Journal Article

Influence of inoculum size of <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> on <i>in vitro</i> activities and <i>in vivo</i> efficacy of fluoroquinolones and carbapenems

Shingo Mizunaga, Tomoko Kamiyama, Yoshiko Fukuda, Masahiro Takahata and Junichi Mitsuyama

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 56, issue 1, pages 91-96
Published in print July 2005 | ISSN: 0305-7453
Published online May 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki163
Influence of inoculum size of Staphylococcus aureus and Pseudomonas aeruginosa on in vitro activities and in vivo efficacy of fluoroquinolones and carbapenems

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Objectives: We investigated the effect of inoculum size on MIC, bactericidal activity and the post-antibiotic effect (PAE) of carbapenems (imipenem, panipenem and meropenem) and injectable quinolones (pazufloxacin and ciprofloxacin) against Staphylococcus aureus and Pseudomonas aeruginosa, and also the relationship between in vivo systemic infection by changing the inoculum size injected in mice.

Results: Increasing the bacterial inoculum (105–108 cfu/mL) had no significant effect on the MIC of any of the tested antimicrobial agents. With the standard inocula (106 cfu/mL) of both test strains, all the antimicrobial agents showed bactericidal activity; however, increasing the inoculum size to >108 cfu/mL resulted in a reduction in bactericidal activity of all the antimicrobial agents against S. aureus Smith. In contrast, increasing the inoculum size of P. aeruginosa exerted only a minimal influence on the bactericidal activity of fluoroquinolones, but resulted in a reduction in the bactericidal activity of carbapenems. With the standard inoculum size of S. aureus Smith, pre-incubation with fluoroquinolones and carbapenems, except for meropenem, was sufficient to produce PAEs. When the inoculum was increased, the duration of the PAEs of these antimicrobial agents was reduced; however, those of fluoroquinolones were longer than carbapenems. Inoculum size had a greater influence on the in vivo efficacy of carbapenems than that of fluoroquinolones.

Conclusions: Our results suggest that decreased bactericidal activity, or the in vitro PAE of carbapenems and fluoroquinolones, is related to the reduced in vivo protective effect against infection caused by high inoculum with S. aureus or P. aeruginosa.

Keywords: bactericidal activity; post-antibiotic effect; protective effect

Journal Article.  3952 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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