Can Nebulised Colistin Be Given With Polymyxin B?
No, nebulised colistin (colistimethate sodium) should not be given concomitantly with polymyxin B because they are both polymyxin antibiotics with overlapping neurotoxic and nephrotoxic effects that can potentiate each other's toxicity. 1, 2
Critical Drug Interaction Warning
The FDA label for colistin explicitly states that "certain other antibiotics (aminoglycosides and polymyxin) have also been reported to interfere with nerve transmission at the neuromuscular junction. Based on this reported activity, they should not be given concomitantly with Colistimethate for Injection except with greatest caution." 1
Similarly, the FDA label for polymyxin B warns that "the concurrent or sequential use of other neurotoxic and/or nephrotoxic drugs with polymyxin B sulfate, particularly bacitracin, streptomycin, neomycin, kanamycin, gentamicin, tobramycin, amikacin, cephaloridine, paromomycin, viomycin, and colistin should be avoided." 2
Why This Combination Is Contraindicated
Overlapping Mechanism of Toxicity
Both drugs are polymyxins: Colistin (polymyxin E) and polymyxin B are members of the same antibiotic class with identical mechanisms of action and toxicity profiles 3
Neuromuscular blockade: Both polymyxins interfere with nerve transmission at neuromuscular junctions, which can result in muscle weakness, respiratory paralysis, and apnea 1, 2
Nephrotoxicity: Both drugs cause dose-dependent kidney injury through similar mechanisms, with nephrotoxicity rates ranging from 10.9-53.7% 4
Specific Toxicity Concerns
Neurotoxic manifestations include irritability, weakness, drowsiness, ataxia, perioral paresthesia, numbness of extremities, and blurring of vision—all associated with high serum levels 2
Nephrotoxicity presents as albuminuria, cellular casts, azotemia, diminishing urine output, and rising BUN 2
Respiratory paralysis from neuromuscular blockade is especially dangerous when polymyxins are given soon after anesthesia and/or muscle relaxants 2
Clinical Algorithm for Polymyxin Selection
Choose ONE Polymyxin Only
If nebulised therapy is needed for respiratory infections:
- Use nebulised colistin (2 million IU every 8-12 hours) PLUS intravenous colistin (not polymyxin B) 5
- Standard dosing: 9 MU (5 mg/kg) loading dose, then 4.5 MU twice daily maintenance 4
If intravenous therapy alone is sufficient:
- Consider polymyxin B over colistin due to lower nephrotoxicity risk (adjusted HR 2.27 for colistin vs polymyxin B) 4, 6
- Polymyxin B nephrotoxicity rate: 11.8% vs colistin 39.3% in prospective comparison 6
Route-Specific Considerations
Nebulised colistin should always be combined with intravenous antimicrobial therapy (which can be colistin or another agent, but NOT polymyxin B) for pneumonia 5
Ultrasonic or vibrating plate nebulizers must be used for proper drug delivery—standard jet nebulizers are inadequate 5
Aerosolized polymyxin in addition to intravenous polymyxin may improve outcomes for respiratory infections, but this refers to using the SAME polymyxin via both routes, not combining different polymyxins 7, 8
Common Pitfall to Avoid
Do not confuse "combination therapy" with "combining two polymyxins": When guidelines recommend polymyxin combination therapy, they mean combining a polymyxin (either colistin OR polymyxin B, not both) with a different class of antibiotic such as carbapenems, aminoglycosides, or tigecycline 7, 4
Monitoring Requirements If Using Any Polymyxin
Monitor renal function closely: serum creatinine, BUN, creatinine clearance, and urine output 1, 2
Watch for neurotoxicity signs: muscle weakness, paresthesias, respiratory depression 1, 2
Discontinue immediately if signs of impaired renal function develop 1
Risk factors for nephrotoxicity include age >65 years, pre-existing renal impairment, concomitant nephrotoxic medications, and vasopressor use 9, 10