Publications by authors named "Stephen Morris-Jones"

30 Publications

  • Page 1 of 1

Bedaquiline as Treatment for Disseminated Nontuberculous Mycobacteria Infection in 2 Patients Co-Infected with HIV.

Emerg Infect Dis 2021 Mar;27(3):944-948

Nontuberculous mycobacteria can cause disseminated infections in immunocompromised patients and are challenging to treat because of antimicrobial resistance and adverse effects of prolonged multidrug treatment. We report successful treatment with bedaquiline, a novel antimycobacterial drug, as part of combination therapy for 2 patients with disseminated nontuberculous mycobacteria co-infected with HIV.
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http://dx.doi.org/10.3201/eid2703.202359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920675PMC
March 2021

Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis.

JCI Insight 2020 09 17;5(18). Epub 2020 Sep 17.

School of Clinical and Experimental Sciences, Faculty of Medicine, and.

BACKGROUNDTuberculosis (TB) kills more people than any other infection, and new diagnostic tests to identify active cases are required. We aimed to discover and verify novel markers for TB in nondepleted plasma.METHODSWe applied an optimized quantitative proteomics discovery methodology based on multidimensional and orthogonal liquid chromatographic separation combined with high-resolution mass spectrometry to study nondepleted plasma of 11 patients with active TB compared with 10 healthy controls. Prioritized candidates were verified in independent UK (n = 118) and South African cohorts (n = 203).RESULTSWe generated the most comprehensive TB plasma proteome to date, profiling 5022 proteins spanning 11 orders-of-magnitude concentration range with diverse biochemical and molecular properties. We analyzed the predominantly low-molecular weight subproteome, identifying 46 proteins with significantly increased and 90 with decreased abundance (peptide FDR ≤ 1%, q ≤ 0.05). Verification was performed for novel candidate biomarkers (CFHR5, ILF2) in 2 independent cohorts. Receiver operating characteristics analyses using a 5-protein panel (CFHR5, LRG1, CRP, LBP, and SAA1) exhibited discriminatory power in distinguishing TB from other respiratory diseases (AUC = 0.81).CONCLUSIONWe report the most comprehensive TB plasma proteome to date, identifying novel markers with verification in 2 independent cohorts, leading to a 5-protein biosignature with potential to improve TB diagnosis. With further development, these biomarkers have potential as a diagnostic triage test.FUNDINGColciencias, Medical Research Council, Innovate UK, NIHR, Academy of Medical Sciences, Program for Advanced Research Capacities for AIDS, Wellcome Centre for Infectious Diseases Research.
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http://dx.doi.org/10.1172/jci.insight.137427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526553PMC
September 2020

Azithromycin susceptibility testing for Salmonella enterica isolates: discordances in results using MIC gradient strips.

J Antimicrob Chemother 2020 07;75(7):1820-1823

Department of Clinical Microbiology, University College London Hospital NHS Foundation Trust, 5th Floor, 250 Euston Road, London NW1 2PG, UK.

Background: Azithromycin resistance is emerging in typhoidal Salmonella. Confirmation of azithromycin MIC is the most frequent antibiotic susceptibility request made to the Gastrointestinal Bacteria Reference Unit (GBRU) laboratory in England by local diagnostic laboratories.

Objectives: (i) Determine concordance between local diagnostic and reference laboratory estimations of azithromycin MIC by gradient strip in Salmonella enterica serovars Typhi and Paratyphi. (ii) Consider causes of variation.

Methods: Isolates from patients with enteric fever attending a central London hospital between May 2011 and April 2019 were tested for azithromycin susceptibility using gradient strips, according to EUCAST methodology. Matched local diagnostic and reference laboratory estimations of azithromycin and ciprofloxacin (as a comparator) MICs were included; concordance in estimations was examined.

Results: Local diagnostic laboratory readings overestimated azithromycin MIC values compared with the reference laboratory, resulting in poor concordance in susceptibility/resistance attribution (concordant susceptibility interpretation in 8/19, κ = 0). In contrast, ciprofloxacin MIC estimation demonstrated superior concordance (concordant susceptibility interpretation in 16/17, κ = 0.85). None of the isolates was resistant to azithromycin at the reference laboratory and no known genes associated with azithromycin resistance were detected in any isolate using WGS.

