What is the difference between Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines for interpreting Burkholderia cepacia antibiograms in a patient with cystic fibrosis or an immunocompromised state?

Comparison of CLSI and EUCAST Guidelines for Burkholderia cepacia Antibiograms

For Burkholderia cepacia complex, use CLSI guidelines exclusively, as EUCAST has not established interpretive criteria for this organism, and recent evidence demonstrates that even CLSI-based antimicrobial susceptibility testing performs poorly and should not be routinely performed. 1, 2

Critical Guideline Differences

EUCAST Limitations

• EUCAST has no published guidelines for antimicrobial susceptibility testing of Burkholderia cepacia complex 1
• The European Committee on Antimicrobial Susceptibility Testing presently lacks breakpoint concentrations for interpreting minimum inhibitory concentrations (MICs) as 'susceptible' or 'resistant' for B. cepacia 1
• This absence of EUCAST criteria means European laboratories must default to CLSI standards when testing is requested 1

CLSI as the Default Standard

• The Cystic Fibrosis Foundation and European Cystic Fibrosis Society jointly recommend that drug susceptibility testing for all organisms in CF patients, including B. cepacia, should be performed in accordance with CLSI guidelines 1
• CLSI provides categorical interpretations (susceptible, intermediate, resistant) based on MIC values expressed as micrograms/mL 1
• However, these CLSI breakpoints have had very limited clinical validation and no clinical validation has been performed specifically in patients with cystic fibrosis 1

Major Problems with Both Systems for B. cepacia

Poor Clinical Correlation

• Recent 2025 evidence demonstrates that routine antimicrobial susceptibility testing should NOT be performed for B. cepacia complex isolates due to poor method performance 2
• Standard susceptibility testing methods have poor predictive value for clinical outcomes in B. cepacia infections, likely because in vitro testing conditions differ dramatically from the lung environment in CF patients 3
• Major discrepancies exist between standard susceptibility results and actual antibiotic activity—some antibiotics like ceftazidime show minimal activity in clinically relevant models despite low MICs 3

Methodological Failures

• If providers request testing, only CLSI reference broth microdilution methodology should be used, with MIC values reported without categorical interpretation 2
• Disk diffusion, agar dilution, and gradient diffusion (ETEST) all perform poorly for B. cepacia, regardless of which Mueller-Hinton agar manufacturer is used 2
• Broth microdilution reproducibility for B. cepacia is acceptable (≥93%) for levofloxacin, meropenem, minocycline, and trimethoprim-sulfamethoxazole, but just below acceptable for ceftazidime (93%) 2

Practical Clinical Approach

When Susceptibility Testing is Requested

• Perform CLSI reference broth microdilution using stored frozen panels 2
• Report MIC values only, without categorical S/I/R interpretations 2
• Inform providers that results have significant limitations and may not predict clinical response 2

Treatment Selection Strategy

• Prioritize trimethoprim-sulfamethoxazole as first-line when susceptible, with ceftazidime, meropenem, or ceftazidime-avibactam as alternatives based on susceptibility testing 4
• Use combination therapy for severe infections rather than relying on monotherapy 4
• Consider that minocycline, meropenem, and ceftazidime are the most active agents in vitro, inhibiting 38%, 26%, and 23% of strains respectively 5
• Clinical evidence shows favorable outcomes in 68-100% of cases treated with ceftazidime and 67% with meropenem 6

Special Considerations for CF Patients

• Discontinue azithromycin immediately following B. cepacia isolation, as macrolides should never be prescribed without two appropriate companion antibiotics 4
• Inhaled tobramycin should not be used for maintenance therapy in B. cepacia colonized patients 4
• B. cepacia tends to colonize rather than cause invasive disease, which should inform treatment duration decisions 4

Key Pitfalls to Avoid

• Do not rely on disk diffusion or ETEST results for B. cepacia—these methods correlate poorly with reference methods 2
• Do not assume susceptibility testing predicts clinical outcomes—treatment decisions should integrate clinical context, not just laboratory results 3, 2
• Do not use EUCAST criteria, as they do not exist for this organism 1
• Avoid generalizing from non-CF patient data, as CF patients have unique pharmacokinetic and pharmacodynamic considerations 1