title: Comparative study of the efficacy and safety of ceftazidime/avibactam plus metronidazole versus meropenem in the treatment of complicated intra-abdominal infections in hospitalized adults: results of a randomized, double-blind, Phase II trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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%).
  
  
  CONCLUSIONS
  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.
authors: South Jersey Infectious Diseases, Somers Point, NJ, USA. infect123@aol.com
authors: Christopher
authors: C
authors: Lucasti
authors: Irinel
authors: I
authors: Popescu
authors: Mayakonda K
authors: MK
authors: Ramesh
authors: Joy
authors: J
authors: Lipka
authors: Carole
authors: C
authors: Sable
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D053961:Azabicyclo Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D002442:Ceftazidime / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D006801:Humans; D059413:Intraabdominal Infections / Q000188:drug therapy*; D008297:Male; D000077731:Meropenem; D008795:Metronidazole / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D013845:Thienamycins / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D010919:Placebos; D013845:Thienamycins; D008795:Metronidazole; C543519:avibactam; D002442:Ceftazidime; D000077731:Meropenem