Hung-Jen Tang1,2, Yi-Tsung Lin3,4, Chi-Chung Chen2,5, Chih-Wei Chen6, Ying-Chen Lu5,7, Wen-Chien Ko8,9, Hung-Jui Chen1, Bo-An Su1, Ping-Chin Chang10, Yin-Ching Chuang1,2, Chih-Cheng Lai11. 1. Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan. 2. Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan. 3. Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. 4. Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei, Taiwan. 5. Department of Food Science, National Chiayi University, Chiayi, Taiwan. 6. Division of Neurosurgery, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan. 7. Department of Occupational Safety and Health/Institute of Industrial Safety and Disaster Prevention, College of Sustainable Environment, Chia Nan University of Pharmacy and Science, Tainan, Taiwan. 8. Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. 9. Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 10. Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan. 11. Department of Internal Medicine, Kaohsiung Veterans General Hospital, Tainan Branch, Tainan, Taiwan.
Abstract
OBJECTIVES: To investigate the in vitro activity of antibiotics against clinical Elizabethkingia anophelis isolates and to find a suitable antibiotic combination with synergistic effects to combat antibiotic-resistant E. anophelis and its associated biofilm. METHODS: E. anophelis isolates were identified by 16S rRNA sequencing; 30 strains with different pulsotypes were identified and the MIC, antibiotic resistance mechanism, antibiotic combination activity and killing effects of antimicrobial agents on biofilms of these strains were determined. RESULTS: All E. anophelis isolates were susceptible to minocycline and cefoperazone/sulbactam (1:1). More than 90% of clinical isolates were susceptible to cefoperazone/sulbactam (1:0.5), piperacillin/tazobactam and rifampicin. Some novel mutations, such as gyrA G81D, parE D585N and parC P134T, that have never been reported before, were identified. The synergistic effect was most prominent for the combination of minocycline and rifampicin, with 93.3% of their FIC index values ≤0.5, and no antagonism was observed using the chequerboard method. This synergistic effect between minocycline and rifampicin was also observed using time-killing methods for clinical E. anophelis isolates at both normal inoculum and high inoculum. Twenty-nine isolates tested positive for biofilm formation. Minocycline remained active against biofilm-embedded and biofilm-released planktonic E. anophelis cells; however, the enhanced effect of minocycline by adding rifampicin was only observed at 24 h (not at 72 and 120 h). CONCLUSIONS: Although E. anophelis was resistant to many antibiotics and could exhibit biofilm formation, minocycline showed potent in vitro activity against this pathogen and its associated biofilm.
OBJECTIVES: To investigate the in vitro activity of antibiotics against clinical Elizabethkingia anophelis isolates and to find a suitable antibiotic combination with synergistic effects to combat antibiotic-resistant E. anophelis and its associated biofilm. METHODS: E. anophelis isolates were identified by 16S rRNA sequencing; 30 strains with different pulsotypes were identified and the MIC, antibiotic resistance mechanism, antibiotic combination activity and killing effects of antimicrobial agents on biofilms of these strains were determined. RESULTS: All E. anophelis isolates were susceptible to minocycline and cefoperazone/sulbactam (1:1). More than 90% of clinical isolates were susceptible to cefoperazone/sulbactam (1:0.5), piperacillin/tazobactam and rifampicin. Some novel mutations, such as gyrA G81D, parE D585N and parC P134T, that have never been reported before, were identified. The synergistic effect was most prominent for the combination of minocycline and rifampicin, with 93.3% of their FIC index values ≤0.5, and no antagonism was observed using the chequerboard method. This synergistic effect between minocycline and rifampicin was also observed using time-killing methods for clinical E. anophelis isolates at both normal inoculum and high inoculum. Twenty-nine isolates tested positive for biofilm formation. Minocycline remained active against biofilm-embedded and biofilm-released planktonic E. anophelis cells; however, the enhanced effect of minocycline by adding rifampicin was only observed at 24 h (not at 72 and 120 h). CONCLUSIONS: Although E. anophelis was resistant to many antibiotics and could exhibit biofilm formation, minocycline showed potent in vitro activity against this pathogen and its associated biofilm.
Authors: Isin Y Comba; Audrey N Schuetz; Anisha Misra; Daniel Z P Friedman; Ryan Stevens; Robin Patel; Zane D Lancaster; Aditya Shah Journal: J Clin Microbiol Date: 2022-05-05 Impact factor: 11.677