Chest
Volume 130, Issue 5, November 2006, Pages 1503-1510
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Original Research
Addition of Inhaled Tobramycin to Ciprofloxacin for Acute Exacerbations of Pseudomonas aeruginosa Infection in Adult Bronchiectasis

https://doi.org/10.1378/chest.130.5.1503Get rights and content

Rationale:Pseudomonas aeruginosa

lung infection in patients with bronchiectasis, a chronic airway disease that is characterized by episodes of exacerbation, is associated with more severe disease and a higher utilization of health-care resources. Inhaled tobramycin solution reduces the number of acute exacerbations in patients with cystic fibrosis (CF)-related bronchiectasis with P aeruginosa infection but remains untested in the treatment of exacerbations in patients with non-CF bronchiectasis.

Objectives

This study tested the effect of adding inhaled tobramycin solution to oral ciprofloxacin (Cip) for the treatment of acute exacerbations of non-CF bronchiectasis in patients with P aeruginosa infection.

Methods

A double-blind, randomized, active comparator, parallel-design study conducted at 17 study centers (5 in the United Kingdom, and 12 in the United States) compared 2 weeks of therapy with Cip with either an inhaled tobramycin solution or placebo in 53 adults with known P aeruginosa infection who were having acute exacerbations of bronchiectasis.

Measurements

Clinical symptoms, pulmonary function, clinical efficacy, and sputum microbiology were investigated prospectively.

Main results

An inhaled solution of Cip with tobramycin, compared to placebo, achieved greater microbiological response but no statistically significant difference in clinical efficacy at days 14 or 21. Clinical and microbiological outcomes at the test of cure (ie, the clinical outcome assessment at day 21) were concordant when an inhaled tobramycin solution was added to therapy with Cip and compared to placebo (p = 0.01). Both subject groups had similar overall adverse event rates, but subjects receiving therapy with an inhaled tobramycin solution reported an increased frequency of wheeze (50%; placebo group, 15%).

Conclusions

The addition of an inhaled tobramycin solution to therapy with oral Cip for the treatment of acute exacerbations of bronchiectasis due to P aeruginosa improved microbiological outcome and was concordant with clinical outcome; the inability to demonstrate an additional clinical benefit may have been due to emergent wheeze resulting from treatment.

Section snippets

Design

A double-blind, randomized, active comparator, parallel-design study was conducted in 17 study centers (12 in the United States and 5 in the United Kingdom). Each center received Institutional Review Board or Ethics Committee approval prior to initiation. All subjects provided written informed consent before enrollment; confirmation of consent was obtained at the time of the exacerbation.

Population

Men and women between 18 and 80 years of age with bronchiectasis confirmed by the results of a central

Subject Demographics

Of 138 subjects screened, 53 were enrolled in the study, 26 were randomized to the TIS/Cip arm, and 27 were randomized to the placebo/Cip arm. Of those screened, 85 subjects were not randomized, 28 subjects either had no history of P aeruginosa infection or had no infection at screening, 24 subjects did not experience an exacerbation before the close of the study, 18 subjects had infection with Cip-resistant P aeruginosa, 4 subjects had no bronchiectasis on review of a high-resolution CT, 4

Discussion

This study represents the first randomized controlled trial of a nebulized antibiotic as adjunctive therapy for patients with an acute exacerbation of P aeruginosa infection in patients with non-CF bronchiectasis. In chronic airway infection with P aeruginosa in CF patients, clinical improvement is associated with a reduction in bacterial density rather than eradication.11 The few comparable studies performed in patients with non-CF bronchiectasis12, 13 have shown that successful treatment does

Participating Study Investigators

The authors present the data in the study on behalf of all the following participating investigators in this study: Wesley R. Bray, Marietta Pulmonary Medicine, Marietta, GA; Leslie Couch, University of Texas Health Center at Tyler, Tyler, TX; James D. DeMaio, Northwest Medical Specialties, Tacoma, WA; Graham Douglas, Aberdeen Royal Infirmary, Aberdeen, UK; Stuart Elborn, Belfast City Hospital, Belfast, Northern Ireland, UK; Gwen Huitt, National Jewish Medical & Research Center, Denver, CO;

ACKNOWLEDGMENT

The authors thank the following Chiron Corporation employees for their support: Uta Meyer, Xin Yu, and Kevin Hou for statistical analyses; Sally Anne Jones, Barbara Schaeffler, Alistair Leigh, Kara MacGowan, Stephen Shrewsbury, and Lyn Waring for clinical operations support; and Dutch VanDevanter, Jill Van Dalfsen, and Debbi Humble for data analyses and critical reading of this manuscript.

References (15)

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    These results reflect the findings of the study by Orriols et al. (2015) (99.7% of the weight of the analysis), were the number of acute exacerbations, the frequency of hospital admissions due to exacerbations and the days of admission were significantly reduced compared to placebo at 15-months follow-up [7]. Two studies including 50 patients reported lung function measured by FEV1 in Liters [15,17]. Treatment with inhaled Tobramycin was not related to a significant difference in lung function compared to placebo (MD -0.20, 95% CI -0.54 to 0.14) (Fig. 8).

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Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

Chiron Corporation, manufacturers of Tobramycin Inhalation Solution (TOBI), sponsored this clinical study, and conducted data management and statistical analyses. Drs. Bilton and Gotfried have acted in the past as clinical consultants for Chiron Corporation. The authors did not receive compensation for either their participation as investigators in this study or for the writing of this article.

Manuscript received September 19, 2005; revision accepted May 4, 2005.

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