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1.
J Antimicrob Chemother ; 78(7): 1748-1756, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37252945

RESUMO

BACKGROUND: Third-generation cephalosporin-resistant Enterobacterales (3GCRE) are increasing in prevalence, leading to greater carbapenem consumption. Selecting ertapenem has been proposed as a strategy to reduce carbapenem resistance development. However, there are limited data for the efficacy of empirical ertapenem for 3GCRE bacteraemia. OBJECTIVES: To compare the efficacy of empirical ertapenem and class 2 carbapenems for the treatment of 3GCRE bacteraemia. METHODS: A prospective non-inferiority observational cohort study was performed from May 2019 to December 2021. Adult patients with monomicrobial 3GCRE bacteraemia receiving carbapenems within 24 h were included at two hospitals in Thailand. Propensity scores were used to control for confounding, and sensitivity analyses were performed in several subgroups. The primary outcome was 30 day mortality. This study is registered with clinicaltrials.gov (NCT03925402). RESULTS: Empirical carbapenems were prescribed in 427/1032 (41%) patients with 3GCRE bacteraemia, of whom 221 received ertapenem and 206 received class 2 carbapenems. One-to-one propensity score matching resulted in 94 pairs. Escherichia coli was identified in 151 (80%) of cases. All patients had underlying comorbidities. Septic shock and respiratory failure were the presenting syndromes in 46 (24%) and 33 (18%) patients, respectively. The overall 30 day mortality rate was 26/188 (13.8%). Ertapenem was non-inferior to class 2 carbapenems in 30 day mortality (12.8% versus 14.9%; mean difference -0.02; 95% CI: -0.12 to 0.08). Sensitivity analyses were consistent regardless of aetiological pathogens, septic shock, source of infection, nosocomial acquisition, lactate levels or albumin levels. CONCLUSIONS: Ertapenem may be of comparable efficacy to class 2 carbapenems in the empirical treatment of 3GCRE bacteraemia.


Assuntos
Bacteriemia , Choque Séptico , Adulto , Humanos , Ertapenem/uso terapêutico , Carbapenêmicos/uso terapêutico , Antibacterianos/uso terapêutico , Pontuação de Propensão , Choque Séptico/tratamento farmacológico , Estudos Prospectivos , Bacteriemia/tratamento farmacológico , Escherichia coli , Cefalosporinas
2.
Clin Infect Dis ; 75(1): e1082-e1091, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34596212

RESUMO

BACKGROUND: We examined community- and hospital-acquired bloodstream infections (BSIs) in coronavirus disease 2019 (COVID-19) and non-COVID-19 patients across 2 epidemic waves. METHODS: We analyzed blood cultures of patients presenting to a London hospital group between January 2020 and February 2021. We reported BSI incidence, changes in sampling, case mix, healthcare capacity, and COVID-19 variants. RESULTS: We identified 1047 BSIs from 34 044 blood cultures, including 653 (62.4%) community-acquired and 394 (37.6%) hospital-acquired. Important pattern changes were seen. Community-acquired Escherichia coli BSIs remained below prepandemic level during COVID-19 waves, but peaked following lockdown easing in May 2020, deviating from the historical trend of peaking in August. The hospital-acquired BSI rate was 100.4 per 100 000 patient-days across the pandemic, increasing to 132.3 during the first wave and 190.9 during the second, with significant increase in elective inpatients. Patients with a hospital-acquired BSI, including those without COVID-19, experienced 20.2 excess days of hospital stay and 26.7% higher mortality, higher than reported in prepandemic literature. In intensive care, the BSI rate was 421.0 per 100 000 intensive care unit patient-days during the second wave, compared to 101.3 pre-COVID-19. The BSI incidence in those infected with the severe acute respiratory syndrome coronavirus 2 Alpha variant was similar to that seen with earlier variants. CONCLUSIONS: The pandemic have impacted the patterns of community- and hospital-acquired BSIs, in COVID-19 and non-COVID-19 patients. Factors driving the patterns are complex. Infection surveillance needs to consider key aspects of pandemic response and changes in healthcare practice.


