key: cord-0864215-v1h83x5q authors: Zhu, Nina; Aylin, Paul; Rawson, Timothy; Gilchrist, Mark; Majeed, Azeem; Holmes, Alison title: Investigating the impact of COVID-19 on primary care antibiotic prescribing in North West London across two epidemic waves date: 2021-02-16 journal: Clin Microbiol Infect DOI: 10.1016/j.cmi.2021.02.007 sha: 05ed41b39cd461a71daf3cf8f768c689b8c7cae7 doc_id: 864215 cord_uid: v1h83x5q OBJECTIVES: We investigated the impact of COVID-19 and national pandemic response on primary care antibiotic prescribing in London. METHODS: Individual prescribing records between 2015 and 2020 for 2 million residents in North West London were analysed. Prescribing records were linked to SARS-CoV-2 test results. Prescribing volumes, in total, and stratified by patient characteristics, antibiotic class, and AWaRe classification, were investigated. Interrupted time series analysis was performed to detect measurable change in the trend of prescribing volume since the national lockdown in March 2020, immediately before the first COVID-19 peak in London. RESULTS: Records covering 366,059 patients, 730,001 antibiotic items, and 848,201 SARS-CoV-2 tests between January and November 2020 were analysed. Before March 2020, there was a background downward trend (decreasing by 584 items/month) in primary care antibiotic prescribing. This reduction rate accelerated to 3504 items/month from March 2020. This rate of decrease was sustained beyond the initial peak, continuing into winter and the second peak. Despite an overall reduction in prescribing volume, co-amoxiclav, a broad-spectrum “Access” antibiotic prescribing rose by 70.1% in patients aged 50 and older from February to April. Commonly prescribed antibiotics within 14 days of a positive SARS-CoV-2 test were amoxicillin (863/2474, 34.9%) and doxycycline (678/2474, 27.4%). This aligned with national guidelines on management of community pneumonia of unclear cause. The proportion of “Watch” antibiotics used decreased during the peak in COVID-19. CONCLUSIONS: A sustained reduction in community antibiotic prescribing was observed since the first lockdown. Investigation of community-onset infectious diseases and potential unintended consequences of reduced prescribing is urgently needed. The coronavirus disease 2019 (COVID-19) pandemic is having significant global impact on 2 healthcare delivery. The influence of COVID-19 on antibiotic use across healthcare and on 3 antimicrobial resistance (AMR) remains unclear. 4 Antibiotics have been used in hospitals to empirically treat patients with suspected COVID-5 19 due to the overlapping clinical and radiological features with bacterial respiratory tract 6 infection [1, 2] . Initial data from hospitals with a high burden of COVID-19 indicates high 7 rates of antibiotic prescribing despite relatively low detected rates of bacterial co-infections 8 in 4] . 9 Whilst there is increasing data regarding the impact of COVID-19 on antibiotic use in acute 10 care, there is very limited data on the impact of COVID-19 on antibiotic use in community 11 settings [2] . Prescribing in primary care accounts for 81% of total antibiotic prescribing in 12 England [5] , and is mainly empirical, based on clinical signs and symptoms rather than a 13 precise diagnosis [6] . Measures implemented in the UK to contain the transmission of 14 COVID-19, such as social distancing, quarantine, and travel restrictions, reduced population 15 mobility and drove a shift from face-to-face appointments to telephone and video 16 consultations. This shift in practice has influenced the process of how patients are assessed 17 [7] , and how antibiotics are prescribed in primary care [8] . Avoiding visits to primary care 18 facilities, to prevent infections and 'protect the National Health Service (NHS)', has led to 19 delays in care-seeking. In the 15-week lockdown period between 23 March 2020 and 5 July 20 2020 in England, face-to-face consultation with primary care physicians, referred as General 21 Practitioners (GPs), accounted for 24% of all GP contacts with patients, compared with over 22 70% in the previous year [9] . 23 AMR is also a pandemic in nature, but a gradual yet implacable process. To minimise the 24 negative impact on human health during this era of the double pandemic of COVID-19 and 25 AMR, data is urgently needed to assess antibiotic prescribing, examine clinical outcomes of 26 We conducted ITSA to determine whether there was a measurable change in the underlying 91 trend of antibiotic prescribing volume in primary care associated with COVID-19 and the 92 national pandemic response. We used the date when the first national lockdown was 93 imposed in England as a clear 'interruption' date, around which the data trends would be analysed [19] . This date was just one week before the peak of the first wave of COVID-19. 95 The impact of the pandemic disease itself cannot be separated from the societal responses. 