Conclusions: Overestimation of azithromycin resistance is likely to be due to difficulty in interpreting the point of intersection of the 'trailing edge' with the gradient strip, used to determine MIC. We advise local diagnostic laboratories to review their experience and consider adopting a 'second reader' system to mitigate this.
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http://dx.doi.org/10.1093/jac/dkaa097DOI Listing
July 2020

Routine Outpatient Parenteral Antimicrobial Therapy Clinic Review Minimizes Inpatient Readmission.

Clin Infect Dis 2020 Dec;71(10):2771-2773

Department of Clinical Microbiology, University College London Hospitals, London, United Kingdom.

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http://dx.doi.org/10.1093/cid/ciaa132DOI Listing
December 2020

Clinical outcomes of teicoplanin use in the OPAT setting.

Int J Antimicrob Agents 2020 Mar 8;55(3):105888. Epub 2020 Jan 8.

Division of Infection, University College London Hospitals, London, UK; Division of Infection & Immunity, University College London, London, UK. Electronic address:

Teicoplanin possesses several convenient properties for use in the delivery of outpatient parenteral antimicrobial therapy (OPAT) services. However, its use is not widespread and data on its efficacy in the OPAT setting are limited. Here we present a case series of patients undergoing OPAT care being treated by either teicoplanin-based (n = 107) or ceftriaxone-based (n = 191) antibiotic regimens. Clinical failure with teicoplanin occurred in five episodes of care (4.7%) compared with only two episodes of ceftriaxone-based OPAT care (1.0%). Teicoplanin-associated clinical failure was observed in 2 (33.3%) of 6 patients with Enterococcus infections compared with 3 (3.0%) of 101 patients with non-Enterococcus infections. Overall, there were four (2.9%) drug-related adverse events for teicoplanin and four (1.8%) for ceftriaxone, prompting a switch to teicoplanin in three patients. These findings support the continued use of teicoplanin in OPAT as well as its consideration in centres where it is not currently being offered.
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http://dx.doi.org/10.1016/j.ijantimicag.2020.105888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068648PMC
March 2020

Clinical and Economic Impact of Implementing OVIVA Criteria on Patients With Bone and Joint Infections in Outpatient Parenteral Antimicrobial Therapy.

Clin Infect Dis 2020 06;71(1):207-210

Division of Infection, University College London Hospitals, London, United Kingdom.

The OVIVA study demonstrated noninferiority for managing bone and joint infections (BJIs) with oral antibiotics. We report that 79.7% of OPAT patients being treated for BJIs at our center would be eligible for oral antibiotics, saving a median (IQR) 19.5 IV-antibiotic days (8.5-37) and GBP 1234 (569-2594) per patient.
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http://dx.doi.org/10.1093/cid/ciz991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312207PMC
June 2020

Ceftriaxone-resistant Salmonella Typhi in a traveller returning from a mass gathering in Iraq.

Lancet Infect Dis 2019 05;19(5):467

Infection Division, Hospital for Tropical Diseases, London, UK; Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.

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http://dx.doi.org/10.1016/S1473-3099(19)30176-8DOI Listing
May 2019

Unusual case of Lemierre's syndrome.

BMJ Case Rep 2018 Nov 28;11(1). Epub 2018 Nov 28.

Infectious diseases, Hospital for Tropical Diseases, London, UK.

A young previously healthy patient presented with sepsis and cavitating pneumonia. was isolated from blood cultures and subsequent CT neck showed an internal jugular vein thrombosis. Treatment was with antibiotics, anticoagulation and supportive management. Lemierre's syndrome is an infectious thrombophlebitis of the internal jugular vein. Although a rare diagnosis since the use of penicillin for treatment of acute pharyngitis, it is being reported with increasing frequency. Usually associated with spp, we believe that this is the first reported case of Lemierre's caused by an anaerobic member of the human oral cavity flora, usually associated with localised periodontal disease. The bacillus was isolated from blood during the acute presentation.
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http://dx.doi.org/10.1136/bcr-2018-226948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301635PMC
November 2018

Seasonal variation in the performance of QuantiFERON-TB Gold In-Tube assays used for the diagnosis of tuberculosis infection.

Tuberculosis (Edinb) 2018 05 8;110:26-29. Epub 2018 Mar 8.

Division of Infection and Immunity, University College London, Gower Street, London, UK; Department of Microbiology, University College London Hospitals NHS Trust, Euston Road, London, UK.

