It has been long recognized that the effect of antimicrobial drugs upon bacteria in tissues does not always parallel their effect upon the same bacteria in broth. One difference may be a slower rate of bactericidal action in tissues.1 Another may be a more prolonged survival in certain tissue sites of "persisters," those bacteria described by Bigger,2 which remain viable in antibioticcontaining milieux after most of their siblings have been killed, but which retain their in vitro sensitivity to the same antibiotic. "Persisters" are probably responsible for relapses in such infections as bacterial endocarditis, and others. They may also bear some biological relation to those pathogens whose presence constitutes the carrier state in patients successfully cured of clinical infections.Most investigations of antimicrobial action have dealt with the events of the early hours of drug-bacteria contact. Also, attention has more often been focused on the point at
HAMBURGER M, CARLETON J. Bactericidal Action of Penicillin and Tetracycline Against Gram-Positive Cocci: In Broth and in Blood Clots, with a Few Observations Concerning "Persisters". AMA Arch Intern Med. 1960;105(3):372–382. doi:10.1001/archinte.1960.00270150026004
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