Publications (19)52.33 Total impact
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Article: Epidemiology of extended-spectrum beta-lactamase-producing Enterobacteriaceae in a UK district hospital; an observational study.
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ABSTRACT: Extended-spectrum beta-lactamases (ESBLs) are an increasingly important cause of resistance in Gram-negative bacteria throughout the world. We investigated the clinical and molecular epidemiology of infections caused by ESBL-producing Enterobacteriaceae in a UK hospital, to identify the types of ESBL produced and risk factors for acquisition. Between July 2008 and June 2009, all patients yielding ESBL-producing Enterobacteriaceae from any clinical specimen were prospectively investigated using a questionnaire. API20E was used for bacterial identification; susceptibility testing and ESBL production were assessed by BSAC disc diffusion and cefpodoxime-clavulanate synergy tests, respectively. Polymerase chain reaction was used to screen a subset of isolates for bla(CTX-M) genes, to assign Escherichia coli isolates to their phylogenetic groups, and to identify members of the uropathogenic ST131 lineage. The overall prevalence of ESBL producers among clinical samples yielding Enterobacteriaceae was 1%; ESBL producers, obtained from 124 patients, were E. coli (N = 105), Klebsiella pneumoniae (N = 12), and others (N = 7). The main risk factors identified include recent antibiotic use (93%) and presence of a urinary catheter (24%). CTX-M group 1 ESBLs dominated (in 59 of 78, 76%, isolates studied). Most E. coli (35 of 56 tested) were phylogroup B2; of these, 23 belonged to the ST131 clone, 12 were phylogroup D, and four each belonged to phylogroups A and B1. ESBLs are an uncommon but significant problem in north-west Cambridgeshire. CTX-M-type enzymes were found in 75% of ESBL-positive isolates. All but two patients had at least one recognized risk factor. This study supports the requirement for interventions to reduce inappropriate urinary catheterization and antibiotic prescribing.The Journal of hospital infection 06/2012; 81(4):270-7. · 3.01 Impact Factor -
Article: An audit of acute bacterial meningitis in a large teaching hospital 2005-10.
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ABSTRACT: Acute bacterial meningitis (ABM) is a rare disease associated with severe neurological sequelae and death. Clinical features on admission may be subtle and thus delay recognition. Previous studies have shown association between early administration of antibiotics and favourable outcomes. To examine the presenting clinical features of patients aged >15 years with ABM admitted to a University teaching hospital. To audit investigations and treatment including lumbar puncture (LP), computed tomography (CT) and antibiotics against British Infection Association guidelines. Retrospective observational audit. Hospital records were reviewed for presenting clinical features and timing of CT scan, LP and antibiotics. Records of 39 patients with ABM were reviewed. The classical triad of fever, neck stiffness and altered mental state was present on admission in only 21% of cases. LP was contraindicated in 69% of cases. Immediate LP was carried out in only 17% of those who had no contraindication. Antibiotics were administered after a median of 79 min (interquartile range 24-213 min); 65% were given within 3 h after arrival. Eighty-five percent of patients had antibiotics in accordance with local guidelines. In patients with ABM, the classical clinical features are uncommon on arrival to hospital and frequently evolve following admission. The majority of patients have contraindications to immediate LP. Efforts should be made to facilitate immediate LP performed in the Emergency Department when there are no contraindications. Earlier administration of antibiotics in cases of suspected ABM and close review following admission is recommended.QJM: monthly journal of the Association of Physicians 08/2011; 104(12):1055-63. · 2.33 Impact Factor -
Article: Posaconazole for the treatment of mucormycosis.
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ABSTRACT: Posaconazole (PCZ) is an orally administered, extended-spectrum triazole antifungal agent with activity against the Mucorales. This article describes the clinical and laboratory data supporting its use against this rare group of pathogens. To date, PCZ has been mostly used for salvage therapy and at present there is no strong published clinical evidence to support its role as a single agent in the treatment of mucormycosis. Further studies are required to explore its role as a single agent and in combination therapy for the management of these infections.International journal of antimicrobial agents 07/2011; 38(6):465-73. · 3.03 Impact Factor -
Article: Outcome for Gram-negative bacteraemia when following restrictive empirical antibiotic guidelines.
