Christopher C Butler

University of Oxford | OX · Department of Primary Care Health Sciences

Background: Trials have identified antimicrobial stewardship (AMS) strategies that effectively reduce antibiotic use in primary care. However, many are not commonly used in England. We co-developed an implementation intervention to improve use of three AMS strategies; enhanced communication strategies, delayed prescriptions, and point-of-care C-Rea...

Background The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions a...

Background Oseltamivir is usually not often prescribed (or reimbursed) for non-high-risk patients consulting for influenza-like-illness (ILI) in primary care in Europe. We aimed to evaluate the cost-effectiveness of adding oseltamivir to usual primary care in adults/adolescents (13 years +) and children with ILI during seasonal influenza epidemics,...

Background Randomised trials provide high-quality evidence on the effects of prescribing antibiotics for urinary tract infection (UTI) but may not reflect the effects in those who consume antibiotics. Moreover, they mostly compare different antibiotic types or regimens but rarely include a ‘no antibiotic’ group. Aim To estimate the effect of antib...

Background: We aimed to evaluate the analytic performance of 3 rapid HIV viral load assays: the novel Xpert HIV-1 VL XC (Xpert XC), Xpert HIV-1 VL (Xpert VL), and m-PIMA HIV-1/2 VL (m-PIMA). Setting: Two South African clinics. Methods: We conducted a prospective diagnostic accuracy study. Site-laboratory technicians and nurses used the Xpert X...

Objectives About 6% of the UK general practice population has a record of a penicillin allergy but fewer than 10% of these are likely to be truly allergic. In the ALABAMA (Allergy Antibiotics and Microbial resistance) feasibility trial, primary care patients with penicillin allergy were randomised to penicillin allergy assessment pathway or usual c...

Objectives: Antimicrobial resistance (AMR) is a public health threat associated with antibiotic consumption. Community-acquired acute respiratory tract infections (CA-ARTIs) are a major driver of antibiotic consumption in primary care. We aimed to quantify the investments required for a large-scale rollout of point-of care (POC) diagnostic testing...

Background: Colchicine has been proposed as a COVID-19 treatment. Aim: To determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community. Design and setting: Prospective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE)...

Objective To identify the experiences and concerns of health workers (HWs), and how they changed, throughout the first year of the COVID-19 pandemic in the UK. Methods Longitudinal, qualitative study with HWs involved in patient management or delivery of care related to COVID-19 in general practice, emergency departments and hospitals. Participant...

p>Background: there is little evidence about the relationship between aetiology, illness severity, and clinical course of respiratory tract infections (RTIs) in primary care. Understanding these associations would aid in the development of effective management strategies for these infections. Aim: to investigate whether clinical presentation and i...

Background: Most antibiotics are prescribed in primary care. Locum or sessional general practitioners (locums) are perceived as contributing to higher prescribing and may face barriers to engaging with antimicrobial stewardship (AMS). Aim: To identify how locums' antibiotic prescribing compares to other general practice prescribers, and how they...

Antibiotic use (and misuse) accelerates antimicrobial resistance (AMR), and addressing this complex problem necessitates behaviour change related to infection prevention and management and to antibiotic prescribing and use. As most antibiotic courses are prescribed in primary care, a key focus of antimicrobial stewardship (AMS) is on changing behav...

Background Between-country differences have been described in antibiotic prescribing for RTI in primary care, but not yet for diagnostic testing procedures and prescribing confidence. Aim To describe between-country differences in RTI management, particularly diagnostic testing and antibiotic prescribing, and investigate which factors relate to an...

The COVID-19 pandemic has had a profound impact on the delivery of primary care services. We aimed to identify general practitioners’ (GPs’) perceptions and experiences of how the COVID-19 pandemic influenced antibiotic prescribing and antimicrobial stewardship (AMS) in general practice in England. Twenty-four semi-structured interviews were conduc...

Background: There is little evidence about the relation between aetiology, illness severity and clinical course of respiratory tract infections (RTI) in primary care. Understanding these associations would aid to develop effective management strategies for these infections. Aim: To investigate whether the clinical presentation and illness course...

Objective Recovery time and treatment effect of oseltamivir in influenza-like illness (ILI) differs between patient groups. A point-of-care test to better predict ILI duration and identify patients who are most likely to benefit from oseltamivir treatment would aid prescribing decisions in primary care. This study aimed to investigate whether a C-r...

