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JAC Advance Access published online on May 12, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki163
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oupjournals.org
Received July 16, 2004
Revised February 17, 2005
Accepted April 20, 2005

Original article

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

Shingo Mizunaga 1*, Tomoko Kamiyama 1, Yoshiko Fukuda 1, Masahiro Takahata 1, and Junichi Mitsuyama 1

1 Research Laboratories, Toyama Chemical Co. Ltd, 2-4-1 Shimo-Okui, Toyama, Japan

* To whom correspondence should be addressed.
Shingo Mizunaga, E-mail: shingo_mizunaga{at}toyama-chemical.co.jp


  Abstract

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.
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