Peptide education
Polymyxin B and Colistin
Polymyxins B and E
Polymyxin B and colistin, also called polymyxin E, are related antibiotics used against selected Gram-negative bacteria. Injectable colistimethate is converted to colistin in the body; polymyxin B is a different drug.
These antibiotics have serious kidney and nervous-system risks. The infection, susceptibility results, formulation, and dose units all matter when a clinical team chooses treatment.
Overview
Quick answer
US injectable labels express polymyxin B in polymyxin B units and colistimethate in milligrams of colistin base activity. The numbers refer to different drugs and dose measures.
Are polymyxin B and colistin the same medicine?
No. They are related polymyxins. Injectable colistimethate is converted to colistin; polymyxin B is administered as an active drug.
What infections do their labels cover?
The injectable labels describe infections caused by susceptible Gram-negative bacteria. The bacteria, infection site, and susceptibility results affect the choice of treatment.
How are the injectable products given?
The polymyxin B label includes intravenous, intramuscular, intrathecal, and ophthalmic use in specified contexts. The colistimethate label describes intravenous or intramuscular administration.
What is the main safety concern?
Kidney injury and neurologic effects can occur. Polymyxin B's boxed warning includes respiratory paralysis from neuromuscular blockade, particularly around anesthesia or muscle relaxants. Colistimethate can also cause breathing problems and neuromuscular blockade.
Why are dose units important?
The polymyxin B label uses polymyxin B units. The colistimethate label uses milligrams of colistin base activity. These are different product measures and are not interchangeable.
Evidence
Evidence snapshot
In 406 adults with serious carbapenem-resistant Gram-negative infections, adding meropenem did not significantly reduce clinical failure at day 14.
The injectable label warns about kidney injury, neurotoxicity, and respiratory paralysis from neuromuscular blockade.
The US injectable label describes dose in milligrams of colistin base activity and calls for reduced dose and frequency in renal impairment.
The product label calls for reduction in renal impairment. International consensus guidance advises against renal adjustment of the polymyxin B daily maintenance dose on the basis of pharmacokinetic evidence.
Claims
Common claims vs evidence
| Claim | Human evidence | Verdict |
|---|---|---|
| Polymyxin B and colistin can be exchanged by matching the dose number. | Polymyxin B is an active drug; injectable colistimethate is a prodrug of colistin. Their US labels express doses in different units. | Drug identity, formulation, and units must be checked separately. |
| Adding meropenem to colistin always improves outcomes. | A randomized trial reported clinical failure at day 14 in 156 of 198 patients receiving colistin alone and 152 of 208 receiving both drugs. The difference was not statistically significant. | The trial did not show that adding meropenem improved its primary outcome. Most infections in the trial were caused by Acinetobacter baumannii. |
| Both drugs have a single universal renal dose adjustment rule. | The US colistimethate label calls for reducing the daily dose and frequency in renal impairment. The polymyxin B label also calls for dose reduction, while international consensus guidance advises against renal adjustment of the polymyxin B daily maintenance dose based on pharmacokinetic evidence. | Clinicians must distinguish the drug and the source of dosing guidance. |
Bottom line
Main takeaway
These antibiotics disrupt the membranes of certain Gram-negative bacteria. Kidney and nerve effects require clinical monitoring.
Polymyxin B and colistimethate are distinct products. Their US labels use polymyxin B units and milligrams of colistin base activity, respectively.
The randomized colistin comparison mostly involved Acinetobacter baumannii and was not powered to answer organism-specific questions for less common bacteria.
Identity
What it is
Polymyxin B and colistin are related cyclic lipopeptide antibiotics. The injectable colistin product discussed in the US label is colistimethate sodium, a prodrug converted to colistin. Polymyxin B products contain related components including B1 and B2; colistin products contain components including colistin A and B.
The injectable labels cover selected infections caused by susceptible Gram-negative organisms, including Pseudomonas aeruginosa. The choice depends on the infection and available alternatives.
Use context
Routes, doses, and cycle patterns
The injectable labels use different dose measures for patients with normal kidney function. The polymyxin B label and expert consensus differ on maintenance-dose adjustment for renal impairment.
Human studies and product labels
Polymyxin B injection, intravenous label
- Purpose
- Susceptible Gram-negative infections within the product indication
- Context
- US polymyxin B product label
- Route
- Intravenous infusion
- Amount
- 15,000 to 25,000 polymyxin B units per kg per day with normal kidney function
- Frequency
- Infusions may be given every 12 hours
The label calls for a lower dose in kidney impairment. International consensus guidance advises against renal adjustment of the polymyxin B daily maintenance dose based on pharmacokinetic evidence. The clinical team weighs the drug, monitoring, and current guidance.
