A survey of the utilization of anti-pseudomonal beta-lactam therapy in cystic fibrosis patients (original) (raw)
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Pediatric Pulmonology, 2017
Acute pulmonary exacerbations (APE) are well-described complications of cystic fibrosis (CF) and are associated with progressive morbidity and mortality. Despite aggressive management with two or more intravenous anti-pseudomonal agents, approximately 25% of exacerbations will result in a loss of lung function. The aim of this review is to provide an overview of the classes of intravenous anti-pseudomonal antibiotics, the findings of anti-pseudomonal antibiotic utilization surveys, the current antibiotic dosing recommendations from the U.S. and Europe, and the pharmacokinetic (PK) and pharmacodynamic (PD) differences between CF and non-CF individuals. Anti-pseudomonal antibiotic classes include beta-lactams, aminoglycosides, fluoroquinolones, and colistimethate sodium. Recent surveys of antibiotic utilization in CF Foundation-accredited care centers have shown that a large number of centers are not following recommended dosing strategies despite published recommendations in the U.S. and Europe. The recommended doses for anti-pseudomonal antibiotics may be higher than FDA-approved doses due to PK and PD differences. As a large portion of CF patients will not regain their lung function following an APE, it seems possible that currently available antipseudomonal agents are being used sub-optimally. As new anti-pseudomonal agents are not currently available, we suggest the need to optimize antibiotic dosing and dosing regimens used to treat pulmonary exacerbations in an effort to improve outcomes for CF patients infected with Pseudomonas aeruginosa.
F1000Research
Background: Cystic fibrosis (CF) is associated with frequent pulmonary exacerbations which increase the mortality risk. Therefore, most CF patients are chronically colonized with respiratory pathogens, the most common being Pseudomonas aeruginosa. Multidrug-resistant organisms are a major problem in CF patients. It’s been hypothesized that continuous-infusion antipseudomonal beta-lactam therapy in CF maintains serum concentrations above the minimum inhibitory concentration of susceptible strains and is more likely than intermittent infusion to achieve optimal pharmacodynamic targets for some intermediate and resistant strains of P. aeruginosa. The most extensively studied antibiotic for continuous-infusion protocol in CF is ceftazidime, which has been shown to improve lung function (forced expiratory volume in 1 second and forced vital capacity) and to increase pulmonary exacerbation free time. There have been no studies to evaluate the cost effectiveness or impact on quality of lif...
Chest, 2018
Several clinical trials have demonstrated the efficacy of continuous infusion (CI) beta-lactam (BL) antibiotics in cystic fibrosis (CF) patients; however, little is known regarding pharmacokinetic changes during treatment of an acute pulmonary exacerbation (APE). Identifying and understanding these changes may assist in optimizing antibiotic dosing during APE treatment. This study is a retrospective cohort study of 162 adult CF patients admitted to the University of Utah Hospital between January 1, 2008 and May 15, 2014 for treatment of an APE with both a CI BL and intravenous tobramycin. We extracted the administered doses of CI BL and tobramycin along with serum drug concentrations and calculated medication clearance rates. The primary outcome was change in clearance rates of CI BL between day 2 and day 7 of APE treatment. BL clearance rate increased 20.7% (95% CI, 11.42 - 32.49; p<0.001), whereas tobramycin clearance rate decreased 6.3% (95% CI, -12.29 - -4.45; p<0.001). Th...
Pediatric Pulmonology, 2013
Acute pulmonary exacerbations (APE) in cystic fibrosis (CF) are associated with loss of lung function that may require aggressive management with intravenous antibiotics. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing aztreonam and anti-pseudomonal carbapenems (i.e., doripenem, imipenem-cilastatin, and meropenem) in the treatment of an APE, and to identify areas where further study is warranted. The current dosing recommendations in the United States and Europe for aztreonam are lower than the literature supported dosing range of 200-300 mg/kg/day divided every 6 hr, maximum 8-12 g/day. In vitro, PK/PD, and tolerability studies show the potential of doripenem 90 mg/kg/day divided every 8 hr, infused over 4 hr, maximum 6 g/day in the treatment of APE. Imipenem-cilastatin 100 mg/kg/day divided every 6 hr, maximum 4 g/day and meropenem 120 mg/kg/day divided every 8 hr, maximum 6 g/day have been shown to be tolerable and effective in the treatment of APE. With availability issues of new anti-pseudomonal agents and a large percentage of CF patients will not regain their lung function following an APE, we suggest the need to determine optimization of aztreonam and meropenem dosing in CF, as well as to determine the clinical efficacy of doripenem in the treatment of APE. The usefulness of imipenem-cilastatin may be limited due to the rapid development of resistance. Pediatr Pulmonol. ß Search results were restricted to the English language without an age limit. Also, reference lists and conference proceedings were reviewed.
