The diagnostic accuracy of the ID NOW COVID-19 point of care test in acute hospital admissions.

BACKGROUND: Prompt identification of patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on admission to hospital is crucial to ensuring initiation of appropriate treatment, optimising infection control and maintaining patient flow. The Abbott ID NOW™ COVID-19 assay (ID NOW) is a point-of-care, isothermal nucleic acid amplification test, capable of producing a result within minutes, potentially placing it as an invaluable tool in helping to control the coronavirus-disease 2019 (COVID-19) pandemic. OBJECTIVES: To evaluate the diagnostic accuracy of ID NOW in acute hospital admissions. STUDY DESIGN: A prospective approach to data collection was undertaken in consecutive patients with ID NOW and Hologic Aptima™ SARS-CoV-2 transcription-mediated amplification assay (Aptima TMA) results, across three hospitals in the south-west of England between 1st March and 30th September 2021. A nasal swab was taken for ID NOW and a combined nose and throat swab for Aptima TMA. Measures of diagnostic accuracy were calculated for ID NOW against Aptima TMA. This study was conducted during a period of alpha and delta strain predominance. RESULTS: 19,698 ID NOW assays were performed, of which 12,821 had an Aptima TMA assay performed within 24 hours. ID NOW had sensitivity of 85.2 % (95 % CI, 82.2-87.9) and specificity of 99.6 % (95 % CI, 99.4-99.7) compared with the reference assay. The overall PPV was 91.0 % (95 % CI, 88.5-93.0) and the overall NPV was 99.3 % (95 % CI, 99.1-99.4). CONCLUSIONS: ID NOW offers a valid diagnostic tool to detect SARS-CoV-2, performing comparably to a reference laboratory-based assay which takes longer to provide results.

Pseudomonas guariconensis Necrotizing Fasciitis, United Kingdom.

We describe a case of necrotizing fasciitis in the United Kingdom in which Pseudomonas guariconensis was isolated from multiple blood culture and tissue samples. The organism carried a Verona integron-encoded metallo-ß-lactamase gene and evidence of decreased susceptibility to ß-lactam antimicrobial agents. Clinicians should use caution when treating infection caused by this rare pathogen.

The Natural History of Antibiotic-Treated Lower Limb Cellulitis: Analysis of Data Extracted From a Multicenter Clinical Trial.

Background: Although cellulitis is a relatively common skin infection, there remains uncertainty about management, particularly the length and route of antimicrobials required. Further information on the symptomatology and biomarker changes associated with cellulitis over time would guide clinicians and patients as to the expected natural history. Methods: We extracted data from a randomized clinical trial (NCT01876628) of clindamycin as adjunctive therapy in cellulitis to illustrate the evolution of local parameters (pain, swelling, local erythema, and warmth) and the resolution of biomarkers over time. Results: Data from 247 individuals with mild to moderate unilateral lower limb cellulitis, who attended at least 1 face-to-face interview following recruitment, were used to examine response dynamics. Although there was a local improvement in swelling, warmth, erythema, and pain by day 5 compared with baseline, some individuals still had evidence of local inflammation at 10 days. Most biomarkers demonstrated a return to normal by day 3, although the initial fall in albumin only returned to baseline by day 10. Conclusions: Although there was initial resolution, a significant number of individuals still had local symptoms persisting to day 10 and beyond. Clinicians can use these data to reassure themselves and their patients that ongoing local symptoms and signs after completion of antibiotic treatment do not indicate treatment failure or warrant extension of the initial antibiotic treatment or a change in antibiotic class or mode of administration.

Parapneumonic effusions related to Streptococcus pneumoniae: serotype and disease severity trends from 2006 to 2018 in Bristol, UK.

