Colistin and polymyxin B protocol

AS A PHARMACIST,, you'll see more focus on optimizing POLYMYXIN antibiotics due to new guidelines from the Infectious Diseases Society of America and others. IV colistin (polymyxin E) and polymyxin B have been around for decades. But nephrotoxicity concerns limit their use. These medications are bactericidal. They exhibit concentration-dependent killing. Their mechanism is mainly breaking up the bacterial cell wall. Now we're reaching for polymyxins more often due to increases in multidrug-resistant (MDR) gram-negative organisms, such as carbapenem-resistant Enterobacteriaceae or some Pseudomonas or Acinetobacter.

          Continue to work with physician to determine when to use a polymyxin and incorporate these strategies if polymyxins are used. Lean toward IV polymyxin B over colistin for systemic infections. There's no evidence one works better than the other. But polymyxin B seems to cause less nephrotoxicity and may work a few hours faster, since colistin is converted from an inactive prodrug. But use colistin for lower urinary tract infections since not much polymyxin B reaches the bladder. And if an inhaled polymyxin is needed for pneumonia, stick with colistin due to more evidence. IV polymyxin B has poor distribution into cerebrospinal fluid.

Avoid name confusion with colistin. It may be as colistin or its prodrug colistimethate. It comes in colistimethate vials, but is dosed in milligrams of "colistin base activity" (CBA). One vial colistin (1 million international units = 33.3 mg colistin base activity [CBA]). 

Consider using fixed doses of IV colistin. Newer data suggest weight-based doses aren't needed. Plus colistin's package insert recommendations may underdose patients, especially if CrCl is less than 50 mL/min. The usual IM or IV dosage of colistimethate sodium for adults and children with normal renal function is 2.5-5 mg/kg of colistin daily given in 2-4 divided doses, depending on the severity of the infection.

Colistimethate sodium has been given by oral inhalation via nebulization in a dosage of 33.33-66.66 mg of colistin 2 or 3 times daily. This corresponds to a dosage of 1-2 million (1 or 2 vials) international units 2 or 3 times daily. 

But continue using weight-based doses for polymyxin B. Generally calculate using total body weight, although evidence is limited. Adjust colistin doses based on renal function. On the other hand, don't renally adjust polymyxin B, this may lead to underdosing.

REFERENCES

• 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;39(1):10-39. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437259

  Vardakas KZ, Falagas ME. Colistin versus polymyxin B for the treatment of patients with multidrug-resistant Gram-negative infections: a systematic review and meta-analysis. Int J Antimicrob Agents. 2017 Feb;49(2):233-238. Available at: https://pubmed.ncbi.nlm.nih.gov/27686609

  Pogue JM, Ortwine JK, Kaye KS. Clinical considerations for optimal use of the polymyxins: A focus on agent selection and dosing. Clin Microbiol Infect. 2017 Apr;23(4):229-233. Available at: https://pubmed.ncbi.nlm.nih.gov/28238870

  Nation RL, Garonzik SM, Thamlikitkul V, Giamarellos-Bourboulis EJ, Forrest A, Paterson DL, Li J, Silveira FP. Dosing guidance for intravenous colistin in critically-ill patients. Clin Infect Dis. 2017 Mar 1;64(5):565-571. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850520