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ABSTRACT: Restrictions in prescribing broad spectrum antimicrobials have been part of a strategy to reduce Clostridium difficile cases in the UK in recent years. However, there has been little work on assessing the safety of alternative antimicrobial agents. We performed an uncontrolled prospective observational survey over a 1-year period to determine the effectiveness and safety of a new antimicrobial stewardship programme in a district hospital in the UK. In total, 227 Gram-negative bacteraemias (203 episodes) occurred in the study period. Guidelines were adequate in 194 of 203 (95%) episodes and 163 episodes (80.2%) received adequate therapy. Patients in the inadequate therapy group had >2-fold increased likelihood of death [odds ratio (OR) = 2.63, 95% confidence interval (CI) = 1.09-6.34] within 30 days and >6-fold increased risk of death (OR = 6.40, 95% CI = 2.22-18.45) within 1 week when compared to patients in the adequate therapy group. Failure to administer gentamicin was the principal reason for not following the guidelines (18 episodes). Eight of these 18 episodes were susceptible to cefuroxime and two of these patients died. Adherence to the guidelines was associated with a correct empirical antibiotic choice and reduced mortality. This study also demonstrates the importance of adopting guidelines based on local susceptibility patterns.QJM: monthly journal of the Association of Physicians 11/2010; 104(5):411-9. · 2.33 Impact Factor -
Article: Bacteraemia and subsequent vertebral osteomyelitis: a retrospective review of 125 patients.
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ABSTRACT: Vertebral osteomyelitis (VO) is associated with considerable morbidity and its incidence seems to be increasing. Haematogenous spread is an important aetiological factor. The objective was to describe a series of patients with VO and to search for a relationship between preceding bacteraemia and subsequent VO with the same pathogen. Design and methods: A retrospective study of all treated cases of VO in a tertiary hospital over a 10-year period. There were 129 cases of VO (involving 125 patients) that received antimicrobial treatment. Eighty-three (66%) were male and the mean age was 59.5 years (range 1 month to 87 years). The vertebral level involved was lumbar in 66 (53%) cases and thoracic in 35 (28%) cases. Seventy-four cases (59%) had a microbiologically confirmed aetiology. The diagnostic yield from procedures was 46 and 36% from blood culture and bone biopsy, respectively. Staphylococcus aureus was the most common pathogen [38 of 74 (51%) cases]. Nine of 38 (24%) cases of Staphylococcus aureus VO had a preceding bacteraemia with the same pathogen in the previous year. Staphylococcus aureus is an important pathogen causing bacteraemia with the ability to cause metastatic complications including VO. The high proportion of cases developing VO following a documented bacteraemia, sometimes many months previously, reinforce the importance of adequate aggressive treatment for bacteraemia. VO must be considered in all patients presenting with back pain up to a year after bacteraemia. Previous bacteraemias with relevant pathogens can help guide antibiotic treatment at presentation of VO and if biopsy cannot be obtained.QJM: monthly journal of the Association of Physicians 10/2010; 104(3):201-7. · 2.33 Impact Factor -
Article: Comment on: Antibiotic stewardship--more education and regulation not more availability?
Journal of Antimicrobial Chemotherapy 03/2010; 65(3):598. · 5.07 Impact Factor -
Article: A review of mortality due to Clostridium difficile infection.
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ABSTRACT: SUMMARY: In this review we examine published literature to ascertain mortality in relation to Clostridium difficile infection (CDI) and the factors associated with mortality. In the 27 studies that had sufficient data, there were 10975 cases of CDI with great heterogeneity in the methods for reporting mortality. We calculated the overall associated mortality to be at least 5.99% within 3 months of diagnosis. The most important finding is that higher mortality is associated with advanced age, being 13.5% in patients over 80 years. Studies performed after 2000 had a significantly higher mortality than those before this date. We propose minimum standards for reporting mortality in future studies.The Journal of infection 03/2010; 61(1):1-8. · 4.13 Impact Factor -
Article: Prevention and medical management of Clostridium difficile infection.
BMJ (Clinical research ed.). 01/2010; 340:c1296. -
Article: Role of interferon-gamma release assays in healthcare workers.
