Is anti-Pseudomonas therapy warranted in acute respiratory exacerbations in children with cystic fibrosis?

Beaudry, Pierre H.; Marks, Melvin I.; McDougall, Dianne M.; Desmond, Katharine J.; Rangel, Raphael

doi:10.1016/s0022-3476(80)80155-7

Cited by 99 publications

(26 citation statements)

References 13 publications

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“…This inherent bacterial resistance seems to be associated with the low permeability of the outer membrane of the cell to some antimicrobial agents (4,17,46). Efficient therapy targeted against P. aeruginosa remains difficult and controversial (8,29). Usually, an aminoglycoside or beta-lactam antibiotic alone or both in combination are used as standard therapy for CF patients colonized with this organism (28,38).…”

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confidence: 99%

Pulmonary retention of free and liposome-encapsulated tobramycin after intratracheal administration in uninfected rats and rats infected with Pseudomonas aeruginosa

Omri

Beaulac

Bouhajib

et al. 1994

Antimicrob Agents Chemother

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The pulmonary residence time of free and liposome-encapsulated tobramycin was studied with uninfected rats and rats infected with Pseudomonas aeruginosa. Chronic infection in lungs was established by intratracheal administration of 108 CFU of P. aeruginosa PA 508 prepared in agar beads. After 3 days, a single dose (300 ,ug) of free or liposome-encapsulated tobramycin was given intratracheally to both infected and uninfected rats. At various time intervals (0.25 to 16 h) after drug instillations, the remaining tobramycin was evaluated in blood, lungs, and kidneys by a microbiological assay. Intratracheal instillation of liposome-encapsulated tobramycin resulted in high and sustained levels of tobramycin in lungs of uninfected and infected rats over the 16-h period studied; however, the tobramycin levels were two times higher in uninfected rats. There was no tobramycin detected in the blood or kidneys from these animals. In contrast, the intratracheally instilled free tobramycin was cleared within 3 and 1 h from the lungs of uninfected and infected animals, respectively. These data suggest that the encapsulation of tobramycin in liposomes can result in a significant increase of its residence time within lungs. This study also shows that pulmonary infection was associated with a lowering of tobramycin levels in lungs.

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confidence: 99%

Pulmonary retention of free and liposome-encapsulated tobramycin after intratracheal administration in uninfected rats and rats infected with Pseudomonas aeruginosa

Omri

Beaulac

Bouhajib

et al. 1994

Antimicrob Agents Chemother

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“…Furthermore, hospital treatment in itself may improve symptoms and well being in cystic fibrosis patients. '4 15 This could be because the whole treatment programme, including physiotherapy, can be performed on a regular basis, which is not always possible at home.…”

Section: Discussionmentioning

confidence: 99%

Treatment of pseudomonas aeruginosa colonisation in cystic fibrosis.

Steinkamp

Tümmler

Malottke

et al. 1989

Archives of Disease in Childhood

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SUMMARY To test whether early treatment could postpone the chronic colonisation of the respiratory tract with mucoid strains of Pseudomonas aeruginosa in patients with cystic fibrosis, we performed a pilot study in 28 patients aged 2 to 18 years. A two week course of azlocillin (150 mg/kg/day) and tobramycin (10 to 15 mg/kg/day) was given after a mean duration of P aeruginosa colonisation of five months (range one to 11 months). Weight for height increased significantly by 3-5% (SEM 0.7%) of the predicted normal after chemotherapy. The eradication of P aeruginosa that was achieved in 18 children directly after hospital treatment was only temporary. Samples from only 10 and five patients remained negative three and six months after treatment, respectively. Five children remained free from P aeruginosa for a prolonged period of 14 to 32 months.We conclude that, apart from the clinical improvement in all patients, some children might benefit from early antipseudomonas treatment with respect to the bacteriological outcome. Most children, however, experience only a temporary reduction in colonisation. Further investigations in form of controlled clinical trials seem justified.Pulmonary infection is the primary cause of morbidity in patients with cystic fibrosis. Pseudomonas aeruginosa acts as the main bacterial pathogen that causes a persisting lung infection. ' The P aeruginosa strains are usually of the mucoid, alginate producing variant, whose presence is usually a diagnostic feature of the disease.2 The chronic colonisation with mucoid P aeruginosa is associated with an appreciable clinical deterioration of the patient. This poses a serious therapeutic problem as the eradication of mucoid P aeruginosa from sputum by antibacterial chemotherapy is virtually impossible.Several reports suggest that the appearance of mucoid P aeruginosa in patients with cystic fibrosis is preceded by an asymptomatic period of colonisation of the upper respiratory tract with non-mucoid P aeruginosa strains.4 A clinical trial with intravenous antipseudomonas treatment during the initial phase of P aeruginosa colonisation has not been reported.Therefore we performed an open study to test the hypothesis as to whether early antipseudomonas treatment can eradicate P aeruginosa for a prolonged period of time, thereby postponing the chronic stage of P aeruginosa colonisation in patients with cystic fibrosis. Patients and methods PATIENTSAll patients with cystic fibrosis attending the cystic fibrosis outpatient centre at the Hanover Medical School were regularly examined for P aeruginosa in the respiratory tract. The patients were included in the study according to the following criteria: (a) primary growth of P aeruginosa in the sputum or deep throat swabs, (b) demonstration of a second P aeruginosa positive specimen four to eight weeks after the initial positive sample, and (c) treatment at our centre for at least 12 months before the initial demonstration of P aeruginosa. Out of the 34

