Ceftazidime-avibactam Versus Doripenem for the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a Phase 3 Randomized Trial Program.
The global emergence of carbapenem-resistant Enterobacteriaceae highlights the urgent need to reduce carbapenem dependence. The phase 3 RECAPTURE program compared the efficacy and safety of ceftazidime-avibactam and doripenem in patients with complicated urinary tract infection (cUTI), including acute pyelonephritis.



Hospitalized adults with suspected or microbiologically confirmed cUTI/acute pyelonephritis were randomized 1:1 to ceftazidime-avibactam 2000 mg/500 mg every 8 hours or doripenem 500 mg every 8 hours (doses adjusted for renal function), with possible oral antibiotic switch after ≥5 days (total treatment duration up to 10 days or 14 days for patients with bacteremia).



Of 1033 randomized patients, 393 and 417 treated with ceftazidime-avibactam and doripenem, respectively, were eligible for the primary efficacy analyses; 19.6% had ceftazidime-nonsusceptible baseline pathogens. Noninferiority of ceftazidime-avibactam vs doripenem was demonstrated for the US Food and Drug Administration co-primary endpoints of (1) patient-reported symptomatic resolution at day 5: 276 of 393 (70.2%) vs 276 of 417 (66.2%) patients (difference, 4.0% [95% confidence interval {CI}, -2.39% to 10.42%]); and (2) combined symptomatic resolution/microbiological eradication at test of cure (TOC): 280 of 393 (71.2%) vs 269 of 417 (64.5%) patients (difference, 6.7% [95% CI, .30% to 13.12%]). Microbiological eradication at TOC (European Medicines Agency primary endpoint) occurred in 304 of 393 (77.4%) ceftazidime-avibactam vs 296 of 417 (71.0%) doripenem patients (difference, 6.4% [95% CI, .33% to 12.36%]), demonstrating superiority at the 5% significance level. Both treatments showed similar efficacy against ceftazidime-nonsusceptible pathogens. Ceftazidime-avibactam had a safety profile consistent with that of ceftazidime alone.



Ceftazidime-avibactam was highly effective for the empiric treatment of cUTI (including acute pyelonephritis), and may offer an alternative to carbapenems in this setting.



NCT01595438; NCT01599806.
Justus-Liebig-University, Giessen, Germany.
Florian M
FM
Wagenlehner
Detroit Medical Center, Michigan.
Jack D
JD
Sobel
AstraZeneca, Alderley Park, Cheshire.
Paul
P
Newell
AstraZeneca, Alderley Park, Cheshire.
Jon
J
Armstrong
AstraZeneca, Cambridge, United Kingdom.
Xiangning
X
Huang
AstraZeneca, Waltham, Massachusetts.
Gregory G
GG
Stone
AstraZeneca, Alderley Park, Cheshire.
Katrina
K
Yates
AstraZeneca, Wilmington, Delaware.
Leanne B
LB
Gasink
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D053961:Azabicyclo Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015780:Carbapenems / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002442:Ceftazidime / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077726:Doripenem; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011704:Pyelonephritis / Q000150:complications / Q000188:drug therapy*; D014552:Urinary Tract Infections / Q000150:complications / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D015780:Carbapenems; D004338:Drug Combinations; C000595613:avibactam, ceftazidime drug combination; D002442:Ceftazidime; D000077726:Doripenem
acute pyelonephritis; ceftazidime-avibactam; complicated urinary tract infection