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[Piperacillin-amikacin combinations: killing curves]
1Laboratoire de Bactériologie-Virologie, Faculté de Médecine, Clermont-Ferrand, France.
Abstract:
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)
Insights
The combination of piperacillin and amikacin demonstrated significant bactericidal activity against common Gram-negative bacteria. A lower dose combination proved effective in preventing bacterial regrowth, offering a promising therapeutic strategy.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Piperacillin and amikacin are critical antibiotics for treating Gram-negative bacterial infections.
- Understanding their combined bactericidal activity is essential for optimizing treatment regimens.
- Evaluating activity against common clinical isolates like E. coli, K. pneumoniae, E. cloacae, and P. aeruginosa is crucial.
Purpose of the Study:
- To evaluate the time-dependent bactericidal activity of piperacillin and amikacin, alone and in combination.
- To assess the efficacy of different drug concentration combinations against various Gram-negative bacterial phenotypes.
- To determine if combinations can prevent bacterial regrowth observed with monotherapy.
Main Methods:
- Killing curves technique was employed to assess bactericidal activity over time.
- Twenty-three clinical isolates of E. coli, K. pneumoniae, E. cloacae, and P. aeruginosa were tested.
- Minimal inhibitory concentrations (MICs) for piperacillin ranged from 0.25 to 64 mg/L, and for amikacin from 1 to 8 mg/L.
Main Results:
- Piperacillin (16 mg/L) combined with amikacin (8 mg/L) showed bactericidal effects against most strains (21/23) and prevented regrowth.
- A low-dose combination of piperacillin (2 mg/L) and amikacin (4 mg/L) achieved bactericidal activity without regrowth for 9 strains.
- High-dose combinations were required for bactericidal activity against Ticarcillin-resistant P. aeruginosa, which were bacteriostatic individually.
Conclusions:
- Piperacillin and amikacin combinations can enhance bactericidal activity and prevent bacterial regrowth.
- Specific dose combinations, including lower ones, show significant potential against susceptible Gram-negative bacteria.
- Combined therapy is essential for overcoming resistance, particularly in challenging pathogens like P. aeruginosa.