Once versus three-times daily regimens of tobramycin treatment for pulmonary exacerbations of cystic fibrosis?the TOPIC study: a randomised controlled trial

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

“…A tobramycin peak serum concentration of 25-30 mg/L and a trough value of Ͻ 1 mg/L were the most frequent targets. These goals were similar to those levels achieved in the Smyth et al 14 study, although an extrapolated trough value of Յ 0.1 mg/L, used by approximately 25% of programs, may actually be a more appropriate trough target as it better reflects the mean trough value of 0.1 mg/L reported by Smyth et al 14 Furthermore, targeting a trough value of Յ 0.1 mg/L (instead of Յ 1 mg/L) may minimize the risk of toxicity that may be associated with elevated areas under the curve over an extended treatment duration. This survey indicates a dosing nomogram is used to guide therapeutic drug monitoring in nearly 25% of adult CF programs.…”

“…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.…”

“…The occurrence of these toxicities does not appear to differ significantly among patients with CF who are treated with once-daily EID and traditional dosing every 8 h. 14,15 As is the case across United States pediatric CF programs, serum creatinine level was measured routinely in nearly all adult CF programs, with weekly assessment being the most common. 19 However, one program did not monitor serum creatinine levels, a practice that may unnecessarily place patients at risk for toxicity.…”

“…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.…”

Cystic fibrosis, aminoglycoside treatment and acute renal failure: the not so gentle micin

“…Once-daily administration of aminoglycoside has been shown to have good clinical efficacy in CF patients [13] but less toxicity than two-or three-times daily administration in animals [14] as well as humans [15]. This makes sense, as megalin-mediated AG uptake in the proximal tubule is saturable.…”