Inhaled Colistin Plus IV Colistin Beats Other Antibiotic Combos for Drug-Resistant Pneumonia in Chinese Cohort

When the last-line antibiotics fail, doctors facing carbapenem-resistant Gram-negative bacilli pneumonia often reach for colistimethate sodium, the intravenous prodrug of the old polymyxin colistin. A new multicenter retrospective cohort study from China, published in BMC Infectious Diseases, now suggests that the intravenous partner matters: patients who received intravenous colistimethate sodium (CMS) alongside nebulized CMS showed better clinical response and bacterial eradication than those who received nebulized CMS combined with intravenous non-CMS antibiotics, without additional safety signals.

The research team, led by Ran Li and Zhancheng Gao of Peking University People’s Hospital together with collaborators across 24 Chinese hospitals, compared two regimens in patients treated for pneumonia caused by carbapenem-resistant Gram-negative bacilli, a group of pathogens that includes carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumoniae (CRKP), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). All patients in the analysis received nebulized CMS, delivered as an inhaled aerosol intended to concentrate the drug at the site of infection in the lung. The study group additionally received intravenous CMS, while the control group received intravenous antibiotics that did not contain CMS.

Among 427 eligible patients, 215 were assigned to the study group and 212 to the control group. Because this was a retrospective cohort study, the investigators used propensity score matching in a 1:1 ratio for the primary analysis, a statistical technique that pairs patients from the two groups who have similar baseline characteristics, thereby reducing the influence of confounding factors such as age, illness severity, and underlying conditions. The matched analysis included 130 pairs. The median age was 69 years in the study group versus 71 years in the control group, and the proportion of male patients was 73.9 percent versus 85.4 percent. Most patients in both groups had no prior Gram-negative bacilli infection, at 86.9 percent and 88.5 percent respectively.

The pathogen mix differed between the matched groups in ways that matter for interpretation. Carbapenem-resistant Acinetobacter baumannii was the predominant organism in both arms but was more frequent in the study group, at 72.9 percent versus 55.3 percent. Carbapenem-resistant Klebsiella pneumoniae accounted for 9.3 percent versus 19.5 percent, and carbapenem-resistant Pseudomonas aeruginosa for 7.8 percent versus 12.2 percent. CRAB is notoriously difficult to eradicate and is a leading cause of hospital-acquired pneumonia in intensive care units, so the higher proportion of CRAB in the intravenous CMS arm makes the observed advantage in that arm particularly notable.

The results favored the intravenous CMS regimen on both effectiveness endpoints. Patients in the study group had a shorter duration of nebulized CMS, a median of 9 days versus 11 days in the control group, a difference that reached statistical significance at p = 0.02. The clinical response rate, a measure of whether the pneumonia improved under treatment, was 82.3 percent in the study group versus 70.8 percent in the control group, at p = 0.03. Bacterial eradication, meaning clearance of the resistant organism, was likewise better with intravenous CMS, at 80.6 percent versus 68.5 percent, again at p = 0.03.

To test whether these findings would hold beyond the matched sample, the researchers ran a supportive multivariable logistic regression using the entire cohort of 427 patients. This approach controls for potential confounding factors by including them as covariates in the regression model. The adjusted odds ratio for clinical response with the intravenous CMS regimen was 2.60, with a 95 percent confidence interval of 1.48 to 4.57 and p = 0.001. In plain terms, after accounting for baseline differences, patients receiving intravenous CMS plus nebulized CMS had roughly two and a half times the odds of clinical response compared with those receiving nebulized CMS plus intravenous non-CMS antibiotics.

Safety was a central concern, because colistin is known for nephrotoxicity, the potential to cause kidney injury, particularly when given systemically. The study found no significant difference in mortality between the two groups, and no significant difference in kidney injury. The absence of additional adverse events in the intravenous CMS arm is an important part of the message, since a regimen that improved effectiveness while adding new safety concerns would be a harder sell for clinicians already managing fragile, critically ill patients.

The technical rationale for combining inhaled and intravenous colistin is rooted in pharmacology. Colistimethate sodium is an inactive prodrug that is converted to the active antibiotic colistin in the body. Intravenous dosing of colistin has well-documented limitations in the lung: the drug penetrates poorly into lung tissue and epithelial lining fluid, which can leave the site of infection underdosed even when plasma concentrations are adequate. Nebulized delivery bypasses this barrier by depositing the aerosolized drug directly into the airways, achieving high local concentrations. The open question addressed by this study is whether the intravenous partner should also be CMS, providing systemic coverage with the same agent, or whether a different intravenous antibiotic with activity against the resistant organism can serve as the systemic component while nebulized CMS handles the local component.

The answer from this cohort favors keeping CMS in the intravenous component as well. One possible explanation is that the non-CMS intravenous antibiotics used in the control group may have had weaker or less reliable activity against the specific resistant pathogens involved, particularly CRAB, for which few alternatives exist. Another is that the dual CMS approach provides a higher total colistin exposure, both systemically and locally, which could translate into faster bacterial killing and shorter treatment courses, consistent with the shorter nebulized CMS duration observed in the study group.

As a retrospective cohort study, the analysis carries inherent limitations that the authors and readers must weigh. Treatment assignment was not randomized, and despite propensity score matching and multivariable adjustment, unmeasured confounding cannot be excluded. The pathogen distribution differed between groups, with more CRAB in the intravenous CMS arm, and the generalizability of findings from 24 Chinese hospitals to other settings remains to be established. The study was approved by the Ethical Review Committee of Peking University People’s Hospital and conducted in compliance with the Declaration of Helsinki, with informed consent waived for the retrospective design. The research received no specific grant from funding agencies, and the authors declare no competing interests. Published as open access on 18 September 2026, the article is citable under DOI 10.1186/s12879-026-14462-5 and is subject to further editorial edits before the final Version of Record replaces it. For clinicians confronting carbapenem-resistant Gram-negative bacilli pneumonia, the study adds evidence that when nebulized CMS is part of the regimen, pairing it with intravenous CMS rather than intravenous non-CMS antibiotics is associated with improved clinical response and bacterial eradication, without additional safety concerns.

Subject of Research: Antimicrobial Resistance

Article Title: Compare intravenous colistimethate sodium (CMS) with non-CMS antibiotics in combination with nebulized CMS for treating Carbapenem-resistant Gram-negative Bacilli (CR-GNB) pneumonia: a multicenter retrospective cohort study

Article References: Li, R., Fu, Y., Mu, G., Cheng, C., Zhao, M., Gu, Y., Zhang, C., Tao, Y., Yi, Y., Xu, H., Li, D., Wang, G., Chai, S., Dai, B., Xu, Y., Deng, S., Dou, L., Wang, Z., Zhang, Y., & Gao, Z. (2026). Compare intravenous colistimethate sodium (CMS) with non-CMS antibiotics in combination with nebulized CMS for treating Carbapenem-resistant Gram-negative Bacilli (CR-GNB) pneumonia: a multicenter retrospective cohort study. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14462-5

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14462-5

Keywords: colistimethate sodium, nebulized colistin, carbapenem-resistant Gram-negative bacilli, CRAB, CRKP, CRPA, pneumonia, antimicrobial resistance, BMC Infectious Diseases, propensity score matching, Compare, intravenous