RATIONALE: Streptococcus pneumoniae epidemiology is changing in response to vaccination and some data suggest that empyema incidence is increasing. However, differences exist between the UK and US studies. We describe trends in the clinical phenotype of adult pneumococcal pleural infection, including simple parapneumonic effusions (SPE) in the pneumococcal conjugate vaccination (PCV) era. OBJECTIVES: To determine whether there were differences in pneumococcal disease presentation and severity associated with pleural infection. METHODS: A retrospective cohort study, all adults ≥16 years admitted to three large UK hospitals, 2006-2018 with pneumococcal disease. 2477 invasive pneumococcal cases were identified: 459 SPE and 100 pleural infection cases. Medical records were reviewed for each clinical episode. Serotype data were obtained from the UK Health Security Agency national reference laboratory. RESULTS: Incidence increased over time, including non-PCV-serotype disease. PCV7-serotype disease declined following paediatric PCV7 introduction, but the effect of PCV13 was less apparent as disease caused by the additional six serotypes plateaued with serotypes 1 and 3 causing such parapneumonic effusions from 2011 onwards.Patients with pleural infection had a median survival 468 days (95% CI 340 to 590) vs 286 days (95% CI 274 to 335) in those with SPE. Pleural infection associated with frank pus had lower 90-day mortality than pleural infection without pus (0% vs 29%, p<0.0001). 90-day mortality could be predicted by baseline increased RAPID (Renal, Age, Purulence, Infection source, and Dietary factors) score (HR 15.01, 95% CI 1.24 to 40.06, p=0.049). CONCLUSIONS: Pneumococcal infection continues to cause severe disease despite the introduction of PCVs. The predominance of serotype 1 and 3 in this adult UK cohort is in keeping with previous studies in paediatric and non-UK studies. Rising non-PCV serotype disease and limited impact of PCV13 on cases caused by serotypes 1 and 3 offset the reductions in adult pneumococcal parapneumonic effusion disease burden observed following the introduction of the childhood PCV7 programme.

UK consensus definitions for necrotising otitis externa: a Delphi study.

OBJECTIVE: To establish consensus definitions for necrotising otitis externa (NOE) to facilitate the diagnosis and exclusion of NOE in clinical practice and expedite future high-quality study of this neglected condition. DESIGN: The work comprised of a systematic review of the literature, five iterative rounds of consultation via a Delphi process and open discussion within the collaborative. An expert panel analysed the results to produce the final outputs which were shared with and endorsed by national specialty bodies. SETTING: Secondary care in the UK. PARTICIPANTS: UK clinical specialists practising in infection, ear nose and throat (ENT) surgery or radiology. MAIN OUTCOME MEASURES: Definitions and statements meeting the following criteria were accepted: (a) minimum of 70% of respondents in agreement or strong agreement with a definition/statement AND (b) <15% of respondents in disagreement or strong disagreement with a definition/statement. RESULTS: Seventy-four UK clinicians specialising in ENT, Infection and Radiology with a special interest in NOE took part in the work which was undertaken between 2019 and 2021. The minimum response rate for a Round was 76%. Consensus criteria for all proposed case definitions, outcome definitions and consensus statements were met in the fifth round. CONCLUSIONS: This work distills the clinical opinion of a large group of multidisciplinary specialists from across the UK to create practical definitions and statements to support clinical practice and research for NOE. This is the first step in an iterative process. Further work will seek to validate and test these definitions and inform their evolution.

Limited phylogenetic overlap between fluoroquinolone-resistant Escherichia coli isolated on dairy farms and those causing bacteriuria in humans living in the same geographical region.

BACKGROUND: Our primary aim was to test whether cattle-associated fluoroquinolone-resistant (FQ-R) Escherichia coli found on dairy farms are closely phylogenetically related to those causing bacteriuria in humans living in the same 50 × 50 km geographical region suggestive of farm-human sharing. Another aim was to identify risk factors for the presence of FQ-R E. coli on dairy farms. METHODS: FQ-R E. coli were isolated during 2017-18 from 42 dairy farms and from community urine samples. Forty-two cattle and 489 human urinary isolates were subjected to WGS, allowing phylogenetic comparisons. Risk factors were identified using a Bayesian regularization approach. RESULTS: Of 489 FQ-R human isolates, 255 were also third-generation-cephalosporin-resistant, with strong genetic linkage between aac(6')Ib-cr and blaCTX-M-15. We identified possible farm-human sharing for pairs of ST744 and ST162 isolates, but minimal core genome SNP distances were larger between farm-human pairs of ST744 and ST162 isolates (71 and 63 SNPs, respectively) than between pairs of isolates from different farms (7 and 3 SNPs, respectively). Total farm fluoroquinolone use showed a positive association with the odds of isolating FQ-R E. coli, while total dry cow therapy use showed a negative association. CONCLUSIONS: This work suggests that FQ-R E. coli found on dairy farms have a limited impact on community bacteriuria within the local human population. Reducing fluoroquinolone use may reduce the on-farm prevalence of FQ-R E. coli and this reduction may be greater when dry cow therapy is targeted to the ecology of resistant E. coli on the farm.

