IN-VITRO DEVELOPMENT OF RESISTANCE OF STREPTOCOCCUS-PNEUMONIAE TO BETA-LACTAM ANTIBIOTICS

In recent years, increasing numbers of Streptococcus pneumoniae strain s displaying relative resistance to penicillin have been reported. Epi demiological studies have shown a correlation between aminopenicillin administration and resistance. We investigated the development of resi stance in six strains (four sensitive and two intermediate-resistant t o penicillin) by serial daily passages in subinhibitory concentrations of amoxicillin (AMX), amoxicillin + clavulanic acid (AMC), imipenem ( IMP), cefixine (CFM), cefatrizine (CTZ), cefadroxil (CDX), and cefurox ime (CXM). MICs were determined by the macrodilution method in brain-h eart broth for each daily passage. The number of daily passages needed to increase the MIC by a factor of 8 was achieved with AMX, AMC, and CFM for most of the strains after a mean of 24, 20, and 11 passages, r espectively, and for one-third of the strains, with CDX, IMP, and CTZ after 11, 11, and 21 passages, respectively. Decreased susceptibility to breakpoints for intermediate-resistant S. pneumoniae populations wa s noted for all strains with CFM, AMX, and AMC after a mean of 10, 18, and 21 serial passages, respectively, and for four of five strains wi th IMP and CTZ after 12 and 13 passages. CTZ-, CDX-, and CXM-passaged variants had increased MIC values only for cephalosporins, while AMX-, AMC-, IMP-, and CFM-passaged variants exhibited increased MICs to all antibiotics tested. These in vitro data appear to be in agreement wit h epidemiological studies and warrant further exploration with respect to possible clinical implications.