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.

Population Pharmacokinetics of Meropenem Across the Adult Lifespan

Posted on by Kayla Korzekwinski

Clinical Pharmacokinetics • February 2025

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Boutzoukas AE, Balevic SJ, Hemmersbach-Miller M, Winokur PL, Gu K, Chan AW, Cohen-Wolkowiez M, Conrad T, An G, Kirkpatrick CMJ, Swamy GK, Walter EB, Schmader KE, Landersdorfer CB.

This study conducted an opportunistic pharmacokinetic study to evaluate the population pharmacokinetics of meropenem, an antimicrobial commonly used to treat Gram-negative infections in adults of different ages, including older adults, and determined optimal dosing regimens. Meropenem dosing should be based on renal function rather than age. For patients without renal impairment, extended infusion may increase the probability of target attainment.

 

Epidemiology and outcomes of bacterial meningitis in the neonatal intensive care unit

Posted on by Kayla Korzekwinski

Journal of Perinatology • July 2024

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Aleem S, Benjamin DK Jr, Burns C, Duncan J, Melaku K, Norbekov A, Graham B, Mantena S, Ladipo T, Jung A, Zimmerman KO, Clark RH, Greenberg RG

This study examined pathogen distribution, antibiotic resistance patterns, and hospital outcomes of infants with bacterial meningitis in neonatal intensive care units (NICUs) in the US from 2013-2018.

Acyclovir Dosing Practices Across a Multicenter Cohort of Neonatal Intensive Care Units

Posted on by Kayla Korzekwinski

The Pediatric Infectious Disease Journal • June 2024

Foote HP, Thomassy H, Baquero L, Cayli M, Jacobs E, Paladugu A, Roy A, Heyward E, Clark RH, Hornik CP, Benjamin DK, Benjamin DK Jr, Greenberg RG

Acyclovir is the first-line therapy for neonatal herpes simplex virus infections. Therapy can mitigate morbidity and mortality but carries a risk for toxicity. This study aimed to compare acyclovir dosing in neonatal intensive care units to published recommendations based on population pharmacokinetic (PopPK) analysis.

Postdiscontinuation Antibiotic Exposure in Hospitalized Infants at Risk for Late-onset Sepsis in the Neonatal Intensive Care Unit

Posted on by Kayla Korzekwinski

The Pediatric Infectious Disease Journal • June 2024

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Wade KC, Greenberg RG, Benjamin DK Jr., Chen L, Vo B, Ang BL, Boutzoukas A, Zimmerman KO, Clark RH, Cohen-Wolkowiez M, Le J on behalf of the Administrative Core Committee of the Best Pharmaceuticals for Children Act – Pediatric Trials Network

In the neonatal intensive care unit, infants are at risk for late-onset sepsis. When blood cultures are negative, antibiotic stewardship efforts encourage stopping antibiotics, yet the duration of therapeutic exposure after the last dose is unknown. Piperacillin and cefepime exposures remained therapeutic long after the expected 8- to 12-hour dosing interval. PDAE is an important consideration for antibiotic stewardship among hospitalized infants, particularly premature infants and those within 1 month postbirth.

Urinary Tract Infection Epidemiology in NICUs in the United States

Posted on by Kayla Korzekwinski

American Journal of Perinatology • May 2024

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Kilpatrick R, Boutzoukas AE, Chan E, Girgis V, Kinduelo V, Kwabia SA, Yan J, Clark RH, Zimmerman KO, Greenberg RG

This study characterized the incidence, associated clinical factors, timing of infection, microbiology, and incidence of concordant blood culture of urinary tract infections (UTIs) in very low birth weight (VLBW <1,500g) infants. UTI is a common cause of infection in VLBW infants, especially among the smallest, most premature, male infants, and those with a longer duration of hospitalization. Neonatal clinicians should consider obtaining urine culture in the setting of late-onset sepsis evaluations in VLBW infants.

Opportunistic dried blood spot sampling validates and optimizes a pediatric population pharmacokinetic model of metronidazole

Posted on by Kayla Korzekwinski

Antimicrobial Agents and Chemotherapy • April 2024

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Randell RL, Balevic SJ, Greenberg RG, Cohen-Wolkowiez M, Thompson EJ, Venkatachalam S, Smith MJ, Bendel C, Bliss JM, Chaaban H, Chhabra R, Dammann CEL, Downey LC, Hornik C, Hussain N, Laughon MM, Lavery A, Moya F, Saxonhouse M, Sokol GM, Trembath A, Weitk

Pharmacokinetic models rarely undergo external validation in vulnerable populations such as critically ill infants, thereby limiting the accuracy, efficacy, and safety of model-informed dosing in real-world settings. Here, we describe an opportunistic approach using dried blood spots (DBS) to evaluate a population pharmacokinetic model of metronidazole in critically ill preterm infants of gestational age (GA) ≤31 weeks from the Metronidazole Pharmacokinetics in Premature Infants study.

Association Between Hypoglycemia and the Occurrence of Early Onset Sepsis in Premature Infants

Posted on by Kayla Korzekwinski

Journal of the Pediatric Infectious Diseases Society • December 2023

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Kumar KR, Shah SJ, Fayyad RM, Turla TM, O’Sullivan LM, Wallace B, Clark RH, Benjamin Jr DK, Greenberg RG, Hornik CP

This study examined the association between hypoglycemia and the occurrence of early onset sepsis (EOS) in premature infants admitted to the neonatal intensive care unit (NICU). Hypoglycemia may be an early marker of EOS, particularly in episodes caused by Gram-negative organisms and when using a stricter definition of hypoglycemia.

Late-Onset Sepsis Evaluation and Empiric Therapy in Extremely Low Gestational Age Newborns

Posted on by Kayla Korzekwinski

Journal of the Pediatric Infectious Diseases Society • December 2023

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Speier RL, Cotton CM, Lewis K, Benajmin DK Jr, Keeler K, Kidimbu G, Roberts W, Clark RH, Zimmerman KO, Stark A, Greenberg RG

Little is known about late-onset sepsis (LOS) evaluations in extremely low gestational age newborns (ELGANs). This study describes frequencies of LOS evaluation in ELGANs, infant characteristics, and empiric therapy choices during evaluations.

Diagnostic Utility of Cerebrospinal Fluid White Blood Cell Components for the Identification of Bacterial Meningitis in Infants

Posted on by Kayla Korzekwinski

Journal of the Pediatric Infectious Diseases Society • December 2023

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Lamb AE, Rent S, Brannon AJ, Greer JL, Ndey-Bongo NP, Cho SH, Greenberg RG, Benjamin DK Jr, Clark RH, Kumar KR

This study evaluated the diagnostic and predictive utility of cerebrospinal fluid (CSF) white blood cell (WBC) components in the diagnosis of bacterial meningitis in infants discharged from the neonatal intensive care unit (NICU). No single clinical prediction rule had the optimal discriminatory power for predicting culture-proven bacterial meningitis, and clinicians should be cautious when interpreting CSF WBC parameters in infants with suspected meningitis.