[Piperacillin-amikacin combinations: killing curves].

Bactericidal activity as a function of time of piperacillin (PIP) and amikacin (AKN) alone and in combination was evaluated by killing curves technique on 23 clinical isolates: E. coli (6), K. pneumoniae (5), E. cloacae (6) and P. aeruginosa (6), for which the minimal inhibitory concentrations ranges of piperacillin were 0.25 to 64 mg/l and of amikacin 1 to 8 mg/l. For each species, the strains were chosen according to the most frequent phenotypes: beta-lactams susceptible, penicillinase (Pase), cephalosporinase (Case) and Pase + Case producers. Killing curves were carried out with the following concentrations (mg/l): piperacillin (2, 16, 64); amikacin (4, 8, 16); piperacillin (2) + amikacin (4); piperacillin (16) + amikacin (8); piperacillin (64) + amikacin (16). Antibiotic concentrations corresponded to pharmacokinetics and/or to critical values of piperacillin and amikacin. Bactericidal activity was defined as a 4 log 10 decrease in CFU/ml between 2 and 24 hours. When piperacillin (64) was combined with amikacin (16), the bactericidal effects were nearly the same as those with amikacin alone. But piperacillin (16) + amikacin (8) combination had bactericidal effect for the majority of strains (21/23) and it prevented for some of them the bacterial regrowth observed with amikacin alone at the same concentration. A bactericidal activity without regrowth (until the 24th hour) was obtained for 9 strains; 2 susceptible E. coli, 3 K. pneumoniae (chromosomal Pase producer) and 4 cefotaxime susceptible E. cloacae, with low dose combination piperacillin (2) + amikacin (4). Finally, only combinations piperacillin (64) + amikacin (16) or piperacillin (16) + amikacin (8) had bactericidal activity on 2 Ticarcillin-resistant P. aeruginosa, the two antibiotics being separatedly bacteriostatic.(ABSTRACT TRUNCATED AT 250 WORDS)