Earn CME/CE in your profession:

Continuing Education Activity

Polymyxins are a class of medications used in the management and treatment of systemic infections caused by susceptible strains of multidrug-resistant organisms such as Pseudomonas aeruginosa. It is in the antibiotic class of drugs. This activity reviews the indications, action, and contraindications for polymyxin as a valuable agent in the treatment of multidrug-resistant infections. This activity will highlight the mechanism of action, adverse event profile, and other key factors pertinent for members of the interprofessional team in the treatment of patients with polymyxins who are infected by susceptible strains of gram-negative pathogens resistant most of the other antibiotic classes.


  • Identify the mechanism of action and administration of polymyxin.
  • Describe the adverse effects and contraindications of polymyxin.
  • Review the appropriate monitoring and toxicity of polymyxin.
  • Outline the importance of collaboration and coordination among the interprofessional team that can enhance patient care when dosing and monitoring polymyxins to improve patient outcomes for patients receiving systemic antibiotic therapy with polymyxins.


Polymyxins comprise a class of antibiotics targeting gram-negative bacterial infections. Polymyxin B and Polymyxin E (colistin) are the two drugs within this antibiotic class used primarily in clinical practice. They are FDA approved for serious infections with multidrug-resistant gram-negative bacteria, especially those caused by Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. Polymyxins are often the only effective antibiotic agent against multidrug-resistant organisms, particularly carbapenem-resistant Enterobacteriaceae. They have become the last line of treatment for infections that are resistant to other antibiotics.[1] They are useful in treating infections of the urinary tract, meninges, and bloodstream by susceptible strains of pseudomonas aeruginosa, Enterobacteriaceae, and Acinetobacter baumannii.

Polymyxin B is available topically in combination with neomycin plus hydrocortisone for the treatment of otitis externa to cover for Pseudomonas aeruginosa.[2] Polymyxin B is also indicated for topical use in combination with trimethoprim in treating bacterial conjunctivitis.[3] Lastly, it is used in combination with bacitracin and neomycin for treating and preventing skin infections after minor skin injuries.[4]

Off Label Use: Adult

Polymyxins are used off label in adults via an inhaled form for patients with cystic fibrosis who have chronic pulmonary infections with Pseudomonas aeruginosa.[5] Also, aerosolized polymyxins have been used as adjunctive antibiotic therapy for the treatment of hospital-acquired and ventilator-associated pneumonia caused by multidrug resistance organisms such as Pseudomonas aeruginosa.[6]

Mechanism of Action

Polymyxins are bactericidal drugs and act on the outer membrane of gram-negative bacteria by destabilizing the phospholipids and lipopolysaccharides (LPS) present. There is an electrostatic interaction between the positively charged polymyxin and the phosphate groups of the negatively charged lipid A membrane, which causes displacement of divalent cations such as calcium and magnesium from the phosphate groups within these membrane lipids. This activity leads to increased permeability, a disrupted outer cell membrane, and intracellular contents begin to leak out, resulting in cellular bacterial death.[7][8] Also, polymyxins can neutralize the endotoxin effect of pathogens. The endotoxin portion of gram-negative bacteria corresponds to the lipid A part of the LPS. Polymyxins can bind to the LPS released as a result of cellular death, which results in the neutralization of the endotoxin and thus reduces its effects in the circulation.[7][8]


Polymyxin B and colistin (polymyxin E) are used clinically from the polymyxin class of antibiotics when indicated for systemic antibiotic therapy. Polymyxin B is the active drug, while colistin is the less toxic prodrug colistin methanesulfonate.[8]  The administration of both may be through intravenous infusion over 1-hour. Polymyxin B is usually the preferred option due to its ability to achieve adequate drug levels more rapidly and reliably than colistin. Polymyxin B is also associated with lower rates of nephrotoxicity.[5][9] Colistin is the preferred option in urinary tract infections where there is a high urinary concentration in comparison to polymyxin B, which is low.[5]

Polymyxin B is administered topically for ophthalmic and otic use via droplet solution for the treatment of bacterial conjunctivitis and bacterial otitis externa.[2] Polymyxin B is also administered topically on the skin as an ointment in combination with other antibiotics for skin infections.[4]

Also, both drugs can be given off label via inhaled administration through a nebulizer. A bronchodilator such as beta-2-agonist is recommended 15 to 20 minutes before aerosolized administration to prevent bronchospasm. Lastly, the administration of both polymyxin B and colistin can be via intrathecal or intraventricular routes, where only preservative-free injections should be given via this latter route of administration.[1][7]

