Antibiotic Safety and Effectiveness in Premature Infants With Complicated Intraabdominal Infections
Michael J Smith, Angelique Boutzoukas, Julie Autmizguine, Mark L Hudak, Erin Zinkhan, Barry T Bloom, Gloria Heresi, Adrian P Lavery, Sherry E Courtney, Gregory M Sokol, C Michael Cotten, Joseph M Bliss, Susan Mendley, Catherine Bendel, Christiane E L Dammann, Jörn-Hendrik Weitkamp, Matthew A Saxonhouse, Gratias T Mundakel, Julie Debski, Gaurav Sharma, Jinson Erinjeri, Jamie Gao, Daniel K Benjamin Jr, Christoph P Hornik, P Brian Smith, Michael Cohen-Wolkowiez, Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee, Michael J Smith, Angelique Boutzoukas, Julie Autmizguine, Mark L Hudak, Erin Zinkhan, Barry T Bloom, Gloria Heresi, Adrian P Lavery, Sherry E Courtney, Gregory M Sokol, C Michael Cotten, Joseph M Bliss, Susan Mendley, Catherine Bendel, Christiane E L Dammann, Jörn-Hendrik Weitkamp, Matthew A Saxonhouse, Gratias T Mundakel, Julie Debski, Gaurav Sharma, Jinson Erinjeri, Jamie Gao, Daniel K Benjamin Jr, Christoph P Hornik, P Brian Smith, Michael Cohen-Wolkowiez, Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee
Abstract
Background: In premature infants, complicated intraabdominal infections (cIAIs) are a leading cause of morbidity and mortality. Although universally prescribed, the safety and effectiveness of commonly used antibiotic regimens have not been established in this population.
Methods: Infants ≤33 weeks gestational age and <121 days postnatal age with cIAI were randomized to ≤10 days of ampicillin, gentamicin, and metronidazole (group 1); ampicillin, gentamicin, and clindamycin (group 2); or piperacillin-tazobactam and gentamicin (group 3) at doses stratified by postmenstrual age. Due to slow enrollment, a protocol amendment allowed eligible infants already receiving study regimens to enroll without randomization. The primary outcome was mortality within 30 days of study drug completion. Secondary outcomes included adverse events, outcomes of special interest, and therapeutic success (absence of death, negative cultures, and clinical cure score >4) 30 days after study drug completion.
Results: One hundred eighty infants [128 randomized (R), 52 nonrandomized (NR)] were enrolled: 63 in group 1 (45 R, 18 NR), 47 in group 2 (41 R, 6 NR), and 70 in group 3 (42 R, 28 NR). Thirty-day mortality was 8%, 7%, and 9% in groups 1, 2, and 3, respectively. There were no differences in safety outcomes between antibiotic regimens. After adjusting for treatment group and gestational age, mortality rates through end of follow-up were 4.22 [95% confidence interval (CI): 1.39-12.13], 4.53 (95% CI: 1.21-15.50), and 4.07 (95% CI: 1.22-12.70) for groups 1, 2, and 3, respectively.
Conclusions: Each of the antibiotic regimens are safe in premature infants with cIAI.
Clinical trial registration: NCT0199499.
Trial registration: ClinicalTrials.gov NCT01994993.
Conflict of interest statement
The other authors have no conflicts of interest to disclose.
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Source: PubMed