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1.
JAC-antimicrobial resistance ; 4(Suppl 2), 2022.
Article in English | EuropePMC | ID: covidwho-1876850

ABSTRACT

Background Less than 10% of hospitalized cases in the United Kingdom during the first wave of the pandemic had bacterial coinfection, but approximately 75% were prescribed antibiotics contrary to NICE guidelines. We have evaluated the relationship between antibiotic prescribing and biomarker use, in hospitalized adult patients with COVID-19 in the UK, as synthesis defined by the pandemic timeline, particularly during ‘Wave 2’ is lacking. Clinical outcomes were compared in the context of antimicrobial stewardship. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT) and white cell count (WCC) were selected based on clinical relevance. Methods Studies (n = 300) dated 2019–22 were identified via EMBASE and Web of Science databases, using relevant search terms. Wave 1 and Wave 2 parameters were defined by the Office for National Statistics. Literature selection was organized by the preferred reporting items for systematic reviews and meta-analyses (PRISMA). PROSPERO registration was commenced mitigating unplanned duplication. Diagnostics, prescribing, clinical outcomes and demographics were tabulated. Ten percent of studies were cross-checked. Results Final selection criteria yielded 29 papers, of which only 4 were from Wave 2. Cohort and retrospective studies accounted for 69% and 80%, respectively. Heterogeneity of studies prevented a meta-analysis. Determining disease severity or coinfection was the focus of ( n= 6) studies. The papers referencing WCC (n = 12) established that leucocytosis, like elevated CRP, was an efficient marker for bacterial infections. Additionally, CRP >100 mg/L was associated with increased prescribing. Another common theme was cut-off values to escalate (n = 9) or de-escalate (n = 12) prescribing. In PCT papers (n = 14), common de-escalation cut-offs were 0.25 ng/mL and 0.50 ng/mL. Lower admission PCT was associated with decreased mortality, admission duration and ICU admission rate. ESR use was unevaluable as it was only mentioned in one case study. During Wave 2, the use of immunomodulatory therapy may have contributed towards lower inflammatory markers. Hospital stays decreased while ICU duration increased. In ICU patient studies (n = 4) biomarker testing was more frequent. The higher 0.50 ng/mL PCT cut-off was employed but with higher mortality and ventilation rate. Conclusions More studies of Wave 2 cohorts are required. A weakness of the evidence base is that cohort study outcomes were reported in varying detail, a potential consequence of the need for rapidly published evidence. Nonetheless, PCT and CRP were demonstrated to be useful as prognosis indicators on hospital admission, and in timely antibiotic prescribing. Updated national guidelines should include standardized biomarker thresholds to improve antimicrobial stewardship.

2.
JAC-antimicrobial resistance ; 4(Suppl 1), 2022.
Article in English | EuropePMC | ID: covidwho-1823913

ABSTRACT

Background A minority of patients presenting to hospital with COVID-19 have bacterial coinfection. Procalcitonin testing may help identify patients for whom antibiotics should be prescribed or withheld. The PEACH study describes the use of procalcitonin in English and Welsh hospitals during the first wave of the COVID-19 pandemic to help diagnose bacterial infections and guide antibiotic treatment. There is a lack of clear evidence to support its use in lung infections, which means in some hospitals, clinicians have used the procalcitonin test to guide antibiotic decisions in COVID-19, whilst in other hospitals, they have not. Our study is analysing data from hospitals that did and did not use procalcitonin testing during the first wave of the COVID-19 pandemic. It will determine whether and how procalcitonin testing should be used in the NHS in future waves of COVID-19 to protect patients from antibiotic overuse. Methods To assess whether the use of PCT testing, to guide antibiotic prescribing, safely reduced antibiotic use among patients who were hospitalized with COVID-19 during the first wave of the pandemic, we are answering this question through three different, and complimentary, work streams (WS), each with discrete work packages (WP): (i) Work Stream 1: utilization of PCT testing to guide antibiotic prescribing during the first wave of COVID-19 pandemic;(ii) Work Stream 2: patient-level impact of PCT testing on antibiotic exposure and clinical outcome (main work stream currently in analysis);and (iii) Work Stream 3: health economics analysis of PCT testing to guide antibiotics in COVID-19. Results Our first publication from Work Stream 1 (Antibiotics 2021, 10: 516) used a web-based survey to gather data from antimicrobial leads about the use of procalcitonin testing. Responses were received from 148/151 (98%) eligible hospitals. During the first wave of the COVID-19 pandemic, there was widespread introduction and expansion of PCT use in NHS hospitals. The number of hospitals using PCT in emergency/acute admissions rose from 17 (11%) to 74/146 (50.7%) and use in ICU increased from 70 (47.6%) to 124/147 (84.4%). This increase happened predominantly in March and April 2020, preceding NICE guidance. Approximately half of hospitals used PCT as a single test to guide decisions to discontinue antibiotics and half used repeated measurements. There was marked variation in the thresholds used for empirical antibiotic cessation and guidance about interpretation of values. Conclusions Procalcitonin testing has been widely adopted in the NHS during the COVID-19 pandemic in an unevidenced, heterogeneous way and in conflict with relevant NICE guidance. Further research is needed urgently that assesses the impact of this change on antibiotic prescribing and patient safety. Work Stream 2 is ongoing, and results will be published once available.

