Effect of increased inoculum of Salmonella typhi on MIC of azithromycin and resultant growth characteristics

This study was designed to investigate the effect of an increased inoculum on the MIC of azithromycin for Salmonella typhi. Growth curves of nine strains were obtained in cation-adjusted Mueller-Hinton broth containing azithromycin at concentrations of 0-32 mg/L, and comparisons made between inoculation with large inocula, estimated as 10(7) cfu/mL, and with small inocula of c. 10(3) cfu/mL. Turbidity developed only with large inocula after 4-8 h in the presence of 8 or 16 mg/L of azithromycin, thus correlating with microscopic appearance of elongated, curved and widened bacteria. Bacteria that had survived exposure to 16 mg/L for 48 h showed low-grade resistance in comparison with those not exposed to antibiotic. Thus, the mechanism of the inoculum effect was expressed as an enlarging bacterial mass during bacteriostasis, with survival of bacterial populations with low-grade resistance of about two-fold increase in MIC.