Can colistin be used as monotherapy?

Colistin Monotherapy vs. Combination Therapy for Multidrug-Resistant Gram-Negative Infections

Colistin monotherapy is appropriate for non-severe infections or low-risk infections caused by multidrug-resistant gram-negative bacteria, while combination therapy is recommended for severe infections, particularly those caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) or carbapenem-resistant Acinetobacter baumannii (CRAB). 1, 2

Recommendations Based on Pathogen and Severity

For Carbapenem-Resistant Acinetobacter baumannii (CRAB):

• Strong recommendation against polymyxin-meropenem combination therapy (high certainty of evidence) 1
• Strong recommendation against polymyxin-rifampin combination therapy (moderate certainty of evidence) 1
• For severe and high-risk CRAB infections, combination therapy with two in vitro active antibiotics is suggested (conditional recommendation, very low certainty evidence) 1
• For CRAB with meropenem MIC <8 mg/L, consider carbapenem combination therapy using high-dose extended-infusion carbapenem dosing 1

For Carbapenem-Resistant Pseudomonas aeruginosa (CRPA):

• For severe CRPA infections treated with polymyxins, aminoglycosides, or fosfomycin, combination therapy with two in vitro active drugs is suggested 1
• For non-severe or low-risk CRPA infections, monotherapy with an in vitro active drug is appropriate 1

Evidence Supporting These Recommendations

Evidence for Monotherapy:

• The OVERCOME trial showed no significant difference in 28-day mortality between colistin monotherapy (46%) and colistin-meropenem combination (42%) for HAP/VAP and BSI caused by CR-GNB, primarily CRAB 1
• The AIDA RCT demonstrated no advantage of colistin-meropenem over colistin monotherapy for CRAB infections with respect to clinical failure or 14-day mortality 1
• For non-severe infections, monotherapy is supported as good clinical practice to promote antibiotic stewardship 1

Evidence for Combination Therapy:

• For severe CRPA infections, very low-certainty evidence suggests an advantage of polymyxin combined with another active antibiotic over polymyxin alone 1
• A retrospective study of XDR-P. aeruginosa nosocomial pneumonia showed colistin given alone was associated with higher mortality than colistin combined with another active antibiotic (adjusted OR 6.63) 1
• For severe CRAB infections, very-low-certainty evidence supports double-covering combination therapy 1

Clinical Considerations

Dosing Recommendations:

• Loading dose of 9 MU (5 mg/kg) followed by maintenance dose of 4.5 MU twice daily for critically ill patients 2, 3
• Careful attention to unit conversion: 1 million U = 80 mg colistin methanesulfonate = 33 mg colistin base activity 2
• Therapeutic drug monitoring is recommended when available 2, 3

Toxicity Concerns:

• Nephrotoxicity is the most significant adverse effect, occurring in 10.9-53.7% of patients 2, 3
• Risk factors include pre-existing renal impairment, older age, and concomitant nephrotoxic medications 2, 3
• Polymyxin B appears to have less nephrotoxicity compared to colistin (adjusted HR 2.27) 1, 2

Special Considerations:

• For respiratory infections, adding aerosolized polymyxin to intravenous therapy may improve clinical outcomes 2, 4
• Source control should always be prioritized to optimize outcomes and shorten antibiotic treatment durations 1, 2
• Follow-up cultures are recommended in case of treatment failure to detect resistance development 1, 2

Pitfalls to Avoid

• Colistin monotherapy may rapidly select resistant subpopulations; this is a concern particularly in severe infections 5
• Inconsistent dosing units and recommendations can lead to medication errors; standardize units when prescribing 5
• Nephrotoxicity monitoring is essential; regular assessment of renal function should be performed 2, 3
• Microbiological studies suggest superiority of combination treatment, which contrasts with some clinical data; clinical context should guide decision-making 6