Antibiotic Safety and Effectiveness in Premature Infants With Complicated Intraabdominal Infections
04/2021
Journal Article
Authors:
Smith, M. J.;
Boutzoukas, A.;
Autmizguine, J.;
Hudak, M. L.;
Zinkhan, E.;
Bloom, B. T.;
Heresi, G.;
Lavery, A. P.;
Courtney, S. E.;
Sokol, G. M.;
Cotten, C. M.;
Bliss, J. M.;
Mendley, S.;
Bendel, C.;
Dammann, C. E. L.;
Weitkamp, J. H;
Saxonhouse, M. A.;
Mundakel, G. T.;
Debski, J.;
Sharma, G.;
Erinjeri, J.;
Gao, J.;
Benjamin, D. K., Jr.;
Hornik, C. P.;
Smith, P. B.;
Cohen-Wolkowiez, M.
Volume:
40
Pagination:
550-555
Issue:
6
Journal:
Pediatr Infect Dis J
PMID:
33902072
URL:
https://www.ncbi.nlm.nih.gov/pubmed/33902072
DOI:
10.1097/INF.0000000000003034
Keywords:
Anti-Bacterial Agents/*standards/*therapeutic use
Humans
Infant
Infant, Newborn
Infant, Premature
Intraabdominal Infections/complications/*drug therapy/mortality
Prospective Studies
Treatment Outcome
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.
