Background

Before the COVID-19 outbreak, since 2015, antimicrobial resistance (AMR) was already a growing concern which led WHO to make it a priority for global public health for the year 2020. With the beginning of the pandemic, the urgent need to discover treatments caused increased consumption of antibiotics around the globe. Mostly, antibiotics have been empiric to reduce infections and inadequate knowledge of the disease per se. For instance, the initial symptoms of COVID-19 resembled bacterial pneumonia. Furthermore, the diagnosis classifying bacterial and viral strains proved ineffective as the differentiation needed immediate treatment. Subsequently, patients were prescribed empiric antibiotics, often in the absence of microbiological confirmation of the same. A report from WHO found that AMR alone has likely caused a third of as many deaths as COVID-19 caused in 2020, estimated to be around 1.8 million1.

Aside from this, the patients with COVID-19 acquired secondary co-infections, which necessitated antimicrobial treatment. Clinicians met the challenging treatment protocol of prescribing a broad-spectrum antibiotic while at the same time avoiding the use of such antimicrobials as a last resort. Inappropriate treatment in either direction has been linked with an increased risk of mortality.

Overall, the measures of national and international interventions to reduce the future impact of AMR on society have been aggravated by the COVID-19 era. The current pandemic may have a much worse effect on society through the inadvertent propagation of AMR. While the main focus of the current healthcare system is on controlling SARS-CoV-2 and alleviating the immediate impact on patients, it must not lose sight of the longer-term threat of AMR.

The Connecting Link Between COVID-19 and AMR

AMR in any population is attributed to three components as emergence, transmission, and population-level infection burden. The COVID-19 outbreak has affected all of these three components through direct or indirect consequences of the pandemic.

Approximately 70% of patients with COVID-19 receive antimicrobials either in the outpatient or inpatient settings1. This may facilitate the emergence of AMR. Antimicrobials have been used for their presumed effect on SARS-CoV-2, leading to resistance in co-infecting pathogens. For instance, the aggressive use of antimalarial drug chloroquine despite lack of evidence on COVID-19 has raised concern for malaria. It remains the drug of choice for the treatment as its use in COVID-19 may encourage chloroquine resistance emergence.

The overlapping symptoms of COVID-19 with other diseases result in inappropriate prescribing or misdiagnosis. The misuse of such drugs could result in future drug resistance levels of different pathogens—for instance, the widespread use of azithromycin for managing initial symptoms of COVID-19.

The lack of information and the severity of the illness, and an emergent need to try all avenues have led to continuing antibiotics. If this crisis persists, this can lead to changes in the antimicrobial concentrations in the environment and affect selective pressures for AMR in water and soil systems. Eventually, similar to the ripple effect, this will affect the animal food supply chain causing AMR infections in humans. Although this might happen yet the extent remains uncertain.

COVID-19, Financial Hardships and AMR

The fiscal hardship of countries amidst the pandemic is apparent. In high-income countries, where prescriptions for antibiotics are required, a reduction in income will likely lead to poorer health. In addition, less prosperous socioeconomic regions within such countries may lead to higher cases of COVID-19 along with a disproportionate increase in AMR prevalence.

Conversely, low-income countries with fewer regulations on antimicrobial purchasing may increase the need for people to use over-the-counter antimicrobials. This unregulated usage of antimicrobials reflects a higher risk of AMR due to suboptimal antibiotic use.

In addition, the economic repercussions of the pandemic to provide sufficient access to antimicrobials to the public may push individuals into greater poverty if access to medicines at all may become less affordable. Also, this may enhance selection pressure in favour of suboptimal antibiotic use, which will again aggravate AMR.

Inadequate Antimicrobial Availability and AMR

COVID-19 has devastated the availability of antimicrobials by disrupting the global manufacturing of antimicrobials and supply chains. These concerns have led the European Medicines Agency to lead ‘urgent and coordinated action to prevent and mitigate drug shortages within the EU’ as most countries are importers of generic medicines, which has been affected by travel restrictions and delayed supply chain.