Streptococcus Pneumoniae septic arthritis in adults in Bristol and Bath, United Kingdom, 2006-2018: a 13-year retrospective observational cohort study.

Few studies on adult pneumococcal septic arthritis are sufficiently large enough to assess both epidemiological trends following routine pneumococcal immunization and clinical disease. With major shifts in serotypes causing invasive pneumococcal disease (IPD), we wanted to determine the clinical phenotype of adult septic arthritis caused by Streptococcus pneumoniae. We conducted a retrospective cohort study of pneumococcal infections in Bristol and Bath, UK, 2006-2018. We defined pneumococcal septic arthritis as adults with clinically-confirmed septic arthritis, with pneumococcus isolated from sterile-site culture or urinary antigen test positivity. Clinical records were reviewed for each patient in the cohort. Septic arthritis accounted for 1.7% of all IPD cases. 45 cases of adult pneumococcal septic arthritis occurred, with disease typically affecting older adults and those with underlying comorbidity. 67% patients had another focus of infection during their illness. 66% patients required increased care on discharge and 43% had reduced range of movement. In-hospital case fatality rate was 6.7%. One-year patient mortality was 31%. Currently most cases of adult pneumococcal septic arthritis are due to non-PCV13 serotypes which are associated with more severe disease. Non-PCV-13 serotypes had higher prevalence of concomitant pneumococcal infection at another site (73.7% versus 36.6%), increased intensive care or high-dependency unit requirement (32.4% versus 0%), and increased inpatient and 1-year case fatality rate (8.8% versus 0%, and 32.4% versus 27.4% respectively) compared to PCV-13 serotypes. Pneumococcal septic arthritis remains a small proportion of IPD. However, there is significant associated morbidity and mortality, and pneumococcal septic arthritis requires monitoring in coming years.

Trade-Offs between Antibacterial Resistance and Fitness Cost in the Production of Metallo-ß-Lactamases by Enteric Bacteria Manifest as Sporadic Emergence of Carbapenem Resistance in a Clinical Setting.

Meropenem is a clinically important antibacterial reserved for treatment of multiresistant infections. In meropenem-resistant bacteria of the family Enterobacterales, NDM-1 is considerably more common than IMP-1, despite both metallo-ß-lactamases (MBLs) hydrolyzing meropenem with almost identical kinetics. We show that blaNDM-1 consistently confers meropenem resistance in wild-type Enterobacterales, but blaIMP-1 does not. The reason is higher blaNDM-1 expression because of its stronger promoter. However, the cost of meropenem resistance is reduced fitness of blaNDM-1-positive Enterobacterales. In parallel, from a clinical case, we identified multiple Enterobacter spp. isolates carrying a plasmid-encoded blaNDM-1 having a modified promoter region. This modification lowered MBL production to a level associated with zero fitness cost, but, consequently, the isolates were not meropenem resistant. However, we identified a Klebsiella pneumoniae isolate from this same clinical case carrying the same blaNDM-1 plasmid. This isolate was meropenem resistant despite low-level NDM-1 production because of a ramR mutation reducing envelope permeability. Overall, therefore, we show how the resistance/fitness trade-off for MBL carriage can be resolved. The result is sporadic emergence of meropenem resistance in a clinical setting.

Antibiotic route and duration of therapy for cellulitis: data extracted from a multi-center clinical trial.

