Antibiotic resistance genotype, phenotype, and clinical outcomes in patients with Gram-negative infections at Rabin Medical Center in Israel
ABSTRACT Antibiotic resistance is a major cause of morbidity and mortality. However, a better understanding of the relationship between bacterial genetic markers, phenotypic resistance, and clinical outcomes is needed. We performed whole-genome sequencing on five medically important pathogens (Acine...
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American Society for Microbiology
2025-01-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00383-24 |
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| author | Rachelle E. Koch Jackson Barth Andrew E. Clark Dhara Desai Jiwoong Kim Christine A. Pybus Xiaowei Zhan Leonard Leibovici Dafna Yahav David E. Greenberg |
| author_facet | Rachelle E. Koch Jackson Barth Andrew E. Clark Dhara Desai Jiwoong Kim Christine A. Pybus Xiaowei Zhan Leonard Leibovici Dafna Yahav David E. Greenberg |
| author_sort | Rachelle E. Koch |
| collection | DOAJ |
| description | ABSTRACT Antibiotic resistance is a major cause of morbidity and mortality. However, a better understanding of the relationship between bacterial genetic markers, phenotypic resistance, and clinical outcomes is needed. We performed whole-genome sequencing on five medically important pathogens (Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) to investigate how resistance genes impact patient outcomes. A total of 168 isolates from 162 patients with Gram-negative infections admitted to Beilinson Hospital at Rabin Medical Center in Israel were included for final analysis. Genomes were analyzed for resistance determinants and correlated with microbiologic and clinical data. Thirty-day mortality from time of culture was 26.5% (43/162). Twenty-nine patients had carbapenem-resistant isolates (29/168, 17.2%), while 63 patients had multidrug-resistant isolates (63/168, 37.5%). Albumin levels were inversely associated with mortality and length of stay, while arrival from a healthcare facility and cancer chemotherapy predicted having a multidrug-resistant isolate. Sequencing revealed possible patient-to-patient transmission events. blaCTX-M-15 was associated with multidrug-resistance in E. coli (OR = 3.888, P = 0.023) on multivariate analysis. Increased blaOXA-72 copy number was associated with carbapenem-resistance in A. baumannii (P = 0.003) and meropenem minimum inhibitory concentration (P = 0.005), yet carbapenem-resistant isolates retained sensitivity to cefiderocol and sulbactam–durlobactam. RJX84154 was associated with multidrug-resistance across all pathogens (P = 0.0018) and in E. coli (P = 0.0024). Low albumin levels were associated with mortality and length of stay in this sample population. blaCTX-M-15 was correlated with multidrug-resistance in E. coli, and blaOXA-72 depth predicted meropenem minimum inhibitory concentration in A. baumannii. RJX84154 may play a role in multidrug-resistance.IMPORTANCEWhile there have been several studies that attempt to find clinical predictors of outcomes in patients hospitalized with bacterial infections, less has been done to combine clinical data with genomic mechanisms of antibiotic resistance. This study focused on a hospitalized patient population in Israel with infections due to medically important bacterial pathogens as a way to build a framework that would unite clinical data with both bacterial antibiotic susceptibility and genomic data. Merging both clinical and genomic data allowed us to find both bacterial and clinical factors that impact certain clinical outcomes. As genome sequencing of bacteria becomes both rapid and commonplace, near real-time monitoring of resistance determinants could help to optimize clinical care and potentially improve outcomes in these patients. |
| format | Article |
| id | doaj-art-e5611efa40294a51bd837349825ec41d |
| institution | Kabale University |
| issn | 2165-0497 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Society for Microbiology |
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| series | Microbiology Spectrum |
| spelling | doaj-art-e5611efa40294a51bd837349825ec41d2025-01-07T14:05:19ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-01-0113110.1128/spectrum.00383-24Antibiotic resistance genotype, phenotype, and clinical outcomes in patients with Gram-negative infections at Rabin Medical Center in IsraelRachelle E. Koch0Jackson Barth1Andrew E. Clark2Dhara Desai3Jiwoong Kim4Christine A. Pybus5Xiaowei Zhan6Leonard Leibovici7Dafna Yahav8David E. Greenberg9Department of Internal Medicine, Tufts Medical Center, Boston, Massachusetts, USADepartment of Statistical Science, Baylor University, Waco, Texas, USADepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USADepartment of Internal Medicine, Infectious Diseases and Geographic Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USAQuantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USADepartment