Clinical Efficacy, Antibiotic Resistance Genes, Virulence Factors and Outcome of Hospital-Acquired Pneumonia Induced by Klebsiella pneumoniae Carbapenemase 2-Producing with Tigecycline Treatment in the ICU

Xiang-Rong Bai; Jing-Rong Cao; Zhi-Zhou Wang; Wen-Chao Li; Dian-Dian Chen; Ran Lou; Xin Qu; Su-Ying Yan

doi:10.2147/IDR.S381280

Clinical Efficacy, Antibiotic Resistance Genes, Virulence Factors and Outcome of Hospital-Acquired Pneumonia Induced by Klebsiella pneumoniae Carbapenemase 2-Producing with Tigecycline Treatment in the ICU

Infect Drug Resist. 2022 Sep 21:15:5545-5555. doi: 10.2147/IDR.S381280. eCollection 2022.

Authors

Xiang-Rong Bai^#¹, Jing-Rong Cao^#², Zhi-Zhou Wang¹, Wen-Chao Li¹, Dian-Dian Chen², Ran Lou³, Xin Qu⁴, Su-Ying Yan¹

Affiliations

¹ Department of Pharmacy, Xuan Wu Hospital Capital Medical University, National Gerontic Disease Clinical Research Center, Beijing, 100053, People's Republic of China.
² Department of Clinical Laboratory, Xuan Wu Hospital Capital Medical University, National Gerontic Disease Clinical Research Center, Beijing, 100053, People's Republic of China.
³ Department of Intensive Medicine, Xuan Wu Hospital Capital Medical University, National Gerontic Disease Clinical Research Center, Beijing, 100053, People's Republic of China.
⁴ Intensive Care Unit, Department of Neurosurgery, Xuan Wu Hospital Capital Medical University, National Gerontic Disease Clinical Research Center, Beijing, 100053, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: Tigecycline is an agent for carbapenemase-producing Klebsiella pneumonia (KPC-KP), given its penetration into lung tissues. Our study focused on the molecular and clinical efficacy of tigecycline for hospital-acquired pneumonia (HAP) in the ICU.

Patients and methods: A retrospective cohort study of 52 adult KPC-KP HAP patients by searching hospital medical records from January 2018 to December 2020 was established to investigate the epidemiology of KPC-KP infections for tigecycline treatment and the associated clinical efficacy of tigecycline. The KPC-KP isolates underwent multilocus sequence typing. Molecular typing, antimicrobial resistance, and virulence profiling were also analyzed by whole-genome sequencing of KPC-KP.

Results: Among 52 patients with KPC-KP, the ICU mortality rate was 14/52 (27%), and there was no significant statistical difference in mortality between the effective group and failure group (p = 0.754). However, the duration of tigecycline was statistically different between the two groups of patients (14.4 vs 10 days, p=0.046). The total bacterial clearance rate was 6/52 (11.5%). There was no significant statistical difference in both groups (p=0.416). Antibiotic resistance genes (aac3iia) and virulence gene (AREO-iutA, Capsule-wzc) were negatively correlated with clinical efficacy (p = 0.011, OR = 1.237).

Conclusions: Bla_kpc was the main carbapenemase in all K. pneumoniae strains. ST11-KL64 KPC-KP was the most common virulence factors in KPC-KP isolates. This study suggested that antibiotic resistance genes (aac3iia) and virulence gene (AREO-iutA, Capsule-wzc) were independent mortality risk factors for patients with Klebsiella pneumoniae carbapenemase-2 producing K. pneumoniae infections, when during the tigecycline treatment. Molecular analysis of K. pneumoniae may provide an option when choosing the antimicrobial treatment.

Keywords: Klebsiella pneumoniae; carbapenemase; hospital-acquired pneumonia; resistance genes; virulence factors.

Grants and funding

This study was funded by Beijing Municipal Science and Technology Commission Special Funding Project (D181100000218002); National Clinical Research Center for Geriatric Disorders, Beijing, China. Beijing Municipal Commission of Health and Family Planning, No. PXM2018_026283_000002; Beijing Municipal Administration of Hospitals Incubating Program (PX2020038); Beijing High-level Public Health Technical Talent Development Plan (2022-01-023).