Colistin

Colistin:

Background:

Two forms of colistin are commercially available: colistin sulfate (available PO for bowel decontamination) and colistimethate sodium (IV or nebulised). When we refer to "colistin" for the Rx of MDRGNs we mean colistimethate sodium.

Dosages:

2mU tds IV, or 80 mg bd NEB. 80mg (=1mU) after each dialysis for ESRF. Dose should be adjusted based on ideal body weight. No data for patients with derranged LFTs. For intraventricular/ intrathecal Rx: 1.6mg od - 10mg bd.

Spectrum of action:

Colistin has excellent bactericidal activity against:

Acinetobacter spp.
P. aeruginosa
Klebsiella spp.
Enterobacter spp.
Escherichia coli
Salmonella spp.
Shigella spp.
Citrobacter spp.
Yersinia pseudotuberculosis
Haemophilus influenzae
Stenotrophomonas maltophilia.

Resistant to colistin:

Burkholderia cepacia
Proteus spp.
Providencia spp.
Serratia spp.
Edwardsiella spp.
Morganella morgannii

In addition, colistin is not active against Gram-negative and Gram-positive aerobic cocci, Gram-positive aerobic bacilli, and all anaerobes.

Mechanisms of Action:

This cationic (positively charged) antibiotic binds to the lipopolysaccharide (LPS) of the bacterial membrane of Gram-negative bacteria (negatively charged), eventually leading to the disruption of the bacterial cell membrane. In addition, by association with the LPS it exerts an antiendotoxin activity and leads subsequently to decreased levels of serum endotoxin and TNF- α.

Side Effects:

The commonest adverse events of colistin are nephrotoxicity (via acute tubular necrosis), neurotoxicity (dizziness, weakness, facial paresthesia, vertigo, visual disturbances, confusion,
ataxia), and neuromuscular blockade, which can lead to respiratory failure or apnea. Another rare but serious complication of colistin afflicting the muscles is rhabdomyolysis.

Resistance:

• Assess in vitro resistance by E-test.
• Heteroresistance has been noted to colistin.
• Lengthy use of colistin (median use of 27 days) has also been reported in a study of a multiclonal colistin-resistant K. pneumoniae.

In vitro data and in vivo animal experimental data suggest that the combination of rifampicin with colistin in the treatment of colistin-resistant Gram-negative bacteria leads to a synergistic effect against these bacteria, despite the fact that rifampicin is primarily active against Gram-positive bacteria and mycobacteria. It has been hypothesized that changes of the outer membrane contribute to this in vitro effectiveness.

Conclusions:

This is a very useful antibiotic. The following points should be noted:

• Incidence of nephrotoxicity is lower than previously reported.
• It should be part of a careful ABx stewardship programme, to prevent PDRGNs.
• Dosing should be checked carefully.
• There is a role for synergism, even if one ABx is reported as (R) on disk testing.

AMH.