What Is Colistin Used For? Approved Uses, Per the Label

Colistin is a prescription medicine in the United States, not an investigational agent. It reaches patients in two approved forms: colistimethate sodium (a prodrug given by injection, marketed as Coly-Mycin M Parenteral and as generic colistimethate for injection products referencing it) and colistin sulfate, which appears as one component of a combination otic suspension. This page summarises what the approved labeling states these products are indicated for, how those indications came to be approved, and what published randomized trials have reported about colistin. It does not provide dosing and does not tell any reader what to do. This page is for educational purposes only and is not medical advice; consult a licensed physician or prescribing clinician about any question involving a specific person, infection or treatment plan.

The short answer

According to the US prescribing information, colistimethate sodium for injection is indicated for the treatment of acute or chronic infections caused by susceptible strains of certain gram-negative bacilli, and the labeling singles out infections caused by susceptible strains of Pseudomonas aeruginosa. The separate otic product containing colistin sulfate alongside neomycin, hydrocortisone and thonzonium bromide is indicated for superficial bacterial infections of the external auditory canal and for infections of mastoidectomy and fenestration cavities caused by susceptible organisms. Everything else that is sometimes discussed in connection with colistin, including nebulized administration, intrathecal or intraventricular administration, and laboratory combination strategies, sits outside those labeled indications.

Approved indications at a glance

Exact indication wording, warnings and the revision date appear on the labeling distributed with each specific product, and those documents differ slightly between the brand and generic versions. Readers who need verbatim text should consult the current prescribing information for the individual product rather than a summary.

Colistimethate sodium for injection: what the labeled indication covers

The parenteral indication is written around organism susceptibility rather than around a named infection syndrome. That is a style of labeling common to antibacterial drugs approved many decades ago, before indications were routinely tied to specific body sites such as complicated urinary tract infection or hospital acquired pneumonia. The labeling directs that susceptibility testing guide selection, and it names the gram-negative organisms against which clinical effectiveness has been described. Pharmacology reviews have noted that colistimethate is an inactive prodrug that converts in the body to colistin, and that this conversion, along with historically inconsistent ways of expressing strength across countries, created long standing confusion in the literature about how the drug is labeled and measured (PMID 33627412).

Organisms named in the parenteral labeling

• Pseudomonas aeruginosa, highlighted in the indication statement
• Escherichia coli
• Klebsiella pneumoniae
• Enterobacter aerogenes

The labeling also carries boxed and general warnings relating to renal function and neuromuscular effects, and it instructs that therapy be guided by culture and susceptibility results. Those safety sections are part of the approved document and sit alongside the indication rather than expanding it.

Colistin sulfate in the combination otic suspension

The otic product is a fixed combination in which colistin sulfate supplies gram-negative coverage, neomycin supplies additional antibacterial coverage, hydrocortisone acetate supplies an anti inflammatory corticosteroid, and thonzonium bromide acts as a surfactant. Its indication is narrow and anatomic: superficial bacterial infection of the external auditory canal, and infection of mastoidectomy and fenestration cavities, in each case when the causative organisms are susceptible to the antibiotic components. This is a separate approval from the injectable product, and the two labels cannot be read interchangeably.

How these indications came to be approved

Colistin entered clinical medicine in the 1950s and its US parenteral approval long predates the era of large randomized registration programs with prespecified primary endpoints. There is therefore no pivotal phase 3 trial underlying the colistimethate indication statement in the way there is for a contemporary antibacterial approval. Pharmacological reviews have described how the polymyxin class, including colistin, was largely abandoned for systemic use for several decades because of toxicity concerns and then returned to practice when few options remained for multidrug resistant gram-negative organisms, with modern pharmacokinetic and pharmacodynamic characterisation arriving only after the drug was already in widespread use (PMID 33627412). A 2024 review described colistin as an antibiotic of last resort for multidrug resistant gram-negative pathogens and reviewed the resistance mechanisms that have emerged around it (PMID 38674716).

The practical consequence is that the regulatory history of colistin runs in the opposite direction from most modern drugs: the indication came first and the controlled trial evidence accumulated afterward, much of it generated by investigators rather than by a sponsor seeking a new indication.

Randomized trial evidence involving colistin

Colistin as the active comparator in the ATTACK trial

The ATTACK trial was a multicentre, randomised, active controlled, phase 3 non-inferiority study comparing sulbactam-durlobactam with colistin in patients with serious infections caused by Acinetobacter baumannii-calcoaceticus complex, and the researchers reported that sulbactam-durlobactam met the non-inferiority criterion for 28 day all cause mortality while nephrotoxicity occurred less often in the sulbactam-durlobactam group than in the colistin group (PMID 37182534). A 2023 pharmacotherapy review of sulbactam-durlobactam described the combination as a beta-lactam and beta-lactamase inhibitor pairing developed specifically for carbapenem resistant Acinetobacter baumannii infections and summarised the ATTACK data supporting its approval (PMID 37052117). In that program colistin served as the standard of care comparator, which is itself a regulatory statement about where colistin sat in practice at the time the study was designed.