INTRODUCTION: Although cellulitis is a relatively common condition, there is uncertainty about the benefit of intravenous (IV) over oral (PO) antibiotic therapy, and the appropriate duration of treatment. METHODS: Data extracted from a clinical trial (NCT01876628) of antibiotic therapy for cellulitis were used to assess the association between the route of administration and duration of treatment, and clinical outcome. RESULTS: Of 323 patients with antibiotic data, 114 received some IV therapy. IV antibiotic therapy was preferred in those who had received antibiotics prior to trial entry (P < 0.001). Patients characterised as having more severe cellulitis (C-reactive protein > 100 mg/L, affected skin surface area > 5% or systemic inflammatory response syndrome score ≥ 1) were more likely to have had IV therapy. Those given only PO therapy were more likely to have improved at day 5 compared with those given at least a single dose of IV therapy (P = 0.015), and were as likely to be back to their normal activities at day 10 (P = 0.90), and day 30 (P = 0.86). There was no association between initial severity and the duration of antibiotic therapy given within the trial. There was no association between duration of antibiotic therapy and outcome as measured at day 10 and day 30. CONCLUSIONS: This study provides evidence that recovery is not associated with the route of antibiotic administration for patients with cellulitis of similar severity, or that a course length of > 5 days results in any additional benefit.

Urinary antigen testing for pneumococcal pneumonia: is there evidence to make its use uncommon in clinical practice?

Microbiological confirmation of pneumonia caused by Streptococcus pneumoniae remains challenging as culture from blood or pleural fluid is positive in only 15-30% cases. It was hoped that a commercially available urine antigen test would improve diagnosis and consequently patient care, with improved antimicrobial stewardship. Urine antigen testing for pneumococcal pneumonia is recommended in current British Thoracic Society guidelines, whilst the National Institute for Health and Care Excellence and The American Thoracic Society and the Infectious Diseases Society of America guidelines consider its usage. Urine antigen testing is therefore widely used in hospital medicine. The assay is noninvasive, simple and culture-independent, producing a result within 15 min. Whilst initial evidence suggested urine antigen testing had a high sensitivity, recently data have suggested the actual sensitivity is lower than expected, at approximately 60-65%. Evidence has also emerged indicating that clinicians infrequently rationalise antibiotics following positive urine antigen testing, with multiple publications evaluating the role of urine antigen testing in clinical care. Furthermore, urine antigen testing does not appear to lead to any cost saving or reduction in length of hospital stay. We therefore conclude that the pneumococcal urinary antigen test does not alter patient management and leads to no cost saving, and has a lower than expected accuracy. Therefore, it may be time to make its use uncommon in clinical practice.

Assessment of Antibiotic Treatment of Cellulitis and Erysipelas: A Systematic Review and Meta-analysis.

IMPORTANCE: The optimum antibiotic treatment for cellulitis and erysipelas lacks consensus. The available trial data do not demonstrate the superiority of any agent, and data are limited on the most appropriate route of administration or duration of therapy. OBJECTIVE: To assess the efficacy and safety of antibiotic therapy for non-surgically acquired cellulitis. DATA SOURCES: The following databases were searched to June 28, 2016: Cochrane Central Register of Controlled Trials (2016, issue 5), Medline (from 1946), Embase (from 1974), and Latin American and Caribbean Health Sciences Information System (LILACS) (from 1982). In addition, 5 trials databases and the reference lists of included studies were searched. Further searches of PubMed and Google Scholar were undertaken from June 28, 2016, to December 31, 2018. STUDY SELECTION: Randomized clinical trials comparing different antibiotics, routes of administration, and treatment durations were included. DATA EXTRACTION AND SYNTHESIS: For data collection and analysis, the standard methodological procedures of the Cochrane Collaboration were used. For dichotomous outcomes, the risk ratio and its 95% CI were calculated. A summary of findings table was created for the primary end points, adopting the GRADE approach to assess the quality of the evidence. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients cured, improved, recovered, or symptom-free or symptom-reduced at the end of treatment, as reported by the trial. The secondary outcome was any adverse event. RESULTS: A total of 43 studies with a total of 5999 evaluable participants, whose age ranged from 1 month to 96 years, were included. Cellulitis was the primary diagnosis in only 15 studies (35%), and in other studies the median (interquartile range) proportion of patients with cellulitis was 29.7% (22.9%-50.3%). Overall, no evidence was found to support the superiority of any 1 antibiotic over another, and antibiotics with activity against methicillin-resistant Staphylococcus aureus did not add an advantage. Use of intravenous antibiotics over oral antibiotics and treatment duration of longer than 5 days were not supported by evidence. CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, only low-quality evidence was found for the most appropriate agent, route of administration, and duration of treatment for patients with cellulitis; future trials need to use a standardized set of outcomes, including severity scoring, dosing, and duration of therapy.

