Epidemiological and Antimicrobial Resistant Patterns, and Molecular Mechanisms of Carbapenem-Resistant Klebsiella pneumoniae Infections in ICU Patients

Abstract

Objective

To study the epidemiological and antimicrobial resistant patterns, clinical characteristics and risk factors of critically ill patients infected with carbapenem-resistant Klebsiella pneumoniae (CRKP) from intensive care units (ICUs). The potential molecular mechanisms of antimicrobial resistance and virulence of CRKP were investigated through evaluation of associated genes.

Methods

Totally, 201 ICU patients infected with K. pneumoniae were recruited from January 2020 through January 2021. K. pneumoniae strains were collected from diverse clinical specimens and identified by microbial cultures and matrix-assisted laser desorption ionization–time-of-flight mass spectrometry. Antimicrobial resistance was measured through broth micro-dilution or Kirby–Bauer assays. The carbapenemase-, virulence-, and capsular serotype-associated genes of CRKP were individually detected by PCR and sequencing. Demographic and clinical profiles were acquired from hospital databases to evaluate the correlation of CRKP infection incidence with clinical risk factors.

Results

Of the 201 K. pneumoniae strains, CRKP accounted for 41.29%. Seasonal bias existed in local prevalence of CRKP infections. CRKP strains mounted significantly strong resistance against major antimicrobial agents except ceftazidime–avibactam, tigecycline and minocycline. Recent exposure to certain antibiotics and prior treatment with invasive interventions were prone to increase CRKP infection risks with worsened infectious outcomes. The local top carbapenemase-encoding and virulence-associated genes of CRKP were bla_KPC and irp2, respectively. Nearly half of CRKP isolates harbored a capsular polysaccharide serotype of K14.K64 (wzi-64) which preferentially emerged in the cohort with worse outcomes of infection.

Conclusion

Featured epidemiology and typical clinical characteristics existed extensively in K. pneumoniae infections among ICU patients. The CRKP cohort exhibited substantially high antimicrobial resistance. Distinctive carbapenemase-, virulence-, and serotype-associated genes were intensively involved in the spread and pathogenesis of CRKP. These findings supported careful management of critically ill patients potentially infected with virulent CRKP in the ICUs.

Keywords:

• carbapenem-resistantKlebsiella pneumoniae
• epidemiology
• clinical features
• antimicrobial resistance
• virulence
• ICU

Abbreviations

K. pneumoniae, Klebsiella pneumoniae; ICU, intensive care unit; CSKP, carbapenem-sensitive Klebsiella pneumoniae; CRKP, carbapenem-resistant Klebsiella pneumoniae; MDR, multidrug-resistant; MALDI-TOF MS, matrix-assisted laser desorption ionization–time-of-flight mass spectrometry; CLSI, Clinical and Laboratory Standards Institute; PCR, polymerase chain reaction; CRRT, continuous renal replacement therapy; ECMO, extracorporeal membrane oxygenation; WBC, white blood cell; PT, prothrombin time; APTT, activated partial thromboplastin time; FIB, fibrinogen; Hb, hemoglobin; Hct, hematocrit; TP, total protein; ALB, albumin; RBC, red blood cell; PLT, platelet; CZA, ceftazidime–avibactam; ESBL, extended-spectrum β-lactamase; KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-β-lactamase; OXA, oxacillinase.

Ethics Approval

The study protocol was approved by the Ethics Committee of Clinical Medicine Research of the First Affiliated Hospital of Anhui Medical University. All the subjects provided written informed consents according to the Helsinki statement.

Author Contributions

Fanbo Lu and Luwen Zhang share first authorship. All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

All the authors declared no competing interests for this work.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (21604079) (JX), and the University Scientific Research Collaborative Key Project of Anhui Province (2022AH040162) (YX).