Polymyxin Benefits: What Studies Report

What polymyxin is and how it is regulated

Polymyxin B is a prescription antibiotic medicine. It is an approved product in the United States and in many other jurisdictions, supplied as an injectable preparation for serious infections caused by susceptible Gram negative bacteria and also formulated into topical, ophthalmic and otic combination products. The same chemical class includes polymyxin E, better known as colistin, which is administered as the prodrug colistimethate sodium. A 2021 review in Pharmacological Reviews described the polymyxins as last line agents whose approved status predates contemporary trial requirements, so the published evidence base rests largely on observational cohorts, pharmacokinetic work and systematic reviews rather than modern randomised pivotal trials (PMID 33627412).

On this page, the word benefit means an outcome that researchers measured and reported in a published study, at the level of the approved label indication. Nothing here describes what any individual should receive, and no outcome is presented as assured. A broader background overview sits on the polymyxin learn page.

Outcome domains at a glance

Infections caused by resistant Gram negative bacteria

Clinical use and reported response

A 2019 review chapter on the clinical use of polymyxin B surveyed how the drug has been administered in hospitalised patients with infections caused by multidrug resistant Gram negative organisms and summarised the reported clinical and microbiological responses alongside its toxicity profile (PMID 31364080). The same review framed polymyxin B as an agent whose use expanded because alternatives lost activity, rather than as an agent selected on the strength of head to head randomised comparisons (PMID 31364080).

A 2019 meta-analysis chapter pooled published patient level reports of polymyxin use and described the difficulty of drawing firm conclusions from studies that differed in population, infection site, comparator and dosing practice (PMID 31364077). That heterogeneity is a recurring limitation across the clinical literature summarised in the 2021 Pharmacological Reviews article (PMID 33627412).

High level carbapenem resistant Klebsiella pneumoniae

A 2023 retrospective analysis published in Infection and Drug Resistance examined the efficacy of polymyxin B in patients with high level carbapenem resistant Klebsiella pneumoniae infections and reported the clinical factors that influenced treatment outcome in that cohort (PMID 37396067). The study was observational, so the researchers could describe associations between patient characteristics and outcome rather than establish cause and effect (PMID 37396067).

Paediatric data

A 2022 study in Frontiers in Pharmacology evaluated intravenous polymyxin B in Chinese children with carbapenem resistant Gram negative bacterial infections and reported both effectiveness outcomes and the frequency of nephrotoxicity in that population (PMID 35712713). Paediatric evidence of this kind is scarce, and the researchers presented it as a single centre style observational dataset rather than a controlled trial (PMID 35712713).

Combination regimens: what reviews reported

A frequent research question is whether adding a second antibiotic to a polymyxin changes outcomes. A 2019 review titled Polymyxins: To Combine or Not to Combine? examined the laboratory rationale for combination therapy alongside the clinical data and described the question as unresolved, with synergy observed in experimental systems not consistently matched by patient outcome data (PMID 30974813).

A 2017 review in The Journal of Infection on the clinical translation of polymyxin based combination therapy set out the same gap between preclinical findings and clinical practice and identified the trial design and pharmacokinetic challenges that researchers would need to address to close it (PMID 27998750). Neither review presented combination therapy as an established label level benefit (PMID 27998750, PMID 30974813).

Pharmacokinetics and pharmacodynamics

A 2019 chapter on in vitro pharmacodynamics and animal pharmacokinetics and pharmacodynamics described the laboratory models and infected animal models that researchers used to define exposure targets for the polymyxins (PMID 31364074). Those models sit upstream of patient care: they inform how exposure relates to bacterial killing in a controlled system, and they do not by themselves demonstrate clinical benefit (PMID 31364074). The 2021 review described the renewed pharmacological work on dosing, toxicity and resistance that followed the return of these older agents to clinical use (PMID 33627412).

Polymyxin B hemoperfusion: a separate device context

Polymyxin B immobilised fibre column hemoperfusion is a blood purification device application that is distinct from giving the antibiotic systemically, and it should not be read as part of the antibiotic label. A 2014 article in Critical Care set out the proposed mechanistic basis for endotoxin adsorption by the polymyxin B immobilised column in sepsis (PMID 25043934). A 2019 commentary in the Journal of Intensive Care discussed the EUPHRATES trial of polymyxin B hemoperfusion and how its findings shaped the design of the subsequent TIGRIS trial (PMID 31131109). Evidence in this area remained under active investigation at the time of that commentary (PMID 31131109).

