Breakpoint Withdrawals and Emerging Evidence: Reframing Clinical Decisions for B. cepacia complex and S. maltophilia

Burkholderia cepacia complex (BCC) and Stenotrophomonas maltophilia are intrinsically resistant non-fermenting gram-negative bacilli increasingly implicated in healthcare-associated infections, especially among immunocompromised patients. Their complex resistance mechanisms and diagnostic ambiguity complicate clinical management. Recent changes in antimicrobial susceptibility testing (AST) guidelines further complicate clinical management.

To outline the impact of breakpoint withdrawals by CLSI and EUCAST on AST interpretation and treatment strategies for BCC and S. maltophilia and emphasize the need for evidence-based, context-specific treatment strategies.

CLSI (2025) and EUCAST (2024) have removed breakpoints for most agents against BCC, requiring MIC reporting based on WT/NWT distributions. For S. maltophilia, CLSI no longer supports monotherapy with Co-trimoxazole or levofloxacin; EUCAST retains a breakpoint only for the Co-trimoxazole. Resistance mechanisms, including β-lactamases and RND efflux pumps, limit AST reliability. Diagnostic challenges include species misidentification and distinguishing infection from colonization. Therapeutic options remain limited. Trimethoprim-sulfamethoxazole has reduced efficacy; minocycline, fluoroquinolones, and cefiderocol show inconsistent outcomes. Combination therapy offers no clear advantage and should be individualized. These changes necessitate MIC-based, genomics-informed approaches to guide therapy, particularly in low-resource settings.