Abstract
A penicillin (PCN) tolerant [minimal inhibitory concentration (MIC) ⩽ 0.02, minimal bactericidal concentration (MBC) = 3.10 μg/ml] group A streptococcus (GAS) was recovered from the bone aspirate of a child with osteomyelitis. The penicillin therapy with 200,000 μm/kg · day, and subsequently ampicillin 360 mg/kg · day, resulting in a serum ampicillin concentration of 74 μg/ml, failed to achieve a serum bactericidal effect > 1:2. Ninety-nine additional isolates of GAS obtained from 99 infants and children with pharyngitis were randomly selected for study. Organisms were screened for tolerance by macrobroth dilution determination at 0.05 and 1.0 μg/ml of penicillin. Twenty-two of 100 organisms had MICs = 0.05 μg/ml and MBCs = 1.0 μg/ml; further tests were performed on these organisms. Twenty of the 22 strains (20% of all GAS) grown in Mueller-Hinton broth with 2% sheep blood were tolerant to penicillin at 24 hr, with MICs ⩽ 0.02 and MBCs = 0.39 μg/ml. When retested at 48 hr the MBCs of the 20 tolerant strains had decreased: three strains by twofold, three strains by fourfold, four strains by eight-fold, one strain by 16-fold, and nine strains by 40-fold or greater. Seven strains were not tolerant after 48 hr of incubation. The detection of tolerance was media dependent; only nine strains were tolerant when grown in Todd-Hewitt broth. Tolerance to GAS was more frequent than generally suspected. The phenomenon of tolerance, and potentially delayed killing may alter prophylaxis and therapy of GAS disease and merits further investigation.
Published Version
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