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ABSTRACT: The advent of interferon-gamma release assays (IGRAs) provides new options for detection of latent tuberculosis infection (LTBI). This is particularly relevant to healthcare workers (HCWs), who are at higher risk of infection, but who have often also been vaccinated. In this article, we discuss the role of IGRAs for the diagnosis of LTBI in various healthcare settings. A search was performed for studies that reported data on IGRAs in HCWs in the last 18 years. Twenty-two studies met the inclusion criteria. IGRAs showed poor agreement with the tuberculin skin test (TST), except in countries with high incidences of tuberculosis (TB), but generally correlated better with markers of exposure to TB including during contact investigation. The T-SPOT.TB assay has not been adequately assessed in HCWs; the few studies available showed enhanced specificity of T-SPOT.TB when compared to TST. This review confirms the utility of IGRAs as important tools in the prevention and control of tuberculosis in healthcare settings.The Journal of hospital infection 09/2009; 73(2):101-8. · 3.01 Impact Factor -
Article: Oral antimicrobial options for the treatment of skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in the UK.
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ABSTRACT: This review outlines the oral treatment options available for treating skin and soft-tissue infections due to methicillin-resistant Staphylococcus aureus (MRSA) in the community and discusses the evidence supporting their use.International journal of antimicrobial agents 01/2009; 33(6):497-502. · 3.03 Impact Factor -
Article: Detection of Mycobacterium avium subspecies paratuberculosis from patients with Crohn's disease using nucleic acid-based techniques: a systematic review and meta-analysis.
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ABSTRACT: This study is a systematic review and meta-analysis of studies using nucleic acid-based techniques to detect Mycobacterium avium paratuberculosis (MAP) in patients with Crohn's disease (CD) compared with controls. Database searches were conducted and risk difference estimates were calculated using meta-analysis. Fifty-eight studies were reviewed, 47 of which were included in the analysis. The pooled estimate of risk difference from all studies was 0.23 (95% confidence interval [CI], 0.14-0.32) using a random effects model. Similarly, MAP was detected more frequently from patients with CD compared with those with ulcerative colitis (risk difference 0.19, 95% CI, 0.10-0.28). Year of study, assay type, and inclusion of children explained some but not all of the observed heterogeneity. The data confirms the observation that MAP is detected more frequently among CD patients compared with controls. However, the pathogenic role of this bacterium in the gut remains uncertain. Our analysis demonstrates that there is an association between MAP and CD, across many sites, by many investigators, and controlling for a number of factors; however, this association remains controversial and inconclusive. Future studies should determine whether there is a pathogenic role.Inflammatory Bowel Diseases 04/2008; 14(3):401-10. · 4.86 Impact Factor -
Article: Treatment of cryptosporidiosis in immunocompromised individuals: systematic review and meta-analysis.
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ABSTRACT: Cryptosporidium is a common cause of gastroenteritis and is associated with severe life-threatening illness among immunocompromised individuals. This review aimed to assess the efficacy of interventions for the treatment and prevention of cryptosporidiosis among immunocompromised patients. A search of Medline, Embase and other electronic databases was carried out up to August 2005. Two reviewers independently extracted data and assessed study quality. The relative risk for each intervention was calculated. Seven trials involving 169 participants were included. Nitazoxanide and paramomycin were associated with a relative risk (RR) of reduction in the duration and frequency of diarrhoea of 0.83 [95% confidence interval (CI) 0.36, 1.94] and 0.74 (95% CI 0.42, 1.31), respectively, showing no evidence of effectiveness. Nitazoxanide led to significant evidence of oocyst clearance compared with placebo with a RR of 0.52 (95% CI 0.30, 0.91). The effect was not significant for HIV-seropositive participants (RR 0.71, 95% CI 0.36, 1.37). HIV-seronegative participants on nitazoxanide had a significantly higher relative risk of achieving parasitological clearance of 0.26 (95% CI 0.09, 0.80) based on a single study. No other intervention was associated with either a reduction in diarrhoea, mortality or a significant parasitological response. This review confirms the absence of evidence for effective agents in the management of cryptosporidiosis. The results indicate that nitaxozanide reduces load of parasites and may be useful in immunocompetent individuals. The absence of effective therapy highlights the importance of preventive interventions in this group of patients.British Journal of Clinical Pharmacology 05/2007; 63(4):387-93. · 2.96 Impact Factor -
Article: Prevention and treatment of cryptosporidiosis in immunocompromised patients.
