[Bactericidal activity of ceftriaxone, amikacin and their combination]

Third-generation cephalosporins such as ceftriaxone are often used alone; however, with Enterobacter (ENT), Citrobacter (CIT), Serratia (SER) and Morganella (MOR), a combination of two drugs is advisable. Aminoglycoside-beta-lactam combinations are often synergistic. However, results are not consistent with the new cephalosporins. We determined the killing kinetics of ceftriaxone (C) alone, amikacin (A) alone and both drugs in combination (AC). The antibiotics were tested in the following concentrations: 0.25, 1, 4 and 16 X MIC for C, 0.5, 2 and 8 X MIC for A, and, for AC, 0.5-0.25 X MIC (1), 0.5-1 X MIC (2) and 2-0.25 X MIC (3). Surviving bacteria were enumerated at 0 h, 1 h, 3 h, 5 h and 24 hours. Amikacin showed a strong, dose-dependent bactericidal activity. Maximal activity of ceftriaxone was observed at 1 or 4 X MIC. Time of contact had a significant influence, indicating a time-dependent activity. In 5 hours, the killing effect of the AC combination rarely exceeded that of each antibiotic alone. Higher killing rates were observed with AC and; the killing effect of AC (3) was similar to amikacin's maximal killing effect. In 24 hours, the AC (3) combination was clearly synergistic with inhibition of late regrowths.