抗菌薬 Phases3を振り返り

先日、ESBLに対して、カルバペネム以外を考える総論を紹介しましたが、

そこで取り上げられていた、Phase3 を振り返りました。

 ASPECT-cIAI

P : cIAI

E : received either ceftolozane/tazobactam (1.5 g) plus metronidazole (500 mg) every 8 hours intravenously for 4-14 days.  n=383

C : meropenem (1 g) every 8 hours intravenously for 4-14 days. n=417

O :  Clinical cure rates at the test-of-cure visit (24-32 days from start of therapy) in the microbiological intent-to-treat (primary).

Ceftolozane/tazobactam plus metronidazole was noninferior to meropenem in the primary (83.0% [323/389] vs 87.3% [364/417]; weighted difference, -4.2%; 95% confidence interval [CI], -8.91 to .54).

The frequency of adverse events (AEs) was similar in both treatment groups (44.0% vs 42.7%) 

T : randomized, double-blind,  phase 3,  noninferiority

"Treatment with ceftolozane/tazobactam plus metronidazole was noninferior to meropenem in adult patients with cIAI, including infections caused by multidrug-resistant pathogens."

Ceftazidime-Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-abdominal Infection

P :cIAI

E : Ceftazidime-avibactam plus metronidazole

C : meropenem

O  : Clinical cure rates with ceftazidime-avibactam plus metronidazole and meropenem, respectively, were as follows: mMITT population, 81.6% and 85.1% (between-group difference, -3.5%; 95% confidence interval -8.64 to 1.58).

Adverse events were similar between groups.

T : randomized, double-blind, phase 3,  noninferiority

"Ceftazidime-avibactam plus metronidazole was noninferior to meropenem in the treatment of complicated intra-abdominal infections. Efficacy was similar against infections caused by ceftazidime-susceptible and ceftazidime-resistant pathogens. The safety profile of ceftazidime-avibactam plus metronidazole was consistent with that previously observed with ceftazidime alone."

RECAPTURE

P : suspected or microbiologically confirmed cUTI/acute pyelonephritis

E : ceftazidime-avibactam

C : 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)　

500 mg of Ciprofloxacin (oral)　or 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral

O : 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%]).

Ceftazidime-avibactam had a safety profile consistent with that of ceftazidime alone.

T : randomized, double-blind,  phase 3,  noninferiority

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