Abstract：
BACKGROUND: The effect of systemic treatment of ventilator-associated pneumonia (VAP) with telavancin, a semisynthetic lipoglycopeptide with good penetration in vitro biofilms, has not been tested in vivo during mechanical ventilation. This study examined the efficacy of telavancin compared with linezolid against endotracheal tube (ETT) biofilms in a porcine model of methicillin-resistant Staphylococcus aureus (MRSA) VAP.
METHODS: VAP was induced in 18 pigs by instilling 107 colony-forming units (CFU/mL) of an MRSA strain susceptible to telavancin and linezolid into each pulmonary lobe. Randomization into three groups was done at pneumonia diagnosis: control (IV glucose 0.5% solution q24); linezolid (10 mg/kg q12) and telavancin groups (22.5 mg/kg q24). After 72 h of MV, data regarding bronchoalveolar lavage (BAL), tracheal aspirate (TA), ETT MRSA biofilm load and thickness measured by scanning electron microscopy were obtained.
RESULTS: All 18 pigs completed the study. MRSA was isolated in 100% of ETTs from the control and linezolid groups and in 67% from the telavancin group. Telavancin treatment presented a lower MRSA load compared to the control and linezolid treatments (telavancin median [interquartile range (IQR)] = 1.94 [0.00-5.45], linezolid 3.99 [3.22-4.68] and control 4.93 [4.41-5.15], P = 0.236). Telavancin treatment also resulted in the lowest biofilm thickness according to the SEM (4.04 [2.09-6.00], P < 0.001). We found a positive correlation between ETT and BAL load (rho = 0.511, P = 0.045).
CONCLUSIONS: In our VAP model, systemic telavancin treatment reduced ETT MRSA occurrence, load, and biofilm thickness. Our findings may have a bearing on ICU patients\' clinical outcomes.
METHODS: VAP was induced in 18 pigs by instilling 107 colony-forming units (CFU/mL) of an MRSA strain susceptible to telavancin and linezolid into each pulmonary lobe. Randomization into three groups was done at pneumonia diagnosis: control (IV glucose 0.5% solution q24); linezolid (10 mg/kg q12) and telavancin groups (22.5 mg/kg q24). After 72 h of MV, data regarding bronchoalveolar lavage (BAL), tracheal aspirate (TA), ETT MRSA biofilm load and thickness measured by scanning electron microscopy were obtained.
RESULTS: All 18 pigs completed the study. MRSA was isolated in 100% of ETTs from the control and linezolid groups and in 67% from the telavancin group. Telavancin treatment presented a lower MRSA load compared to the control and linezolid treatments (telavancin median [interquartile range (IQR)] = 1.94 [0.00-5.45], linezolid 3.99 [3.22-4.68] and control 4.93 [4.41-5.15], P = 0.236). Telavancin treatment also resulted in the lowest biofilm thickness according to the SEM (4.04 [2.09-6.00], P < 0.001). We found a positive correlation between ETT and BAL load (rho = 0.511, P = 0.045).
CONCLUSIONS: In our VAP model, systemic telavancin treatment reduced ETT MRSA occurrence, load, and biofilm thickness. Our findings may have a bearing on ICU patients\' clinical outcomes.
摘要：
背景：使用telavancin全身治疗呼吸机相关性肺炎（VAP）的效果，一种在体外生物膜中具有良好渗透性的半合成脂糖肽，尚未在机械通气期间进行体内测试。这项研究在耐甲氧西林金黄色葡萄球菌（MRSA）VAP的猪模型中，研究了泰拉万星与利奈唑胺对气管内导管（ETT）生物膜的疗效。
方法：将107个菌落形成单位（CFU/mL）的对特拉万星和利奈唑胺敏感的MRSA菌株滴入每个肺叶，在18头猪中诱导VAP。在肺炎诊断时随机分为三组：对照组（静脉葡萄糖0.5％溶液q24）；利奈唑胺（10mg/kgq12）和泰拉万星组（22.5mg/kgq24）。经过72小时的MV，有关支气管肺泡灌洗（BAL）的数据，气管抽吸物（TA），获得了用扫描电镜测得的ETTMRSA生物膜载量和厚度。
结果：18头猪全部完成研究。从对照组和利奈唑胺组中分离出100％的ETT和从telavancin组中分离出67％的MRSA。与对照和利奈唑胺治疗相比，Telavancin治疗的MRSA负荷较低（telavancin中位数[四分位距（IQR）]=1.94[0.00-5.45]，利奈唑胺3.99[3.22-4.68]和对照4.93[4.41-5.15]，P=0.236）。Telavancin处理也导致最低的生物膜厚度根据SEM（4.04[2.09-6.00]，P<0.001)。我们发现ETT和BAL负荷之间呈正相关(rho=0.511,P=0.045)。
结论：在我们的VAP模型中，全身telavancin治疗减少了ETTMRSA的发生，负载,和生物膜厚度。我们的发现可能与ICU患者的临床结局有关。
方法：将107个菌落形成单位（CFU/mL）的对特拉万星和利奈唑胺敏感的MRSA菌株滴入每个肺叶，在18头猪中诱导VAP。在肺炎诊断时随机分为三组：对照组（静脉葡萄糖0.5％溶液q24）；利奈唑胺（10mg/kgq12）和泰拉万星组（22.5mg/kgq24）。经过72小时的MV，有关支气管肺泡灌洗（BAL）的数据，气管抽吸物（TA），获得了用扫描电镜测得的ETTMRSA生物膜载量和厚度。
结果：18头猪全部完成研究。从对照组和利奈唑胺组中分离出100％的ETT和从telavancin组中分离出67％的MRSA。与对照和利奈唑胺治疗相比，Telavancin治疗的MRSA负荷较低（telavancin中位数[四分位距（IQR）]=1.94[0.00-5.45]，利奈唑胺3.99[3.22-4.68]和对照4.93[4.41-5.15]，P=0.236）。Telavancin处理也导致最低的生物膜厚度根据SEM（4.04[2.09-6.00]，P<0.001)。我们发现ETT和BAL负荷之间呈正相关(rho=0.511,P=0.045)。
结论：在我们的VAP模型中，全身telavancin治疗减少了ETTMRSA的发生，负载,和生物膜厚度。我们的发现可能与ICU患者的临床结局有关。
