TY - JOUR
T1 - Antibiotic Safety and Effectiveness in Premature Infants with Complicated Intraabdominal Infections
AU - Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee
AU - Smith, Michael J.
AU - Boutzoukas, Angelique
AU - Autmizguine, Julie
AU - Hudak, Mark L.
AU - Zinkhan, Erin
AU - Bloom, Barry T.
AU - Heresi, Gloria
AU - Lavery, Adrian P.
AU - Courtney, Sherry E.
AU - Sokol, Gregory M.
AU - Cotten, C. Michael
AU - Bliss, Joseph M.
AU - Mendley, Susan
AU - Bendel, Catherine
AU - Dammann, Christiane E.L.
AU - Weitkamp, Jörn Hendrik
AU - Saxonhouse, Matthew A.
AU - Mundakel, Gratias T.
AU - Debski, Julie
AU - Sharma, Gaurav
AU - Erinjeri, Jinson
AU - Gao, Jamie
AU - Benjamin, Daniel K.
AU - Hornik, Christoph P.
AU - Smith, P. Brian
AU - Cohen-Wolkowiez, Michael
N1 - Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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.
AB - 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.
KW - antibiotics
KW - complicated intraabdominal infection
KW - infants
KW - safety
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U2 - 10.1097/INF.0000000000003034
DO - 10.1097/INF.0000000000003034
M3 - Article
C2 - 33902072
AN - SCOPUS:85105817221
SN - 0891-3668
VL - 40
SP - 550
EP - 555
JO - Pediatric Infectious Disease Journal
JF - Pediatric Infectious Disease Journal
IS - 6
ER -