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ABSTRACT: Cryptosporidiosis is a disease that causes diarrhoea lasting about one to two weeks, sometimes extending up to 2.5 months among the immunocompetent and becoming a more severe life-threatening illness among immunocompromised individuals. Cryptosporidium is a common cause of gastroenteritis. Cryptosporidiosis is common in HIV-infected individuals. The objective of the review was to assess the efficacy of interventions for the treatment and prevention of cryptosporidiosis among immunocompromised individuals. We searched the following databases for randomised controlled trials up to August 2005: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, AIDSLINE, AIDSearch, EMBASE, CINAHL, Current Contents, Geobase, and the Environmental Sciences and Pollution Management. Randomised controlled trials that compared the use of any intervention to treat or prevent cryptosporidiosis in immunocompromised persons were included. The outcome measures for treatment studies included symptomatic diarrhoea and oocyst clearance. Two reviewers independently assessed the trials for quality of randomisation, blinding, withdrawals, and adequacy of allocation concealment. The relative risk for each intervention was calculated using a random effects model. Seven trials involving 169 participants were included. There were 130 adults with AIDS enrolled in five studies. Evidence of significant heterogeneity was present. There was no evidence for a reduction in the duration or frequency of diarrhoea by nitazoxanide (RR 0.83 (95% CI 0.36-1.94)) and paramomycin (RR 0.74 (95% CI 0.42-1.31)) compared with placebo. Nitazoxanide led to a significant evidence of oocyst clearance compared with placebo among all children with a relative risk of 0.52 (95% CI 0.30-0.91). The effect was not significant for HIV-seropositive participants (RR 0.71 (95% CI 0.36-1.37)). HIV-seronegative participants on nitazoxanide had a significantly higher relative risk of achieving parasitological clearance of 0.26 (95% CI 0.09-0.80) based on a single study. The single study comparing spiramycin with placebo found no significant difference in reduction of the duration of hospitalisation (mean difference -0.40 days (95% CI -6.62-5.82)) or in mortality between the two arms of the trial (RR 0.43 (95% CI 0.04-4.35)). One study assessed the role of bovine dialyzable leukocyte extract, reporting a relative risk for decreased stool frequency of 0.19 (95% CI 0.03-1.19), while another compared bovine hyperimmune colostrum with placebo and found no evidence for improvement of stool volume (RR 3.00 (95% CI 0.61-14.86)) or in oocyst concentration per ml of stool (RR 0.27 (95% CI 0.02-3.74)). No studies were found that assessed prevention. This review confirms the absence of evidence for effective agents in the management of cryptosporidiosis. The results indicate that nitaxozanide reduces the load of parasites and may be useful in immunocompetent individuals. Due to the seriousness of the potential outcomes of cryptosporidiosis, the use of nitaxozanide should be considered in immunocompromised patients. The absence of effective therapy highlights the need to ensure that infection is avoided. Unfortunately, evidence for the effectiveness and cost-effectiveness of preventive interventions is also lacking.Cochrane database of systematic reviews (Online) 02/2007; · 5.72 Impact Factor -
Article: Candidaemia in a large teaching hospital: a clinical audit.
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ABSTRACT: Candidaemias are associated with significant morbidity and mortality. The British Society of Medical Mycology and Infectious Diseases Society of America recently published audit standards, to address the changing epidemiology of candidaemia and to improve outcomes. To investigate the local epidemiology of candidaemia and the standard of care in a large teaching hospital. Retrospective audit. Data were obtained for all candidaemia episodes over the 4-year period ending July 2004, from the medical and nursing notes, laboratory computer and patient administration system. We identified 92 episodes in 90 patients. The main predisposing factors were being on an intensive care unit, having a central venous catheter, and (for neonates) prematurity. Central venous catheters were removed at a mean 1.8 days following candidaemia; 79% (37/47) were removed within 48 h (the audit standard). Identification and susceptibility tests were performed for 94.7% of isolates. All were susceptible to amphotericin B; 87% were susceptible to fluconazole. Antifungal treatment was started within 24 h of a positive blood culture in 84% of episodes. Initial antifungal therapy was appropriate in 95% (61/64) of treated cases. Most patients (81%) who survived or completed their intended course of treatment before death received at least 2 weeks treatment. However, only 45% of those transferred to other hospitals had accompanying guidance on the intended further duration of therapy. Thirty-day mortality was 41%. After adjustment for age, the presence of Candida-related complications was associated with an odds ratio for mortality of 6.5 (95% CI 1.2-36.5, p = 0.03). Overall the audit standards set by the BSMM and IDSA were met, and discrepancies did not lead to a change in outcome. Improved intravenous catheter care, a more pro-active approach to searching for complications, and improvement in the inter-hospital transfer process, will assist in reducing morbidity and mortality.QJM: monthly journal of the Association of Physicians 11/2006; 99(10):655-63. · 2.33 Impact Factor -
Article: Molecular diagnosis of Fusobacterium necrophorum infection (Lemierre's syndrome).