This study aimed to determine whether there are seasonal changes in the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) assays, an interferon-gamma release assay widely used for the diagnosis of tuberculosis infection. Results of 31,932 QFT-GIT assays performed at a large independent, accredited diagnostic service provider in London, UK over a 4.5-year-period were analysed. The proportion of positive results was significantly lower in autumn (14.8%) than in spring (16.0%; p = 0.0366) and summer (17.5%; p < 0.0001), but similar to winter (15.2%; p = 0.4711). The proportion of indeterminate results was significantly higher in autumn (8.2%) than in spring (6.2%; p < 0.0001), summer (4.8%; p < 0.0001), and winter (6.2%; p < 0.0001). The highest proportions of indeterminate results were observed in October (8.4%) and November (8.8%), the lowest in June (4.5%). Our data show that significant seasonal variation occurs in the performance of QFT-GIT assays in a temperate climate setting. Potential underlying mechanisms, including host and environmental factors, are discussed.
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http://dx.doi.org/10.1016/j.tube.2018.03.002DOI Listing
May 2018

Missed opportunities for tuberculosis prevention among patients accessing a UK HIV service.

Int J STD AIDS 2018 10 11;29(12):1234-1237. Epub 2018 May 11.

1 Bloomsbury Clinic, Mortimer Market Centre, Central & North West London NHS Foundation Trust, London, UK.

United Kingdom guidelines recommend screening for and treatment of latent tuberculosis infection (LTBI) in HIV-positive patients at high risk of active tuberculosis (TB) disease, but implementation is suboptimal. We investigated potential missed opportunities to identify and treat LTBI among HIV-positive patients accessing a large HIV outpatient service in London. Case records of all adult patients attending our service for HIV care diagnosed with active TB between 2011 and 2015 were reviewed to determine whether they met criteria for LTBI screening and whether screening was undertaken. Twenty-five patients were treated for TB. Of 15 (60%) patients who started TB treatment ≥6 months after HIV diagnosis, 14 (93%) met UK guideline-recommended criteria for LTBI screening and treatment; only one (7%) had been screened for LTBI. Eight of these 15 (53%) patients had additional risk factors for TB which are not reflected in current UK guidelines. Of 15 patients treated for TB ≥6 months after diagnosis of HIV, 14 (93%) had not been screened for LTBI, suggesting missed opportunities for TB prevention. People living with HIV may benefit from a broader approach to LTBI screening which takes into account additional recognised TB risk factors and ongoing TB exposure.
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http://dx.doi.org/10.1177/0956462418773010DOI Listing
October 2018

Rapid identification of a Mycobacterium tuberculosis full genetic drug resistance profile through whole genome sequencing directly from sputum.

Int J Infect Dis 2017 Sep 14;62:44-46. Epub 2017 Jul 14.

Division of Infection and Immunity, University College London, London, UK.

Introduction: Resistance to second-line tuberculosis drugs is common, but slow to diagnose with phenotypic drug sensitivity testing. Rapid molecular tests speed up diagnosis, but can only detect limited mutations. Whole genome sequencing (WGS) of culture isolates can generate a complete genetic drug resistance profile, but is delayed by the initial culture step. In the case presented here, successful WGS directly from sputum was achieved using targeted enrichment.

Case Report: A 29-year-old Nigerian woman was diagnosed with tuberculosis. Xpert MTB/RIF and Hain line probe assays identified rpoB and inhA mutations consistent with rifampicin and intermediate isoniazid resistance, and a further possible mutation conferring fluoroquinolone resistance. WGS directly from sputum identified a further inhA mutation consistent with high-level isoniazid resistance and confirmed the absence of fluoroquinolone resistance. Isoniazid was stopped, and the patient has completed 18 months of a fluoroquinolone-based regimen without relapse.

Discussion: Compared to rapid molecular tests (which can only examine a limited number of mutations) and WGS of culture isolates (which requires a culture step), WGS directly from sputum can quickly generate a complete genetic drug resistance profile. In this case, WGS altered the clinical management of drug-resistant tuberculosis and demonstrated potential for guiding individualized drug treatment where second-line drug resistance is common.
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http://dx.doi.org/10.1016/j.ijid.2017.07.007DOI Listing
September 2017

Correspondence to invasive shigellosis in MSM.

Int J STD AIDS 2017 03 26;28(4):421-422. Epub 2017 Jan 26.

