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Antimicrobial stewardship (AMS) is a system-wide approach to guiding, promoting and overseeing the safe and judicious use of antimicrobials. An AMS programme aims to safeguard antimicrobials, especially antibiotics, for future use. Whilst minimising emergence of antimicrobial resistance and drug-resistant infections is the ultimate aim of AMS, other objectives include minimising unwarranted variation, unnecessary use and reducing antimicrobial-associated harms including C. difficile infection and antibiotic adverse events. In normal circumstances, in advanced health systems, AMS is primarily a behaviour change challenge. In resource-poor settings, AMS is further confounded by limited access to medicines, concerns regarding counterfeit antibiotics and inadequate infection control infrastructure in hospitals.

The COVID-19 pandemic is challenging all aspects of healthcare in resource-rich nations, including the management of chronic disease as well as delivery of acute care for non-COVID-19 disease including acute bacterial infection. The impact in resource-poor settings where healthcare provision is already fragile is likely to be considerably worse. In both settings, the impact on AMS is likely to be significant.

The dilemma of antibiotics and SARS-CoV-2 virus infection

A key AMS strategy is promoting the message that antibiotics should not be prescribed for viral infections. In most cases, COVID-19 is like most other viral respiratory tract infections and is self-limiting. Whilst it is unlikely that medical assistance will be sought when symptoms are mild this will vary geographically and by health-seeking behaviour and experience. “Stay home” advice for those with symptoms of fever or persistent cough reduces unnecessary GP visits but also limits early unnecessary antibiotic use. In those with persistent or worsening symptoms, clinical assessment is advisable to differentiate between viral and bacterial infection and to determine if hospitalisation is required. In the absence of anti-viral treatment, deciding when antibiotics would be beneficial is the key therapeutic decision. In those with suspected severe COVID-19 requiring hospitalisation (and in contrast to experience with severe influenza) bacterial co-infection appears to be infrequent. Unfortunately, however, many of the features of severe COVID-19 may be difficult to distinguish from bacterial infection, with fever, breathlessness and hypoxia with often indeterminant radiographic changes and increase in the biomarker C-Reactive Protein (CRP), otherwise usually a reasonable indicator of bacterial infection.

If unchecked, the additional prescribing of antibiotics related to COVID-19 will add to the already increasing global challenge of antimicrobial resistance.

What is the antibiotic prescribing experience to date in the context of COVID-19?

Reports from China, a country already disproportionately affected by drug-resistant infections¹ has shown that almost all of those hospitalised with COVID-19 infection received antibiotics despite little evidence of associated bacterial infection at presentations². The need for very prolonged and difficult ventilatory support in severe COVID-19 is well recognised and prevention of bacterial and fungal nosocomial infection with escalating antimicrobial use is a real challenge. According to the International Severe Acute Respiratory Infection Consortium (ISARIC), outside of China antibiotic prescribing is reported in more than half of those hospitalised with COVID-19. The extent of antibiotic prescribing in those who have not been hospitalised is currently unquantified however local experience in Glasgow indicates increased prescribing of antibiotics typically used in the treatment of respiratory tract infections in both hospitals and the community.

What is the best practice with respect to antibiotic prescribing in suspected COVID-19?

As most cases of SARS-CoV-2 infection are not associated with bacterial co-infection, antibiotics should not be prescribed if COVID-19 is suspected. Rather symptomatic measures should be encouraged. Antibiotics should be reserved for those where differentiation between bacterial and viral aetiology is not possible on clinical grounds and particularly if symptoms are severe. When antibiotics are prescribed they should target the likely bacterial pathogens and the narrowest spectrum agent should be chosen e.g. doxycycline or amoxicillin and the oral route should be prioritised where possible. Evidence supporting shorter course therapy with a duration of 5 days is appropriate for both pneumonia and bacterial exacerbations of chronic obstructive pulmonary disease (COPD). Guidelines based on local epidemiology and consensus should be followed. If SARS-CoV-2 infection is confirmed, the antibiotic prescription should be reviewed and discontinued unless there is clear evidence of bacterial co-infection. The Scottish Antimicrobial Prescribing Group and NICE have recently published recommendations for prescribing in the context of COVID-19 ^3,4.

Antimicrobial stewardship strategies must adapt to this changing landscape

Implications of COVID-19 on antimicrobial stewardship

If unchecked, the additional prescribing of antibiotics related to COVID-19 will add to the already increasing global challenge of antimicrobial resistance. Uncertainties over SARS-CoV-2 immunity, the likelihood of seasonal epidemics and lack of a vaccine mean that COVID-19 will be of significant and continued concern. AMS strategies must adapt to this changing landscape. Indication for antibiotics must be clearly defined and care must be taken to only prescribe to those in whom serious bacterial infection is suspected. In resource-rich nations, early identification of SARS-CoV-2 through point-of-care testing should inform and reduce unnecessary antibiotic prescribing. Measurement of C-reactive protein (CRP), however, may become obsolete as a biomarker of bacterial respiratory tract infection given its poor discriminatory value in COVID-19 (and to an extent in influenza). Procalcitonin, already widely used in critical care, may be elevated in severe COVID-19 pneumonia and its utility in differentiating this from bacterial co-infection needs to be formally evaluated. Timely use of antiviral or immunomodulatory therapy may reduce progression of infection and admission to the intensive care unit and so minimise healthcare-associated complications and further antimicrobial prescribing. Unfortunately at the time of writing there do not appear to be any clear therapeutic advances. Ultimately, as with other serious viral infections, the most valuable AMS intervention to limit antibiotic use in the context of COVID-19 will be its prevention through SARS-CoV-2 vaccination once a vaccine is available.

References:

1. Xiao Y and Li L, China’s national plan to combat antimicrobial resistance. Lancet Infect Dis; 2019; 16: 1216-1218 
2. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z et al., Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-1062.
3. Scottish Antimicrobial Prescribing Group (SAPG). SAPG response to COVID-19. 2020.  
4. National Institute for Health and Care Excellence (NICE) COVID-19 rapid guideline: managing suspected or confirmed pneumonia in adults in the community. 2020.