The COVID-19 pandemic has had a profound impact on the delivery of primary care services. We aimed to identify general practitioners (GPs) perceptions and experiences of how the COVID-19 pandemic influenced antibiotic prescribing and antimicrobial stewardship (AMS) in general practice in England. Twenty-four semi-structured interviews were conducte...

Background: Urine collection devices (UCD) are being marketed and used in clinical settings to reduce urine sample contamination, despite inadequate supporting evidence. Aim: To determine whether UCDs, compared to standardised instructions for urine sample collection, reduce the proportion of contaminated samples. Design, Setting: Single blind r...

Background: Clinical findings do not accurately predict laboratory diagnosis of influenza. Early identification of influenza is considered useful for proper management decisions in primary care. Objective: We evaluated the diagnostic value of the presence and the severity of symptoms for the diagnosis of laboratory-confirmed influenza infection...

Objectives The ALIC⁴E trial has shown that oseltamivir reduces recovery time while increasing the risk of nausea. This secondary analysis of the ALIC⁴E trial aimed to determine the gain in quality-adjusted life-years (QALYs) associated with adding oseltamivir to usual primary care in patients presenting with influenza-like illness (ILI). Methods P...

Objectives: Colchicine has been proposed as a COVID-19 treatment, but its effect on time to recovery is unknown. We aimed to determine whether colchicine is effective at reducing time to recovery and COVID-19 related hospitalisations/deaths among people in the community. Design: Prospective, multicentre, open-label, multi-arm, adaptive Platform Ran...

Background Trials show that antimicrobial stewardship (AMS) strategies, including communication skills training, point-of-care C-reactive protein testing (POC-CRPT) and delayed prescriptions, help optimise antibiotic prescribing and use in primary care. However, the use of these strategies in general practice is limited and inconsistent. We aimed t...

Background: Minimising primary care professionals' (PCPs) risk of SARS-CoV-2 infection is crucial to ensure their safety as well as functioning health care system. PCPs' perspectives on the support they needed in the early stages of a public health crisis can inform future preparedness. Aim: To understand PCPs' experiences of providing care during...

Background Antibiotic resistance is a global public health threat. Antibiotics are very commonly prescribed for children presenting with uncomplicated lower respiratory tract infections (LRTIs), but there is little evidence from randomised controlled trials of the effectiveness of antibiotics, both overall or among key clinical subgroups. In ARTIC...

Background Delayed (or “backup”) antibiotic prescription, where the patient is given a prescription but advised to delay initiating antibiotics, has been shown to be effective in reducing antibiotic use in primary care. However, this strategy is not widely used in the United Kingdom. This study aimed to identify factors influencing preferences amon...

Background A previous efficacy trial found benefit from inhaled budesonide for COVID-19 in patients not admitted to hospital, but effectiveness in high-risk individuals is unknown. We aimed to establish whether inhaled budesonide reduces time to recovery and COVID-19-related hospital admissions or deaths among people at high risk of complications i...

Objective: To describe primary health care (consultation characteristics and management) for patients contacting their general practitioner (GP) with a respiratory tract infection (RTI) early on in the COVID-19 pandemic in contrasting European countries, with comparison to prepandemic findings. Setting: Primary care in 16 countries (79 practices...

Background and objective: Influenza-like illness (ILI) leads to a substantial disease burden every winter in Europe; however, oseltamivir is not frequently prescribed to ILI patients in the primary-care setting. An open-label, multi-country, multi-season, randomised controlled trial investigated the effectiveness of oseltamivir for treating ILI in...

Background Doxycycline is often used for treating COVID-19 respiratory symptoms in the community despite an absence of evidence from clinical trials to support its use. We aimed to assess the efficacy of doxycycline to treat suspected COVID-19 in the community among people at high risk of adverse outcomes. Methods We did a national, open-label, mu...

Background Six percent of patients are allergic to penicillin according to their medical records. While this designation protects a small number of truly allergic patients from serious reactions, those who are incorrectly labelled may be denied access to recommended first line treatment for many infections. Removal of incorrect penicillin allergy m...

Introduction There is an urgent need to idenfy treatments for COVID-19 that reduce illness duration and hospital admission in those at higher risk of a longer illness course and complications. Methods and analysis The Platform Randomised trial of INterventions against COVID-19 In older peoPLE trial is an open-label, multiarm, prospective, adaptive...

