Impact of introducing procalcitonin testing on antibiotic usage in acute NHS hospitals during the first wave of COVID-19 in the UK: a controlled interrupted time series analysis of organization-level data.

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.

Test performance of lateral flow rapid antigen tests for COVID-19 in Welsh adult care home staff using routine surveillance data.

BACKGROUND: Lateral flow tests (LFTs) have been used to screen for SARS-CoV2 in Wales since January 2021. Between May and August 2021, adult care home staff policy was for biweekly Innova LFT and weekly Polymerase Chain Reaction (PCR) testing while asymptomatic. We estimated test performance of LFTs conducted in adult care home staff using PCR tests as a reference standard. METHODS: Test results from surveillance data were matched by individual where both LFT and PCR were taken on the same day. We calculated sensitivity, specificity, positive and negative predictive values, and agreement using Matthew's correlation coefficient. Ct values of positive PCR results were compared by matched LFT result. Analysis was conducted using R v4.1.3. RESULTS: We analysed 115,593 test pairs, 499 (0.43%) of which were PCR positive. Median age was 48 (IQR: 22) and 85.00% of the study population were female. Test result agreement was 99.59% (95%CI 99.55-99.63; MCC: 0.38, p<0.001). Sensitivity and specificity were 25.65% (95%CI 22.02-29.67) and 99.91% (95%CI 99.89-99.93), respectively. PPV was 55.90% (95%CI 49.42-62.17) and NPV was 99.68% (95%CI 99.64-99.71). Crude Ct values were significantly lower in positive PCR tests matched to a positive LFT compared to a negative LFT. CONCLUSIONS: Specificity and negative predictive value were high in an asymptomatic population of care home staff indicating this test is an effective tool for identifying cases of SARS-CoV-2 infection during periods of high prevalence where transmission is likely, due to the presence of high viral loads. Positive predictive value results are lower than existing literature yet should be considered in light of the asymptomatic study population and low prevalence (under 1%) at the time most of these tests were conducted. Performance improved at times of higher prevalence during the study. These results suggest that whilst lateral flow tests are effective for identifying SARS-COV-2 infections with high viral loads, they are not effective at identifying cases with a low viral load. When an LFT provides a negative result, false negatives should be considered and additional diagnostic tests performed.

Long-term outcomes of urinary tract infection (UTI) in Childhood (LUCI): protocol for an electronic record-linked cohort study.

INTRODUCTION: Current guidelines advise the prompt diagnosis and treatment of urinary tract infection (UTI) in children to improve both short and longer term outcomes. However, the risk of long-term complications following childhood UTI is unclear.UTI is relatively common but difficult to diagnose in children as symptoms are non-specific. Diagnosis requires a urine sample, but sampling is difficult and infrequent, and it is not clear if sampling should be given greater priority in primary care. The LUCI study will assess the short, medium and longer term outcomes of childhood UTI associated with routine and systematic sampling practices. METHODS AND ANALYSIS: Two data sets will be established. The first will consist of routinely collected data (hospital, general practice (GP), microbiology) from children born and resident in Wales, linked via the Secure Anonymised Information Linkage (SAIL) Databank (an 'e-cohort'). Urine sampling in this data set reflects normal practice 'routine sampling'. Outcomes (including renal scarring, hypertension, end-stage renal failure, hospital admissions, GP consultations, antibiotic prescriptions) for children with at least one UTI confirmed with microbiological culture (mcUTI) or no mcUTI before the age of 5 will be compared.The second will combine data from two prospective observational studies ('DUTY' and 'EURICA') employing systematic urine sampling for children presenting to primary care with acute, undifferentiated illness, linked to routine data via SAIL (Wales) and NHS Digital (England). Outcomes (as above, plus features of mcUTI) for children with an mcUTI in this data set, identified through systematic urine sampling, will be compared with those with an mcUTI identified through routine urine sampling (data set 1). ETHICS AND DISSEMINATION: The study protocol has been approved by NHS Wales Research Ethics Committee and the Health Research Authority's Confidentiality Advisory Group. Methods of innovative study design and findings will be disseminated through peer-review journals and conferences. Results will be of interest to clinical and policy stakeholders in the UK.

Containing antibiotic resistance: decreased antibiotic-resistant coliform urinary tract infections with reduction in antibiotic prescribing by general practices.

