In vitro effects of azithromycin on Salmonella typhi: early inhibition by concentrations less than the MIC and reduction of MIC by alkaline pH and small inocula
T. Butler et al., In vitro effects of azithromycin on Salmonella typhi: early inhibition by concentrations less than the MIC and reduction of MIC by alkaline pH and small inocula, J ANTIMICRO, 47(4), 2001, pp. 455-458
To explain good clinical results of azithromycin in patients with typhoid f
ever, 10 strains of Salmonella typhi were grown in cation-adjusted Mueller-
Hinton broth. MICs of azithromycin were 4-16 mg/L. At a sub-MIC of 2 mg/L,
early inhibition of growth was shown at 2, 4 and 8 h of incubation, but at
24 and 48 h growth to turbidity occurred. At 4 mg/L, inhibition occurred up
to 8 h, after which growth towards turbidity followed. Elongated curved ba
cilli formed in broth containing 4 mg/L after 24-48 h. Adjusting the pH of
the broth with phosphate-citrate buffer to 7.5 and 8.0 caused reductions in
MICs to 0.25-0.5 mg/L. Large inocula of 10(6) cfu/mL resulted in median MI
Cs four- to six-fold greater than with inocula of 10(1)-10(3) cfu/mL. An in
oculum of 10 bacteria per mt in broth at pH 7.5 resulted in an MIC of 0.13
mg/L. Clinical benefits in patients may occur because of early inhibition b
y sub-MIC concentrations of azithromycin, and due to lower MICs at alkaline
pH and lower MICs with small inocula that may correspond to the low-grade
bacteraemia in typhoid fever.