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2.
Emerg Infect Dis ; 27(1)2020 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-33256890

RESUMEN

We investigated the dynamics of seroconversion in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During March 29-May 22, 2020, we collected serum samples and associated clinical data from 177 persons in London, UK, who had SARS-CoV-2 infection. We measured IgG against SARS-CoV-2 and compared antibody levels with patient outcomes, demographic information, and laboratory characteristics. We found that 2.0%-8.5% of persons did not seroconvert 3-6 weeks after infection. Persons who seroconverted were older, were more likely to have concurrent conditions, and had higher levels of inflammatory markers. Non-White persons had higher antibody concentrations than those who identified as White; these concentrations did not decline during follow-up. Serologic assay results correlated with disease outcome, race, and other risk factors for severe SARS-CoV-2 infection. Serologic assays can be used in surveillance to clarify the duration and protective nature of humoral responses to SARS-CoV-2 infection.

3.
Pediatr Infect Dis J ; 39(12): 1081-1087, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32947600

RESUMEN

BACKGROUND: The prevalence of extended-spectrum beta-lactamase producing Εnterobacteriaceae (ESBL-PE) is increasing globally. ESBL-PE are an important cause of urinary tract infections (UTIs) in children. We aimed to characterize the clinical presentation, treatment and outcomes of childhood UTI caused by ESBL-PE in Europe. METHODS: Multicenter retrospective cohort study. Children 0 to 18 years of age with fever, positive urinalysis and positive urine culture for an ESBL-PE uropathogen, seen in a participating hospital from January 2016 to July 2017, were included. MAIN OUTCOME MEASURES: Primary outcome measure: day of defervescence was compared between (1) initial microbiologically effective treatment (IET) versus initial microbiologically ineffective treatment (IIT) and (2) single initial antibiotic treatment versus combined initial antibiotic treatment. SECONDARY OUTCOME MEASURES: Clinical and microbiologic failure of initial treatment. RESULTS: We included 142 children from 14 hospitals in 8 countries. Sixty-one children had IET and 77 IIT. There was no statistical difference in time to defervescence for effective/ineffective groups (P = 0.722) and single/combination therapy groups (P = 0.574). Two of 59 (3.4%) and 4/66 (6.1%) patients exhibited clinical failure during treatment (P = 0.683) when receiving IET or IIT, respectively. Eight of 51 (15.7%) receiving IET and 6/58 (10.3%) receiving IIT patients (P = 0.568) had recurring symptoms/signs suggestive of a UTI. Recurrence of a UTI occurred 15.5 days (interquartile range, 9.0-19.0) after the end of treatment. CONCLUSIONS: Time to defervescence and clinical failure did not differ between IET/IIT groups. Non-carbapenem beta-lactam antibiotics may be used for the empiric treatment of ESBL febrile UTIs, until susceptibility testing results become available.

4.
Sex Transm Infect ; 2020 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-32883750

RESUMEN

OBJECTIVES: Oropharyngeal squamous cell carcinoma is the most common human papillomavirus (HPV)-associated cancer in the UK, but little is known about the prevalence of oropharyngeal HPV in sexually active teenagers. We investigated reported HPV vaccination coverage (in females) and prevalence of oropharyngeal HPV in sexually active students attending six technical colleges in London, UK. METHODS: In 2017, we obtained mouthwash samples and questionnaires from male and female students taking part in the 'Test n Treat' chlamydia screening trial. Samples were subjected to HPV genotyping. RESULTS: Of 232 participants approached, 202 (87%) provided a mouthwash sample and questionnaire. Participants' median age was 17 years and 47% were male. Most (73%) were from black and minority ethnic groups, 64% gave a history of oral sex, 52% reported having a new sexual partner in the past 6 months, 33% smoked cigarettes, 5.9% had concurrent genitourinary Chlamydia trachomatis infection and 1.5% Neisseria gonorrhoeae and 5.0% were gay or bisexual. Only 47% (50/107) of females reported being vaccinated against HPV 16/18, of whom 74% had received ≥2 injections. HPV genotyping showed three mouthwash samples (1.5%, 95% CI 0.3% to 4.3%) were positive for possible high-risk human papillomavirus (HR-HPV), one (0.5%, 0.0% to 2.7%) for low-risk HPV 6/11, but none (0.0%, 0.0% to 1.8%) for HR-HPV. Four samples (2.0%, 0.5% to 5.0%) were positive for HPV16 using a HPV16 type-specific quantitative PCR, but these were at a very low copy number and considered essentially negative. CONCLUSIONS: Despite the high prevalence of oral sex and genitourinary chlamydia and low prevalence of HPV vaccination, the prevalence of oropharyngeal HR-HPV in these adolescents was negligible.

