2024 IDSA S. maltophilia infections 治療策略

General Principles

1. Colonization vs. True Infection

   • Carefully distinguish between colonization and true infection to avoid unnecessary antibiotic use.
   • True infections are common in vulnerable populations such as immunocompromised patients, individuals with pulmonary diseases, and those with hematological malignancies.

2. Preferred Approach

   • Combination therapy is generally favored to enhance efficacy and prevent resistance, particularly in moderate to severe infections.
   • Select agents with complementary mechanisms of action, considering in vitro activity, PK/PD properties, and clinical evidence.

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First-Line Agents and Recommendations

1. Cefiderocol

   • Role: Preferred agent in combination therapy.
   • Rationale: Nearly 100% in vitro susceptibility, strong PK/PD data, and potent activity demonstrated in animal models.
   • Limitation: Limited clinical data; use in combination therapy is recommended until clinical improvement.

2. Ceftazidime-Avibactam + Aztreonam

   • Role: Preferred treatment combination to overcome intrinsic β-lactamase-mediated resistance.
   • Rationale: Effective against both L1 and L2 β-lactamases; ~92% in vitro susceptibility to aztreonam-avibactam.
   • Limitation: Limited clinical data; monitor for liver enzyme elevations.

3. Minocycline (High Dose: 200mg q12h)

   • Role: Option as part of combination therapy.
   • Rationale: ~70-90% in vitro susceptibility (when using the previous CLSI breakpoint of ≤4 µg/mL, 2023年後改1µg/mL); better PK/PD and tolerability compared to other tetracycline derivatives.
   • Limitation: Avoid in UTIs and use cautiously for bloodstream infections due to poor serum levels.

4. Trimethoprim-Sulfamethoxazole (TMP-SMX: 10-15mg/kg based on TMP)

   • Role: Option as part of combination therapy.
   • Rationale: >90% susceptibility; extensive clinical use history.
   • Limitation: Only bacteriostatic against S. maltophilia; associated with significant adverse effects (e.g., hypersensitivity, nephrotoxicity).

5. Levofloxacin

   • Role: Option as part of combination therapy.
   • Rationale: Preferred fluoroquinolone with CLSI breakpoints; may offer marginal mortality benefits in some cases.
   • Limitation: High MIC variability, emergence of resistance during therapy, and PK/PD limitations.

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Agents Not Recommended

1. Ceftazidime

   • Reason: Intrinsic resistance due to L1 and L2 β-lactamases. CLSI breakpoints no longer available.

2. Eravacycline and Omadacycline

   • Reason: Limited in vitro activity against S. maltophilia; not supported by clinical data.

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Dosing Recommendations

• Cefiderocol: Standard dosing based on clinical guidelines.
• Ceftazidime-Avibactam + Aztreonam: Administer based on established combination protocols.
• Minocycline: 200 mg IV every 12 hours for optimal PK/PD target attainment.
• TMP-SMX: 10-15 mg/kg/day (trimethoprim component) to balance efficacy and toxicity. Higher doses (>15 mg/kg/day of trimethoprim) are associated with increased toxicity without clear clinical benefit.
• Levofloxacin: 750 mg IV daily (adjust dose based on renal function).

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Special Considerations

1. Monitoring

   • Regularly monitor for adverse effects such as hepatotoxicity (e.g., with ceftazidime-avibactam + aztreonam), nephrotoxicity (e.g., TMP-SMX), and emergence of resistance (e.g., levofloxacin).

2. Infection Sites

   • Avoid tetracyclines in UTIs due to poor urinary concentrations.
   • Use combination therapy in bloodstream infections to improve outcomes.

3. Tailored Therapy

   • Adjust based on antimicrobial susceptibility testing (AST) results and patient-specific factors.

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Conclusion

The management of S. maltophilia infections requires a nuanced approach that balances efficacy, resistance prevention, and adverse effect profiles. Combination therapy is generally preferred for moderate to severe infections, with cefiderocol and ceftazidime-avibactam + aztreonam being the most reliable options. TMP-SMX, minocycline, and levofloxacin serve as alternative agents within combination regimens, depending on susceptibility, site of infection, and patient tolerance.