Reply to: Efficacy and pharmacodynamics of simulated human-like treatment with levofloxacin on experimental pneumonia induced with penicillin-resistant pneumococci with various susceptibilities to fluoroquinolones
Abstract
Sir, Croisier et al.1 described an experimental model of pneumococcal pneumonia in the rabbit caused by penicillin-resistant Streptococcus pneumoniae with different susceptibilities to fluoroquinolones. In this model, levofloxacin, at a dose that simulated human treatment with 500 mg twice a day, was effective against strains with levofloxacin MIC < 1.5 mg/L, but ineffective against strains with MIC ≥ 2 mg/L (strains with parC and parC+gyrA mutations). This interesting and elaborate study raises several issues that may cast doubt on the relevance of its findings to the clinical situation: the animal model employed (rabbit) has not been used traditionally, or validated, for the study of experimental pneumococcal pneumonia, except by the same group.2 Indeed, the high bacterial inoculum used (1010 cfu/mL), whereas certainly facilitating the emergence of resistant mutants, is far higher than inocula used for other experimental infection models of S. pneumoniae (106–108 cfu/mL)3–5 and raises the possibility of a toxic effect by the bacteria on the host.
How strong is the evidence?
Evidence Hub reads this as a editorial / letter, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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