Colistimethate injection label
- Purpose
- Susceptible Gram-negative infections within the product indication
- Context
- US COLY-MYCIN M product label
- Route
- Intravenous or intramuscular
- Amount
- 2.5 to 5 mg of colistin base activity per kg per day with normal kidney function
- Frequency
- Two to four divided doses per day
The label calls for reductions in daily dose and frequency when kidney function is impaired. The vial strength is expressed as colistin base activity, not milligrams of polymyxin B.
Colistimethate with or without meropenem trial
- Purpose
- Serious carbapenem-resistant Gram-negative infections in adults
- Context
- Randomized superiority trial
- Route
- Intravenous
- Amount
- 9 million international units of colistimethate as a loading dose, then 4.5 million international units
- Frequency
- Every 12 hours after the loading dose, adjusted for kidney function
Participants received colistin alone or with meropenem. The trial registration identifies colistimethate sodium and renal adjustment. The primary endpoint was clinical failure at day 14.
What varies
- Product identity and dose units matter. Polymyxin B units and milligrams of colistin base activity describe different labeled products.
- Both labels address kidney monitoring. The polymyxin B label and international consensus differ on renal adjustment of the daily maintenance dose.
- For invasive carbapenem-resistant A. baumannii infections, the IDSA guidance reserves polymyxin B with another agent as an alternative when resistance precludes sulbactam-durlobactam or while access is pending.
Research
Research evidence
A randomized trial compared colistin alone with colistin plus meropenem in adults with serious carbapenem-resistant Gram-negative infections. Most infections were caused by A. baumannii, and clinical failure at day 14 remained common in both groups.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Colistin alone versus colistin plus meropenem | 406 adults with serious carbapenem-resistant Gram-negative infections | Randomized, open-label superiority trial with blinded outcome assessment | Intravenous colistin with or without meropenem | Clinical failure at day 14 occurred in 156 of 198 patients on colistin alone and 152 of 208 on the combination. The difference was not statistically significant. | A. baumannii caused most infections. The trial was not powered to answer organism-specific questions for less common bacteria and did not compare colistin with polymyxin B. | Controlled human evidence for the studied comparison |
| Polymyxin product labels and consensus guidance | Patients treated for selected Gram-negative infections | US prescribing information and international expert consensus | Polymyxin B injection and colistimethate injection | Labels describe different dose units and warn about kidney and neurologic toxicity. The label and consensus differ on renal adjustment of the polymyxin B maintenance dose. | Product labels and expert guidance address different evidence and dosing conventions. The named medicine and clinical setting determine which information is relevant. | Product-specific labeling and clinical guidance |
Cautions
Safety and unknowns
- Kidney injury can occur with either medicine. The labels describe renal monitoring and warn about toxicity from other kidney-damaging medicines.
- Neurologic effects can include numbness, tingling, and dizziness. Polymyxin B's boxed warning includes neuromuscular blockade and respiratory paralysis, particularly after anesthesia or muscle relaxants. The colistimethate label also warns about apnea and neuromuscular blockade, particularly with impaired kidney function, and cautions about muscle relaxants and other medicines that affect nerve transmission.
- Polymyxin B is contraindicated after a hypersensitivity reaction to a polymyxin. Colistimethate is contraindicated in patients with a history of sensitivity to that drug or its components.
- The labels describe electrolyte abnormalities associated with renal tubulopathy and discuss monitoring during treatment.
Product quality
Product identity and quality
Injectable polymyxin B and colistimethate have different vial strengths, product instructions, and dose expressions.
Named drug
Polymyxin B and colistimethate are related but distinct medicines.
Dose units
The US labels use polymyxin B units and milligrams of colistin base activity for their respective products.
Route
The labels specify different routes and clinical settings for each formulation.
Mechanism
How it is proposed to work
Polymyxins damage the membranes of susceptible Gram-negative bacteria. Colistimethate is converted to the active antibiotic colistin.
The polymyxin B label describes increased bacterial membrane permeability. The colistimethate label also describes membrane disruption.
Infectious-disease guidance describes colistin formation from its prodrug and distinguishes its handling from that of polymyxin B.
FAQ
Common questions
Are polymyxin B and colistin the same drug?
No. They are related polymyxins. Injectable colistimethate is a prodrug converted to colistin, while polymyxin B is administered as an active drug.
Why do dose units matter?
The cited US polymyxin B label uses polymyxin B units, while the colistimethate label uses milligrams of colistin base activity. These measures identify different products and cannot be substituted directly.
Details
Technical details
Sources
References
- 1.
- 2.
- 3.
doi:10.1016/S1473-3099(18)30099-9 PMID:29456043 NCT01732250
- 4.
ClinicalTrials.gov. Colistin alone versus colistin plus meropenem trial registration
NCT01732250
The registered colistin intervention identifies colistimethate sodium, international units, and renal adjustment.
- 5.
PubMed. Antimicrobial activity and toxicity of the major lipopeptide components of polymyxin B and colistin
doi:10.1021/acsinfecdis.5b00085 PMID:27525307
- 6.
PubMed Central. International consensus guidelines for the optimal use of the polymyxins
PMID:30710469
- 7.