In vitro Bactericidal Activities of Combination Antibiotic Therapies Against Carbapenem-Resistant Klebsiella pneumoniae With Different Carbapenemases and Sequence Types
Carbapenem-resistant Klebsiella pneumoniae (CRKP) is becoming increasingly problematic due to the limited effectiveness of new antimicrobials or other factors such as treatment cost. Thus, combination therapy remains a suitable treatment option. We aimed to evaluate the in vitro bactericidal activit...
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| Format: | Article |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.779988/full |
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| author | Jocelyn Qi-Min Teo Jocelyn Qi-Min Teo Nazira Fauzi Jayden Jun-Yuan Ho Si Hui Tan Shannon Jing-Yi Lee Tze Peng Lim Tze Peng Lim Tze Peng Lim Yiying Cai Hong Yi Chang Nurhayati Mohamed Yusoff James Heng-Chiak Sim Thuan Tong Tan Rick Twee-Hee Ong Andrea Lay-Hoon Kwa Andrea Lay-Hoon Kwa Andrea Lay-Hoon Kwa |
| author_facet | Jocelyn Qi-Min Teo Jocelyn Qi-Min Teo Nazira Fauzi Jayden Jun-Yuan Ho Si Hui Tan Shannon Jing-Yi Lee Tze Peng Lim Tze Peng Lim Tze Peng Lim Yiying Cai Hong Yi Chang Nurhayati Mohamed Yusoff James Heng-Chiak Sim Thuan Tong Tan Rick Twee-Hee Ong Andrea Lay-Hoon Kwa Andrea Lay-Hoon Kwa Andrea Lay-Hoon Kwa |
| author_sort | Jocelyn Qi-Min Teo |
| collection | DOAJ |
| description | Carbapenem-resistant Klebsiella pneumoniae (CRKP) is becoming increasingly problematic due to the limited effectiveness of new antimicrobials or other factors such as treatment cost. Thus, combination therapy remains a suitable treatment option. We aimed to evaluate the in vitro bactericidal activity of various antibiotic combinations against CRKP with different carbapenemase genotypes and sequence types (STs). Thirty-seven CRKP with various STs and carbapenemases were exposed to 11 antibiotic combinations (polymyxin B or tigecycline in combination with β-lactams including aztreonam, cefepime, piperacillin/tazobactam, doripenem, meropenem, and polymyxin B with tigecycline) in static time-kill studies (TKS) using clinically achievable concentrations. Out of the 407 isolate-combination pairs, only 146 (35.8%) were bactericidal (≥3 log10CFU/mL decrease from initial inoculum). Polymyxin B in combination with doripenem, meropenem, or cefepime was the most active, each demonstrating bactericidal activity in 27, 24, and 24 out of 37 isolates, respectively. Tigecycline in combination with β-lactams was rarely bactericidal. Aside from the lower frequency of bactericidal activity in the dual-carbapenemase producers, there was no apparent difference in combination activity among the strains with other carbapenemase types. In addition, bactericidal combinations were varied even in strains with similar STs, carbapenemases, and other genomic characteristics. Our findings demonstrate that the bactericidal activity of antibiotic combinations is highly strain-specific likely owing to the complex interplay of carbapenem-resistance mechanisms, i.e., carbapenemase genotype alone cannot predict in vitro bactericidal activity. The availability of WGS information can help rationalize the activity of certain combinations. Further studies should explore the use of genomic markers with phenotypic information to predict combination activity. |
| first_indexed | 2024-12-22T22:14:03Z |
| format | Article |
| id | doaj.art-7e5bb80322584be7a5cc76c79951a76c |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-22T22:14:03Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-7e5bb80322584be7a5cc76c79951a76c2022-12-21T18:10:48ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-12-011210.3389/fmicb.2021.779988779988In vitro Bactericidal Activities of Combination Antibiotic Therapies Against Carbapenem-Resistant Klebsiella pneumoniae With Different Carbapenemases and Sequence TypesJocelyn Qi-Min Teo0Jocelyn Qi-Min Teo1Nazira Fauzi2Jayden Jun-Yuan Ho3Si Hui Tan4Shannon Jing-Yi Lee5Tze Peng Lim6Tze Peng Lim7Tze Peng Lim8Yiying Cai9Hong Yi Chang10Nurhayati Mohamed Yusoff11James Heng-Chiak Sim12Thuan Tong Tan13Rick Twee-Hee Ong14Andrea Lay-Hoon Kwa15Andrea Lay-Hoon Kwa16Andrea Lay-Hoon Kwa17Department of Pharmacy, Singapore General Hospital, Singapore, SingaporeSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, SingaporeDepartment of Pharmacy, Singapore General Hospital, Singapore, SingaporeDepartment of Pharmacy, Singapore General Hospital, Singapore, SingaporeDepartment of Pharmacy, Singapore General Hospital, Singapore, SingaporeDepartment of Pharmacy, Singapore General Hospital, Singapore, SingaporeDepartment of Pharmacy, Singapore General Hospital, Singapore, SingaporeSinghealth Duke-NUS Pathology Academic Clinical Programme, Singapore, SingaporeSinghealth