Serum Bactericidal Activity of Ceftazidime Increased by Netilmicin

Abstract

Cephalosporins are often used in combination with aminoglycoside antibiotics in the treatment of gram-negative infections. Although ceftazidime possesses activity against gram-negative bacteria, especially against Pseudomonas, combined use with aminoglycosides is useful. In this study, 12 healthy volunteers (6 men, 6 women; mean age 21.5 yr) received a single dose of ceftazidime 1 g iv and one week later ceftazidime 1 g iv with netilmicin 100 mg iv. Both antibiotics were infused over five minutes. Concentrations of ceftazidime were determined by high performance liquid chromatography. Serum bactericidal activity (SBA) was evaluated against seven microorganisms isolated from clinical specimens. The mean peak serum level of ceftazidime was 113.4 μg/ml. At eight hours, we observed a concentration of 2.6 μg/ml. The total clearance was 126 ml/min, while the renal clearance was 100 ml/min. Ceftazidime exhibited a half-life of 1.9 hours. Up to ten hours, the SBA of ceftazidime against Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, and Salmonella typhi was > 1:8 in more than 90 percent of samples. At one hour, ceftazidime exhibited a SBA of 1:4 for Staphylococcus aureus, and 1:16 for Pseudomonas aeruginosa. With the addition of netilmicin, median SBA against Staph. aureus and P. aeruginosa were 1:32 and 1:64, respectively, at one hour. Netilmicin enhanced the SBA of ceftazidime. The combination was not effective against Streptococcus faecalis.