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1.
Age Ageing ; 53(7)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-39003235

RESUMO

BACKGROUND: Hybrid SARS-CoV-2 immunity may provide longer duration protection against severe SARS-CoV-2 infection and hospitalisation than purely vaccine-derived immunity. Older adults represent a high-risk group for severe disease, yet available data is skewed towards younger adults. METHODS: A prospective longitudinal study at a large London long-term care facility (LTCF) was conducted from March 2020 to April 2022 to assess the effect of hybrid versus vaccine-only immunity on SARS-CoV-2 infection in older adults during Omicron variant dominance. Hybrid immunity was assessed by a combination of SARS-CoV-2 polymerase chain reaction testing weekly (asymptomatic screening) and as required (symptomatic testing), as well as serial SARS-CoV-2 serology. RESULTS: 280 participants (median age 82 yrs, IQR 76-88 yrs; 95.4% male) were followed up. 168/280 (60%) had evidence of hybrid immunity prior to the Omicron variant wave. Participants with hybrid immunity had substantially lower odds of acquiring COVID-19 infection during the Omicron wave compared to those with vaccine-only immunity (unadjusted odds ratio 0.26, 95% CI 0.14-0.47, chi-squared P < .0001). Participants with hybrid immunity had an odds ratio of 0.40 (0.19-0.79) for asymptomatic infection and 0.15 (0.06-0.34) for symptomatic infection (Likelihood ratio test, P < .0001). DISCUSSION: Our data highlight potential opportunities to target ongoing booster vaccination campaigns for those most at risk of severe infection. Reporting of data in older adults will be of particular value to examine the effect of hybrid immunity as new variants continue to emerge and vaccination strategies evolve.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , Masculino , Idoso , Feminino , Idoso de 80 Anos ou mais , SARS-CoV-2/imunologia , Estudos Prospectivos , Estudos Longitudinais , Vacinas contra COVID-19/imunologia , Londres/epidemiologia , Fatores de Risco
2.
Bull World Health Organ ; 101(8): 501-512F, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37529028

RESUMO

Objective: To assess how national antimicrobial susceptibility data used to inform national action plans vary across surveillance platforms. Methods: We identified available open-access, supranational, interactive surveillance platforms and cross-checked their data in accordance with the World Health Organization's (WHO's) Data Quality Assurance: module 1. We compared platform usability and completeness of time-matched data on the antimicrobial susceptibilities of four blood isolate species: Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus pneumoniae from WHO's Global Antimicrobial Resistance and Use Surveillance System, European Centre for Disease Control's (ECDC's) network and Pfizer's Antimicrobial Testing Leadership and Surveillance database. Using Bland-Altman analysis, paired t-tests, and Wilcoxon signed-rank tests, we assessed susceptibility data and number of isolate concordances between platforms. Findings: Of 71 countries actively submitting data to WHO, 28 also submit to Pfizer's database; 19 to ECDC; and 16 to all three platforms. Limits of agreement between WHO's and Pfizer's platforms for organism-country susceptibility data ranged from -26% to 35%. While mean susceptibilities of WHO's and ECDC's platforms did not differ (bias: 0%, 95% confidence interval: -2 to 2), concordance between organism-country susceptibility was low (limits of agreement -18% to 18%). Significant differences exist in isolate numbers reported between WHO-Pfizer (mean of difference: 674, P-value: < 0.001, and WHO-ECDC (mean of difference: 192, P-value: 0.04) platforms. Conclusion: The considerable heterogeneity of nationally submitted data to commonly used antimicrobial resistance surveillance platforms compromises their validity, thus undermining local and global antimicrobial resistance strategies. Hence, we need to understand and address surveillance platform variability and its underlying mechanisms.


