A tale of two pandemics: what the COVID-19 pandemic can teach us about antimicrobial resistance

18 May 2021

What’s in a name?

 

A Dictionary of Epidemiology defines a pandemic as: “an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and usually affecting a large number of people.”

Upgrading an infectious disease situation from outbreak or epidemic to pandemic level is a serious business. At the media briefing on COVID-19 (11 March 2020), the WHO Director-General, Dr Tedros Adhanom Ghebreyesus [@DrTedros] warned that: “Pandemic is not a word to use lightly or carelessly. It is a word that, if misused, can cause unreasonable fear, or unjustified acceptance that the fight is over, leading to unnecessary suffering and death.”

Announcement of a pandemic may achieve the following:

  • Communicates the level of infectious disease risk, indicating a serious and urgent threat to health
  • Initiates different public health strategies and encourages a large-scale public health response
  • Prompts different actions, such as release of funds and other resources necessary to tackle the pandemic
  • Requires an intensive level of international coordination and collaboration.

 

AMR: the silent pandemic

Drug-resistant pathogens have spread worldwide, crossed international boundaries, and affected a large number of people; yet unlike COVID-19, AMR is not ‘officially’ classed as a pandemic and is often referred to as a ‘silent’ or ‘hidden’ pandemic.

The reasons for this are complex but may be in part related to the resource and response implications, as described above. Another reason likely relates to the lack of reliable, quality data regarding AMR infections and deaths. Hay and colleagues (2018) [@simonihay] describe the challenges of worldwide data collection required to estimate the burden of AMR.

Public understanding of the size and significance of the COVID-19 pandemic has benefited from appealing data graphics, constantly updated with numbers of cases and deaths (See WHO resource, Worldometer, and The New York Times for a selection of examples).

There are no such resources for AMR cases/deaths. Reliable data collection, easy-to-understand data presentation, and freely available data dissemination for AMR are essential but complicated components of AMR surveillance, not least agreeing a standard case definition of an AMR infection or AMR-related death.

How do the COVID-19 and AMR situations compare?

 

With a better appreciation of the gravity associated with pandemic status and nuances associated with AMR, we can now look at the similarities/differences between the COVID-19 pandemic and that of AMR.

The COVID-19 pandemic is caused by a newly emerged, single virus, SARS-CoV-2. Antimicrobial resistance on the other hand, spans all microorganism groups (bacteria, fungi, parasites and viruses). Each of these groups of microorganisms is diverse, some species are associated with antimicrobial resistance more than others and resistance to antimicrobial drugs is emerging/evolving all the time.

Table 1 serves to highlight the similarities/differences in disease, transmission, treatment, data collection, collaboration and dissemination, between SARS-CoV-2 and one well-known pathogen associated with antimicrobial resistance: methicillin-resistant Staphylococcus aureus (MRSA).

Table 1: A comparison of the COVID-19 pandemic and AMR situation, using methicillin-resistant Staphylococcus aureus (MRSA) as an AMR example.

COVID-19 MRSA
Official Pandemic Yes No
Causative agent SARS-CoV-2 (virus) Staphylococcus aureus (bacterium)
Route of transmission Airborne Direct contact, droplets (if respiratory)
Asymptomatic transmission Yes Yes
Infections caused Respiratory Skin, respiratory, bloodstream, endocarditis, bone and joint
Diagnosis SARS-CoV-2 not routinely grown in the laboratory.
Molecular methods of detection are common, as are rapid antigen detection methods.
Point-of-care tests common
Traditional methods still used (microscopy, culture etc).
Molecular tests are available but are more expensive and require specialist equipment.
Limited point-of-care tests
Treatment No specific treatment for the virus yet but treatments are available to reduce the effect of the immune system to the virus, such as dexamethasone. Anti-MRSA drugs are available
Prevention Hand washing, social distancing, masks Hand washing
Vaccine Yes
Vaccines were rapidly developed and deployed within 12 months of the pandemic
No
Mutation and variants Yes
Mutations occur during viral replication
Yes
Mutations occur during bacterial replication. Bacteria also have the ability to swap pieces of DNA, therefore, resistance can spread between different bacteria.
Cases >160,000,000 (publicly available on Worldometer since Jan 2020) Unknown – not systematically counted
Deaths >3,000,000 (publicly available on Worldometer since Jan 2020) Unknown – not systematically counted
Data availability Worldwide, coordinated sequencing activity – see COG-UK >1 million SARS-CoV-2 genome sequences widely available via GISAID Some sequencing data are available but it is not in a widely shared format or a freely available platform.

