MBEC Determination Guides to Choose the Optimal Drug And Dose in Biofilm Forming Hypervirulent Klebsiella pneumoniae: Value Addition to Antimicrobial Stewardship

Abstract

Purpose: Traditionally, MIC values are considered gold standard for determining the susceptibility of clinical pathogens. However, for strong biofilm-forming hypervirulent (hv) Klebsiella pneumoniae pathotypes MBEC values serve as a better indicator in therapy Methods & Materials: This study includes a total of 180 carbapenem-resistant K. pneumoniae (CR-Kp) from bloodstream infections archived at the Department of Clinical Microbiology, Christian Medical College, Vellore, India during 2019-2020. Study isolates were screened for mucoviscous phenotype by string test and rmpA, rmpA2 and iutA gene PCR. Biofilm forming potential and antimicrobial susceptibility were determined by crystal violet assay and broth microdilution respectively. Further, a subset of 16 isolates was subjected to MBEC assay against meropenem, colistin, ceftazidime/avibactam, and ceftazidime/avibactam with aztreonam. Clinical outcomes were correlated with biofilm formation. Results: Based on string test and gene screening by PCR, study isolates were classified into classical (82/180) and hypervirulent (98/180) pathotypes of. Among the subset of 16 isolates, 25% were also resistant to colistin. Based on biofilm-forming potential, the isolates were categorized as strong, moderate, weak and negative biofilm formers of which 50%, 33.3%, 25% and 0% were resistant to colistin. MIC ranges for these isolates were determined as 0.5 to >64 for ceftazidime/avibactam, 64 for minocycline. In contrast, MBEC ranges from 64 to >1024 µg/mL, 32 to 512 µg/mL, 2 to 64 µg/mL, 4 to >64 µg/mL and 16 to 128 µg/mL respectively for the same subset. Our findings are in line with 2 to 4 fold higher MBEC requirements in comparison with MIC as observed previously. Though colistin MBEC values ranged from 4 to >64, the fold reduction of MBEC in comparison to MIC makes minocycline a better treating option than colistin for biofilm infections Conclusion: From this study, minocycline or colistin were observed to be optimal drug for biofilm-forming K. pneumoniae in comparison to ceftazidime/avibactam with aztreonam. The potential of cefipime+zidebactam against biofilm-forming K. pneumoniae needs further exploration. MBEC value determination plays a vital role in selecting optimal drug of strong biofilm-forming K. pneumoniae