CHLORAMPHENICOL-FASTNESS: DEVELOPMENT IN VIVO AND EXPERIMENTAL PRODUCTION IN VITRO1

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Abstract
Bacterial resistance to chloramphenicol developed during treatment with this drug in 9 of 33 Gram-negative organisms isolated from the urine of 24 patients with chronic pyelonephritis. Fastness appeared in single or successive 2- to 8-fold steps during the 1st wk. of therapy. In most instances it was associated with failure of treatment. Small nos. of bacterial variants exhibiting low degrees of fastness to chloramphenicol were demonstrated in a susceptible strain of Klebsiella pneumoniae. These variants had properties that were common to mutants and gave rise to other variants with higher degrees of drug fastness than the parent organism. The clinical and laboratory observations suggest that chloramphenicol-fast strains are produced by a process of drug selection and successive mutation of rare drug-fast variants that exist in otherwise susceptible spp. of bacteria.