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

Abstract

Background: 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.

Objective: 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.

Content: 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.

Keywords: Antimicrobial resistance; Burkholderia cepacia; CLSI/EUCAST; Combination therapy; Stenotrophomonas maltophilia.