Adverse Effects

The most common and clinically concerning the adverse effect of intravenous polymyxins is nephrotoxicity, which has the highest incidence. Polymyxins have correlations with hematuria, proteinuria, oliguria, and acute renal failure. As a result, renal function should be followed closely during administration. Colistin needs to be dose adjusted for renal impairment; however, it is not necessary for polymyxin B. Clinicians should avoid concurrent use of other nephrotoxic drugs if possible.[10][11][12]

Neurotoxicity can also occur due to intravenous polymyxin administration with an incidence rate of 7 percent, according to initial studies. Adverse effects include dizziness, numbness, paresthesia, slurred speech, tingling, vertigo, and neuromuscular blockade, which can lead to respiratory failure. Paresthesias were the main neurotoxic adverse effect seen in patients treated with polymyxins. Neurotoxic adverse effects may be more common in cystic fibrosis individuals with the use of polymyxins, with the main effect being paresthesias and ataxia. Clinicians should avoid concurrent use of neurotoxic drugs if possible.[10][13][14]

Other rarer adverse effects include hypersensitivity reactions such as rash, pruritus, urticaria, and fever. Aerosolization of polymyxins into the airway can cause bronchospasm; therefore, bronchodilation prior to administration may be beneficial.[10][15] Polymyxin also reportedly can cause skin hyperpigmentation.[16]


Contraindications to polymyxins include any hypersensitivity to polymyxin B, colistin methanesulfonate, colistin, or any formulation component.[10]


Renal function requires close monitored during the administration of intravenous polymyxins as a result of the high frequency of nephrotoxicity and potential severity. Therapeutic drug monitoring of polymyxins is also a recommendation due to a narrow therapeutic window for efficacy and toxicity.[5] However, therapeutic drug monitoring for the polymyxins is not universally available. Decreasing urine output, increasing BUN, and creatinine may require discontinuation of systemic therapy with polymyxins. The recommended target serum concentration level is 2 mg/mL for susceptible strains. Off label use of polymyxins for aerosolized use requires monitored for signs of bronchospasm. Monitoring for neurotoxic symptoms such as paresthesias and signs of superinfection is also necessary.[5]


When there are signs of renal impairment present, it is necessary to discontinue polymyxin therapy. Supportive care should be given, including close monitoring of fluid intake and output, as well as electrolytes when there is renal dysfunction resulting from polymyxin use.[10] With mild neurologic symptoms due to polymyxins such as dizziness or numbness, these typically subside after discontinuation of the drug. When there is respiratory depression present due to neuromuscular blockade, intravenous polymyxin therapy must be discontinued immediately, as well as any other medications causing neurotoxicity. If apnea begins to develop, further management involves using mechanical ventilation. The administration of cholinesterase inhibitors, such as neostigmine for treatment of the neuromuscular blockade, has not been shown to provide any benefit in treating respiratory depression from the adverse effects of polymixin use.[10]

Enhancing Healthcare Team Outcomes

Evaluating the use of polymyxin therapy in treating multidrug-resistant organism infections requires a team of healthcare professionals that includes a nurse, laboratory technologists, pharmacists, and several physician specialists to achieve excellent outcomes. Without proper management, the morbidity of polymyxin overdose is high. Clinicians have a vital role in determining the need for directed treatment with polymyxins. They need to determine which polymyxin is necessary, how to dose the medication correctly, and what the duration of therapy needs to be for thoroughly treating the patient without causing harm. Some of the points of care may involve the following:

  • Ordering drug levels in the blood
  • Monitor the patient for signs and symptoms of respiratory depression, hematuria, or acute renal failure.
  • Consult with the pharmacist about the dosing of polymyxins
  • Consult with a nephrologist on further management, which may include dialysis

Therapeutic drug monitoring should take place for patients to meet the target serum concentration with polymixins. The physician initiates polymyxin therapy, and the pharmacist will typically handle subsequent dosing adjustments. Nurses need to assess these patients for any potential toxicities, such as nephrotoxicity or neurotoxicity, that may develop for patients. The outcome of potential damage due to these toxicities depends on early identification, so the healthcare team needs to monitor patients for adverse effects closely and determine the next best step in treatment. Lastly, laboratory technicians are crucial for determining the BUN and creatinine in patients on intravenous polymyxins since there is a high risk of nephrotoxicity. All of these healthcare professionals working together have a vital role in managing patients on this systemic antibiotic therapy, so collaboration becomes essential to provide them with the best outcome possible. 

