Polymyxin B Side Effects: What Studies Report

What the published literature covers

Polymyxin B is a polypeptide antibiotic used in hospital settings against certain multidrug-resistant Gram-negative organisms, and it also appears in the literature in a very different form: as a ligand immobilised on an extracorporeal cartridge used to bind circulating endotoxin. Because these two contexts differ so much, the reported adverse-effect profiles differ too. This page gathers what published studies reported about safety signals and does not offer guidance of any kind. For background on polymyxin B's structure, classification and mechanism, PeptideU's learning course at /learn/polymyxin-b/ covers that teaching material separately; this page stays focused on what the safety literature describes.

Across the verified sources below, the recurring themes were kidney toxicity, dermatologic pigment change described in case reports, an isolated report of a tubular electrolyte syndrome, adverse effects documented in horses, and trial-level data on the hemoperfusion device rather than the systemic drug.

Kidney Effects: What Studies Report

Clinical observations in transplant recipients

Nephrotoxicity has been the most consistently examined concern in the polymyxin B literature. A 2022 retrospective analysis published in Infection and Drug Resistance assessed both nephrotoxicity and efficacy of polymyxin B use specifically in renal transplant patients, a population in which baseline kidney function is already a central clinical variable (PMID 35115795). The study framed kidney injury not as an incidental observation but as a primary outcome to be measured alongside treatment response, which reflects how prominently the concern features in this drug class (PMID 35115795).

Readers should note what that design can and cannot establish. Retrospective hospital analyses describe what happened in patients who were already severely unwell and often receiving several nephrotoxic agents; researchers in such studies can report associations and incidence within their cohort, but attribution to a single drug remains an inference rather than a demonstrated cause.

Mechanistic laboratory work

Laboratory research has attempted to explain how kidney injury arises. A 2023 study in the Journal of Biochemical and Molecular Toxicology reported that polymyxin B exerted nephrotoxic effects through inhibition of the Nrf2/NQO1 pathway-mediated antioxidant response (PMID 36992629). In that framing, the researchers described oxidative stress handling in renal tissue as the affected process rather than a direct structural insult alone (PMID 36992629).

Mechanistic findings of this kind are hypothesis-generating. They describe a biological pathway in an experimental system and do not, on their own, predict how often kidney injury occurs in people, how reversible it is, or which patients are most susceptible.

Skin Hyperpigmentation: What Studies Report

One of the more distinctive signals in the polymyxin B literature is diffuse darkening of the skin, described in several independent case reports. A 2017 report in the Journal of Clinical and Diagnostic Research documented polymyxin B-induced diffuse cutaneous hyperpigmentation (PMID 28384882). A 2020 case report in Case Reports in Medicine likewise described polymyxin B-induced skin hyperpigmentation (PMID 33014066), and a separate 2020 report in Transplant Infectious Disease reported the same phenomenon in the transplant-infection setting (PMID 32386075).

The value of a repeated case-report signal is that independent clinicians in different settings and different years described a similar presentation and attributed it to the same drug. The limitation is equally clear: case reports carry no denominator. They cannot tell a reader how common hyperpigmentation is, who is at risk, or how it evolves over time, because only the notable cases are written up.

Electrolyte and Tubular Disturbance: What Studies Report

A 2024 case report in BMJ Case Reports described polymyxin B-induced Bartter syndrome, a renal tubular salt-wasting picture, in a patient receiving the drug (PMID 38702070). Because Bartter syndrome is classically an inherited tubular disorder, a drug-associated presentation is unusual enough to warrant publication, which is itself a reminder that the report describes a rare observation rather than an expected outcome (PMID 38702070).

Taken together with the nephrotoxicity work, this report places the kidney and its tubules at the centre of the documented polymyxin B safety literature. That does not mean other organ systems are unaffected; it means they are less represented in the verified evidence summarised here.

Animal Studies: What Studies Report

Veterinary research has examined tolerability in horses, where polymyxin B has been used for its endotoxin-binding properties. A 2022 study in the Journal of Veterinary Internal Medicine investigated adverse effects of polymyxin B administration to healthy horses (PMID 35801274). A 2023 paper in Antibiotics presented a preliminary investigation of side effects of polymyxin B administration in hospitalised horses, extending the question from healthy animals to animals already receiving treatment for illness (PMID 37237756).

Animal data are useful because dosing and monitoring can be controlled in ways that retrospective human chart reviews cannot match. They are also species-specific: drug handling, kidney physiology and neurological expression of toxicity differ between horses and humans, so findings in equine subjects are not transferable to people. The distinction between the healthy-animal study and the hospitalised-animal study also illustrates a general point in safety research — underlying illness can change how a drug is tolerated (PMID 35801274, PMID 37237756).

