Increasing resistance to multiple antimicrobial agents including penicillins is a current problem with Streptococcus pneumoniae. Seven cases of severe infection due to penicillin G-resistant pneumococci were seen in two teaching hospitals in Paris (France) during the first half of 1991; six of the strains were recovered from pulmonary secretions (protected brush specimens) and one from cerebrospinal fluid (CSF). The bacteriostatic activity and killing curves of eight antimicrobials against these seven strains were studied. Antimicrobial agents tested included penicillin G (PEN), amoxicillin (AMX), cefotaxime (CTX), imipenem (IPM), rifampin (RIF), vancomycin (VAN), fosfomycin (FOS), and erythromycin (ERO). MICs were determined using the agar dilution method. Killing curves were obtained using a liquid medium inoculated with 10(5) to 10(6) CFU/ml and subjected to continuous agitation; survivors were counted at baseline and after 1, 3 and 5 hours incubation. MICs of each antimicrobial (mg/l) for the seven strains were in the following ranges: PEN: 0.5-2, AMX: 0.5-2; CTX: 0.125-1; IPM: 0.03-0.25; RIF: 0.12-0.25; VAN: 0.25-1; FOS: 16; ERO: 0.06 greater than 4. Overall, bactericidal activity was greatest with vancomycin, followed by imipenem, then amoxicillin. The cefotaxime-fosfomycin combination proved synergistic and exhibited bactericidal activity (2MIC + 2MIC) for three of the seven strains. This study demonstrated the value of the cefotaxime-fosfomycin combination. Both these antimicrobials seem appropriate for the treatment of meningitis caused by penicillin G-resistant pneumococci provided their dosage is adjusted to achieve adequate drug levels in the cerebrospinal fluid.