Characteristics of hypervirulent multi-drug resistant Klebsiella pneumoniae strains in inpatients with severe COVID-19

Abstract

Severe course of COVID-19 in inpatients can be caused by a number of reasons, including viral and bacterial superinfections. Empirical use of antibiotics, as well as poor infectious control stimulate the emergence and spread of multidrug-resistant bacteria. Klebsiella pneumoniae is the most common carbapenemase-producing bacterial pathogen causing nosocomial infections. These strains became significantly widespread during the COVID-19 pandemic. Objective. To analyze phenotypic and genetic characteristics of K. pneumoniae strains as the dominant bacterial pathogen in severe COVID-19 patients in the intensive care unit. Patients and methods. This study included 38 COVID-19 patients (including 6 patients with severe disease) treated in the intensive care units of Moscow and Saint Petersburg hospitals for infectious diseases between July 2020 and December 2020. All patients signed an informed consent to participate in the study; patient data was anonymized. The following samples were collected: sputum, bronchoalveolar lavage, and nasopharyngeal swabs. We performed bacteriological identification of isolated bacterial strains, drug susceptibility testing, and whole genome sequencing of K. pneumoniae strains. Results. The majority of K. pneumoniae strains isolated from patients with severe COVID-19 contained clusters of aerobactin and enterobacterin genes. However, some of them (strains 90 and 124) also contained clusters of yersiniabactin genes. These genes are associated with high virulence and ability to form biofilms. The isolated strains belonged to four sequence types (ST874, ST395, ST147, ST15) that are characterized by high virulence and antibiotic resistance. These K. pneumoniae strains can be considered as one of the major causes of severe and lethal COVID-19. Conclusion. Our findings suggest that the detection rate of K. pneumoniae in COVID-19 patients increased from 30% to 70% during the pandemic. Phenotypic tests demonstrated that more than 80% of the strains were resistant to most antibiotics used in patients with complicated COVID-19. The combination of gypervirulence and antibiotic resistance is crucial for nosocomial transmission of these strains and their effect on the disease outcome. The emergence of hyper-resistant pathogens necessitates regular epidemiological monitoring and robust infection control in Russian hospitals, especially in intensive care units. Key words: COVID-19, severe disease, Klebsiella pneumoniae, genome sequencing, carbapenemases, hypervirulence, antibiotic resistance