Ceftazidime-avibactam Versus Doripenem for the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a Phase 3 Randomized Trial Program

September 21, 2016 at 4:49 pm

Clinical Infectious Diseases September 15, 2016 V.63 N.6 P. 754-762

Florian M. Wagenlehner, Jack D. Sobel, Paul Newell, Jon Armstrong, Xiangning Huang, Gregory G. Stone, Katrina Yates, and Leanne B. Gasink

1Justus-Liebig-University, Giessen, Germany

2Detroit Medical Center, Michigan

3AstraZeneca, Alderley Park, Cheshire

4AstraZeneca, Cambridge, United Kingdom

5AstraZeneca, Waltham, Massachusetts

6AstraZeneca, Wilmington, Delaware

Background

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.

Methods

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).

Results

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.

Conclusions

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

PDF

http://cid.oxfordjournals.org/content/63/6/754.full.pdf+html

Entry filed under: Antimicrobianos, Bacterias, Bacteriemias, Infecciones urinarias, Metodos diagnosticos, Resistencia bacteriana, Sepsis, Update. Tags: .

HIV infection results in metabolic alterations in the gut microbiota different from those induced by other diseases. IDSA GUIDELINE – 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis


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