Polymyxins for ESBL-Producing Bacterial Infections
Polymyxins are NOT first-line agents for ESBL-producing bacteria and should be reserved exclusively for carbapenem-resistant organisms when other options have failed. 1, 2
Why Polymyxins Are Not Appropriate for ESBL Infections
Carbapenems remain the definitive first-line treatment for serious ESBL infections, particularly in critically ill patients, as they provide superior outcomes with established safety profiles. 1, 2 Polymyxins should be reserved as last-resort antibiotics specifically for carbapenem-resistant Gram-negative bacilli (CRGNB), not for ESBL-producers that remain carbapenem-susceptible. 3
The Treatment Hierarchy for ESBL Infections
For ESBL-producing bacteria, the evidence-based treatment algorithm prioritizes:
Critically ill patients with ESBL infections:
- Group 2 carbapenems (meropenem 1g IV q6h by extended infusion, imipenem/cilastatin 500mg IV q6h, or doripenem 500mg IV q8h) are the immediate first-line choice 1, 2
- These agents have proven activity against non-fermentative Gram-negative bacilli and ESBL-producers 3, 1
Moderate severity ESBL infections in stable patients:
- Piperacillin/tazobactam (6g/0.75g loading dose, then 4g/0.5g IV q6h or 16g/2g continuous infusion) can be considered, though this remains controversial 3, 1
- Ceftazidime/avibactam plus metronidazole demonstrates activity against ESBL-producers and some KPC-producing organisms 1, 2
- Ceftolozane/tazobactam plus metronidazole is effective for carbapenem-sparing strategies 1, 2
Mild ESBL infections:
- Group 1 carbapenems like ertapenem 1g IV q24h have activity against ESBL-producing pathogens (but not Pseudomonas aeruginosa) 3, 1
When Polymyxins Are Actually Indicated
Polymyxins should only be used for carbapenem-resistant Gram-negative bacilli (CRGNB), not ESBL-producers. 3 The 2023 guidelines for carbapenem-resistant infections provide clear evidence:
For CRGNB infections requiring polymyxin treatment:
- Polymyxin combination therapy is strongly recommended over monotherapy (strong recommendation, moderate-quality evidence) 3
- Combination therapy reduces mortality by 14 fewer deaths per 1000 patients (RR 0.97), treatment failures by 119 per 1000 patients (RR 0.82), and pathogen eradication failures by 74 per 1000 patients (RR 0.81) 3
Specific polymyxin-carbapenem combinations are recommended only when:
- Meropenem MIC is ≤8 mg/L for CRE infections, using high-dose extended-infusion meropenem for 3 hours 3
- Carbapenem MIC is ≤32 mg/L for CRAB infections 3
Critical Pitfalls to Avoid
Using polymyxins for ESBL infections when carbapenems are available wastes a last-resort antibiotic and increases resistance pressure. 4, 5 The revival of polymyxins since the mid-1990s has already led to emergence of polymyxin-resistant strains, making preservation of their activity crucial. 4, 5
Nephrotoxicity monitoring is mandatory if polymyxins must be used:
- Renal failure develops in 14% of patients with normal baseline function 6
- Mortality increases to 57% in those who develop renal failure versus 20% overall 6
- Development of renal failure is significantly associated with older age (76 vs 59 years, P=0.02) 6
- Avoid combining polymyxins with other nephrotoxic or ototoxic drugs 3
- Therapeutic drug monitoring (TDM) should be performed where possible 3
Dosing confusion is a common error:
- Colistin methanesulfonate (CMS): 1 million U = 80 mg mass CMS = 33 mg colistin base activity (CBA) 3
- Polymyxin B sulfate: 1 mg = 10,000 U 3
- Colistin sulfate: 1 mg = 22,700 U 3
The Bottom Line
For ESBL-producing bacteria, use carbapenems or newer beta-lactam/beta-lactamase inhibitor combinations—never polymyxins as first-line therapy. 1, 2 Polymyxins are exclusively reserved for carbapenem-resistant organisms where they represent the last available option, and even then, combination therapy is strongly preferred over monotherapy. 3 Preserving polymyxin activity by restricting use to truly resistant organisms is essential for maintaining this last-resort option. 4, 5