Assuntos
Antibacterianos , Anti-Infecciosos , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana
3.
BMC Infect Dis ; 22(1): 959, 2022 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-36566229

RESUMO

BACKGROUND: European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint criteria for methicillin-susceptible Staphylococcus aureus (MSSA) treatment with ceftriaxone are based upon high dose (4 g/day) rather than standard dose (2 g/day) posology. This is particularly relevant for invasive infections, and for patients managed via Outpatient Parenteral Antimicrobial Therapy (OPAT), but may result in increased drug toxicity. We quantified the incidence of neutropenia, thrombocytopenia and raised liver enzymes between standard and high dose ceftriaxone in adult patients. METHOD: Adult outpatients prescribed ≥ 7 days of ceftriaxone therapy were identified, and clinical, pharmacological, and laboratory parameters extracted from electronic health records between May 2021 and December 2021. Incidence and median time to haematological and hepto-toxicity were analysed. Univariate odds ratios were calculated for neutrophil count and ALT levels with 95% confidence level and Chi squared/Fisher's exact test used to identify statistical significance. RESULTS: Incidence of neutropenia was comparable between both groups; 8/47 (17%) in the 2 g group vs 6/39 (15.4%) in the 4 g group (OR 0.89 (95% CI 0.26-2.63), p > 0.999). Median time to neutropenia was 12 and 17 days in the 2 g and 4 g groups respectively. Thrombocytopenia was observed in 0/47 in the 2 g group compared with 3/39 (7.7%) in the 4 g group (p 0.089). Median time to thrombocytopenia was 7 days in the 4 g group. Elevated liver enzymes did not clearly correlate with ceftriaxone dosing; present in 5/47 (10.6%) and 2/39 (5.1%) for 2 g and 4 g respectively (OR 0.45 (95% CI 0.87-2.36), p 0.448). Treatment cessation due to any adverse effect was similar between both groups 2/47 (4.3%) for 2 g and 3/39 (7.7%) for 4 g (OR 1.86 (95% CI 0.36-10.92), p 0.655). CONCLUSIONS: Increased adverse effects with 4 g (over 2 g) daily dosing of ceftriaxone was not observed in an OPAT population. However absolute development of haematological and liver dyscrasias was appreciable-monitoring of liver function and full blood count in patients receiving prolonged ceftriaxone is indicated irrespective of dosing.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neutropenia , Trombocitopenia , Adulto , Humanos , Ceftriaxona/uso terapêutico , Antibacterianos/efeitos adversos , Estudos Retrospectivos , Assistência Ambulatorial , Neutropenia/induzido quimicamente , Fígado , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia , Trombocitopenia/tratamento farmacológico
4.
Clin Exp Dermatol ; 47(12): 2150-2158, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36040400

RESUMO

Panton-Valentine leucocidin (PVL) is a virulence factor produced by certain strains of Staphylococcus aureus (SA). Through its cytolytic action on the cell membranes of human polymorphonuclear neutrophils, PVL causes a range of pathologies collectively known as PVL-SA disease. The hallmark clinical signs of PVL-SA are recurrent boils and necrotizing skin and soft tissue infections (SSTIs) in otherwise healthy patients; however, it can lead to more severe and invasive presentations, including necrotizing haemorrhagic pneumonia, necrotizing fasciitis and purpura fulminans. Young adults with minimal previous exposure to healthcare settings tend to be at highest risk for acquiring PVL-SA disease, with close physical contact playing a central role in disease transmission. The prevalence of PVL-SA varies globally; however, this is often underestimated owing to a lack of routine PVL testing. In the UK, PVL-positive SA isolates have been rising over the past decade alongside an increasing prevalence of multidrug resistance in larger cities. This review article aims to raise awareness of the PVL toxin, to aid clinicians with diagnostic pointers and to provide guidance with treatment, with an emphasis on the need for further population-based studies.