Laboratory and preclinical work: clearly labelled as non-clinical

A 2025 laboratory report in Antimicrobial Agents and Chemotherapy described hyperforin potentiating polymyxin B against multidrug resistant Gram negative pathogens through membrane disruption, biofilm eradication and oxidative stress in non-clinical experiments (PMID 41222309). Findings of this kind are in vitro and preclinical and were not reported as patient outcomes (PMID 41222309).

A 2019 chapter on the discovery of novel polymyxin-like antibiotics reviewed medicinal chemistry efforts to design analogues with improved properties (PMID 31364086). Those molecules are discovery stage compounds described in the chemical literature, and the chapter presented them as development candidates rather than treatments (PMID 31364086).

Nephrotoxicity and Other Adverse Events: What Studies Report

Kidney injury is the most consistently reported harm in the polymyxin literature. The 2022 paediatric study reported nephrotoxicity alongside effectiveness in children receiving intravenous polymyxin B for carbapenem resistant Gram negative infections (PMID 35712713). The 2019 clinical use review described toxicity as the factor that historically limited dosing of polymyxin B and that drove the search for better exposure guidance (PMID 31364080). The 2021 review placed nephrotoxicity, neurotoxicity and emerging resistance at the centre of the scientific agenda for rescuing these last line agents (PMID 33627412).

Safety monitoring, dose adjustment and the balance between infection severity and organ risk are clinical judgements made by the treating team. This page is for educational purposes only and is not medical advice; consult a licensed physician about any medicine, infection or treatment decision.

Where the evidence is thin or absent

• Modern randomised pivotal trials. The 2021 review described the polymyxins as agents that entered practice long before current trial standards, leaving the clinical evidence base dominated by observational and pooled analyses (PMID 33627412).
• Comparative superiority claims. The 2019 meta-analysis chapter highlighted heterogeneity across included studies as a barrier to firm comparative conclusions (PMID 31364077).
• Combination therapy as a settled benefit. Two reviews described the monotherapy versus combination question as open (PMID 30974813, PMID 27998750).
• Non-infectious or wellness uses. The verified literature summarised here addressed antibacterial use, device based hemoperfusion research and drug discovery only; no study in this set examined metabolic, cosmetic, performance or longevity outcomes (PMID 33627412, PMID 31364080).

Questions a prescribing clinician can answer

1. Whether a given infection involves organisms for which a polymyxin is among the options under consideration, in light of local susceptibility testing.
2. How kidney function, age and concurrent medicines factor into monitoring decisions, given the toxicity patterns described in published cohorts (PMID 35712713).
3. How the uncertainty around combination regimens described in published reviews applies to a specific case (PMID 30974813).
4. How polymyxin B hemoperfusion research differs from systemic antibiotic therapy (PMID 25043934).

References

• Clinical Use of Polymyxin B (Advances in Experimental Medicine and Biology, 2019)
• In vitro Pharmacodynamics and PK/PD in Animals (Advances in Experimental Medicine and Biology, 2019)
• Rescuing the Last-Line Polymyxins: Achievements and Challenges (Pharmacological Reviews, 2021)
• Polymyxin B hemoperfusion: a mechanistic perspective (Critical Care, 2014)
• Effectiveness and Nephrotoxicity of Intravenous Polymyxin B in Carbapenem-Resistant Gram-Negative Bacterial Infections Among Chinese Children (Frontiers in Pharmacology, 2022)
• Polymyxins: To Combine or Not to Combine? (Antibiotics, 2019)
• The Efficacy and Influencing Factors of Polymyxin B in High-Level Carbapenem-Resistant Klebsiella pneumoniae Infections (Infection and Drug Resistance, 2023)
• Hyperforin potentiates polymyxin B against multidrug-resistant Gram-negative pathogens via membrane disruption, biofilm eradication, and oxidative stress (Antimicrobial Agents and Chemotherapy, 2025)
• Discovery of Novel Polymyxin-Like Antibiotics (Advances in Experimental Medicine and Biology, 2019)
• Clinical translation of polymyxin-based combination therapy: Facts, challenges and future opportunities (The Journal of Infection, 2017)
• Meta-analysis of Polymyxin Use in Patients (Advances in Experimental Medicine and Biology, 2019)
• The wind changed direction and the big river still flows: from EUPHRATES to TIGRIS (Journal of Intensive Care, 2019)