Assuntos
Bacteriemia , COVID-19 , Infecções Comunitárias Adquiridas , Infecção Hospitalar , Sepse , Bacteriemia/epidemiologia , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Infecções Comunitárias Adquiridas/epidemiologia , Cuidados Críticos , Infecção Hospitalar/epidemiologia , Escherichia coli , Humanos , Armazenamento e Recuperação da Informação , Estudos Retrospectivos , SARS-CoV-2
3.
J Antimicrob Chemother ; 77(9): 2364-2372, 2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-35726853

RESUMO

OBJECTIVES: To explore the literature comparing the pharmacokinetic and clinical outcomes from adding probenecid to oral ß-lactams. METHODS: Medline and EMBASE were searched from inception to December 2021 for all English language studies comparing the addition of probenecid (intervention) with an oral ß-lactam [flucloxacillin, penicillin V, amoxicillin (±â€Šclavulanate), cefalexin, cefuroxime axetil] alone (comparator). ROBINS-I and ROB-2 tools were used. Data on antibiotic therapy, infection diagnosis, primary and secondary outcomes relating to pharmacokinetics and clinical outcomes, plus adverse events were extracted and reported descriptively. For a subset of studies comparing treatment failure between probenecid and control groups, meta-analysis was performed. RESULTS: Overall, 18/295 (6%) screened abstracts were included. Populations, methodology and outcome data were heterogeneous. Common populations included healthy volunteers (9/18; 50%) and those with gonococcal infection (6/18; 33%). Most studies were crossover trials (11/18; 61%) or parallel-arm randomized trials (4/18; 22%). Where pharmacokinetic analyses were performed, addition of probenecid to oral ß-lactams increased total AUC (7/7; 100%), Cmax (5/8; 63%) and serum t½ (6/8; 75%). Probenecid improved PTA (2/2; 100%). Meta-analysis of 3105 (2258 intervention, 847 control) patients treated for gonococcal disease demonstrated a relative risk of treatment failure in the random-effects model of 0.33 (95% CI 0.20-0.55; I2 = 7%), favouring probenecid. CONCLUSIONS: Probenecid-boosted ß-lactam therapy is associated with improved outcomes in gonococcal disease. Pharmacokinetic data suggest that probenecid-boosted oral ß-lactam therapy may have a broader application, but appropriately powered mechanistic and efficacy studies are required.


Assuntos
Gonorreia , Probenecid , Amoxicilina , Antibacterianos/efeitos adversos , Gonorreia/tratamento farmacológico , Humanos , Monobactamas , Probenecid/efeitos adversos , beta-Lactamas/efeitos adversos
4.
J Antimicrob Chemother ; 77(12): 3408-3413, 2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-36227686

RESUMO

BACKGROUND: Bacterial central nervous system (CNS) infection is challenging to treat and carries high risk of recurrence, morbidity, and mortality. Low CNS penetration of antibiotics may contribute to poor clinical outcomes from bacterial CNS infections. The current application of therapeutic drug monitoring (TDM) to management of bacterial CNS infection was reviewed. METHODS: Studies were included if they described adults treated for a suspected/confirmed bacterial CNS infection and had antibiotic drug concentration(s) determined that affected individual treatment. RESULTS: One-hundred-and-thirty-six citations were retrieved. Seventeen manuscripts were included describing management of 68 patients. TDM for vancomycin (58/68) and the beta-lactams (29/68) was most common. Timing of clinical sampling varied widely between studies and across different antibiotics. Methods for setting individual PK-PD targets, determining parameters and making treatment changes varied widely and were sometimes unclear. DISCUSSION: Despite increasing observational data showing low CNS penetration of various antibiotics, there are few clinical studies describing practical implementation of TDM in management of CNS infection. Lack of consensus around clinically relevant CSF PK-PD targets and protocols for dose-adjustment may contribute. Standardised investigation of TDM as a tool to improve treatment is required, especially as innovative drug concentration-sensing and PK-PD modelling technologies are emerging. Data generated at different centres offering TDM should be open access and aggregated to enrich understanding and optimize application.


