Comparison of Inhaled Antibiotics for the Treatment of Chronic Pseudomonas aeruginosa Lung Infection in Patients With Cystic Fibrosis: Systematic Literature Review and Network Meta-analysis.
In Europe, 4 inhaled antibiotics (tobramycin, colistimethate sodium, aztreonam, and levofloxacin) are currently approved for the treatment of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis (CF). Levofloxacin inhalation solution (LIS) is the most recently approved inhaled antibiotic for adult patients with CF. A systematic literature review and Bayesian network meta-analysis (NMA) was conducted to compare the relative short-term (4 weeks) and long-term (24 weeks) outcomes of these inhaled antibiotics versus LIS.



A systematic literature search was conducted on February 16, 2016, using EMBASE and Medline via OvidSP. All randomized controlled trials comparing any of the aforementioned inhaled antibiotics with 4 or 24 weeks of follow-up were evaluated. NMA was performed for the following outcomes: relative and absolute percent changes from baseline in forced expiratory volume in 1 second (FEV1%) predicted, change in P aeruginosa sputum density, respiratory symptoms score from the CF questionnaire-revised, hospitalization, additional antibiotics use, and study withdrawal rates.



Of the 685 articles identified, 7 unique studies were included in the 4 weeks' NMA and 9 unique studies were included in the 24 weeks' NMA. Aztreonam was predicted to result in the greatest numerically increase in FEV1% predicted at 4 weeks, whereas LIS were predicted to be numerically greater than colistimethate sodium, tobramycin inhaled solution (TIS), and tobramycin inhaled powder (TIP). However, all of the 95% credibility intervals (CrIs) of these comparisons included zero. At 24 weeks, none of the treatments was significantly more effective than LIS. The estimates for the mean change from baseline to 24 weeks in relative FEV1% versus LIS was -0.55 (95% CrI, -3.91 to 2.80) for TIS, -2.36 (95% CrI, -7.32 to 2.63) for aztreonam, -2.95 (95% CrI, -10.44 to 4.51) for TIP, and -9.66 (95% CrI, -15.01 to -4.33) for placebo. Compared with LIS, the odds ratio for hospitalization at 24 weeks was 1.92 (95% CrI, 1.01-3.30) for TIS, 2.25 (95% CrI, 1.01-4.34) for TIP, and 3.16 (95% CrI, 1.53-5.78) for placebo, all statistically worse than LIS. P aeruginosa sputum density scores, additional use of antipseudomonal antibiotics, and study withdrawal rates were comparable among all inhaled antibiotics at all times.



Based on this NMA, the analyses for many of the outcomes did not provide significant evidence to indicate that the other approved inhaled antibiotics were more effective than LIS for the treatment of chronic P aeruginosa lung infection in patients with CF. Study withdrawal rates seemed to be comparable among these inhaled antibiotics.
School of Medicine, Dentistry & Biomedical Sciences, Queen׳s University Belfast, Belfast, United Kingdom.
J Stuart
JS
Elborn
Health Economics and Outcomes Research, Creativ-Ceutical, Paris, France.
Anne-Lise
AL
Vataire
Health Economics and Outcomes Research, Creativ-Ceutical, Paris, France.
Ayako
A
Fukushima
Health Economics and Outcomes Research, Creativ-Ceutical, Paris, France.
Samuel
S
Aballea
Health Economics and Outcomes Research, Creativ-Ceutical, Paris, France.
Amine
A
Khemiri
Raptor Pharmaceuticals, Inc, Novato, California.
Curtis
C
Moore
Raptor Pharmaceuticals Europe BV, Amsterdam, the Netherlands; Unit of Pharmacoepidemiology and Pharmacoeconomics, Department of Pharmacy, University of Groningen, Groningen, the Netherlands.
Goran
G
Medic
Raptor Pharmaceuticals Europe BV, Amsterdam, the Netherlands. Electronic address: mhemels@raptorpharma.com.
Michiel E H
ME
Hemels
D000280:Administration, Inhalation; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001499:Bayes Theorem; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000188:drug therapy*; D005060:Europe; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D016032:Randomized Controlled Trials as Topic; D012141:Respiratory Tract Infections / Q000188:drug therapy
D000900:Anti-Bacterial Agents
cystic fibrosis; levofloxacin inhalation solution; network meta-analysis