title: Pilot Screening to Determine Antimicrobial Synergies in a Multidrug-Resistant Bacterial Strain Library.
abstract: With the rise in multidrug-resistant (MDR) bacterial infections, there has been increasing interest in combinations of ≥2 antimicrobial agents with synergistic effects. We established an MDR bacterial strain library to screen for in vitro antimicrobial synergy by using a broth microdilution checkerboard method and high-throughput luciferase-based bacterial cell viability assay. In total, 39 MDR bacterial strains, including 23 carbapenem-resistant gram-negative bacteria, 9 vancomycin-intermediate Staphylococcus aureus, and 7 vancomycin-resistant Enterococcus faecalis, were used to screen for potential antimicrobial synergies. Synergies were more frequently identified with combinations of imipenem plus trimethoprim-sulfamethoxazole for carbapenem-resistant Acinetobacter baumannii in the library. To verify this finding, we tested 34 A. baumannii clinical isolates resistant to both imipenem and trimethoprim-sulfamethoxazole by the checkerboard method. The imipenem plus trimethoprim-sulfamethoxazole combination showed synergy in the treatment of 21 (62%) of the clinical isolates. The results indicate that pilot screening for antimicrobial synergy in the MDR bacterial strain library could be valuable in the selection of combination therapeutic regimens to treat MDR bacterial infections. Further studies are warranted to determine whether this screening system can be useful to screen for the combined effects of conventional antimicrobials and new-generation antimicrobials or nonantimicrobials.
authors.affiliation: 1 Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.|2 Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Incheon St. Mary's Hospital, Incheon, Republic of Korea.|3 Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Si-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: 1 Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Chulmin
authors.initials: C
authors.lastname: Park
authors.affiliation: 1 Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Chun
authors.affiliation: 1 Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.|3 Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Dong-Gun
authors.initials: DG
authors.lastname: Lee
authors.affiliation: 1 Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.|3 Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Jae-Ki
authors.initials: JK
authors.lastname: Choi
authors.affiliation: 1 Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.|3 Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: 1 Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.|3 Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Sung-Yeon
authors.initials: SY
authors.lastname: Cho
authors.affiliation: 1 Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.|3 Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Park
authors.affiliation: 1 Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.|3 Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Su-Mi
authors.initials: SM
authors.lastname: Choi
authors.affiliation: 1 Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.|2 Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Incheon St. Mary's Hospital, Incheon, Republic of Korea.|3 Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Choi
authors.affiliation: 1 Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.|3 Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Jin-Hong
authors.initials: JH
authors.lastname: Yoo
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004357:Drug Synergism; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D015870:Gene Expression; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D057166:High-Throughput Screening Assays; D015378:Imipenem / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology*; D001618:beta-Lactamases / Q000145:classification / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D015378:Imipenem; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D001618:beta-Lactamases