Assuntos
Infecções dos Tecidos Moles , Infecções Estafilocócicas , Humanos , Exotoxinas/metabolismo , Leucocidinas/metabolismo , Prevalência , Infecções dos Tecidos Moles/epidemiologia , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus
5.
Euro Surveill ; 27(4)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35086612

RESUMO

IntroductionImmunoassays targeting different SARS-CoV-2-specific antibodies are employed for seroprevalence studies. The degree of variability between immunoassays targeting anti-nucleocapsid (anti-NP; the majority) vs the potentially neutralising anti-spike antibodies (including anti-receptor-binding domain; anti-RBD), particularly in mild or asymptomatic disease, remains unclear.AimsWe aimed to explore variability in anti-NP and anti-RBD antibody detectability following mild symptomatic or asymptomatic SARS-CoV-2 infection and analyse antibody response for correlation with symptomatology.MethodsA multicentre prospective cross-sectional study was undertaken (April-July 2020). Paired serum samples were tested for anti-NP and anti-RBD IgG antibodies and reactivity expressed as binding ratios (BR). Multivariate linear regression was performed analysing age, sex, time since onset, symptomatology, anti-NP and anti-RBD antibody BR.ResultsWe included 906 adults. Antibody results (793/906; 87.5%; 95% confidence interval: 85.2-89.6) and BR strongly correlated (ρ = 0.75). PCR-confirmed cases were more frequently identified by anti-RBD (129/130) than anti-NP (123/130). Anti-RBD testing identified 83 of 325 (25.5%) cases otherwise reported as negative for anti-NP. Anti-NP presence (+1.75/unit increase; p < 0.001), fever (≥ 38°C; +1.81; p < 0.001) or anosmia (+1.91; p < 0.001) were significantly associated with increased anti-RBD BR. Age (p = 0.85), sex (p = 0.28) and cough (p = 0.35) were not. When time since symptom onset was considered, we did not observe a significant change in anti-RBD BR (p = 0.95) but did note decreasing anti-NP BR (p < 0.001).ConclusionSARS-CoV-2 anti-RBD IgG showed significant correlation with anti-NP IgG for absolute seroconversion and BR. Higher BR were seen in symptomatic individuals, particularly those with fever. Inter-assay variability (12.5%) was evident and raises considerations for optimising seroprevalence testing strategies/studies.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Anticorpos Antivirais , Formação de Anticorpos , Estudos Transversais , Humanos , Imunoglobulina G , Londres , Estudos Prospectivos , Estudos Soroepidemiológicos , Glicoproteína da Espícula de Coronavírus
6.
BMC Infect Dis ; 21(1): 556, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34116643

RESUMO

BACKGROUND: We investigated for change in blood stream infections (BSI) with Enterobacterales, coagulase negative staphylococci (CoNS), Streptococcus pneumoniae, and Staphylococcus aureus during the first UK wave of SARS-CoV-2 across five London hospitals. METHODS: A retrospective multicentre ecological analysis was undertaken evaluating all blood cultures taken from adults from 01 April 2017 to 30 April 2020 across five acute hospitals in London. Linear trend analysis and ARIMA models allowing for seasonality were used to look for significant variation. RESULTS: One hundred nineteen thousand five hundred eighty-four blood cultures were included. At the height of the UK SARS-CoV-2 first wave in April 2020, Enterobacterales bacteraemias were at an historic low across two London trusts (63/3814, 1.65%), whilst all CoNS BSI were at an historic high (173/3814, 4.25%). This differed significantly for both Enterobacterales (p = 0.013), CoNS central line associated BSIs (CLABSI) (p < 0.01) and CoNS non-CLABSI (p < 0.01), when compared with prior periods, even allowing for seasonal variation. S. pneumoniae (p = 0.631) and S. aureus (p = 0.617) BSI did not vary significant throughout the study period. CONCLUSIONS: Significantly fewer than expected Enterobacterales BSI occurred during the UK peak of the COVID-19 pandemic; identifying potential causes, including potential unintended consequences of national self-isolation public health messaging, is essential. High rates of CoNS BSI, with evidence of increased CLABSI, but also likely contamination associated with increased use of personal protective equipment, may result in inappropriate antimicrobial use and indicates a clear area for intervention during further waves.


