Tobramycin inhalation solution safe for bronchiectasis with Pseudomonas aeruginosa
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Key takeaways:
- Tobramycin inhalation solution was effective in lowering bacterial density and positively influenced quality of life.
- Adverse event frequency was similar in the treatment and placebo groups.
Adults with bronchiectasis and a Pseudomonas aeruginosa infection had lower bacterial density and better quality of life when treated with tobramycin inhalation solution, according to study results published in CHEST.
“In adult patients with bronchiectasis with P. aeruginosa infection, two cycles of tobramycin inhalation solution nebulization significantly reduce the sputum P. aeruginosa density and improve quality of life,” Wei-Jie Guan, PhD, of the First Affiliated Hospital of Guangzhou Medical University, and colleagues wrote. “Tobramycin inhalation solution has an acceptable safety profile among adults with bronchiectasis.”
The phase 3, multicenter, randomized, placebo-controlled, double-blind trial included 339 adults (median number of exacerbations in past 2 years, 2) with bronchiectasis and an P. aeruginosa infection. Guan and colleagues evaluated the patients over 16 weeks to see if nebulized tobramycin inhalation solution changes sputum P. aeruginosa density and the patient’s quality of life using Quality-of-Life Bronchiectasis Respiratory Symptoms scores.
Of the total cohort, 167 patients (mean age, 53 years; 65.3% women) received 300 mg/5 mL of tobramycin two times a day, whereas 172 (mean age, 54 years; 65.1% women) received 5 mL of normal saline two times a day in the intention-to-treat analysis. Both groups received the treatment/placebo through a vibrating-mesh nebulizer.
In this study, patients received their respective treatments for 28 days then no treatment for 28 days. This was then followed by another 28 days with treatment and another 28 days without treatment.
Within the study population, slightly more patients receiving tobramycin experienced an adverse event that resulted in stopping treatment (n = 11), whereas only five patients receiving placebo stopped treatment for this reason.
Main outcomes
When evaluating changes in P. aeruginosa density on day 29, researchers found that patients receiving tobramycin inhalation solution showed larger decreases in this variable vs. patients receiving placebo (adjusted mean difference, 1.74 log10 colony-forming units/g; 95% CI, 1.12-2.35). This was also observed in per-protocol analysis (n = 324; between group difference, 1.94 log10 colony-forming units/g; P < .001).
Further, the treatment group had better quality of life with higher scores on day 29 compared with the placebo group (adjusted mean difference, 7.91 points; 95% CI, 5.72-10.11), and this was also found in per-protocol analysis.
Researchers additionally found that only 10.6% of patients receiving the placebo were culture negative for P. aeruginosa on the 29th day compared with 29.3% of patients receiving tobramycin.
Jumping to day 85, researchers noted comparable outcomes to day 29, with those receiving tobramycin demonstrating lower bacterial density (mean difference, 1.35; 95% CI, 0.7-1.99) and higher quality of life scores (mean difference, 6.72 points; 95% CI, 4.18-9.27) than those receiving placebo.
Secondary outcomes
Researchers additionally observed improvements in secondary outcomes for those receiving tobramycin, such as significantly lower 24-hour sputum volume on day 29 (mean difference, 10.04 mL; 95% CI, 4.43-15.64), day 57 (mean difference, 7.25 mL; 95% CI, 1.18-13.32) and on day 85 (mean difference, 6.94 mL; 95% CI, 1.41-12.46).
Across these three time periods, sputum purulence scores in the tobramycin group were also reduced (day 29 mean difference, 0.61; 95% CI, 0.42-0.81; day 57, 0.62; 95% CI, 0.32-0.93; day 85, 0.45; 95% CI, 0.16-0.74).
In terms of safety of tobramycin, researchers found a similar number of patients who experienced adverse events in both those receiving tobramycin (81.5%) and those receiving placebo (81.6%), with the majority of events being mild or moderate in severity. A similar number of patients with serious adverse events was also observed in the tobramycin group (11.2%) and the placebo group (10.6%).
Notably, researchers observed that only 36 patients from each group had exacerbations during the entire study period.
In subgroup analysis, patients not treated with maintenance macrolides or inhaled corticosteroids within 6 months prior had larger mean changes in P. aeruginosa density and quality of life scores, signaling a more effective treatment option for these patients, according to researchers.
“Tobramycin inhalation solution effectively reduced sputum bacterial density and improved quality of life among the nonfrequent exacerbators, suggesting that the therapeutic benefits of tobramycin inhalation solution extended beyond exacerbation frequency reductions,” Guan and colleagues wrote. “The magnitude of exacerbation frequency reductions associated with tobramycin inhalation solution, however, might depend considerably on the prior exacerbation history and the baseline sputum bacterial density. Tobramycin inhalation solution might be suited for low- to middle-income countries or disadvantaged regions where essential treatment for P. aeruginosa has been scarce.”
Future studies
This study by Guan and colleagues adds to growing literature on inhaled antibiotics for treating bronchiectasis, but most patients in this study did not experience frequent exacerbations, signaling that more studies need to be conducted in different patient populations with more severe symptoms, according to an accompanying editorial by Conroy Wong, MD, adjunct associate professor of medicine at the University of Auckland in New Zealand, and Miguel Angel Martinez-Garcia, MD, of the department of respiratory medicine at La Fe University and Polytechnic Hospital and the Biomedical Network Research Center at the Carlos III Health Institute in Spain.
“In the study by Guan et al, the median number of exacerbations of participants in the previous 2 years was 2, and at least 25% of patients had no exacerbations,” Wong and Martinez-Garcia wrote. “Therefore, nebulized tobramycin appears to improve quality of life in symptomatic patients who have relatively few exacerbations. The benefit of nebulized tobramycin treatment relative to cost and risk in this patient population is uncertain, but there may be a role for treatment in selected patients with severe and persistent symptoms.
“More studies are required, and consideration should be given to designing studies with longer treatment duration, continuous rather than cyclical treatment, and pulmonary exacerbations as a primary outcome measure,” they added. “Clinicians ultimately must have treatments that can halt the relentless progression of disease induced by P. aeruginosa.”