avibactam and Drug-Related-Side-Effects-and-Adverse-Reactions

Avibactam, a novel non-β-lactam β-lactamase inhibitor, restores the in vitro activity of ceftazidime against class A, C and some class D β-lactamase-producing pathogens, including those commonly associated with complicated intra-abdominal infections (cIAIs). This randomized, active-controlled, double-blind, Phase II trial (NCT00752219) aimed to evaluate the safety and efficacy of ceftazidime/avibactam plus metronidazole compared with meropenem in hospitalized patients with cIAI.. Adults with confirmed cIAI requiring surgical intervention and antibiotics were randomized 1 : 1 to receive intravenously either (i) 2000 mg of ceftazidime plus 500 mg of avibactam plus a separate infusion of 500 mg of metronidazole or (ii) 1000 mg of meropenem plus placebo every 8 h for a minimum of 5 days and a maximum of 14 days. The primary efficacy endpoint was the clinical response in microbiologically evaluable (ME) patients at the test-of-cure (TOC) visit 2 weeks after the last dose of study therapy.. Overall, 101 patients received ceftazidime/avibactam plus metronidazole; 102 received meropenem. The median duration of treatment was 6.0 and 6.5 days, respectively. Favourable clinical response at the TOC visit in the ME population was observed in 91.2% (62/68) and 93.4% (71/76) of patients in the ceftazidime/avibactam plus metronidazole and meropenem groups, respectively (observed difference: -2.2%; 95% CI: -20.4%, 12.2%). The incidence of treatment-emergent adverse events was similar for ceftazidime/avibactam plus metronidazole (64.4%) and meropenem (57.8%).. Ceftazidime/avibactam plus metronidazole was effective and generally well tolerated in patients with cIAI, with a favourable clinical response rate in the ME population of >90%, similar to that of meropenem.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Intraabdominal Infections; Male; Meropenem; Metronidazole; Middle Aged; Placebos; Thienamycins; Treatment Outcome; Young Adult