Colistin: A Literature Course

This page is for educational purposes only and is not medical advice; consult a licensed physician for any question about health, medication or treatment. Nothing here is a protocol, a recommendation or an endorsement. Every claim below is tied to a specific published paper, and where a paper did not examine something, that gap is stated rather than filled in.

Module 1 — What Colistin Is and How It Has Been Studied

Colistin, also named polymyxin E, is a cyclic cationic polypeptide antibiotic. An extended review covering the years 2000 to 2019 described colistin as a polymyxin-class agent originally derived from bacterial fermentation and reintroduced into clinical use because of the spread of multidrug-resistant Gram-negative organisms (PMID 32284036). That same review framed colistin as a "last-line" option, meaning the literature positions it after other antibiotic classes rather than as a first choice.

Forms described in the literature

Two chemical forms appear repeatedly in published work: colistin sulfate and colistimethate sodium, an inactive prodrug that converts to colistin. The 2000–2019 review discussed both the parenteral use of the prodrug and the pharmacological complexity this creates for measuring active drug (PMID 32284036). Beyond systemic use, investigators have studied non-standard routes: a 2019 case report described intra-vesical colistin instillation for a Pseudomonas aeruginosa urinary tract infection (PMID 30756071). Formulation science has also been applied to the molecule — a 2016 study prepared colistin-entrapped liposomes driven by electrostatic interaction and characterised them for intravenous administration (PMID 27388548).

How the evidence base is shaped

Most of the retrievable colistin literature falls into a few buckets: narrative and extended reviews, in vitro susceptibility and synergy testing, resistance-mechanism molecular studies, animal or cell-culture toxicity work, and single-patient case reports. Large, modern, randomised controlled trials are notably scarce in the verified set used for this course.

Limits of the evidence (Module 1): a review summarising two decades of publication (PMID 32284036) inherits the heterogeneity of its sources; case reports such as the intra-vesical description (PMID 30756071) describe one patient and cannot establish frequency, comparative effect or safety. Formulation work in the liposome paper was laboratory characterisation, not a clinical outcome study (PMID 27388548).

Module 2 — Mechanism as Described in the Literature

The mechanism described across reviews is electrostatic and membrane-based. Colistin carries positive charge and interacts with the negatively charged lipid A component of lipopolysaccharide (LPS) in the Gram-negative outer membrane, displacing divalent cations and destabilising membrane integrity. The extended 2000–2019 review set out this outer-membrane target and linked it to colistin's Gram-negative-restricted spectrum (PMID 32284036).

Mechanism inferred from resistance

Much of what the literature asserts about mechanism is read backwards from resistance. A 2019 review of molecular mechanisms in Enterobacteriaceae described modification of the lipid A target — including addition of cationic moieties that reduce the negative surface charge — as a principal route to colistin resistance, alongside plasmid-mediated determinants (PMID 31190901). A 2020 mBio study reported that the O-antigen epitope governed susceptibility to colistin in Salmonella enterica, implicating LPS architecture beyond lipid A alone (PMID 31992619).

Regulatory and phage-associated modulation

A 2025 preprint reported that the combinatorial action of bacterial regulatory systems generated colistin heteroresistance — a state in which subpopulations within a nominally susceptible isolate survive exposure (PMID 40832241). Separately, a 2024 paper described phage-mediated colistin resistance in Acinetobacter baumannii, adding bacteriophage biology to the list of factors that shift susceptibility (PMID 38301486).

Limits of the evidence (Module 2): mechanism descriptions in reviews are syntheses, not fresh experiments (PMID 32284036). The heteroresistance regulatory work was posted as a preprint (PMID 40832241), meaning it had not completed peer review at the time of posting. The Salmonella O-antigen finding was species-specific and does not automatically transfer to other Gram-negative genera (PMID 31992619).

Module 3 — Reported Outcomes by Study

The table below groups the verified literature by model and endpoint. No entry should be read as a promise of benefit; each records what researchers set out to measure and what they said they observed.

Combination and adjuvant work

A 2018 study in Frontiers in Microbiology reported synergistic activity when colistin was combined with resveratrol against colistin-resistant Gram-negative pathogens (PMID 30131787). In the same year, researchers reported synergistic activity of colistin-containing combinations against colistin-resistant Enterobacteriaceae (PMID 30061285). A 2024 paper reported that cinnamaldehyde and baicalin reversed colistin resistance in Enterobacterales and A. baumannii strains (PMID 39066966). These were laboratory susceptibility findings, not patient outcomes.