An 11-year analysis of microbial keratitis in the South West of England using brain-heart infusion broth.

BACKGROUND: The aims of this study were to identify the organisms responsible for microbial keratitis, as identified by corneal scrape using brain-heart infusion broth, trends over time and antimicrobial sensitivities, over an 11-year period at two eye units in the South West of England; Bristol Eye Hospital and Royal United Hospital, Bath. METHODS: All corneal scrapes performed and sent for microbiological analysis between 4th April 2006 and 31st October 2017 at the two eye units were retrospectively reviewed. First-line treatment was monotherapy with levofloxacin 0.5% and second-line treatment was a combination of cefuroxime 5% and gentamicin 1.5%. Both direct and enrichment cultures were used. RESULTS: In total, 2614 corneal scrapes from 2116 patients (1082 female, mean age 47.7 ± 21.2 years) were identified. 38.1% (n = 996) were culture positive and 1195 organisms were cultured. In all, 91.6% were bacteria (69.4% were gram-positive, 30.6% gram-negative). Coagulase-negative Staphylococci (CoNS) were the most commonly cultured organism (n = 430). Pseudomonas aeruginosa was the most commonly identified gram-negative organism (n = 189). In total, 6.9% (n = 83) of organisms cultured were fungi. In all, 1.4% (n = 17) were acanthamoeba. There was no statistically significant trend in the organisms observed over the study period. Sensitivity testing confirmed reasonable sensitivity to the empiric antibiotics used in clinical practice. CONCLUSIONS: This is the first report on microbial keratitis trends in the South West of England. Virulent organisms were likely to be detected on direct culture, whereas low virulent organisms such as CoNS were more likely to be detected on enrichment alone. Antibiotic sensitivity testing confirmed fluoroquinolone monotherapy as appropriate first-line treatment.

The successful treatment of a multidrug-resistant Achromobacter xylosoxidans corneal ulcer with topical meropenem.

Microbial keratitis is a common corneal condition, with many known risk factors. We present a case of an 88-year-old female patient with a multidrug-resistant Achromobacter xylosoxidans corneal ulcer in a previously failed second penetrating keratoplasty, successfully managed with topical meropenem drops administered hourly around the clock, for five days preceding and then hourly day only, for five days following a repeat third penetrating keratoplasty. Topical meropenem 50 mg/mL was prepared by mixing a 500 mg vial of meropenem with 10 mL of sterile water with pharmacy advice that administration should be within an hour. To the best of our knowledge, this is the first report of the use of topical meropenem in the management of A.xylosoxidans keratitis. This case highlights the importance of the mean inhibitory concentrations for antibiotics when considering sensitivities. Topical meropenem may be a useful treatment option for multidrug-resistant bacterial corneal ulcers that are resistant to conventional therapy.

Prediction of Fluoroquinolone Susceptibility Directly from Whole-Genome Sequence Data by Using Liquid Chromatography-Tandem Mass Spectrometry To Identify Mutant Genotypes.

Fluoroquinolone resistance in Gram-negative bacteria is multifactorial, involving target site mutations, reductions in fluoroquinolone entry due to reduced porin production, increased fluoroquinolone efflux, enzymes that modify fluoroquinolones, and Qnr, a DNA mimic that protects the drug target from fluoroquinolone binding. Here we report a comprehensive analysis, using transformation and in vitro mutant selection, of the relative importance of each of these mechanisms for fluoroquinolone nonsusceptibility using Klebsiella pneumoniae as a model system. Our improved biological understanding was then used to generate 47 rules that can predict fluoroquinolone susceptibility in K. pneumoniae clinical isolates. Key to the success of this predictive process was the use of liquid chromatography-tandem mass spectrometry to measure the abundance of proteins in extracts of cultured bacteria, identifying which sequence variants seen in the whole-genome sequence data were functionally important in the context of fluoroquinolone susceptibility.

Adjunctive clindamycin for cellulitis: a clinical trial comparing flucloxacillin with or without clindamycin for the treatment of limb cellulitis.