Duke-NUS Medicine Academic Clinical Programme, Singapore, SingaporeDepartment of Pharmacy, Singapore General Hospital, Singapore, SingaporeDepartment of Pharmacy, Singapore General Hospital, Singapore, SingaporeDepartment of Pharmacy, Singapore General Hospital, Singapore, SingaporeDepartment of Microbiology, Singapore General Hospital, Singapore, SingaporeDepartment of Infectious Diseases, Singapore General Hospital, Singapore, SingaporeSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, SingaporeDepartment of Pharmacy, Singapore General Hospital, Singapore, SingaporeSinghealth Duke-NUS Medicine Academic Clinical Programme, Singapore, SingaporeEmerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, SingaporeCarbapenem-resistant Klebsiella pneumoniae (CRKP) is becoming increasingly problematic due to the limited effectiveness of new antimicrobials or other factors such as treatment cost. Thus, combination therapy remains a suitable treatment option. We aimed to evaluate the in vitro bactericidal activity of various antibiotic combinations against CRKP with different carbapenemase genotypes and sequence types (STs). Thirty-seven CRKP with various STs and carbapenemases were exposed to 11 antibiotic combinations (polymyxin B or tigecycline in combination with β-lactams including aztreonam, cefepime, piperacillin/tazobactam, doripenem, meropenem, and polymyxin B with tigecycline) in static time-kill studies (TKS) using clinically achievable concentrations. Out of the 407 isolate-combination pairs, only 146 (35.8%) were bactericidal (≥3 log10CFU/mL decrease from initial inoculum). Polymyxin B in combination with doripenem, meropenem, or cefepime was the most active, each demonstrating bactericidal activity in 27, 24, and 24 out of 37 isolates, respectively. Tigecycline in combination with β-lactams was rarely bactericidal. Aside from the lower frequency of bactericidal activity in the dual-carbapenemase producers, there was no apparent difference in combination activity among the strains with other carbapenemase types. In addition, bactericidal combinations were varied even in strains with similar STs, carbapenemases, and other genomic characteristics. Our findings demonstrate that the bactericidal activity of antibiotic combinations is highly strain-specific likely owing to the complex interplay of carbapenem-resistance mechanisms, i.e., carbapenemase genotype alone cannot predict in vitro bactericidal activity. The availability of WGS information can help rationalize the activity of certain combinations. Further studies should explore the use of genomic markers with phenotypic information to predict combination activity.https://www.frontiersin.org/articles/10.3389/fmicb.2021.779988/fullin vitrobactericidalcombinationcarbapenemaseenterobacteralestigecycline |
| spellingShingle | Jocelyn Qi-Min Teo Jocelyn Qi-Min Teo Nazira Fauzi Jayden Jun-Yuan Ho Si Hui Tan Shannon Jing-Yi Lee Tze Peng Lim Tze Peng Lim Tze Peng Lim Yiying Cai Hong Yi Chang Nurhayati Mohamed Yusoff James Heng-Chiak Sim Thuan Tong Tan Rick Twee-Hee Ong Andrea Lay-Hoon Kwa Andrea Lay-Hoon Kwa Andrea Lay-Hoon Kwa In vitro Bactericidal Activities of Combination Antibiotic Therapies Against Carbapenem-Resistant Klebsiella pneumoniae With Different Carbapenemases and Sequence Types Frontiers in Microbiology in vitro bactericidal combination carbapenemase enterobacterales tigecycline |
| title | In vitro Bactericidal Activities of Combination Antibiotic Therapies Against Carbapenem-Resistant Klebsiella pneumoniae With Different Carbapenemases and Sequence Types |
| title_full | In vitro Bactericidal Activities of Combination Antibiotic Therapies Against Carbapenem-Resistant Klebsiella pneumoniae With Different Carbapenemases and Sequence Types |
| title_fullStr | In vitro Bactericidal Activities of Combination Antibiotic Therapies Against Carbapenem-Resistant Klebsiella pneumoniae With Different Carbapenemases and Sequence Types |
| title_full_unstemmed | In vitro Bactericidal Activities of Combination Antibiotic Therapies Against Carbapenem-Resistant Klebsiella pneumoniae With Different Carbapenemases and Sequence Types |
| title_short | In vitro Bactericidal Activities of Combination Antibiotic Therapies Against Carbapenem-Resistant Klebsiella pneumoniae With Different Carbapenemases and Sequence Types |
| title_sort | in vitro bactericidal activities of combination antibiotic therapies against carbapenem resistant klebsiella pneumoniae with different carbapenemases and sequence types |
| topic | in vitro bactericidal combination carbapenemase enterobacterales tigecycline |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.779988/full |
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