Comparative study of the antibacterial activity of amikacin and tobramycin during Pseudomonas pulmonary infection in patients with cystic fibrosis (original) (raw)
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Antimicrobial agents and chemotherapy, 1999
The in vitro activity of tobramycin was compared with those of six other antimicrobial agents against 1,240 Pseudomonas aeruginosa isolates collected from 508 patients with cystic fibrosis during pretreatment visits as part of the phase III clinical trials of tobramycin solution for inhalation. The tobramycin MIC at which 50% of isolates are inhibited (MIC(50)) and MIC(90) were 1 and 8 microg/ml, respectively. Tobramycin was the most active drug tested and also showed good activity against isolates resistant to multiple antibiotics. The isolates were less frequently resistant to tobramycin (5.4%) than to ceftazidime (11.1%), aztreonam (11.9%), amikacin (13.1%), ticarcillin (16.7%), gentamicin (19.3%), or ciprofloxacin (20.7%). For all antibiotics tested, nonmucoid isolates were more resistant than mucoid isolates. Of 56 isolates for which the tobramycin MIC was > or = 16 microg/ml and that were investigated for resistance mechanisms, only 7 (12.5%) were shown to possess known ami...
Journal of Microbiology and Infectious Diseases, 2017
Clinical and Microbiological Impact of Inhaled Tobramycin Treatment on Cystic Fibrosis Patients with Pseudomonas aeruginosa Francesca Dickhaus 1 , Mutasim Abu Hasan 2 , Elizabeth Tremblay 3 , Kenneth Klinker 4 , Kenneth Rand 5,6 Stacy G. Beal 5 1 University of Florida College of Medicine, Gainesville, Florida, USA 2 University of Florida College of Medicine, Department of Pediatrics, Pediatric Pulmonary and Allergy Division, Gainesville, Florida, USA 3 UF Health Shands Hospital, Department of Infection Control, Gainesville, Florida, USA 4 UF Health Shands Hospital, Department of Pharmacy Practice, Gainesville, Florida, USA 5 University of Florida College of Medicine, Department of Pathology, Immunology, and Laboratory Medicine, Gainesville, Florida, USA 6 University of Florida College of Medicine, Department of Internal Medicine, Division of Infectious Diseases and Global Medicine, Gainesville, Florida, USA ABSTRACT Objective: Patients’ with cystic fibrosis respiratory systems becom...
Multidisciplinary Respiratory Medicine, 2017
It is estimated that about 60-70% of Cystic Fibrosis patients develop Pseudomonas aeruginosa chronic infection, with progressive loss of lung function, as well as increased antibiotic resistance and mortality. The current strategy is to maintain lung function by chronic suppressive antipseudomonas antibiotic therapy. Tobramycin inhalation solution was the first approved aerosolised antibiotic to be used against P. aeruginosa; inhalatory tobramycin frequency of administration is twice daily and inhalation time is estimated to be 15 to 20 min. From the pharmacokinetic point of view, aminoglycosides are dose-dependent antibiotics and therefore once-daily dosing intravenous regimens have shown to be superior to the conventional multiple daily dosing. Therefore, there is no pharmacological reason to prefer the b.i.d administration as it is usually performed in current clinical practice. Should this be confirmed also for inhalatory route, the use of once-daily dosed aerosolized tobramycin could be an important step in making treatment burden easier in CF patients. The aim of this proof of concept study was to explore the effectiveness of treatment with once daily inhaled tobramycin in reducing P. aeruginos a density in sputum of chronically infected patients.
Archives of Disease in Childhood, 1998
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.
Therapeutic Advances in Respiratory Disease, 2017
Chronic airway infection with Pseudomonas aeruginosa is a major cause of increased morbidity and mortality in patients with cystic fibrosis (CF). The development and widespread use of nebulized antibacterial therapies, including tobramycin inhalation solution (TIS), has led to improvements in lung function and quality of life. However, the use of nebulizers is associated with various challenges, including extended administration times and the need for frequent device cleaning and disinfection. Multiple therapies are required for patients with CF, which poses a considerable burden to patients, and adherence to the recommended treatments remains a challenge. Tobramycin inhalation powder (TIP), delivered via the T-326 Inhaler, has been shown to have similar clinical efficacy and safety as compared to TIS, with improved patient convenience, satisfaction, and treatment adherence. Long-term safety studies have shown that TIP was well tolerated with no unexpected adverse events in patients...
Thorax, 2021
RationaleInhaled tobramycin and oral azithromycin are common chronic therapies in people with cystic fibrosis and Pseudomonas aeruginosa airway infection. Some studies have shown that azithromycin can reduce the ability of tobramycin to kill P. aeruginosa. This trial was done to test the effects of combining azithromycin with inhaled tobramycin on clinical and microbiological outcomes in people already using inhaled tobramycin. We theorised that those randomised to placebo (no azithromycin) would have greater improvement in forced expiratory volume in one second (FEV1) and greater reduction in P. aeruginosa sputum in response to tobramycin.MethodsA 6-week prospective, randomised, placebo-controlled, double-blind trial testing oral azithromycin versus placebo combined with clinically prescribed inhaled tobramycin in individuals with cystic fibrosis and P. aeruginosa airway infection.ResultsOver a 6-week period, including 4 weeks of inhaled tobramycin, the relative change in FEV1 did ...
Pediatric Pulmonology, 2013
Intravenous (IV) anti-pseudomonal aminoglycosides (i.e., amikacin and tobramycin) have been shown to be tolerable and effective in the treatment of acute pulmonary exacerbations (APEs) in both pediatric and adult patients with cystic fibrosis. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic, tolerability, and efficacy studies utilizing IV amikacin, gentamicin, and tobramycin in the treatment of APE and to highlight areas where further investigation is needed. The Cystic Fibrosis Foundation Pulmonary Guidelines recommend that once-daily administration of aminoglycosides is preferred over three times per day in the treatment of an APE. The literature supports dosing ranges for amikacin and tobramycin of 30-35 and 7-15 mg/kg/day, respectively, given once daily, with subsequent doses determined by therapeutic drug concentration monitoring. The literature does not support the routine use of gentamicin in the treatment of APE due to a lack of studies showing efficacy and evidence indicating an increased risk of nephrotoxicity. Further studies are needed to determine the optimal dosing strategy of amikacin in the treatment of an APE, and to further identify risk factors and determinants that influence the development of P. aeruginosa resistance with once-daily administration of tobramycin.