Assuntos
Infecções do Sistema Nervoso Central , Monitoramento de Medicamentos , Adulto , Humanos , beta-Lactamas/uso terapêutico , Antibacterianos/uso terapêutico , Vancomicina/uso terapêutico , Infecções do Sistema Nervoso Central/tratamento farmacológico
5.
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
6.
Mycoses ; 65(4): 490-495, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35080057

RESUMO

BACKGROUND: We evaluated the recovery of fungal pathogens from clinical external ear samples from patients with otitis externa (OE) using the UK national Standard Microbiology Investigations of ear infection (SMI B1). METHOD: The UK SMI B1 protocol including a single Sabouraud dextrose agar with chloramphenicol (SABC) incubated at 37°C for 48 hours was compared with a standard fungal-specific culture method using two SABC agar plates incubated at 28 and 37°C for 2 weeks with an extra Candida chromogenic agar incubated at 37°C for 5 days. This real-life evaluation was undertaken on ear samples from patients with OE from January 2020 to December 2020. RESULTS: Altogether, 304 individual patient ear swabs were prospectively examined. The positivity rate of UK standard was 14% (42/304) versus 26% (79/304) for the fungal-specific protocol (p < .05). The standard protocol identified seven compared with 17 species using the fungal-specific protocol. A total of 93 fungal isolates were recovered; nine different yeasts and eight filamentous fungal species. Candida parapsilosis (38/304; 13%), C. albicans (10/304; 3%) and C. orthopsilosis (6/304; 2%) were common yeast species. Aspergillus niger complex (16/304; 5%) was the most common mould, followed by A. fumigatus complex (3/304; 1%). Many less common and emerging yeasts and moulds were only isolated from samples cultured using a fungal-specific protocol. CONCLUSION: Our results suggest that the UK SMI B1 media and procedures are inadequate to detect all fungal agents causing otomycosis. Fungal-specific culture protocols increase the recovery rate and diversity of fungal pathogens isolated from external ear samples.


Assuntos
Otite Externa , Otomicose , Candida albicans , Técnicas de Laboratório Clínico , Humanos , Otite Externa/diagnóstico , Otomicose/diagnóstico , Otomicose/microbiologia , Reino Unido
7.
Clin Infect Dis ; 72(12): 2103-2111, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32246143

RESUMO

BACKGROUND: A locally developed case-based reasoning (CBR) algorithm, designed to augment antimicrobial prescribing in secondary care was evaluated. METHODS: Prescribing recommendations made by a CBR algorithm were compared to decisions made by physicians in clinical practice. Comparisons were examined in 2 patient populations: first, in patients with confirmed Escherichia coli blood stream infections ("E. coli patients"), and second in ward-based patients presenting with a range of potential infections ("ward patients"). Prescribing recommendations were compared against the Antimicrobial Spectrum Index (ASI) and the World Health Organization Essential Medicine List Access, Watch, Reserve (AWaRe) classification system. Appropriateness of a prescription was defined as the spectrum of the prescription covering the known or most-likely organism antimicrobial sensitivity profile. RESULTS: In total, 224 patients (145 E. coli patients and 79 ward patients) were included. Mean (standard deviation) age was 66 (18) years with 108/224 (48%) female sex. The CBR recommendations were appropriate in 202/224 (90%) compared to 186/224 (83%) in practice (odds ratio [OR]: 1.24 95% confidence interval [CI]: .392-3.936; P = .71). CBR recommendations had a smaller ASI compared to practice with a median (range) of 6 (0-13) compared to 8 (0-12) (P < .01). CBR recommendations were more likely to be classified as Access class antimicrobials compared to physicians' prescriptions at 110/224 (49%) vs. 79/224 (35%) (OR: 1.77; 95% CI: 1.212-2.588; P < .01). Results were similar for E. coli and ward patients on subgroup analysis. CONCLUSIONS: A CBR-driven decision support system provided appropriate recommendations within a narrower spectrum compared to current clinical practice. Future work must investigate the impact of this intervention on prescribing behaviors more broadly and patient outcomes.


