title: Efficacy and safety of ceftazidime-avibactam versus imipenem-cilastatin in the treatment of complicated urinary tract infections, including acute pyelonephritis, in hospitalized adults: results of a prospective, investigator-blinded, randomized study.
abstract: OBJECTIVE
  The aim of this prospective phase II, randomized, investigator-blinded study (NCT00690378) was to compare the efficacy and safety of ceftazidime-avibactam and imipenem-cilastatin in hospitalized adults with serious complicated urinary tract infection (cUTI) due to Gram-negative pathogens.
  
  
  METHODS
  Patients aged between 18 and 90 years with cUTI were enrolled and stratified by infection type (acute pyelonephritis or other cUTI) and randomized 1:1 to receive intravenous ceftazidime 500 mg plus avibactam 125 mg every 8 hours or imipenem-cilastatin 500 mg every 6 hours. Patients meeting pre-specified improvement criteria after 4 days could be switched to oral ciprofloxacin. Patients were treated for a total of 7-14 days. The primary efficacy objective was a favorable microbiological response at the test-of-cure (TOC) visit 5-9 days post-therapy in microbiologically evaluable (ME) patients.
  
  
  RESULTS
  Overall, 135 patients received study therapy (safety population); 62 were included in the ME population (ceftazidime-avibactam, n = 27; imipenem-cilastatin, n = 35). The predominant uropathogen was Escherichia coli. Favorable microbiological response was achieved in 70.4% of ME patients receiving ceftazidime-avibactam and 71.4% receiving imipenem-cilastatin at the TOC visit (observed difference -1.1% [95% CI: -27.2%, 25.0%]). Among ME patients with ceftazidime-resistant uropathogens, response was observed in 6/7 (85.7%) receiving ceftazidime-avibactam. Adverse events were observed in 67.6% and 76.1% of patients receiving ceftazidime-avibactam and imipenem-cilastatin, respectively. Limitations of the study include the small number of patients in the ME population.
  
  
  CONCLUSIONS
  The results suggest that the efficacy and safety of ceftazidime-avibactam may be similar to that of imipenem-cilastatin.
authors.affiliation: Division of Infectious Diseases, Henry Ford Hospital, Detroit, MI 48202, USA. JVAZQUE1@hfhs.org
authors.forename: José A
authors.initials: JA
authors.lastname: Vazquez
authors.forename: Luis Demetrio
authors.initials: LD
authors.lastname: González Patzán
authors.forename: David
authors.initials: D
authors.lastname: Stricklin
authors.forename: Dipesh D
authors.initials: DD
authors.lastname: Duttaroy
authors.forename: Zouheir
authors.initials: Z
authors.lastname: Kreidly
authors.forename: Joy
authors.initials: J
authors.lastname: Lipka
authors.forename: Carole
authors.initials: C
authors.lastname: Sable
mesh_terms: D000208:Acute Disease; 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; D015377:Cilastatin / Q000008:administration & dosage / Q000009:adverse effects; D004359:Drug Therapy, Combination / Q000379:methods; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000188:drug therapy*; D005260:Female; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011704:Pyelonephritis / Q000188:drug therapy*; D014552:Urinary Tract Infections / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D011480:Protease Inhibitors; D015377:Cilastatin; D015378:Imipenem; C543519:avibactam; D002442:Ceftazidime