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

Cephalexin is increasingly used as initial and oral transition therapy for severe infections, but optimal dosing in this setting remains uncertain.MethodsFour 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.ResultsSeventy-one subjects (age 9 days-29 years) contributed 360 plasma samples, best described by a one-compartment model with first-order absorption and lag time. Apparent volume and clearance scaled with fat-free mass, and clearance increased with post-menstrual age. Absorption was slower in neonates. Cephalexin 25 mg/kg/dose, maximum 1,000 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 1,500 mg, every 6 hours) achieved CFRs >90% for 40-50% fT>MIC targets when cefazolin MICs were ≤2 mg/L.ConclusionsCephalexin 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.

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Oseltamivir for Critically Ill Patients with Influenza: A Randomised Trial

​Background: The antiviral oseltamivir is widely used for the treatment of critically ill patients with influenza. Evidence from randomised trials about its eff

papers.ssrn.com

Getting It Right the Second Time: How Can we Optimize First‐Generation Cephalosporin Dosing for Skin and Soft Tissue Infections in the 21st Century?

Optimal cephalexin and cefadroxil dosing for skin and soft tissue infections (SSTIs) is unclear. We summarize clinical and pharmacokinetic/pharmacodynamic (PK/PD) data that compare dosing strategies ...

accpjournals.onlinelibrary.wiley.com

Communicable E52: ESCMID Global Trials, PETER PEN and ASTARTE | Communicable | Episode 52

In this collaborative episode of Breakpoints and Communicable, the hosts revisit the “trial run” session from ESCMID Global, a format designed to facilitate critical discussion of major infectious dis...

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Duration of therapy for Pseudomonas aeruginosa bacteremia – a post hoc subgroup analysis from the BALANCE randomized controlled trial

Despite the clinical significance of P. aeruginosa bacteremia, the optimal duration of antibiotic therapy is unclear. We aimed to explore the association of antibiotic duration on mortality in hospitalized patients with P. aeruginosa bacteremia.MethodsThis study was a post hoc analysis of all patients with P. aeruginosa bacteremia included in the BALANCE randomized controlled trial comparing 7 versus 14 days of antibiotic therapy for bacteremia. The primary outcome was 90-day mortality. Unadjusted risk differences [RDs] with 95% confidence intervals [CIs] for outcomes were calculated for patients randomized to 7 versus 14 days of treatment. Multivariable logistic regression was used to evaluate independent predictors of mortality.ResultsAmong 157 patients with P. aeruginosa bacteremia, 74 were randomized to 7 days antibiotic treatment, and 83 to 14 days. Patients in the 7-day group were more likely to be men and acquire infection in hospital. Crude mortality at 90 days in the intention-to-treat population was 22/74 (29.7%) in the 7-day group versus 17/83 (20.5%) in the 14-day group (risk difference 9.2, 95% confidence interval [CI] -4.8 to 23.2). Age was associated with 90-day mortality (odds ratio [OR] 1.06, 95% CI 1.02-1.09), but randomization group (7 or 14 days) was not (OR 1.47, 95% CI 0.66-3.27).ConclusionsAmong patients with P. aeruginosa bacteremia included in an international trial testing duration of antibiotic treatment, no significant difference in mortality was demonstrated between 7 vs 14 days of antibiotic therapy; however, a limited sample size precludes a conclusion of non-inferiority, benefit or harm.

academic.oup.com

Combination of Amoxicillin 3000 mg and Probenecid Versus 1500 mg Amoxicillin Monotherapy for Treating Syphilis in Patients With Human Immunodeficiency Virus: An Open-Label, Randomized, Controlled, Non...

In this open-label, randomized, controlled, non-inferiority trial, amoxicillin-based treatments showed high efficacy for treating early and late syphilis a

academic.oup.com

Volume 232 Issue Supplement_3 | The Journal of Infectious Diseases | Oxford Academic

An official journal of the Infectious Diseases Society of America. Publishes research results on microbiology, immunology, and epidemiology; pathogenesis, diagnosis, and treatment of infectious diseas...

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Infectious Diseases Pharmacotherapy Specialist - University of California San Francisco - Job Details

Job Details: The Department of Pharmaceutical Services provides a full range of services for patients cared for by the Medi

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Linezolid-related Optic Nerve Disorders: Insight from a Pharmacovigilance Analysis of the U.S. FDA Adverse Event Reporting System

AbstractObjective. Linezolid is a crucial oxazolidinone used to treat multidrug-resistant gram-positive infections; however, it is associated with optic ne

academic.oup.com

I really don’t like ChatGPT’s new memory dossier

Last month ChatGPT got a major upgrade. As far as I can tell the closest to an official announcement was this tweet from @OpenAI: Starting today [April 10th 2025], memory …

simonwillison.net

Navigating the Muddled Middle: A Case-Based Exploration of Oral β-Lactams for Systemic Gram-Negative Infections

We describe 3 common scenarios where oral β-lactams may be used for systemic gram-negative infections, and through a coupling of patient cases, we provide

academic.oup.com

Navigating the Muddled Middle: A Case-Based Exploration of Oral β-Lactams for Systemic Gram-Negative Infections

We describe 3 common scenarios where oral β-lactams may be used for systemic gram-negative infections, and through a coupling of patient cases, we provide

academic.oup.com

Mass Intelligence

From GPT-5 to nano banana: everyone is getting access to powerful AI

oneusefulthing.org

FAQ on Fall Vaccines

💡Looking for my 2025-2026 vaccine guide? Find it on Substack here. This page answers follow-up questions from readers. Can doctors still prescribe the Covid-19 vaccine "off-label" to other patients w...

forceofinfection.com