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Peptide

Polymyxins (polymyxin B and colistin)

Older peptide antibiotics now used as a last resort against multidrug-resistant gram-negative bacteria (Acinetobacter, Pseudomonas, carbapenemase-producing Enterobacterales).
Regulatory status
Approved (FDA / EMA)
Family
Lipopeptide antibiotics (polymyxins)
Scientific evidence
Moderate
Number of findings
1
Where it acts
Immunity and defense
Also known as
polymyxin B, colistin, colistina, polimixina E, colistimetato de sodio, colistimethate, Coly-Mycin M, Promixin, Colobreathe

Regulatory status

FDA (US): Approved for decades: injectable polymyxin B and colistimethate (Coly-Mycin M) for serious infections caused by susceptible gram-negative bacteria

EMA (EU): Authorized through national procedures (in Spain, injectable and inhaled colistimethate and others). Colistimethate powder for inhalation (2012, Colobreathe) was approved through the centralized route for Pseudomonas lung infection in cystic fibrosis. The EMA reviewed colistimethate dosing in 2014

Dose

Intravenous colistimethate in adults: loading dose of 9 million IU and then 9 million IU a day divided into 2–3 doses, adjusting in renal impairment (EMA recommendation 2014). Polymyxin B: 15,000–25,000 IU/kg/day intravenously divided every 12 hours (FDA label).

Safety

Frequent kidney toxicity and neurological toxicity (tingling, dizziness, muscle weakness and, rarely, neuromuscular blockade with respiratory arrest). Inhaled, it can cause bronchospasm. They require monitoring of kidney function. Hospital use only and under the supervision of infectious disease specialists.

Interactions

More kidney damage with aminoglycosides, vancomycin, and other nephrotoxic drugs. They potentiate muscle relaxants and anesthetics (risk of neuromuscular blockade).

Effect by goal · level of evidence

Colistin alone vs colistin plus meropenem in serious infections

no clear effect Moderate RCT (AA) in people
Failure 79% vs 73% (not significant)

AIDA trial with 406 adults with carbapenem-resistant gram-negative infections, mostly Acinetobacter. Clinical failure at 14 days was high in both groups (79% with colistin alone and 73% with the combination), with no significant difference. The combination caused more diarrhea.

View the study (RCT) →

In depth

Where it acts

Immunity and defense

Defenses and infections

How it works

They have a positively charged part that binds to the lipopolysaccharide of the outer membrane of gram-negative bacteria. They displace the calcium and magnesium that stabilize it and disorganize it, and the bacterium loses its contents and dies. Colistin is administered as a prodrug (colistimethate), which is converted to colistin in the body.

What the evidence says

In people

  • Colistin alone versus colistin plus meropenem in serious infections. AIDA trial with 406 adults with carbapenem-resistant gram-negative infections, mainly Acinetobacter. Clinical failure at 14 days was high in both groups (79% with colistin alone and 73% with the combination), with no significant difference. The combination caused more diarrhea. PubMed 29456043

Variants and related programs

Group profile: includes polymyxin B and colistin (polymyxin E), administered as colistimethate sodium intravenously or by inhalation.

References

  1. PubMed 29456043

Information, not medical advice. Prescription or unapproved peptides should only be used under medical supervision.

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