Assuntos
Bacteriemia , Bactérias , COVID-19 , Adulto , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Bactérias/classificação , Bactérias/isolamento & purificação , Humanos , Pandemias , Estudos Retrospectivos , Atenção Secundária à Saúde , Reino Unido
7.
Mycoses ; 64(4): 394-404, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33314345

RESUMO

Outbreaks of fungal infections due to emerging and rare species are increasingly reported in healthcare settings. We investigated a pseudo-outbreak of Rhinocladiella similis in a bronchoscopy unit of a tertiary care teaching hospital in London, UK. We aimed to determine route of healthcare-associated transmission and prevent additional infections. From July 2018 through February 2019, we detected a pseudo-outbreak of R. similis isolated from bronchoalveolar lavage (BAL) fluid samples collected from nine patients who had undergone bronchoscopy in a multispecialty teaching hospital, during a period of 8 months. Isolates were identified by MALDI-TOF mass spectrometry. Antifungal susceptibility testing was performed by EUCAST broth microdilution. To determine genetic relatedness among R. similis isolates, we undertook amplified fragment length polymorphism analysis. To determine the potential source of contamination, an epidemiological investigation was carried out. We reviewed patient records retrospectively and audited steps taken during bronchoscopy as well as the subsequent cleaning and decontamination procedures. Fungal cultures were performed on samples collected from bronchoscopes and automated endoscope washer-disinfector systems. No patient was found to have an infection due to R. similis either before or after bronchoscopy. One bronchoscope was identified to be used among all affected patients with positive fungal cultures. Physical damage was found in the index bronchoscope; however, no fungus was recovered after sampling of the affected scope or the rinse water of automated endoscope washer-disinfectors. Use of the scope was halted, and, during the following 12-month period, Rhinocladiella species were not isolated from any BAL specimen. All pseudo-outbreak isolates were identified as R. similis with high genetic relatedness (>90% similarity) on ALFP analysis. The study emphasises the emergence of a rare and uncommon black yeast R. similis, with reduced susceptibility to echinocandins, in a bronchoscope-related pseudo-outbreak with a potential water-related reservoir. Our findings highlight the importance of prolonged fungal culture and species-level identification of melanised yeasts isolated from bronchoscopy samples. Possibility of healthcare-associated transmission should be considered when R. similis is involved in clinical microbiology samples.


Assuntos
Ascomicetos/isolamento & purificação , Broncoscópios/microbiologia , Hospitais de Ensino/estatística & dados numéricos , Micoses/epidemiologia , Atenção Terciária à Saúde/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/farmacologia , Ascomicetos/química , Ascomicetos/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/microbiologia , Broncoscopia , Infecção Hospitalar/microbiologia , Surtos de Doenças , Contaminação de Equipamentos , Feminino , Humanos , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Micoses/transmissão , Estudos Retrospectivos
8.
J Med Internet Res ; 22(8): e20259, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32735549

RESUMO

BACKGROUND: The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is a public health emergency and the case fatality rate in the United Kingdom is significant. Although there appear to be several early predictors of outcome, there are no currently validated prognostic models or scoring systems applicable specifically to patients with confirmed SARS-CoV-2. OBJECTIVE: We aim to create a point-of-admission mortality risk scoring system using an artificial neural network (ANN). METHODS: We present an ANN that can provide a patient-specific, point-of-admission mortality risk prediction to inform clinical management decisions at the earliest opportunity. The ANN analyzes a set of patient features including demographics, comorbidities, smoking history, and presenting symptoms and predicts patient-specific mortality risk during the current hospital admission. The model was trained and validated on data extracted from 398 patients admitted to hospital with a positive real-time reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2. RESULTS: Patient-specific mortality was predicted with 86.25% accuracy, with a sensitivity of 87.50% (95% CI 61.65%-98.45%) and specificity of 85.94% (95% CI 74.98%-93.36%). The positive predictive value was 60.87% (95% CI 45.23%-74.56%), and the negative predictive value was 96.49% (95% CI 88.23%-99.02%). The area under the receiver operating characteristic curve was 90.12%. CONCLUSIONS: This analysis demonstrates an adaptive ANN trained on data at a single site, which demonstrates the early utility of deep learning approaches in a rapidly evolving pandemic with no established or validated prognostic scoring systems.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Idoso , Idoso de 80 Anos ou mais , Inteligência Artificial , COVID-19 , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Prognóstico , Curva ROC , SARS-CoV-2 , Reino Unido
9.
BMC Med Inform Decis Mak ; 20(1): 299, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213435

