. 2022 Dec 14;15:7271–7292. doi: 10.2147/IDR.S318173

Table 3.

Studies on the Efficacy/Effectiveness and Safety of Colistin in Bronchiectasis Patients, in Chronological Order According to the Year of Publication

First Author Country Publication Year	Type of Study	Objectives of the Study	Inclusion Criteria	Number and Characteristics of Patients Included	Dose and Duration of the Inhaled Treatment	Efficacy / Effectiveness Results	Antibiotic Resistance and Safety Results
Steinfort, DP Australia 2007⁵²	Prospective, non-controlled.	To examine the utility of long-term nebulized colistin in patients with COPD and non-CF bronchiectasis.	Patients with bronchiectasis or severe COPD (FEV₁<40%), as well as repeated isolates of multi-drug resistant Gram-negative bacteria in sputum cultures with the following clinical features: High rates of exacerbations or admissions to hospital. Difficulty with symptom control. High volume of sputum production in between exacerbations.	18 patients: 14 idiopathic bronchiectasis. 4 severe COPD/chronic infective bronchitis. 66% women Age: 69 ± 10.2 years.	Nebulized colistin 30 mg daily Duration: 41 ± 25.6 months (6–116).	Compared with the previous period, after the start of colistin treatment, significant differences were found in: Mean decline in FEV₁ was slower. Mean decline in FVC was slower. Improvement in patient-reported quality of life using a visual analogue scale. Three patients showed clearance of Pseudomonas spp. at the end of the study period.	No resistance to colistin was recorded among the bacterial isolates obtained. Patients in the cohort reported no side effects. One patient ceased colistin because of perceived ineffectiveness.
Dhar, R United Kingdom 2010⁵³	Retrospective.	To assess the efficacy of nebulized colomycin in P. aeruginosa-colonized bronchiectasis patients.	Patients with bronchiectasis colonized by P. aeruginosa who had received a minimum of 6 months of treatment. Patients who received concomitant prophylactic macrolide treatment for >4 weeks were excluded.	19 patients 53% women Mean age: 66 years.	Nebulized colomycin 1–2 MU twice daily Mean duration: 21.2 months (6–39).	After initiation of colomycin, there was a significant reduction in: Exacerbations/year. Hospitalizations/year. Sputum P aeruginosa positivity/year. Sputum volume.	NS
Berlana, D Spain 2011⁵⁴	Prospective, observational cohort study.	To compare clinical and microbiologic outcomes in non-CF patients with P. aeruginosa bronchial colonization who were receiving nebulized colistin or colistin + tobramycin with those who were receiving tobramycin alone.	Patients with bronchiectasis or COPD with chronic P. aeruginosa bronchial colonization who were receiving long-term inhaled antibiotic (minimum 12 weeks) with colistin and/or tobramycin, between January 2004 and December 2008. Patients with treatment adherence lower than 80% were excluded.	81 patients with 97 courses of inhaled antibiotic: colistin (n=31), colistin + tobramycin (n=16) or tobramycin (n=50). 86% bronchiectasis 14% COPD 45% women Age: 62.5 ± 14.3 years.	Nebulized colistin 1–2 MU every 12h and/or tobramycin 100–200 mg every 12h. Duration: 577.9 ± 470.1 days.	No significant differences between colistin and tobramycin were found in the mean number of hospital admissions, duration of hospitalizations, duration of antibiotic treatment, mortality, or emergence of other opportunistic microorganisms. Patients treated with both inhaled antibiotics had significantly fewer days of hospitalization and fewer days of antibiotic use than those treated with tobramycin alone.	Emergence of resistance to colistin was lower than resistance to tobramycin. The overall frequency of adverse events was 40% (30.3% as probable and 9.8% as definite), mainly respiratory. Events leading to discontinuation in 18% (colistin 26%, tobramycin 13%). No significant differences between colistin and tobramycin were found in adverse events.
