A Prospective Trial of Nebulized Amikacin in the Treatment of Bronchiectasis Exacerbation

Abstract

Background: Pseudomonas aeruginosa is the most common pathogenic bacteria in bronchiectasis (BE) patients. The availability and security of nebulized amikacin treatment are unknown. Objective: The purpose of this study was to explore the efficiency and adverse effects of nebulized amikacin treatment for 2 weeks, administered as intravenous therapy during exacerbation of BE patients infected with P. aeruginosa. Methods: A total of 143 patients with exacerbation of BE were screened between January 2013 and March 2016 at five tertiary hospitals in Shandong Province, China. The BE patients were diagnosed by high-resolution computed tomography scans, and all of them were confirmed to be infected with P. aeruginosa after sputum culture test. Seventy-four patients were assigned to the intervention group and received amikacin nebulization (0.2 g) treatment twice daily for 2 weeks along with intravenous antibiotic therapy. Sixty-nine patients were assigned to the control group and received standard antibiotic therapy alone. The primary outcome was the rate of bacterial eradication from the sputum, and the secondary outcomes were drug resistance and adverse effects. Results: The bacterial eradication rate of sputum in the intervention group (51.4%) was significantly higher compared to that in the control group (23.2%) (χ² = 14.211, p = 0.030). Drug sensitivity testing showed that there were 5 drug-resistant cases in the intervention group and 7 in the control group, which was not significantly different. Three patients dropped out of the trial due to adverse effects. None of the patients hat renal injury. Conclusions: Nebulized amikacin treatment is a safe treatment for exacerbation of BE and significantly increases the bacterial eradication rate of sputum.

A systematic review of pharmacotherapeutic clinical trial end-points for bronchiectasis in adults

“…We found, however, that exacerbation end-points were also used in short studies where the chance of a patient exacerbating within such a brief time frame is low [17,20,21,23,24]. From the trials reviewed, Mannitol BILTON [20] Ciprofloxacin DPI WILSON [21] BAT ALTENBURG [12] BLESS SERISIER [22] ORBIT-2 SERISIER [23] Azithromycin DE DIEGO [24] Azithromycin LOURDESAMY [28] Inhaled mannitol BILTON [29] Roxithromycin LIU [15] Tobramycin ORRIOLS [13] STRATUS DE SOYZA [30] Inhaled colistin HAWORTH [25] Atorvastatin MANDAL [26] AIR-BX1 and AIR-BX2 BARKER [27] RESPIRE I and II DE SOYZA [8] and AKSAMIT [9] Hyaluronic acid plus 7% hypertonic saline, HERRERO-CORTINA [10] Nebulised amikacin AILIYAER [31] Green: end-point(s) passed; pink: end-point(s) failed; orange: not clear or mixed results. HRQoL: healthrelated quality of life.…”

“…Several studies have shown good reductions in bacterial load with no clear or consistent clinical efficacy raising questions about the value of this standard end-point for phase 2 antibiotic trials [11,21,23,25,31].…”

Nebulized Antibiotics in Acute Exacerbation of Non-Cystic Fibrosis Bronchiectasis: Shifting the Goal Posts or a Post Too Far?

“…I read with interest the trial on nebulized amikacin in addition to parenteral therapy during acute exacerbations of non-cystic fibrosis bronchiectasis (AE-NCFB) published recently in this journal [1]. I disagree with the authors about their rationale, timing, duration of therapy and end points of inhaled antibiotics (IA) in NCFB.…”

“…In stable NCFB, use of IA causes bronchospasm and medication withdrawal in 10–12% of cases [6]. Against this background, the ability to perform multiple spirometry manoeuvers during an exacerbation of NCFB, the high tolerability (withdrawal < 4%) of a preservative-containing amikacin preparation during AE-NCFB, and improvement in spirometry with IA all seem truly remarkable [1]. …”

“…The use of IA would be justified for a reduction in exacerbations, hospitalisations, or mortality, but not for microbiological clearance alone [4, 6]. This is especially true if clearance is defined by a single negative culture and not by at least 2 consecutive negative cultures 1 month apart [1]. …”