Assuntos
Anti-Infecciosos , Gestão de Antimicrobianos , Idoso , Algoritmos , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Escherichia coli , Feminino , Humanos , Prescrição Inadequada , Padrões de Prática Médica
8.
BMC Infect Dis ; 21(1): 932, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496795

RESUMO

BACKGROUND: To characterise the longitudinal dynamics of C-reactive protein (CRP) and Procalcitonin (PCT) in a cohort of hospitalised patients with COVID-19 and support antimicrobial decision-making. METHODS: Longitudinal CRP and PCT concentrations and trajectories of 237 hospitalised patients with COVID-19 were modelled. The dataset comprised of 2,021 data points for CRP and 284 points for PCT. Pairwise comparisons were performed between: (i) those with or without significant bacterial growth from cultures, and (ii) those who survived or died in hospital. RESULTS: CRP concentrations were higher over time in COVID-19 patients with positive microbiology (day 9: 236 vs 123 mg/L, p < 0.0001) and in those who died (day 8: 226 vs 152 mg/L, p < 0.0001) but only after day 7 of COVID-related symptom onset. Failure for CRP to reduce in the first week of hospital admission was associated with significantly higher odds of death. PCT concentrations were higher in patients with COVID-19 and positive microbiology or in those who died, although these differences were not statistically significant. CONCLUSIONS: Both the absolute CRP concentration and the trajectory during the first week of hospital admission are important factors predicting microbiology culture positivity and outcome in patients hospitalised with COVID-19. Further work is needed to describe the role of PCT for co-infection. Understanding relationships of these biomarkers can support development of risk models and inform optimal antimicrobial strategies.


Assuntos
COVID-19 , Pró-Calcitonina , Antibacterianos , Proteína C-Reativa , Humanos , SARS-CoV-2
9.
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
10.
Clin Infect Dis ; 71(9): 2459-2468, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-32358954

RESUMO

BACKGROUND: To explore and describe the current literature surrounding bacterial/fungal coinfection in patients with coronavirus infection. METHODS: MEDLINE, EMBASE, and Web of Science were searched using broad-based search criteria relating to coronavirus and bacterial coinfection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-CoV-2, and other coronavirus) and bacterial/fungal coinfection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal coinfections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-CoV-2 even in absence of coinfection was performed. RESULTS: 1007 abstracts were identified. Eighteen full texts reporting bacterial/fungal coinfection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140; 61%). Nine of 18 (50%) studies reported on COVID-19, 5/18 (28%) on SARS-1, 1/18 (6%) on MERS, and 3/18 (17%) on other coronaviruses. For COVID-19, 62/806 (8%) patients were reported as experiencing bacterial/fungal coinfection during hospital admission. Secondary analysis demonstrated wide use of broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy. No antimicrobial stewardship interventions were described. For non-COVID-19 cases, bacterial/fungal coinfection was reported in 89/815 (11%) of patients. Broad-spectrum antibiotic use was reported. CONCLUSIONS: Despite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus-associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial/fungal coinfection. Generation of prospective evidence to support development of antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic is urgently required.


Assuntos
Anti-Infecciosos/uso terapêutico , Tratamento Farmacológico da COVID-19 , Coinfecção/tratamento farmacológico , SARS-CoV-2/efeitos dos fármacos , Gestão de Antimicrobianos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , COVID-19/epidemiologia , COVID-19/microbiologia , Coinfecção/epidemiologia , Coinfecção/microbiologia , Resistência Microbiana a Medicamentos , Humanos , Micoses/tratamento farmacológico , Micoses/epidemiologia , Micoses/microbiologia
11.
J Antimicrob Chemother ; 75(7): 1681-1684, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32433765

RESUMO

The emergence of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has required an unprecedented response to control the spread of the infection and protect the most vulnerable within society. Whilst the pandemic has focused society on the threat of emerging infections and hand hygiene, certain infection control and antimicrobial stewardship policies may have to be relaxed. It is unclear whether the unintended consequences of these changes will have a net-positive or -negative impact on rates of antimicrobial resistance. Whilst the urgent focus must be on controlling this pandemic, sustained efforts to address the longer-term global threat of antimicrobial resistance should not be overlooked.


