Comparative kinetics and efficacy of amikacin administered once or twice daily in the treatment of systemic gram-negative infections

Abstract

In an open randomized study the safety, efficacy and kinetics of a twice-daily amikacin (7.5 mg/kg bd) regimen (group A) was compared with a once-daily dosage (15 mg/kg) schedule (group B). Thirty patients were enrolled in each group. They were suffering from urinary tract infections (37), respiratory tract infections (17), soft-tissue infections (3), exacerbation of chronic prostatitis (1), acute cholangitis (1) and abdominal abscess (1). Aggravating factors were present in 77% and 60% of the groups respectively. The pathogens isolated included strains of various Enterobacteriaceae (53) and Pseudomonas aeruginosa (10) In 76.7 vs 97% (P less than 0.05) the clinical result was satisfactory with pathogen eradication in 80 vs 86.7%. However, there were proportionately more patients in the 7.5 mg/kg bd regimen with respiratory tract infection (40 vs 13%) and fewer patients with urinary tract infections (40 vs 80%). Mild and transient nephrotoxicity and ototoxicity was observed in five and three patients respectively. More patients in group B had amikacin trough concentrations less than or equal to 5 mg/l and peak levels greater than 40 mg/l (P less than 0.001) as well as serum bactericidal titres greater than or equal to 1:16 (P less than 0.05) without significant serum amikacin accumulation over time. It is concluded that amikacin administered once daily is well tolerated and provides better serum bactericidal activity than the twice-daily regimen.