5.
Br J Haematol ; 2020 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-32798327

RESUMEN

Multiple myeloma is associated with significant early morbidity and mortality, with considerable end organ damage often present at diagnosis. The Tackling EArly Morbidity and Mortality in Multiple Myeloma (TEAMM) trial was used to evaluate routes to diagnosis in patients with myeloma and the relationship between diagnostic pathways, time to diagnosis and disease severity. A total of 915 participants were included in the study. Fifty-one per cent were diagnosed by direct referral from primary care to haematology; 29% were diagnosed via acute services and 20% were referred via other secondary care specialties. Patients diagnosed via other secondary care specialties had a longer diagnostic interval (median 120 days vs. 59 days) without an increase in features of severe disease, suggesting they had a relatively indolent disease. Marked intrahospital delay suggests possible scope for improvement. A quarter of those diagnosed through acute services reported >30 days from initial hospital consultation to haematology assessment. Participants diagnosed through acute services had poorer performance status (P < 0·0001) and higher burden of end organ damage (P < 0·0001) with no difference in the overall length of diagnostic pathway compared to those diagnosed by direct referral (median 59 days). This suggests that advanced disease in patients presenting through acute services predominantly reflects disease aggression.

7.
Health Technol Assess ; 23(67): 1-40, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31855555

RESUMEN

BACKGROUND: Group B streptococcus is the leading cause of infection in infants. Currently, intrapartum antibiotic prophylaxis is the major strategy to prevent invasive group B streptococcus disease. However, intrapartum antibiotic prophylaxis does not prevent maternal sepsis, premature births, stillbirths or late-onset disease. Maternal vaccination may offer an alternative strategy. Multivalent polysaccharide protein conjugate vaccine development is under way and a serocorrelate of protection is needed to expedite vaccine licensure. OBJECTIVES: The ultimate aim of this work is to determine the correlate of protection against the major group B streptococcus disease-causing serotypes in infants in the UK. The aim of this feasibility study is to test key operational aspects of the study design. DESIGN: Prospective cohort study of pregnant women and their infants in a 6-month period (1 July to 31 December 2018). SETTING: Five secondary and tertiary hospitals from London and South England. National iGBS disease surveillance was conducted in all trusts in England and Wales. PARTICIPANTS: Pregnant women aged ≥ 18 years who were delivering at one of the selected hospitals and who provided consent during the study period. There were no exclusion criteria. INTERVENTIONS: No interventions were performed. MAIN OUTCOME MEASURES: (1) To test the feasibility of collecting serum at delivery from a large cohort of pregnant women. (2) To test the key operational aspects for a proposed large serocorrelates study. (3) To test the feasibility of collecting samples from those with invasive group B streptococcus. RESULTS: A total of 1823 women were recruited during the study period. Overall, 85% of serum samples were collected at three sites collecting only cord blood. At the two sites collecting maternal, cord and infant blood samples, the collection rate was 60%. A total of 614 women were screened for group B streptococcus with a colonisation rate of 22% (serotype distribution: 30% III, 25% Ia, 16% II, 14% Ib, 14% V and 1% IV). A blood sample was collected from 34 infants who were born to colonised women. Maternal and infant blood and the bacterial isolates for 15 newborns who developed invasive group B streptococcal disease during the study period were collected (serotype distribution: 29% III, 29% II, 21% Ia, 7% Ib, 7% IV and 7% V). LIMITATIONS: Recruitment and sample collection were dependent on the presence of research midwives rather than the whole clinical team. In addition, individualised consent limited the number of women who could be approached each day, and site set-up for the national surveillance study and the limited time period of this feasibility study limited recruitment of all eligible participants. CONCLUSIONS: We have verified the feasibility of collecting and processing rectovaginal swabs and blood samples in pregnant women, as well as samples from those with invasive group B streptococcal disease. We have made recommendations for the recruitment of cases within the proposed GBS3 study and for controls both within GBS3 and as an extension of this feasibility study. FUTURE WORK: A large case-control study comparing specific immunoglobulin G levels in mothers whose infants develop invasive group B streptococcal disease with those in colonised mothers whose infants do not develop invasive group B streptococcal disease is recommended. TRIAL REGISTRATION: Current Controlled Trials ISRCTN49326091; IRAS project identification number 246149/REC reference number 18/WM/0147. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 67. See the NIHR Journals Library website for further project information.


