Colistin (Plamocin) Should NOT Be Used for ESBL Infections When Carbapenems Are Available
Colistin is NOT recommended for treating ESBL-producing bacterial infections and should only be considered as a last-resort option when carbapenems and newer beta-lactam/beta-lactamase inhibitor combinations cannot be used. 1, 2
Why Colistin Performs Poorly Against ESBL Infections
The evidence strongly demonstrates that colistin has significantly worse outcomes compared to carbapenems for ESBL infections:
Mortality rates are dramatically higher with colistin: A 2021 study showed that loading-dose colistin was associated with 7.97 times higher 30-day mortality compared to carbapenems (HR 7.97; 95% CI 3.68-17.25; P = 0.001) in patients with ESBL-producing E. coli and K. pneumoniae infections 2
Clinical failure rates are substantially elevated: Colistin treatment resulted in 4.30 times higher clinical failure rates (HR 4.30; 95% CI 1.93-9.57; P = 0.001) compared to carbapenem therapy 2
Microbiological eradication is poor: Bacteriological failure was 9.49 times more likely with colistin versus carbapenems (HR 9.49; 95% CI 3.76-23.96; P = 0.001) 2
Recommended Treatment Algorithm for ESBL Infections
First-Line Treatment (Preferred)
- Carbapenems remain the gold standard: Group 2 carbapenems (meropenem, imipenem/cilastatin, doripenem) are the most reliable antibiotics for serious ESBL infections 1, 3, 4
- Dosing for critically ill patients: Meropenem 1g IV every 8 hours by extended infusion, or imipenem/cilastatin 500mg IV every 6 hours by extended infusion 1
Carbapenem-Sparing Alternatives (For Stable Patients)
- Ceftazidime/avibactam plus metronidazole: Demonstrates activity against ESBL-producers and some KPC-producing organisms 1
- Ceftolozane/tazobactam plus metronidazole: Effective for ESBL-producing Enterobacteriaceae while preserving carbapenems 1
- Piperacillin/tazobactam: May be considered for ESBL-producing E. coli specifically (not Klebsiella) in hemodynamically stable patients 1
When Colistin Context Actually Matters
Colistin's role is reserved for carbapenem-resistant organisms, not ESBL producers:
- For MBL-producing CRE: Even in this context, colistin-containing regimens showed the highest mortality rates compared to ceftazidime/avibactam plus aztreonam (19.2% vs 44% mortality; P = 0.007) 5
- For carbapenem-resistant Enterobacteriaceae: Colistin may be added to tigecycline plus carbapenem combinations in severe infections, but only as part of combination therapy 5
- For carbapenem-resistant A. baumannii: Colistin should be preserved for infections showing resistance to all beta-lactams, fluoroquinolones, and tigecycline 5
Critical Dosing Considerations If Colistin Must Be Used
If colistin is absolutely necessary (carbapenem allergy, carbapenem-resistant organism):
- Loading dose is essential: 6-9 million IU loading dose, followed by 4.5 million IU every 12 hours in critically ill patients with creatinine clearance >50 mL/min 5
- Suboptimal plasma concentrations are common: Standard dosing without a loading dose results in subtherapeutic levels for 2-3 days 5
- Nephrotoxicity monitoring required: Colistin is highly nephrotoxic, and serum levels should be monitored closely 5
Common Pitfalls to Avoid
- Never use colistin as first-line for ESBL infections: The mortality and failure data are unequivocal—carbapenems are superior 2
- Don't confuse ESBL with carbapenem resistance: ESBL-producing organisms remain carbapenem-susceptible by definition 3, 4, 6
- Avoid monotherapy with colistin: Even when colistin must be used for carbapenem-resistant organisms, combination therapy is preferred 5
- Don't delay carbapenem therapy: Clinical experience with colistin for ESBL infections is limited to case reports and shows poor outcomes 5
Antimicrobial Stewardship Perspective
- Reserve newer agents appropriately: Ceftazidime/avibactam and ceftolozane/tazobactam should be reserved for multidrug-resistant infections to preserve their activity 1
- Carbapenem stewardship is important but not at the expense of mortality: While carbapenem-sparing strategies are valuable for stable patients, critically ill patients with ESBL infections require carbapenems 1
- Local epidemiology guides therapy: In areas with high carbapenem resistance, carbapenem-sparing regimens become more important even for ESBL infections 1