Molecular-based Optimization of Pathogen Identification in Sepsis Patients in the Indonesian National Referral Hospital
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 415
- 试验地点
- 1
- 主要终点
- All-cause mortality
研究概览
简要总结
This study aims to compare the diagnostic performance of conventional blood culture with two molecular-based diagnostic approaches, Hybrispot DNA Flow and metagenomic next-generation sequencing (mNGS), for the identification of microorganisms in patients with sepsis. The study will evaluate the turnaround time of each diagnostic method and assess their potential impact on the time to definitive antimicrobial therapy and subsequent clinical outcomes.
The study is led by Robert Sinto, an infectious disease physician at Dr. Cipto Mangunkusumo National Referral Hospital (RSCM), the national referral hospital in Indonesia.
Conventional blood culture, which serves as the standard microbiological diagnostic method, may require about 5 to 7 days to obtain a final result. In comparison, Hybrispot DNA Flow and mNGS detect microbial genetic material and may provide microbiological results within approximately 2 to 3 days. By comparing these diagnostic strategies, the study seeks to determine whether molecular-based approaches can facilitate more rapid pathogen identification and support earlier optimization of antimicrobial therapy.
Participation in the study is voluntary. Participants may withdraw from the study at any time without affecting the medical care they receive. Participants may also request information about their diagnostic results and may ask the research team to clarify any aspect of the study that they do not understand.
详细描述
Background Sepsis is an important global health problem, with 49.9 million cases and 11 million sepsis-related deaths reported during 1990-2017. Approximately 85% of sepsis cases and sepsis-related deaths worldwide occur in low- and middle-income countries, including Indonesia, which accounts for approximately 64% of sepsis cases, with mortality reaching 69%.
Antimicrobial therapy is a critical component of sepsis management and should be initiated as soon as possible after sepsis is diagnosed. In practice, however, antimicrobial treatment may be delayed or used excessively for several reasons. Delays may occur because of difficulties in accurately diagnosing sepsis, particularly in cases with atypical presentations. Access to antimicrobials may also be limited. Conversely, broad-spectrum antimicrobials may be overused, including in cases that do not involve sepsis. Both situations may result in short-term adverse effects, such as drug reactions or allergies, and long-term consequences, including antimicrobial resistance.
Therefore, rapid and accurate diagnosis of sepsis, together with identification of the causative microorganisms, is essential. The conventional method for identifying microorganisms in the blood is blood culture, in which microorganisms are grown in culture media. This process may require 5 - 7 days from blood collection to final results.
This study will investigate the efficacy of diagnostic tools for identifying microorganisms causing sepsis using polymerase chain reaction (PCR), specifically Hybrispot DNA Flow, and 16S rRNA metagenomics. Hybrispot DNA Flow combines multiplex PCR and flow-through hybridization to enable rapid simultaneous detection of multiple pathogens and antimicrobial resistance genes in a shorter time than conventional culture. In addition, the 16S rRNA metagenomic approach enables comprehensive identification of microorganisms without requiring culture, including fastidious bacteria, low-abundance microorganisms, and unexpected pathogens. This approach may also provide broader information regarding microbiota composition, virulence factors, and antimicrobial resistance determinants that may contribute to disease progression.
Objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years.
- •Sepsis or septic shock according to Sepsis-3 criteria, defined as suspected or confirmed infection with acute organ dysfunction (SOFA score increase ≥2 points from baseline) within 24 hours of inclusion.
- •Hospitalized at RSCM and undergoing microbiological testing, including blood culture as part of standard care.
- •At least one risk factor for multidrug-resistant (MDR) pathogens according to the 2026 Surviving Sepsis Campaign, including:
- •Previous colonization or infection with a relevant MDR pathogen.
- •Prolonged exposure to broad-spectrum antibiotics.
- •Prolonged hospitalization in a setting with a high prevalence of MDR pathogens, such as the ICU or a ward with a high antimicrobial resistance burden.
- •Written informed consent from the patient or legal representative, where applicable for prospective enrollment.
排除标准
- •Unable to provide specimens according to the study protocol.
- •Received intravenous antimicrobial regimen for more than 24 hours prior to study enrollment, with the regimen continued as empirical therapy for the current sepsis diagnosis.
- •Opt out of best treatment according to medical advice.
- •Dropout criteria:
- •- Discharge from the hospital or death within 24 hours after blood collection.
研究组 & 干预措施
Standard-of-care
Blood culture will be performed for identification and antimicrobial susceptibility testing as standard care in accordance with the hospital's current standard operating procedures (SOPs).
干预措施: Standard-of-care blood culture (Diagnostic Test)
PCR
Multiplex PCR will be performed in addition to standard care using standard blood culture. Blood samples will be incubated using BACT/ALERT system. As soon as a signal is detected from the respective sample (either positive or negative signal), multiplex PCR using Hybrispot will be performed.
干预措施: Standard-of-care blood culture (Diagnostic Test)
PCR
Multiplex PCR will be performed in addition to standard care using standard blood culture. Blood samples will be incubated using BACT/ALERT system. As soon as a signal is detected from the respective sample (either positive or negative signal), multiplex PCR using Hybrispot will be performed.
干预措施: Hybrispot DNA Flow (Diagnostic Test)
Metagenomic
16s metagenomic will be performed in addition to standard care using standard blood culture. Following blood collection in an EDTA tube, DNA extraction, targeted PCR, electrophoresis, and metagenomic NGS will be performed. Only PCR-positive sample will continued to the mNGS process. PCR-negative sample will be reported as negative.
干预措施: Standard-of-care blood culture (Diagnostic Test)
Metagenomic
16s metagenomic will be performed in addition to standard care using standard blood culture. Following blood collection in an EDTA tube, DNA extraction, targeted PCR, electrophoresis, and metagenomic NGS will be performed. Only PCR-positive sample will continued to the mNGS process. PCR-negative sample will be reported as negative.
干预措施: Metagenomic 16s RNA (Diagnostic Test)
结局指标
主要结局
All-cause mortality
时间窗: 28 days after study enrollment
次要结局
- Length of hospital stay(Within a single hospital admission or within 28 days of sepsis diagnosis)
- Diagnostic turnaround time(Within 28 days of study enrollment, or within the same hospital stay)
- Duration of antimicrobial therapy(From study enrollment up to 28 days after enrollment, within a single hospital stay and one episode of sepsis)
- Time from empirical antimicrobial therapy to definitive therapy(Within same hospital stay, from enrollment up to 28 days)
- Use of mechanical ventilation within 28 days of enrollment(28 days after study enrollment)
- Total cost of hospitalization per participant(Within a single hospital stay during study enrollment)
- Total Diagnostic Cost per Participant for Hybrispot DNA Flow and 16S rRNA Metagenomics Compared With Conventional Blood Culture(From study enrollment to completion of diagnostic testing within a single hospital stay)
- Number of participants admitted to the ICU(28 days after study enrollment, within a single hospital stay)
- Rate of participants with pathogen identification by Hybrispot DNA Flow compared to conventional blood culture(Within a single hospital stay, or 28 days after study enrollment)
- Rate of participants with pathogen identification by 16S rRNA Metagenomics compared to conventional blood culture(Within a single hospital stay, or 28 days after study enrollment)
研究者
Robert Sinto
Principal Investigator
Dr Cipto Mangunkusumo General Hospital