BACKGROUND Inhaled budesonide has shown efficacy for treating COVID-19 in the community but has not yet been tested in effectiveness trials. METHODS We performed a multicenter, open-label, multi-arm, adaptive platform randomized controlled trial involving people aged ≥65 years, or ≥50 years with comorbidities, and unwell ≤14 days with suspected COV...

p style="-webkit-font-smoothing: antialiased; margin: 0px 0px 15px; padding: 0px; border: 0px; outline: 0px; vertical-align: baseline; font-style: inherit; font-variant: inherit; font-weight: inherit; font-stretch: inherit; font-size: inherit; line-height: inherit; overflow-wrap: break-word;"> Background C-reactive protein (CRP) point-of-care testi...

Background Care homes are an increasingly important sector of care. Care home residents are particularly vulnerable to infections and are often prescribed antibiotics, driving antibiotic resistance. Probiotics may be a cheap and safe way to reduce antibiotic use. Efficacy and possible mechanisms of action are yet to be rigorously evaluated in this...

Background: The HIV protease inhibitor lopinavir, boosted with ritonavir, has been used off-label to treat COVID-19. We aimed to synthesise the clinical evidence for lopinavir/ritonavir as a treatment for COVID-19. Methods: We performed a rapid review by searching databases including PubMed, GoogleScholar, medRxiv, ClinicalTrials.gov and the Coc...

Background Azithromycin, an antibiotic with potential antiviral and anti-inflammatory properties, has been used to treat COVID-19, but evidence from community randomised trials is lacking. We aimed to assess the effectiveness of azithromycin to treat suspected COVID-19 among people in the community who had an increased risk of complications. Metho...

Background In the UK, consultations for prescription medicines are available via private providers such as online pharmacies. However, these providers may have lower thresholds for prescribing certain drugs. This is a particular concern for antibiotics, given the increasing burden of antimicrobial resistance. Public preferences for consultations wi...

Aging is associated with a decline in many components of the immune system (immunosenescence). Probiotics may improve the immune response in older people. The objective was to determine the effect of the combination of two probiotic organisms [Lacticaseibacillus (previously known as Lactobacillus) rhamnosus GG (LGG) and Bifidobacterium animalis sub...

Ageing entails changes to the immune system, collectively termed immunosenescence and inflammageing. The relationships among age, frailty and immune parameters in older people resident in care homes deserves better exploration. We assessed immune and inflammatory parameters in UK care home residents aged over 65 yr and how they relate to age, frail...

Introduction Access to HIV viral load testing remains difficult for many people on antiretroviral therapy (ART) in low-income and middle-income countries. Weak laboratory and clinic systems often delay the detection and management of viraemia, which can lead to morbidity, drug resistance and HIV transmission. Point-of-care testing could overcome th...

Background Trials have shown that delayed antibiotic prescriptions (DPs) and point-of-care C-Reactive Protein testing (POC-CRPT) are effective in reducing antibiotic use in general practice, but these were not typically implemented in high-prescribing practices. We aimed to explore views of professionals from high-prescribing practices about uptake...

Objective: While various interventions have helped reduce antibiotic prescribing, further gains can be made. This study aimed to identify ways to optimise antimicrobial stewardship (AMS) interventions by assessing the extent to which important influences on antibiotic prescribing are addressed (or not) by behavioural content of AMS interventions....

Antibiotic prescribing in England varies considerably between Clinical Commissioning Groups (CCGs) and general practices. We aimed to assess social and contextual factors affecting antibiotic prescribing and engagement with antimicrobial stewardship (AMS) initiatives. Semi-structured telephone interviews were conducted with 22 CCG professionals and...

Introduction: Identifying predictors of bacterial and viral pathogens in sputum from patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) may help direct management. Methods: We used data from a trial evaluating a C-reactive protein (CRP) point of care guided approach to managing COPD exacerbations in primary care. W...

Objective Identifying influenza A or B as cause of influenza-like illness (ILI) is a challenge due to non-specific symptoms. An accurate, cheap and easy to use biomarker might enhance targeting influenza-specific management in primary care. The aim of this study was to investigate if C-reactive protein (CRP) is associated with influenza A or B, con...

Influenza-like illnesses (ILI) account for a significant portion of inappropriate antibiotic use. Patient expectations for antibiotics for ILI are likely to play a substantial role in 'unnecessary' antibiotic consumption. This study aimed to investigate trends in awareness of appropriate antibiotic use and antimicrobial resistance (AMR). Three sequ...