COVID-19 and antimicrobial stewardship in secondary care

 

The advent of the COVID-19 pandemic in December 2019 heralded an unfamiliar and rapidly changing healthcare situation.

In the early wave of SARS-CoV-2 infections, the rate of antibiotic prescribing in hospitals increased as the number of severely unwell COVID-19 patients increased (see Langford et al., 2020). Diagnostic uncertainly and concern about secondary bacterial infections may have contributed to this adverse change in antibiotic prescribing, which was seen worldwide.

As the pandemic progressed, interventions were introduced to reduce the spread of infection, diagnosis of COVID-19 improved, treatment options became available and we learnt that the rate of secondary bacterial infections in those presenting to hospital was low (<10%). These monumental changes in knowledge occurred over a short period but had a positive effect on antibiotic prescribing during the second, larger wave of infections (late 2020). While rates of antibiotic prescribing rose again in hospitalised COVID-19 patients in England, the increase was not as pronounced as during the initial wave (Dr Susan Hopkins, BSAC Spring Conference 2021). [@SMHopkins]

COVID-19 and antimicrobial stewardship in primary care

 

Rates of antibiotic prescribing in primary care decreased on a local level (North West London: Zhu et al., 2021) and a national level (Scotland: Malcolm et al., 2020 and UK-wide (Rezel-Potts et al., 2021); however, increased prescribing occurred for certain antibiotics, such as broad-spectrum co-amoxiclav.

Reasons for this decrease in prescribing are likely to be manyfold. The introduction of public health interventions to reduce the spread of SARS-CoV-2 would have served to reduce other transmissible infections, as highlighted by the lower than usual rates of influenza and Streptococcus pneumoniae during the winter of 2020.  Further investigation of the data are required to evaluate the effects of reduced access to healthcare and subsequent reduction in antibiotic prescribing and determine patient outcomes. For instance, were there more deaths in the community as a result of patients not presenting to healthcare/hospitals for treatment?

Conversely, antibiotic prescribing in dentistry a marked increase. During the pandemic access to dental surgeries was severely restricted; leaving dentists with the tools of advice, analgesics and antibiotics, when appropriate. [@wendythedentist]

COVID-19 and AMR: an ambiguous relationship

 

Table 2 summarises some examples of how the COVID-19 pandemic has affected antimicrobial stewardship in different aspects of healthcare. As you will see, the relationship between COVID-19 and AMR is ambiguous (See CIDRAP post).

 

Table 2. Effects of the COVID-19 pandemic on antimicrobial stewardship

 

Negative effect on antimicrobial stewardship

 

Positive effect on antimicrobial stewardship

 

Increased use of antibiotics for respiratory infections in hospitalised patient due to:

·       Diagnostic uncertainty (chest X-ray changes, raised CRP)

·       Concern about secondary infections

 

Decreased use of antibiotics for respiratory infections in primary care

 

Prescribing of amoxicillin or doxycycline recommended for community acquired pneumonia in adults by early NICE guidelines when the cause was unclear

 

Lower rates of influenza and Streptococcus pneumoniae infections, likely due to social distancing and limited mixing

 

Increased use of antibiotics in dental care due to restricted access to dental surgeries and ban on aerosol-generating procedures

 

Changes in hospital patient demographics:

·       Decreased elective hospital admissions

·       Decrease in non-COVID patients with complex health needs and comorbidities seeking care – those at high risk of developing an infection caused by a resistant pathogen not being admitted

 

Increase in hospital-acquired pneumonia (HAP) caused by Gram-negative bacteria, requiring IV antibiotics

 

No changes in rates of MRSA or Clostridioides difficile infections despite increased antibiotic use in hospitals

 

Increase in hospital-onset methicillin-susceptible S. aureus bloodstream infections, possibly due to central venous catheter line care

 

Improved hand hygiene and use of personal protective equipment (PPE)

 

Increase in hospital-onset Pseudomonas aeruginosa, and Klebsiella spp. bloodstream infections, possibly due to increases in rates of hospital-acquired pneumonia

 

