Postantibiotic effect of ceftriaxone and amikacin on Klebsiella pneumoniae ATCC 43816

Introduction and Methods: The postantibiotic effect (PAE) refers to a suppression of bacterial growth that persists after limited exposure of organisms to antimicrobial agents. The major clinical relevance of the PAE pertains to its impact on antimicrobial dose and dosing interval. There is a method-to-method variation in determination of PAE. In case of Gram negative organisms, β-lactams do not demonstrate PAE on the basis of viable count method, a conventional standard. However, as several Gram negative organisms aggregate to form a filament after exposure to β-lactams, the number of colony may not be precisely counted. To overcome this problem, we also used another indicator of assessing PAE - i.e., growth value which represents CO₂ generation from colony. In this study, PAE of ceftriaxone alone and in combination with amikacin were determined for the standard strain of K. pneumoniae using viable counting method and BACTEC blood culture system. Results: (1) Using the disk diffusion method, the checkerboard method, the time kill method and the E-test, we could not find synergistic effects with ceftriaxone and amikacin against K. pneumoniae. (2) On the basis of the viable counting method, PAE of ceftriaxone (x1 MIC, 0.03 μg/mL) was negative (-0.4 hours) and that of amikacin (x4 MIC, 4 μg/mL) was 2.7 hours. (3) Following 2-hour exposure to ciprofloxacin at various concentration, the correlation between the cell count (y) and GV (x) measured by BACTEC blood culture system was significantly high (log y=0.0514x+4, r=0.88, p<0.0001). Although recalculating the PAE of ceftriaxone using the above curve, the subsequently corrected PAE value was 0 hour. (4) The ceftriaxone-amikacin combination caused additive effect for PAE against K. pneumoniae compared with the PAE observed after ceftriaxone or amikacin alone measured by the viable counting method. Discussion: (1) Although it is evident that the viable count method underestimated the PAE of β-lactams against K. pneumoniae, PAE was absent in spite of correction by BACTEC blood culture system. (2) It may be possible the ceftriaxone does show no PAE against K. pneumoniae naturally not because of filament formation.