Colistin Benefits: What Studies Report

What colistin is, and how its regulatory status is described

Colistin, also known as polymyxin E, is a prescription medicine approved by medicines regulators and dispensed only under the supervision of a licensed clinician. In hospital practice it is given as the prodrug colistimethate sodium, and inhaled colistimethate products are authorised in some jurisdictions for chronic lung infection with Pseudomonas aeruginosa in cystic fibrosis. Product labelling describes treatment of acute and chronic infections caused by susceptible strains of certain gram-negative bacilli. A 2024 review characterised colistin as an antibiotic of last resort that returned to clinical use because of multidrug-resistant gram-negative pathogens (PMID 38674716). On this page, "benefits" means outcomes that researchers measured and reported at label level: survival, clinical response and microbiological response in gram-negative infection. Whether colistin is appropriate in any individual case is a decision for a prescribing clinician.

This page is for educational purposes only and is not medical advice; consult a licensed physician or qualified prescriber about any infection, medicine or treatment decision. No dosing directions appear here.

Outcome domain 1: survival and clinical response in serious gram-negative infection

The largest recent randomised evidence involving colistin comes from trials in which it served as the active comparator for a newer antibiotic. In the phase 3 ATTACK trial, researchers randomised patients with serious infections caused by the Acinetobacter baumannii-calcoaceticus complex to sulbactam-durlobactam or to colistin, and the study reported lower 28-day all-cause mortality in the sulbactam-durlobactam group than in the colistin group, meeting its non-inferiority endpoint (PMID 37182534). That design means the trial documented what outcomes looked like on colistin-based therapy in a severely ill population, rather than testing colistin against placebo.

A 2018 observational comparison in patients with infections due to carbapenem-resistant Enterobacteriaceae compared colistin-containing regimens with ceftazidime-avibactam, and the researchers reported outcomes that favoured ceftazidime-avibactam on their combined measure of death, kidney injury and failure to improve (PMID 29020404). Observational work of this kind cannot separate drug effect from differences between the patients who received each regimen, a limitation the authors themselves addressed through statistical adjustment (PMID 29020404).

How to read these comparisons

Neither of these studies described colistin producing a benefit over an inactive control; both described how colistin-treated groups fared beside a newer comparator, and in both the newer agent looked at least as good or better on the reported endpoints (PMID 37182534, PMID 29020404). Readers looking for evidence that colistin improves survival relative to no treatment will not find modern randomised trials of that design, because withholding antibiotic therapy from patients with serious gram-negative infection is not studied.

Outcome domain 2: colistin alone compared with colistin-based combinations

A recurring clinical question has been whether adding a second antibiotic to colistin improves outcomes. A randomised trial published in 2023 compared colistin monotherapy with colistin plus meropenem in patients with infections caused by carbapenem-resistant organisms, and the researchers reported no significant difference between the two strategies on the primary clinical outcome (PMID 37538951).

Narrative and systematic reviews have reached similarly cautious conclusions. A 2019 review of polymyxin combination therapy summarised the laboratory rationale for synergy alongside clinical data and reported that the clinical evidence did not consistently establish an advantage for combinations (PMID 30974813). An earlier 2014 review of combination therapy for carbapenem-resistant gram-negative bacteria described observational signals favouring combinations in some severely ill subgroups while noting the absence of adequately powered randomised data at that time (PMID 24872346).

Outcome domain 3: inhaled colistimethate in hospital-acquired pneumonia

Delivering colistimethate directly to the airway has been studied as a way to raise lung concentrations. A 2023 review examined high-dose nebulised colistimethate sodium in hospital-acquired pneumonia caused by gram-negative bacteria with difficult-to-treat resistance, and the authors reported that pharmacokinetic work supported higher airway exposure while clinical outcome data remained limited and heterogeneous (PMID 37374959). The review described adjunctive inhaled use as an area where the evidence base had not resolved whether clinical outcomes improve (PMID 37374959). Approved inhaled colistimethate products exist for chronic Pseudomonas aeruginosa lung infection in cystic fibrosis in several regions; the pneumonia question addressed in that review sits outside that labelled setting, and route decisions belong to a treating clinician.

Outcome domain 4: laboratory and preclinical findings

Several of the most frequently cited colistin papers are in vitro or preclinical and do not describe patient outcomes.

• Efflux pump inhibition (laboratory): a 2025 laboratory study described colistin acting as an efflux pump inhibitor in multidrug-resistant Klebsiella pneumoniae isolates, a mechanism the researchers reported at the bacterial level rather than in treated patients (PMID 41044168).
• Flavonoid potentiation (laboratory and animal): a 2023 study reported that natural flavonoids disrupted bacterial iron homeostasis and increased colistin activity against resistant bacteria in experimental models (PMID 37294761). Findings of this type are hypothesis-generating and have not been shown in that work to change human outcomes (PMID 37294761).
• Surface disinfection (laboratory): a 2018 quantitative carrier test evaluated germicidal products against carbapenem-resistant and colistin-resistant Enterobacteriaceae on surfaces, and the researchers reported activity data for environmental disinfection rather than for treatment (PMID 29735565).
• Strategies against resistant isolates (review of preclinical work): a 2025 review catalogued adjuvants, combinations and alternative approaches under investigation against colistin-resistant isolates, and reported that most remained at laboratory or early experimental stages (PMID 41134327).

