Colistin and Polymyxin B medical comic

This comic explains the polymyxins, the 'detergents' kept for multidrug-resistant Gram-negative infections. It covers how they burst the bacterial membrane, why colistin and polymyxin B are not interchangeable, which bacteria resist them naturally and how resistance spreads, their kidney and nerve toxicity, and why only broth microdilution gives a reliable result.

For MBBS, NEET-PG, FMGE, NEXT and USMLE revision.

Colistin and polymyxin B: what the comic covers

High-yield points

Colistin (polymyxin E) and polymyxin B are reserve 'salvage' drugs for multidrug-resistant and extensively drug-resistant Gram-negative bacilli, such as carbapenem-resistant Klebsiella, Acinetobacter and Pseudomonas.
They are cationic peptides that bind lipid A in the outer membrane and act like detergents, causing rapid, bactericidal lysis; they also bind and neutralise endotoxin.
Colistin is given as an inactive prodrug (colistimethate) that is slowly converted in the body and cleared by the kidneys, so it suits urinary infections but needs careful renal dosing.
Polymyxin B is given in its active form with predictable levels and mainly non-renal clearance, so it is preferred for bloodstream infections and pneumonia.
Proteus, Providencia, Morganella, Serratia and Burkholderia are naturally resistant, because phosphoethanolamine added to lipid A reduces the negative charge.
Acquired resistance comes from mutations in PmrA/PmrB, PhoP/PhoQ or mgrB (common in Klebsiella) and from the plasmid-borne mcr genes, which can spread between bacteria.
The main toxicities are kidney damage and neurotoxicity; polymyxin-induced neuromuscular blockade is not reversed by neostigmine.
Disc diffusion and E-tests are unreliable because the large molecules diffuse poorly; broth microdilution is required to measure the MIC.

Mnemonics from the comic

Intrinsic resistance: P-M-S-B: Proteus/Providencia, Morganella, Serratia, Burkholderia.

Quick questions

What is the difference between colistin and polymyxin B?

Colistin is given as the inactive prodrug colistimethate, which is slowly activated and cleared by the kidneys, making it useful for urinary infections. Polymyxin B is given in its active form with mainly non-renal clearance, so it reaches reliable blood levels quickly.

Which bacteria are naturally resistant to colistin?

Proteus, Providencia, Morganella, Serratia and Burkholderia, as well as Gram-positive bacteria.

How should colistin susceptibility be tested?

By broth microdilution. Disc diffusion and gradient strips give unreliable results because polymyxins diffuse poorly through agar.

Is this comic free to read?

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