TY - JOUR
T1 - Efficacy and safety of ceftazidime-avibactam versus imipenem-cilastatin in the treatment of complicated urinary tract infections, including acute pyelonephritis, in hospitalized adults
T2 - Results of a prospective, investigator-blinded, randomized study
AU - Vazquez, José A.
AU - González Patzán, Luis Demetrio
AU - Stricklin, David
AU - Duttaroy, Dipesh D.
AU - Kreidly, Zouheir
AU - Lipka, Joy
AU - Sable, Carole
N1 - Funding Information:
Medical writing support was provided by Liz Anfield, Prime Medica Ltd, Knutsford, Cheshire, and was funded by AstraZeneca. She prepared a preliminary outline and subsequent revisions of the manuscript based on extensive critical input from all the authors.
PY - 2012/12
Y1 - 2012/12
N2 - 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.
AB - 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.
KW - Ceftazidime-resistant
KW - Microbiological response
KW - Uropathogens
UR - http://www.scopus.com/inward/record.url?scp=84870399321&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870399321&partnerID=8YFLogxK
U2 - 10.1185/03007995.2012.748653
DO - 10.1185/03007995.2012.748653
M3 - Article
C2 - 23145859
AN - SCOPUS:84870399321
SN - 0300-7995
VL - 28
SP - 1921
EP - 1931
JO - Current Medical Research and Opinion
JF - Current Medical Research and Opinion
IS - 12
ER -