Trial reportThe Journal of antimicrobial chemotherapy2022
Simultaneous pharmacokinetic/pharmacodynamic (PKPD) assessment of ampicillin and gentamicin in the treatment of neonatal sepsis.
Trial report in The Journal of antimicrobial chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03453177 (Intravenous and Oral Fosfomycin in Hospitalised Neonates With Clinical Sepsis), which is not on this map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Intravenous and Oral Fosfomycin in Hospitalised Neonates With Clinical Sepsis: an Open-label Safety and Pharmacokinetics Study (neoFosfo)
Who cites it
3 citing papers in PubMed, 6 citations in OpenAlex.
- Successful Management of Severe COVID-19 in a Kidney Transplant Recipient Safe Co-Administered Tacrolimus and Ensitrelvir: A Case Report.Reports (MDPI) · 2026Article
- An Overview of Antibiotic Therapy for Early- and Late-Onset Neonatal Sepsis: Current Strategies and Future Prospects.Antibiotics (Basel, Switzerland) · 2024Review
- Physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPK.Frontiers in pharmacology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 9 institutions in 5 countries.
Funding
Abstract
objectivesThis study aimed to simultaneously investigate the pharmacokinetics of ampicillin and gentamicin, currently the WHO standard of care for treating neonatal sepsis.
methodsPharmacokinetic data were collected in 59 neonates receiving ampicillin and gentamicin for suspected or proven sepsis in the NeoFosfo trial (NCT03453177). A panel of 23 clinical Escherichia coli isolates from neonates with sepsis, resistant to either ampicillin, gentamicin or both, were tested for susceptibility using chequerboards. Pharmacokinetic/pharmacodynamic (PKPD) modelling and simulations were used to compare single-agent (EUCAST MIC) and combination (chequerboard MIC) target attainment with standard dosing regimens.
resultsA model was established that simultaneously estimated parameters of a one-compartment ampicillin model and a two-compartment gentamicin model. A common clearance for both drugs was used (6.89 L/h/70 kg) relating to glomerular filtration (CLGFR), with an additional clearance term added for ampicillin (5.3 L/h/70 kg). Covariate modelling included a priori allometric weight and post-menstrual age scaling of clearance. Further covariate relationships on renal clearance were postnatal age and serum creatinine.Simulation-based PKPD assessments suggest good Gram-positive (MIC ≤ 0.25 mg/L) cover. However, less than one-quarter of neonates were predicted to receive efficacious coverage against Enterobacterales (MIC ≤ 2 mg/L). The benefit of the ampicillin/gentamicin combination was limited, with only 2/23 E. coli clinical strains showing FIC index < 0.5 (synergy) and most in the range 0.5-1 (suggesting additivity). Simulations showed that feasible dosing strategies would be insufficient to cover resistant strains.
conclusionsPKPD simulations showed ampicillin and gentamicin combination therapy was insufficient to cover Enterobacterales, suggesting the need for alternative empirical treatment options for neonatal sepsis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.