Colistin vs Polymyxin B: What the Research Compares

Colistin and polymyxin B are approved prescription antibiotics in the polymyxin class. Both have long regulatory histories, both were reintroduced into intensive care practice as carbapenem resistance spread, and both are described in detail in international consensus guidance on polymyxin use (PMID 30710469). This page summarises what the published literature reports when the two agents are discussed side by side. It does not rank them, does not name a preferred agent, and does not provide dosing directions. This page is for educational purposes only and is not medical advice; consult a licensed physician for any question about treatment.

Is There a Head-to-Head Randomized Trial?

Stated plainly: within the verified literature summarised here, no large randomized controlled trial has been identified that randomly assigned patients to colistin versus polymyxin B with a shared primary endpoint. The international consensus guidelines on optimal polymyxin use, endorsed by ACCP, ESCMID, IDSA, ISAP, SCCM and SIDP, assembled the available evidence and issued recommendations drawn largely from pharmacokinetic and pharmacodynamic data, observational cohorts and expert consensus rather than from direct randomized comparisons between the two polymyxins (PMID 30710469). An extended review covering colistin from 2000 to 2019 likewise described the colistin evidence base as dominated by retrospective series, pharmacokinetic studies and in vitro work rather than head-to-head randomized comparisons (PMID 32284036).

Because no such trial anchors the comparison, the sections below set the two separate evidence bases next to each other, which is how the reviews themselves handle the question (PMID 28275006, PMID 31364080).

Class and Mechanism

Both agents belong to the polymyxins, a family of cyclic lipopeptide antibiotics. A comprehensive review in Clinical Microbiology Reviews described polymyxins as binding the lipid A component of lipopolysaccharide in the Gram-negative outer membrane, displacing divalent cations and disrupting membrane integrity, with activity directed at Gram-negative organisms including Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae (PMID 28275006). The same review reported that colistin and polymyxin B differ by a single amino acid residue in the cyclic peptide ring, which is the structural basis for their nearly overlapping antibacterial spectra (PMID 28275006).

A key practical difference described in the literature is formulation chemistry. The extended colistin review reported that colistin is administered parenterally as the inactive prodrug colistimethate sodium, which must be converted in vivo to colistin base, whereas polymyxin B is given directly as the active sulfate salt (PMID 32284036). The consensus guidelines reported that this prodrug step is the reason plasma concentrations of formed colistin rise comparatively slowly, a point that shaped the guideline discussion of loading approaches (PMID 30710469).

Side-by-Side Summary of What Reviews Report

Pharmacokinetics: What Studies Report

The consensus guidelines reported that the pharmacokinetics of colistimethate sodium and formed colistin differ meaningfully from those of polymyxin B, and that polymyxin B exposure is relatively predictable because the active molecule is administered directly (PMID 30710469). Researchers summarising polymyxin pharmacokinetics in animals reported that interspecies and interindividual variability has complicated extrapolation of exposure targets, and that distinct handling of colistimethate and polymyxin B has been documented across animal models (PMID 31364073).

In critically ill patients receiving continuous renal replacement therapy, a dosing optimisation review reported that polymyxins are among the agents for which extracorporeal clearance alters exposure and for which published adjustment recommendations exist, with colistimethate handled differently from polymyxin B because of its renal elimination and prodrug conversion (PMID 32547394). The specific regimens discussed in that review are study and guideline design details and are matters for a prescribing clinician, not for self-interpretation.

Clinical Settings Where Both Appear in the Literature

Reviews of Acinetobacter baumannii management reported that polymyxins have been central to treatment of carbapenem-resistant isolates, often in combination with other agents, and that comparative evidence between regimens remained limited (PMID 30520737). A review focused specifically on Acinetobacter pneumonia reported continued reliance on polymyxins alongside debate about inhaled administration and combination therapy, again without a defining randomized comparison between the two polymyxins (PMID 31335380).

Molecular work on carbapenem-resistant Acinetobacter baumannii reported co-resistance mechanisms that narrow the remaining options and help explain why polymyxins re-entered routine use (PMID 32084020).