RESUMO

BACKGROUND: Accurately predicting patient outcomes in Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could aid patient management and allocation of healthcare resources. There are a variety of methods which can be used to develop prognostic models, ranging from logistic regression and survival analysis to more complex machine learning algorithms and deep learning. Despite several models having been created for SARS-CoV-2, most of these have been found to be highly susceptible to bias. We aimed to develop and compare two separate predictive models for death during admission with SARS-CoV-2. METHOD: Between March 1 and April 24, 2020, 398 patients were identified with laboratory confirmed SARS-CoV-2 in a London teaching hospital. Data from electronic health records were extracted and used to create two predictive models using: (1) a Cox regression model and (2) an artificial neural network (ANN). Model performance profiles were assessed by validation, discrimination, and calibration. RESULTS: Both the Cox regression and ANN models achieved high accuracy (83.8%, 95% confidence interval (CI) 73.8-91.1 and 90.0%, 95% CI 81.2-95.6, respectively). The area under the receiver operator curve (AUROC) for the ANN (92.6%, 95% CI 91.1-94.1) was significantly greater than that of the Cox regression model (86.9%, 95% CI 85.7-88.2), p = 0.0136. Both models achieved acceptable calibration with Brier scores of 0.13 and 0.11 for the Cox model and ANN, respectively. CONCLUSION: We demonstrate an ANN which is non-inferior to a Cox regression model but with potential for further development such that it can learn as new data becomes available. Deep learning techniques are particularly suited to complex datasets with non-linear solutions, which make them appropriate for use in conditions with a paucity of prior knowledge. Accurate prognostic models for SARS-CoV-2 can provide benefits at the patient, departmental and organisational level.


Assuntos
Infecções por Coronavirus , Aprendizado Profundo , Pandemias , Pneumonia Viral , Algoritmos , Betacoronavirus , COVID-19 , Feminino , Humanos , Londres , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Redes Neurais de Computação , Modelos de Riscos Proporcionais , SARS-CoV-2
16.
J Infect ; 89(3): 106224, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38986748

RESUMO

Severe burns are a major component of conflict-related injuries and can result in high rates of mortality. Conflict and disaster-related severe burn injuries present unique challenges in logistic, diagnostic and treatment options, while wider conflict is associated with driving local antimicrobial resistance. We present a targeted review of available literature over the last 10 years on the use of systemic antimicrobial antibiotics in this setting and, given limited available data, provide an expert consensus discussion. While international guidelines do not tend to recommend routine use of prophylactic systemic antibiotics, the challenges of conflict settings and potential for polytrauma are likely to have ongoing impacts on antimicrobial decision-making and use. Efforts must be made to develop a suitable evidence base in this unique setting. In the interim, a pragmatic approach to balancing selective pressures of antimicrobial use with realistic access is possible.

