Collateral impacts of pandemic COVID-19 drive the nosocomial spread of antibiotic resistance: A modelling study

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.

Methods and findings

We developed a mathematical model in which Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and MRB cocirculate among patients and staff in a theoretical hospital population. Responses to COVID-19 were captured mechanistically via a range of parameters that reflect impacts of SARS-CoV-2 outbreaks on factors relevant for pathogen transmission. COVID-19 responses include both “policy responses” willingly enacted to limit SARS-CoV-2 transmission (e.g., universal masking, patient lockdown, and reinforced hand hygiene) and “caseload responses” unwillingly resulting from surges in COVID-19 caseloads (e.g., abandonment of antibiotic stewardship, disorganization of infection control programmes, and extended length of stay for COVID-19 patients). We conducted 2 main sets of model simulations, in which we quantified impacts of SARS-CoV-2 outbreaks on MRB colonization incidence and antibiotic resistance rates (the share of colonization due to antibiotic-resistant versus antibiotic-sensitive strains).

The first set of simulations represents diverse MRB and nosocomial environments, accounting for high levels of heterogeneity across bacterial parameters (e.g., rates of transmission, antibiotic sensitivity, and colonization prevalence among newly admitted patients) and hospital parameters (e.g., rates of interindividual contact, antibiotic exposure, and patient admission/discharge). On average, COVID-19 control policies coincided with MRB prevention, including 28.2% [95% uncertainty interval: 2.5%, 60.2%] fewer incident cases of patient MRB colonization. Conversely, surges in COVID-19 caseloads favoured MRB transmission, resulting in a 13.8% [−3.5%, 77.0%] increase in colonization incidence and a 10.4% [0.2%, 46.9%] increase in antibiotic resistance rates in the absence of concomitant COVID-19 control policies. When COVID-19 policy responses and caseload responses were combined, MRB colonization incidence decreased by 24.2% [−7.8%, 59.3%], while resistance rates increased by 2.9% [−5.4%, 23.2%]. Impacts of COVID-19 responses varied across patients and staff and their respective routes of pathogen acquisition.

The second set of simulations was tailored to specific hospital wards and nosocomial bacteria (methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase producing Escherichia coli). Consequences of nosocomial SARS-CoV-2 outbreaks were found to be highly context specific, with impacts depending on the specific ward and bacteria evaluated. In particular, SARS-CoV-2 outbreaks significantly impacted patient MRB colonization only in settings with high underlying risk of bacterial transmission. Yet across settings and species, antibiotic resistance burden was reduced in facilities with timelier implementation of effective COVID-19 control policies.

Conclusions

Our model suggests that surges in nosocomial SARS-CoV-2 transmission generate selection for the spread of antibiotic-resistant bacteria. Timely implementation of efficient COVID-19 control measures thus has 2-fold benefits, preventing the transmission of both SARS-CoV-2 and MRB, and highlighting antibiotic resistance control as a collateral benefit of pandemic preparedness.

Abstract

In this modelling study, David Smith and colleagues, demonstrate the potential of COVID-19 to impact the in-hospital epidemiology of antibiotic resistance.

Author summary

Why was this study done?

• Antibiotic resistance is a major global health problem, and healthcare settings are hotspots for the spread of antibiotic-resistant bacteria.

• Healthcare settings have been heavily impacted by the Coronavirus Disease 2019 (COVID-19) pandemic, in particular due to sudden surges of COVID-19 cases, the ensuing disorganization of care delivery, and the enactment of infection control measures designed to curb viral transmission.

• The COVID-19 pandemic has led to shifts in the epidemiological dynamics of diverse infectious diseases, but its impacts on the spread of antibiotic-resistant bacteria remain poorly understood, due in part to the largely unobserved nature of bacterial colonization.

What did the researchers do and find?

• A mathematical model was developed and used to assess how outbreaks of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in healthcare settings may impact patient colonization with antibiotic-resistant bacteria.

• Surges in COVID-19 cases fostered conditions favourable for bacterial transmission, on average resulting in a 14% increase in colonization acquisition and a 10% increase in rates of antibiotic resistance.

• Conversely, the implementation of COVID-19 control measures provided the unintended benefit of limiting bacterial spread, leading to a 28% reduction in patient acquisition of drug-resistant bacteria.

• Impacts of SARS-CoV-2 outbreaks on antibiotic resistance were found to depend fundamentally on the particular characteristics of different hospital wards and bacterial species, but more timely implementation of effective COVID-19 control policies helped to limit the spread of antibiotic resistance across a wide range of contexts.

What do these findings mean?

• Outbreaks of respiratory pathogens like SARS-CoV-2 risk aggravating the concomitant spread of antibiotic-resistant bacteria.

• Healthcare facilities with greater underlying risk of bacterial transmission are likely more vulnerable to surges in antibiotic resistance in the event of a pandemic.

• Limiting the spread of antibiotic resistance should be considered as a collateral benefit of pandemic preparedness initiatives that enable more efficient public health responses to counter emerging infectious threats.