Study-by-study summary table

Adverse Events: What Studies Report

Toxicity is the most consistently documented feature of colistin in the clinical literature. A 2023 review of critically ill patients treated with colistimethate sodium reported nephrotoxicity as the dominant adverse event, alongside neurotoxicity and the emergence of resistance during therapy (PMID 36925725). In the randomised ATTACK trial, researchers reported a lower incidence of nephrotoxicity in the sulbactam-durlobactam group than in the colistin group (PMID 37182534). The 2018 observational comparison likewise incorporated kidney injury into its composite outcome measure, which favoured ceftazidime-avibactam (PMID 29020404). Monitoring, dose selection and management of any adverse effect are matters for the prescribing clinician and are not covered here.

Resistance: what the reviews documented

A 2024 review of colistin resistance described chromosomal and plasmid-mediated mechanisms, including mobile mcr genes, and reported that resistance has been detected across human, animal and environmental sources (PMID 38674716). A 2025 review surveying countermeasures against colistin-resistant isolates reported that proposed strategies were largely experimental rather than established clinical practice (PMID 41134327). A 2018 carrier-test study also reported germicidal activity data against colistin-resistant Enterobacteriaceae on surfaces, which belongs to infection prevention rather than treatment (PMID 29735565).

Where the evidence is thin or absent

• Placebo-controlled benefit: the modern randomised literature cited here used active comparators rather than placebo, so no trial on this page reported colistin against an untreated control (PMID 37182534, PMID 37538951).
• Combination advantage: randomised and review evidence did not establish a consistent outcome advantage for colistin-based combinations (PMID 37538951, PMID 30974813).
• Inhaled route outcomes: the 2023 review reported limited and heterogeneous clinical outcome data for nebulised colistimethate in pneumonia (PMID 37374959).
• Non-infection uses: the verified literature on this page concerns antibacterial activity, toxicity and resistance only; laboratory findings such as efflux pump inhibition were reported at the bacterial level, not as patient benefits (PMID 41044168).

Key takeaways

1. Colistin is an approved prescription antibiotic used under clinician supervision for infections caused by susceptible gram-negative bacteria, and a 2024 review described it as a last-resort option (PMID 38674716).
2. Randomised and observational comparisons reported mixed and sometimes unfavourable results for colistin against newer agents, as in the ATTACK trial (PMID 37182534) and a ceftazidime-avibactam comparison (PMID 29020404), while reviews documented nephrotoxicity in critically ill patients (PMID 36925725) and spreading resistance (PMID 38674716).
3. Adding meropenem to colistin did not significantly change the primary outcome in a 2023 randomised trial (PMID 37538951).
4. Laboratory and preclinical findings, including flavonoid potentiation, have not been shown in those studies to translate into patient outcomes (PMID 37294761).

References

• Efficacy and safety of sulbactam-durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii-calcoaceticus complex (ATTACK) (The Lancet Infectious Diseases, 2023)
• Colistin Monotherapy versus Combination Therapy for Carbapenem-Resistant Organisms (NEJM Evidence, 2023)
• Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae (Clinical Infectious Diseases, 2018)
• Polymyxins: To Combine or Not to Combine? (Antibiotics, 2019)
• Combination therapy for carbapenem-resistant Gram-negative bacteria (Journal of Antimicrobial Chemotherapy, 2014)
• High-Dose Nebulized Colistin Methanesulfonate and the Role in Hospital-Acquired Pneumonia Caused by Gram-Negative Bacteria with Difficult-to-Treat Resistance: A Review (Microorganisms, 2023)
• Adverse Events and Drug Resistance in Critically Ill Patients Treated with Colistimethate Sodium: A Review of the Literature (Infection and Drug Resistance, 2023)
• A Review on Colistin Resistance: An Antibiotic of Last Resort (Microorganisms, 2024)
• Novel strategies for combating colistin-resistant isolates: a review (Archives of Microbiology, 2025)
• A novel role for colistin as an efflux pump inhibitor in multidrug-resistant Klebsiella pneumoniae (Scientific Reports, 2025)
• Natural flavonoids disrupt bacterial iron homeostasis to potentiate colistin efficacy (Science Advances, 2023)
• Germicidal Activity against Carbapenem/Colistin-Resistant Enterobacteriaceae Using a Quantitative Carrier Test Method (Antimicrobial Agents and Chemotherapy, 2018)