Antibiotic Consumption During the Coronavirus Disease 2019 Pandemic and Emergence of Carbapenemase-Producing Klebsiella pneumoniae Lineages Among Inpatients in a Chilean Hospital: A Time-Series Study and Phylogenomic Analysis

Abstract

Background: The impact of coronavirus disease 2019 (COVID-19) on antimicrobial use (AU) and resistance has not been well evaluated in South America. These data are critical to inform national policies and clinical care.

Methods: At a tertiary hospital in Santiago, Chile, between 2018 and 2022, subdivided into pre- (3/2018-2/2020) and post-COVID-19 onset (3/2020-2/2022), we evaluated intravenous AU and frequency of carbapenem-resistant Enterobacterales (CRE). We grouped monthly AU (defined daily doses [DDD]/1000 patient-days) into broad-spectrum β-lactams, carbapenems, and colistin and used interrupted time-series analysis to compare AU during pre- and post-pandemic onset. We studied the frequency of carbapenemase-producing (CP) CRE and performed whole-genome sequencing analyses of all carbapenem-resistant (CR) Klebsiella pneumoniae (CRKpn) isolates collected during the study period.

Results: Compared with pre-pandemic, AU (DDD/1000 patient-days) significantly increased after the pandemic onset, from 78.1 to 142.5 (P < .001), 50.9 to 110.1 (P < .001), and 4.1 to 13.3 (P < .001) for broad-spectrum β-lactams, carbapenems, and colistin, respectively. The frequency of CP-CRE increased from 12.8% pre-COVID-19 to 51.9% after pandemic onset (P < .001). The most frequent CRE species in both periods was CRKpn (79.5% and 76.5%, respectively). The expansion of CP-CRE harboring blaNDM was particularly noticeable, increasing from 40% (n = 4/10) before to 73.6% (n = 39/53) after pandemic onset (P < .001). Our phylogenomic analyses revealed the emergence of two distinct genomic lineages of CP-CRKpn: ST45, harboring blaNDM, and ST1161, which carried blaKPC.

Conclusions: AU and the frequency of CP-CRE increased after COVID-19 onset. The increase in CP-CRKpn was driven by the emergence of novel genomic lineages. Our observations highlight the need to strengthen infection prevention and control and antimicrobial stewardship efforts.

Keywords: Antibiotic consumption; Antimicrobial resistance; COVID-19; Carbapenemase-producing organisms.

Figure 1.

Hospital-wide antibiotic consumption in DDD per 1000 patient-days (A) and monthly percentage change over time (B), by antibiotics group, 2018–2022. Colistin is classified as a compound active against CP organisms. Broad-spectrum β-lactam ATBs include piperacillin/tazobactam, cefepime, ceftazidime, meropenem, and imipenem. Carbapenems include imipenem, meropenem, and ertapenem. (B) Percentage change in antibiotic consumption over time (compared with the average antibiotic consumption between March 2018 and February 2019). Abbreviations: ATB, antibiotic; COVID-19, coronavirus disease 2019; CP, carbapenemase-producing; DDD, defined daily dose.

Figure 2.

(A, B) Carbapenem-resistant Enterobacterales and carbapenem-resistant Klebsiella pneumoniae over the study period and proportion of isolates harboring bla_KPC, bla_NDM, or bla_VIM carbapenemases before and after the COVID-19 pandemic, 2018–2022. Abbreviations: bla_KPC, Klebsiella pneumoniae carbapenemase; bla_NDM, New Delhi metallo-β-lactamase; bla_VIM, Verona integron-encoded metallo-β-lactamase; COVID-19, coronavirus disease 2019; PCR, polymerase chain reaction.

Figure 3.

Genomic characterization of 140 carbapenem-resistant Klebsiella pneumoniae isolates. Upper panel: Maximum-likelihood recombination-free phylogenomic tree rooted to the midpoint of the genomic distances. The inner colored ring shows the ST; the external colored ring represents the year of isolation. The external red circles indicate the presence of the carbapenemase-encoding genes bla_KPC, and bla_NDM. Lower panel. Frequency ST by year of isolation. Abbreviations: bla_KPC, Klebsiella pneumoniae carbapenemase; bla_NDM, New Delhi metallo-β-lactamase; ST, sequence type.