Table 4.

Main publications on the long-term use of systemic antibiotics in patients with stable COPD.

Study and Design	Study Population	Main Results	Other Results
Sethi et al. (2010) [29] Double-blind, randomized, placebo-controlled trial Moxifloxacin 400 mg once daily for 5 days, every 8 weeks for a total of six courses vs placebo 1157 patients 48-week treatment period Further 24-week follow-up	Stable COPD patients with chronic bronchitis and at least two exacerbations in the 12 months prior to enrolment. Exclusions: tendon disease, arrhythmias, hepatic impairment, other respiratory disease, chronic colonization of pathogenic organisms resistant to moxifloxacin, systemic or inhaled antibiotic therapy during the 6 weeks prior to screening, need for home ventilatory support for COPD.	Reduced odds of exacerbation: 20% in the ITT population 25% among the PP population 45% in PP patients with purulent/mucopurulent sputum at baseline.	No differences in hospitalization or mortality rates, lung function or changes in SGRQ total scores. Significant difference in favor of moxifloxacin in the SGRQ symptom domain. More adverse events with moxifloxacin (mainly gastrointestinal). Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility.
Brill et al. (2015) [84] Single-blind, randomized, placebo-controlled trial 4 treatment groups -Moxifloxacin 400 mg daily for 5 days every 4 weeks -Doxycycline 100 mg/day -Azithromycin 250 mg 3 times a week - Placebo 99 patients 13-weeks treatment period	Stable COPD patients with chronic bronchitis. Exclusions: Other clinically significant respiratory disease, COPD exacerbation in the 4 weeks preceding screening or before randomization, hepatic or renal impairment, evidence of tuberculosis, uncontrolled hypertension, prolonged Q-T interval, long term antibiotics for any reason.	Non-significant reduction in bacterial load in the treatment arms, compared to placebo. No significant improvements in bacterial load measured by 16S qPCR or in airway inflammation.	More treatment-related adverse events with moxifloxacin. Mean inhibitory concentrations increased x3 times over placebo in all treatment arms.
Pettigrew (2016) [85] Retrospective study Fluorquinolones vs. macrolides 77 patients 15 years follow-up	COPD patients with chronic bronchitis and at least 1 H. influenzae isolation. Exclusions: asthma, bronchiectasis, inability to comply with a schedule of monthly clinical visits, immunosuppressive or other life-threatening disorders.	Fluoroquinolone administration was associated with increased H. influenzae eradication compared to macrolides. No difference in H. influenzae eradication when comparing macrolide administration to no antibiotic.	19% strains developed x4 increase in azithromycin MIC. No mutations in quinolone resistance-determining regions.

ITT: intention to treat; PP per protocol; SGRQ: St. George’s Respiratory Questionnaire; COPD: chronic obstructive pulmonary disease; MIC: Minimum inhibitory concentration.