Polymyxin B Hemoperfusion: What Studies Report

A large part of the modern polymyxin B literature concerns the molecule bound to an extracorporeal adsorption cartridge rather than infused as an antibiotic. The EUPHRATES randomised clinical trial, published in JAMA in 2018, evaluated the effect of targeted polymyxin B hemoperfusion on 28-day mortality in patients with septic shock and elevated endotoxin level, and researchers reported that the intervention did not produce a significant mortality benefit in the enrolled population (PMID 30304428).

A 2022 review in Critical Care covered technical aspects and the state of the art in hemoperfusion, situating polymyxin B-immobilised cartridges within the broader family of blood-purification devices and their practical considerations (PMID 35549999). Device-based use raises a different safety vocabulary from systemic dosing: circuit-related, procedural and adsorption-related issues dominate, rather than the organ toxicity associated with drug exposure in the bloodstream.

For anyone reading adverse-event claims about polymyxin B, separating these two contexts matters. A finding about hemoperfusion tolerability is not evidence about intravenous antibiotic tolerability, and the reverse is equally true.

Analogue Research and the Tolerability Problem

The search for structurally modified polymyxins is itself indirect evidence that tolerability limits the parent compound. A 2020 paper in The Journal of Antibiotics described the design, synthesis and antimicrobial evaluation of polymyxin analogues, reporting activity data for the new compounds (PMID 31831870). Medicinal-chemistry programmes of this type typically aim to retain antibacterial potency while altering properties associated with toxicity, though the study itself reported synthesis and antimicrobial results rather than clinical safety outcomes (PMID 31831870).

How the Evidence Types Compare

Where Human Data Are Limited or Absent

Several gaps are worth stating plainly rather than filling with inference:

• Frequency of hyperpigmentation is not established here. The verified literature contains individual case reports (PMID 33014066, PMID 32386075), not incidence studies.
• Long-term outcomes after kidney injury are not addressed in the sources summarised above, which reported nephrotoxicity as an in-treatment outcome (PMID 35115795).
• No non-clinical, non-hospital human use is documented in these papers. Every human report cited here arose in a supervised medical setting, and the literature summarised provides no data on any other context of exposure.
• Equine findings stand alone. The horse studies reported adverse effects in that species only (PMID 37237756), and no human equivalent of those designs appears in the verified set.

Reading Adverse-Event Claims Critically

Three habits make polymyxin B safety literature easier to interpret. First, check whether a source describes the systemic antibiotic or the hemoperfusion cartridge, since the trial evidence concerns the latter (PMID 30304428). Second, check the population: transplant recipients, critically ill patients with septic shock and healthy horses are not interchangeable groups (PMID 35115795, PMID 35801274). Third, distinguish mechanism from incidence — a pathway finding explains how harm might occur without quantifying how often it does (PMID 36992629).

This page is for educational purposes only and is not medical advice; consult a licensed physician about any medication, symptom or treatment decision. Nothing here describes a protocol, and no statement should be read as a recommendation to use or avoid any substance. Polymyxin B is a prescription antibiotic and a regulated medical device component depending on its form, and decisions about its clinical use belong to treating clinicians working from full patient information.

References

• Nephrotoxicity and Efficacy Assessment of Polymyxin B Use in Renal Transplant Patients (Infection and Drug Resistance, 2022)
• Polymyxin B exerts nephrotoxicity effects via inhibition of the Nrf2/NQO1 pathway-mediated antioxidant response (Journal of Biochemical and Molecular Toxicology, 2023)
• Polymyxin B-Induced Diffuse Cutaneous Hyperpigmentation (Journal of Clinical and Diagnostic Research, 2017)
• Polymyxin B-Induced Skin Hyperpigmentation (Case Reports in Medicine, 2020)
• Polymyxin B-induced skin hyperpigmentation (Transplant Infectious Disease, 2020)
• Polymyxin B-induced Bartter syndrome (BMJ Case Reports, 2024)
• Adverse effects of polymyxin B administration to healthy horses (Journal of Veterinary Internal Medicine, 2022)
• Preliminary Investigation of Side Effects of Polymyxin B Administration in Hospitalized Horses (Antibiotics, 2023)
• Effect of Targeted Polymyxin B Hemoperfusion on 28-Day Mortality in Patients With Septic Shock and Elevated Endotoxin Level: The EUPHRATES Randomized Clinical Trial (JAMA, 2018)
• Hemoperfusion: technical aspects and state of the art (Critical Care, 2022)
• Design, synthesis and antimicrobial studies of some polymyxin analogues (The Journal of Antibiotics, 2020)