1 Mortimer Market Centre, Central North West London NHS Foundation Trust, London, UK.

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http://dx.doi.org/10.1177/0956462417691441DOI Listing
March 2017

Blood transcriptomic diagnosis of pulmonary and extrapulmonary tuberculosis.

JCI Insight 2016 Oct 6;1(16):e87238. Epub 2016 Oct 6.

Division of Infection and Immunity, University College London, London, United Kingdom.

Novel rapid diagnostics for active tuberculosis (TB) are required to overcome the time delays and inadequate sensitivity of current microbiological tests that are critically dependent on sampling the site of disease. Multiparametric blood transcriptomic signatures of TB have been described as potential diagnostic tests. We sought to identify the best transcript candidates as host biomarkers for active TB, extend the evaluation of their specificity by comparison with other infectious diseases, and to test their performance in both pulmonary and extrapulmonary TB. Support vector machine learning, combined with feature selection, was applied to new and previously published blood transcriptional profiles in order to identify the minimal TB‑specific transcriptional signature shared by multiple patient cohorts including pulmonary and extrapulmonary TB, and individuals with and without HIV-1 coinfection. We identified and validated elevated blood basic leucine zipper transcription factor 2 () transcript levels as a single sensitive biomarker that discriminated active pulmonary and extrapulmonary TB from healthy individuals, with receiver operating characteristic (ROC) area under the curve (AUC) scores of 0.93 to 0.99 in multiple cohorts of HIV-1-negative individuals, and 0.85 in HIV-1-infected individuals. In addition, we identified and validated a potentially novel 4-gene signature comprising CD177, haptoglobin, immunoglobin J chain, and galectin 10 that discriminated active pulmonary and extrapulmonary TB from other febrile infections, giving ROC AUCs of 0.94 to 1. Elevated blood transcript levels provide a sensitive biomarker that discriminates active TB from healthy individuals, and a potentially novel 4-gene transcriptional signature differentiates between active TB and other infectious diseases in individuals presenting with fever. MRC, Wellcome Trust, Rosetrees Trust, British Lung Foundation, NIHR.
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http://dx.doi.org/10.1172/jci.insight.87238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053151PMC
October 2016

Propionibacterium acnes as a cause of lung abscess in a cardiac transplant recipient.

BMJ Case Rep 2015 Dec 16;2015. Epub 2015 Dec 16.

Department of Infectious Diseases, University College London Hospital, London, UK.

A 29-year-old man was admitted with fevers, cough, left-sided chest pain and lethargy for 1 week. He had a cardiac transplant 10 years prior and was on immunosuppressive drugs. He was found to have a pulmonary lesion and went on to develop a lung abscess. Propionibacterium acnes was identified on matrix-assisted laser desorption ionisation mass spectrometry-time of flight and 16s rRNA gene sequencing after drainage. He was curatively treated with co-trimoxazole and co-amoxiclav. He divulged a longstanding history of seborrhoeic dermatitis with frequent flares leading to large volumes of squames collecting on his bed sheets. We hypothesise this was a possible route of entry: inhalation of the Propionibacterium. This case highlights how a common commensal bacterium, P. acnes, was able to cause pathology in an immunosuppressed patient. This is the only case of a patient with transplantation developing a P. acnes pulmonary infection and the only case of P. acnes causing these clinical features to be reported in the literature.
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http://dx.doi.org/10.1136/bcr-2015-212431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691863PMC
December 2015

A novel approach for evaluating the performance of real time quantitative loop-mediated isothermal amplification-based methods.

Biomol Detect Quantif 2014 Dec 22;2:4-10. Epub 2014 Nov 22.

LGC, Queens Road, Teddington, UK.

Molecular diagnostic measurements are currently underpinned by the polymerase chain reaction (PCR). There are also a number of alternative nucleic acid amplification technologies, which unlike PCR, work at a single temperature. These 'isothermal' methods, reportedly offer potential advantages over PCR such as simplicity, speed and resistance to inhibitors and could also be used for quantitative molecular analysis. However there are currently limited mechanisms to evaluate their quantitative performance, which would assist assay development and study comparisons. This study uses a sexually transmitted infection diagnostic model in combination with an adapted metric termed isothermal doubling time (IDT), akin to PCR efficiency, to compare quantitative PCR and quantitative loop-mediated isothermal amplification (qLAMP) assays, and to quantify the impact of matrix interference. The performance metric described here facilitates the comparison of qLAMP assays that could assist assay development and validation activities.
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http://dx.doi.org/10.1016/j.bdq.2014.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121211PMC
December 2014

Staphylococcus lugdunensis septic arthritis and epidural abscess in a patient with rheumatoid arthritis receiving anti-tumour necrosis factor therapy.

