Safety of Metronidazole in Late Pre-term and Term Infants with Complicated Intra-abdominal Infections
05/2020
Journal Article
Authors:
Commander, S. J.;
Gao, J.;
Zinkhan, E. K.;
Heresi, G.;
Courtney, S. E.;
Lavery, A. P.;
Delmore, P.;
Sokol, G. M.;
Moya, F.;
Benjamin, D.;
Bumpass, T. G.;
Debski, J.;
Erinjeri, J.;
Sharma, G.;
Tracy, E. T.;
Smith, P. B.;
Cohen-Wolkowiez, M.;
Hornik, C. P.
Volume:
39
Pagination:
e245-e248
Issue:
9
Journal:
Pediatr Infect Dis J
PMID:
32453198
URL:
https://www.ncbi.nlm.nih.gov/pubmed/32453198
DOI:
10.1097/INF.0000000000002698
Keywords:
Anti-Bacterial Agents/standards/*therapeutic use
Cohort Studies
Drug Therapy, Combination
Drug-Related Side Effects and Adverse Reactions
Female
Gestational Age
Humans
Infant
Infant, Newborn
Intraabdominal Infections/*drug therapy/*microbiology
Male
Metronidazole/standards/*therapeutic use
United States
Abstract:
BACKGROUND: Metronidazole is frequently used off-label in infants with complicated intra-abdominal infections (cIAI) to provide coverage against anaerobic organisms, but its safety and efficacy in this indication are unknown. METHODS: In the Antibiotic Safety in Infants with Complicated Intra-Abdominal Infections open-label multicenter trial infants >/=34 weeks gestation at birth and <121 days postnatal age with cIAIs were administered metronidazole as part of multimodal therapy. Metronidazole safety was evaluated by reporting of adverse events (AEs) and safety events of special interest. Cure from disease was determined by blood cultures and a clinical cure score >4. A blinded adjudication committee reviewed all safety events of special interest. RESULTS: Fifty-five infants were included, median gestational age was 36 weeks (range: 34-41) and postnatal age was 7 days (0-63). The most common additional antibiotics received included gentamicin, piperacillin-tazobactam, ampicillin and vancomycin. Only one AE, a candidal rash, was identified to be potentially caused by metronidazole administration. One infant died of cardiopulmonary failure, which was deemed unrelated to metronidazole. The most common events of special interest included feeding intolerance in 18 (33%) infants, and exploratory laparotomy in 10 (18%) requiring intestinal anastomosis in 7 (13%) infants. There was 1 (2%) intestinal stricture. Fifty-three infants (96%) achieved overall therapeutic success, 54 (98%) were alive through 30 days post-study therapy, and 54 (98%) had 30-day clinical cure score >4. CONCLUSIONS: In a cohort of late pre-term and term infants with cIAIs, combination antibiotic therapy that included metronidazole was safe, and therapeutic success was high.