Colistin monotherapy compared with colistin based combination therapy

A randomized trial published in 2023 compared colistin monotherapy with colistin plus meropenem in patients with infections caused by carbapenem resistant organisms, and the study reported no significant difference between the two strategies in the primary mortality outcome (PMID 37538951). The study addressed a strategy question about how colistin is combined rather than whether colistin is indicated, so it does not alter the labeled indication wording.

How reviews describe colistin's place in therapy

A 2024 narrative review of infections caused by metallo-beta-lactamase producing gram-negative bacteria discussed the limited treatment options for these organisms and the role polymyxins have occupied among them (PMID 39467989). A 2025 review of strategies for combating colistin resistant isolates summarised approaches under investigation for organisms that no longer respond to colistin (PMID 41134327). Review articles and treatment guidance documents describe practice patterns; they do not change what the FDA approved labeling states, and the distinction matters when answering the question of what colistin is approved for.

Why resistance research appears alongside the indication

Much of the recent colistin literature concerns resistance rather than new indications. Researchers reported that the plasmid associated colistin resistance gene mcr-2 could be mobilised in Escherichia coli through an insertion sequence element, describing one route by which resistance determinants spread between organisms (PMID 33510713). A 2024 review catalogued the chromosomal and plasmid mediated mechanisms that reduce colistin activity and discussed the surveillance implications (PMID 38674716). This body of work explains why susceptibility testing is built into the labeled indication rather than expanding what the label permits.

Adverse Events in Comparative Trials: What Studies Report

In the ATTACK trial, researchers reported that nephrotoxicity was observed more frequently among patients randomised to colistin than among those randomised to sulbactam-durlobactam (PMID 37182534). Pharmacological reviews of the polymyxin class have described nephrotoxicity and neurotoxicity as the dose limiting toxicities that drove the historical decline of systemic polymyxin use and that continue to constrain it (PMID 33627412). The randomized comparison of colistin monotherapy with colistin plus meropenem also reported renal adverse events among colistin treated participants (PMID 37538951). The approved labeling carries its own warnings and precautions sections covering renal and neuromuscular risks, and those sections are the authoritative safety text for prescribing.

A note on uses that are not approved indications

Nebulized or inhaled colistimethate, intrathecal or intraventricular administration, compounded preparations, veterinary and agricultural applications, and laboratory work such as the investigation of colistin as an efflux pump inhibitor in multidrug resistant Klebsiella pneumoniae (PMID 41044168) or the testing of dipyrrin adjuvants intended to restore colistin activity (PMID 35704751) are outside the approved US indications and are presented here only as context, not as uses.

Questions a prescribing clinician can answer

Whether colistin fits a particular clinical situation depends on culture and susceptibility results, renal function, concurrent medications, infection site and locally available alternatives. Those judgments belong to a licensed prescribing clinician with access to the full clinical picture and the current product labeling. Published trials describe what happened in defined study populations; they are not a substitute for individual medical advice, and no part of this summary should be read as a recommendation for any person.

References

• Efficacy and safety of sulbactam-durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii-calcoaceticus complex: a multicentre, randomised, active-controlled, phase 3, non-inferiority clinical trial (ATTACK) (The Lancet Infectious Diseases, 2023)
• Sulbactam-durlobactam: A novel beta-lactam-beta-lactamase inhibitor combination targeting carbapenem-resistant Acinetobacter baumannii infections (Pharmacotherapy, 2023)
• Rescuing the Last-Line Polymyxins: Achievements and Challenges (Pharmacological Reviews, 2021)
• A Review on Colistin Resistance: An Antibiotic of Last Resort (Microorganisms, 2024)
• Colistin Monotherapy versus Combination Therapy for Carbapenem-Resistant Organisms (NEJM Evidence, 2023)
• The Challenge of Treating Infections Caused by Metallo-beta-Lactamase-Producing Gram-Negative Bacteria: A Narrative Review (Drugs, 2024)
• Novel strategies for combating colistin-resistant isolates: a review (Archives of Microbiology, 2025)
• ISEc69-Mediated Mobilization of the Colistin Resistance Gene mcr-2 in Escherichia coli (Frontiers in Microbiology, 2020)
• A novel role for colistin as an efflux pump inhibitor in multidrug-resistant Klebsiella pneumoniae (Scientific Reports, 2025)
• Simple Dipyrrin Analogues of Prodigiosin for Use as Colistin Adjuvants (ChemMedChem, 2022)