Resistance

Because the two agents share a target, the resistance literature largely treats them together. The Clinical Microbiology Reviews analysis reported chromosomal and plasmid-encoded mechanisms of polymyxin resistance, including lipid A modification pathways, and described the discovery of plasmid-borne mobile colistin resistance determinants as a shift in the resistance landscape (PMID 28275006). A later survey of mcr gene-bearing organisms from horses reported the presence of mobile colistin resistance genes outside human clinical settings, illustrating the breadth of their distribution (PMID 35893557). The extended colistin review likewise reported that resistance emergence became a central concern as colistin use expanded between 2000 and 2019 (PMID 32284036).

Interest in related chemotypes has followed. A review of the octapeptins reported renewed investigation of this structurally related lipopeptide family as researchers searched for compounds retaining activity against polymyxin-resistant organisms (PMID 28180225).

Adverse Events: What Studies Report

Kidney effects

Nephrotoxicity is the adverse event most consistently reported for both agents. The extended colistin review reported nephrotoxicity as the dose-limiting toxicity associated with colistin therapy (PMID 32284036). The clinical use chapter on polymyxin B reported nephrotoxicity as a principal safety concern for that agent as well, alongside discussion of how exposure relates to renal injury (PMID 31364080). The consensus guidelines addressed monitoring and exposure targets in the context of this shared toxicity (PMID 30710469).

Nervous system effects

Neurotoxicity appears in the colistin literature in both clinical reviews and preclinical work. The extended colistin review reported neurotoxicity among the recognised toxicities of colistin (PMID 32284036). A mouse study reported that curcumin attenuated colistin-induced peripheral neurotoxicity in that model, which researchers framed as mechanistic exploration rather than as a clinical intervention (PMID 32037797).

Skin effects

The polymyxin B clinical use chapter reported skin hyperpigmentation among adverse effects documented with polymyxin B therapy (PMID 31364080).

Any individual assessment of these risks, including monitoring, belongs with a licensed prescribing clinician who can evaluate the full clinical picture.

How the Literature Frames the Comparison

Across these sources, the comparison is framed as a set of trade-offs in pharmacology rather than a hierarchy. The consensus guidelines reported differences in urinary exposure, renal handling and the prodrug step, and recommended that choice between agents be individualised by clinicians according to infection site and patient factors (PMID 30710469). The polymyxin B clinical use chapter and the extended colistin review each described their respective agent's evidence base without asserting superiority over the other (PMID 31364080, PMID 32284036). Readers interested in each agent individually can review the dedicated pages at /learn/colistin/ and /learn/polymyxin-b/.

Limitations of the Current Evidence

• No identified large randomized head-to-head trial compares the two agents on a single primary endpoint; the consensus document relied heavily on pharmacokinetic reasoning and expert agreement (PMID 30710469).
• Much of the colistin clinical literature is observational, as the extended review reported (PMID 32284036).
• Animal pharmacokinetic data show variability that complicates extrapolation, as reported in the animal pharmacokinetics review (PMID 31364073).
• Susceptibility testing for polymyxins has methodological challenges that affect comparative interpretation, as the Clinical Microbiology Reviews analysis reported (PMID 28275006).

References

• International Consensus Guidelines for the Optimal Use of the Polymyxins (Pharmacotherapy, 2019)
• Colistin and its role in the Era of antibiotic resistance: an extended review (2000-2019) (Emerging Microbes & Infections, 2020)
• Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes (Clinical Microbiology Reviews, 2017)
• Clinical Use of Polymyxin B (Advances in Experimental Medicine and Biology, 2019)
• Pharmacokinetics of Polymyxins in Animals (Advances in Experimental Medicine and Biology, 2019)
• Recommendation of Antimicrobial Dosing Optimization During Continuous Renal Replacement Therapy (Frontiers in Pharmacology, 2020)
• Managing Acinetobacter baumannii infections (Current Opinion in Infectious Diseases, 2019)
• How should we treat acinetobacter pneumonia? (Current Opinion in Critical Care, 2019)
• Molecular mechanisms of antibiotic co-resistance among carbapenem resistant Acinetobacter baumannii (Journal of Infection in Developing Countries, 2019)
• Epidemiology and Traits of Mobile Colistin Resistance (mcr) Gene-Bearing Organisms from Horses (Microorganisms, 2022)
• Curcumin Attenuates Colistin-Induced Peripheral Neurotoxicity in Mice (ACS Infectious Diseases, 2020)
• Rediscovering the octapeptins (Natural Product Reports, 2017)