Safety and Efficacy of Ceftazidime-Avibactam Plus Metronidazole in the Treatment of Children >= 3 Months to < 18 Years With Complicated Intra-Abdominal Infection: Results From a Phase 2, Randomized, Controlled Trial
Por:
Bradley, JS, Broadhurst, H, Cheng, K, Mendez, M, Newell, P, Prchlik, M, Stone, GG, Talley, AK, Tawadrous, M, Wajsbrot, D, Yates, K, Zuzova, A and Gardner, A
Publicada:
1 ago 2019
Resumen:
Background: Ceftazidime-avibactam plus metronidazole is effective in the treatment of complicated intra-abdominal infection (cIAI) in adults. This single-blind, randomized, multicenter, phase 2 study (NCT02475733) evaluated the safety, efficacy and pharmacokinetics of ceftazidime-avibactam plus metronidazole in children with cIAI.
Methods: Hospitalized children (>= 3 months to <18 years) with cIAI were randomized 3: 1 to receive intravenous ceftazidime-avibactam plus metronidazole, or meropenem, for a minimum of 72 hours (9 doses), with optional switch to oral therapy thereafter for a total treatment duration of 7-15 days. Safety and tolerability were assessed throughout the study, along with clinical and microbiologic outcomes, and pharmacokinetics. A blinded observer determined adverse event (AE) causality, and clinical outcomes up to the late follow-up visit.
Results: Eighty-three children were randomized and received study drug (61 ceftazidime-avibactam plus metronidazole and 22 meropenem); most (90.4%) had a diagnosis of appendicitis. Predominant Gram-negative baseline pathogens were Escherichia coli (79.7%) and Pseudomonas aeruginosa (33.3%); 2 E. coli isolates were ceftazidime-non-susceptible. AEs occurred in 52.5% and 59.1% of patients in the ceftazidime-avibactam plus metronidazole and meropenem groups, respectively. Serious AEs occurred in 8.2% and 4.5% of patients, respectively; none was considered drug related. No deaths occurred. Favorable clinical/microbiologic responses were observed in >= 90% of patients in both treatment groups at end-of-intravenous treatment and test-of-cure visits.
Conclusions: Ceftazidime-avibactam plus metronidazole was well tolerated, with a safety profile similar to ceftazidime alone, and appeared effective in pediatric patients with cIAI due to Gram-negative pathogens, including ceftazidime-non-susceptible strains.
Filiaciones:
Bradley, JS:
Univ Calif San Diego, Sch Med, Rady Childrens Hosp, San Diego, CA 92103 USA
Broadhurst, H:
AstraZeneca, Alderley Pk, Macclesfield, Cheshire, England
Cheng, K:
Pfizer, Sandwich, Kent, England
:
Hosp Univ Germans Tries & Pujol, Barcelona, Spain
Newell, P:
AstraZeneca, Alderley Pk, Macclesfield, Cheshire, England
Prchlik, M:
Thomayerova Nemocnice, Prague, Czech Republic
Stone, GG:
Pfizer, Groton, CT USA
Talley, AK:
Allergan Plc, Madison, NJ USA
Tawadrous, M:
Pfizer, Groton, CT USA
Wajsbrot, D:
Pfizer, New York, NY USA
Yates, K:
AstraZeneca, Alderley Pk, Macclesfield, Cheshire, England
Zuzova, A:
Smolensk State Med Univ, Smolensk, Russia
Gardner, A:
Pfizer, Cambridge, MA USA
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