Tolerance, pharmacokinetics and efficacy of once daily amikacin for treatment of Pseudomonas aeruginosa pulmonary exacerbations in cystic fibrosis patients

1996 ◽  
Vol 155 (11) ◽  
pp. 948-953 ◽  
Author(s):  
P. Vic ◽  
S. Ategbo ◽  
D. Turck ◽  
M. O. Husson ◽  
E. Tassin ◽  
...  
2020 ◽  
pp. AAC.02327-20 ◽  
Author(s):  
Claire L Keating ◽  
Jonathan B Zuckerman ◽  
Pradeep K Singh ◽  
Matthew McKevitt ◽  
Oksana Gurtovaya ◽  
...  

Rationale: Approval of aztreonam lysine for inhalation solution (AZLI) raised concerns that additional antibiotic exposure would potentially affect susceptibility profiles of Pseudomonas aeruginosa (PA) isolates from cystic fibrosis (CF) patients.Objective: This 5-year, prospective, observational study tracked susceptibility changes and clinical outcomes in CF patients in the United States with chronic PA infection.Methods: Sputum cultures were collected annually (2011-2016). The primary study endpoint was the proportion of subjects whose least susceptible PA isolate had an aztreonam minimum inhibitory concentration (MIC) that was >8 μg/mL (parenteral breakpoint) and increased ≥4-fold compared with the least susceptible isolate from the previous year. Annualized data for pulmonary exacerbations, hospitalizations, and FEV1% predicted were obtained from the CF Foundation Patient Registry and compared between subjects meeting/not meeting the primary endpoint.Results: 510 subjects were enrolled; 334 (65%) completed the study. A consistent proportion of evaluable subjects (13-22%) met the primary endpoint each year; and AZLI use during the previous 12 months was not associated with meeting the primary endpoint. While the annual decline in lung function was comparable for subjects meeting/not meeting the primary endpoint, more pulmonary exacerbations and hospitalizations were experienced by those who met it.Conclusions: Aztreonam susceptibility of PA remained consistent during the 5-year study. The relationship between PA isolate susceptibilities and clinical outcomes is complex; reduced susceptibility was not associated with accelerated decline in lung function, but was associated with more exacerbations and hospitalizations, likely reflecting increased overall antibiotic exposure.


2011 ◽  
Vol 16 (4) ◽  
pp. 262-269 ◽  
Author(s):  
William A Prescott

OBJECTIVES The Cystic Fibrosis Foundation recently deemed the use of extended-interval dosing (EID) of aminoglycosides acceptable for the treatment of cystic fibrosis (CF) pulmonary exacerbations, but current practices across United States (US) pediatric CF accredited care centers and affiliate programs are unknown. The objectives of this research are to characterize the practice trends, dosing strategies, therapeutic drug monitoring practices, and adverse drug reaction monitoring of EID of aminoglycosides in the treatment of pulmonary exacerbations across US pediatric CF programs. METHODS A 38-question online survey was distributed on behalf of the author by the CF Foundation to all US pediatric CF accredited care centers and affiliate programs. RESULTS Of the 70 participating CF programs (42.2% survey response rate), 94.3% reported using EID of aminoglycosides (as once-daily or twice-daily dosing), whereas 84.3% reported using once-daily EID in their pediatric CF population. The frequency of EID use increased with patient age. Tobramycin dosed 10 mg/kg per day every 24 hours, infused over the course of 30 minutes, in combination with an antipseudomonal beta-lactam, was the most commonly cited regimen. Monitoring of aminoglycoside serum concentrations was reported by 98.5% of programs, with a tobramycin peak of 25 to 30 mg/L and trough of less than 1 mg/L targeted most frequently. Nephrotoxicity was commonly monitored through serum creatinine measurements, whereas ototoxicity was monitored by audiometry in approximately one-half of programs. CONCLUSIONS This study indicates that the use of EID of aminoglycosides across US pediatric CF accredited care centers and affiliate programs is common, particularly among adolescents, with tobramycin being the preferred agent.


Author(s):  
Marco Mantero ◽  
Andrea Gramegna ◽  
Giovanna Pizzamiglio ◽  
Alice D’Adda ◽  
Paolo Tarsia ◽  
...  

2001 ◽  
Vol 31 (5) ◽  
pp. 367-376 ◽  
Author(s):  
Vahid Master ◽  
G.W. Roberts ◽  
K.P. Coulthard ◽  
P.A. Baghurst ◽  
A. Martin ◽  
...  

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