Article Details

Article Author

Genti Shatri

Article Editor:

Prasanna Tadi


8/22/2022 9:19:41 PM



Nation RL,Li J,Cars O,Couet W,Dudley MN,Kaye KS,Mouton JW,Paterson DL,Tam VH,Theuretzbacher U,Tsuji BT,Turnidge JD, Framework for optimisation of the clinical use of colistin and polymyxin B: the Prato polymyxin consensus. The Lancet. Infectious diseases. 2015 Feb;     [PubMed PMID: 25459221]


Rosenfeld RM,Schwartz SR,Cannon CR,Roland PS,Simon GR,Kumar KA,Huang WW,Haskell HW,Robertson PJ, Clinical practice guideline: acute otitis externa. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2014 Feb;     [PubMed PMID: 24491310]


Williams L,Malhotra Y,Murante B,Laverty S,Cook S,Topa D,Hardy D,Wang H,Gigliotti F, A single-blinded randomized clinical trial comparing polymyxin B-trimethoprim and moxifloxacin for treatment of acute conjunctivitis in children. The Journal of pediatrics. 2013 Apr;     [PubMed PMID: 23092529]


Dire DJ,Coppola M,Dwyer DA,Lorette JJ,Karr JL, Prospective evaluation of topical antibiotics for preventing infections in uncomplicated soft-tissue wounds repaired in the ED. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 1995 Jan;     [PubMed PMID: 7606610]


Tsuji BT,Pogue JM,Zavascki AP,Paul M,Daikos GL,Forrest A,Giacobbe DR,Viscoli C,Giamarellou H,Karaiskos I,Kaye D,Mouton JW,Tam VH,Thamlikitkul V,Wunderink RG,Li J,Nation RL,Kaye KS, International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). Pharmacotherapy. 2019 Jan;     [PubMed PMID: 30710469]


Kalil AC,Metersky ML,Klompas M,Muscedere J,Sweeney DA,Palmer LB,Napolitano LM,O'Grady NP,Bartlett JG,Carratalà J,El Solh AA,Ewig S,Fey PD,File TM Jr,Restrepo MI,Roberts JA,Waterer GW,Cruse P,Knight SL,Brozek JL, Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2016 Sep 1;     [PubMed PMID: 27418577]


Poirel L,Jayol A,Nordmann P, Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes. Clinical microbiology reviews. 2017 Apr;     [PubMed PMID: 28275006]


Trimble MJ,Mlynárčik P,Kolář M,Hancock RE, Polymyxin: Alternative Mechanisms of Action and Resistance. Cold Spring Harbor perspectives in medicine. 2016 Oct 3;     [PubMed PMID: 27503996]


Akajagbor DS,Wilson SL,Shere-Wolfe KD,Dakum P,Charurat ME,Gilliam BL, Higher incidence of acute kidney injury with intravenous colistimethate sodium compared with polymyxin B in critically ill patients at a tertiary care medical center. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2013 Nov;     [PubMed PMID: 23840000]


Falagas ME,Kasiakou SK, Toxicity of polymyxins: a systematic review of the evidence from old and recent studies. Critical care (London, England). 2006 Feb;     [PubMed PMID: 16507149]


Kubin CJ,Ellman TM,Phadke V,Haynes LJ,Calfee DP,Yin MT, Incidence and predictors of acute kidney injury associated with intravenous polymyxin B therapy. The Journal of infection. 2012 Jul;     [PubMed PMID: 22326553]


Justo JA,Bosso JA, Adverse reactions associated with systemic polymyxin therapy. Pharmacotherapy. 2015 Jan;     [PubMed PMID: 25266910]


Wolinsky E,Hines JD, Neurotoxic and nephrotoxic effects of colistin in patients with renal disease. The New England journal of medicine. 1962 Apr 12;     [PubMed PMID: 14008070]


Lindesmith LA,Baines RD Jr,Bigelow DB,Petty TL, Reversible respiratory paralysis associated with polymyxin therapy. Annals of internal medicine. 1968 Feb;     [PubMed PMID: 4306125]


Koch-Weser J,Sidel VW,Federman EB,Kanarek P,Finer DC,Eaton AE, Adverse effects of sodium colistimethate. Manifestations and specific reaction rates during 317 courses of therapy. Annals of internal medicine. 1970 Jun;     [PubMed PMID: 5448745]


Mattos KPH,Cintra ML,Gouvêa IR,Ferreira LÁ,Velho PENF,Moriel P, Skin hyperpigmentation following intravenous polymyxin B treatment associated with melanocyte activation and inflammatory process. Journal of clinical pharmacy and therapeutics. 2017 Oct;     [PubMed PMID: 28497462]