Polymyxins are a class of antibiotics used as a last resort against multidrug-resistant gram-negative bacteria. If you’re working through a practice question about what is NOT true of polymyxins, the false statement typically involves one of a few common traps: claiming they work against gram-positive bacteria, that they are bacteriostatic, or that they are well absorbed from the gut. All three of those claims are false. Here’s a breakdown of the key facts so you can spot the incorrect statement in any version of this question.
Spectrum: Gram-Negative Only
Polymyxins are active exclusively against gram-negative bacteria. They target organisms like Pseudomonas aeruginosa, Acinetobacter baumannii, and the majority of Enterobacteriaceae. Gram-positive bacteria, fungi, and mammalian cells are not affected. Any statement suggesting polymyxins cover gram-positive organisms is incorrect.
Even within the gram-negative world, there are natural gaps. Proteus, Providencia, Serratia, and Burkholderia cepacia species are inherently resistant. A question that claims polymyxins cover all gram-negative bacteria would also be false.
Mechanism of Action
Polymyxins are positively charged molecules that bind to lipopolysaccharide (LPS) in the outer membrane of gram-negative bacteria. They work by displacing the calcium and magnesium ions that normally stabilize the membrane’s structure. This loosens the packing of the outer membrane, creates defects, and ultimately causes the cell contents to leak out, killing the bacterium. The process is rapid and concentration-dependent.
This makes polymyxins bactericidal, not bacteriostatic. They actively destroy bacteria rather than simply stopping them from growing. Any exam statement calling polymyxins bacteriostatic is a classic false answer.
Poor Oral Absorption
Polymyxins have very poor permeability and absorption in the gastrointestinal tract. They are not effective for systemic infections when taken by mouth. For systemic use, they must be given intravenously or intramuscularly. Oral formulations are occasionally used for gut decontamination precisely because the drug stays in the GI tract and isn’t absorbed. A statement suggesting good oral bioavailability or routine oral use for systemic infections is false.
Polymyxin B vs. Colistin
The two clinically used polymyxins are polymyxin B and colistin (also called polymyxin E). Their chemical structures, mechanism of action, resistance patterns, and antibacterial spectrum are nearly identical, but they differ in how they’re administered and metabolized.
Colistin is given intravenously as colistimethate sodium (CMS), an inactive prodrug that converts to active colistin in the body. Polymyxin B, by contrast, is administered in its active form. This distinction matters clinically: colistin converts to its active form partly in the urinary tract, making it useful for urinary infections. Polymyxin B is cleared primarily through nonrenal routes, so it should not be used for bladder infections. Current IDSA guidance recommends avoiding both agents for most serious infections when alternatives exist, reserving colistin as a last-resort option for certain urinary tract infections caused by resistant organisms.
Nephrotoxicity and Neurotoxicity
The most significant downside of polymyxins is kidney damage. In clinical studies, acute kidney injury occurs in roughly 40 to 45 percent of patients receiving either polymyxin B or colistin. The good news is that kidney injury reverses after stopping the drug in the majority of cases, around 80 to 92 percent depending on which polymyxin was used.
Neurotoxicity is less common, occurring in about 9.5 percent of patients overall, though rates are much higher with polymyxin B (around 18 percent) than with colistin (about 1.4 percent). Symptoms include tingling or numbness around the mouth and extremities, dizziness, vertigo, and slurred speech. These effects resolve after the drug is discontinued. In rare cases, polymyxins can cause neuromuscular blockade that leads to respiratory muscle paralysis, a potentially fatal complication that can develop within hours of a dose.
Any statement claiming polymyxins are free of serious side effects or have no renal toxicity is incorrect.
Resistance Through Membrane Modification
Bacteria resist polymyxins by changing the chemical makeup of their outer membrane. The key strategy is modifying lipid A, the part of LPS that polymyxins bind to. By attaching positively charged molecules to the normally negative phosphate groups on lipid A, bacteria reduce the electrostatic attraction that pulls polymyxins to the membrane surface.
In 2015, researchers identified a gene called mcr-1 (mobile colistin resistance) on a plasmid from bacteria collected at a pig farm in China. This was alarming because plasmids can transfer between bacterial species, meaning resistance can spread horizontally rather than arising independently in each organism. The MCR-1 enzyme adds a chemical group to the phosphate on lipid A, reducing its negative charge and weakening polymyxin binding. A statement claiming polymyxin resistance cannot be transferred between bacteria would be false.
Common False Statements to Watch For
- “Polymyxins are effective against gram-positive bacteria.” False. They target only gram-negative organisms.
- “Polymyxins are bacteriostatic.” False. They are bactericidal, killing bacteria by disrupting the cell membrane.
- “Polymyxins are well absorbed orally.” False. GI absorption is very poor; systemic use requires parenteral administration.
- “Polymyxins have no significant toxicity.” False. Nephrotoxicity rates exceed 40 percent, and neurotoxicity is a recognized risk.
- “Polymyxin resistance cannot spread between bacteria.” False. Plasmid-mediated resistance via mcr-1 allows horizontal transfer.