of Internal Medicine, Infectious Diseases and Geographic Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USAQuantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USAResearch Authority, Beilinson Hospital, Rabin Medical Center, Petah Tikva, IsraelSackler School of Medicine, Tel Aviv University, Tel Aviv, IsraelDepartment of Internal Medicine, Infectious Diseases and Geographic Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USAABSTRACT Antibiotic resistance is a major cause of morbidity and mortality. However, a better understanding of the relationship between bacterial genetic markers, phenotypic resistance, and clinical outcomes is needed. We performed whole-genome sequencing on five medically important pathogens (Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) to investigate how resistance genes impact patient outcomes. A total of 168 isolates from 162 patients with Gram-negative infections admitted to Beilinson Hospital at Rabin Medical Center in Israel were included for final analysis. Genomes were analyzed for resistance determinants and correlated with microbiologic and clinical data. Thirty-day mortality from time of culture was 26.5% (43/162). Twenty-nine patients had carbapenem-resistant isolates (29/168, 17.2%), while 63 patients had multidrug-resistant isolates (63/168, 37.5%). Albumin levels were inversely associated with mortality and length of stay, while arrival from a healthcare facility and cancer chemotherapy predicted having a multidrug-resistant isolate. Sequencing revealed possible patient-to-patient transmission events. blaCTX-M-15 was associated with multidrug-resistance in E. coli (OR = 3.888, P = 0.023) on multivariate analysis. Increased blaOXA-72 copy number was associated with carbapenem-resistance in A. baumannii (P = 0.003) and meropenem minimum inhibitory concentration (P = 0.005), yet carbapenem-resistant isolates retained sensitivity to cefiderocol and sulbactam–durlobactam. RJX84154 was associated with multidrug-resistance across all pathogens (P = 0.0018) and in E. coli (P = 0.0024). Low albumin levels were associated with mortality and length of stay in this sample population. blaCTX-M-15 was correlated with multidrug-resistance in E. coli, and blaOXA-72 depth predicted meropenem minimum inhibitory concentration in A. baumannii. RJX84154 may play a role in multidrug-resistance.IMPORTANCEWhile there have been several studies that attempt to find clinical predictors of outcomes in patients hospitalized with bacterial infections, less has been done to combine clinical data with genomic mechanisms of antibiotic resistance. This study focused on a hospitalized patient population in Israel with infections due to medically important bacterial pathogens as a way to build a framework that would unite clinical data with both bacterial antibiotic susceptibility and genomic data. Merging both clinical and genomic data allowed us to find both bacterial and clinical factors that impact certain clinical outcomes. As genome sequencing of bacteria becomes both rapid and commonplace, near real-time monitoring of resistance determinants could help to optimize clinical care and potentially improve outcomes in these patients.https://journals.asm.org/doi/10.1128/spectrum.00383-24antibiotic resistanceGram-negative infectionswhole-genome sequencingclinical outcomes |
| spellingShingle | Rachelle E. Koch Jackson Barth Andrew E. Clark Dhara Desai Jiwoong Kim Christine A. Pybus Xiaowei Zhan Leonard Leibovici Dafna Yahav David E. Greenberg Antibiotic resistance genotype, phenotype, and clinical outcomes in patients with Gram-negative infections at Rabin Medical Center in Israel Microbiology Spectrum antibiotic resistance Gram-negative infections whole-genome sequencing clinical outcomes |
| title | Antibiotic resistance genotype, phenotype, and clinical outcomes in patients with Gram-negative infections at Rabin Medical Center in Israel |
| title_full | Antibiotic resistance genotype, phenotype, and clinical outcomes in patients with Gram-negative infections at Rabin Medical Center in Israel |
| title_fullStr | Antibiotic resistance genotype, phenotype, and clinical outcomes in patients with Gram-negative infections at Rabin Medical Center in Israel |
| title_full_unstemmed | Antibiotic resistance genotype, phenotype, and clinical outcomes in patients with Gram-negative infections at Rabin Medical Center in Israel |
| title_short | Antibiotic resistance genotype, phenotype, and clinical outcomes in patients with Gram-negative infections at Rabin Medical Center in Israel |
| title_sort | antibiotic resistance genotype phenotype and clinical outcomes in patients with gram negative infections at rabin medical center in israel |
| topic | antibiotic resistance Gram-negative infections whole-genome sequencing clinical outcomes |
| url | https://journals.asm.org/doi/10.1128/spectrum.00383-24 |
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