Asunto(s)
Profilaxis Antibiótica , Serogrupo , Infecciones Estreptocócicas/prevención & control , Vacunas Estreptocócicas/administración & dosificación , Adulto , Estudios de Factibilidad , Femenino , Sangre Fetal , Humanos , Lactante , Recién Nacido , Embarazo , Estudios Prospectivos , Suero , Streptococcus agalactiae/aislamiento & purificación , Reino Unido
8.
Health Technol Assess ; 23(62): 1-94, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31690402

RESUMEN

BACKGROUND: Myeloma causes profound immunodeficiency and recurrent serious infections. There are approximately 5500 new UK cases of myeloma per annum, and one-quarter of patients will have a serious infection within 3 months of diagnosis. Newly diagnosed patients may benefit from antibiotic prophylaxis to prevent infection. However, the use of prophylaxis has not been established in myeloma and may be associated with health-care-associated infections (HCAIs), such as Clostridium difficile. There is a need to assess the benefits and cost-effectiveness of the use of antibacterial prophylaxis against any risks in a double-blind, placebo-controlled, randomised clinical trial. OBJECTIVES: To assess the risks, benefits and cost-effectiveness of prophylactic levofloxacin in newly diagnosed symptomatic myeloma patients. DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. A central telephone randomisation service used a minimisation computer algorithm to allocate treatments in a 1 : 1 ratio. SETTING: A total of 93 NHS hospitals throughout England, Northern Ireland and Wales. PARTICIPANTS: A total of 977 patients with newly diagnosed symptomatic myeloma. INTERVENTION: Patients were randomised to receive levofloxacin or placebo tablets for 12 weeks at the start of antimyeloma treatment. Treatment allocation was blinded and balanced by centre, estimated glomerular filtration rate and intention to give high-dose chemotherapy with autologous stem cell transplantation. Follow-up was at 4-week intervals up to 16 weeks, with a further follow-up at 1 year. MAIN OUTCOME MEASURES: The primary outcome was to assess the number of febrile episodes (or deaths) in the first 12 weeks from randomisation. Secondary outcomes included number of deaths and infection-related deaths, days in hospital, carriage and invasive infections, response to antimyeloma treatment and its relation to infection, quality of life and overall survival within the first 12 weeks and beyond. RESULTS: In total, 977 patients were randomised (levofloxacin, n = 489; placebo, n = 488). A total of 134 (27%) events (febrile episodes, n = 119; deaths, n = 15) occurred in the placebo arm and 95 (19%) events (febrile episodes, n = 91; deaths, n = 4) occurred in the levofloxacin arm; the hazard ratio for time to first event (febrile episode or death) within the first 12 weeks was 0.66 (95% confidence interval 0.51 to 0.86; p = 0.002). Levofloxacin also reduced other infections (144 infections from 116 patients) compared with placebo (179 infections from 133 patients; p-trend of 0.06). There was no difference in new acquisitions of C. difficile, methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase Gram-negative organisms when assessed up to 16 weeks. Levofloxacin produced slightly higher quality-adjusted life-year gains over 16 weeks, but had associated higher costs for health resource use. With a median follow-up of 52 weeks, there was no significant difference in overall survival (p = 0.94). LIMITATIONS: Short duration of prophylactic antibiotics and cost-effectiveness. CONCLUSIONS: During the 12 weeks from new diagnosis, the addition of prophylactic levofloxacin to active myeloma treatment significantly reduced febrile episodes and deaths without increasing HCAIs or carriage. Future work should aim to establish the optimal duration of antibiotic prophylaxis and should involve the laboratory investigation of immunity, inflammation and disease activity on stored samples funded by the TEAMM (Tackling Early Morbidity and Mortality in Myeloma) National Institute for Health Research Efficacy and Mechanism Evaluation grant (reference number 14/24/04). TRIAL REGISTRATION: Current Controlled Trials ISRCTN51731976. FUNDING DETAILS: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 62. See the NIHR Journals Library website for further project information.