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“…Clinical improvement, chest radiograph changes, evidence of airway obstruction and bacteriological flora of sputum did not differ between the groups regardless of which regimen was used. Beaudry et al (5) interpreted these results to mean that antipseudomonas medication may not always be necessary for exacerbations.…”

Section: Doubts About the Value Of Antibiotic Therapy In Cf Carementioning

confidence: 99%

Pseudomonas Aeruginosa and Cystic Fibrosis: Antibiotic Therapy and the Science behind the Magic

MacDonald

1997

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Respiratory failure secondary to chronic bronchiectasis is the cause of death in more than 90% of patients with cystic fibrosis (CF). The predominant microbes involved in CF lung disease are unusual: Pseudomonas aeruginosa, Staphylococcus aureus and Burkolderia cepacia. While antimicrobial therapy has been a component of CF care programs for decades, randomized controlled studies in the 1980s and early 1990s failed to show consistent measurable benefit. Research that stemmed from the discovery of the CF gene has shed new light on the inter-relationship of these microbes and the respiratory epithelial lung changes secondary to the CF gene. Five mechanisms have been proposed to explain the increased P aeruginosa colonization of the lower airway in CF. Recent research has also shown that antimicrobial therapy in CF may be effective not through eradication of the organism but by decreasing bacterial density and exoproduct production in the lung and thus decreasing inflammatory stimulus; by protecting against the consequences of an overexhuberant host response and in patients with stop mutations, potentially by correcting the gene defect. This tale of misunderstanding of the role and value of antimicrobial therapy in CF care illustrates the importance of ensuring close communiation between clinicians and researchers. The randomized controlled studies of the 1980s were not designed to answer the 'right' questions. The clinicians' observations that the CF patients did improve with antimicrobial therapy have been validated by recent studies using different endpoints. Key Words: Antibiotic therapy, Cystic fibrosis, Pseudomonas aeruginosaPseudomonas aeruginosa et la mucoviscidose : Antibiothérapie et science font miracle RÉSUMÉ : L'insuffisance respiratoire secondaire à la bronchiectasie chronique est la cause de décès chez plus de 90 % des patients atteints de mucoviscidose (MV). Les principaux agents infectieux dans la maladie pulmonaire qui accompagne la MV sont inhabituels : Pseudomonas aeruginosa, Staphylococcus aureus et Burkolderia cepacia. Depuis des dizaines d'années on a recours à l'antibiothérapie dans la MV, mais des études contrôlées randomisées menées au cours des années 1980 et 1990 n'ont pu en confirmer un avantage mesurable. La recherche qui a suivi la découverte du gène de la MV a éclairé d'un jour nouveau l'interrelation entre les organismes pathogènes et les anomalies de l'épithélium pulmonaire associées au gène de la MV. Cinq mécanismes ont été proposés pour expliquer l'accroissement de la colonisation des voies respiratoires inférieures par P. aeruginosa dans la MV. De récentes recherches ont également démontré que C ystic fibrosis (CF) is the most common serious disease among Caucasian children, affecting between one in 2000 and one in 4500 children (1,2). While cystic fibrosis was thought to be a gastrointestinal disease when it was first described by Anderson in the late 1930s, it is now well recognized as a multisystem disorder, with lung involvement as the major cause of morbidity and mortality ...

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Is anti-Pseudomonas therapy warranted in acute respiratory exacerbations in children with cystic fibrosis?

Cited by 99 publications

References 13 publications

Pulmonary retention of free and liposome-encapsulated tobramycin after intratracheal administration in uninfected rats and rats infected with Pseudomonas aeruginosa

Pulmonary retention of free and liposome-encapsulated tobramycin after intratracheal administration in uninfected rats and rats infected with Pseudomonas aeruginosa

Treatment of pseudomonas aeruginosa colonisation in cystic fibrosis.

Pseudomonas Aeruginosa and Cystic Fibrosis: Antibiotic Therapy and the Science behind the Magic

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