Cefuroxime pharmacokinetics and pharmacodynamics for intravenous dosage regimens with 750 mg or 1500 mg doses in healthy young volunteers

Abstract

Introduction. Cefuroxime is an important antibiotic to treat several serious infections. Rapid elimination through the kidneys and the variation in MICs of various susceptible pathogens such as Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus pneumoniae give rise to dosing issues, especially in otherwise healthy patients. Aim. To investigate the probability of target attainment (PTA) for obtaining the optimal dosage regimens for cefuroxime in healthy young people. Methodology. Two weeks apart 750 and 1500 mg cefuroxime were administered as an intravenous bolus to 20 healthy volunteers (mean age: 27 years). Population modelling and simulation studies were done based on the obtained data for cefuroxime plasma concentration. Results. With a target value of time above MIC (T >MIC) greater than 50 % the simulations revealed that a PTA of >99 % is obtained for S. pneumoniae with a dosage regimen of 750 mg q12h. For E. coli and K. pneumoniae the PTA was <90 % even with the highest, simulated dosage of 1500 mg q6h. For S. aureus a dosage of 1500 mg q8h gave a PTA above 97 %. Conclusions. S. pneumoniae is most likely treatable with a two-daily dose of 750 mg cefuroxime. Not treatable are K. pneumoniae and E. coli . For S. aureus 1500 mg q8h constitutes an optimal dosing schedule.

The Use of Pregnancy Physiologically Based Pharmacokinetic Modeling for Renally Cleared Drugs

“…A second, very limited data set, for patients in the third trimester and with samples at 1 and 8 hours 18 shows that the 8‐hour sample is underpredicted by the model. Of note, the reported 8‐hour sample seems unexpectedly higher than other studies 16,17 . Unfortunately, there are no distinct data for the different gestational trimesters to allow changes during pregnancy to be fully explored.…”

“…The model adequately describes the observed data in nonpregnant subjects following dosing at 750 and 1500 mg using data from the publications of Philipson and Stiernstedt 16 and Thønnings et al 17 (Figure 2c). PBPK simulation in pregnancy appears to adequately capture observed data from Philipson and Stiernstedt, which included subjects at delivery and a range of gestational weeks from 11 to 35 weeks (Figure 2d).…”

“…Of note, the reported 8-hour sample seems unexpectedly higher than other studies. 16,17 Unfortunately, there are no distinct data for the different gestational trimesters to allow changes during pregnancy to be fully explored.…”

Community-acquired pneumonia: selection of empirical treatment and sequential therapy. SARS-CoV-2 implications

“…Cefixima, posee escasa actividad frente a microorganismos grampositivos, motivo por el cual no debe ser utilizada en el tratamiento empírico de procesos como la NAC o la exacerbación de la EPOC, en los que el neumococo es uno de los agentes etiológicos principales. En cuanto a cefuroxima, se plantea el problema de su limitado perfil PK/PD en la infección pulmonar por S. pneumoniae que conlleva problemas de difusión al foco pulmonar [37]. De hecho, ninguna de estas dos cefalosporinas tiene indicación en su ficha técnica para el tratamiento de la NAC en adultos.…”