Objective Evidence for necrotising otitis externa (NOE) diagnosis and management is limited, and outcome reporting is heterogeneous. International best practice guidelines were used to develop consensus diagnostic criteria and a core outcome set (COS).Methods The study was pre-registered on the Core Outcome Measures in Effectiveness Trials (COMET) database. Systematic literature review identified candidate items. Patient-centred items were identified via a qualitative study. Items and their definitions were refined by multidisciplinary stakeholders in a two-round Delphi exercise and subsequent consensus meeting.Results The final COS incorporates 36 items within 12 themes: Signs and symptoms; Pain; Advanced Disease Indicators; Complications; Survival; Antibiotic regimes and side effects; Patient comorbidities; Non-antibiotic treatments; Patient compliance; Duration and cessation of treatment; Relapse and readmission; Multidisciplinary team management. Consensus diagnostic criteria include 12 items within 6 themes: Signs and symptoms (oedema, otorrhoea, granulation); Pain (otalgia, nocturnal otalgia); Investigations (microbiology [does not have to be positive], histology [malignancy excluded], positive CT and MRI); Persistent symptoms despite local and/or systemic treatment for at least two weeks; At least one risk factor for impaired immune response; Indicators of advanced disease (not obligatory but mut be reported when present at diagnosis). Stakeholders were unanimous that there is no role for secondary, graded, or optional diagnostic items. The consensus meeting identified themes for future research.Results The final COS incorporates 36 items within 12 themes: Signs and symptoms; Pain; Advanced Disease Indicators; Complications; Survival; Antibiotic regimes and side effects; Patient comorbidities; Non-antibiotic treatments; Patient compliance; Duration and cessation of treatment; Relapse and readmission; Multidisciplinary team management. Consensus diagnostic criteria include 12 items within 6 themes: Signs and symptoms (oedema, otorrhoea, granulation); Pain (otalgia, nocturnal otalgia); Investigations (microbiology [does not have to be positive], histology [malignancy excluded], positive CT and MRI); Persistent symptoms despite local and/or systemic treatment for at least two weeks; At least one risk factor for impaired immune response; Indicators of advanced disease (not obligatory but mut be reported when present at diagnosis). Stakeholders were unanimous that there is no role for secondary, graded, or optional diagnostic items. The consensus meeting identified themes for future research.Conclusion The adoption of consensus-defined diagnostic criteria and COS facilitates standardised research reporting and robust data synthesis. Inclusion of patient and professional perspectives ensures best practice stakeholder engagement.

Tularemia, caused by Francisella tularensis, is not known to occur in the United Kingdom. We report a case of tularemia diagnosed in July 2023 in a UK patient with no travel in the 6 weeks before symptom onset. We describe the subsequent multiagency investigation into possible routes of acquisition.

OBJECTIVES:Acute otitis media (AOM) and otitis externa (OE) are common ear infections which may warrant antibiotic therapy. For many infections, there is a rise in antimicrobial resistance, which is associated with treatment failure, morbidity, prolonged hospitalisation and mortality. This study aimed to identify longitudinal changes in microbiology and antimicrobial resistance in aural swabs taken from patients with AOM or OE.DESIGN:Retrospective observational analysis.SETTING:Aural samples processed at Manchester Medical Microbiology Partnership Laboratories between January 2008 and December 2018 were analysed to record organism isolated and antimicrobial sensitivity.PARTICIPANTS:Individual aural swabs from 7200 patients.MAIN OUTCOME MEASURES:Changes in the incidence of organisms and antimicrobial resistance between two time periods (2008-2012 and 2013-2018) were compared using the chi-squared test (alpha = 0.05).RESULTS:From 7200 swabs, 2879 (40%) were from children. The most frequently isolated organisms were Staphylococcus aureus (25%), Pseudomonas aeruginosa (24.4%), yeast (9.1%), mixed anaerobes (7.9%) and Haemophilus influenzae (6.1%). In children aged 0-4 years, H. influenzae had particularly high incidence (25%). Overall, the incidence of P. aeruginosa decreased significantly with time (p = 0.05). Isolates displaying resistance to one or more antimicrobial agents increased significantly in number in the second time period for P. aeruginosa (p = 0.04) and H. influenzae (p =  0.03). There was increased resistance to amoxicillin for P. aeruginosa (p = 0.01) and to erythromycin for H. influenzae (p < 0.01).CONCLUSION:Variations in type and frequency of organisms with increasing age likely result from differences in the preponderance of AOM compared to OE in children versus adults. We found increasing antimicrobial resistance for two organisms commonly isolated from AOM and OE infections, suggesting that aspects of current UK treatment practices and national recommendations may need to be revised.

