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.

Amikacin levels in bronchial secretions of 10 pneumonia patients with respiratory support treated once daily versus twice daily

“…Regarding P. aeruginosa and Enterobacter cloacae, Garraffo et al demonstrated that the length of time for which amikacin levels were main- on May 12, 2018 by guest http://aac.asm.org/ tained above the MICs was an important parameter for bactericidal activity. In bronchial secretions from patients administered amikacin once daily, amikacin levels were above 8 mg/ liter for more than 12 h. Several clinical studies, some including critically ill patients, have shown that once-daily amikacin treatment can be as effective as the usual regimen (3,11,16). In a population of 45 patients with gram-negative bronchopneumonias, once-daily amikacin treatment could achieve a high clinical success rate, above 70%; moreover, Acinetobacter spp.…”

Postantibiotic Effect, and Postantibiotic Effect of Subinhibitory Concentrations, of Sparfloxacin on Gram-Negative Bacteria

“…In addition, pharmacodynamic pa rameters such as concentration-dependent killing, inoculum-dependent killing, PAEs and PA SMEs have usually not been taken into consideration when dose and dose inter vals are determined for a new drug. The con centration-dependent killing and the long PAE of aminoglycosides have lately, however, led to a suggestion of once-daily dosage of these drugs instead of more frequently [10][11][12][13][14][15][16][17][18][19][20][21][22].…”

Once daily dosing of aminoglycoside: one step forward

“…In patients treated with netilmicin, the once-daily regimen delayed the occurrence of nephrotoxicity in comparison with multiple daily dosing (ter Braak et al, 1990). Of the five studies dealing with more than 700 paediatric and adult patients, using the conventional regimen as control, less nephrotoxicity was observed with the once-daily dosing regimen in one study (P. E. Marik, personal communication), a second study supported the same trend (using phospholipiduria as the criterion; Tulkens, 1991), while the three other studies failed to indicate a significant difference (Giamarellou et al, 1991;Mailer et al, 1991;S. Lauwers, personal communication).…”

“…These patients had various infectious conditions mainly caused by Gram-negative bacilli, and were most often treated with amikacin plus a /Mactam. One study favoured once daily dosing (Giamarellou et al, 1991), while the others indicated similar efficacy of the two regimens Tulkens, 1991;S. Lauwers, personal communication).…”