Polymixins

Question 1

Polymixins

Answer 1

Colistin (colistimethate sodium)
Polymixin B

Older class
Revived due to resistant Gram- infections
Have not been evaluated with rigor of modern drug approval process
PK and efficacy data are limited

Useful in highly resistant G- organisms
Acinetobacter baumannii
P. aeruginosa
Carbapenem resistant Enterobacteriaceae (CRE), like K. pneumoniae

Question 2

Polymixins MOA

Answer 2

Bind to outer membrane of G- bacteria- leading to disruption of membrane stability and leakage of cellular components

Question 3

Polymixins Spectrum

Answer 3

Good
Many GNRs (highly drug resistant AB, PA, and KP

Moderate
Stenotrophomonas maltophilia

Poor
All G+ organisms 
Anaerboes
Proteus 
Providencia 
Burkholderia 
Serratia 
G- Cocci

Question 4

Polymixins Adverse Effects

Answer 4

Renal
Most common adverse effect is nephrotoxicity (due to acute tubular necrosis)
Acute kidney injury commonly occurs in clinical use; incidence is hard to estimate because most recent studies are non-comparative evaluations of salvage therapies in very ill patients
PB is less nephrotoxic than colistin
Avoid concomitant nephrotoxins if possible

Neurological
Neurotoxicity is less common
Can manifest as dizziness, weakness, paresthesias, or mental status changes
Neuromuscular blockade can lead to fatal respiratory arrest

Question 5

Polymixins Important Facts

Answer 5

Very similar drugs
Colistin may be more active (administered as colistimethate sodium in order to be given systemically- the converted to active colistin in the body)
Cmethate is renally cleared; only the portion not cleared is converted to colistin

In US dosed as mg of colistin base activity (~400 mg Cmethate = 150mg of CBA)
The amount that is systemically active differs in each patient
Colistin itself is not used systemically
When a text refers to colistin, they are referring to Cmethate sodium

Differ in PK
Colistin given as renally eliminated prodrug
PB given in active form and has more predictable PK
Give both drugs with loading doses

PB not eliminated renally; do not adjust dose in renal dysfunction
Unlikely to be successful in UTIs

Europe and other parts of world dose in international units
1mg of CBA ~ 30,000 units (actual calculation is 33,333 units but many references round)

1,000,000 units ~ 80mg Cmethate ~ 30mg CBA
1mg CBA ~ 2.7mg Cmethate ~ 30,000 units

Never prescribe or recommend dose in mg of Cmethate; a misinterpretation can be fatal

PB dosing: 1mg = 10,000 units

Generally last line drugs and given in combination with other drugs
Combos can include colistin with rifampin and meropenem and may be better than colistin alone

Oral formulation of colistin given only for vowel decontamination (such as before GI surgery)
Don’t convert IV to PO for systemic infection

Aerosolized polymixins used to decrease colonization with G- bacteria (mainly Pseudomonas) in some patients (mainly CF)
Prepare just before administration
Some also use to treat pneumonia (not very strong evidence)

Estimates of polymixin nephrotoxicity vary but he incidence is substantial (especially in critically ill patients who may not be able to tolerate the renal insult
Avoid other nephrotoxins if possible (including Vanco)

Question 6

Polymixins Good For

Answer 6

Multi-drug resistant G- infections
Pneumonia 
Bacteremia
Sepsis
Complicated UTIs

Polymixins are poorly studied in many of these disease states so use other drugs if pathogens are susceptible