Skip to content
DraconiticResearch
Search Sources API
190,839 studies31 sourcesUpdated 18 min ago
Peer-reviewedCC BYOpen forum infectious diseases

Cephalexin Model-Informed Dosing Recommendations for Severe Infections: A Pooled Pharmacokinetic Analysis From Infancy to Adulthood.

  • Andrew S Haynes1,2
  • Daniel Gonzalez3,4
  • Kevin Messacar1,2
  • Julie Autmizguine5,6,7
  • Amanda Gwee8,9,10
  • Richard Everts11
  • Peter Anderson12
12 affiliations
  1. 1Department of Pediatrics, Section of Pediatric Infectious Diseases, Children's Hospital Colorado, Aurora, Colorado, USA.
  2. 2School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
  3. 3Division of Clinical Pharmacology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
  4. 4Duke Clinical Research Institute, Durham, North Carolina, USA.
  5. 5Department of Pediatrics, Section of Pediatric Infectious Diseases, Sainte-Justine University Hospital, Montreal, Canada.
  6. 6Azrieli Sainte-Justine Research Center, Montréal, Canada.
  7. 7Department of Pharmacology and Physiology, Université de Montréal, Montréal, Canada.
  8. 8Antimicrobials Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
  9. 9Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.
  10. 10Department of General Medicine and Infectious Diseases, Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.
  11. 11Infectious Disease Service, Nelson Bays Primary Health, Nelson, New Zealand.
  12. 12Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA.
Read full textPDFDOICite

Abstract

Background

Cephalexin is increasingly used as initial and oral transition therapy for severe infections, but optimal dosing in this setting remains uncertain.Methods

Four cephalexin pharmacokinetic (PK) datasets spanning preterm neonates through young adults were pooled to develop a unified population PK model. Simulations estimated probability of target attainment (PTA) and cumulative fractional response (CFR, target attainment weighted across the pathogen MIC distribution) across fT > MIC targets (free drug time above the minimum inhibitory concentration), MIC distributions for methicillin-susceptible Staphylococcus aureus (MSSA) and Enterobacterales, and multiple dosing regimens.Results

Seventy-one subjects (age 9 days-29 years) contributed 360 plasma samples, best described by a 1-compartment model with first-order absorption and lag time. Apparent volume and clearance scaled with fat-free mass, and clearance increased with postmenstrual age. Absorption was slower in neonates. Cephalexin 25 mg/kg/dose, maximum 1000 mg, every 8 hours, achieved 1-log kill targets for MSSA (PTA ≥ 98% for 35% fT > MIC at MIC = 4 mg/L); every 6-hour dosing was needed at MIC = 8 mg/L. For Enterobacterales, a 60% fT > MIC target was achieved only in infants < 2 months. However, higher-dose regimens (37.5-50 mg/kg, maximum 1500 mg, every 6 hours) achieved CFRs > 90% for 40%-50% fT > MIC targets when cefazolin MICs were ≤2 mg/L.Conclusions

Cephalexin PK varies with age but is well-captured by a unified size- and maturation-scaled model. These data support dosing within the FDA-approved range for systemic MSSA infections. Higher-dose regimens are necessary for adequate target attainment against Enterobacterales. Appropriately dosed cephalexin represents a viable option for selected severe infections, including oral transition therapy.