Countries like India, which are manufacturing and exporting antibiotics, are standing up to high home market demands due to COVID-19, which has caused a reduction in export. For instance, ten manufacturers have reported shortages of azithromycin to the US FDA due to potential use in COVID-19 treatment1.

In such a scenario, inappropriate use of antimicrobials as an alternative when the recommended antimicrobial is unavailable can worsen the situation. For instance, in the case of TB, which requires prolonged multi-drug therapy, one consequence of drug shortage will cause an interruption in the treatment, risk of treatment failure, and development of resistance.

Thus, the AMR picture post-COVID-19 is going to be different with resistance to readily available antimicrobials. 

Future Antimicrobial Usage

Patients cannot avoid the high use of antimicrobials in patients with COVID-19. However, with a better understanding of risk factors and the prevalence of co-infection in patients with COVID-19 and better data collection, we can improve empiric use of antimicrobials.

Furthermore, we still need good data on what antimicrobials are being used or prescribed for what, where, and when alongside environmental data on residual concentrations. For instance, we need a study to check the efficacy of hydroxychloroquine and azithromycin across all settings.

As a global community, the healthcare sector needs to ensure that the potential individual benefits of antimicrobial prescribing are weighed against the population impact of AMR emergence. Existing efforts to optimize empiric prescribing and support adherence to well-designed guidelines need to be in practice looking at the situation.

Although the impact of COVID-19 on drug-resistant pathogens is still unknown yet we know that there will be a shift in AMR global challenge from this point forward. We need to work together as a multidisciplinary community to collect data on these changes and solve the arising challenge effectively.

References

• Knight GM, Glover RE, McQuaid CF, et al. Antimicrobial resistance and COVID-19: Intersections and implications. Elife. 2021;10:e64139. Published 2021 Feb 16. doi:10.7554/eLife.64139. Last accessed 22 June 2021.
• Adepoju P. Tuberculosis and HIV responses threatened by COVID-19. The Lancet HIV. 2020;7:e319–e320. Last accessed 23 June 2021.
• Chanda-Kapata P, Kapata N, Zumla A. COVID-19 and malaria: a symptom screening challenge for malaria endemic countries. International Journal of Infectious Diseases. 2020;94:151–153. Last accessed 22 June 2021.
• National Taskforce for COVID-19, India Revised advisory on the use of hydroxychloroquine (HCQ) as prophylaxis for SARS-CoV-2 infection (in supersession of previous advisory dated 23rd march, 2020) (p. 4) [March 23, 2020];2020. Last accessed 22 June 2021
• WHO Global action plan on antimicrobial resistance. [May 26, 2015];2015a. Last accessed 23 June 2021
• WHO AWaRe: handle antibiotics with care. [February 9, 2021];2019. Last Accessed 23 June 2021
• WHO World health Organization (WHO) Information note: tuberculosis and COVID-19. [February 9, 2021];2020k. Last accessed 23 June 2021
• WHO Global partnership to make available 120 million affordable, quality COVID-19 rapid tests for low- and middle-income countries. [September 28, 2020];2020m. Last accessed 23 June 2021

FAQ’s

What is AMR?

Antimicrobials comprising antibiotics, antivirals, antifungals and antiparasitic are medicines that are used to prevent and treat various infections. Antimicrobial resistance or AMR occurs when these bacteria, viruses, fungi and parasites transform over time and no longer respond to medicines making such infections harder to treat and increasing the risk of disease spread.

Are Antimicrobials prescribed to COVID-19 patients?

Yes, as the symptoms of COVID-19 are varied. The initial therapy involves administering antimicrobials for urgent treatment and management of crisis.

Are COVID-19 patients susceptible to AMR?

Due to empiric and over-use of antimicrobials in the COVID-19 arena, the patients are more likely to develop AMR which creates a threat for further treatments.

What role does WHO play in AMR?

WHO being the key organizational body has developed a global action plan for management of AMR. This involves restricted use of antimicrobials and providing action plans for treatments without antimicrobials.

Has AMR turned into a threat?

Owing to the current situation, AMR can likely be a bigger challenge in the near future. However, a detailed study is yet needed to ascertain the extent of AMR globally.