Impact of Susceptibility Testing Directly on the Deep Respiratory Samples of Patients Suspected Pneumonia Ventilator ( VAP ) Late ( > 5 Days) in Intensive Care Unit on the Adequacy of Antibiotic Treatment to Carbapenems Sparing on Day 1
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 91
- 试验地点
- 3
- 主要终点
- The proportion of patients with an adequate antimicrobial therapy without carbapenem (imipenem, meropenem) at Day 1
研究概览
简要总结
Inappropriate antibiotic therapy in ventilator-associated pneumonia (VAP) is associated with increased mortality. The international guidelines recommend using broad spectrum antimicrobials especially in patients who received previous antimicrobials, with risk factors of muti-drug resistant (MDR) VAP or after 5 days of mechanical ventilation. Using broad-spectrum antibiotics for 48h until the results of conventional cultures and antimicrobial susceptibility testing (AST) are available, may promote the emergence of drug-resistant bacteria. Exposure to imipenem, as short as 1 to 3 days, is associated with a 5-fold increase in the risk of imipenem resistance in the gut microbiota of ICU patients (Armand-Lefevre AAC 2013). Performing AST directly on clinical respiratory samples would hasten the process by at least 24h.
The diagnostic performance of a rapid method combining mass spectrometry and direct AST [DAST] are previously analyzed, and compared it with the conventional method (mass spectrometry with conventional AST [CAST]) and its potential impact was assessed on antimicrobial use in 85 patients (Le DORZE M et al - Clin. Microbiol. Infect. 2015).
The results produced by the dast were useable in 85,9% of the cases and the sensitivity and negative predictive values of DAST were 100% for all antibiotics tested, except gentamicin (97.1% [95%CI = 93.3-101] and 97.4% [93.7-101], respectively) and amikacin (88.9% [81.7-96.1] and 96.4% [92.1-100.7], respectively), compared with CAST. Specificity and positive predictive values ranged from 82.9 (74.2-91.5) to 100%, and from 86.4 (78.5-94.2) to 100%, respectively. If results had been reported to the clinicians, that DAST would have saved carbapenem prescription in 17 cases (22%) and would have allowed immediate narrow spectrum antimicrobials in 35/85 (41.2%) cases. But, the benefit of DAST was based on a simulation and should be now tested in a randomized fashion. This project is a prospective multicenter study. The hypothesis is that, DAST compared to CAST, would increase the number of adequate antimicrobial therapy within 24 hours in case of late VAP (> 5 days under mechanical ventilation) with Gram negative bacilli (GNB) in IC patients while sparing carbapenems (imipenem and meropenem). The primary objective is to determine the impact of a strategy using DAST on the rate of day1 adequate therapy without carbapenems in case of late VAP due to GNB.
详细描述
Inappropriate antibiotic therapy in ventilator-associated pneumonia (VAP) is associated with increased mortality. The international guidelines recommend using broad spectrum antimicrobials especially in patients who received previous antimicrobials, with risk factors of muti-drug resistant (MDR) VAP or after 5 days of mechanical ventilation. Using broad-spectrum antibiotics for 48h until the results of conventional cultures and antimicrobial susceptibility testing (AST) are available, may promote the emergence of drug-resistant bacteria. Exposure to imipenem, as short as 1 to 3 days, is associated with a 5-fold increase in the risk of imipenem resistance in the gut microbiota of ICU patients (Armand-Lefevre AAC 2013). Performing AST directly on clinical respiratory samples would hasten the process by at least 24h.
The diagnostic performance of a rapid method combining mass spectrometry and direct AST [DAST], are previously analyzed and compared it with the conventional method (mass spectrometry with conventional AST [CAST]) and its potential impact was assessed on antimicrobial use in 85 patients (Le DORZE M et al - ICAAC 2013, and clinical microbiology and infections submitted).
The results produced by the dast were useable in 85,9% of the cases and the sensitivity and negative predictive values of DAST were 100% for all antibiotics tested, except gentamicin (97.1% [95%CI = 93.3-101] and 97.4% [93.7-101], respectively) and amikacin (88.9% [81.7-96.1] and 96.4% [92.1-100.7], respectively), compared with CAST. Specificity and positive predictive values ranged from 82.9 (74.2-91.5) to 100%, and from 86.4 (78.5-94.2) to 100%, respectively. If results had been reported to the clinicians, that DAST would have saved carbapenem prescription in 17 cases (22%) and would have allowed immediate narrow spectrum antimicrobials in 35/85 (41.2%) cases. But, the benefit of DAST was based on a simulation and should be now tested in a randomized fashion.