Assuntos
Gestão de Antimicrobianos/organização & administração , Infecções por Coronavirus , Atenção à Saúde/organização & administração , Resistência Microbiana a Medicamentos , Pandemias , Pneumonia Viral , Betacoronavirus , COVID-19 , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Higiene das Mãos , Humanos , Controle de Infecções/métodos , Pandemias/prevenção & controle , Isolamento de Pacientes , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , SARS-CoV-2
12.
BMC Infect Dis ; 19(1): 768, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481023

RESUMO

BACKGROUND: Bacterial ophthalmic infections are common. Empirical treatment with topical broad-spectrum antibiotics is recommended for severe cases. Antimicrobial resistance (AMR) to agents used for bacterial ophthalmic infections make it increasingly important to consider changing resistance patterns when prescribing, however UK data in this area are lacking. We evaluate the epidemiology and antimicrobial susceptibilities of ophthalmic pathogens across care settings and compare these with local and national antimicrobial prescribing guidelines. METHODS: A retrospective, multi-centre observational analysis was undertaken of ophthalmic microbiology isolates between 2009 and 2015 at a centralised North-West London laboratory (incorporating data from primary care and five London teaching hospitals). Data were analysed using descriptive statistics with respect to patient demographics, pathogen distribution (across age-groups and care setting), seasonality, and susceptibility to topical chloramphenicol, moxifloxacin, and fusidic acid. RESULTS: Two thousand six hundred eighty-one isolates (n = 2168 patients) were identified. The commonest pathogen in adults was Staphylococcus spp. across primary, secondary, and tertiary care (51.7%; 43.4%; 33.6% respectively) and in children was Haemophilus spp. (34.6%;28.2%;36.6%). AMR was high and increased across care settings for chloramphenicol (11.8%;15.1%;33.8%); moxifloxacin (5.5%;7.6%;25.5%); and fusidic acid (49.6%;53.4%; 58.7%). Pseudomonas spp. was the commonest chloramphenicol-resistant pathogen across all care settings, whilst Haemophilus spp. was the commonest fusidic acid-resistant pathogen across primary and secondary care. More isolates were recorded in spring (31.6%) than any other season, mostly due to a significant rise in Haemophilus spp. CONCLUSIONS: We find UK national and local antimicrobial prescribing policies for ophthalmic infections may not be concordant with the organisms and antimicrobial susceptibilities found in clinical samples. We also find variations in microbial incidence related to patient age, clinical setting, and season. Such variations may have further important implications for prescribing practices and modification of antimicrobial guidelines.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/epidemiologia , Infecções Oculares Bacterianas/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Padrões de Prática Médica/estatística & dados numéricos , Estudos Retrospectivos , Estações do Ano , Staphylococcus/efeitos dos fármacos , Reino Unido/epidemiologia , Adulto Jovem
13.
Ther Drug Monit ; 40(3): 315-321, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29561305

RESUMO

BACKGROUND: C-reactive protein (CRP) pharmacodynamic (PD) models have the potential to provide adjunctive methods for predicting the individual exposure response to antimicrobial therapy. We investigated CRP PD linked to a vancomycin pharmacokinetic (PK) model using routinely collected data from noncritical care adults in secondary care. METHODS: Patients receiving intermittent intravenous vancomycin therapy in secondary care were identified. A 2-compartment vancomycin PK model was linked to a previously described PD model describing CRP response. PK and PD parameters were estimated using a Non-Parametric Adaptive Grid technique. Exposure-response relationships were explored with vancomycin area-under-the-concentration-time-curve (AUC) and EC50 (concentration of drug that causes a half maximal effect) using the index, AUC:EC50, fitted to CRP data using a sigmoidal Emax model. RESULTS: Twenty-nine individuals were included. Median age was 62 (21-97) years. Fifteen (52%) patients were microbiology confirmed. PK and PD models were adequately fitted (r 0.83 and 0.82, respectively). There was a wide variation observed in individual Bayesian posterior EC50 estimates (6.95-48.55 mg/L), with mean (SD) AUC:EC50 of 31.46 (29.22). AUC:EC50 was fitted to terminal CRP with AUC:EC50 >19 associated with lower CRP value at 96-120 hours of therapy (100 mg/L versus 44 mg/L; P < 0.01). CONCLUSIONS: The use of AUC:EC50 has the potential to provide in vivo organism and host response data as an adjunct for in vitro minimum inhibitory concentration data, which is currently used as the gold standard PD index for vancomycin therapy. This index can be estimated using routinely collected clinical data. Future work must investigate the role of AUC:EC50 in a prospective cohort and explore linkage with direct patient outcomes.