Asunto(s)
Antibacterianos/uso terapéutico , Levofloxacino/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Profilaxis Antibiótica , Análisis Costo-Beneficio , Infección Hospitalaria/prevención & control , Inglaterra , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Irlanda del Norte , Evaluación de la Tecnología Biomédica , Gales
9.
Lancet Oncol ; 20(12): 1760-1772, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31668592

RESUMEN

BACKGROUND: Myeloma causes profound immunodeficiency and recurrent, serious infections. Around 5500 new cases of myeloma are diagnosed per year in the UK, and a quarter of patients will have a serious infection within 3 months of diagnosis. We aimed to assess whether patients newly diagnosed with myeloma benefit from antibiotic prophylaxis to prevent infection, and to investigate the effect on antibiotic-resistant organism carriage and health care-associated infections in patients with newly diagnosed myeloma. METHODS: TEAMM was a prospective, multicentre, double-blind, placebo-controlled randomised trial in patients aged 21 years and older with newly diagnosed myeloma in 93 UK hospitals. All enrolled patients were within 14 days of starting active myeloma treatment. We randomly assigned patients (1:1) to levofloxacin or placebo with a computerised minimisation algorithm. Allocation was stratified by centre, estimated glomerular filtration rate, and intention to proceed to high-dose chemotherapy with autologous stem cell transplantation. All investigators, patients, laboratory, and trial co-ordination staff were masked to the treatment allocation. Patients were given 500 mg of levofloxacin (two 250 mg tablets), orally once daily for 12 weeks, or placebo tablets (two tablets, orally once daily for 12 weeks), with dose reduction according to estimated glomerular filtration rate every 4 weeks. Follow-up visits occurred every 4 weeks up to week 16, and at 1 year. The primary outcome was time to first febrile episode or death from all causes within the first 12 weeks of trial treatment. All randomised patients were included in an intention-to-treat analysis of the primary endpoint. This study is registered with the ISRCTN registry, number ISRCTN51731976, and the EU Clinical Trials Register, number 2011-000366-35. FINDINGS: Between Aug 15, 2012, and April 29, 2016, we enrolled and randomly assigned 977 patients to receive levofloxacin prophylaxis (489 patients) or placebo (488 patients). Median follow-up was 12 months (IQR 8-13). 95 (19%) first febrile episodes or deaths occurred in 489 patients in the levofloxacin group versus 134 (27%) in 488 patients in the placebo group (hazard ratio 0·66, 95% CI 0·51-0·86; p=0·0018. 597 serious adverse events were reported up to 16 weeks from the start of trial treatment (308 [52%] of which were in the levofloxacin group and 289 [48%] of which were in the placebo group). Serious adverse events were similar between the two groups except for five episodes (1%) of mostly reversible tendonitis in the levofloxacin group. INTERPRETATION: Addition of prophylactic levofloxacin to active myeloma treatment during the first 12 weeks of therapy significantly reduced febrile episodes and deaths compared with placebo without increasing health care-associated infections. These results suggest that prophylactic levofloxacin could be used for patients with newly diagnosed myeloma undergoing anti-myeloma therapy. FUNDING: UK National Institute for Health Research.


Asunto(s)
Antibacterianos/uso terapéutico , Profilaxis Antibiótica/métodos , Neutropenia Febril/prevención & control , Infecciones/tratamiento farmacológico , Levofloxacino/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Anciano , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Pronóstico , Estudios Prospectivos
10.
PLoS One ; 13(12): e0205941, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30517094