Failure as an endpoint

Not all reported outcomes are favourable. A 2025 preprint reported that resistance, heteroresistance and fitness costs drove colistin treatment failure during Acinetobacter baumannii pneumonia (PMID 40777351). The study framed failure mechanistically rather than as a dosing problem alone.

Limits of the evidence (Module 3): synergy demonstrated in broth or on agar (PMID 30131787, PMID 30061285) does not establish clinical efficacy, tolerability or achievable tissue concentrations in humans. The resistance-reversal study tested defined strains under laboratory conditions (PMID 39066966). The treatment-failure work was a preprint (PMID 40777351) and single case reports cannot be generalised (PMID 30756071).

Module 4 — Colistin Side Effects: What Studies Report

Adverse-event reporting is one of the more consistent themes in the colistin literature. The extended review of publications from 2000 to 2019 discussed toxicity as a defining constraint on colistin use, with nephrotoxicity and neurotoxicity described as the principal reported concerns associated with the drug (PMID 32284036).

Neuronal cell findings

A 2024 study in Antioxidants reported that colistin induced oxidative stress and apoptotic cell death through activation of the AhR/CYP1A1 pathway in PC12 cells, a neuronal-like cell line (PMID 39061896). Researchers in that work framed oxidative stress as a candidate mechanism underlying neurotoxicity described elsewhere in the clinical literature (PMID 39061896).

Toxicity as a driver of formulation research

Interest in altered delivery is partly a response to toxicity. Investigators prepared colistin-entrapped liposomes for intravenous administration and characterised the resulting particles, an approach the field has pursued in the context of colistin's narrow therapeutic margin (PMID 27388548). Similarly, the localised intra-vesical route described in a 2019 case report reflects attempts to concentrate drug at a site of infection (PMID 30756071).

• Nephrotoxicity — discussed as a recurring reported concern in the 2000–2019 extended review (PMID 32284036).
• Neurotoxicity — described in the same review (PMID 32284036), with a cell-level oxidative and apoptotic mechanism reported in PC12 cells (PMID 39061896).
• Oxidative stress and apoptosis — reported via AhR/CYP1A1 activation in a neuronal cell model (PMID 39061896).

Limits of the evidence (Module 4): the PC12 findings were generated in cultured cells and cannot be translated directly to human incidence, severity or reversibility (PMID 39061896). The review summarised published reports rather than pooling standardised safety data (PMID 32284036). No verified paper here provides adverse-event rates per exposure, risk stratification by kidney function, or long-term follow-up.

Module 5 — Pharmacokinetics Where Data Exist

Colistin pharmacokinetics are complicated by the prodrug relationship between colistimethate sodium and active colistin. The extended review across 2000–2019 addressed pharmacokinetic and pharmacodynamic considerations as part of its account of colistin's re-emergence, including the difficulty of relating administered prodrug to active drug exposure (PMID 32284036).

Delivery and distribution research

Formulation studies address distribution indirectly. Researchers prepared and characterised colistin-entrapped liposomes formed through electrostatic interaction, explicitly for intravenous administration (PMID 27388548). Route selection also appears in the case literature: the 2019 report described intra-vesical administration for a urinary tract infection, a strategy predicated on local rather than systemic exposure (PMID 30756071).

Why exposure interacts with resistance

Pharmacokinetics and microbiology intersect in the heteroresistance literature. A 2025 preprint reported that resistance, heteroresistance and fitness costs drove treatment failure during A. baumannii pneumonia, a setting where drug penetration into lung tissue is a known variable (PMID 40777351). Another 2025 preprint reported that combinatorial regulatory-system action generated heteroresistance, implying that subpopulation behaviour under exposure is not captured by a single susceptibility number (PMID 40832241).

Limits of the evidence (Module 5): no verified paper in this set reports human plasma concentration–time curves, half-life values, clearance, volume of distribution or dose-exposure relationships, and none are stated here. The liposome study characterised a preparation rather than measuring in-human kinetics (PMID 27388548), and the review's pharmacological discussion is a synthesis of prior sources (PMID 32284036).

Module 6 — Regulatory Status, Stated Factually

Colistin is a licensed antibiotic in many jurisdictions, most commonly marketed as colistimethate sodium for injection or inhalation and as colistin sulfate for topical or oral-luminal use, with the exact product list, indications and labelling determined by each national regulator. The 2000–2019 extended review described colistin's clinical reintroduction as an approved antibacterial in the setting of multidrug-resistant Gram-negative infection (PMID 32284036).

