What is it about?
Methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections are usually treated with cefazolin or anti-staphylococcal penicillins. Ceftriaxone is attractive because it is given once a day, but a recent study found it was associated with more treatment failures. In this letter we point out that in that study ceftriaxone was mostly given at the standard dose of 2 g once daily. However, S. aureus needs higher concentrations of ceftriaxone than other bacteria, and the European committee EUCAST recommends only high doses (2 g twice daily or 4 g once daily) for staphylococcal infections. Laboratory and modelling studies show that standard doses often fail to kill MSSA, while high doses achieve bactericidal activity. The comparison was therefore between drugs at high doses and ceftriaxone at a standard dose.
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Why is it important?
Concluding that ceftriaxone is inferior could lead clinicians to abandon a practical, once-daily option, particularly useful for outpatient therapy. Our letter argues that the real issue may be the dose, and calls for clinical studies testing high-dose ceftriaxone in MSSA bacteremia before drawing conclusions.
Perspectives
Pharmacokinetics and pharmacodynamics are often the hidden variable behind apparently disappointing clinical results. With Milo Gatti and Luigi Principe, I wanted to stress that a drug cannot be judged fairly if it is not given at the right dose. Dosing matters as much as the choice of molecule.
Professor Stefano Di Bella
Universita degli Studi di Trieste
Read the Original
This page is a summary of: Ceftriaxone for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia: a matter of dosages?, European Journal of Clinical Microbiology & Infectious Diseases, April 2023, Springer Science + Business Media,
DOI: 10.1007/s10096-023-04612-x.
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