Comparative study of serum bactericidal activity of cefotaxime alone or in combination with tobramycin

Abstract

The objectives of this study were to investigate the bactericidal activity in serum of cefotaxime alone or in combination with tobramycin against clinical strains and to determine the influence of tobramycin on the pharmacokinetics of cefotaxime. The The bactericidal activity test in serum has been recommended to monitor antimicrobial therapy in patients with serious infections. It is generally agreed upon that a bactericidal activity in serum of >1:8 correlates with the clinical effectiveness of antibiotics (3, 5a, 11), but in a recent review Wolfson and Swartz (12) have concluded that convincing proof of the utility of the bactericidal activity test in serum in the management of infective endocarditis is lacking. Lagast and co-workers studied the bactericidal activity in serum of cefotaxime alone and in association with tobramycin against clinical strains of Pseudomonas aeruginosa and Staphylococcus aureus (4). They observed increased activity of cefotaxime against both strains when used in combination with tobramycin. In this study we extend the investigation of the bactericidal activity in serum of cefotaxime alone or in combination with tobramycin to clinical isolates of Klebsiella oxytoca, Enterobacter aerogenes, Serratia marcescens, Pseudomonas cepacia, and Listeria monocytogenes.(This paper was presented at the 14th International Congress of Chemotherapy, Kyoto, Japan, in June 1985.) Twelve healthy subjects (six females, six males) between the ages of 20 and 24 years (mean, 21.7 years) gave written informed consent to participate in the study. The protocol was approved by the Centre Hospitalier de l'Universite Laval Human Research Review and PharmacologyTherapeutic Committees. The mean weight of the subjects was 64.4 kg (range, 57.0 to 84.5 kg). Based on creatinine and blood urea nitrogen values in serum, these young volunteers had normal renal function. The subjects received 1 g of cefotaxime and, 1 week later, 1 g of cefotaxime with 80 mg of tobramycin. Both antibiotics were diluted in 50 ml of 0.9% sodium chloride and given intravenously over 5 min. When both drugs were given simultaneously, they were never mixed in vitro but were administered at separate venipuncture sites. Tobramycin inactivation by cefotaxime is minimal, even in vitro (2).Blood samples were drawn from a catheter (contralateral to the one used for cefotaxime infusion) by the following * Corresponding author. sequence: before drug was administered and at 10, 30, 45, and 60 min and 1.5, 2, 2.5, 3,4,6,8,10, and 24 h after antibiotic administration. Urine was collected on both study days immediately before injection(s) and at intervals between 0 and 2, 2 and 4, 4 and 8, and 8 and 24 h after antibiotic(s) administration. Each urine sample was stored at -20°C until it was assayed.Serum and urine samples were analyzed in triplicate for cefotaxime by the high-pressure liquid chromatographic procedure described previously (5); however, the following modifications were made. The serum (0.5 ml) sample preparation involved protein precipita...