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

Jose Antonio Vazquez, Luis Demetrio González Patzán, David Stricklin, Dipesh D. Duttaroy, Zouheir Kreidly, Joy Lipka, Carole Sable

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Objectives: 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. Patients and 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 500mg plus avibactam 125mg every 8 hours or imipenem-cilastatin 500mg 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. Conclusion: The results suggest that the efficacy and safety of ceftazidime-avibactam may be similar to that of imipenem-cilastatin.

Original languageEnglish (US)
Pages (from-to)1921-1931
Number of pages11
JournalCurrent Medical Research and Opinion
Volume28
Issue number12
DOIs
StatePublished - Dec 1 2012
Externally publishedYes

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Pyelonephritis
Urinary Tract Infections
Research Personnel
Safety
Therapeutics
Ceftazidime
ceftazidime drug combination avibactam
imipenem drug combination cilastatin
Population
Ciprofloxacin
Escherichia coli

Keywords

  • Ceftazidime-resistant
  • Microbiological response
  • Uropathogens

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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. / Vazquez, Jose Antonio; González Patzán, Luis Demetrio; Stricklin, David; Duttaroy, Dipesh D.; Kreidly, Zouheir; Lipka, Joy; Sable, Carole.

In: Current Medical Research and Opinion, Vol. 28, No. 12, 01.12.2012, p. 1921-1931.

Research output: Contribution to journalArticle

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abstract = "Objectives: 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. Patients and 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 500mg plus avibactam 125mg every 8 hours or imipenem-cilastatin 500mg 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. Conclusion: The results suggest that the efficacy and safety of ceftazidime-avibactam may be similar to that of imipenem-cilastatin.",
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AU - Stricklin, David

AU - Duttaroy, Dipesh D.

AU - Kreidly, Zouheir

AU - Lipka, Joy

AU - Sable, Carole

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