Arsanis Biosciences GmbH, Vienna, Austria.
Arsanis, Inc, Waltham, MA, USA.
Clin Infect Dis. 2017 Apr 15;64(8):1081-1088. doi: 10.1093/cid/cix055.
Airway-colonization by Staphylococcus aureus predisposes to the development of ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). Despite extensive antibiotic treatment of intensive care unit patients, limited data are available on the efficacy of antibiotics on bacterial airway colonization and/or prevention of infections. Therefore, microbiologic responses to antibiotic treatment were evaluated in ventilated patients.
Results of semiquantitative analyses of S. aureus burden in serial endotracheal-aspirate (ETA) samples and VAT/VAP diagnosis were correlated to antibiotic treatment. Minimum inhibitory concentrations of relevant antibiotics using serially collected isolates were evaluated.
Forty-eight mechanically ventilated patients who were S. aureus positive by ETA samples and treated with relevant antibiotics for at least 2 consecutive days were included in the study. Vancomycin failed to reduce methicillin-resistant S. aureus (MRSA) or methicillin-susceptible S. aureus (MSSA) burden in the airways. Oxacillin was ineffective for MSSA colonization in approximately 30% of the patients, and responders were typically coadministered additional antibiotics. Despite antibiotic exposure, 15 of the 39 patients (approximately 38%) colonized only by S. aureus and treated with appropriate antibiotic for at least 2 days still progressed to VAP. Importantly, no change in antibiotic susceptibility of S. aureus isolates was observed during treatment. Staphylococcus aureus colonization levels inversely correlated with the presence of normal respiratory flora.
Antibiotic treatment is ineffective in reducing S. aureus colonization in the lower airways and preventing VAT or VAP. Staphylococcus aureus is in competition for colonization with the normal respiratory flora. To improve patient outcomes, alternatives to antibiotics are urgently needed.
金黄色葡萄球菌(Staphylococcus aureus)引起的气道定植会导致呼吸机相关性气管支气管炎(ventilator-associated tracheobronchitis,VAT)和呼吸机相关性肺炎(ventilator-associated pneumonia,VAP)。尽管对重症监护病房(intensive care unit,ICU)患者进行了广泛的抗生素治疗,但关于抗生素对细菌气道定植和/或预防感染的疗效的数据有限。因此,评估了抗生素治疗对微生物学的反应。
对连续气管抽吸(endotracheal-aspirate,ETA)样本中金黄色葡萄球菌负荷的半定量分析结果与抗生素治疗相关,并评估了连续采集的分离株的相关抗生素最低抑菌浓度(minimum inhibitory concentration,MIC)。
本研究纳入了 48 例机械通气患者,他们的 ETA 样本中金黄色葡萄球菌呈阳性,并接受了至少连续 2 天的相关抗生素治疗。万古霉素未能降低耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus,MRSA)或甲氧西林敏感金黄色葡萄球菌(methicillin-susceptible Staphylococcus aureus,MSSA)在气道中的负担。约 30%的患者对苯唑西林的 MSSA 定植无效,而有反应的患者通常联合使用其他抗生素。尽管进行了抗生素暴露,仍有 15 例(约 38%)仅被金黄色葡萄球菌定植且接受至少 2 天适当抗生素治疗的患者仍进展为 VAP。重要的是,在治疗期间未观察到金黄色葡萄球菌分离株的抗生素敏感性发生变化。金黄色葡萄球菌定植水平与正常呼吸道菌群的存在呈反比。
抗生素治疗不能有效减少下呼吸道金黄色葡萄球菌定植和预防 VAT 或 VAP。金黄色葡萄球菌与正常呼吸道菌群竞争定植。为了改善患者预后,迫切需要替代抗生素的方法。