A modified Kirby-Bauer disc diffusion (mKB) method for accurately testing tigecycline susceptibility: a nation-wide multicenter comparative study

Introduction. Tigecycline is one of the important antibiotics available for treating infection caused by multiple-drug resistant pathogens. However, the conventional AST methods which are commonly used in clinical microbiology laboratories usually lead to false intermediate or resistant results in testing tigecycline susceptibility, and further mislead clinical antimicrobial therapies. Hypothesis. The modified Kirby-Bauer disc diffusion (mKB) method was performed based on the traditional standard Kirby-Bauer disc diffusion (sKB) method. Aim. To evaluate a modified Kirby-Bauer disc diffusion (mKB) method for tigecycline susceptibility testing, for the purpose of providing accurate tigecycline susceptibility results in clinical practice. Methodology. A total of 4271 nonduplicate clinical strains were isolated from 37 hospitals across China to perform the mKB method, standard Kirby-Bauer disc diffusion (sKB) method, comparing with the reference broth microdilution (BMD) according to the CLSI. Parameters of categorical agreement (CA), minor errors (mE), major errors (ME), and very major errors (VME) were used in this methodological evaluation research. Results. BMD testing showed that 91.3-98.9 % of the A. baumannii, K. pneumoniae, E. coli, E. cloacae, S. marcescens, and C. freundii strains were susceptible, while 0-3.1% strains were resistant to tigecycline. When testing A. baumannii, mKB demonstrated higher CA than sKB (90.6 % vs 44.8%) compared to reference BMD. The mE (9.0 % vs 45.2%), ME (0.5% vs 10.6%) and VME (both 0 %) all satisfied the acceptability criteria. mKB also showed higher CA (87.2% vs 52.0%) than sKB in comparison with BMD when testing Enterobacterales (mainly K. pneumonia). The ME (0.45 % vs 8.1%) and VME (both 0 %) but not mE (12.4 % vs 40.4%) met the acceptability criteria. Conclusion. The mKB method can test bacterial susceptibility to tigecycline more accurately than sKB. For the tigecycline-intermediate or -resistant strains by sKB method, BMD or mKB method should be used to verify the results and report reliable tigecycline susceptibility results.