Is polymyxin (Polymyxin B) effective against Extended-Spectrum Beta-Lactamase (ESBL)-producing infections?

Is Polymyxin Active Against ESBL-Producing Bacteria?

Yes, polymyxins (polymyxin B and colistin) have in vitro bactericidal activity against ESBL-producing Enterobacteriaceae, but they should NOT be used as first-line therapy for ESBL infections when carbapenems or newer beta-lactam/beta-lactamase inhibitor combinations are available. 1, 2

Treatment Hierarchy for ESBL Infections

First-Line Options (Use These First)

• Carbapenems are the definitive first-line treatment for serious ESBL infections, particularly in critically ill patients, due to superior outcomes and established safety profiles 1, 2
• Group 2 carbapenems (meropenem, imipenem/cilastatin, doripenem) are preferred for critically ill patients with high bacterial loads or serious infections 2
• Group 1 carbapenems (ertapenem) have activity against ESBL-producing pathogens but lack activity against Pseudomonas aeruginosa 2

Second-Line Carbapenem-Sparing Options

• Ceftazidime/avibactam plus metronidazole demonstrates activity against ESBL-producers and some KPC-producing organisms 2
• Ceftolozane/tazobactam plus metronidazole can be considered for carbapenem-sparing strategies 1
• Piperacillin/tazobactam may be considered for moderate severity ESBL infections in stable patients, though this remains controversial 1

When Polymyxins Should Be Used

• Polymyxins should be reserved exclusively as last-resort antibiotics for carbapenem-resistant Gram-negative bacilli (CRGNB), NOT for ESBL-producers that remain carbapenem-susceptible 1
• Polymyxins have been "resurrected" for treating multidrug-resistant infections in critically ill patients when other options are exhausted 3
• They demonstrate rapid in vitro bactericidal activity against major MDR Gram-negative bacteria including Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae 4

Critical Rationale: Why NOT to Use Polymyxins for ESBL

Microbiological Activity vs. Clinical Appropriateness

• While polymyxins possess in vitro activity against ESBL-producing organisms 4, using them for ESBL infections wastes a last-resort antibiotic and increases resistance pressure when superior alternatives exist 1
• Recent CLSI revisions set polymyxin 'intermediate' breakpoints at ≤2 mg/L for Enterobacterales, implying limited clinical efficacy even at this MIC value 5

Safety and Efficacy Concerns

• Nephrotoxicity is a significant concern, occurring in approximately 10% of patients, requiring mandatory monitoring if polymyxins must be used 1, 6
• Suboptimal pharmacokinetics/pharmacodynamics, particularly in lung environments, limit efficacy 5
• Polymyxin combination therapy is strongly recommended over monotherapy when treating CRGNB to reduce mortality and treatment failures 1

Algorithmic Approach to ESBL Treatment

Step 1: Confirm ESBL and assess severity

• Critically ill/septic shock → Group 2 carbapenems immediately 2
• Stable patient with adequate source control → Consider carbapenem-sparing options 2

Step 2: Check local resistance patterns

• High carbapenem-resistant Klebsiella pneumoniae rates → Strongly favor carbapenem-sparing regimens 2
• Low resistance rates → Carbapenems remain appropriate 1

Step 3: Reserve polymyxins ONLY if:

• Documented carbapenem resistance (not just ESBL) 1
• All other options exhausted or contraindicated 3
• Always use combination therapy, never monotherapy 1

Common Pitfalls to Avoid

• Never use polymyxins as first-line for ESBL when carbapenems are available - this accelerates resistance to last-resort antibiotics 1
• Avoid combining polymyxins with other nephrotoxic or ototoxic drugs 1
• Do not confuse dosing regimens between colistin methanesulfonate (CMS), polymyxin B sulfate, and colistin sulfate 1
• Therapeutic drug monitoring should be performed where possible to minimize nephrotoxicity risk 1
• First-generation cephalosporins and fluoroquinolones (in high-resistance areas) lack activity against ESBL-producers and should not be used 2