Tabernero Huguet, E Spain 2015⁵⁹	Prospective, controlled, open label study.	To assess the effectiveness of inhaled colistin in reducing hospital readmissions in elderly patients with bronchiectasis and chronic bronchial P. aeruginosa infection.	Elderly patients (>65 years) with bronchiectasis, in whom at least one month after admission and correct treatment with two intravenous antibiotics for 15 days, P. aeruginosa isolation persisted in culture with the stable patient. Patients with dementia, or associated terminal illness, were excluded.	38 patients: 19-patient control group: treatment optimization + comprehensive (standardized education and respiratory physiotherapy). 19-patient intervention group: in addition to the above, inhaled colistin. Women: 22% (control group) and 15% (intervention group). Mean age: 78.1 years (control group); 77.7 years (intervention group).	Nebulized colistin 1 MU every 12h with i-neb nebulizer. Duration: 1 year.	There were no differences in the annual number of hospital admissions between the control group and the colistin group, or in the length of the hospitalization. There were no differences in lung function or clinical symptoms between both groups. P. aeruginosa was eradicated in 45% of the intervention group, and in only one of the control groups (P<0.05).	No significant changes were observed in P. aeruginosa antibiotic sensitivity or in sputum flora. Five patients (25%) stopped the nebulized treatment because of adverse effects.
Bruguera-Avila, N Spain 2017⁶¹	Retrospective	To analyze whether the introduction of nebulized colistin in patients with COPD and infection with P. aeruginosa is associated with a decrease of the number and duration of severe exacerbations.	Patients with severe COPD (FEV₁<50%), frequent exacerbations and chronic/intermittent bronchial colonization by P. aeruginosa who received nebulized colistin for at least 3 months, between January 2010 and December 2014. Patients with asthma, malignancy, unstable heart disease, or a main diagnosis of bronchiectasis were excluded.	36 patients (75% had bronchiectasis). 0% women. Age: 72.7 ± 2.1 years.	Nebulized colistin 1 MU every 12h with i-neb nebulizer. Duration: 10.7±4.2 months.	After initiation of colomycin, there was a significant reduction in: Number of admissions. Duration of admissions. These results were similar in patients with and without bronchiectasis. No pre-post differences were detected in the number of moderate exacerbations not requiring admission. Eradication of P. aeruginosa in 38.9% of patients.	No differences in the culture results during follow-up were found between patients with and without bronchiectasis. Resistance to colistin was only reported in bacteria known as constitutively resistant. Four patients reported bronchospasm (11.1%) and three of these dropped out for this reason (8.4%).
Blanco-Aparicio, M Spain 2019⁵⁵	Prospective, observational cohort study.	To evaluate the efficacy of an antibiotic eradication protocol for P. aeruginosa infection consisting of the administration of systemic antibiotics followed by inhaled colistin for 12 months in patients with NCFB.	Patients with bronchiectasis, ≥1 positive culture for P. aeruginosa, follow-up for at least 1 year after eradication treatment. Patients without systemic antibiotic treatment (oral or IV) prior to starting inhaled antibiotic, and those who achieved successful P. aeruginosa eradication only with systemic antibiotic treatment, were excluded.	67 patients. Women: 40.3%. Age: 67.2 ± 14.6 years.	Eradication protocol: Oral ciprofloxacin (750 mg twice daily) for 3 weeks OR IV tobramycin (5 mg/kg) plus beta-lactam antipseudomonal antibiotics for 2 weeks. - Nebulized colistin 1 MU every 12h with i-neb nebulizer, for 1 year.	After initiation of colistin, there was a significant reduction in: Number of exacerbations. Number of hospital admissions. Number of antibiotic cycles. Eradication of P. aeruginosa was achieved in: 61.2% after 3 months; 50.7% after 6 months; 43.3% after 9 months; 40.3% after 1 year. No significant differences in the eradication rate of P. aeruginosa in the short or long term, depending on the number of previous positive sputum cultures.	Mild adverse effects (cough and/or wheezing) were reported by five (7.5%) patients during the first month of treatment but did not result in discontinuation of therapy.
López-Gil, MM Spain 2019⁵⁶	Retrospective	To evaluate whether treatment with nebulized colistin for at least 6 months reduces the number of admissions and visits to the emergency department.	Patients with bronchiectasis with CBI by P. aeruginosa, who had received inhaled colistin for at least 6 months. Patients with lung transplant or interstitial lung disease were excluded.	44 patients. Women: 45.5%. Age: 71.4 ± 11.3 years.	Nebulized colistin 1 MU every 12h with i-neb nebulizer. Duration: 18.27 months.	After initiation of colistin, there was a significant reduction in: P. aeruginosa positive cultures. Number of antibiotic cycles and days of antibiotic treatment. Number of emergency room visits, admissions, and hospitalization days.	There was a slight (not significant) tendency to isolate microorganisms other than P. aeruginosa during treatment, especially S. aureus. 90.9% of patients did not experience any adverse effects attributable to nebulized colistin.