Research-use-only material

Colistin sulfate is also sold by chemical suppliers as a research-use-only (RUO) reagent for laboratory microbiology — for example, the susceptibility, synergy and resistance-reversal experiments described in the literature (PMID 30061285, PMID 39066966). RUO material is labelled as not for diagnostic or therapeutic use in humans or animals; that designation is a regulatory classification of the material, not a statement about the molecule's pharmacology.

Compounding and non-standard routes

Non-labelled routes appear in the published record. The intra-vesical instillation described in 2019 is an example of an administration route that falls outside typical product labelling and would depend on institutional pharmacy preparation and local rules (PMID 30756071). Compounding of sterile preparations is governed in the United States by federal and state pharmacy law and standards such as USP chapters on sterile compounding; specific permissions vary. This is general regulatory information, not legal advice.

Veterinary and agricultural context

Colistin's use outside human medicine features in the resistance literature. A 2019 review of molecular resistance mechanisms in Enterobacteriaceae discussed mobile resistance determinants that spread across bacterial populations (PMID 31190901), and the 2000–2019 extended review treated resistance emergence as central to colistin's regulatory and stewardship story (PMID 32284036).

Limits of the evidence (Module 6): regulatory status is jurisdiction-specific and changes over time; none of the verified papers is a regulatory document, and none of them lists approved products, indications or label text. Readers seeking authoritative status should consult the relevant national medicines agency directly.

What the Studies Did Not Test

Across the verified literature used in this course, several questions remain unaddressed:

1. Non-infection uses. No verified paper here evaluated colistin for any purpose other than antibacterial activity or its associated toxicity.
2. Human dose–response. No verified paper here reports a human dosing regimen with matched exposure and outcome data, so none is described on this page.
3. Comparative clinical trials. The set contains reviews, in vitro work, cell models, preprints and a case report (PMID 30756071) — not randomised head-to-head trials.
4. Long-term safety. The neuronal-cell toxicity study measured cellular endpoints, not durable human organ outcomes (PMID 39061896).
5. Whether adjuvants work in patients. Resveratrol, cinnamaldehyde and baicalin combinations were reported in vitro only (PMID 30131787, PMID 39066966).
6. Whether phage-associated and regulatory heteroresistance findings generalise. These were reported in specific organisms and, in two cases, in preprint form (PMID 38301486, PMID 40832241).

Colistin is a prescription antibiotic whose use, where it occurs, sits with treating clinicians and infectious-disease specialists. This page describes literature; it does not describe practice.

References

• Colistin and its role in the Era of antibiotic resistance: an extended review (2000-2019) (Emerging Microbes & Infections, 2020)
• Intra-Vesical Colistin for Pseudomonas aeruginosa Urinary Tract Infections (European Journal of Case Reports in Internal Medicine, 2019)
• Combinatorial action of regulatory systems generates colistin heteroresistance (bioRxiv, 2025)
• Resistance, heteroresistance and fitness costs drive colistin treatment failure during Acinetobacter baumannii pneumonia (bioRxiv, 2025)
• Cinnamaldehyde and baicalin reverse colistin resistance in Enterobacterales and Acinetobacter baumannii strains (European Journal of Clinical Microbiology & Infectious Diseases, 2024)
• Phage-mediated colistin resistance in Acinetobacter baumannii (Drug Resistance Updates, 2024)
• Synergistic Activity of Colistin in Combination With Resveratrol Against Colistin-Resistant Gram-Negative Pathogens (Frontiers in Microbiology, 2018)
• Preparation and characterisation of the colistin-entrapped liposome driven by electrostatic interaction for intravenous administration (Journal of Microencapsulation, 2016)
• Synergistic Activity of Colistin-Containing Combinations against Colistin-Resistant Enterobacteriaceae (Antimicrobial Agents and Chemotherapy, 2018)
• The O-Antigen Epitope Governs Susceptibility to Colistin in Salmonella enterica (mBio, 2020)
• Colistin Induces Oxidative Stress and Apoptotic Cell Death through the Activation of the AhR/CYP1A1 Pathway in PC12 Cells (Antioxidants, 2024)
• Molecular mechanisms related to colistin resistance in Enterobacteriaceae (Infection and Drug Resistance, 2019)