RESUMEN

BACKGROUND: Laboratory diagnosis of Clostridium difficile infection (CDI) remains unsettled, despite updated guidelines. We investigated the potential utility of quantitative data from a nucleic acid amplification test (NAAT) for C. difficile toxin gene (tg) for patient management. METHODS: Using data from the largest ever C. difficile diagnostic study (8853 diarrhoeal samples from 7335 patients), we determined the predicative value of C. difficile tgNAAT (Cepheid Xpert C.diff) low cycle threshold (CT) value for patient toxin positive status, CDI severity, mortality and CDI recurrence. Reference methods for CDI diagnosis were cytotoxicity assay (CTA) and cytotoxigenic culture (CTC). RESULTS: Of 1281 tgNAAT positive faecal samples, 713 and 917 were CTA and CTC positive, respectively. The median tgNAAT CT for patients who died was 25.5 vs 27.5 for survivors (p = 0.021); for toxin-positivity was 24.9 vs 31.6 for toxin-negative samples (p<0.001) and for patients with a recurrence episode was 25.6 vs 27.3 for those who did not have a recurrent episode (p = 0.111). Following optimal cut-off determination, low CT was defined as ≤25 and was significantly associated with a toxin-positive result (P<0.001, positive predictive value 83.9%), presence of PCR-ribotype 027 (P = 0.025), and mortality (P = 0.032). Recurrence was not associated with low CT (p 0.111). CONCLUSIONS: Low tgNAAT CT could indicate CTA positive patients, have more severe infection, increased risk of mortality and possibly recurrence. Although, the limited specificity of tgNAAT means it cannot be used as a standalone test, it could augment a more timely diagnosis, and optimise management of these at-risk patients.


Asunto(s)
Toxinas Bacterianas/genética , Enterocolitis Seudomembranosa , Heces/microbiología , Genes Bacterianos , Técnicas de Amplificación de Ácido Nucleico , Supervivencia sin Enfermedad , Enterocolitis Seudomembranosa/genética , Enterocolitis Seudomembranosa/mortalidad , Femenino , Humanos , Masculino , Tasa de Supervivencia
11.
J Antimicrob Chemother ; 73(7): 1908-1916, 2018 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-29684147

RESUMEN

Background: Sepsis and bacterial meningitis are major causes of mortality and morbidity in neonates and infants. Meropenem, a broad-spectrum antibiotic, is not licensed for use in neonates and infants below 3 months of age and sufficient information on its plasma and CSF disposition and dosing in neonates and infants is lacking. Objectives: To determine plasma and CSF pharmacokinetics of meropenem in neonates and young infants and the link between pharmacokinetics and clinical outcomes in babies with late-onset sepsis (LOS). Methods: Data were collected in two recently conducted studies, i.e. NeoMero-1 (neonatal LOS) and NeoMero-2 (neonatal meningitis). Optimally timed plasma samples (n = 401) from 167 patients and opportunistic CSF samples (n = 78) from 56 patients were analysed. Results: A one-compartment model with allometric scaling and fixed maturation gave adequate fit to both plasma and CSF data; the CL and volume (standardized to 70 kg) were 16.7 (95% CI 14.7, 18.9) L/h and 38.6 (95% CI 34.9, 43.4) L, respectively. CSF penetration was low (8%), but rose with increasing CSF protein, with 40% penetration predicted at a protein concentration of 6 g/L. Increased infusion time improved plasma target attainment, but lowered CSF concentrations. For 24 patients with culture-proven Gram-negative LOS, pharmacodynamic target attainment was similar regardless of the test-of-cure visit outcome. Conclusions: Simulations showed that longer infusions increase plasma PTA but decrease CSF PTA. CSF penetration is worsened with long infusions so increasing dose frequency to achieve therapeutic targets should be considered.


Asunto(s)
Antibacterianos/sangre , Antibacterianos/líquido cefalorraquídeo , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Meropenem/sangre , Meropenem/líquido cefalorraquídeo , Sepsis/tratamiento farmacológico , Antibacterianos/farmacocinética , Europa (Continente) , Femenino , Humanos , Lactante , Recién Nacido , Infusiones Intravenosas , Masculino , Meningitis Bacterianas/tratamiento farmacológico , Meropenem/farmacocinética , Método de Montecarlo , Sepsis Neonatal/tratamiento farmacológico , Sepsis/microbiología
12.
Lancet ; 391(10121): 668-678, 2018 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-29249276

RESUMEN

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment.


