Is polymyxin B (Polymyxin B) and cefoperazone-sulbactam (Cefoperazone-Sulbactam) a good combination for treating infections?

Polymyxin B and Cefoperazone-Sulbactam Combination for Treating Resistant Infections

Polymyxin B combined with cefoperazone-sulbactam is an effective combination therapy for treating carbapenem-resistant Gram-negative bacterial infections, particularly those caused by Acinetobacter baumannii, with demonstrated synergistic activity and improved bacterial clearance rates. 1, 2

Efficacy of the Combination

Evidence Supporting the Combination

• The combination of polymyxin B with sulbactam-containing agents (including cefoperazone-sulbactam) has demonstrated higher pathogen eradication rates compared to polymyxin combined with tigecycline or polymyxin monotherapy 1
• A 2022 clinical study showed that polymyxin B combined with cefoperazone-sulbactam and tigecycline significantly improved bacterial clearance rates in patients with multidrug-resistant Acinetobacter baumannii pneumonia 2
• Sulbactam has inherent antimicrobial activity against Acinetobacter species (MIC50 of 1.0 μg/ml), making it particularly valuable in combination regimens 3

Mechanism of Synergy

• Sulbactam has a higher affinity and binding constant for plasmid-mediated β-lactamases compared to cefoperazone alone (≥10-fold difference) 3
• The addition of sulbactam to polymyxin B and other antibiotics can significantly improve their action against OXA-producing A. baumannii isolates 4
• In vitro studies have shown synergistic activity (FICI ≤0.281) when sulbactam is added to combinations with meropenem and polymyxin B, even against polymyxin-resistant isolates 4

Clinical Applications

Recommended Scenarios for Use

• Particularly effective for carbapenem-resistant Acinetobacter baumannii (CRAB) infections 1
• Suitable for respiratory tract infections caused by multidrug-resistant Gram-negative bacteria 5, 2
• Effective for bloodstream infections caused by CRAB 1

Dosing Considerations

• For severe CRAB infections, the dose of sulbactam can be increased to 6.0-9.0 g/day 1
• In fixed-dose combinations, cefoperazone 1.5 g/sulbactam 1.5 g every 6 hours has been used effectively 1
• For polymyxin B, careful dosing with attention to renal function is essential 1

Advantages Over Other Regimens

• A retrospective study in China showed that cefoperazone-sulbactam group had significantly lower 28-day mortality rate (29.3%) compared to tigecycline group (51.9%) in CRAB bloodstream infections 1
• Cefoperazone-sulbactam combined with imipenem-cilastatin demonstrated lower mortality than cefoperazone-sulbactam alone 1
• Polymyxin-based combinations with sulbactam have shown fewer nephrotoxicity events compared to other polymyxin-based regimens 1

Potential Limitations and Monitoring

• Nephrotoxicity is a concern with polymyxin B, though studies show it may be less common when used in combination with sulbactam compared to other combinations 1, 5
• Patients should be monitored for renal function during treatment 1
• Not indicated for patients with hypersensitivity to penicillin 1

Treatment Algorithm

1. Confirm susceptibility: Verify susceptibility of the isolate to both polymyxin B and cefoperazone-sulbactam before initiating therapy
2. Assess infection severity:
   • For severe CRAB infections: Consider high-dose sulbactam (6-9 g/day) in the combination 1
   • For less severe infections: Standard dosing may be sufficient
3. Evaluate renal function:
   • Adjust polymyxin B dosing based on renal function
   • Monitor renal function regularly during treatment
4. Duration of therapy:
   • Mean duration in successful treatment courses has been approximately 14-19 days 5, 2
5. Monitoring response:
   • Track inflammatory markers (WBC, CRP, PCT) to assess treatment efficacy 2
   • Follow-up cultures are recommended to detect potential resistance development 1

Common Pitfalls to Avoid

• Failure to perform susceptibility testing before initiating therapy
• Inadequate dosing of sulbactam component (doses ≥6 g/day may be needed for severe infections) 1
• Not monitoring renal function during polymyxin B therapy
• Using the combination in patients with penicillin hypersensitivity 1
• Discontinuing therapy prematurely before complete bacterial eradication

This combination represents an important therapeutic option in the era of increasing antimicrobial resistance, particularly for carbapenem-resistant Gram-negative infections where treatment options are limited.