Inhaled ceftazidime compared with gentamicin and carbenicillin in older patients with cystic fibrosis infected with Pseudomonas aeruginosa

doi:10.1016/0007-0971(87)90161-6

British Journal of Diseases of the Chest

Volume 81, 1987, Pages 272-279

https://doi.org/10.1016/0007-0971(87)90161-6 Get rights and content

Abstract

A randomized cross-over study was undertaken to compare nebulized (1) ceftazidime with (2) a combination of gentamicin and carbenicillin, and (3) saline, each given for 4 months, in patients with cystic fibrosis infected with Pseudomonas aeruginosa. Mean peak expiratory flow on ceftazidime, 299 litres/min, and on gentamicin and carbenicillin, 297 litres/min, were greater than on saline, 278 litres/min (P<0.02 and P<0.05 respectively). Similarly, mean forced expiratory volume in 1 second on ceftazidime, 1.70 litres, and on gentamicin and carbenicillin, 1.70 litres, were greater than on saline, 1.48 litres (P<0.02 and P<0.01 respectively). Mean forced vital capacity on gentamicin and carbenicillin, 2.93 litres, was also greater than on saline (P<0.05). We were unable to demonstrate any difference in efficacy between the antibiotic regimens. The patients were admitted to hospital less frequently during the study year compared with the previous year (P<0.05). Sixty-nine per cent of patients had a clinically significant (20%) increase in forced expiratory volume in 1 second on an antibiotic regimen compared with that on entry to study, but a minority of patients appear not to respond to this form of treatment.

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Cited by (99)