Assuntos
Antibacterianos/sangue , Proteína C-Reativa/metabolismo , Vancomicina/sangue , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vancomicina/administração & dosagem , Vancomicina/farmacocinética , Adulto Jovem
14.
Health Expect ; 21(1): 222-229, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28732138

RESUMO

BACKGROUND: Public sources fund the majority of UK infection research, but citizens currently have no formal role in resource allocation. To explore the feasibility and willingness of citizens to engage in strategic decision making, we developed and tested a practical tool to capture public priorities for research. METHOD: A scenario including six infection themes for funding was developed to assess citizen priorities for research funding. This was tested over two days at a university public festival. Votes were cast anonymously along with rationale for selection. The scenario was then implemented during a three-hour focus group exploring views on engagement in strategic decisions and in-depth evaluation of the tool. RESULTS: 188/491(38%) prioritized funding research into drug-resistant infections followed by emerging infections(18%). Results were similar between both days. Focus groups contained a total of 20 citizens with an equal gender split, range of ethnicities and ages ranging from 18 to >70 years. The tool was perceived as clear with participants able to make informed comparisons. Rationale for funding choices provided by voters and focus group participants are grouped into three major themes: (i) Information processing; (ii) Knowledge of the problem; (iii) Responsibility; and a unique theme within the focus groups (iv) The potential role of citizens in decision making. Divergent perceptions of relevance and confidence of "non-experts" as decision makers were expressed. CONCLUSION: Voting scenarios can be used to collect, en-masse, citizens' choices and rationale for research priorities. Ensuring adequate levels of citizen information and confidence is important to allow deployment in other formats.


Assuntos
Doenças Transmissíveis , Prioridades em Saúde , Pesquisa sobre Serviços de Saúde/métodos , Opinião Pública , Adulto , Idoso , Doenças Transmissíveis Emergentes , Participação da Comunidade , Tomada de Decisões , Resistência Microbiana a Medicamentos , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Alocação de Recursos
15.
BMC Med Educ ; 18(1): 166, 2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-30005595

RESUMO

BACKGROUND: We report the development and evaluation of a web-based tool designed to facilitate student extra-curricular engagement in medical research through project matching students with academic supervisors. UK based university students were surveyed to explore their perceptions of undergraduate research, barriers and facilitators to current engagement. Following this, an online web-based intervention ( www.ProjectPal.org ) was developed to support access of students to research projects and supervisors. A pilot intervention was undertaken across a London-based university in January 2013 to February 2016. In March 2016, anonymised data were extracted from the prospective data log for analysis of website engagement and usage. Supervisors were surveyed to evaluate the website and student outputs. RESULTS: Fifty-one students responded to the electronic survey. Twenty-four (47%) reported frustration at a perceived lack of opportunities to carry out extra-curricular academic projects. Major barriers to engaging in undergraduate research reported were difficulties in identifying suitable supervisors (33/51; 65%) and time pressures (36/51; 71%) associated with this. Students reported being opportunistic in their engagement with undergraduate research. Following implementation of the website, 438 students signed up to ProjectPal and the website was accessed 1357 times. Access increased on a yearly basis. Overall, 70 projects were advertised by 35 supervisors. There were 86 applications made by students for these projects. By February 2016, the 70 projects had generated 5 peer-review publications with a further 7 manuscripts under peer-review, 14 national presentations, and 1 national prize. CONCLUSION: The use of an online platform to promote undergraduate engagement with extra-curricular research appears to facilitate extra-curricular engagement with research. Further work to understand the impact compared to normal opportunistic practices in enhancing student engagement is now underway.


