Complicated intra-abdominal infections

Metronidazole exposure-response and safety in infants

Posted on by Jeannine Sato

Antimicrobial Agents and Chemotherapy, November 2025

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Randell RL, Balevic SJ, Greenberg RG, Cohen-Wolkowiez M, Smith MJ, Benjamin DK Jr, Bendel C, Bliss JM, Chaaban H, Chhabra R, Dammann CEL, Downey LC, Hornik CD, Hussain N, Laughon MM, Lavery A, Moya F, Saxonhouse M, Sokol GM, Trembath A, Weitkamp J-H, Hornik CP; Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee.

The nitroimidazole antibiotic, metronidazole, is frequently prescribed to infants with serious intra-abdominal infections, and multiple dosing recommendations exist. We sought to evaluate the extent to which metronidazole doses and associated exposures achieved desired efficacy and safety in infants enrolled in the Antibiotic Safety in Infants with Complicated Intra-abdominal Infections (SCAMP) trial (NCT01994993). SCAMP participants received intravenous metronidazole as part of multimodal antimicrobial therapy.

Safety of Metronidazole in Late Preterm and Term Infants With Complicated Intraabdominal Infections

Posted on by Kayla Korzekwinski

Pediatric Infectious Disease Journal • September 2020

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Commander SJ, Gao J, Zinkhan EK, Heresi G, Courtney SE, Lavery AP, Delmore P, Sokol GM, Moya F, Benjamin DK Jr, Bumpass TG, Debski J, Erinjeri J, Sharma G, Tracy ET, Cohen-Wolkowiez M, Hornik CP; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee

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. Metronidazole safety was evaluated by reporting of adverse events (AEs) and safety events of special interest. 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.

Physiologically Based Pharmacokinetic (PBPK) Modeling of Meropenem in Preterm and Term Infants

Posted on by Kayla Korzekwinski

Clinical Pharmacokinetics • June 2021

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Ganguly S, Edginton A, Gerhart JG, Cohen-Wolkowiez M, Greenberg RG, Gonzalez D; on behalf of the Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee
This study applied physiologically based pharmacokinetic (PBPK) modeling to characterize the disposition of the antibiotic meropenem in preterm and term infants. Meropenem is approved by the US Food and Drug Administration for use in pediatric patients, including treating complicated intra-abdominal infections in infants < 3 months of age. The PBPK model-based simulations were performed to evaluate meropenem dosing in the product label for infants < 3 months of age treated for complicated intra-abdominal infections. The PBPK model used supports the meropenem dosing regimens recommended in the product label for infants <3 months of age.

Antibiotic Safety and Effectiveness in Premature Infants With Complicated Intraabdominal Infections

Posted on by Kayla Korzekwinski

The Pediatric Infectious Disease Journal • June 2021

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Smith MJ, Boutzoukas A, Autmizguine J, Hudak M, Zinkhan E, Bloom BT, Heresi G, Lavery A, Courtney S, Sokol GR, Cotton CM, Bliss J, Mendley S, Bendel C, Dammann C, Weitkamp JH, Saxonhouse MA, Mundakel GT, Debski J, Lewandowski A, Erinjeri J, Gao J, Benjamin DK, Hornik C, Smith PB, Cohen-Wolkowiez M, on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network
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. One hundred eighty 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). There were no differences in safety outcomes between antibiotic regimens. Each of the antibiotic regimens are safe in premature infants with cIAI.

Intestinal Fatty-Acid Binding Protein and Metronidazole Response in Premature Infants

Posted on by Kayla Korzekwinski

Journal of Neonatal and Perinatal Medicine • November 2014

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Sampson MR, Bloom BT, Arrieta A, Capparelli E, Benjamin DK Jr, Smith PB, Kearns GL, van den Anker J, Cohen-Wolkowiez M.

