白念珠菌气道定植对铜绿假单胞菌所致呼吸机相关性肺炎的影响

The impact of Candida albicans colonization in the airway on ventilator-associated pneumonia caused by Pseudomonas aeruginosa

摘要

目的  探讨白念珠菌气道定植对多重耐药铜绿假单胞菌所致呼吸机相关性肺炎（ventilator-associated pneumonia，VAP）患者病死率、抗菌药物疗程、免疫状态及炎症状态的影响。方法  本前瞻性多中心队列研究以2018年6月至2023年6月收治于6所三级甲等综合教学医院重症医学科的多重耐药铜绿假单胞菌所致VAP患者为研究对象。根据患者呼吸道是否存在白念珠菌定植分为定植组及非定植组。比较两组患者30 d全因死亡率、抗菌药物敏感性及疗程、诊断VAP后第 1、3、5、7天免疫指标及炎症指标变化。结果  5年研究期间共纳入多重耐药铜绿假单胞菌导致VAP患者232例，其中白念珠菌定植组105例，非定植组127例。非定植组患者检出的铜绿假单胞菌对于氨基糖苷类、头孢菌素类及碳青霉烯类抗菌药物的敏感性均高于定植组（P<0.05），但两组患者对于16种抗菌药物的敏感性均低于中国细菌耐药监测网（China antimicrobial surveillance network, CHINET）2022年水平（P<0.05）。研究发现非定植组患者白介素-17A、（1,3）-β-D葡聚糖在各时间节点均低于定植组，且其他炎性指标更容易恢复至正常范围（P<0.05），同时非定植组患者的T 及Th 淋巴细胞绝对值可以在第7天更快地恢复至正常水平（P<0.05）。两组患者30 d全因死亡率差异无统计学意义（25.7% vs 22.8%，P=0.61），但非定植组抗菌药物的疗程明显短于定植组［（11.3±3.1)d vs （14.2±4.7)d，P<0.01）］，且存在重症医学科住院时间缩短的趋势。结论  气道白念珠菌定植不影响多重耐药铜绿假单胞菌所致VAP患者的30 d全因死亡率，但会延长炎症反应及抗菌药物使用时间并导致免疫功能延迟恢复。

Abstract

Objective  To investigate the impact of Candida albicans colonization on the mortality, duration of antibiotic therapy, immune and inflammation status in patients with ventilator-associated pneumonia (VAP) caused by multidrug-resistant Pseudomonas aeruginosa. Methods  This prospective multicenter cohort study included patients with VAP caused by multidrug-resistant Pseudomonas aeruginosa (MDR-Pa) admitted to six tertiary teaching hospitals from June 2018 to June 2023. The patients were divided into colonization group and non-colonization group based on the presence of Candida albicans detected in the broncho-alveolar lavage fluid (BALF). The 30-d all-cause mortality, duration of antibiotic therapy, immune and inflammation status were compared between the two groups after VAP diagnosis on the day1, day3, day5, and day7. Results  During the five-year research period, a total of 232 VAP patients caused by MDR-Pa were included from six participating units in the intensive care unit (ICU), with 105 cases in the colonization group and 127 cases in the non-colonization group. The Pseudomonas aeruginosa detected in BALF samples from the non-colonization group showed higher sensitivity to aminoglycosides, cephalosporins, and carbapenems compared to the colonization group (P<0.05). However, both groups showed lower sensitivity to 16 antibiotics compared to China antimicrobial surveillance network (CHINET) 2022 (P<0.05).  Interleukin-17A and (1,3)-β-D glucan levels in the non-colonization group were consistently lower than those in the colonization group at various time points, and other inflammatory markers were more likely to return to normal values (P<0.05). Additionally, the absolute values of T and Th lymphocytes in the non-colonization group recovered to normal levels faster on the day 7 (P<0.05). There was no statistically significant difference in the 30-d all-cause mortality between the two groups (25.7% vs 22.8%, P=0.61), but the non-colonization group had a significantly shorter duration of antibiotic therapy compared to the colonization group ［(11.3±3.1)d vs （14.2±4.7)d, P<0.01］, with a trend towards shorter ICU hospitalization time. Conclusion  The colonization of Candida albicans in the airway does not affect the 30-d all-cause mortality of patients with VAP caused by MDR-Pa. However, it does prolong the inflammatory response and the duration of antibiotic use, as well as delay the recovery of immune function.

关键词

呼吸机相关性肺炎 / 白念珠菌 / 铜绿假单胞菌 / 定植 / 共生长

Key words

ventilator-associated pneumonia / Candida albicans / Pseudomonas aeruginosa / colonization / co-exist