Tobramycin Nebulizer Solution in severe COPD patients colonized with Pseudomonas aeruginosa: effects on bronchial Inflammation

Negro, Roberto; Micheletto, Claudio; Tognella, Silvia; Visconti, Marilia; Turati, C.

doi:10.1007/s12325-008-0105-2

Cited by 57 publications

(38 citation statements)

References 36 publications

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“…Two-week treatment with inhaled tobramycin decreased the frequency of exacerbations by 42%, when compared with the 6-month period prior to initiating inhaled tobramycin therapy. 117 Although this study has many limitations, including its open-label design and its small size, it does suggest a therapeutic role for inhaled antibiotics in COPD patients, particularly those colonised with multiresistant P. aeruginosa. Nevertheless, a recent phase II study investigating the efficacy of MP-376 (levofloxacin inhaled solution) in COPD patients at high risk for exacerbations (n Z 322) failed to demonstrate a significant reduction in the exacerbation rate or an increase in the time to the next exacerbation compared with placebo.…”

Section: Impact Of Acute Antibiotic Treatment On Longterm Outcome In mentioning

confidence: 89%

“…Antibiotics for treatment and prevention of AE-COPD 11 117 examined the impacts of 14-day, twice daily treatment with inhaled tobramycin nebuliser solution on clinical outcome as well as inflammatory markers in bronchial secretions from a small cohort (n Z 13) of multiresistant P. aeruginosa-colonised patients with severe COPD (FEV 1 < 50% predicted). P. aeruginosa infection is associated with a severe degree of functional impairment in COPD, 118 and colonisation could well herald the presence of bronchiectasis, 41,119 suggesting a potential role for inhaled antibiotics.…”

Section: Impact Of Acute Antibiotic Treatment On Longterm Outcome In mentioning

confidence: 99%

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Antibiotics for treatment and prevention of exacerbations of chronic obstructive pulmonary disease

Wilson

Sethi

Anzueto

et al. 2013

Journal of Infection

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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.

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Section: Impact Of Acute Antibiotic Treatment On Longterm Outcome In mentioning

confidence: 89%

Section: Impact Of Acute Antibiotic Treatment On Longterm Outcome In mentioning

confidence: 99%

Antibiotics for treatment and prevention of exacerbations of chronic obstructive pulmonary disease

Wilson

Sethi

Anzueto

et al. 2013

Journal of Infection

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“…Tobramycin is known to have both antibacterial and anti-inflammatory activities (75,76). Our results indicated the benefits of administration of LipoBiEDT-TOB intratracheally on P. aeruginosa infection and showed lowered inflammation by reduced IL-8 levels in lungs and sera.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Liposomal Bismuth-Ethanedithiol-Loaded Tobramycin after Intratracheal Administration in Rats with Pulmonary Pseudomonas aeruginosa Infection

Alhariri

Omri

2013

Antimicrob Agents Chemother

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We sought to investigate alterations in quorum-sensing signal molecule N-acyl homoserine lactone secretion and in the release of Pseudomonas aeruginosa virulence factors, as well as the in vivo antimicrobial activity of bismuth-ethanedithiol incorporated into a liposome-loaded tobramycin formulation (LipoBiEDT-TOB) administered to rats chronically infected with P. aeruginosa. The quorum-sensing signal molecule N-acyl homoserine lactone was monitored by using a biosensor organism. P. aeruginosa virulence factors were assessed spectrophotometrically. An agar beads model of chronic Pseudomonas lung infection in rats was used to evaluate the efficacy of the liposomal formulation in the reduction of bacterial count. The levels of active tobramycin in the lungs and the kidneys were evaluated by microbiological assay. LipoBiEDT-TOB was effective in disrupting both quorumsensing signal molecules N-3-oxo-dodeccanoylhomoserine lactone and N-butanoylhomoserine lactone, as well as significantly (P < 0.05) reducing lipase, chitinase, and protease production. At 24 h after 3 treatments, the CFU counts in lungs of animals treated with LipoBiEDT-TOB were of 3 log 10 CFU/lung, comparated to 7.4 and 4.7 log 10 CFU/lung, respectively, in untreated lungs and in lungs treated with free antibiotic. The antibiotic concentration after the last dose of LipoBiEDT-TOB was 25.1 g/ lung, while no tobramycin was detected in the kidneys. As for the free antibiotic, we found 6.5 g/kidney but could not detect any tobramycin in the lungs. Taken together, LipoBiEDT-TOB reduced the production of quorum-sensing molecules and virulence factors and could highly improve the management of chronic pulmonary infection in cystic fibrosis patients.

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“…Recientemente se han puesto en marcha diversos ensayos clínicos con formulaciones para uso inhalado 32 de levofloxacino 90,91 y ciprofloxacino 92 en pacientes con EPOC para evaluar su seguridad, su tolerancia y su farmacocinética, así como su efecto en la prevención de las exacerbaciones. Dal Negro et al 93 , en un estudio no controlado, investigan el efecto de la tobramicina nebulizada (300 mg/14 días) sobre los marcadores inflamatorios en las secreciones bronquiales en 13 pacientes con EPOC severa colonizados por PA multirresistentes, consiguiendo una reducción significativa de los marcadores de inflamación y, durante el período de seguimiento de 6 meses, de la densidad bacteriológica y de las exacerbaciones graves. En el estudio de Steinfort y Steinfort 76 con colistina nebulizada también se incluyeron 4 pacientes con EPOC severa infectados crónicamente por bacterias gramnegativas multirresistentes, observándose mejoría de la calidad de vida y una disminución en el declinar de la función pulmonar.…”

Section: Antibióticos Nebulizados En Bronquiectasias No Fibrosis Quísunclassified

Terapia nebulizada. Año SEPAR

Olveira

Muñoz

Domenech

2014

Archivos de Bronconeumología

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Tobramycin Nebulizer Solution in severe COPD patients colonized with Pseudomonas aeruginosa: effects on bronchial Inflammation

Abstract: TNS reduced the inflammatory impact of P aeruginosa in multiresistant, P aeruginosa-colonized patients with severe COPD. A therapeutic role for TNS can be strongly suggested in these particular conditions.

Cited by 57 publications

References 36 publications

Antibiotics for treatment and prevention of exacerbations of chronic obstructive pulmonary disease

Antibiotics for treatment and prevention of exacerbations of chronic obstructive pulmonary disease

Efficacy of Liposomal Bismuth-Ethanedithiol-Loaded Tobramycin after Intratracheal Administration in Rats with Pulmonary Pseudomonas aeruginosa Infection

Terapia nebulizada. Año SEPAR

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