Serum bactericidal activity and postantibiotic effect in serum of patients with urinary tract infection receiving high-dose amikacin

Abstract

Ten patients received a 30-min infusion of amikacin (30 mg/kg) on day 1 and 15 mg/kg on day 2. Mean serum creatinine was 1.1 +/- 0.3 (standard deviation) mg/dl before and 1.0 +/- 0.3 mg/dl 3 days after the second infusion. Mean serum amikacin concentrations before, at the end of infusion, and 1, 6, 12, and 24 h after 30 and 15 mg/kg were 0, 157, 79, 31, 16, 5, 5, 85, 51, 19, 12, and 5 mg/liter, respectively. Five strains each of Staphylococcus aureus, Staphylococcus epidermidis susceptible and resistant to oxacillin, Streptococcus (Enterococcus) faecalis, corynebacterium sp. strain JK, Listeria monocytogenes, Mycobacterium fortuitum (three strains), Klebsiella pneumoniae, Serratia marcescens, Acinetobacter calcoaceticus, and Pseudomonas aeruginosa were tested. Serum bactericidal activities (SBAs) were greater than or equal to 1:8 in greater than or equal to 80% of the sera 1 and 6 h after 30 mg/kg and in greater than or equal to 60% of the sera 1 and 6 h after 15 mg/kg against Staphylococcus aureus and Staphylococcus epidermidis susceptible to oxacillin, A. calcoaceticus, and K. pneumoniae. L. monocytogenes, Serratia marcescens, and P. aeruginosa had lower SBAs. Very low or no activity was observed against oxacillin-resistant staphylococci and Streptococcus faecalis. The study of the killing rate in serum confirmed these results. Postantibiotic effect was studied by incubating a strain from each species in serum samples obtained 1 and 6 h after both regimens for 0.5, 1, or 2 h. The duration of postantibiotic effect depended on the duration of contact and the concentration of amikacin for the following organisms: oxacillin-susceptible staphylococci, L. monocytogenes, P. aeruginosa, A. calcoaceticus, K. pneumoniae, and Serratia marcescens. M. fortuitum was killed after 30 min of contact. No postantibiotic effect was observed with Streptococcus faecalis, Corynebacterium sp. strain JK, or oxacillin-resistant staphylococci. Amikacin at 30 mg/kg provided high levels and SBAs against susceptible pathogens. Prolonged postantibiotic effects were observed. No signs of nephrotoxicity occurred.