96 We constructed a monthly time series of the number of antibiotic items prescribed from 97 January 2015 to November 2020, and set the lockdown date as March 2020 [19] . We 98 adjusted for seasonality by including each calendar month as an independent variable. We 99 performed ITSA to produce Newey-West standard errors for coefficients estimated by During the 11-month study period, 730,001 GP antibiotic prescriptions were identified, after 127 excluding prescriptions of anti-mycobacterial drugs. We observed a decreasing trend of 128 prescribing volume following the introduction of the first national lockdown in March 2020 129 ( Figure 1) . The predicted weekly prescribing volume is presented in Figure 1 The observed decline in prescribing volume following the first national lockdown and the 156 first peak of COVID-19 occurred consistently across all gender, age, ethnic, and 157 socioeconomic groups (Supplementary material 2) . However, such a decline was not 158 J o u r n a l P r e -p r o o f sustained in BAME population since August. The potential relationships between antibiotic 159 prescribing and ethnicity in the context of COVID-19 is being explored further. 160 Antibiotic prescribing volume reached its lowest in August 2020. From January to August, 161 prescribing of penicillins decreased most, by 57.2%, followed by macrolides (54.6%) and 162 tetracyclines (45.0%). The reduction in prescribing of cephalosporins (14.1%), and 163 nitrofurantoin and UTI drugs (16.9%) was smaller (Figure 3) . accident and emergency departments) were reduced in the early lockdown period. However, 234 our analysis revealed that while consultation rates were returning to normal levels, schools 235 were re-opened and social distancing measures were relaxed, the decline in antibiotic 236 prescribing sustained. Further analysis is required to assess whether the reduced 237 community prescribing will have a continuing effect on community infection rates and AMR. 238 We will also need to evaluate the longer-term impact of a shift to remote consultations in 239 primary care on antibiotic prescribing and clinical outcomes such as delayed treatment of 240 bacterial infections, increase in hospital admissions and deaths [27] . 241 Our study also has several limitations that provide scope for future research. First, the 243 analysis of prescribing for SARS-CoV-2 positive patients was limited due to the lack of 244 documented indication for the antibiotic. The testing capacity and specificity further 245 restricted the comparison between COVID-19 and non COVID-19 patients. We aim to link 246 primary care and hospital records for SARS-CoV-2 positive patients to assess whether they 247 required hospital admission and the outcomes of treatment. Second, we did not assess how 248 the shift from face-to-face to remote GP consultations might have influenced antibiotic 249 prescribing and dispensing. Remote delivery of primary care service grew dramatically in the 250 pandemic, formal evaluation is urgently required to re-design antimicrobial stewardship 251 interventions, maintain quality of antibiotic prescribing, and avoid unintended 252 consequences [28] . Third, GP-led 'hot hubs' were providing face-to-face consultations and 253 issuing pre-packed antibiotics with pneumonia symptoms in NWL [29] . Antibiotics dispensed in this route outside standard opening hours was not captured in our data, however this 255 was estimated to account for less than 0.5% of GP prescribing in NWL [30] . Imperial's Clinical Analytics Evaluation (iCARE) project started in Autumn 2019 as a proof-of-concept high 332 performance analytics environment, funded by NIHR Imperial BRC information/publications/statistical/appointments-in-general-practice English indices of deprivation World Health Organization. ATC/DDD Index 2019 World Health Organization. WHO releases the 2019 AWaRe Classification Antibiotics Heal. Prod. 2019.WHO releases the 2019 AWaRe Classification Interrupted time series regression for the 349 evaluation of public health interventions: A tutorial Prime Minister's statement on coronavirus (COVID-19 356 21 National Institute for Health and Care Excellence. COVID-19 rapid guideline : 357 managing suspected or confirmed pneumonia in adults in the community Clinical management of COVID-19 Interim Guidance World Health Organ The impact of a national antimicrobial 365 stewardship program on antibiotic prescribing in primary care: An interrupted time 366 series analysis Age-related decline in antibiotic 368 prescribing for uncomplicated respiratory tract infections in primary care in England 369 following the introduction of a national financial incentive (the Quality Premium) for 370 health commissioners to reduce use of antibiotic Communicable and respiratory disease reports Impact of Remote Consultations on Antibiotic 375 Prescribing in Primary Healthcare: Systematic Review An assessment of potential 378 unintended consequences following a national antimicrobial stewardship program in An interrupted time series analysis GPs set to diagnose Covid-19 face to face in 'hot hubs'. Pulse Quantifying where human acquisition of 386 antibiotic resistance occurs: A mathematical modelling study 397 398 399 400 401