Infection and Drug Resistance (Oct 2022)
Clinical Outcomes, Microbiological Characteristics and Risk Factors for Difficult-to-Treat Resistance to Klebsiella pneumoniae Infection
Abstract
Ping Yang,1,2 Chao Liu,3 Zhenchao Wu,2 Jiajia Zheng,4 Juan Yi,1 Nan Wu,2 Zhangli Wu,1,2 Ming Lu,2,3 Liyan Cui,4,* Ning Shen1– 3,* 1Institute of Medical Technology, Peking University Health Science Center, Beijing, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 3Department of Infectious Diseases, Peking University Third Hospital, Beijing, People’s Republic of China; 4Department of Laboratory Medicine, Peking University Third Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liyan Cui; Ning Shen, Email [email protected]; [email protected]: This study aimed to identify the clinical outcomes, microbiological features and risk factors for difficult-to-treat resistance (DTR) Klebsiella pneumoniae (Kp) infection.Materials and Methods: A retrospective study was conducted at Peking University Third Hospital from January 2020 to March 2021. DTR was defined as resistance to ≥ 1 carbapenem, ≥ 1 extended-spectrum cephalosporin, and ≥ 1 fluoroquinolone. Hypervirulent Kp (HvKp) was defined as peg-344-, iroB-, iucA-, rmpA-, or rmpA2-positive. Clinical data were collected. Antimicrobial susceptibility testing and string tests were performed to determine resistance and hypermucoviscosity phenotype. Whole genome sequencing was performed to analyze the sequence type (ST), capsular serotypes, resistance and virulence genes. Risk factors for 30-day mortality were analyzed.Results: Fifty DTR-Kp (50.0%) strains were identified among 100 patients. Compared to non-DTR-Kp group, a significant number of patients with DTR-Kp infection experienced ICU admission (44.0% versus 10.0%, P< 0.001) and mechanical ventilation after Kp detection (26.0% versus 10.0%, P=0.037). Notably, the percentage of hvKp among the DTR-Kp isolates increased consistently over the 15 months evaluated. Most DTR-Kp strains belonged to ST11 (82.0%), followed by ST15 (12.0%), ST86 (2.0%), ST996 (2.0%), and ST3157 (2.0%). DTR-Kp isolates possessed various resistance genes, such as blaKPC-2, blaTEM-1D and fosA3 (90.0%, 80.0% and 72.0%, respectively). Importantly, the yersiniabactin genes were significantly clustered in DTR group (48/50, 96.0%). The 30-day mortality was significantly higher in patients with DTR-Kp infection than non-DTR-Kp group (38.0% versus 8.2%, P=0.001). DTR-Kp infection (odds ratio [OR] = 4.196) was an independent risk factor for the 30-day mortality of Kp-infected patients. Additionally, cerebrovascular disease (OR = 2.780) and Charlson comorbidity index (OR= 1.584) were independent risk factors for DTR-Kp infections.Conclusion: DTR-hvKp is rapidly emerging. The DTR-Kp strains harbored various resistance genes and high rates of yersiniabactin siderophore genes. DTR-Kp infection was an independent risk factor for mortality, suggesting that enhanced awareness essential.Keywords: Klebsiella pneumoniae, difficult-to-treat resistance, mortality, risk factor