Asunto(s)
Antibióticos Antituberculosos/administración & dosificación , Bacteriemia/tratamiento farmacológico , Rifampin/administración & dosificación , Infecciones Estafilocócicas/tratamiento farmacológico , Administración Intravenosa , Administración Oral , Anciano , Antibióticos Antituberculosos/farmacología , Bacteriemia/microbiología , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infección Hospitalaria/tratamiento farmacológico , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rifampin/farmacología , Insuficiencia del Tratamiento
15.
J Clin Microbiol ; 53(5): 1473-83, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25673793

RESUMEN

The treatment of drug-resistant tuberculosis cases is challenging, as drug options are limited, and the existing diagnostics are inadequate. Whole-genome sequencing (WGS) has been used in a clinical setting to investigate six cases of suspected extensively drug-resistant Mycobacterium tuberculosis (XDR-TB) encountered at a London teaching hospital between 2008 and 2014. Sixteen isolates from six suspected XDR-TB cases were sequenced; five cases were analyzed in a clinically relevant time frame, with one case sequenced retrospectively. WGS identified mutations in the M. tuberculosis genes associated with antibiotic resistance that are likely to be responsible for the phenotypic resistance. Thus, an evidence base was developed to inform the clinical decisions made around antibiotic treatment over prolonged periods. All strains in this study belonged to the East Asian (Beijing) lineage, and the strain relatedness was consistent with the expectations from the case histories, confirming one contact transmission event. We demonstrate that WGS data can be produced in a clinically relevant time scale some weeks before drug sensitivity testing (DST) data are available, and they actively help clinical decision-making through the assessment of whether an isolate (i) has a particular resistance mutation where there are absent or contradictory DST results, (ii) has no further resistance markers and therefore is unlikely to be XDR, or (iii) is identical to an isolate of known resistance (i.e., a likely transmission event). A small number of discrepancies between the genotypic predictions and phenotypic DST results are discussed in the wider context of the interpretation and reporting of WGS results.


Asunto(s)
Técnicas Bacteriológicas/métodos , Tuberculosis Extensivamente Resistente a Drogas/diagnóstico , Genoma Bacteriano , Técnicas de Diagnóstico Molecular/métodos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Análisis de Secuencia de ADN/métodos , Genes Bacterianos , Genotipo , Hospitales de Enseñanza , Humanos , Londres , Mutación , Mycobacterium tuberculosis/aislamiento & purificación , Factores de Tiempo
16.
Infect Dis Clin North Am ; 29(1): 63-82, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25595842

RESUMEN

Accurate diagnosis of Clostridium difficile infection (CDI) is important not only for patient care but also for epidemiology and disease research. As it is not possible clinically to reliably differentiate CDI from other causes of health care-associated diarrhea, the laboratory confirmation of CDI is essential. Rapid commercial assays, including nucleic acid amplification tests and immunoassays for C difficile toxin and glutamate dehydrogenase, have largely superseded the use of older assays. Although assays that detect the presence of free C difficile toxin in feces are less frequently positive than tests for organism, they are preferable for the detection of CDI.


Asunto(s)
/aislamiento & purificación , Infecciones por Clostridium/diagnóstico , Enfermedades Gastrointestinales/diagnóstico , Toxinas Bacterianas/análisis , Técnicas de Tipificación Bacteriana , /genética , Infecciones por Clostridium/microbiología , Citotoxinas/análisis , Heces/microbiología , Enfermedades Gastrointestinales/microbiología , Humanos , Técnicas para Inmunoenzimas , Técnicas de Amplificación de Ácido Nucleico , Sensibilidad y Especificidad
17.
J Clin Pathol ; 67(11): 1013-6, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25078330

RESUMEN

The only method currently available to perform Neisseria gonorrhoeae antimicrobial susceptibility testing (Ng-AST) requires a viable organism obtained by culture. Reports of in vitro resistance to extended-spectrum cephalosporins, the treatment of choice for gonorrhoea, coupled with increasing gonorrhoea diagnoses is worrying. The aim of this study was to identify various methodologies employed by the UK microbiology laboratories to perform Ng-AST. Of the 118 laboratories that responded, 114 offered Ng-AST; the majority (82.5%, 94/114) of the laboratories used British Society for Antimicrobial Chemotherapy methodology for Ng-AST. The other main findings were infrequent use of quality control procedures and inconsistent susceptibility testing of the antibiotics used routinely for treatment.


