Chest
Volume 121, Issue 6, June 2002, Pages 1754-1760
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Clinical Investigations
Cystic Fibrosis
Factors Affecting the Incidence of Stenotrophomonas maltophilia Isolation in Cystic Fibrosis

https://doi.org/10.1378/chest.121.6.1754Get rights and content

Study objectives

To identify factors predisposing cystic fibrosis (CF) patients to Stenotrophomonas maltophilia infection and to determine whether coinfection with S maltophilia affects the clinical response to therapy with tobramycin solution for inhalation (TSI), 300 mg bid.

Design

Retrospective review of data collected from two identical, 6-month, randomized, placebo-controlled trials.

Setting

Sixty-nine CF centers in the United States.

Interventions

Active drug administration of 300 mg TSI.

Patients

Five hundred twenty CF patients with chronic Pseudomonas aeruginosa endobronchial infections.

Measurements and results

A logistic regression analysis identified factors contributing to increased S maltophilia isolation frequency. In this multivariate analysis, the only significant predictors of S maltophilia isolation during the last month of the trial were the concomitant use of oral quinolones (primarily ciprofloxacin; p = 0.0015) and S maltophilia isolation prior to treatment (p < 0.0001). Treatment group, gender, age, use of systemic or inhaled steroids, use of oral sulfonamide, IV cephalosporins, or penicillin antibiotics, baseline FEV1 percent predicted, and pretreatment Aspergillus isolation were not significant predictors of subsequent S maltophilia infection. In addition, S maltophilia-positive culture frequency was compared to the change in pulmonary function. Patients who either never had culture results positive for S maltophilia or who were positive at <25% of observations had greater clinical response to TSI at the final study visit compared to patients who were positive at ≥ 25% of observations.

Conclusions

TSI therapy did not result in a greater risk for isolation of S maltophilia than standard care alone. In contrast, oral quinolone antibiotic use during the trial was associated with a 2.7-fold increased risk of having a culture positive for S maltophilia (p = 0.0015). The use of TSI to suppress P aeruginosa resulted in improved lung function, regardless of S maltophilia culture frequency. However, improvement was not as great among patients who were persistently coinfected with S maltophilia.

Section snippets

Study Design

Two identical, randomized, placebo-controlled trials of TSI were conducted.13 Patients were randomized to treatment either with 300 mg bid TSI (TOBI; Chiron; Emeryville, CA) or a taste-masked placebo administered bid. The study drug was administered in a series of cycles consisting of 28 days receiving the drug followed by 28 days not receiving the drug.13 The study design, study drug formulation, and drug delivery have been described previously.13 During the trials, patients could receive any

Demographic Data

A total of 520 patients were enrolled in the trials (TSI group, 258 patients; placebo group, 262 patients). Of these, 464 (89.2%) completed 6 months of treatment (TSI group, 232 patients [89.9%]; placebo group, 232 patients [88.6%]). There were no significant differences in the baseline characteristics of the two treatment groups (Table 1). When evaluated by S maltophilia culture status (ie, yes/no), demographic data revealed proportionally more pediatric patients and fewer adult patients among

Discussion

S maltophilia is an opportunistic pathogen that commonly infects the respiratory tract of patients with CF. The role that S maltophilia plays in the pathophysiology of CF lung disease is uncertain, but in light of the resistance to the antibiotic agents commonly used to manage CF patients, the reported increase in the isolation of S maltophilia from CF sputum3,5,6,7 has become a cause for concern within the CF community. The current study was undertaken to determine whether inhaled tobramycin

ACKNOWLEDGMENT

We gratefully acknowledge the contribution of the staff of Chiron Corporation, including Diane Gordon, Dutch VanDevanter, Blake Hoskins, Jill Van Dalfsen, Xin Yu, and Uta Meyer, in the preparation of this manuscript.

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Data for this study were obtained from the tobramycin solution for inhalation trials, provided by Chiron. Chiron also provided statistical analysis of the data presented under supervision of the authors. The authors received no financial support for the preparation of this manuscript, although they have received grant support and/or honoraria from Chiron for other projects.

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