17.
BMJ Open ; 13(11): e073577, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37989388

RESUMO

OBJECTIVES: Point-of-care tests (POCTs) for infection offer accurate rapid diagnostics but do not consistently improve antibiotic stewardship (ASP) of suspected ventilator-associated pneumonia. We aimed to measure the effect of a negative PCR-POCT result on intensive care unit (ICU) clinicians' antibiotic decisions and the additional effects of patient trajectory and cognitive-behavioural factors (clinician intuition, dis/interest in POCT, risk averseness). DESIGN: Observational cohort simulation study. SETTING: ICU. PARTICIPANTS: 70 ICU consultants/trainees working in UK-based teaching hospitals. METHODS: Clinicians saw four case vignettes describing patients who had completed a course of antibiotics for respiratory infection. Vignettes comprised clinical and biological data (ie, white cell count, C reactive protein), varied to create four trajectories: clinico-biological improvement (the 'improvement' case), clinico-biological worsening ('worsening'), clinical improvement/biological worsening ('discordant clin better'), clinical worsening/biological improvement ('discordant clin worse'). Based on this, clinicians made an initial antibiotics decision (stop/continue) and rated confidence (6-point Likert scale). A PCR-based POCT was then offered, which clinicians could accept or decline. All clinicians (including those who declined) were shown the result, which was negative. Clinicians updated their antibiotics decision and confidence. MEASURES: Antibiotics decisions and confidence were compared pre-POCT versus post-POCT, per vignette. RESULTS: A negative POCT result increased the proportion of stop decisions (54% pre-POCT vs 70% post-POCT, χ2(1)=25.82, p<0.001, w=0.32) in all vignettes except improvement (already high), most notably in discordant clin worse (49% pre-POCT vs 74% post-POCT). In a linear regression, factors that significantly reduced clinicians' inclination to stop antibiotics were a worsening trajectory (b=-0.73 (-1.33, -0.14), p=0.015), initial confidence in continuing (b=0.66 (0.56, 0.76), p<0.001) and involuntary receipt of POCT results (clinicians who accepted the POCT were more inclined to stop than clinicians who declined it, b=1.30 (0.58, 2.02), p<0.001). Clinician risk averseness was not found to influence antibiotic decisions (b=-0.01 (-0.12, 0.10), p=0.872). CONCLUSIONS: A negative PCR-POCT result can encourage antibiotic cessation in ICU, notably in cases of clinical worsening (where the inclination might otherwise be to continue). This effect may be reduced by high clinician confidence to continue and/or disinterest in POCT, perhaps due to low trust/perceived utility. Such cognitive-behavioural and trajectorial factors warrant greater consideration in future ASP study design.


Assuntos
Antibacterianos , Testes de Diagnóstico Rápido , Humanos , Antibacterianos/uso terapêutico , Testes Imediatos , Reação em Cadeia da Polimerase , Unidades de Terapia Intensiva , Cognição
18.
Commun Med (Lond) ; 3(1): 83, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37328651

RESUMO

BACKGROUND: Older adults, particularly in long-term care facilities (LTCF), remain at considerable risk from SARS-CoV-2. Data on the protective effect and mechanisms of hybrid immunity are skewed towards young adults precluding targeted vaccination strategies. METHODS: A single-centre longitudinal seroprevalence vaccine response study was conducted with 280 LCTF participants (median 82 yrs, IQR 76-88 yrs; 95.4% male). Screening by SARS-CoV-2 polymerase chain reaction with weekly asymptomatic/symptomatic testing (March 2020-October 2021) and serology pre-/post-two-dose Pfizer-BioNTech BNT162b2 vaccination for (i) anti-nucleocapsid, (ii) quantified anti-receptor binding domain (RBD) antibodies at three time-intervals, (iii) pseudovirus neutralisation, and (iv) inhibition by anti-RBD competitive ELISA were conducted. Neutralisation activity: antibody titre relationship was assessed via beta linear-log regression and RBD antibody-binding inhibition: post-vaccine infection relationship by Wilcoxon rank sum test. RESULTS: Here we show neutralising antibody titres are 9.2-fold (95% CI 5.8-14.5) higher associated with hybrid immunity (p < 0.00001); +7.5-fold (95% CI 4.6-12.1) with asymptomatic infection; +20.3-fold, 95% (CI 9.7-42.5) with symptomatic infection. A strong association is observed between antibody titre: neutralising activity (p < 0.00001) and rising anti-RBD antibody titre: RBD antibody-binding inhibition (p < 0.001), although 18/169 (10.7%) participants with high anti-RBD titre (>100BAU/ml), show inhibition <75%. Higher RBD antibody-binding inhibition values are associated with hybrid immunity and reduced likelihood of infection (p = 0.003). CONCLUSIONS: Hybrid immunity in older adults was associated with considerably higher antibody titres, neutralisation and inhibition capacity. Instances of high anti-RBD titre with lower inhibition suggests antibody quantity and quality as independent potential correlates of protection, highlighting added value of measuring inhibition over antibody titre alone to inform vaccine strategy.


