Flomoxef for neonates: extending options for treatment of neonatal sepsis caused by ESBL-producing Enterobacterales

Darlow, Christopher A ORCID: 0000-0002-5400-3413 and Hope, William ORCID: 0000-0001-6187-878X
(2021) Flomoxef for neonates: extending options for treatment of neonatal sepsis caused by ESBL-producing Enterobacterales. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 77 (3). pp. 711-718.

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<h4>Background</h4>Neonatal sepsis is a serious and frequently lethal infection, often complicated by antimicrobial resistance (including ESBLs) in low- and middle-income countries (LMICs). Flomoxef is an off-patent oxacephem β-lactam with stability against non-AmpC ESBLs, with potential for utility in these settings. To date, there has been no published flomoxef neonatal population pharmacokinetic (PopPK) model.<h4>Objectives</h4>To summarize the clinical data available for flomoxef, build a neonatal PopPK model and assess the adequacy of different neonatal flomoxef regimens.<h4>Methods</h4>A systematic literature search returned all available clinical or pharmacokinetic data of flomoxef use in neonates. Pharmacokinetic data were used to construct a PopPK model, with progressive incorporation of covariates into the final model. Monte Carlo simulations were performed using this final model to simulate drug exposures of different flomoxef regimens to calculate PTAs.<h4>Results</h4>Individual-level clinical and pharmacokinetic data were extracted for 313 and 146 neonates, respectively, with population clinical data extracted for a further 199 neonates. Clinical and microbiological success rates were 89.71% and 82.8%, respectively, with minimal side effects. The final PopPK model incorporated body weight and postnatal age as covariates. PTA analyses predicted that IV regimens of 20 mg/kg q12h, 20 mg/kg q6-8h and 40 mg/kg q6-8h are adequate for neonates aged 0-7, 7-14 and 14-28 days, respectively.<h4>Conclusions</h4>To the best of our knowledge, this is the first published neonatal PopPK model for flomoxef. Given the high treatment success rates, low toxicity rates and off-patent status, this drug has potential for use in the treatment of neonatal sepsis in ESBL-prevalent LMIC settings.

Item Type: Article
Uncontrolled Keywords: Humans, Cephalosporins, beta-Lactamases, Anti-Bacterial Agents, Microbial Sensitivity Tests, Infant, Newborn, Neonatal Sepsis
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 27 May 2022 08:33
Last Modified: 18 Jan 2023 21:00
DOI: 10.1093/jac/dkab468
Open Access URL: https://doi.org/10.1093/jac/dkab468
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3155590