The inoculum effect with gram-negative bacteria in vitro and in vivo.

The in-vitro MICs and MBCs of ciprofloxacin, cefoperazone, ceftazidime, ceftriaxone, gentamicin and imipenem were measured for five strains each of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa with standard and high inocula. The MBC was raised more than the MIC at the higher inoculum for all the drugs except ciprofloxacin. However, the MBC of imipenem against P. aeruginosa was increased relatively little at the higher inoculum in contrast to the findings with other beta-lactam drugs. In a rabbit model of endophthalmitis both cefoperazone and imipenem were markedly more bactericidal against a high inoculum of K. pneumoniae than would have been predicted from the results of in-vitro time kill curve studies. We conclude that the therapeutic relevance of the inoculum effect remains to be proved.