Here we describe a retrospective clinical evaluation of the QIAGEN artus® SARS-CoV-2 Prep&Amp UM RT-PCR assay that detects SARS-CoV-2 RNA without the need for a nucleic acid eluate extraction procedure. Using Roche SARS-CoV-2 RT-PCR on the cobas® 8800 platform as a reference standard, a total of 225 confirmed SARS-CoV-2 positive and 320 negative nasopharyngeal swabs in viral transport media, were used to evaluate the artus® assay. Using the RT-PCR cycle threshold as a semi-quantitative marker of viral load, an assessment of over 370,000 SARS-CoV-2 RT-PCR positive results was used in the design of the reference positive specimen cohort. The viral load of all reference positive specimens used in the evaluation was a unique and accurate representation of the range and levels of SARS-CoV-2 positivity observed over a 13-month period of the COVID-19 pandemic. The artus® RT-PCR detects the presence of SARS-CoV-2 RNA, an internal control, and the human RNase P gene to ensure specimen quality. The diagnostic sensitivity of artus® was 92.89% with a specificity of 100%. To assess the analytical sensitivity, a limit of detection was performed using the 1st WHO NIBSC SARS-CoV-2 international standard, recording a 95% LOD of 1.1 × 103 IU/ml. The total invalid rate of specimens was 7.34% due to a lack of detectable RNase P (Ct >35). The artus® SARS-CoV-2 Prep&Amp UM RT-PCR assay is a new rapid RT-PCR assay, which may be considered to produce acceptable levels of diagnostic sensitivity and specificity whilst potentially halving the laboratory processing time.

Objectives: To assess whether resistance estimates obtained from sentinel surveillance for antimicrobial resistance (AMR) in community-acquired urinary tract infections (UTIs) differ from routinely collected laboratory community UTI data. Methods: All patients aged >= 18 years presenting to four sentinel general practices with a suspected UTI, from 13 November 2017 to 12 February 2018, were asked to provide urine specimens for culture and susceptibility. Specimens were processed at the local diagnostic laboratory. Antibiotic susceptibility testing was conducted using automated methods. We calculated the proportion of Escherichia coli isolates that were non-susceptible (according to contemporaneous EUCAST guidelines) to trimethoprim, nitrofurantoin, cefalexin, ciprofloxacin and amoxicillin/clavulanic acid, overall and by age group and sex, and compared this with routine estimates. Results: Sentinel practices submitted 740 eligible specimens. The specimen submission rate had increased by 28 specimens per 1000 population per year (95% CI 21-35). Uropathogens were isolated from 23% (169/740) of specimens; 67% were E. coli (113/169). Non-susceptibility of E. coli to trimethoprim was 28.2% (95% CI 20.237.7) on sentinel surveillance (33.4%; 95% CI 29.5-37.6 on routine data) and to nitrofurantoin was 0.9% (95% CI 0-5.7) (1.5%; 95% CI 0.7-3.0 on routine data). Conclusions: Routine laboratory data resulted in a small overestimation in resistance (although the difference was not statistically significant) and our findings suggest that it provides an adequate estimate of non-susceptibility to key antimicrobials in community-acquired UTIs in England. This study does not support the need for ongoing local sentinel surveillance.

