An international panel of the foremost researchers on
infectious disease and antimicrobials has formed new guidelines on the use of
polymyxins, a class of antibiotics employed as a last resort to treat deadly,
drug-resistant bacteria.

The guidelines, published in Pharmacotherapy, set new standards for the clinical use of
polymyxins, including on maximum dosage, treatment strategies and best practice
for use in combination with other antibiotics.

The recommendations have been endorsed worldwide by six
international societies and organizations across the globe: American College of
Clinical Pharmacy, European Society of Clinical Microbiology and Infectious
Diseases, Infectious Diseases Society of America, International Society for
Anti-infective Pharmacology, Society of Critical Care Medicine and Society of
Infectious Diseases Pharmacists.

The expert panel was co-led by Brian Tsuji, PharmD,
professor of pharmacy practice in the University at Buffalo School of Pharmacy
and Pharmaceutical Sciences; Jason Pogue, PharmD, clinical pharmacist
specialist at the Detroit Medical Center; and Keith Kaye, MD, professor of
infectious disease and internal medicine in the University of Michigan Medical

“There is considerable confusion on how to optimally use the
polymyxin antibiotics,” said Tsuji.

“These guidelines represent consensus recommendations from
expert clinicians and scientists around the globe to guide polymyxin therapy in
Gram-negative infections where no treatments appear to exist.”

First introduced in the 1950s, polymyxins are an older
generation of antibiotics that fell out of favour due to their toxicity to the
kidneys. However, the drug was recently resurrected by researchers and
clinicians to aid in the fight against increasingly antibiotic-resistant

But while polymyxins have made a comeback, the clinical
standards that guide its use are outdated. Variations in conventions used to
describe doses, differing formulations and dated product information have led
to confusion on how to best use and dose the drug.

The recent publication provides clinicians with 34
recommendations for using polymyxin B and colistin – also known as polymyxin E.
Highlights from the paper include:

  • The maximum tolerable dosage of polymyxin B and colistin is
    set at two milligrams per liter.
  • Polymyxin B is preferred for routine systemic use against
    invasive infections, while colistin is preferred for the treatment of lower
    urinary tract infections and for delivery to the heart, brain and spinal canal.
  • Patients receiving polymyxins should avoid agents that are
    toxic to the kidneys, such as nonsteroidal anti-inflammatory drugs (common pain
    relievers that include aspirin and ibuprofen) and angiotensin-converting-enzyme
    inhibitors (drugs used primarily to treat hypertension and congestive heart
  • To reduce confusion over labeling conventions used in
    different parts of the world, hospitals and prescription orders should specify
    doses of colistin in either international units (IU) or milligrams of colistin
    base activity (CBA).
  • In the treatment of the superbugs carbapenem-resistant P.
    aeruginosa (CRPA) and carbapenem-resistant Enterobacteriaceae (CRE), polymyxins
    should be used in combination with one or more antibiotics, ideally a drug the
    bacteria is susceptible to.
  • In the treatment of the superbug carbapenem-resistant A.
    baumannii (CRAB), polymyxins should only be used in combination with an
    antibiotic that the bacteria is susceptible to. If no such drug is available,
    the polymyxin should be delivered alone.

The panel recommended several areas of research needed in
the future, including studies that compare the effectiveness and toxicity of
polymyxin B and colistin, investigate biomarkers that rapidly respond to kidney
damage to better detect the adverse effects of polymyxins, weigh the risks and
benefits of curing infection at the expense of kidney damage, and measure the
effectiveness of various combination therapies.


Reference: 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). Pharmacology. Published
February 2019. .