Inhaled antibiotics beyond aminoglycosides, polymyxins and aztreonam: A systematic review
2015, International Journal of Antimicrobial Agents
Citation Excerpt :
Two randomised, double-blind, placebo-controlled, crossover trials, published in the 1980s investigated the impact of an inhaled combination of carbenicillin and gentamicin [35,36] and inhaled ceftazidime in the management of chronic P. aeruginosa LRTI in patients with CF. In the study by Hodson et al. [35], a treatment course of 6 months with inhaled carbenicillin and gentamicin resulted in significantly higher mean peak expiratory flow rate (PEFR), forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) values compared with placebo (PEFR, 323 L/min vs. 283 L/min, P < 0.001; FEV1, 1566 mL vs. 1300 mL, P < 0.001; and FVC, 2656 mL vs. 2314 mL, P < 0.02). The benefit of this inhaled combination compared with placebo was reproduced by Stead et al. [36] in a treatment course of 4 months (PEFR, 297 L/min vs. 278 L/min, P < 0.05; FEV1, 1700 mL vs. 1480 mL, P < 0.001; and FVC, 2930 mL vs. 2700 mL; P < 0.05). In this same study, inhaled ceftazidime for a period of 4 months also achieved significantly higher mean PEFR and FEV1 values in comparison with placebo (PEFR, 299 L/min vs. 278 L/min, P < 0.02; and FEV1, 1700 mL vs. 1480 mL, P < 0.02) but the increase in mean FVC did not reach statistical significance (FVC, 2950 mL vs. 2700 mL; P > 0.05).
We sought to evaluate published evidence regarding clinical or microbiological outcomes related to the use of inhaled antibiotics other than aminoglycosides, polymyxins and aztreonam. A systematic search of PubMed and Scopus databases as well as bibliographies of eligible articles was performed. In total, 34 eligible studies were identified. Among several inhaled β-lactams, ceftazidime was used with varying success in the prevention and treatment of ventilator-associated pneumonia (VAP) and improved clinical outcomes in chronic Pseudomonas aeruginosa lower respiratory tract infections (LRTIs) in patients with cystic fibrosis (CF) or bronchiectasis. Inhaled vancomycin, as an adjunctive therapy, was effective in treating Gram-positive VAP, whilst inhaled levofloxacin, ciprofloxacin and an inhaled combination of fosfomycin and tobramycin were associated with improved microbiological or clinical outcomes in chronic LRTI in patients with CF or bronchiectasis. In conclusion, published evidence is heterogeneous with regard to antibiotics used, studied indications, patient populations and study designs. Therefore, although the currently available data are encouraging, no safe conclusion regarding the effectiveness and safety of the drugs in question can be reached.
Antibiotics for treatment and prevention ofexacerbations of chronic obstructive pulmonary disease
2013, Journal of Infection
Citation Excerpt :
The concept of long-term antibiotic use comes from a number of other chronic respiratory tract conditions in which chronic bacterial infection occurs. The well-established indication for the long-term use of inhaled antibiotics is the prevention of exacerbations in cystic fibrosis patients,67–71 and more recently in non-cystic fibrosis bronchiectasis.72 Long-term macrolide therapy was first shown to be of significant benefit in a predominantly Japanese respiratory disease, diffuse pan-bronchiolitis.73
Acute exacerbations (AE) can be recurrent problems for patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) increasing morbidity and mortality. Evidence suggests that ≥50% of acute exacerbations involve bacteria requiring treatment with an antibiotic which should have high activity against the causative pathogens. However, sputum analysis is not a pre-requisite for antibiotic prescription in outpatients as results are delayed and patients are likely to be colonised with bacteria in the stable state. Clinicians rely on the clinical symptoms, sputum appearance and the patient's medical history to decide if an AE-COPD should be treated with antibiotics. This article reviews the available data of antibiotic trials in AE-COPD. Management of frequent exacerbators is particularly challenging for physicians. This may include antibiotic prophylaxis, especially macrolides because of anti-inflammatory properties; though successful in reducing exacerbations, concerns about resistance development remain. Inhalation of antibiotics achieves high local concentrations and minimal systemic exposure; therefore, it may represent an attractive alternative for antibiotic prophylaxis in certain COPD patients. Inhaled antibiotic prophylaxis has been successfully used in other respiratory conditions such as non-cystic fibrosis bronchiectasis which itself might be present in COPD patients who have chronic bacterial infection, particularly with Pseudomonas aeruginosa.
Aerosolized antibiotic therapy for chronic cystic fibrosis airway infections: Continuous or intermittent?
2011, Respiratory Medicine
The use of inhaled therapies for chronic respiratory infections in cystic fibrosis represents a substantive treatment burden to patients. In this paper, we review the evidence supporting two commonly used inhaled antibiotic regimens for chronic respiratory infections – continuous vs. intermittent (28 days on followed by 28 days off) therapy. We included trials of good methodological quality and excluded those in which the primary intent was eradication. In total, we included 13 trials (5 of intermittent therapy and 8 of continuous therapy) and summarized their main findings, placing particular emphasis on change in FEV₁, emergence of resistance and patient adherence. What is evident from our review is that both continuous and intermittent inhaled therapies work. Although an intermittent regimen would be intuitively “better” in terms of cost savings and patient tolerability, there is currently a lack of head-to-head trials that compare the same drugs (and dosages) using the two different regimens to make such a recommendation based on robust clinical evidence.
Aminoglycoside therapy against Pseudomonas aeruginosa in cystic fibrosis: A review
2009, Journal of Cystic Fibrosis
Citation Excerpt :
Additionally, studies reported a reduction in the number of hospital admissions related to respiratory events [25,78,82,83] and reduced use of parenteral antibiotic treatment [14]. Reduction in P. aeruginosa density has been reported in several studies [13,14,19,74–79]. A clinical pharmacology study showed that peak sputum concentrations using tobramycin for nebulization were higher than the threshold for a significant antibacterial effect against P. aeruginosa (>400 µg/g) for two different tobramycin nebulizer formulations [79].
In patients with cystic fibrosis (CF), respiratory infections with the opportunistic bacterial pathogen Pseudomonas aeruginosa have a major impact on morbidity and mortality. Aminoglycosides, especially tobramycin, have been used successfully to combat these infections. Aminoglycoside penetration of bronchial secretions is poor when the antibiotic is administered intravenously. Nebulization allows direct delivery of the drug to the sites of infection within the airways, while avoiding systemic exposure. Published clinical data show that inhaled tobramycin reduces the bacterial load, improves lung function and reduces the number of hospital admissions. Inhaled tobramycin has been used successfully to eradicate P. aeruginosa in patients with early infection. Maintaining clinical benefits requires chronic tobramycin treatment, and the concept of chronic intermittent inhaled treatment (typically, alternating drug and drug-free periods of 28 days) was introduced to minimize the emergence of aminoglycoside resistant P. aeruginosa strains. Other therapeutic advances include the development of different tobramycin formulations and nebulizers that reduce delivery time without compromising efficacy. An optimal treatment regimen for patients with CF with early or intermittent P. aeruginosa infections remains a high priority to maintain long-term lung health.
New Inhaled Antibiotics and Forms of Administration
2020, Open Respiratory Archives
La vía inhalatoria es la de elección en el tratamiento de la infección bronquial crónica. Con esta forma de administrar los antibióticos se reducen el volumen y la purulencia del esputo, el número y la gravedad de las agudizaciones, y se enlentece la pérdida de función pulmonar, con menores efectos secundarios que si se utilizasen por vía sistémica. Existen dos tipos de antibióticos inhalados: nebulizados (si el antibiótico se presenta en suspensión o solución) y en polvo seco. Los antibióticos en polvo seco presentan una eficacia y una seguridad similares a las de las formulaciones nebulizadas, aunque suelen producir más tos, que en algunos casos obliga a la suspensión del tratamiento. Tienen la ventaja añadida de tener dispositivos con un tamaño reducido, el menor tiempo de limpieza, la reducción del tiempo de inhalación —lo que facilita la adhesión al tratamiento— y una menor contaminación del dispositivo comparados con los nebulizadores. Actualmente hay cuatro antibióticos en solución comercializados (tobramicina, colistina, aztreonam y levofloxacino) y dos en polvo seco (tobramicina y colistina). En diferentes fases de desarrollo clínico se encuentran cuatro formulaciones de antibióticos, dos en solución (ciprofloxacino y amikacina —formulaciones liposomales—) y otros dos en polvo seco (ciprofloxacino y vancomicina). En un futuro próximo dispondremos de otros antibióticos en polvo seco, lo que permitirá su utilización tanto en pacientes con fibrosis quística como en pacientes con bronquiectasias no secundarias a ella.
Inhalation is the route of choice in the treatment of chronic bronchial infection. Administering antibiotics in this way reduces sputum volume and purulence and the number and severity of exacerbations, and slows lung function decline, while producing fewer side effects than the systemic route. There are two types of inhaled antibiotics, nebulized (if the antibiotic is presented in suspension or solution) and dry powder. The efficacy and safety of dry powder antibiotics are similar to nebulized formulations, but they often produce more cough, leading in some cases to discontinuation of treatment. Additional advantages include presentation in small devices, shorter cleaning time, reduced inhalation time — facilitating therapeutic adherence — and less contamination of the device compared to nebulizers. Currently, 4 antibiotics are available in solution (tobramycin, colistin, aztreonam, and levofloxacin) and 2 in dry powder (tobramycin and colistin). Four formulations of antibiotics are currently in clinical development, 2 in solution (liposomal formulations of ciprofloxacin and amikacin) and 2 in dry powder (ciprofloxacin and vancomycin). In the near future, other dry powder antibiotics suitable for use in both patients with cystic fibrosis (CF) and in patients with non-CF bronchiectasis will become available.
Brazilian guidelines for the pharmacological treatment of the pulmonary symptoms of cystic fibrosis. Official document of the sociedade brasileira de pneumologia e tisiologia (sbpt, brazilian thoracic association)
2023, Jornal Brasileiro de Pneumologia