Asunto(s)
Antibacterianos/uso terapéutico , Gonorrea/tratamiento farmacológico , Laboratorios/normas , Pruebas de Sensibilidad Microbiana/normas , Neisseria gonorrhoeae/efectos de los fármacos , Estudios Transversales , Gonorrea/diagnóstico , Gonorrea/microbiología , Adhesión a Directriz/normas , Encuestas de Atención de la Salud , Humanos , Neisseria gonorrhoeae/aislamiento & purificación , Guías de Práctica Clínica como Asunto/normas , Valor Predictivo de las Pruebas , Control de Calidad , Indicadores de Calidad de la Atención de Salud/normas , Encuestas y Cuestionarios , Reino Unido
19.
Sex Transm Infect ; 89(2): 105-7, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23038711

RESUMEN

OBJECTIVES: Environmental contamination with DNA from Chlamydia trachomatis (CT) has previously been found in Genitourinary Medicine (GUM) clinics. There are no known cases of cross-contamination of clinical samples and no known nosocomial infections. We investigated whether diagnostic samples could become contaminated from the environment by running dummy sample and carrying out a patient-throughput analysis. A total of 29 748 patients attended clinics over a year. Of these, 2860 (9.6%) had a positive Chlamydia test result. METHOD: (1) A run of dummy samples (60 urine samples and 10 swabs) were processed as normal clinic specimens. (2) Patient-throughput analysis: Patient numbers attending the GUM clinic on a given day was categorised as low, moderate or high. χ(2) Tests were used to look for associations between categorical variables and Chlamydia test positivity. A Poisson regression model was fitted to look at the effect of the number of people in the clinic on the number of positive results in a given day. As some clinics were only run on certain days of the week, a sensitivity analysis was later performed with attendances at non-daily clinics removed. RESULTS: All dummy samples tested negative and we did not find evidence of an association between daily Chlamydia positivity and clinic attendance. CONCLUSIONS: It is unlikely that environmental or cross-contamination of CT has lead to significant numbers of false positive results. Laboratories check for possible cross-contamination routinely. The extension of this simple routine practice to all clinical areas could provide quality assurance, improving confidence in the results in clinics.


Asunto(s)
Infecciones por Chlamydia/diagnóstico , Chlamydia trachomatis/aislamiento & purificación , Infección Hospitalaria/epidemiología , Contaminación de ADN , Errores Diagnósticos/estadística & datos numéricos , Microbiología Ambiental , Adulto , Femenino , Humanos , Masculino
20.
Trials ; 13: 241, 2012 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-23249501

RESUMEN

BACKGROUND: Staphylococcus aureus bacteraemia is a common and serious infection, with an associated mortality of ~25%. Once in the blood, S. aureus can disseminate to infect almost any organ, but bones, joints and heart valves are most frequently affected. Despite the infection's severity, the evidence guiding optimal antibiotic therapy is weak: fewer than 1,500 patients have been included in 16 randomised controlled trials investigating S. aureus bacteraemia treatment. It is uncertain which antibiotics are most effective, their route of administration and duration, and whether antibiotic combinations are better than single agents. We hypothesise that adjunctive rifampicin, given in combination with a standard first-line antibiotic, will enhance killing of S. aureus early in the treatment course, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. Our aim is to determine whether adjunctive rifampicin reduces all-cause mortality within 14 days and bacteriological failure or death within 12 weeks from randomisation. METHODS: We will perform a parallel group, randomised (1:1), blinded, placebo-controlled trial in NHS hospitals across the UK. Adults (≥ 18 years) with S. aureus (meticillin-susceptible or resistant) grown from at least one blood culture who have received ≤ 96 h of active antibiotic therapy for the current infection and do not have contraindications to the use of rifampicin will be eligible for inclusion. Participants will be randomised to adjunctive rifampicin (600-900 mg/day; orally or intravenously) or placebo for the first 14 days of therapy in combination with standard single-agent antibiotic therapy. The co-primary outcome measures will be all-cause mortality up to 14 days from randomisation and bacteriological failure/death (all-cause) up to 12 weeks from randomisation. 940 patients will be recruited, providing >80% power to detect 45% and 30% reductions in the two co-primary endpoints of death by 14 days and bacteriological failure/death by 12 weeks respectively. DISCUSSION: This pragmatic trial addresses the long-standing hypothesis that adjunctive rifampicin improves outcome from S. aureus bacteraemia through enhanced early bacterial killing. If proven correct, it will provide a paradigm through which further improvements in outcome from S. aureus bacteraemia can be explored.


Asunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Protocolos Clínicos , Rifampin/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Bacteriemia/mortalidad , Humanos , Rifampin/efectos adversos , Tamaño de la Muestra , Infecciones Estafilocócicas/mortalidad
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