Antibiotic Synergy Testing in Klebsiella Infections

Introduction to Synergy Testing

• The Infectious Diseases Society of America recommends antibiotic synergy testing for Klebsiella infections when drug choices are limited, such as in cases of carbapenem-resistant Klebsiella pneumoniae (CRKP) 1, 2, 3

When to Order Synergy Testing

• Synergy testing is indicated for patients with poor response to initial monotherapy after 48-72 hours of appropriate antibiotics, particularly in cases of carbapenem-resistant isolates 1
• The European Society of Clinical Microbiology and Infectious Diseases suggests synergy testing for multidrug-resistant (MDR) Klebsiella infections in critically ill patients 2, 3

Preferred Testing Methods

• The American Society for Microbiology recommends the checkerboard method as the first choice for synergy testing, which uses fractional inhibitory concentration (FIC) as a quantitative index to evaluate synergy level 1, 3, 4
• The broth disc elution method is a suitable alternative, demonstrating 100% sensitivity and 100% specificity when compared to modified broth microdilution 1, 2, 4

Most Effective Antibiotic Combinations

• The Infectious Diseases Society of America recommends polymyxin-based combinations, such as colistin + meropenem, for CRKP infections, with a synergism rate of 12.5% mortality when used in combination versus 66.7% with colistin monotherapy 1, 4
• Carbapenem-based combinations, despite resistance, show considerable synergistic effect when used in combination with polymyxin and tigecycline/fosfomycin/amikacin 1, 4

Critical Implementation Considerations

• The American Society for Microbiology suggests contacting the microbiology laboratory before ordering synergy testing to confirm availability and turnaround time, and to specify the testing method based on local laboratory capabilities 1, 2
• Therapeutic drug monitoring is crucial when using synergy-guided combination therapy, particularly for polymyxins and aminoglycosides, to optimize efficacy and minimize nephrotoxicity 5

Important Caveats and Pitfalls

• The European Society of Clinical Microbiology and Infectious Diseases notes that in vitro synergism between colistin and meropenem did not translate into clinical benefit in severe CRGNB infections, highlighting the importance of clinical judgment in interpreting synergy testing results 1, 4
• The Infectious Diseases Society of America recommends monitoring for emergence of resistance during combination therapy, particularly with Acinetobacter and Klebsiella 6