Colistimethate

Colistimethate, also called colistin or polymyxin E, is a cationic peptide. It targets Gram-negative bacteria, whose outer membrane is lined with a lipopolysaccharide. Its positive charges bind to the lipid A of this lipopolysaccharide and displace calcium and magnesium, two divalent cations that stabilise the membrane. Deprived of these supports, the membrane is destabilised, its permeability increases and the bacterium dies.

This mechanism explains its specificity: it acts on the wall unique to Gram-negative bacteria, and not on others. It is a so-called bactericidal antibiotic, because it directly kills the bacterium instead of merely slowing its growth. This membrane-disrupting action makes it effective where other antibiotic families fail.

Colistimethate is reserved for serious infections caused by multidrug-resistant Gram-negative bacilli. The organisms involved include Pseudomonas aeruginosa, Acinetobacter baumannii and carbapenem-resistant Enterobacteriaceae. These bacteria resist most common antibiotics, which makes them difficult to manage.

It serves as a last-line antibiotic: it is used when other treatments have failed. This particular place stems from its profile: it remains active against highly resistant organisms, but it requires careful monitoring. Its prescription belongs to a hospital or specialist setting, tailored to each infection.

Systemically, colistimethate is given by injection, intravenous or intramuscular, and not by mouth. The question of taking it with or without a meal therefore does not arise. In a patient whose renal function is normal, the reference dosage ranges from 2.5 to 5 mg/kg per day of colistin base, split into 2 to 4 administrations. After injection, the blood concentration declines with a half-life of 2 to 3 hours, which justifies this close rhythm.

There is also an inhaled form, Colobreathe, intended for chronic pulmonary infections caused by Pseudomonas aeruginosa in patients with cystic fibrosis from the age of 6. The schedule relies on one inhaled capsule twice a day, about 12 hours apart. Whatever the form, the treatment follows a precise schedule, and it is not stopped on one’s own initiative: regularity determines effectiveness against resistant organisms.

Nephrotoxicity is the most frequent and most concerning adverse effect of systemic colistimethate. It is probably dose-related and usually regresses when treatment is stopped. Kidney damage shows as a fall in urine output, a rise in blood urea and serum creatinine, and a fall in creatinine clearance. The official label also mentions abnormalities of electrolytes and acid-base balance, linked to this reduction in urine output.

The nervous system can also react during intravenous administration. Neurotoxicity occurs with an incidence of about 7 percent according to early studies. It manifests mainly through paraesthesia: tingling around the mouth, numbness of the extremities. These signs are most often transient and fade with adjustment of the treatment.

Combining colistimethate with other drugs toxic to the kidney, such as cephalothin sodium, can increase renal toxicity: these combinations are to be avoided. Colistimethate also potentiates the effect of curare-like drugs and other neuromuscular blocking agents, for example tubocurarine. The risk is a neuromuscular block that can extend to respiratory depression and apnoea, which calls for extreme caution during these combinations.

Follow-up rests on monitoring renal function. Urine output, blood urea, serum creatinine and creatinine clearance are checked throughout treatment. These parameters make it possible to detect kidney damage in time and to adjust the dose. Since nephrotoxicity is dose-dependent and regresses on stopping, this monitoring guides every decision.