Introduction Serious PCP infections are known to develop in immuno-compromised individuals. The risk and risk factors in patients with retroviral infections is well established but the data in HSCT recipients is scanty. With use of newer methods of graft versus host disease (GVHD) prevention like alemtuzumab and reduced intensity transplants (RIC) this analysis was undertaken to establish the incidence and identify the risk factors for PCP infections in HSCT patients. Methods 1129 patients (M: 732, F: 397; median age: 49yr., range: 14:73) undergoing 1149 HSCT procedures from 2002 to 2012 were analyzed (20 had more than 1 procerdure). HSCT type was autologous (n=786) or allogeneic (n=363) for malignacies [Ac. Leukaemia (n=235), chr. leukaemia (n=38), lymphoma (n=390), myeloma (n=424), aplastic anaemia (n=8) and other conditions (n= 34)]. Patients either had HSCT during this period or were alive post HSCT and at risk of PCP during the same time frame. Patients were evaluated for routine bacteriology, PCP and respiratory viruses using PCR if they had clinical signs and symptoms of respiratory infection. All patients received PCP prophylaxis (Co-trimoxazole prefereed; azithromycin, pentamidine and dapsone in cases intolerant to co-trimoxazole). Cummulative incidence rate was calculated using competing risk analysis with death as competing risk factor. Estimate of incidence was calculated per period of prophylactic drug used in cases where there was change in the medication (total 1930 spells in 1129 patients following 1149 procedures). Risk factors were analysed for the entire group and also separately for allograft and autograft population. Results In allograft group, donor was sibling (n=162) or MUD (n=201). Conditioning was full intensity (n=154) or reduced intensity (n=210). Alemtuzumab was used in conditioning in 167 procedures, ATG in 23 and TBI in 208 cases (2Gy as RIC in 26). Stem cell source was PBSC (n=1050), BM (n=78), both (n=20) and 1 had cord blood. In 275/363 (76%) donor recipient pairs where CMV status was recorded, at least one of the pair was positive in 140/275 (51%) cases. 32 patients (2.8%) developed symptomatic, PCR positive PCP infection (5yr. risk 1.02%, 95% CI: 1.01-1.03%, SE: +0.004). In all but 4 cases PCP was the only identified pathogen (4 had respiratory virus in addition to PCP). Median time to develop PCP was 765 days (range: 70-2066 days). In univariate analysis, risk of PCP was not influenced by gender (M:24/1304 vs. F:8/626, p=0.33), age at HSCT (<49 yr.: 11/841 vs. >49yr.: 21/1089, p=0.21), CMV status of patient (Neg: 14/ 974 vs. Pos: 16/908, p=0.70), risk category of disease (Good: 24/1401, Poor: 8/438, p=0.33), or primary diagnosis (AL: 14/539, MM: 6/707, rest: 12/684, p=0.08). The risk was significantly higher with allograft (25/887 vs. 7/1043, p<0.0001), RIC (RIC: 22/541, Full: 3/350, Auto: 7/1039, p=0.0001) and use of alemtuzumab (19/388 vs. ATG: 1/69 vs. rest: 12/1473, p=0.0001). 11/537 episodes developed when patients were off PCP prophylaxis but risk was significantly higher during the period of azithromycin as PCP prophylaxis (17/321, vs. Co-trimoxazole: 3/844 vs. Pentamidine: 1/222, p=0.0001). Mutivariate analysis for the entire group showed Azithromycin use (HR: 1.6, 95% CI: 1.14-2.3, p=0.007) and RIC (HR: 3.1, 95% CI: 1.2-7.9, p=0.019) to be independently associated with risk of PCP. In autograft group, there was trend towards higher incidence with Azithromycin prophylaxis (HR: 1.74, 95% CI: 0.91-3.0, p=0.073) while in allograft group use of azithromycin (HR: 1.67, 95% CI: 1.1-2.5, p=0.013) and RIC (HR: 5.14, 95% CI: 1.2-22.1, p=0.028) were independently associated with higher risk of PCP. Maximum risk of reactivation was in patients receiving alemtuzumab conditioned RIC allograft during azithromycin prophylaxis. Out of the 11 who were off prophylaxis, 4 had stopped azithromycin in prior 6 weeks. There was no relation to lymphocyte recovery and PCP infection in allograft patients. Conclusion Even though the overall risk of PCP is small in HSCT patients, there is a significantly higher risk in alemtuzumab conditioned RIC allograft. Infections seem to develop late and azithromycin as prophylaxis may be sub-optimal in this group. Future studies need to determine the duration of PCP prophylaxis in RIC allografts. Disclosures: Cavet: Lilly: Membership on an entity’s Board of Directors or advisory committees; Celgene: Consultancy, Honoraria.