Limited international travel – reduced imports of resistant pathogens

 

Disruption to treatment programmes for infections associated with antimicrobial resistance, such as TB and HIV

 

Randomised controlled trials investigating the role of biomarkers and diagnostics (i.e., procalcitonin)

 

Disruption to vaccination programmes

 

PHE data dashboard developments for COVID-19 may lead to similar developments for healthcare associated infections

 

Learning points from the COVID-19 pandemic

 

COVID-19 has opened people’s minds to infectious diseases. Now is a good time to raise awareness of the AMR crisis” – Dr Elizabeth Klemm, BSAC Spring Conference 2021 [@elizabethjklemm]

Below are some examples of how the COVID-19 pandemic has raised awareness of infectious diseases in general and implications of the ‘silent’ AMR pandemic.

 

The need for robust pandemic preparedness

 

Not only for future viral pandemics, which may fit the ‘respiratory infection’ model seen previously (i.e., influenza/SARS-CoV-2), but also preparedness for an AMR pandemic, which is likely to require different strategies, messaging and management

 

How healthcare is delivered

 

Care pathways and service delivery had to change rapidly in order for the NHS to respond to the COVID-19 pandemic. Perhaps these changes will lead the way to more efficient, innovative health and social care provision?

 

The need for rapid diagnostic tests

 

Currently, there are >500 tests on the market or in development for diagnosis of COVID-19 (RNA, antigen and antibody tests). The use of lateral flow tests for COVID-19 diagnosis has become commonplace. Microbiological diagnosis at the point of care may encourage appropriate antibiotic prescribing and reduce the development of AMR.

 

The importance of vaccines and vaccine development

 

Vaccines can reduce the prevalence of AMR by

1.     Directly preventing infection, carriage and transmission of pathogens (not just those with drug resistance)

2.     Reducing the occurrence of symptoms and the need for antibiotic use

3.     Preventing secondary bacterial infections, which may be antibiotic-resistant, and reduce the need for antibiotics

 

When it comes to infectious diseases, we are all in this together

 

The world is a global community. Microorganisms do not respect boundaries or require a passport to travel. As SARS-CoV-2 has shown us, dissemination of the ‘right virus’, at the ‘right time’ can happen rapidly and with devastating consequences

 

 

A tale of two pandemics: the moral of the story

 

…the current pandemic has shown both the health cost and disruption to society when health systems do not have treatments in place for infectious diseases” – Dr Kieran Hand, BSAC Spring Conference 2021 [@DrKieranHand]

COVID-19 has been a stark reminder about what happens when there is no available treatment for an infection, which could become a reality for other infections should AMR become more widespread.

Only time will tell what the longer-term impact of the COVID-19 pandemic will be on AMR. Unlike COVID-19, which has made an obvious and immediate impact, we may not see the immediate consequences of the silent AMR pandemic but it is equally, if not more, important.

There are many lessons to be learnt from the COVID-19 pandemic that may be applicable to AMR. The science of AMR is likely to benefit from advances in the availability of rapid diagnostics, treatment options for resistant pathogens and widespread access to data.

And now, over to you!

 

Here are some suggestions how you can make a difference to the ongoing COVID-19 pandemic and that of AMR:

  • Keep up the good hygiene! Handwashing is the single most effective action you can take to prevent the spread of infection. Combine handwashing with good respiratory hygiene and cough/sneeze etiquette and you are well on your way to prevent all manner of infections (e.g., colds, sickness bugs).
  • Get vaccinated against SARS-CoV-2, influenza, other infections (when appropriate)
  • Follow advice and use antibiotics appropriately.
  • Maintain your health and wellbeing. Reduce your risk of infection by exercising regularly, not smoking, not carrying extra weight etc.

You are braver than you believe, stronger than you feel, and smarter than you think

 

Since the arrival of SARS-CoV-2, times have been challenging. Working from home full-time, home schooling, and social isolation were new situations for many, and often not by choice. While there have been many losses and much sadness, may I encourage you to take some time to acknowledge and celebrate your resilience during the pandemic situation.

Call-to-Action

 

Una Health would like to hear from you! What do you think the long-term effects of the COVID-19 pandemic will be on AMR? What lessons can we learn from the COVID-19 pandemic that can be translated to AMR? Drop Una a line on our social media channels and let us know your thoughts/experiences.