Extended‐Interval Once‐Daily Dosing of Aminoglycosides in Adult and Pediatric Patients with Cystic Fibrosis

Abstract

Extended-interval once-daily dosing with the aminoglycoside tobramycin has been proven to be equally efficacious as traditional thrice-daily dosing for treatment of the pulmonary exacerbations of cystic fibrosis in adults and children older than 5 years. The frequencies of acute ototoxicity and nephrotoxicity do not appear to be significantly different between patients treated with once- versus thrice-daily dosing, and the risk of acute nephrotoxicity may actually be lower in pediatric patients when once-daily dosing is used. Long-term studies are needed to fully assess the impact that cumulative treatments with once-daily dosing have on renal and auditory function. An increase in antimicrobial resistance has been suggested with once-daily dosing in the cystic fibrosis population. The extended-interval aminoglycoside dose should be determined based on previous therapeutic drug monitoring. If the patient is aminoglycoside (tobramycin) naïve, a dose of 10 mg/kg once/day is suggested, with the dose adjusted by using therapeutic drug monitoring to individualize therapy.

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

“…improved lung function comparably well (Table 4); however, a statistically significant increase in MICs was observed for the once-daily group compared to the three-times-daily group (221). Comparable results were generated by others (296)(297)(298).…”

Bayesian Estimation of Tobramycin Exposure in Patients with Cystic Fibrosis

“…once daily, is a first-line antibiotic to treat and prevent infection (1,4,5,24). However, the TR for tobramycin is often difficult to achieve with standard dosing and monitoring methods (11,17,25), which is hazardous, as toxicity is linked to severe adverse effects such as irreversible nephrotoxicity and ototoxicity (7,26,27).…”

“…Tobramycin is most commonly administered as a daily i.v. injection in doses ranging from 7 to 15 mg/kg of body weight per day (1,4,5). The bactericidal actions of tobramycin are directly linked to drug exposure; however, dosing is complicated, as exposure must be maintained within a narrow therapeutic range (TR) (4)(5)(6).…”

“…injection in doses ranging from 7 to 15 mg/kg of body weight per day (1,4,5). The bactericidal actions of tobramycin are directly linked to drug exposure; however, dosing is complicated, as exposure must be maintained within a narrow therapeutic range (TR) (4)(5)(6). Exposures above the TR increase the risk of nephrotoxicity (1) and ototoxicity, of which the latter can be irreversible (1,7).…”

Acute renal failure after high-dose antibiotic bone cement: case report and review of the literature

“…A significant concern associated with scenarios like this ALBC elution case is the persistent exposure to aminoglycoside levels 41.0 mcg/mL for an extended period since elevated troughs and plasma concentration-time area under the curve are considered risk factors for aminoglycoside-induced nephrotoxicity. [51][52][53][54][55] We postulate that this likely contributed to the prolonged AKI since the spacers were not removed until the subsequent amputation two months later. Hemodialysis was never initiated which would have assisted with systemic aminoglycoside removal when it was at its highest.…”