David R. M. Smith, George Shirreff, Laura Temime, Lulla Opatowski
Abstract
Background
Circulation of multidrug-resistant bacteria (MRB) in healthcare facilities is a major public health problem. These settings have been greatly impacted by the Coronavirus Disease 2019 (COVID-19) pandemic, notably due to surges in COVID-19 caseloads and the implementation of infection control measures. We sought to evaluate how such collateral impacts of COVID-19 impacted the nosocomial spread of MRB in an early pandemic context.
Introduction
The Coronavirus Disease 2019 (COVID-19) pandemic has impacted the epidemiology of diverse infectious diseases, including sexually transmitted infections (e.g., HIV) [1], vector-borne illnesses (e.g., dengue virus) [2], and invasive bacterial diseases (e.g., Streptococcus pneumoniae) [3]. Antibiotic resistance is a leading global driver of infectious morbidity and mortality [4], yet impacts of the pandemic on the transmission and control of antibiotic-resistant bacteria remain poorly understood. There are many ways by which the COVID-19 pandemic is believed to have influenced antibiotic resistance dynamics, particularly in healthcare settings, which face a disproportionately large share of the epidemiological burden of both antibiotic resistance and COVID-19. On one hand, surges in COVID-19 cases have led to conditions favourable for the proliferation of antibiotic-resistant bacteria, including hospital disorganization, increased demand on healthcare workers (HCWs), abandonment of antimicrobial stewardship programmes, and high rates of antibiotic prescribing among COVID-19 patients. On the other, public health interventions implemented to control nosocomial Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission—including patient lockdowns, hand hygiene education, and provisioning of alcohol-based hand rub—may provide the unintended benefit of preventing bacterial transmission.
Materials and method
We used ordinary differential equations (ODEs) to formalize a deterministic, compartmental model describing the transmission dynamics of SARS-CoV-2 (V) and a commensal bacterium (B) among inpatients (pat) admitted to a healthcare facility, and among HCWs (hcw) providing care to patients (Fig 1). SARS-CoV-2 is conceptualized as transmitting via exhaled respiratory droplets/aerosols, while bacteria are conceptualized as transmitting via fomites and physical touch. We assume no within-host ecological interactions between V and B: bacterial colonization does not directly impact SARS-CoV-2 infection, nor does infection directly impact colonization.
Results
Impacts of COVID-19 responses on generic MRB in generic hospitals
The first simulation set accounts for broad parameter ranges, representing “generic multidrug-resistant bacteria” (MRB) across “generic hospitals” in the context of COVID-19 responses of intermediate magnitude (τ = 0.5) (see parameter distributions in Table B in S1 Appendix). In the absence of COVID-19, these hospitals and MRB are characterized by substantial epidemiological heterogeneity (Figures H and I in S1 Appendix).
Discussion
This study demonstrates how collateral impacts of COVID-19 may both favour and prevent against the spread of antibiotic resistance in healthcare settings. Surges in COVID-19 cases—and associated consequences like abandonment of antibiotic stewardship programmes and disorganization of patient care—were found to favour the spread of resistant bacteria. Conversely, COVID-19 control policies like patient lockdown, universal masking, and reinforcement of hand hygiene were effective for prevention of bacterial colonization. Such policies work not only by directly preventing bacterial transmission, but also by limiting surges in COVID-19 cases and the conditions favourable for bacterial spread that they create. These findings thus suggest that limiting the proliferation of antibiotic resistance is an important collateral benefit of nosocomial COVID-19 prevention. This further suggests that various other public health strategies effective for prevention of SARS-CoV-2 transmission in healthcare settings—including vaccination, mass testing, and HCW cohorting—may help to alleviate the spread of antibiotic resistance [28–30].
Acknowledgments
We thank the members of the EMAE-MESuRS Working Group on Nosocomial SARS-CoV-2 Modelling for helpful discussion. We are also grateful for material support provided by the French National Institute for Health and Medical Research (Inserm), Institut Pasteur, le Conservatoire National des Arts et Métiers, and l’Université Versailles Saint-Quentin-en-Yvelines/Université Paris-Saclay.
Citation: Smith DRM, Shirreff G, Temime L, Opatowski L (2023) Collateral impacts of pandemic COVID-19 drive the nosocomial spread of antibiotic resistance: A modelling study. PLoS Med 20(6): e1004240. https://doi.org/10.1371/journal.pmed.1004240
Received: September 16, 2022; Accepted: May 9, 2023; Published: June 5, 2023
Copyright: © 2023 Smith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All data used in and produced by this study are available at https://github.com/drmsmith/covR/.
Funding: The Epidemiology & Modelling of Antibiotic Evasion team and the Anti-infective Evasion and Pharmacoepidemiology team received funding from the MODCOV project from the Fondation de France as part of the alliance framework “Tous unis contre le virus” (#106059), the Université Paris-Saclay (AAP Covid-19 2020) and the French National Research Agency and the “Investissement d’Avenir” program, Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases” (ANR-10-LABX-62- IBEID). Researchers were also supported by research grants from the French National Research Agency (SPHINX-17-CE36-0008-01 to L.T and L.O) and the Canadian Institutes of Health Research (Doctoral Foreign Study Award #164263 to D.R.M.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: L.O. reports grants from Pfizer outside the submitted work. Authors declare no other competing interests
Abbreviations: COVID-19, Coronavirus Disease 2019; ESBL, extended-spectrum beta-lactamase-producing; HCW, healthcare worker; IPC, infection prevention and control; MRB, multidrug-resistant bacteria; MRSA, methicillin-resistant Staphylococcus aureus; ODE, ordinary differential equation; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2; SEIR, Susceptible-Exposed-Infectious-Recovered; UI, uncertainty interval; VRE, vancomycin-resistant Enterococci
https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004240#sec021
