Guest posting from Mr Joe Hessell, Dr Gaetan Khim, and Mr Mona Kheng, DMDP Staff Members.  See also these recent PRIDA AMS lectures. 

A high rate of antimicrobial prescribing has been recognized for those with symptoms of COVID-19, much of which is unnecessarily promoting antimicrobial resistance (AMR). Long after the pandemic subsides, AMR will continue to be a global threat. On May 28^th, 2020, WHO SEARO hosted a webinar on “Antimicrobial stewardship (AMS) in the era of Covid-19 pandemic: best practice and guidance on prescribing antibiotics”, which we will summarize here.

The rationale for antibiotic treatment in patients with COVID-19 seems to be based on the experience with bacterial superinfection in influenza, where most studies report initial co-infection or secondary bacterial pneumonia in 11-35% of hospitalized patients.¹ A review of eighteen studies that reported co-infection among patients diagnosed with COVID-19 (9/18) and other coronaviruses (9/18) was recently conducted. For COVID-19, 62/806 (8%) patients were reported as experiencing co-infection during hospital admission, a lower rate than observed in influenza. Secondary analyses demonstrated wide use of broad-spectrum antibiotics, despite a paucity of evidence for bacterial coinfection: 1450/2010 (72%) of patients received antimicrobial therapy.² The relatively low rate of co-infection and high rate of antimicrobial prescribing observed highlights a need for AMS.

The WHO released updated interim guidance for the clinical management of COVID-19 on May 27^th, taking into consideration the latest evidence on rates of co-infection.³ Antibiotic treatment use recommendations are dependent on classification of disease severity, which is clearly defined in the guidelines. WHO recommends against antibiotic use in all patients with mild COVID-19, as well as for those with moderate COVID-19, unless there is clinical suspicion of a bacterial infection. For moderate cases, consider providing empiric antibiotic treatment for possible pneumonia in the elderly, especially those in long-term care facilities, and children < 5 years. Unnecessary antibiotic use in mild to moderate cases (which make up the majority of those infected with COVID-19) increases the risk of emergence and transmission of multidrug-resistant bacteria. Antibiotics should for the most part be reserved for those suffering from severe COVID-19. A retrospective cohort study from Wuhan, China reported that out of 354 hospitalized patients with COVID-19, 23.5% of severe cases and 24.4% of critical cases were co-infected with other respiratory pathogens.⁴

Clinicians should keep in mind these key principles for optimal antimicrobial prescribing, even during a pandemic:

• Collection of necessary microbiology samples, e.g. blood cultures, before antibiotic initiation
• Prompt initiation, particularly for severe cases (within 1 hour of initial assessment if possible)
• Proper antibiotic selection, to cover all likely pathogens, based on clinical judgment, patient host factors and local epidemiology
• Daily assessment for possible de-escalation, based on microbiology results and clinical judgement
• Proper duration, using as short a duration that is necessary; generally 5-7 days

It can be challenging for clinicians to differentiate between a viral vs bacterial pneumonia; the National Institute for Health and Care Excellence (NICE) from the UK provides some guidance on this.⁵

WHO developed the AWaRe classification, which categorizes antibiotics into three different groups (Access, Watch and Reserve) based on their indication for common infectious syndromes, their spectrum of activity, and their potential for increasing antibiotic resistance.⁶ See figure below to see description and examples of each group. The AWaRe classification is a tool for AMS at local, national and global levels with the aim of optimizing antibiotic use and reducing antibiotic resistance. WHO aims to reduce the use of Watch and Reserve Group antibiotics (the antibiotics most crucial for human medicine and at higher risk of resistance), and to increase the use of Access antibiotics where availability is low. For moderate COVID-19 patients that are not hospitalized and suspected of bacterial co-infection, WHO recommends the use of an Access antibiotic, over a more broad-spectrum Watch or Reserve antibiotic. WHO recommends the use of a Watch or Reserve antibiotic in the case of suspected and confirmed severe COVID-19 infection after the collection of appropriate specimen.³ Patients should be reviewed daily to assess the possibility of antimicrobial de-escalation.

In 2019, WHO developed a comprehensive AMS toolkit, geared towards supporting healthcare facilities in low- and middle-income countries.⁶ The toolkit provides comprehensive practical guidance on how to develop AMS at the facility and national level.  For a recent discussion on the WHO and CDC AMS approaches see these PRIDA lectures.

References

1. Huttner BD et al., COVID-19: don’t neglect antimicrobial stewardship principles!, Clinical Microbiology and Infection.
2. Rawson TM, Moore LSP, Zhu N, Ranganathan N, Skolimowska K, Gilchrist M, et al. Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing. Clin Infect Dis. 2020.
3. Clinical management of COVID-19. Interim Guidance. Geneva: World Health Organization; 27 May 2020.
4. Lv et al., Clinical characteristics and co-infections of 354 hospitalized patients with COVID-19 in Wuhan, China: a retrospective cohort study, Microbes and Infection.
5. COVID-19 rapid guideline: antibiotics for pneumonia in adults in hospital. United Kingdom: National Institute for Health and Care Excellence; 1 May 2020.
6. Antimicrobial stewardship programmes in health-care facilities in low- and middle-income countries. A practical toolkit. Geneva: World Health Organization; 2019.