Abstract Introduction E.coli are one of the commonest organisms causing blood stream infections (BSI) in oncology and hematology patients. With the growing incidence of extended spectrum beta lactam resistance (ESBL) this single centre retrospective analysis was undertaken to identify the predictors of outcome of E.coli septicaemia in hemato-oncology patients. From 2002 to 2012, 1089 patients with haematological malignancies had 3528 episodes of BSI and of them 257 in 177 patients (7.3%) were with E.coli. Methods 177 (M: 114, F: 63; median age: 52yr., range: 16-89) patients with haematological malignancies treated from April 2002 to April 2012 were included in analysis. Underlying diagnosis was AML (n=47), ALL (n=23), Lymphoma (n=73), MDS (n=6), myeloma (n=19) or other conditions (n=9). There were 257 episodes of E.coli septicaemia in 177 patients and each episode was analysed as an individual event. Of the 257 episodes, 34 (13%) developed following stem cell transplant (Allo=18, Auto=16), 85 (33%) following intensive chemotherapy, 55 (21%) after non-intensive therapy, 47 (18%) after various other forms of chemotherapy and 36 (14%) did not have any therapy prior to BSI. E.coli were isolated from peripheral blood (PB, n=112, 44%), central venous access (Line, n=130, 51%) or unspecified source (NK, n=15, 6%). At the time of developing E.coli BSI, ANC was below 0.5 in 136 cases (53%), 167 (65%) had platelet count below 100, 78 (30%) had BUN above 10, 69(27%) had creatinine above 120, 74(29%) had serum bilirubin above 34 and 129 (50%) had trans-aminitis. E.coli BSI increased significantly from year 2007 onwards (110/2073, 5% vs. 137/1455, 9%; p=0.0001). Mortality within 30 days of BSI with E.coli was used as a marker to estimate the impact of the event. 28 of 257 episodes (10.9%) resulted in death within 30 days. In univariate analysis, mortality was significantly higher with age above 45yr. (26/185 vs. 2/72, p=0.01), GGT more than 50 (25/180 vs. 3/77, p=0.02), BUN above 10 (17/78 vs. 11/179, p=0.0002), creatinine above 120 (12/22 vs. 16/188, p=0.035) and PB as source of BSI (18/112 vs. 10/145, p=0.02). In Cox multivariate analysis, PB as source (HR: 2.2, 95% CI: 1.0-4.9, p=0.048), GGT above 50 (HR: 4.4, 95% CI: 1.2-15.5, p=0.022), age above 45 yr. (HR: 4.5, 95% CI: 1.1-19.6, p=0.04) and creatinine above 120 (HR: 3.1, 95% CI: 1.1-8.7, p=0.03) were independently associated with mortality within 30 days of E.coli BSI. Mortality increased significantly with the number of risk factors [0-1: 2/68 (3%), 2-3: 22/140 (16%), 4: 8/25 (32%), HR: 3.9, 95% CI: 2.0-7.4, p=0.0001]. 16% of E.coli were resistant to beta lactam antibiotics but the number was too small to assess the impact on mortality. HSCT was not associated with increased mortality. Conclusion E.coli BSI are associated with significant mortality that is not associated with underlying diagnosis but with the age and associated organ dysfunction. Continued surveillance is needed to assess the impact of ESBL incidence, status and its clinical significance. Disclosures: Cavet: Celgene: Consultancy, Honoraria; Eli Lilly: Honoraria.