Global call to healthcare providers treating COVID-19 patients to implement diagnostic stewardship/microbial diagnostics and exercise prudence in prescribing antibiotics

21 April 2020

Sabiha Y. Essack^{1, 4}, Ariel J. Blocker^{2, 4} and Maarten van Dongen^{3, 4}

¹Antimicrobial Research Unit, University of KwaZulu-Natal, Durban, South Africa
²Evotec ID Lyon, Severe Bacterial Infections Unit and Bacteriology/Bacteriomics Platform Lyon, France
³AMR Insights, Amsterdam, The Netherlands
⁴AMR Insights Ambassador Network

Corona virus disease 2019 (COVID-19) is a viral respiratory tract infection with clinical manifestations ranging from a mild influenza-like illness to severe pneumonia. Non-severe cases are managed by self-isolation, good hygiene practices and symptomatic treatment and at-risk populations are closely monitored for escalation to secondary bacterial infections.¹ Although anti-retrovirals² anti-malarials³ and antibiotics⁴, singly and in combination, are currently being used in the management of COVID-19, there is minimal robust evidence to support their use.

Inappropriate antibiotic treatment, in particular, is apparent in hospitalized COVID-19 patients. In a multi-center retrospective cohort study of 191 COVID-19 patients in Wuhan, China, 95%, 98% and 93% of the total, non-survivors and survivors respectively were administered antibiotics despite procalcitonin levels of >0.5 ng/ml in 9%, 25% and 1% and a secondary infection outcome in just 15%, 50% and 1% of the cohorts.⁵ In a single center study of 99 COVID-19 patients in Wuhan, China, 71% of patients were prescribed antibiotics despite elevated procalcitonin levels in only 6% of patients and bacterial co-infection in a mere 1%.⁶A report on the first 12 COVID-19 patients in the United States mentioned that some patients received empiric antibiotic treatment for possible secondary bacterial pneumonia in the absence of bacterial co-infection,⁷ while a case series of the first 18 COVID-19 patients in Singapore reported that patients clinically suspected of having community-acquire pneumoniae were prescribed empiric broad spectrum antibiotics.⁸ Such indiscriminate use in the absence of bacterial infection exerts avoidable selection pressure for the escalation of antibiotic resistance in the hospital setting.

Approximately 14% of COVID-19 patients develop severe disease that requires hospitalization and oxygen support, 5% require admission to an intensive care unit while the vast majority of patients develop uncomplicated illness¹ and can be managed on an outpatient basis. Although there is a dearth of literature on the management of non-hospitalized COVID-19 cases, inappropriate antibiotic use in upper respiratory tract infections (URTIs) of viral aetiology in community settings is well documented.

Although most URTIs have a viral aetiology and are self-limiting, inappropriate antibiotic prescribing for respiratory indications continues to be widespread. For example, 46% of antibiotic prescriptions for URTIs by general practitioners in the Netherlands were not indicated by guidelines^9,while the top 10% of highest prescribing general practices in the UK prescribed antibiotics for 72% of colds/URTIs, 67% of coughs/bronchitis, 90% of patients with otitis media, 78% of sore throats and 100% of cases of rhino-sinusitis.¹⁰ Antibiotic use at community level may be higher in countries where antibiotics can be procured over the counter without a prescription and from informal drug sellers.

The causal relationship between inappropriate antibiotic use and antibiotic resistance is well established in both hospital and community settings. We thus call on all AMR Insights Ambassadors and other healthcare providers treating COVID-19 patients to implement diagnostic stewardship/microbial diagnostics and exercise prudence in prescribing antibiotics for risk of the collateral damage of escalating antibiotic resistance by undue selection pressure of inappropriate antibiotic use.

References:

World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected 2020 [Available from: https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected.
Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. New England Journal of Medicine. March 18, DOI: 10.1056/NEJMoa2001282
Touret F, de Lamballerie X. Of chloroquine and COVID-19. Antiviral Research. 2020 Mar 5; 177:104762. doi: 10.1016/j.antiviral.2020.104762.
Molina JM, et al. No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection. Medecine et Maladies Infectieuses March 30, doi: 10.1016/j.medmal.2020.03.006
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 March 9, doi: 10.1016/S0140-6736(20)30566-3
Chen N, Zhou M, Dong X, Qu J, Gong F. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020 395: 507–13 doi: 10.1016/S0140-6736(20)30211-7
Kujawski SA, Wong KK, Collins JP, Epstein L, Killerby ME et al. First 12 patients with coronavirus disease 2019 (COVID-19) in the United States medRxiv doi: 1101/2020.03.09.20032896
Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY et al. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA. 2020 March 20, doi:10.1001/jama.2020.3204
Dekker AR, Verheij TJ, van der Velden AW. Inappropriate antibiotic prescription for respiratory tract indications: most prominent in adult patients. Family Practice 2015; 32(4):401-407.
Gulliford MC, Dregan A, Moore MV, et al. Continued high rates of antibiotic prescribing to adults with respiratory tract infection: survey of 568 UK general practices. BMJ Open. 2014; 4(10):e006245.

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