Cefepime pharmacokinetics in critically ill children and young adults undergoing continuous kidney replacement therapy.

OBJECTIVES: Cefepime is an antibiotic commonly used to treat sepsis and is cleared by renal excretion. Cefepime dosing requires adjustment in patients with decreased kidney function and in those receiving continuous kidney replacement therapy (CKRT). We aimed to characterize cefepime PK in a diverse cohort of critically ill paediatric patients on CKRT. METHODS: Patients were identified from an ongoing pharmacokinetic/pharmacodynamic (PK/PD) study of beta-lactam antibiotics, and were included if they had received at least two cefepime doses in the ICU and were on CKRT for at least 24 h. PK parameters were estimated using MwPharm++ with Bayesian estimation and a paediatric population PK model. Target attainment was assessed as time of free cefepime concentrations above minimum inhibitory concentration (fT > 1× or 4 × MIC). RESULTS: Seven patients were included in the study (ages 2 to 20 years). CKRT indications included liver failure (n = 1), renal failure (n = 4) and fluid overload (n = 2). Total effluent flow rates ranged from 1833 to 3115 (mean 2603) mL/1.73 m2/h, while clearance was 2.11-3.70 (mean 3.0) L/h/70 kg. Effluent flows were lower, but clearance and fT > MIC were similar to paediatric data published previously. Using Pseudomonas aeruginosa MIC breakpoints, all patients had 100% of dosing interval above MIC, but only one had 100% of dosing interval above 4× MIC. CONCLUSIONS: Since most patients failed to attain stringent targets of 100% fT > 4×  MIC, model-informed precision dosing may benefit such patients.

Rectal Douching Among Men Who Have Sex with Men in Paris: Implications for HIV/STI Risk Behaviors and Rectal Microbicide Development.

Rectal douching is a common but potentially risky practice among MSM; MSM who douche may be ideal candidates for rectal microbicides as HIV prevention. Herein we explored rectal douching and its association with condomless receptive anal intercourse (CRAI), group sex, rates of HIV and other STIs, and likelihood to use rectal microbicide gels. We recruited a sample of 580 MSM from a geosocial-networking smartphone application in Paris, France in 2016. Regression models estimated adjusted risk ratios (aRRs) for associations between rectal douche use and (1) engagement in CRAI, (2) group sex, (3) self-reported HIV and STI diagnoses, and (4) likelihood to use rectal microbicide gels for HIV prevention. 54.3% of respondents used a rectal douche or enema in the preceding 3 months. Douching was significantly associated with CRAI (aRR: 1.77), participation in group sex (aRR: 1.42), HIV infection (aRR: 3.40), STI diagnosis (aRR: 1.73), and likelihood to use rectal microbicide gels (aRR: 1.78). Rectal douching is common among MSM, particularly those who practice CRAI, and rectal microbicide gels may be an acceptable mode of HIV prevention for MSM who use rectal douches.