In premature infants with suspected intra-abdominal infection, biomarkers for treatment response to antimicrobial therapy are lacking. Intestinal fatty acid-binding protein (I-FABP) is specific to the enterocyte and is released in response to intestinal mucosal injury. I-FABP has not been evaluated as a surrogate marker of disease response to antimicrobial therapy. We examined the relationship between metronidazole exposure and urinary I-FABP concentrations in premature infants with suspected intra-abdominal infection.

Adverse events associated with meropenem versus imipenem/cilastatin therapy in a large retrospective cohort of hospitalized infants

Posted on by Kayla Korzekwinski

The Pediatric Infectious Disease Journal • July 2013

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Hornik CP, Herring AH, Benjamin DK Jr, Capparelli EV, Kearns GL, van den Anker J, Cohen-Wolkowiez M, Clark RH, Smith PB; Best Pharmaceuticals for Children Act-Pediatric Trials Network.

Carbapenems are commonly used in hospitalized infants despite a lack of complete safety data and associations with seizures in older children. We compared the incidence of adverse events in hospitalized infants receiving meropenem versus imipenem/cilastatin. We conducted a retrospective cohort study of 5566 infants treated with meropenem or imipenem/cilastatin in neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2010.

Determining population and developmental pharmacokinetics of metronidazole using plasma and dried blood spot samples from premature infants

Posted on by Kayla Korzekwinski

The Pediatric Infectious Disease Journal • July 2013

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Cohen-Wolkowiez M, Sampson M, Bloom BT, Arrieta A, Wynn JL, Martz K, Harper B, Kearns GL, Capparelli EV, Siegel D, Benjamin DK Jr, Smith PB; Best Pharmaceuticals for Children Act–Pediatric Trials Network.

Limited pharmacokinetic (PK) data of metronidazole in premature infants have led to various dosing recommendations. Surrogate efficacy targets for metronidazole are ill-defined and therefore aimed to exceed minimum inhibitory concentration of organisms responsible for intra-abdominal infections. We evaluated the PK of metronidazole using plasma and dried blood spot samples from infants ≤32 weeks gestational age in an open-label, PK, multicenter (N = 3) study using population PK modeling (NONMEM).

Safety and effectiveness of meropenem in infants with suspected or complicated intra-abdominal infections

Posted on by Kayla Korzekwinski

Clinical Infectious Disease • December 2012

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Cohen-Wolkowiez M, Poindexter B, Bidegain M, Weitkamp JH, Schelonka RL, Randolph DA, Ward RM, Wade K, Valencia G, Burchfield D, Arrieta A, Mehta V, Walsh M, Kantak A, Rasmussen M, Sullivan JE, Finer N, Rich W, Brozanski BS, van den Anker J, Blumer J, Laughon M, Watt KM, Kearns GL, Capparelli EV, Martz K, Berezny K, Benjamin DK Jr, Smith PB; Meropenem Study Team.

Intra-abdominal infections are common in young infants and lead to significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial with excellent activity against pathogens associated with intra-abdominal infections. The purpose of this study was to determine the safety and effectiveness of meropenem in young infants with suspected or complicated intra-abdominal infections.

Population pharmacokinetics of meropenem in plasma and cerebrospinal fluid of infants with suspected or complicated intra-abdominal infections

Posted on by Kayla Korzekwinski

The Pediatric Infectious Disease Journal • October 2011

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Smith PB, Cohen-Wolkowiez M, Castro LM, Poindexter B, Bidegain M, Weitkamp JH, Schelonka RL, Ward RM, Wade K, Valencia G, Burchfield D, Arrieta A, Bhatt-Mehta V, Walsh M, Kantak A, Rasmussen M, Sullivan JE, Finer N, Brozanski BS, Sanchez P, van den Anker J, Blumer J, Kearns GL, Capparelli EV, Anand R, Benjamin DK Jr; Meropenem Study Team.

Suspected or complicated intra-abdominal infections are common in young infants and lead to significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial agent with excellent activity against pathogens associated with intra-abdominal infections in this population. The purpose of this study was to determine the pharmacokinetics (PK) of meropenem in young infants as a basis for optimizing dosing and minimizing adverse events.