Rheumatology (Oxford) 2014 Dec 8;53(12):2231. Epub 2014 Sep 8.

Department of Clinical Pharmacology and Department of Clinical Microbiology, University College Hospital, London, UK.

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http://dx.doi.org/10.1093/rheumatology/keu365DOI Listing
December 2014

Needles and the damage done: reasons for admission and financial costs associated with injecting drug use in a Central London Teaching Hospital.

J Infect 2013 Jan 12;66(1):95-102. Epub 2012 Oct 12.

Hospital for Tropical Diseases, University College London Hospital, United Kingdom.

Objectives: To establish the clinical reasons for inpatient admissions among injecting drug users. To determine the frequency of behavioural issues during their care and to estimate the financial implications of injecting drug use to the health service.

Methods: Retrospective cohort study at University College London Hospital. Clinical, laboratory and financial data were extracted from case notes and electronic records. The cost of each admission was compared to the income received for the period of care.

Results: 124 injecting drug users required 191 admissions between 2005 and 2009. Skin and soft tissue infections (58%) and pneumonia (18%) were the commonest reasons for admission. Bacteraemia at admission was often not accompanied by an inflammatory response. Exposure to HIV (4%), hepatitis B (49%) and C (84%) was common. Drug misuse (16%) during admission was frequent. The cost to the NHS of treating soft tissue infections in drug users was approximately £77 million per annum. After a median follow-up of 40 months, 10 patients (8%) had died. All deaths were attributable to drug use.

Conclusions: Bacterial and viral infections are largely responsible for the significant mortality and morbidity of injecting drug users presenting to secondary care. The financial burden to the NHS is substantial.
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http://dx.doi.org/10.1016/j.jinf.2012.10.004DOI Listing
January 2013

Travel-associated skin disease.

Infect Dis Clin North Am 2012 Sep 9;26(3):675-89. Epub 2012 Jul 9.

Dermatology Department, Kings College Hospital, Kings College London, London, UK.

Travel associated skin disease is extremely common and a frequent cause of the returning traveller seeking medical attention. Widespread cutaneous eruptions usually represent reactive rashes, indicating an underlying systemic infection or allergic reaction. Patients with disseminated or spreading rashes following travel often present with fever and malaise. In contrast, those presenting with localised skin disease such as a blister, nodule, plaque, ulcer etc are usually well in themselves but have sustained a bite/sting/penetrating injury or introduction of infection directly into the skin at the affected site. As a general rule widespread rashes are investigated with blood tests/serology and localised lesions with a skin biopsy for culture and histology.
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http://dx.doi.org/10.1016/j.idc.2012.05.010DOI Listing
September 2012

Management of quinolone-resistant typhoid osteomyelitis.

Br J Hosp Med (Lond) 2011 Aug;72(8):468-9

Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK.

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http://dx.doi.org/10.12968/hmed.2011.72.8.468DOI Listing
August 2011

Utility of endobronchial ultrasound-guided transbronchial needle aspiration in patients with tuberculous intrathoracic lymphadenopathy: a multicentre study.

Thorax 2011 Oct 3;66(10):889-93. Epub 2011 Aug 3.

Centre for Respiratory Research, University College London, 5 University Street, London WC1E 6JJ, UK.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as an important tool for the diagnosis and staging of lung cancer but its role in the diagnosis of tuberculous intrathoracic lymphadenopathy has not been established. The aim of this study was to describe the diagnostic utility of EBUS-TBNA in patients with intrathoracic lymphadenopathy due to tuberculosis (TB).

Methods: 156 consecutive patients with isolated intrathoracic TB lymphadenitis were studied across four centres over a 2-year period. Only patients with a confirmed diagnosis or unequivocal clinical and radiological response to antituberculous treatment during follow-up for a minimum of 6 months were included. All patients underwent routine clinical assessment and a CT scan prior to EBUS-TBNA. Demographic data, HIV status, pathological findings and microbiological results were recorded.

