Comparative Effectiveness Randomized Clinical Trial Using Next-generation Microbial Sequencing to Direct Prophylactic Antibiotic Choice Before Urologic Stone Lithotripsy Using an Interprofessional Model
Background: Next-generation sequencing (NGS) methods for microbial profiling have increased sensitivity to detect urinary pathogens. Objective: To determine whether NGS microbial profiling can be used to guide antibiotic prophylaxis and reduce infection compared with the standard of care. Design, se...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | European Urology Open Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666168323010820 |
| _version_ | 1797643568134750208 |
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| author | Michael A. Liss Kelly R. Reveles Craig D. Tipton Jonathan Gelfond Timothy Tseng |
| author_facet | Michael A. Liss Kelly R. Reveles Craig D. Tipton Jonathan Gelfond Timothy Tseng |
| author_sort | Michael A. Liss |
| collection | DOAJ |
| description | Background: Next-generation sequencing (NGS) methods for microbial profiling have increased sensitivity to detect urinary pathogens. Objective: To determine whether NGS microbial profiling can be used to guide antibiotic prophylaxis and reduce infection compared with the standard of care. Design, setting, and participants: A prospective randomized controlled clinical trial of patients undergoing urologic stone interventions at an academic health center from December 2019 to January 2022 was conducted. Urine was collected at the preoperative visit for standard culture and intervention NGS diagnostics. Evaluable patients were culture negative, met 2-wk follow-up, and did not cancel surgery. Of 240 individuals (control = 121, intervention = 119), 83 control and 74 intervention patients were evaluable. Intervention: Microbial findings (paired quantitative polymerase chain reaction and NGS) were sent to an infectious disease pharmacist to recommend prophylactic antimicrobial regimen. Outcome measurements and statistical analysis: The primary outcome was postoperative urinary infection within the follow-up period (Fisher’s exact test). The primary outcome was analyzed by modified intent-to-treat (mITT) and per-protocol analyses. Secondary endpoints considered included positive culture concordance, antibiotic use, and adverse events. Additional post hoc analyses investigated factors contributing to infection (univariate logistic regression). Results and limitations: The intervention significantly reduced postsurgical urinary infection risk by 7.1% (–0.73%, 15%) compared with the standard of care in the mITT analysis (1.4% vs 8.4%, p = 0.045) or by 8.5% (0.88%, 16%) compared with the per-protocol analysis (0% vs 8.5%, p = 0.032). NGS-guided treatment altered the distribution of antibiotics used (p = 0.025), and antibiotics poorly matched with NGS findings were associated with increased infection odds (odds ratio [OR] = 5.9, p = 0.046). Women were at greater odds to develop infection (OR = 10, p = 0.03) and possessed differentiated microbial profiles (p < 0.001). Conclusions: Urinary microbial NGS-guided antibiotic prophylaxis before endoscopic urologic stone lithotripsy improves antibiotic selection to reduce healthcare-associated urinary infections; however, treatment efficacy may be limited by the ability to adhere to the recommended protocol. Patient summary: We investigated whether microbial DNA sequencing could improve the selection of antibiotics before kidney stone surgery in patients not known to have any bacteria in the urine on standard culture. We found that using microbe DNA to guide antibiotic choices decreased postoperative infection rate and may encourage individualized use of available antibiotics. |
| first_indexed | 2024-03-11T14:16:57Z |
| format | Article |
| id | doaj.art-2c1ec2884e25482aa382415074f166b2 |
| institution | Directory Open Access Journal |
| issn | 2666-1683 |
| language | English |
| last_indexed | 2024-03-11T14:16:57Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Urology Open Science |
| spelling | doaj.art-2c1ec2884e25482aa382415074f166b22023-11-01T04:48:04ZengElsevierEuropean Urology Open Science2666-16832023-11-01577483Comparative Effectiveness Randomized Clinical Trial Using Next-generation Microbial Sequencing to Direct Prophylactic Antibiotic Choice Before Urologic Stone Lithotripsy Using an Interprofessional ModelMichael A. Liss0Kelly R. Reveles1Craig D. Tipton2Jonathan Gelfond3Timothy Tseng4Department of Urology, University of Texas Health San Antonio, San Antonio, TX, USA; Corresponding author. Division of Urologic Oncology, Department of Urology, 7703 Floyd Curl Drive, San Antonio, TX 78299, USA. Tel. +1 210 567 5676; Fax: +1 210 567 6868.College of Pharmacy, University of Texas, Austin, TX, USA; Pharmacotherapy Education & Research Center, University of Texas Health San Antonio, San Antonio, TX, USARTL Genomics, MicroGen DX, Lubbock, TX, USA; Department of Biological Sciences, Texas Tech