Infectious Disease Compendium

Colistin

Dosing

(PubMed)

CrCl Formula

CrCl > 80: 2.5-5 mg/kg/day IM or IV in 2 to 4 divided doses, maximum 5 mg/kg/day. 1 million units bid inhaled has been used to treat multidrug resistant pneumonia (PubMed).

Comes as an inactive prodrug that has to be metabolized to colistin. Much of the prodrug is cleared by the kidneys before it is converted but is converted in the urine so good for UTI. Great patient variability in blood levels.

Higher dose (9 MIU vs 4 MIU) did not decrease mortality but did increase nephrotoxicity (PubMed).

CrCl 80-50: 75% of the normal dose.

(PubMed).

CrCl 50-10: 50% of the normal dose.

CrCl < 10: 25% of the normal dose.

The above is US dosing. European dosing has higher doses at lower gfr and is better.

Hemodialysis:

Peritoneal dialysis:

Important side effects

Neurotoxic (confusion, muscle weakness, visual disturbances, vertigo, paraesthesia, neuropathy) and nephrotoxic (about half will develop some degree of renal insufficiency, esp at higher doses (PubMed)).

Important drug interactions

Alcuronium, amikacin, atracurium, cisatracurium, doxacurium, fazadinium, gallamine, hexafluorenium, metocurine, mivacurium, pancuronium, pipecuronium, rapacuronium, rocuronium, tubocurarine, vecuronium.

Inhaled colistin can be fatal or cause ARDS.

Rants and Screeds

There are issues with purity and potency due to the way the antibiotic is produced that cannot be predicted (PubMed).

Pearls

''We put forth the view that overall polymyxin B has superior clinical pharmacological properties compared with CMS/colistin (PubMed)."

May be using more of it as resistance rates keep on going up.

Higher dosing leads to better outcomes but more renal dysfunction (PubMed), although other studies suggest ONLY increased toxicity with higher doses (Pubmed).

Treatment of choice

Use for

Aerobic gram negative rods including Acinetobacter, Citrobacter, Haemophilus influenzae, Enterobacter, Escherichia coli, Klebsiella, Morganella morganii, Pseudomonas aeruginosa, Salmonella, Shigella, Stenotrophomonas maltophilia, Yersinia pseudotuberculosis.

For hospital acquired pneumonias, it is probably no worse than 'usual' antibiotics (PubMed).

If you should have to resort to colistin, adding inhaled to iv probably adds nothing for the treatment of pneumonia (PubMed), although the data is variable and not without potential complications.

Resistance, unfortunately plasmid mediated, is starting to be seen as of 2016.

Don't use for

Pseudomonas mallei, Burkholderia cepacia, Proteus species, Providencia species, Serratia species, Edwardsiella species, and Brucella species are all resistant to colistin.

Class

Detergent. But it will get out those pesky grass stains.