Related

  1. Possible Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS) Presenting in Late Adolescence and Early Adulthood: A Case Series.
    Tariq A Madani, Fahd S Alsallum, Ola H Abudaowd +1
    Clinical case reportsPeer-reviewedCC BYFull textNeurologyEurope PMCDOAJ
  2. AFSSAPS recommendations for the management of urinary tract infections in children
    L Barbeau, C Renoux, H Barbeau +2
    Exercer. La revue francophone de médecine généralePeer-reviewedPublisher termsFull textEcologyEpidemiology & public healthHAL
  3. Wild Boar-Related Injuries in Wilderness Environments: Field-Oriented Management Principles and Evidence-Informed Clinical Recommendations
    Markus Maier, Leonard P. N. Maier, Simon Hackl +2
    Journal of clinical medicinePeer-reviewedCC BYFull textGeneral medicineEurope PMC
  4. Mapping the subcellular pharmacokinetic-pharmacodynamic landscape: a systems-pharmacology framework for predicting combination therapies against intracellular bacterial infections
    Venkata Bharat Kumar Pinnelli, Surendra Babu Thangachi, C. A. Jayashankar +8
    Frontiers in PharmacologyPeer-reviewedCC BY 4.0Full textPharmacology & toxicologyCrossref
  5. Syndrome-oriented CNS infectious complications after haematopoietic stem-cell transplantation and CAR T-cell therapy, part 2—focal brain infections and meningitis of bacterial, fungal, and parasitic origin: recommendations from the EBMT Practice and Harmonization Committee
    Malgorzata Mikulska, Dina Averbuch, Dionysios Neofytos +12
    eClinicalMedicinePeer-reviewedCC BY 4.0Full textGeneral medicineCrossrefDOAJ

Cite

BibTeXRIS
BibTeX
@article{haynes2026cephalexin,
  title = {{Cephalexin Model-Informed Dosing Recommendations for Severe Infections: A Pooled Pharmacokinetic Analysis From Infancy to Adulthood.}},
  author = {Andrew S Haynes and Daniel Gonzalez and Kevin Messacar and Julie Autmizguine and Amanda Gwee and Richard Everts and Peter Anderson},
  journal = {Open forum infectious diseases},
  year = {2026},
  month = sep,
  doi = {10.1093/ofid/ofag611},
  url = {https://europepmc.org/article/MED/42898747},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Cephalexin Model-Informed Dosing Recommendations for Severe Infections: A Pooled Pharmacokinetic Analysis From Infancy to Adulthood.
AU  - Andrew S Haynes
AU  - Daniel Gonzalez
AU  - Kevin Messacar
AU  - Julie Autmizguine
AU  - Amanda Gwee
AU  - Richard Everts
AU  - Peter Anderson
PY  - 2026
DA  - 2026/09/26
JO  - Open forum infectious diseases
DO  - 10.1093/ofid/ofag611
UR  - https://europepmc.org/article/MED/42898747
AB  - Background  Cephalexin is increasingly used as initial and oral transition therapy for severe infections, but optimal dosing in this setting remains uncertain.Methods  Four cephalexin pharmacokinetic (PK) datasets spanning preterm neonates through young adults were pooled to develop a unified population PK model. Simulations estimated probability of target attainment (PTA) and cumulative fractional response (CFR, target attainment weighted across the pathogen MIC distribution) across fT > MIC targets (free drug time above the minimum inhibitory concentration), MIC distributions for methicillin-susceptible Staphylococcus aureus (MSSA) and Enterobacterales, and multiple dosing regimens.Results  Seventy-one subjects (age 9 days-29 years) contributed 360 plasma samples, best described by a 1-compartment model with first-order absorption and lag time. Apparent volume and clearance scaled with fat-free mass, and clearance increased with postmenstrual age. Absorption was slower in neonates. Cephalexin 25 mg/kg/dose, maximum 1000 mg, every 8 hours, achieved 1-log kill targets for MSSA (PTA ≥ 98% for 35% fT > MIC at MIC = 4 mg/L); every 6-hour dosing was needed at MIC = 8 mg/L. For Enterobacterales, a 60% fT > MIC target was achieved only in infants < 2 months. However, higher-dose regimens (37.5-50 mg/kg, maximum 1500 mg, every 6 hours) achieved CFRs > 90% for 40%-50% fT > MIC targets when cefazolin MICs were ≤2 mg/L.Conclusions  Cephalexin PK varies with age but is well-captured by a unified size- and maturation-scaled model. These data support dosing within the FDA-approved range for systemic MSSA infections. Higher-dose regimens are necessary for adequate target attainment against Enterobacterales. Appropriately dosed cephalexin represents a viable option for selected severe infections, including oral transition therapy.
SN  - 2328-8957
ER  -