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This minireview is the second of a two-part series which summarizes the major points of a symposium and roundtable discussion held at the 25th Interscience Conference on Antimicrobial Agents and Chemotherapy in Minneapolis in 1985. Part one considered phenotypic tolerance, tolerance in animal models, and controversies as to the definition and mechanisms of genotypic tolerance (60), and this part focuses on the techniques used to detect genotypic antibiotic tolerance in clinical isolates of bacteria. Antibiotic tolerance, as first described by Tomasz et al. (57) in autolysin-deficient mutants of Streptococcus pneumoniae, has been the subject of many publications dealing with its detection, its occurrence among clinical isolates of various genera and species, and its therapeutic significance. Despite this activity, no clear consensus has emerged as to the incidence and medical implications of tolerance, and the greatest discrepancies in results have been in studies on Staphylococcus aureus (5, 7, 11, 13, 18, 19, 25, 39, 44, 49, 51-56, 62, 63). Likewise, studies on the significance of S. aureus tolerance in experimental infections have yielded variable results (17, 19, 20, 59). Concern with the topic was stimulated by observations of the poor reproducibility of measurements of antibiotic MBCs for this organism and thus of the impact of these observations on the detection and occurrence of tolerance as determined in clinical laboratornes.

Problems in in vitro determination of antibiotic tolerance in clinical isolates