Assuntos
Pesquisa Biomédica/estatística & dados numéricos , Educação de Graduação em Medicina , Internet/estatística & dados numéricos , Mentores , Revisão da Pesquisa por Pares , Estudantes de Medicina/estatística & dados numéricos , Inquéritos e Questionários , Distinções e Prêmios , Pesquisa Biomédica/organização & administração , Escolha da Profissão , Feminino , Humanos , Londres , Masculino , Desenvolvimento de Programas , Estudos Prospectivos , Fatores de Tempo
17.
J Antimicrob Chemother ; 71(2): 554-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26498747

RESUMO

BACKGROUND: Antimicrobial resistance (AMR) is a public health priority and leading patient safety issue. Globally, antimicrobial stewardship (AMS) has been integral in promoting therapeutic optimization whilst minimizing harmful antimicrobial use. A cross-sectional, observational study was undertaken to investigate the coverage of AMS and antibacterial resistance across clinical scientific conferences in 2014, as a surrogate marker for current awareness and attributed importance. METHODS: Clinical specialties were identified, and the largest corresponding clinical scientific/research conferences in 2014 determined (i) within the UK and (ii) internationally. Conference characteristics and abstracts were interrogated and analysed to determine those related to AMS and AMR. Inter-specialty variation was assessed using χ(2) or Fisher's exact statistical analysis. RESULTS: In total, 45 conferences from 23 specialties were analysed representing 59,682 accepted abstracts. The UK had a significantly greater proportion of AMS-AMR-related abstracts compared with international conferences [2.8% (n = 221/7843) compared with 1.8% (n = 942/51,839); P < 0.001]. Infection conferences contained the greatest proportion of AMS-AMR abstracts, representing 20% (732/3669) of all abstracts [UK 66% (80/121) and international 18% (652/3548); P < 0.0001]. AMS-AMR coverage across all general specialties was poor [intensive care 9% (116/1287), surgical 1% (8/757) and medical specialties 0.64% (332/51,497)] despite high usage of antimicrobials across all. CONCLUSIONS: Despite current AMS-AMR strategies being advocated by infection specialists and discussed by national and international policy makers, AMS-AMR coverage remained limited across clinical specialty scientific conferences in 2014. We call for further intervention to ensure specialty engagement with AMS programmes and promote the AMR agenda across clinical practice.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Uso de Medicamentos/normas , Estudos Transversais , Humanos , Reino Unido
18.
J Antimicrob Chemother ; 71(11): 3284-3292, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27432603

RESUMO

OBJECTIVES: Antimicrobial resistance (AMR) is a global political and patient safety issue. With ongoing strategic interventions to improve the shape of UK postgraduate clinical training, ensuring that all clinicians have appropriate knowledge and practical skills in the area of AMR is essential. To assess this, a cross-sectional analysis was undertaken of the coverage and quality of antimicrobial stewardship (AMS)/AMR within UK postgraduate clinical training curricula. METHODS: UK clinical specialty training curricula were identified. Topics and individual learning points relating to AMS or AMR were extracted for each specialty. Learning points were quality assessed against the expected level of clinical competence. Inter-specialty analysis was performed. RESULTS: Overall 37 specialties were assessed, equating to 2318 topics and 42 527 learning points. Of these, 8/2318 (0.3%) topics and 184/42 527 (0.4%) learning points were related to AMS/AMR. Infectious diseases represented all eight topics and 43/184 (23%) of the learning points. In contrast, primary care, which is responsible for the highest proportion of antimicrobial usage, had no topics and only 2/1368 (0.15%) of the AMS/AMR learning points. This paucity of representation was reflected across most of the remaining specialties. On quality assessment, the majority of learning points (111/184; 60%) required knowledge only, with no demonstration of behaviour in clinical practice required. CONCLUSIONS: Coverage of AMS/AMR is poor across the majority of UK postgraduate clinical training curricula, with little depth of learning required. Given the threat of AMR, and evolving changes in clinical training pathways, we call for cross-specialty action to address this current lack of engagement.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Currículo , Uso de Medicamentos/normas , Educação de Pós-Graduação em Medicina/métodos , Política de Saúde , Estudos Transversais , Farmacorresistência Bacteriana , Humanos , Reino Unido
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