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British Journal of Diseases of the Chest

Abstract

References (11)

Cystic fibrosis in adults

Aerosol carbenicillin and gentamicin treatment of Pseudomonas aeruginosa infection in patients with cystic fibrosis

Lancet

Inhaled antibiotics in cystic fibrosis

Lancet

Nebulised colomycin for early pseudomonas colonisation in cystic fibrosis

Lancet

Pseudomonas infection, allergy, and cystic fibrosis

Arch Dis Child

Cited by (99)

Inhaled antibiotics beyond aminoglycosides, polymyxins and aztreonam: A systematic review

Antibiotics for treatment and prevention ofexacerbations of chronic obstructive pulmonary disease

Aerosolized antibiotic therapy for chronic cystic fibrosis airway infections: Continuous or intermittent?

Aminoglycoside therapy against Pseudomonas aeruginosa in cystic fibrosis: A review

New Inhaled Antibiotics and Forms of Administration

Brazilian guidelines for the pharmacological treatment of the pulmonary symptoms of cystic fibrosis. Official document of the sociedade brasileira de pneumologia e tisiologia (sbpt, brazilian thoracic association)

Original articleInhaled ceftazidime compared with gentamicin and carbenicillin in older patients with cystic fibrosis infected with Pseudomonas aeruginosa

Abstract

Lancet

Lancet

Lancet

Pseudomonas infection, allergy, and cystic fibrosis

Arch Dis Child

Original article
Inhaled ceftazidime compared with gentamicin and carbenicillin in older patients with cystic fibrosis infected with Pseudomonas aeruginosa