Buffalo, NY—Polymyxins were first introduced in the 1950s, although use of the antibiotics declined because of kidney toxicity. The drugs recently made a comeback to help fight superbugs, but clinicians have found guidelines on their use to be outdated in terms of dosage and formulation.

Now, new guidelines published recently in Pharmacotherapy revise the advice on how to use polymyxins, including maximum dosage, treatment strategies, and best practice for use in combination with other antibiotics.

The recommendations have been endorsed by the American College of Clinical Pharmacy; the European Society of Clinical Microbiology and Infectious Diseases; the Infectious Diseases Society of America; the International Society for Anti-infective Pharmacology; the Society of Critical Care Medicine; and the Society of Infectious Diseases Pharmacists.

“There is considerable confusion on how to optimally use the polymyxin antibiotics,” explained Brian Tsuji, PharmD, a professor of pharmacy practice at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences, who co-led the expert panel.

“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.”

The study points out that because polymyxin antibiotics colistin (polymyxin E) and polymyxin B became available in the 1950s, they did not undergo contemporary drug development procedures. “Since their reintroduction into the clinic, significant confusion remains due to the existence of several different conventions used to describe doses of the polymyxins, differences in their formulations, outdated product information, and uncertainties about susceptibility testing that has led to lack of clarity on how to optimally utilize and dose colistin and polymyxin B,” the study authors write.

Included in the guidelines are 34 recommendations for using polymyxin B and colistin, also known as polymyxin E. A press release from the University of Buffalo described the following as highlights:
• The maximum tolerable dosage of polymyxin B and colistin is set at 2 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 and ACE inhibitors.
• 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 or milligrams of colistin base activity.
• In the treatment of the superbugs carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae, 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 Acinetobacter baumannii, polymyxins should be used only in combination with an antibiotic that the bacteria are susceptible to. If no such drug is available, the polymyxin should be delivered alone.

The panel also called for research to 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.

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