Clinical implications of differences in the pharmacokinetic and pharmacodynamic profiles of ceftriaxone and cefotaxime: A narrative review

Third-generation cephalosporins have been widely used in clinical practice for many years. Among them, cefotaxime and ceftriaxone are the most commonly administered agents. Despite their nearly identical spectra of antibacterial activity, these antibiotics differ substantially in their pharmacokinetic and pharmacodynamic profiles. Such dissimilarities may influence the course and outcome of antimicrobial therapy. Furthermore, several additional factors can affect the antimicrobial efficacy of these agents. Cefotaxime and ceftriaxone exhibit markedly different degrees of albumin binding - approx. 25-40% and 95%, respectively. Hypoalbuminemia increases the proportion of the free, pharmacologically active fraction of the drug in the bloodstream; however, it may also lead to prolonged exposure to sub-MIC concentrations. This situation not only reduces the likelihood of therapeutic success but also increases the risk of selecting resistant bacterial strains. Although cefotaxime and ceftriaxone share a similar antibacterial spectrum, antibiotic selection should always be individualized according to the patient's clinical status and treatment context. A direct comparison of their clinical efficacy undoubtedly warrants further investigation, as suggested by the clear differences in their pharmacokinetic profiles.