Jen-Yu Hsu1, Yu-Chung Chuang2, Jann-Tay Wang3, Yee-Chun Chen4, Szu-Min Hsieh5. 1. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: hsujenyu@gmail.com. 2. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: weischuang@gmail.com. 3. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: wangjt1124@ntu.edu.tw. 4. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: yeechunchen@gmail.com. 5. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: hsmaids@hotmail.com.
Abstract
BACKGROUND: 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. METHODS: 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 blaKPC and blaNDM gene among the included CRKP strains, and performed antimicrobial susceptibility testing (including susceptibility to colistin, aminoglycoside, tigecycline, and ceftazidime/avibactam). RESULTS: 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 blaNDM gene and 35 (97%) had low minimum inhibitory concentrations (≤8/4 μg/ml) of ceftazidime/avibactam by the E test method. CONCLUSION: 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.
BACKGROUND: 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. METHODS: 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 blaKPC and blaNDM gene among the included CRKP strains, and performed antimicrobial susceptibility testing (including susceptibility to colistin, aminoglycoside, tigecycline, and ceftazidime/avibactam). RESULTS: 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 blaNDM gene and 35 (97%) had low minimum inhibitory concentrations (≤8/4 μg/ml) of ceftazidime/avibactam by the E test method. CONCLUSION: 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.