Results: EBUS-TBNA was diagnostic of TB in 146 patients (94%; 95% CI 88% to 97%). Pathological findings were consistent with TB in 134 patients (86%). Microbiological investigations yielded a positive culture of TB in 74 patients (47%) with a median time to positive culture of 16 days (range 3-84) and identified eight drug-resistant cases (5%). Ten patients (6%) did not have a specific diagnosis following EBUS; four underwent mediastinoscopy which confirmed the diagnosis of TB while six responded to empirical antituberculous therapy. There was one complication requiring an inpatient admission.

Conclusions: EBUS-TBNA is a safe and effective first-line investigation in patients with tuberculous intrathoracic lymphadenopathy.
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http://dx.doi.org/10.1136/thoraxjnl-2011-200063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361304PMC
October 2011

Drug fever and DRESS syndrome.

Br J Hosp Med (Lond) 2011 Apr;72(4):224-8

Basildon University Hospital, Essex, UK.

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http://dx.doi.org/10.12968/hmed.2011.72.4.224DOI Listing
April 2011

Selective testing of ß-galactosidase activity in the laboratory identification of Salmonella and Shigella species.

J Clin Pathol 2010 Dec 5;63(12):1101-4. Epub 2010 Oct 5.

Department of Clinical Microbiology, University College London Hospital, London, UK.

Background: Salmonella and Shigella species are pathogens of great medical and public health importance. However, laboratory identification of these organisms is time consuming. Using current standard laboratory algorithms, the vast majority of organisms submitted for serological typing with Salmonella-specific and Shigella-specific antisera are not clinically significant.

Aims: To assess the addition of the O-nitrophenyl-β-d-galactopyranoside (ONPG) test to the standard screening protocol for identification of Salmonella and Shigella species, and to describe a revised algorithm for the identification of these pathogens.

Methods: 71 non-lactose-fermenting isolates that were urease negative, indole negative, and produced acid and gas in triple sugar iron agar, with no H(2)S production in the agar, were tested for β-galactosidase activity using the ONPG test. The test results were read at half-hourly intervals over a 4 h incubation period in O(2) at 37°C.

Results: 42 isolates (59.2%) were found to be Hafnia alvei, of which 36 strains (85.7%) were ONPG positive. All 18 of the Enterobacter species (25.4%) were ONPG positive. Overall, about 79% of the ONPG-positive isolates were positive at the end of the first half-hour of incubation. The two pathogenic isolates obtained during this study were both identified as Salmonella enterica serovar Paratyphi A, and they were ONPG negative.

Conclusions: Incorporation of a 30 min ONPG test for non-lactose-fermenting organisms that are indole negative, urease negative, producers of acid and gas from glucose, oxidase negative and non-H(2)S gas producers eliminates the need for further serological testing of 79% of isolates, substantially improving the efficiency of the identification protocol.
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http://dx.doi.org/10.1136/jcp.2010.079723DOI Listing
December 2010

Imported enteric fever: case series from the hospital for tropical diseases, London, United Kingdom.

Am J Trop Med Hyg 2010 Jun;82(6):1121-6

Hospital for Tropical Diseases, London, United Kingdom.

Our current knowledge of the clinical characteristics of enteric fever is drawn mainly from population-based studies in disease-endemic countries, and there are limited data published on cases in returning travelers. We report the clinical characteristics of enteric fever in 92 travelers returning to London, United Kingdom. Salmonella typhi and S. paratyphi resulted in an almost indistinguishable clinical picture. Rose spots and relative bradycardia were found only in a few patients. A total of 91% of the patients had a normal leukocyte count, which was associated with a markedly increased level of alanine aminotransferase in 82%. A total of 57% of the S. typhi isolates had decreased susceptibility to ciprofloxacin and resistance to nalidixic acid; these isolates were from southern Asia. Thirty percent were multidrug resistant; all were from southern Asia and Nigeria. None of the paratyphoid isolates were multidrug resistant but rates of decreased susceptibility to fluoroquinolones were higher than in S. typhi (74%).
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http://dx.doi.org/10.4269/ajtmh.2010.10-0007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877422PMC
June 2010

Thoracic empyema: current opinions in medical and surgical management.

Curr Opin Pulm Med 2010 May;16(3):194-200

Department of Medical Microbiology, University College London Hospital NHS Foundation Trust, London, UK.

Purpose Of Review: Empyema is defined as pus in the thoracic cavity due to pleural space infection and has a multifactorial underlying cause, although a majority of them are post-bacterial pneumonia caused by tuberculosis or by infection following penetrating chest injuries or surgical procedures. It is still associated with significant morbidity and mortality in adults and children despite optimal management according to current guidelines. Historically, empyema management has been empirical, but more recent data are leading to more focused management guidelines.