Older adults continue to be at risk of COVID-19, particularly in residential care home settings. We investigated the effect of infection and vaccination on antibody development and subsequent SARS-CoV-2 infection in older adults. Antibodies are proteins that the immune system produces on infection or vaccination that can help respond to subsequent infection with SARS-CoV-2. We found that older adults produce antibodies to SARS-CoV-2 after 2-doses of Pfizer BioNTech BNT162b2 vaccine. The strongest immune responses were seen among those older adults who also had prior history of infection. The results highlight the importance of both antibody quality and quantity when considering possible indicators of protection against COVID-19 and supports the need for a third, booster, vaccination in this age group..

19.
JAC Antimicrob Resist ; 4(4): dlac080, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35898430

RESUMO

Background: Acute kidney injury (AKI) is a potential complication of systemic infection. Optimizing antimicrobial dosing in this dynamic state can be challenging with sub- or supra-therapeutic dosing risking treatment failure or toxicity, respectively. Locally, unadjusted renal dosing for the first 48 h of infection is recommended. Objectives: To determine the outcomes associated with this dosing strategy. Methods: A retrospective cohort analysis was undertaken in patients treated for Gram-negative bacteraemia with concurrent non-filtration dependent AKI from a single-centre NHS acute hospital (April 2016-March 2020). Patient demographics, microbiology data, antimicrobial treatment and patient outcome (in-hospital mortality and kidney function) were analysed. Results: In total, 647 episodes of Gram-negative bacteraemia (608 patients) were included; 305/608 (50.2%) were male with median age 71 years (range 18-100). AKI was present in 235/647 (36.3%); 78/647 (12.1%) and 45/647 (7.0%) having Kidney Disease Improving Global Outcomes-defined injury (stage 2) or failure (stage 3), respectively. In-hospital 30 day mortality was 25/352 (7.1%), 14/112 (12.5%), 26/123 (21.1%) and 11/60(18.3%) in patients with normal renal function, AKI stage 1, AKI stage ≥2 and established chronic kidney disease, respectively. Recovery of renal function at Day 21 or discharge was present in 105/106 surviving patients presenting with AKI stage ≥2. Time to recovery of AKI was similar in patients receiving full, low or no aminoglycoside (3 versus 4 versus 3 days, P = 0.612) and those receiving full- and low-dose ß-lactam (3 versus 5 days, P = 0.077). Conclusions: There is a high burden of AKI in patients with Gram-negative bacteraemia. Dose adjustments of ß-lactams may not be necessary in the first 48 h of infection-induced AKI and single-dose aminoglycosides may be considered for early empirical coverage.

20.
Eur J Hosp Pharm ; 29(5): 280-283, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-33414257

RESUMO

INTRODUCTION: Oral antimicrobials, including ciprofloxacin, levofloxacin and doxycycline, are susceptible to binding with enteral therapies such as calcium and iron therapies. Administered together, the bioavailability of these antimicrobials is expected to be reduced. METHODS: A retrospective case series of patients receiving oral antimicrobials (ciprofloxacin, levofloxacin and doxycycline) was analysed at a single-centre NHS acute hospital (April 2016-September 2019). Patient demographics, including concurrent enteral therapies, were recorded using medical records. Clinically important interactions were defined as doses administered within 2 hours of antimicrobial therapy. RESULTS: A total of 4067 prescriptions for the study antimicrobials (ciprofloxacin, n=1905; levofloxacin, n=538; and doxycycline, n=1624) were prescribed for 3584 patients. 1918/3583 (53.5%) of the patients were female, and the median age was 67 years (range 0.5-105.0 years). 810/4067 (19.3%) prescriptions reviewed had an interacting enteral therapy (calcium or iron salt) administered within 2 hours of the study medication. CONCLUSION: The concomitant administration of enteral calcium and iron with oral antimicrobials is common within the acute care hospital setting. Approximately one in five patients has a clinically important interaction which may impair oral bioavailability and limit treatment efficacy. As antimicrobial stewardship teams strive for increased intravenous-to-oral de-escalation, it is important that optimum dosing administration is followed to optimise patient outcomes.


Assuntos
Anti-Infecciosos , Levofloxacino , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cálcio , Criança , Pré-Escolar , Ciprofloxacina , Doxiciclina , Feminino , Humanos , Lactente , Ferro , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
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