title: 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.
authors.affiliation: 1st Department of Propaedeutic Medicine, Athens University School of Medicine, Laïko General Hospital, Greece.
authors.forename: H
authors.initials: H
authors.lastname: Giamarellou
authors.forename: K
authors.initials: K
authors.lastname: Yiallouros
authors.forename: G
authors.initials: G
authors.lastname: Petrikkos
authors.forename: E
authors.initials: E
authors.lastname: Moschovakis
authors.forename: E
authors.initials: E
authors.lastname: Vavouraki
authors.forename: D
authors.initials: D
authors.lastname: Voutsinas
authors.forename: P
authors.initials: P
authors.lastname: Sfikakis
mesh_terms: D000328:Adult; D000368:Aged; D000583:Amikacin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001424:Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D004755:Enterobacteriaceae / Q000187:drug effects; D005260:Female; D006090:Gram-Negative Bacteria; D006309:Hearing / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000378:metabolism; D015610:Serum Bactericidal Test; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000378:metabolism
chemical_list: D000583:Amikacin