Chronic P aeruginosa infection remains a challenge for bronchiectasis patients, and treatment options are limited, write Wei-jie Guan, MD, of the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China, and colleagues. Tobramycin has demonstrated anti-pseudomonal effects, but previous studies have been small, results have been inconclusive, and there are safety concerns with the currently approved method of intravenous injection.
In a study published in the journal Chest, the researchers randomly assigned 167 patients to receive nebulized tobramycin inhalation solution (TIS) and 172 patients to receive placebo. Patients in the active-treatment group received 300 mg/5 mL of TIS twice daily in two cycles of 28 days on- and off-treatment alternating periods. The primary endpoints were changes in P aeruginosa density from baseline and scores on the Quality-of-Life–Bronchiectasis questionnaire at day 29. Follow-up data were collected every 4 weeks for 16 weeks. Secondary endpoints included rate of negative P aeruginosa culture at day 29, change in P aeruginosa density from baseline, quality of life at day 85, and 24-hour sputum volume and purulence at day 29, 57, and 85.
The study population included adults aged 18 to 75 years with symptomatic bronchiectasis. The participants' conditions had been clinically stable for 4 weeks. Sputum cultures tested positive for P aeruginosa at two consecutive screening visits prior to randomization. The study was conducted at 33 sites within mainland China.
Overall, among the patients in the TIS group, there was a significantly greater reduction in P aeruginosa density compared to placebo patients, with an adjusted mean difference of 1.74 Log10 colony forming units/g (P < .001). TIS patients also showed significantly greater improvement in Quality-of-Life–Bronchiectasis respiratory symptom scores, with an adjusted mean difference of 7.91 (P < .001) at day 29.
In addition, more TIS patients became culture negative for P aeruginosa by day 29 compared to placebo patients (29.3% vs 10.6%), and 24-hour sputum volume and sputum purulence scores were significantly lower for TIS patients at day 29, day 57, and day 85, compared to placebo patients.
Adverse events were similar and occurred in 81.5% of TIS patients and 81.6% of placebo patients. The most common were hemoptysis, chest discomfort, and acute upper respiratory tract infections. A total of 10 patients in the TIS group experienced transient wheezing that resolved within 30 minutes. A total of 11 TIS patients and five placebo patients experienced an adverse event that caused them to discontinue participation in the study. These events included blurred vision and dizziness, which occurred in two TIS patients and was deemed related to the study drug. One TIS patient died as a result of acute myocardial infarction, but this was deemed to be unrelated to the study drug.
The findings were limited by several factors, including the short duration of treatment and relatively young population, which might affect generalizability, the researchers note. Other limitations include a lack of data on the effects of TIS on microorganisms other than P aeruginosa, as well as limited outpatient visits, owing to COVID-19 restrictions.
However, the results confirm the ability of TIS nebulization to reduce P aeruginosa and improve quality of life for adult patients with bronchiectasis, the authors conclude.
The study was funded by grants to multiple researchers from the National Science and Technology Major Project of the Ministry of Science and Technology of China and other government sources. The researchers have disclosed no relevant financial relationships.
Chest. Published online July 18, 2022. Abstract
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