3.
J Antimicrob Chemother ; 77(4): 1189-1196, 2022 03 31.
Article in English | MEDLINE | ID: covidwho-1684714

ABSTRACT

BACKGROUND: Blood biomarkers have the potential to help identify COVID-19 patients with bacterial coinfection in whom antibiotics are indicated. During the COVID-19 pandemic, procalcitonin testing was widely introduced at hospitals in the UK to guide antibiotic prescribing. We have determined the impact of this on hospital-level antibiotic consumption. METHODS: We conducted a retrospective, controlled interrupted time series analysis of organization-level data describing antibiotic dispensing, hospital activity and procalcitonin testing for acute hospitals/hospital trusts in England and Wales during the first wave of COVID-19 (24 February to 5 July 2020). RESULTS: In the main analysis of 105 hospitals in England, introduction of procalcitonin testing in emergency departments/acute medical admission units was associated with a statistically significant decrease in total antibiotic use of -1.08 (95% CI: -1.81 to -0.36) DDDs of antibiotic per admission per week per trust. This effect was then lost at a rate of 0.05 (95% CI: 0.02-0.08) DDDs per admission per week. Similar results were found specifically for first-line antibiotics for community-acquired pneumonia and for COVID-19 admissions rather than all admissions. Introduction of procalcitonin in the ICU setting was not associated with any significant change in antibiotic use. CONCLUSIONS: At hospitals where procalcitonin testing was introduced in emergency departments/acute medical units this was associated with an initial, but unsustained, reduction in antibiotic use. Further research should establish the patient-level impact of procalcitonin testing in this population and understand its potential for clinical effectiveness.


Subject(s)
COVID-19 , Procalcitonin , Anti-Bacterial Agents/therapeutic use , COVID-19/diagnosis , COVID-19/drug therapy , Hospitals , Humans , Interrupted Time Series Analysis , Pandemics , Retrospective Studies , State Medicine , United Kingdom
4.
Lancet ; 398(10309): 1417-1426, 2021 10 16.
Article in English | MEDLINE | ID: covidwho-1432164

ABSTRACT

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 PC, we assessed whether amoxicillin reduces the duration of moderately bad symptoms in children presenting with uncomplicated (non-pneumonic) LRTI in primary care, overall and in key clinical subgroups. METHODS: ARTIC PC was a double-blind, randomised, placebo-controlled trial done at 56 general practices in England. Eligible children were those aged 6 months to 12 years presenting in primary care with acute uncomplicated LRTI judged to be infective in origin, where pneumonia was not suspected clinically, with symptoms for less than 21 days. Patients were randomly assigned in a 1:1 ratio to receive amoxicillin 50 mg/kg per day or placebo oral suspension, in three divided doses orally for 7 days. Patients and investigators were masked to treatment assignment. The primary outcome was the duration of symptoms rated moderately bad or worse (measured using a validated diary) for up to 28 days or until symptoms resolved. The primary outcome and safety were assessed in the intention-to-treat population. The trial is registered with the ISRCTN Registry (ISRCTN79914298). FINDINGS: Between Nov 9, 2016, and March 17, 2020, 432 children (not including six who withdrew permission for use of their data after randomisation) were randomly assigned to the antibiotics group (n=221) or the placebo group (n=211). Complete data for symptom duration were available for 317 (73%) patients; missing data were imputed for the primary analysis. Median durations of moderately bad or worse symptoms were similar between the groups (5 days [IQR 4-11] in the antibiotics group vs 6 days [4-15] in the placebo group; hazard ratio [HR] 1·13 [95% CI 0·90-1·42]). No differences were seen for the primary outcome between the treatment groups in the five prespecified clinical subgroups (patients with chest signs, fever, physician rating of unwell, sputum or chest rattle, and short of breath). Estimates from complete-case analysis and a per-protocol analysis were similar to the imputed data analysis. INTERPRETATION: Amoxicillin for uncomplicated chest infections in children is unlikely to be clinically effective either overall or for key subgroups in whom antibiotics are commonly prescribed. Unless pneumonia is suspected, clinicians should provide safety-netting advice but not prescribe antibiotics for most children presenting with chest infections. FUNDING: National Institute for Health Research.


Subject(s)
Amoxicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Respiratory Tract Infections/drug therapy , Administration, Oral , Amoxicillin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Child , Child, Preschool , Double-Blind Method , England , Female , Humans , Infant , Male , Primary Health Care , Treatment Outcome
5.
Antibiotics (Basel) ; 10(5)2021 May 01.
Article in English | MEDLINE | ID: covidwho-1223911

ABSTRACT

A minority of patients presenting to hospital with COVID-19 have bacterial co-infection. Procalcitonin testing may help identify patients for whom antibiotics should be prescribed or withheld. This study describes the use of procalcitonin in English and Welsh hospitals during the first wave of the COVID-19 pandemic. A web-based survey of antimicrobial leads gathered data about the use of procalcitonin testing. Responses were received from 148/151 (98%) eligible hospitals. During the first wave of the COVID-19 pandemic, there was widespread introduction and expansion of PCT use in NHS hospitals. The number of hospitals using PCT in emergency/acute admissions rose from 17 (11%) to 74/146 (50.7%) and use in Intensive Care Units (ICU) increased from 70 (47.6%) to 124/147 (84.4%). This increase happened predominantly in March and April 2020, preceding NICE guidance. Approximately half of hospitals used PCT as a single test to guide decisions to discontinue antibiotics and half used repeated measurements. There was marked variation in the thresholds used for empiric antibiotic cessation and guidance about interpretation of values. Procalcitonin testing has been widely adopted in the NHS during the COVID-19 pandemic in an unevidenced, heterogeneous way and in conflict with relevant NICE guidance. Further research is needed urgently that assesses the impact of this change on antibiotic prescribing and patient safety.

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