Efficacy, tolerance, and pharmacokinetics of once daily tobramycin for pseudomonas exacerbations in cystic fibrosis

Abstract

Objective-To compare once daily with thrice daily tobramycin for treatment of Pseudomonas aeruginosa infection in patients with cystic fibrosis. Design-22 patients with cystic fibrosis, mean (SD) age 11 (3.4) years (range 5.6-19.3), with pulmonary pseudomonas exacerbations were randomly assigned to receive a 14 day course of tobramycin (15 mg/kg/day) either in three infusions (group A) (n = 10) or a single daily infusion (group B) (n = 12), combined with ceftazidime (200 mg/kg/day as three intravenous injections). EYcacy was assessed by comparison of pulmonary, nutritional, and inflammatory indices on days 1 and 14. Cochlear and renal tolerance were assessed on days 1 and 14. Tobramycin concentration was measured in serum and sputum 1, 2, 3, 4, 8, and 24 hours after the start of the infusion. Analysis was by non-parametric Wilcoxon test. Results-Variables improving (p < 0.05) in both groups A and B were, respectively: weight/height (+4% and +3.1%), plasma prealbumin (+66 and +63 mg/l), forced vital capacity (FVC) (+14% and +11%), forced expiratory volume in one second (+15% and +14%), and forced expiratory flow between 25% and 75% of FVC (+13% and +21%). Improvement was not significantly diVerent between groups. Renal and cochlear indices remained within the normal range. Serum peak concentration of tobramycin on day 1 was 13.2 (7.1) mg/l in group A and 42.5 (11.2) mg/l in group B (p < 0.001); serum trough was 1.1 (0.8) mg/l in group A and 0.3 (0.2) mg/l in group B (p < 0.01). Tobramycin concentrations in sputum were two to three times higher in group B than group A. Conclusions-Once daily tobramycin combined with three injections of ceftazidime is safe and eVective for the treatment of pseudomonas exacerbations in cystic fibrosis patients. (Arch Dis Child 1998;78:536-539)

Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus

“…Once daily dosing of amikacin and tobramycin achieves higher airway concentrations than multiple daily dosing [68]. The general applicability of once daily dosing is, however, pending.…”

“…Indeed, 12 hourly high peak aminoglycoside dosing has been shown to be less toxic and equally efficacious as 8 hourly dosing [103]. Similarly, a study comparing once daily with thrice daily intravenous tobramycin suggested that once daily tobramycin combined with three injections of ceftazidime is safe and effective in CF [68]. To fully answer the question on efficacy and toxicity in this context, a multicentre study is currently being carried out in the UK.…”

Clinical Issues Surrounding Once‐Daily Aminoglycoside Dosing in Children

“…6,11,[44][45][46][47][48][49][50][51][52][53][54][55][56] This regimen also was investigated in neonates up to 1 month of age but is not discussed here due to the decreased renal function in that patient population. Infectious processes included neutropenic fever, suspected or confirmed gramnegative infections, cystic fibrosis, and suspected or confirmed surgical infections.…”

A Survey of Extended-Interval Aminoglycoside Dosing Practices in United States Adult Cystic Fibrosis Programs

“…8 In light of the emergence of safety and efficacy data in the CF population, the Cystic Fibrosis Foundation deemed once-daily aminoglycoside dosing as acceptable for Pseudomonas aeruginosa (grade C recommendation) in its September 2009 pulmonary exacerbation guidelines. [9][10][11][12][13][14][15][16][17][18] A 2009 survey of United States pediatric CF centers and affiliate programs distributed after the publication of these guidelines reported the use of EID (with once-daily or twice-daily dosing) in the pediatric CF population to be 94%, a significant increase from previous reports. 19 While empiric evidence suggests the use of EID of aminoglycosides to be increasingly common in the United States CF population, the prevalence of EID use across United States adult CF centers as well as the dosing and monitoring practices associated with this regimen following publication of the CF pulmonary exacerbation guidelines remain to be elicited.…”

“…This likely reflects the availability of well-designed safety and efficacy studies and meta-analyses evaluating tobramycin EID in this population, and the lack of published research studies assessing the use of gentamicin and amikacin EID in those with CF. 10,11,[13][14][15][16][17][18] As in the pediatric CF population, empiric dosing of tobramycin was most commonly prescribed at 10 mg/kg/d. 19 This practice is consistent with the dose used in a large, randomized, controlled, noninferiority study published in 2005.…”