Healthcare-associated carbapenem-resistant Klebsiella pneumoniae bloodstream infections: Risk factors, mortality, and antimicrobial susceptibility, 2017-2019

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 bla_KPC and bla_NDM 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 bla_NDM 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.

Keywords: Bacteremia; Carbapenem-resistant enterobacteriaceae; Healthcare-associated infections; Mortality; Risk factors.