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ABSTRACT: Presented here is the case of a 27-year-old male with atypical features of Lemierre's syndrome in which a definitive diagnosis was achieved using molecular methods. While routine investigations, including bacterial cultures, were unhelpful, two real-time PCR assays demonstrated Fusobacterium necrophorum-specific DNA in aspirates from brain and renal abscesses. This is the first report demonstrating that a laboratory diagnosis can be made using molecular methods in suspected cases of Lemierre's syndrome. Use of these methods can thus resolve diagnostic confusion, prevent unnecessary investigation, and direct specific antimicrobial treatment.European Journal of Clinical Microbiology 04/2005; 24(3):226-9. · 2.86 Impact Factor -
Article: Molecular diagnosis of Fusobacterium necrophorum infection (Lemierre’s syndrome)
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ABSTRACT: Presented here is the case of a 27-year-old male with atypical features of Lemierres syndrome in which a definitive diagnosis was achieved using molecular methods. While routine investigations, including bacterial cultures, were unhelpful, two real-time PCR assays demonstrated Fusobacterium necrophorum-specific DNA in aspirates from brain and renal abscesses. This is the first report demonstrating that a laboratory diagnosis can be made using molecular methods in suspected cases of Lemierres syndrome. Use of these methods can thus resolve diagnostic confusion, prevent unnecessary investigation, and direct specific antimicrobial treatment.European Journal of Clinical Microbiology 02/2005; 24(3):226-229. · 2.86 Impact Factor -
Article: Real-time PCR investigation into the importance of Fusobacterium necrophorum as a cause of acute pharyngitis in general practice.
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ABSTRACT: Fusobacterium necrophorum is recognized as the cause of a severe life-threatening illness characterized by bacteraemia with metastatic abscesses following an acute sore throat (Lemierre's disease). However, the importance of F. necrophorum as a cause of simple sore throat in the community is unknown. Using quantitative real-time PCR with primers targeting the rpoB gene, 100 routine throat swabs collected from patients presenting to general practitioners with pharyngitis were analysed for the presence of F. necrophorum-specific DNA. The results were compared with those obtained from throat swabs collected from 100 healthy subjects. Ten clinical samples were positive for F. necrophorum DNA, identified as F. necrophorum subspecies funduliforme, using a haemagglutinin-related protein gene-specific PCR assay. All the healthy controls were negative (two-tailed P value = 0.0015; Fisher exact test). These findings suggest that F. necrophorum may play a more important role as a cause of simple sore throat in the community than has been previously appreciated.Journal of Medical Microbiology 11/2004; 53(Pt 10):1029-35. · 2.50 Impact Factor -
Article: Prevención y tratamiento de la criptosporidiosis para pacientes inmunocomprometidos
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Article: Tuberculous Meningitis and Hydrocephalus Treated Successfully with a Combination of Immunomodulation and Cerebrospinal Fluid Diversion
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ABSTRACT: The management of tuberculous meningitis with hydrocephalus is complex with most centres advocating ventriculoperitoneal shunting only in the presence of raised CSF pressure. This article reports a case of tuberculous meningitis with hydrocephalus treated with a combination of early surgical and immunomodulatory therapy in addition to conventional steroids and antituberculous agents. This case demonstrates that during the early phase of tuberculous meningitis with hydrocephalus, a combined multi-disciplinary approach will help prevent neuronal injury due to progressive ventricular enlargement and inflammation.
Top Journals
Institutions
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2004–2011
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Addenbrooke's Hospital
Cambridge, ENG, United Kingdom
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2010
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The Bracton Centre, Oxleas NHS Trust
Dartford, ENG, United Kingdom
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2009
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Peterborough City Hospital
Peterborough, ENG, United Kingdom
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