Polymyxins

Agents: colistin (colistimethate sodium),polymyxin B

Polymyxins are an older class of antibiotics that had nearly vanished from systemic use years ago in favor of the “safer” aminoglycosides. Unfortunately,  the continuous evolution of bacterial resistance has reinvigorated the use of colistin and polymyxin B in the treatment of resistant Gram-negative infections. This is problematic because these drugs have not been evaluated with the rigor of the modern drug approval process, and pharmacokinetic and efficacy data on their use are limited. However, they have been found to be useful in the treatment of infections caused by highly resistant Gram-negative organisms such as  Acinetobacter baumannii and carbapenemase-producing Klebsiella pneumoniae.

Spectrum

Good: many GNRs, including multi-drug resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae

Moderate: Stenotrophomonas maltophilia

Poor : All Gram-positive organisms, anaerobes, Proteus,  Providencia,  Burkholderia,  Serratia, Gram-negative cocci

Adverse Effects

Renal: The most common adverse effect is nephrotoxicity because of acute tubular necrosis.  Nephrotoxicity is common in clinical use, though the incidence is hard to estimate be-cause most recent studies of polymyxins are non-comparative evaluations of last-line indications in very ill patients. 

Neurological: Neurotoxicity is less common. It can manifest as dizziness, weakness, paresthesias, or mental status changes. Neuromuscular blockade can also occur and may lead to fatal respiratory arrest.

Important Facts

• Colistin and polymyxin B are very similar drugs. Colistin may be more active, but to be given systemically it is administered as colistimethate sodium. Colistimethate is then converted into active colistin in the body. Colistimethate is renally cleared, and only the pro-portion that is not cleared is converted to colistin. It is dosed as milligrams of active colistin (360 mg colistimethate = 150 mg of base colistin). Colistin itself is not used systemically. When most references refer to “colistin” (including this one), they are referring to “colistimethate”.

• To further confound colistin use, different standards of dosing are used by different countries.  The U.S. formulation is dosed in milligrams, while Europe and many other countries dose in international units. When comparing, it is important to know that 1 mg = 12,500 units.

• Because polymyxin drugs are generally last-line antibiotics, they are sometimes used in combination with other drugs. Various combinations of colistin and other drugs such as rifampin may be better than colistin use alone; this is an area of active study.

• The oral formulation of colistin is given only for bowel decontamination, such as before GI surgery. Don’t try to convert someone from IV to PO colistin to treat a systemic infection.

What they’re Good For

Polymyxins are useful in the treatment of multi-drug resistant Gram-negative infections including pneumonia, bacteremia, sepsis, and complicated UTIs. Because polymyxins are poorly studied in many of these disease states, other drugs should be used if pathogens are susceptible.

Don’t Forget!

While estimates of polymyxin nephrotoxicity vary, the incidence is substantial, particularly in critically ill patients who may not be able to tolerate the renal insult. Monitor renal function closely in patients receiving polymyxins.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.