RIQUELME NEIRA, ROBERTO ANDRES
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RIQUELME NEIRA, ROBERTO ANDRES
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neegaz@gmail.com
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55787389700

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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

2023 , Kasim Allel , Anne Peters , José Conejeros , José R W Martínez , Maria Spencer-Sandino , Roberto Riquelme-Neira , RIVAS JIMENEZ, LINA MARIA , Pamela Rojas , Cristian Orellana Chea , Patricia García , ARAOS BRALIC, RAFAEL IGNACIO , Olivia McGovern , Twisha S Patel , Cesar A Arias , Fernanda C Lessa , Eduardo A Undurraga , MUNITA SEPULVEDA, JOSE MANUEL

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.

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Role of the multi-drug efflux systems on the baseline susceptibility to ceftazidime/avibactam and ceftolozane/tazobactam in clinical isolates of non-carbapenemase-producing carbapenem-resistant Pseudomonas aeruginosa

2022 , María José Contreras-Gómez , José R. W. Martinez , RIVAS JIMENEZ, LINA MARIA , Juan A. Ugalde , Roberto Riquelme-Neira , Aniela Wozniak , Patricia García , Jorge Olivares-Pacheco , MUNITA SEPULVEDA, JOSE MANUEL , ALCALDE RICO, MANUEL

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is one of the pathogens that urgently needs new drugs and new alternatives for its control. The primary strategy to combat this bacterium is combining treatments of beta-lactam with a beta-lactamase inhibitor. The most used combinations against P. aeruginosa are ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T). Although mechanisms leading to CZA and C/T resistance have already been described, among which are the resistance-nodulation-division (RND) efflux pumps, the role that these extrusion systems may play in CZA, and C/T baseline susceptibility of clinical isolates remains unknown. For this purpose, 161 isolates of non-carbapenemase-producing (Non-CP) CRPA were selected, and susceptibility tests to CZA and C/T were performed in the presence and absence of the RND efflux pumps inhibitor, Phenylalanine-arginine β-naphthylamide (PAβN). In the absence of PAβN, C/T showed markedly higher activity against Non-CP-CRPA isolates than observed for CZA. These results were even more evident in isolates classified as extremely-drug resistant (XDR) or with difficult-to-treat resistance (DTR), where CZA decreased its activity up to 55.2% and 20.0%, respectively, whereas C/T did it up to 82.8% (XDR), and 73.3% (DTR). The presence of PAβN showed an increase in both CZA (37.6%) and C/T (44.6%) activity, and 25.5% of Non-CP-CRPA isolates increased their susceptibility to these two combined antibiotics. However, statistical analysis showed that only the C/T susceptibility of Non-CP-CRPA isolates was significantly increased. Although the contribution of RND activity to CZA and C/T baseline susceptibility was generally low (two-fold decrease of minimal inhibitory concentrations [MIC]), a more evident contribution was observed in a non-minor proportion of the Non-CP-CRPA isolates affected by PAβN [CZA: 25.4% (15/59); C/T: 30% (21/70)]. These isolates presented significantly higher MIC values for C/T. Therefore, we conclude that RND efflux pumps are participating in the phenomenon of baseline susceptibility to CZA and, even more, to C/T. However, the genomic diversity of clinical isolates is so great that deeper analyzes are necessary to determine which elements are directly involved in this phenomenon.

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Dynamics of the MRSA Population in a Chilean Hospital: a Phylogenomic Analysis (2000–2016)

2023 , José R. W. Martínez , Paul J. Planet , Maria Spencer-Sandino , RIVAS JIMENEZ, LINA MARIA , Ahmed M. Moustafa , Lorena Díaz , Blake Hanson , RIQUELME NEIRA, ROBERTO ANDRES , ALCALDE RICO, MANUEL , Ana Quesille-Villalobos , Lina P. Carvajal , Sandra Rincón , Jinnethe Reyes , Marusella Lam , Patricia García , ARAOS BRALIC, RAFAEL IGNACIO , César A. Arias , Juan F. Calderon , MUNITA SEPULVEDA, JOSE MANUEL , Adriana E. Rosato

Methicillin-resistant Staphylococcus aureus (MRSA) is a major public health pathogen that disseminates through the emergence of successful dominant clones in specific geographic regions. Knowledge of the dissemination and molecular epidemiology of MRSA in Latin America is scarce and is largely based on small studies or more limited typing techniques that lack the resolution to represent an accurate description of the genomic landscape.

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