Montón C et al Spain 2019⁶³	Retrospective	To establish whether a combination of nebulized colistin plus continuous azithromycin in severe COPD patients with CBI due to P. aeruginosa reduces the frequency of exacerbations, and to assess its microbiological effect.	Patients with severe COPD and chronic bronchial infection by P. aeruginosa treated with nebulized colistin for at least 3 months between 2005 and 2015, in combination with long-term oral azithromycin. Patients with a main diagnosis of bronchiectasis were excluded.	32 patients (78% had bronchiectasis). Women: 0% Age: 74.7 ± 7 years.	Nebulized colistin 1–2 MU every 12h with Jet nebulizer or 0.5–1 MU every 12h with I-neb nebulizer. Median duration: 17 months (7–24).	Comparing the 24 months prior to the start of treatment with the subsequent 24 months, the following were observed: Reduction in COPD exacerbations (38.3%), hospitalizations (41.5%), and days of admission (41.9%). P. aeruginosa sputum isolates in both exacerbations and stable phase. - Eradication of P. aeruginosa in 47% of patients in the first year of follow-up; 28% patients remained negative after two years.	P. aeruginosa sputum isolates were multidrug-resistant to antibiotics in 43.7% of the patients at baseline; this percentage did not increase throughout follow-up. No resistance to colistin was observed. 3 patients (9%) presented bronchospasm as a late adverse event (after the first 3-month period of treatment).
Martínez-García, MÁ Spain 2020⁶⁷	Multi-center study of historic cohorts.	To identify the efficacy and safety of treatment with inhaled antibiotics in a dry powder formulation. To identify the patient profile most susceptible to adverse effects and withdrawal of the treatment.	Patients with bronchiectasis who had received at least one dose in a dry powder formulation. There were no criteria for exclusion due to the intention to perform a real-life study.	164 patients from 33 centers: 86% were treated with colistin and 14% with tobramycin. Women: 53% Age: 65.7 ± 14.4 years.	Dose: NS Duration: 6 ± 6.5 months (1–30).	After initiation of colistin, there was a significant reduction in: The number of non-severe and severe exacerbations. Percentage of patients with CBI due to P. aeruginosa (81% vs 52%) and other PPM (29% vs 10%). No differences were found in sputum production, dyspnea severity. or lung function impairment. There were no statistically significant differences between the efficacy of colistin and tobramycin.	At least one adverse effect was observed in 54.2% of the patients, and 24.4% had to interrupt their treatment as a result of an adverse effect (cough in 84% of these cases). These patients had more severe bronchiectasis, more time of symptoms, previous coughing, more difficulty in handling the device, and less therapeutic education about use of the device. Patients with colistin presented a lower proportion of withdrawals from treatment, less difficulty in using the device, and a smaller proportion of resistances to P. aeruginosa than patients under tobramycin treatment.
de la Rosa-Carrillo, D Spain 2021⁶⁴	Multicenter, retrospective cohort study.	To describe the effectiveness and safety of inhaled antibiotics in COPD patients, as well as the patient profile in which they are usually prescribed and the patient groups that can most benefit from this treatment.	COPD patients who had received at least one dose of any inhaled antibiotic treatment in the five years prior to their inclusion in the study (2013–2018), and for whom exacerbation data were available for at least 1 year.	693 patients from 35 centers (73.9% of them had bronchiectasis). Different treatments: colistin (82.5%), tobramycin (15.3%), ceftazidime (1.6%), gentamicin (0.4%), or amikacin (0.1%). Women: 13.7% Age: 74.1 ± 8.5 years.	Dose: NS Median treatment duration: 8.9 months (0.1–71.5).	After initiation of inhaled antibiotics, there was a significant reduction in: Number of exacerbations (−33.3%), hospital admissions (−33.3%), and hospitalization days (−26.2%). Frequency and purulence of expectoration. Isolation of any PPM. CBI by any PPM. - CBI by PA.	25.4% of patients presented non-severe side effects, the most frequent of these being bronchospasm (10.5%), dyspnea (8.8%), and cough (1.7%).

Abbreviations: CBI, chronic bronchial infection; CF, cystic fibrosis; CI, confidence interval; COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; HR, hazard ratio; IV, intravenous; MU, mega units; NS, not specified; PPM, potentially pathogenic microorganism; RR, relative risk.