BACKGROUND: GPs are urged to prescribe antibiotics less frequently, despite lack of evidence linking reduced antibiotic prescribing with reductions in resistance at a local level. AIM: To investigate associations between changes in antibiotic dispensing and changes in antibiotic resistance at general-practice level. DESIGN OF STUDY: Seven-year study of dispensed antibiotics and antibiotic resistance in coliform isolates from urine samples routinely submitted from general practice. SETTING: General practices in Wales. METHOD: Multilevel modelling of trends in resistance to ampicillin and trimethoprim, and changes in practice total antibiotic dispensing and amoxicillin and trimethoprim dispensing. RESULTS: The primary analysis included data on 164 225 coliform isolates from urine samples submitted from 240 general practices over the 7-year study period. These practices served a population of 1.7 million patients. The quartile of practices that had the greatest decrease in total antibiotic dispensing demonstrated a 5.2% reduction in ampicillin resistance over the 7-year period with changes of 0.4%, 2.4%, and -0.3% in the other three quartiles. There was a statistically significant overall decrease in ampicillin resistance of 1.03% (95% confidence interval [CI] = 0.37 to 1.67%) per decrease of 50 amoxicillin items dispensed per 1000 patients per annum. There were also significant reductions in trimethoprim resistance in the two quartiles of practices that reduced total antibiotic dispensing most compared with those that reduced it least, with an overall decrease in trimethoprim resistance of 1.08% (95% CI = 0.065 to 2.10%) per decrease of 20 trimethoprim items dispensed per 1000 patients per annum. Main findings were confirmed by secondary analyses of 256 370 isolates from 527 practices that contributed data at some point during the study period. CONCLUSION: Reducing antibiotic dispensing at general-practice level is associated with reduced local antibiotic resistance. These findings should further encourage clinicians and patients to use antibiotics conservatively.

When do general practitioners request urine specimens for microbiology analysis? The applicability of antibiotic resistance surveillance based on routinely collected data.

OBJECTIVES: We do not know how representative reported levels of resistance to antibiotics in urinary tract infections (UTIs) are as there is wide variation in the rate of urine specimens submitted to microbiology laboratories by general practices. We used a questionnaire to investigate variation in sampling for patients with suspected UTI to explore any systematic bias that may influence interpretation of surveillance data based on routine data. METHODS: We sent a questionnaire to a stratified random sample of general practitioners (GPs) in Wales for self-completion. The GPs were presented with six clinical scenarios and asked about their proposed clinical management. RESULTS: We found that nearly all of the GPs indicated they would request a specimen for scenarios representing a probable UTI in a female child and a probable asymptomatic UTI in pregnancy. There was some variation between the GPs about sampling in a situation of treatment failure in an older woman and recurrent UTI in a male diabetic, with 90% and 81%, respectively, indicating they would request a specimen for these scenarios. The greatest variation was in relation to scenarios concerning the management of a probable uncomplicated UTI, and early patient symptoms with pressure to prescribe, with 56% and 33% of GPs, respectively, indicating they would request a urine specimen for laboratory analysis. CONCLUSIONS: In the light of this reported sampling behaviour, it is likely that there is a systematic bias in surveillance data based on routinely collected data, with samples from cases of uncomplicated UTI being under represented, potentially leading to an overestimation of true resistance rates.

Finding a strategy: the case for co-operative research on resistance epidemiology.

Progress on rational intervention to prevent increasing antibiotic resistance has been slow. We suggest that this is because the science of resistance epidemiology has received little attention, and that a systematic, co-operative investigation of this area might yield a relevant knowledge base, analogous to the basis for effective public health intervention in infectious disease given by infection epidemiology. The steps required to progress this approach in the UK are discussed, along with a summary of what is known and speculation on what might emerge.

Laboratory testing policies and their effects on routine surveillance of community antimicrobial resistance.

OBJECTIVE: To investigate the effects of laboratory testing policies, particularly selective testing, rule-based reporting and isolate identification, on estimates of community antimicrobial resistance. MATERIALS AND METHODS: Antibiotic resistance estimates were analysed from an all-Wales dataset for approximately 300 000 community isolates of common pathogens. RESULTS: Selective testing policies were often associated with markedly increased resistance, particularly for second-line testing. Site-specific testing tended to yield variant resistance estimates for eye and ear isolates. Estimates from rule-based reporting deviated markedly from test-result-based reporting. Urinary isolates reported as Escherichia coli showed greater susceptibility than those reported as undifferentiated urinary 'coliforms'. The proportion of isolates tested for an antibiotic by a laboratory was a useful indicator of selective testing in this dataset. Selective testing policies had invariably been applied where the proportion of isolates of a species tested against an antibiotic was <90%. As this proportion fell with increasingly selective policies, divergence from pooled-all-Wales non-selective estimates tended to increase, with a bias to increased resistance. CONCLUSIONS: Selective testing, rule-based reporting and urinary coliform identification policies all had significant effects upon resistance estimates. Triage based upon the proportion of isolates tested seemed a useful tool in assigning analysis resources. Where <20% of isolates were tested, selective policies with inherent bias to increased resistance were common, the low number of isolates gave high potential sampling errors, and little confidence could be placed in the resistance estimate. Where 20-90% of isolates were tested, detailed analysis sometimes revealed resistance estimates that might be usefully retrieved. Where >/=90% of isolates were tested, there was no evidence of selective testing, and inter-laboratory variation in estimates appeared to be safely ascribable to other effects, e.g. methodology or real variation in resistance levels.