Delayed antibiotic prescription in primary care has been shown to reduce antibiotic consumption, without increasing risk of complications, yet is not widely used in the UK. We sought to quantify the relative importance of factors affecting the decision to give a delayed prescription, using a stated-choice survey among UK general practitioners. Resp...

Background Differences in clinical impact between rhinovirus (RVs) species and types in adults are not well established. The objective of this study was to determine the epidemiology and clinical impact of the different RV species. Methods We conducted a prospective study of RVs infections in adults with acute cough/lower respiratory tract infecti...

Annual influenza epidemics cause substantial morbidity and mortality, and the majority of patients with influenza-like illness present to primary care. Point-of-care influenza tests could support treatment decisions. It is critical to establish analytic performance of these platforms in real-life patient samples before uptake can be considered. We...

Catheter-associated urinary tract infections (CAUTI) are common yet preventable. Healthcare professional behaviours, such as reducing unnecessary catheter use, are key for preventing CAUTI. Previous research has focused on identifying gaps in the national response to CAUTI in multiple settings in England. This study aimed to identify how national i...

Importance Probiotics are frequently used by residents in care homes (residential homes or nursing homes that provide residents with 24-hour support for personal care or nursing care), although the evidence on whether probiotics prevent infections and reduce antibiotic use in these settings is limited. Objective To determine whether a daily oral p...

Background: The Quality Premium (QP) was introduced for Clinical Commissioning Groups (CCGs) in England to optimize antibiotic prescribing, but it remains unclear how it was implemented. Objectives: To understand responses to the QP and how it was perceived to influence antibiotic prescribing. Methods: Semi-structured telephone interviews were...

Background Patients infected with the novel coronavirus (SARS-CoV-2) are being treated empirically with oseltamivir, but there is little evidence from randomised controlled trials to support the treatment of coronavirus infections with oseltamivir. Aim To determine whether adding oseltamivir to usual care reduces time to recovery in symptomatic pa...

Background Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed antibiotics, but these may not be beneficial, and they can cause side effects and increase the risk of subsequent resistant infections. Point-of-care tests (POCTs) could safely reduce inappropriate antibiotic...

Objectives: To determine the effect of ventilation tube (VT) surgery on quality of life (QoL) in children with persistent otitis media with effusion (OME). Design: Secondary analysis of trial data (oral steroids versus placebo for persistent OME), comparing QoL by history of VT surgery performed between 5 weeks and 12 months post randomisation....

Background: Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary...

Objectives: The public and patients are primary contributors and beneficiaries of pandemic-relevant clinical research. However, their views on research participation during a pandemic have not been systematically studied. We aimed to understand public views regarding participation in clinical research during a hypothetical influenza pandemic. Stu...

Background: Point-of-care testing of C-reactive protein (CRP) may be a way to reduce unnecessary use of antibiotics without harming patients who have acute exacerbations of chronic obstructive pulmonary disease (COPD). Methods: We performed a multicenter, open-label, randomized, controlled trial involving patients with a diagnosis of COPD in the...

Purpose Clinical guidelines recommend at least 7 days of antibiotic treatment for older men with urinary tract infection (UTI). There may be potential benefits for patients, health services, and antimicrobial stewardship if shorter antibiotic treatment resulted in similar outcomes. We aimed to determine if treatment duration could be reduced by est...

The Spanish Flu of 1918 reached every continent, infected one-third of the world's population and claimed over 50 million lives [1]. The centenary of this event presented a stark reminder of the threat of infectious disease epidemics to global health and security. These threats persist, fuelled in part by features of modern-day living such as clima...

Purpose. C-Reactive-Protein (CRP) has diagnostic utility for lower respiratory tract infections (RTI). A large international trial documented that internet-based training in communication skills, CRP point-of-care-test (POCT), or both, reduced antibiotic prescribing at 3 months (risk ratios (RR) 0.68, 0.53, 0.38, respectively). We report the longer...

Background Nitrofurantoin is widely recommended for empirical treatment of urinary tract infection (UTI) but primary care clinicians may prescribe alternative antibiotics to improve prognosis in older, sicker patients. We assessed if prescribing alternative antibiotics was associated with reduced risk of adverse outcomes in older patients. Methods...