Hypothesis - DAST as compared to CAST, would increase the number of adequate antimicrobial therapy within 24 hours in case of late VAP (> 5 days under mechanical ventilation) with Gram negative bacilli (GNB) in ICUs while sparing carbapenems (imipenem and meropenem).
Primary objective - To determine the impact of a strategy using DAST on the rate of day1 adequate therapy while sparing carbapenems in case of late VAP due to GNB.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Single (Investigator)
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
- •Adults (18 years or older)
- •Need for mechanical ventilation expected for at least 5 days at any time during the ICU stay (including if the intubation was performed before the ICU admission)
- •VAP suspected and clinical respiratory samples with GNB at direct smear examination
- •At least one condition with a risk factor of multidrug resistant infection:
- •Previous use of antimicrobials (at least 2 days in the past 7 days)
- •Risk of colonization or infection with MDR or XDR bacteria within 3 months
- •Written informed consent has to be obtained from the patients or a surrogate. The patient or his surrogate can withdraw from the study at any time.
排除标准
- •Pregnant or lactating women
- •VAP suspected and respiratory samples without GNB at direct smear examination
- •VAP that occurred without neither previous antimicrobial exposure in the past 5 days or neither risk of MDR colonization
- •Samples send to the lab during night and weekend in center if respiratory samples are not performed during this period
- •Active therapeutic limitation
- •Known allergy to antibiotics
- •Social welfare unavailable
研究组 & 干预措施
Direct Antimicrobial Susceptibility Testing
At day 0: Direct antibiotic susceptibility testing performed directly (DAST) on the respiratory sample At day 1: both results of isolated GNB identification using mass spectrometry and DAST will be given to the physician in charge in order to switch antimicrobial therapy to an antibiotic with a spectrum as narrow as possible with the main objective to avoid whenever possible carbapenems. Conventional antibiotic susceptibility testing (CAST) performed on isolated GNB.
At day 2-3: results of CAST will be given to the physician in charge in order to change antimicrobial therapy in case of differences between CAST and DAST (2nd switch to an antibiotic with a spectrum as narrow as possible with the main objective to avoid whenever possible carbapenems)
干预措施: Direct Antimicrobial Susceptibility Testing (Other)
Conventional Antimicrobial Susceptibility Testing
At day 1 identification of isolated GNB bacilli using mass spectrometry will be given to the physician in charge (usual care in ICU involved) to adapt antibiotic regimen. Conventional antibiotic susceptibility testing (CAST) performed on isolated GNB.
At day 2-3: results of CAST will be given to the physician in charge in order to switch antimicrobial therapy to an antibiotic with a spectrum as narrow as possible with the main objective to avoid whenever possible carbapenems.
结局指标
主要结局
The proportion of patients with an adequate antimicrobial therapy without carbapenem (imipenem, meropenem) at Day 1
时间窗: 2 days
The proportion of patients with an adequate antimicrobial therapy without carbapenem (imipenem, meropenem) at Day 1
次要结局
- The proportion of patients with an adequate antimicrobial therapy at Day1(2 days)
- The number of days alive without carbapenem between day 1 and day 28(28 days)
- The number of days alive without a broad spectrum antibiotic therapy between day 1 and day 28(28 days)
- The proportion of patients with a de-escalation at Day 1 according to previous definition (Weiss et al.)(2 day)
- The proportion of patients with a relapse or a new VAP occured between day 1 and day 28(28 days)
- The proportion of patients with a multidrug-resistant bacteria isolated from clinical or screening samples between day 1 and day 28(28 days)
- The proportion of concordant antibiotic susceptibility results between DAST and CAST(2 days)
- Evolution of the CPIS score between day 1 and day 28(28 days)
- Evolution of the PaO2/FiO2 ratio between day 1 and day 28(28 days)
- Evolution of the SOFA score between day 1 and day 28(28 days)
- The number of days alive without mechanical ventilation between day 1 and day 28(28 days)
- The length of ICU stay(28 days)
- ICU-mortality at day 28(28 days)
- Cost minimization because of the DAST strategy(2 days)