Recent Findings: The number of therapeutic agents licensed for intrapleural use or undergoing clinical trials in the management of empyema continues to expand, although their use is currently controversial and probably best limited to trials and specialist centers. Although their use is limited by availability, ultrasound and guided aspiration is the investigation of choice in suspected empyema. It is safer, more sensitive, provides more information, and, in the case of guided-drainage, is more likely to be effective. Finally, there is a growing body of literature that supports very early involvement of thoracic surgeons in empyema management. An emerging question for the future is whether some or indeed all patients with empyema should now bypass medical thoracostomy and proceed directly to video-assisted thoracoscopic surgery for both acute and chronic empyemas.

Summary: A summary of the most recent opinions and results in thoracic empyema management is outlined. Treatment of empyema can be summarized as appropriate antibiotic therapy combined with medical or surgical pleural space drainage, management of any underlying factors, with further surgery indicated for chronic disease.
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http://dx.doi.org/10.1097/MCP.0b013e32833883f5DOI Listing
May 2010

Differential susceptibility of PCR reactions to inhibitors: an important and unrecognised phenomenon.

BMC Res Notes 2008 Aug 28;1:70. Epub 2008 Aug 28.

Centre for Infectious Diseases and International Health, Windeyer Institute for Medical Sciences, 46 Cleveland Street, University College London, London, W1T 4JF, UK.

Background: PCR inhibition by nucleic acid extracts is a well known yet poorly described phenomenon. Inhibition assessment generally depends on the assumption that inhibitors affect all PCR reactions to the same extent; i.e. that the reaction of interest and the control reaction are equally susceptible to inhibition. To test this assumption we performed inhibition assessment on DNA extracts from human urine samples, fresh urine and EDTA using different PCR reactions.

Results: When copurified inhibitors were assessed using two different PCR reactions one reaction appeared to be inhibited whilst the other was not. Further experiments using various concentrations of unextracted urine to inhibit six different PCR reactions revealed that susceptibility to inhibition was highly variable between reactions. Similar results were obtained using EDTA as the PCR inhibitor. We could find no obvious explanation why one reaction should be more susceptible to inhibition than another, although a possible association with amplicon GC content was noted.

Conclusion: These findings have serious implications for all PCR-based gene expression studies, including the relatively new PCR array method, and for both qualitative and quantitative PCR-based molecular diagnostic assays, suggesting that careful consideration should be given to inhibition compatibility when conducting PCR analyses. We have demonstrated unequivocally that it is not safe to assume that different PCR reactions are equally susceptible to inhibition by substances co-purified in nucleic acid extracts.
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http://dx.doi.org/10.1186/1756-0500-1-70DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2564953PMC
August 2008

Focal Salmonella enteritidis infection in a patient with HIV infection and other multiple causes of immunodeficiency.

Int J STD AIDS 2008 Jul;19(7):491-2

T8, University College London Hospitals, London NW1 2BU.

An HIV-infected man receiving antiretroviral therapy-who also had lupus-like vasculitis and membranous glomerulonephritis (treated with prednisolone and azathioprine), beta-thalassaemia minor trait and post-radiotherapy functional asplenia (mimicking sickle cell disease-induced hyposplenism)-developed focal soft issue and bone infection caused by Salmonella enteritidis at the site of previous mycobacterial infection.
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http://dx.doi.org/10.1258/ijsa.2008.007320DOI Listing
July 2008

Synthesis of melanin pigment by Candida albicans in vitro and during infection.

Infect Immun 2005 Sep;73(9):6147-50

St. John's Institute of Dermatology, St. Thomas' Hospital, London SE1 9RT, United Kingdom.

Melanins are implicated in the pathogenesis of several important human diseases. This study confirmed the presence of melanin particles in Candida albicans in vitro and during infection. Dark particles were isolated from the digestion of C. albicans cultures and from infected tissue, as established by electron microscopy and immunofluorescence techniques.
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http://dx.doi.org/10.1128/IAI.73.9.6147-6150.2005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1231073PMC
September 2005

Medical mystery: painless ulcers--the answer.

N Engl J Med 2004 May;350(22):2313-4; discussion 2313-4

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http://dx.doi.org/10.1056/NEJMc045252DOI Listing
May 2004