Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
J Formos Med Assoc. 2021 Nov;120(11):1994-2002. doi: 10.1016/j.jfma.2021.04.014. Epub 2021 May 5.
In Taiwan, carbapenem-resistant Klebsiella pneumoniae (CRKP) now became a leading cause of difficult-to-treat healthcare-associated infection, for which there are a lack of recent hospital epidemiological studies on risk factors, mortality, and antimicrobial susceptibility.
We prospectively enrolled patients with healthcare-associated CRKP monomicrobial bloodstream infection (mBSI) and matched patients with carbapenem susceptible K. pneumoniae (CSKP) mBSI at National Taiwan University Hospital (Taipei, Taiwan) from October 2017 through December 2019 in a 1:2 ratio. Multivariable logistic regression and Kaplan-Meier analyses were applied to identify factors associated with CRKP mBSI and to compare the 14-day survival curves, respectively. We detected the presence of bla and bla gene among the included CRKP strains, and performed antimicrobial susceptibility testing (including susceptibility to colistin, aminoglycoside, tigecycline, and ceftazidime/avibactam).
A total of 36 CRKP cases and 72 CSKP controls were enrolled. Patients with CRKP mBSI were more likely to have liver cirrhosis (adjusted odds ratio [aOR], 5.61; P = 0.024), length of hospital stay over the previous 14 days (aOR, 1.23; P = 0.001) and prior use of carbapenems in the previous 14 days (aOR, 6.07; P = 0.004) than patients with CSKP mBSI. The 14-day survival was significantly worse for patients with CRKP mBSI than those with CSKP mBSI (all CRKP cases: 50.0% vs. 87.5%; P < 0.001; CRKP cases treated with colistin as an appropriate backbone antibiotic: 58.3% vs. 87.5%; P = 0.007). Compared with the CSKP isolates, CRKP isolates were significantly less susceptible to colistin, amikacin, and tigecycline. Of the 36 CRKP isolates, none harbor bla gene and 35 (97%) had low minimum inhibitory concentrations (≤8/4 μg/ml) of ceftazidime/avibactam by the E test method.
Prior exposure to carbapenems, longer hospital stay, and the presence of liver cirrhosis predicted CRKP instead of CSKP mBSI. Even with colistin therapy, CRKP mBSIs was still associated with a very high risk of mortality within 14 days. Ceftazidime/avibactam is a potentially useful therapeutic choice for cases caused by in vitro susceptible CRKP strains.
在台湾，耐碳青霉烯肺炎克雷伯菌（CRKP）已成为治疗困难的医源性感染的主要原因，目前缺乏有关其危险因素、死亡率和抗菌药物敏感性的近期医院流行病学研究。
我们前瞻性地招募了 2017 年 10 月至 2019 年 12 月在国立台湾大学医院（台北，中国台湾）发生医源性耐碳青霉烯肺炎克雷伯菌单一致病菌血症（mBSI）的患者，并以 1:2 的比例匹配了耐碳青霉烯敏感肺炎克雷伯菌（CSKP）mBSI 患者。多变量逻辑回归和 Kaplan-Meier 分析用于确定与 CRKP mBSI 相关的因素，并分别比较 14 天的生存曲线。我们检测了纳入的 CRKP 菌株中 bla 和 bla 基因的存在，并进行了抗菌药物敏感性试验（包括对多粘菌素、氨基糖苷类、替加环素和头孢他啶/阿维巴坦的敏感性）。
共纳入 36 例 CRKP 病例和 72 例 CSKP 对照。与 CSKP mBSI 患者相比，CRKP mBSI 患者更有可能患有肝硬化（调整后的优势比 [aOR]，5.61；P=0.024）、前 14 天的住院时间更长（aOR，1.23；P=0.001）和前 14 天使用过碳青霉烯类药物（aOR，6.07；P=0.004）。与 CSKP mBSI 患者相比，CRKP mBSI 患者的 14 天生存率明显更差（所有 CRKP 病例：50.0% vs. 87.5%；P<0.001；用多粘菌素作为适当的基础抗生素治疗的 CRKP 病例：58.3% vs. 87.5%；P=0.007）。与 CSKP 分离株相比，CRKP 分离株对多粘菌素、阿米卡星和替加环素的敏感性显著降低。在 36 株 CRKP 分离株中，没有一株携带 bla 基因，35 株（97%）对头孢他啶/阿维巴坦的最低抑菌浓度（≤8/4μg/ml）较低，采用 E 试验法。
先前接触碳青霉烯类药物、较长的住院时间和肝硬化的存在预测了 CRKP 而不是 CSKP mBSI。即使使用多粘菌素治疗，CRKP mBSI 仍与 14 天内极高的死亡率相关。头孢他啶/阿维巴坦可能是治疗体外敏感 CRKP 菌株引起的感染的有效治疗选择。