Pediatric Pulmonology, 2013
Acute pulmonary exacerbations (APE) in cystic fibrosis (CF) are associated with loss of lung function that may require aggressive management with intravenous antibiotics. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing aztreonam and anti-pseudomonal carbapenems (i.e., doripenem, imipenem-cilastatin, and meropenem) in the treatment of an APE, and to identify areas where further study is warranted. The current dosing recommendations in the United States and Europe for aztreonam are lower than the literature supported dosing range of 200-300 mg/kg/day divided every 6 hr, maximum 8-12 g/day. In vitro, PK/PD, and tolerability studies show the potential of doripenem 90 mg/kg/day divided every 8 hr, infused over 4 hr, maximum 6 g/day in the treatment of APE. Imipenem-cilastatin 100 mg/kg/day divided every 6 hr, maximum 4 g/day and meropenem 120 mg/kg/day divided every 8 hr, maximum 6 g/day have been shown to be tolerable and effective in the treatment of APE. With availability issues of new anti-pseudomonal agents and a large percentage of CF patients will not regain their lung function following an APE, we suggest the need to determine optimization of aztreonam and meropenem dosing in CF, as well as to determine the clinical efficacy of doripenem in the treatment of APE. The usefulness of imipenem-cilastatin may be limited due to the rapid development of resistance. Pediatr Pulmonol. ß Search results were restricted to the English language without an age limit. Also, reference lists and conference proceedings were reviewed.
Pediatric Pulmonology, 2013
Acute pulmonary exacerbations (APE) in cystic fibrosis (CF) are associated with loss of lung function that may require aggressive management with intravenous antibiotics. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing aztreonam and anti-pseudomonal carbapenems (i.e., doripenem, imipenem-cilastatin, and meropenem) in the treatment of an APE, and to identify areas where further study is warranted. The current dosing recommendations in the United States and Europe for aztreonam are lower than the literature supported dosing range of 200-300 mg/kg/day divided every 6 hr, maximum 8-12 g/day. In vitro, PK/PD, and tolerability studies show the potential of doripenem 90 mg/kg/day divided every 8 hr, infused over 4 hr, maximum 6 g/day in the treatment of APE. Imipenem-cilastatin 100 mg/kg/day divided every 6 hr, maximum 4 g/day and meropenem 120 mg/kg/day divided every 8 hr, maximum 6 g/day have been shown to be tolerable and effective in the treatment of APE. With availability issues of new anti-pseudomonal agents and a large percentage of CF patients will not regain their lung function following an APE, we suggest the need to determine optimization of aztreonam and meropenem dosing in CF, as well as to determine the clinical efficacy of doripenem in the treatment of APE. The usefulness of imipenem-cilastatin may be limited due to the rapid development of resistance. Pediatr Pulmonol. ß Search results were restricted to the English language without an age limit. Also, reference lists and conference proceedings were reviewed.
Australian and New Zealand journal of medicine, 1999
Although anti-pseudomonal antibiotics are routinely used in the treatment of acute respiratory exacerbations of adult cystic fibrosis (CF), the specific efficacy of such treatment remains uncertain, the mechanism of action of these agents is not fully understood, and the role of sputum susceptibility testing in clinical decision making is controversial. We investigated the relationship between susceptibility testing and clinical outcome in adult CF patients colonised with Pseudomonas aeruginosa. Sputum samples were collected before, during and after respiratory exacerbations from 31 admissions (17 patients). Sputum colony counts and MIC of P. aeruginosa were performed. Sputum colony counts did not change significantly during or after intravenous (IV) antibiotic therapy. Clinical outcome parameters (lung function, 12-minute walking distance, sputum weight and quality of life) were compared with susceptibility of P. aeruginosa colonies isolated at admission to the antibiotics used, an...
The Journal of Pediatrics, 1981
A double-blind controlled trial ofanti-Pseudomonas chemotherapy was carried out in 24 exacerbations of pulmonary disease in patients with ~ystic fibrosis. Fifteen exacerbations were treated with oxacillin plus sisomicin and carbenicillin (treatment group); nine were treated with oxacillin alone (control group). The planned length of treatment was 14 days. The d(fference between the failure rate in the treatment group (3/15) and the control group (7/9) was statistically significant (P < 0.015). The d(fference in improvement of forced expiratory volume in I second was also significant (P < 0.025). At the end of the study, Pseudomonas aeruginosa was still present in the sputum of all nine patients in the control group, but was not isolated fi'om six of the 15 patients in the treatment group. The data suggest a beneficial role for anti-Pseudomonas chemotherapy in the treatment of acute pulmonary exacerbations in pa/ients with cystic .fibrosis.