In Vitro and In Vivo Mutation Frequencies to Resistance — do they Correlate in the Long Term?

Abstract

Very unusually among antibacterial agents the 4-quinolones are rarely if ever affected by plasmid-mediated resistance and, perhaps as a consequence of this, the frequency of clinical resistance to the 4-quinolones is much less than that seen with the other major groups of antibiotics and chemotherapeutic agents (Burman 1977). Despite nalidixic acid being discovered as long ago as 1962 it is only very recently that plasmid-mediated resistance to it has been claimed to exist (Panhotra et al. 1985; Munshi et al. 1987). This contrasts sharply with the situation seen with the penicillins, cephalosporins, aminoglycosides, tetracyclines, sulphonamides, macrolides, trimethoprim and chloramphenicol, which have been plagued by plasmid-mediated resistance much earlier after their introduction and, in some cases, even before their introduction. Worse still, resistance to these antibacterials shows every sign of becoming more frequent due no doubt to the transferable nature of the resistance genes. The 4-quinolones have so far escaped completely, or very lightly, from transferable drug resistance because even the Plasmids claimed to confer nalidixic acid resistance do not confer resistance to modern 4-quinolones, although they seem to make their hosts more able to mutate to become ciprofloxacin-resistant (Munshi et al. 1987).