneumonia in adults requiring hospital admission in Ukraine.

BACKGROUND AND AIM: Empiric therapy of community-acquired pneumonia (CAP) remains the standard care and guidelines are mostly based on published data from the United States or Europe. In this study, we determined the bacterial etiology of CAP and evaluated the clinical outcomes under antimicrobial treatment of CAP in Ukraine. METHODS: A total of 98 adult subjects with CAP and PORT risk II-IV were recruited for the study. The sputum diagnostic samples were obtained from all patients for causative pathogen identification. Subjects were randomly assigned in a 1:1 ratio to receive delafloxacin 300 mg (n=51) or moxifloxacin 400 mg (n=47) with blinding placebo. The switch to oral treatment was after a minimum of 6 IV doses according to clinical criteria. The total duration of antibacterial treatment was 5-10 days. In vitro susceptibility of pathogens to delafloxacin and other comparator antibiotics was determined. RESULTS: The most frequently isolated pathogens in adults with CAP were S. pneumoniae - 19.5%, M. pneumoniae - 15.3%, H. influenzae - 13.2%, S. aureus - 10.5%, K. pneumoniae - 10.1%, and H. parainfluenzae - 6.4%. All isolates of S. pneumoniae, S. aureus, M. pneumoniae had sufficient susceptibility to appropriate antibiotics. 9.0% of H. influenzae strains were susceptible to azithromycin. 94.8 % of patients had a successful clinical response to delafloxacin at the end of treatment and 93.9 % - at test-of-cure. CONCLUSIONS: In Ukraine, the major bacterial agents that induced CAP in adults were S. pneumoniae, M. pneumoniae, H. influenzae, S. aureus, K. pneumoniae, H. parainfluenzae, E. cloacae, L. pneumophila. Delafloxacin is a promising effective antibiotic for monotherapy for CAP in adults and could be used in cases of antimicrobial-resistant strains.

Omadacycline for Community-Acquired Bacterial Pneumonia.

BACKGROUND: Omadacycline, a new once-daily aminomethylcycline antibiotic agent that can be administered intravenously or orally, reaches high concentrations in pulmonary tissues and is active against common pathogens that cause community-acquired bacterial pneumonia. METHODS: In a double-blind trial, we randomly assigned (in a 1:1 ratio) adults with community-acquired bacterial pneumonia (Pneumonia Severity Index risk class II, III, or IV) to receive omadacycline (100 mg intravenously every 12 hours for two doses, then 100 mg intravenously every 24 hours), or moxifloxacin (400 mg intravenously every 24 hours). A transition to oral omadacycline (300 mg every 24 hours) or moxifloxacin (400 mg every 24 hours), respectively, was allowed after 3 days; the total treatment duration was 7 to 14 days. The primary end point was early clinical response, defined as survival with improvement in at least two of four symptoms (cough, sputum production, pleuritic chest pain, and dyspnea) and no worsening of symptoms at 72 to 120 hours, without receipt of rescue antibacterial therapy. A secondary end point was investigator-assessed clinical response at a post-treatment evaluation 5 to 10 days after the last dose, with clinical response defined as resolution or improvement in signs or symptoms to the extent that further antibacterial therapy was unnecessary. A noninferiority margin of 10 percentage points was used. RESULTS: The intention-to-treat population included 386 patients in the omadacycline group and 388 patients in the moxifloxacin group. Omadacycline was noninferior to moxifloxacin for early clinical response (81.1% and 82.7%, respectively; difference, -1.6 percentage points; 95% confidence interval [CI], -7.1 to 3.8), and the rates of investigator-assessed clinical response at the post-treatment evaluation were 87.6% and 85.1%, respectively (difference, 2.5 percentage points; 95% CI, -2.4 to 7.4). Adverse events that emerged after treatment initiation were reported in 41.1% of the patients in the omadacycline group and 48.5% of the patients in the moxifloxacin group; the most frequent events were gastrointestinal (10.2% and 18.0%, respectively), and the largest difference was for diarrhea (1.0% and 8.0%). Twelve deaths (8 in the omadacycline group and 4 in the moxifloxacin group) occurred during the trial. CONCLUSIONS: Omadacycline was noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia in adults. (Funded by Paratek Pharmaceuticals; OPTIC ClinicalTrials.gov number, NCT02531438 .).

A phase II, randomized, placebo-controlled, double-blind, multi-dose study of SRT2104, a SIRT1 activator, in subjects with type 2 diabetes.

AIM: SRT2104 is a selective activator of SIRT1. In animal models, SRT2104 improves glucose homeostasis and increases insulin sensitivity. We evaluated the tolerability and pharmacokinetics of SRT2104, and its effects on glycaemic control, in adults with type 2 diabetes mellitus. METHOD: Type 2 diabetics with glycosylated haemoglobin (HbA1c) ≥ 7.5% and ≤10.5%, fasting glucose ≥160 and ≤240 mg dl(-1) , and on stable doses of metformin were evenly randomized to placebo or SRT2104 0.25 g, 0.5 g, 1.0 g or 2.0 g, administered orally once daily for 28 days. Changes in fasting and post-prandial glucose and insulin were analyzed. RESULTS: Safety evaluation found no major differences between groups in the frequency of adverse events. SRT2104 concentrations did not increase in a dose-proportional fashion. Significant variability in exposure was observed. Treatment with SRT2104 did not lead to any consistent, dose-related changes in glucose or insulin. Day 28 change from baseline (mean (SD)): fasting glucose (mmol l(-1) ) = -1.17 (2.42), -1.11 (3.45), -0.52 (2.60), -0.97 (2.83) and -0.15 (2.38) for placebo, 0.25 g, 0.5 g, 1.0 g and 2.0 g, respectively. Day 28 change from baseline (mean (SD)): fasting insulin (mmol l(-1) ) = 1.0 (51.66), 8.9 (95.04), -6.9 (41.45), 4.1 (57.16) and 15.2 (138.79) for placebo, 0.25 g, 0.5 g, 1.0 g and 2.0 g, respectively) Treatment with SRT2104 was associated with improvement in lipid profiles. CONCLUSION: Treatment with SRT2104 for 28 days did not result in improved glucose or insulin control which is likely due to the observed pharmacokinetics which were not dose proportional and had large between subject variability.