Prevalence and molecular characteristics of carbapenem-, fosfomycin- and colistin-nonsusceptible ST11 hypervirulent Klebsiella pneumoniae in a teaching hospital

Abstract

Background: Infections caused by carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HVKP) are a great challenge for physicians in the administration of clinical therapy, and clarification of virulence factors and resistance mechanisms can aid in the selection of appropriate antimicrobial agents. Methods: We analysed the clinical characteristics of patients with CRKP infection, CRKP susceptibility to clinical first-line antimicrobial agents and resistance genotypes. The lethality and associated virulence factors of CR-HVKP are described. The possibility of the transfer of virulence and resistance genes was also explored. The susceptibility of CRKP and CR-HVKP to last-resort antimicrobial agents was also tested. Results: CRKP strains were predominantly derived from sputum specimens, urine specimens and blood specimens. Patients with CRKP infections predominantly had pulmonary infections and were predominantly elderly males in the intensive care unit (ICU). CRKP exhibited high resistance to other β-lactam antibiotics, mainly due to the presence of bla_KPC, high resistance to quinolones mediated by the carriage of aac (6''-Ib-cr), QnrS and QnrB, and high resistance to aminoglycosides mediated by the carriage of rmtB, ant(3'')-I and armA, respectively. CR-HVKP is mainly composed of ST11 and capsule K1. Aerobactin (iucA, iutA), Ent siderophore (fepA, entB), Salmochelin (iroN), Yersiniabactin (ybtS), Type 3 fimbriae (mrkD), Type I fimbriae (fimH), and Regulation (_prmpA) were detected in the CR-HVKP isolates. The CR-HVKP strains had a median lethal dose (LD₅₀₎ of 2 × 10³ to 5 × 10³ CFU in the mice, which was similar to that of the positive control NTUH-K2044. Conjugation assays revealed that the genes iucA, iutA, iroN, _prmpA, bla_KPC, bla_NDM, bla_VIM, bla_SHV, bla_TEM, QnrA, QnrB, QnrS, and rmtB can be transferred to E. coli J53. Compared with those of the recipient E. coli J53, the MICs of meropenem, imipenem, levofloxacin and amikacin in the transconjugants increased by 4-128 times. Conclusions: These findings suggest that virulence and resistance genes may spread rapidly in Enterobacteriaceae, posing a public health risk and a significant threat to clinical care. Therefore, it is necessary to further strengthen hospital infection monitoring, prevention and control measures and to provide strict management and training on the rational use of antimicrobial agents in intensive care units.