Influence of inoculum size of Staphylococcus aureus and Pseudomonas aeruginosa on in vitro activities and in vivo efficacy of fluoroquinolones and carbapenems.
OBJECTIVE
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 (10(5)-10(8) cfu/mL) had no significant effect on the MIC of any of the tested antimicrobial agents. With the standard inocula (10(6) cfu/mL) of both test strains, all the antimicrobial agents showed bactericidal activity; however, increasing the inoculum size to >10(8) 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.
Mizunaga
Shingo
S
Research Laboratories, Toyama Chemical Co. Ltd, Japan. shingo_mizunaga@toyama-chemical.co.jp
Kamiyama
Tomoko
T
Fukuda
Yoshiko
Y
Takahata
Masahiro
M
Mitsuyama
Junichi
J
D000818:Animals; D015780:Carbapenems / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D024841:Fluoroquinolones / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests / Q000379:methods*; D010078:Oxazines / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects*
D015780:Carbapenems; D024841:Fluoroquinolones; D010078:Oxazines; C078052:pazufloxacin; D002939:Ciprofloxacin