OBJECTIVE: To compare flucloxacillin with clindamycin to flucloxacillin alone for the treatment of limb cellulitis. DESIGN: Parallel, double-blinded, randomised controlled trial. SETTING: Emergency department attendances and general practice referrals within 20 hospitals in England. INTERVENTIONS: Flucloxacillin, at a minimum of 500 mg 4 times per day for 5 days, with clindamycin 300 mg 4 times per day for 2 days given orally versus flucloxacillin given alone. MAIN OUTCOME MEASURES: The primary outcome was improvement at day 5. This was defined as being afebrile with either a reduction in affected skin surface temperature or a reduction in the circumference of the affected area. Secondary outcomes included resolution of systemic features, resolution of inflammatory markers, recovery of renal function, reduction in the affected area, decrease in pain, return to work or normal activities and the absence of increased side effects. RESULTS: 410 patients were included in the trial. No significant difference was seen in improvement at day 5 for flucloxacillin with clindamycin (136/156, 87%) versus flucloxacillin alone (140/172, 81%)-OR 1.55 (95% CI 0.81 to 3.01), p=0.174. There was a significant difference in the number of patients with diarrhoea at day 5 in the flucloxacillin with clindamycin allocation (34/160, 22%) versus flucloxacillin alone (16/176, 9%)-OR 2.7 (95% CI 1.41 to 5.07), p=0.002. There was no clinically significant difference in any secondary outcome measures. There was no significant difference in the number of patients stating that they had returned to normal activities at the day 30 interview in the flucloxacillin with clindamycin allocation (99/121, 82%) versus flucloxacillin alone (104/129, 81%)-adjusted OR 0.90 (95% CI 0.44 to 1.84). CONCLUSIONS: The addition of a short course of clindamycin to flucloxacillin early on in limb cellulitis does not improve outcome. The addition of clindamycin doubles the likelihood of diarrhoea within the first few days. TRIAL REGISTRATION NUMBER: NCT01876628, Results.

Antibiotic Prescribing in Primary Care and Antimicrobial Resistance in Patients Admitted to Hospital with Urinary Tract Infection: A Controlled Observational Pilot Study.

There is growing evidence that primary care prescribed antibiotics lead to antibiotic resistance in bacteria causing minor infections or being carried by asymptomatic adults, but little research to date has investigated links between primary care prescribed antibiotics and resistance among more serious infections requiring hospital care. Knowledge of these effects is likely to have a major influence on public expectations for, and primary care use of, antibiotics. This study aimed to assess the feasibility of recruiting symptomatic adult patients admitted to hospital with urinary infections and to link primary and secondary data information to investigate the relationship between primary care prescribed antibiotics and antimicrobial resistance in these patients. A microbiology database search of in patients who had submitted a urine sample identified 740 patients who were potentially eligible to take part in the study. Of these, 262 patients did not meet the eligibility criteria, mainly due to use of a urinary catheter (40%). Two-hundred and forty three patients could not be recruited as the nurse was unable to visit the patients prior to discharge, as they were too unwell. Eighty patients provided complete information. Results indicate that there is evidence that prior antibiotic use is associated with resistant infections in hospital patients. A fully powered study, conducted using routinely collected data is proposed to fully clarify the precision of the association.

Comparison of a frozen human foreskin fibroblast cell assay to an enzyme immunoassay and toxigenic culture for the detection of toxigenic Clostridium difficile.

This study set out to validate the Hs27 ReadyCell assay (RCCNA) as an alternative CCNA method compared against a commonly used commercial enzyme immunoassay (EIA) method and toxigenic culture (TC) reference standard. A total of 860 samples were identified from those submitted to the Health Protection Agency microbiology laboratories over a 30-week period. RCCNA performed much better than EIA when using TC as a gold standard, with sensitivities of 90.8% versus 78.6% and positive predictive value of 87.3% to 81.9%, respectively. The Hs27 Human Foreskin Fibroblast ReadyCells are an easy-to-use and a sensitive CCNA method for the detection of toxigenic Clostridium difficile directly from stool. A turnaround time of up to 48 h for a negative result and possible need for repeat testing make it an unsuitable method to be used in most clinical laboratory setting.