Polymyxin antibiotics · gram-negatives
Two closely related older antibiotics, polymyxin B and colistin (also called polymyxin E). Hospitals use them against gram-negative bacteria that resist most other drugs. Polymyxin B is given as polymyxin B sulfate, and colistin as colistimethate sodium, a chemically modified form. In hospitals both are given by injection, and both carry serious kidney and nerve warnings.
Polymyxins are positively charged peptides that kill gram-negative bacteria by attacking their membranes. They are drawn by electrical attraction to lipid A, the negatively charged anchor of lipopolysaccharide in the bacterial outer membrane3. Once bound, they disrupt the membrane barrier, the cell becomes leaky and it dies1,2. Gram-positive bacteria, fungi and some gram-negative groups, such as Proteus, are naturally resistant1. Other bacteria can become resistant by chemically changing lipid A so it carries less negative charge, which pushes the drug away. The genes behind these changes can sit on the bacterial chromosome or on mobile genetic elements that can spread between bacteria3.
Polymyxin B and colistin became available in the 1950s, so they never went through modern drug-development studies; their use has returned as salvage therapy for otherwise untreatable gram-negative infections6. Randomized trials have asked whether adding a second antibiotic helps.
In the open-label AIDA trial, 406 adults with serious carbapenem-resistant infections, mostly from Acinetobacter baumannii, received colistin alone or colistin plus meropenem. Clinical failure at day 14 was similar (79% vs 73%), and the combination caused more diarrhea4. The double-blind OVERCOME trial included 423 evaluable patients with pneumonia or bloodstream infections. It also found no benefit from adding meropenem: 28-day mortality was 43% with colistin alone and 37% with the combination, a difference that was not significant5. Consensus guidelines endorsed by six professional societies cover how to choose between the two drugs and how to monitor treatment6.
Polymyxin B for injection and colistimethate for injection are FDA-approved, with generic versions on the US market, for serious infections caused by susceptible gram-negative bacteria such as Pseudomonas aeruginosa1,2. The original colistimethate brand, Coly-Mycin M, is listed as discontinued.
Both FDA labels warn of kidney damage (rising BUN and creatinine) and nerve toxicity, such as tingling around the mouth or limbs, dizziness, slurred speech, unsteadiness and blurred vision1,2. Nerve-muscle blockade can stop breathing, especially after anesthesia or muscle relaxants or with poor kidney function. Polymyxin B's boxed warning covers these risks and says to avoid other kidney- or nerve-toxic drugs1. Fever, rash, injection-site pain, seizures (colistimethate) and C. difficile diarrhea are also listed. In OVERCOME, about half of colistin-treated patients had acute kidney injury5.
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