Infection in patients with cystic fibrosis (original) (raw)
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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.
Clinical Microbiology and Infection, 2005
Pseudomonas aeruginosa colonisation has a negative effect on pulmonary function in cystic fibrosis patients. The organism can only be eradicated in the early stage of colonisation, while reduction of bacterial density is desirable during chronic colonisation or exacerbations. Monthly, or at least 3-monthly, microbiological culture is advisable for patients without previous evidence of P. aeruginosa colonisation. Cultures should be performed at least every 2-3 months in patients with well-established colonisation, and always during exacerbations or hospitalisations. Treatment of patients following the first isolation of P. aeruginosa, but with no clinical signs of colonisation, should be with oral ciprofloxacin (15-20 mg ⁄ kg twice-daily for 3-4 weeks) plus inhaled tobramycin or colistin (intravenous treatment with or without inhaled treatment can be used as an alternative), while patients with acute infection should be treated for 14-21 days with high doses of two intravenous antimicrobial agents, with or without an inhaled treatment during or at the end of the intravenous treatment. Maintenance treatment after development of chronic P. aeruginosa infection ⁄ colonisation (pathogenic colonisation) in stable patients (aged > 6 years) should be with inhaled tobramycin (300 mg twice-daily) in 28-day cycles (on-off) or, as an alternative, colistin (1-3 million units twice-daily). Colistin is also a possible choice for patients aged < 6 years. Treatment can be completed with oral ciprofloxacin (3-4 weeks every 3-4 months) for patients with mild pulmonary symptoms, or intravenously (every 3-4 months) for those with severe symptoms or isolates with ciprofloxacin resistance. Moderate and serious exacerbations can be treated with intravenous ceftazidime (50-70 mg ⁄ kg threetimes-daily) or cefepime (50 mg ⁄ kg three-times-daily) plus tobramycin (5-10 mg ⁄ kg every 24 h) or amikacin (20-30 mg ⁄ kg every 24 h) for 2-3 weeks. Oral ciprofloxacin is recommended for patients with mild pulmonary disease. If multiresistant P. aeruginosa is isolated, antimicrobial agents that retain activity are recommended and epidemiological control measures should be established.
Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus
European Respiratory Journal, 2000
Cystic fibrosis (CF) is the most common lethal hereditary disorder with autosomal recessive heredity in caucasians. The majority of CF patients suffer from chronic respiratory infection with the opportunistic bacterial pathogen Pseudomonas aeruginosa. No consensus among clinicians has been reached so far concerning antibiotic treatment against P. aeruginosa in CF patients.
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.
The Scientific World Journal, 2013
The optimal antibiotic regimen is unclear in management of pulmonary infections due to pseudomonas andstaphylococcusin cystic fibrosis (CF). We systematically searched all the published literature that has considered the evidence for antimicrobial therapies in CF till June 2013. The key findings were as follows: inhaled antipseudomonal antibiotic improves lung function, and probably the safest/most effective therapy; antistaphylococcal antibiotic prophylaxis increases the risk of acquiringP. aeruginosa; azithromycin significantly improves respiratory function after 6 months of treatment; a 28-day treatment with aztreonam or tobramycin significantly improves respiratory symptoms and pulmonary function; aztreonam lysine might be superior to tobramycin inhaled solution in chronicP. aeruginosainfection; oral ciprofloxacin does not produce additional benefit in those with chronic persistent pseudomonas infection but may have a role in early or first infection. As it is difficult to estab...
Management of refractory Pseudomonas aeruginosa infection in cystic fibrosis
Cystic fibrosis (CF) is the most common life-limiting inherited disease in Caucasian populations. The main cause of death in CF patients is respiratory failure resulting from chronic pulmonary infection. Pseudomonas aeruginosa is the most prevalent organism in the airway colonization of CF patients, and its persistence in the airways has been related to greater morbidity with a more rapid deterioration in lung function. P. aeruginosa has enormous genetic and metabolic flexibility that allows it to adapt and persist within the airways of CF patients, and it has the ability to easily acquire antimicrobial resistance. For these reasons, the management of infections and chronic colonization by P. aeruginosa remains a challenge for physicians. This article reviews the current and future antibacterial chemotherapy options for respiratory pseudomonal infection in CF patients.
Diagnostic Microbiology and Infectious Disease, 2019
The in vitro activity of ceftolozane-tazobactam (C-T) was evaluated comparatively to other antibiotics against 188 Pseudomonas aeruginosa isolates collected from cystic fibrosis (CF) patients. Overall, the activity of C-T was comparable to colistin (susceptibility rate: 85.1% vs. 89.4%) but significantly higher than other antimicrobials. Particularly, C-T was active against 70% of meropenem nonsusceptible isolates and 64.1% of those nonsusceptible to betalactams. C-T was active against 70%, 58.1%, and 100% of multidrug-resistant, extensively drug-resistant (XDR), and pandrug-resistant isolates, respectively. No differences in C-T activity were found between isolates from children and adult patients, except for XDR ones significantly more susceptible in older patients. C-T and colistin exhibited comparable susceptibility rate (91.1% vs. 86.7%) also against 68 isolates collected during pulmonary exacerbations. Activity of C-T towards mucoid isolates was less than colistin (82.9% vs. 97.6%) but higher compared with other antibiotics. C-T represents a promising agent for treating CF lung infections.
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.
Early eradication therapy against Pseudomonas aeruginosa in cystic fibrosis patients
European Respiratory Journal, 2005
In cystic fibrosis (CF) patients early antibiotic treatment of lung infection has been shown to lead to Pseudomonas aeruginosa eradication. The present study determined: 1) the time period from eradication to new P. aeruginosa acquisition; 2) P. aeruginosa re-growth and new acquisition; and 3) the impact of eradication therapy on lung function, antimicrobial resistance, emergence of other pathogens and treatment costs.