University, Lubbock, TX, USADepartment of Population Sciences, University of Texas Health San Antonio, San Antonio, TX, USADepartment of Urology, University of Texas Health San Antonio, San Antonio, TX, USABackground: Next-generation sequencing (NGS) methods for microbial profiling have increased sensitivity to detect urinary pathogens. Objective: To determine whether NGS microbial profiling can be used to guide antibiotic prophylaxis and reduce infection compared with the standard of care. Design, setting, and participants: A prospective randomized controlled clinical trial of patients undergoing urologic stone interventions at an academic health center from December 2019 to January 2022 was conducted. Urine was collected at the preoperative visit for standard culture and intervention NGS diagnostics. Evaluable patients were culture negative, met 2-wk follow-up, and did not cancel surgery. Of 240 individuals (control = 121, intervention = 119), 83 control and 74 intervention patients were evaluable. Intervention: Microbial findings (paired quantitative polymerase chain reaction and NGS) were sent to an infectious disease pharmacist to recommend prophylactic antimicrobial regimen. Outcome measurements and statistical analysis: The primary outcome was postoperative urinary infection within the follow-up period (Fisher’s exact test). The primary outcome was analyzed by modified intent-to-treat (mITT) and per-protocol analyses. Secondary endpoints considered included positive culture concordance, antibiotic use, and adverse events. Additional post hoc analyses investigated factors contributing to infection (univariate logistic regression). Results and limitations: The intervention significantly reduced postsurgical urinary infection risk by 7.1% (–0.73%, 15%) compared with the standard of care in the mITT analysis (1.4% vs 8.4%, p = 0.045) or by 8.5% (0.88%, 16%) compared with the per-protocol analysis (0% vs 8.5%, p = 0.032). NGS-guided treatment altered the distribution of antibiotics used (p = 0.025), and antibiotics poorly matched with NGS findings were associated with increased infection odds (odds ratio [OR] = 5.9, p = 0.046). Women were at greater odds to develop infection (OR = 10, p = 0.03) and possessed differentiated microbial profiles (p < 0.001). Conclusions: Urinary microbial NGS-guided antibiotic prophylaxis before endoscopic urologic stone lithotripsy improves antibiotic selection to reduce healthcare-associated urinary infections; however, treatment efficacy may be limited by the ability to adhere to the recommended protocol. Patient summary: We investigated whether microbial DNA sequencing could improve the selection of antibiotics before kidney stone surgery in patients not known to have any bacteria in the urine on standard culture. We found that using microbe DNA to guide antibiotic choices decreased postoperative infection rate and may encourage individualized use of available antibiotics.http://www.sciencedirect.com/science/article/pii/S2666168323010820Kidney stoneLithotripsyNext-generation sequencingMicrobiomeInfection |
| spellingShingle | Michael A. Liss Kelly R. Reveles Craig D. Tipton Jonathan Gelfond Timothy Tseng Comparative Effectiveness Randomized Clinical Trial Using Next-generation Microbial Sequencing to Direct Prophylactic Antibiotic Choice Before Urologic Stone Lithotripsy Using an Interprofessional Model European Urology Open Science Kidney stone Lithotripsy Next-generation sequencing Microbiome Infection |
| title | Comparative Effectiveness Randomized Clinical Trial Using Next-generation Microbial Sequencing to Direct Prophylactic Antibiotic Choice Before Urologic Stone Lithotripsy Using an Interprofessional Model |
| title_full | Comparative Effectiveness Randomized Clinical Trial Using Next-generation Microbial Sequencing to Direct Prophylactic Antibiotic Choice Before Urologic Stone Lithotripsy Using an Interprofessional Model |
| title_fullStr | Comparative Effectiveness Randomized Clinical Trial Using Next-generation Microbial Sequencing to Direct Prophylactic Antibiotic Choice Before Urologic Stone Lithotripsy Using an Interprofessional Model |
| title_full_unstemmed | Comparative Effectiveness Randomized Clinical Trial Using Next-generation Microbial Sequencing to Direct Prophylactic Antibiotic Choice Before Urologic Stone Lithotripsy Using an Interprofessional Model |
| title_short | Comparative Effectiveness Randomized Clinical Trial Using Next-generation Microbial Sequencing to Direct Prophylactic Antibiotic Choice Before Urologic Stone Lithotripsy Using an Interprofessional Model |
| title_sort | comparative effectiveness randomized clinical trial using next generation microbial sequencing to direct prophylactic antibiotic choice before urologic stone lithotripsy using an interprofessional model |
| topic | Kidney stone Lithotripsy Next-generation sequencing Microbiome Infection |
| url | http://www.sciencedirect.com/science/article/pii/S2666168323010820 |
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