How did the COVID-19 pandemic impact the epidemiology of antibiotic resistant bacteria?

By Nidhi Saha, BDSAug 11 2022Reviewed by Danielle Ellis, B.Sc.

In an article published on the bioRxiv* preprint server, a mathematical model was used to explore how behavioral responses to the coronavirus disease 2019 (COVID-19) pandemic impacts the anti-microbial resistance (AMR) across communities.

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

The findings depicted that behavioral responses to the COVID-19 pandemic can influence antibiotic resistance in populations.

Background

AMR is an emerging threat to disease treatment and management and is regarded as a silent pandemic. A major concern is the rapid global spread of multi- and pan-resistant pathogenic bacteria (also known as "superbugs") that are not susceptible to the existing antimicrobial agents.

The evolution of bacteria, viruses, fungi, and parasites over time, results in antimicrobial resistance, which makes infections difficult to treat and increases the risk for disease transmission, life-threatening illness, and death. Antimicrobial resistance renders antibiotics and other antimicrobial medications ineffective because of drug resistance – making the treatment increasingly arduous or impossible.

Amid global efforts to tackle AMR, the ongoing COVID-19 pandemic has diverted considerable public health resources––which have been redirected towards combatting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 containment.

Evidence suggests that COVID-19-associated antimicrobial overuse or abuse worsens antimicrobial resistance, as demonstrated during and after the initial pandemic wave. Meanwhile, initiatives designed to control SARS-CoV-2 transmissions such as lockdowns, social distancing, travel restrictions, and the use of barrier protective equipment like face masks could have simultaneously reduced the spread of antimicrobial-resistant pathogens.

It is unclear how other global epidemic effects, such as inadequate surveillance capacity, disrupted antimicrobial supply, and altered human microbiome composition may alter the epidemiological dynamics of antimicrobial resistance.

Previous studies have explored the bacteria-virus interaction to understand how pathogen interactions, such as influenza and Streptococcus pneumoniae may impact public health. However, a systematic search conducted through PubMed found no epidemiological models that described the simultaneous propagation of SARS-CoV-2 and antibiotic-resistant bacteria.

The objective of the current research was to unravel the impact of the ongoing COVID-19 pandemic on the prevalence and incidence of antibiotic-resistant bacteria.

To study the mechanism and impact of the SARS-CoV-2 infection burden on epidemiological parameters, researchers developed a transmission model that simulated the infection and colonization of sensitive and resistant bacteria that concur with SARS-CoV-2. S. pneumoniae was used as an indicator of bacterial colonization due to its high occurrence in community settings, the varied multi-drug resistance amongst countries, and the demographic differences, and also because the 2020 COVID-19 lockdowns happened to control the transmission of this species effectively.

About the study

The current study examined six varying pandemic circumstances over 90 days – each budgeting for the effects of COVID-19 on antibiotic prescribing and inter-individual contact behavior, as well as the presence or absence of a population-wide lockdown. SARS-CoV-2 infections were deemed a Susceptible-Exposed-Infectious-Recovered (SEIR) process – that leads to infection transmissions on exposure to infected individuals.

Further, the circumstances were analyzed using simulation to assess the effects of microbial carriage prevalence, antibiotic resistance levels, and the incidence of invasive bacterial disease (IBD) caused by antibiotic-resistant bacteria. The study examined how factors like newer SARS-CoV-2 variant emergence, within-host viral interactions, and heterogenous immunity levels in populations might influence the IBD incidence.

Heeding the greater than 100 different serotypes of S. pneumoniae, as well as the fact that the duration of pneumococcal carriage varies according to age, two separate sensitivity analyses were performed. Here, the researchers examined how these parameters may influence the incidence of IBD and antibiotic resistance by adjusting the bacterial carriage duration [20, 30, and 50 days] and the viability cost of resistance [0, 0.03, and 0.05] while maintaining the same R0 value of bacterial colonization as in the first study.

The researchers also examined changes in the IBD incidence and antimicrobial resistance for different parameter combinations to ascertain the impacts with the same baseline bacterial resistance, as well as with varying baseline bacterial resistance. This model could be applied to any resistant bacterial pathogen that may colonize simultaneously along with SARS-CoV-2 infection.

The findings

It was observed that the COVID-19 pandemic waves enhanced antibiotic resistance despite lockdowns and restricted bacterial colonization. Antimicrobial resistance rates tended to rise with the increase in settings of rampant SARS-CoV-2 infections.

It was found that population-wide lockdowns suppressed colonization of antibiotic-sensitive bacteria and antibiotic-resistant bacteria prevalence, as well as IBD incidence – by more than 70%. Whereas non-implementation of lockdowns in the pandemic setting increased the prevalence of antibiotic-resistant bacteria relative to antibiotic-sensitive bacteria. Consequently, an increase in the rate of antibiotic resistance was recorded in all scenarios, albeit with varying degrees––which had long-lasting impacts, majorly after the non-adherence to the preventive measures against COVID-19.

In addition, periods of absence of lockdowns saw an increasing trend for antibiotic prescriptions, especially when the number of SARS-CoV-2 infections peaked––which led to the highest increase in the resistance rate (23%) and resistant IBD incidence (6%). SARS-CoV-2 variants and population immunity seemed to drive the magnitude of pandemic impacts on resistant IBD incidences through within-community exposures. A sensitivity analysis revealed that the magnitude of these effects varied between bacterial species.

In addition to their extensive heterogeneity within and amongst countries, SARS-CoV-2 variants with different transmissibility levels and severity may confer differential effects on AMR. Infection with SARS-CoV-2 can promote progression from colonization to disease, while COVID-19 outbreaks appeared to precipitate increased antibiotic-resistant immune-mediated conditions (IBD).

However, the overall impact of COVID-19 on AMR remains uncertain and will vary significantly over the short, medium, and long term, depending on the organism and the environment in question.

It is important to note that, while the model used in this study was built and parameterized around S. pneumoniae, other bacterial species may have been impacted differently by the COVID-19 outbreak.

The findings suggest that COVID-19 pandemic responses might significantly impact antibiotic resistance in the community – emphasizing the importance of monitoring resistance during pandemic outbreaks.

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.