J Cohen

University of Sussex, Brighton, England, United Kingdom

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Publications (84)713.99 Total impact

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    ABSTRACT: Antibody levels to Clostridium difficile toxin A (TcdA), but not toxin B (TcdB), have been found to determine risk of C. difficile infection (CDI). Historically, TcdA was thought to be the key virulence factor; however the importance of TcdB in disease is now established. We re-evaluated the role of antibodies to TcdA and TcdB in determining patient susceptibility to CDI in two separate patient cohorts. In contrast to earlier studies, we find that CDI patients have lower pre-existing IgA titres to TcdB, but not TcdA, when compared to control patients. Our findings suggest that mucosal immunity to TcdB may be important in the early stages of infection and identifies a possible target for preventing CDI progression.
    Full-text · Article · Jun 2014 · Anaerobe
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    ABSTRACT: Cohorting of patients with Clostridium difficile infection (CDI) is recommended when single side-rooms are unavailable. Although patients may remain infectious after cessation of diarrhoea, continued cohorting may place them at increased risk of reinfection. To identify risk factors for CDI recurrence and to determine whether cohorting of patients is associated with increased risk of recurrence. Data describing patient demographics, comorbidity, CDI severity and treatment were collected for 248 CDI patients at our hospital between October 2008 and June 2011. The primary outcome was symptomatic recurrence within 30 days of diagnosis. One hundred and thirty-eight (55.6%) CDI patients were admitted to the cohort ward. These patients were more likely to have severe CDI (odds ratio: 1.95; 95% confidence interval: 1.10-3.46; P = 0.022) and receive vancomycin (1.59; 0.94-2.68; P = 0.083) than patients who were not cohorted. Twenty-six patients (10.5%) suffered recurrence (21 cohorted and five not cohorted). Urinary infection on admission (5.16; 2.10-12.64; P < 0.001), cohorting (3.77; 1.37-10.35; P = 0.01) and concomitant antibiotics (2.07; 0.91-4.72; P = 0.083) were associated with increased risk of recurrence. On multivariate analysis, cohorting (3.94; 1.23-12.65; P = 0.021) and urinary infection (4.27; 1.62-11.24; P = 0.003) were significant predictors of recurrence. Patients admitted to a C. difficile cohort ward may be at increased risk of recurrence because they are at increased risk of reinfection. Hospitals using cohort wards to control C. difficile should manage patient flow through the cohort to minimize this risk.
    No preview · Article · Aug 2013 · The Journal of hospital infection
  • J Cohen · P Gard · I Haq · M Llewelyn

    No preview · Article · Sep 2009 · The Lancet
  • M. Llewelyn · J. Cohen
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    ABSTRACT: This chapter is concerned with the diagnosis and immediate treatment of patients with septic shock. Most clinicians will have a mental image of this condition and would expect to have little difficulty in recognising it from the end of the bed, but despite this there is no universally accepted definition. Indeed, when clinical investigators attempt to arrive at a consensus there are wide variations in terms. Thus, a necessary preface to this chapter is a brief discussion of the controversy surrounding the nomenclature of these syndromes.
    No preview · Chapter · Jan 2007
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    ABSTRACT: Oropharyngeal candidiasis is a frequent infection in cancer patients who receive cytotoxic drugs. In this study, the efficacy, safety and tolerance of fluconazole and itraconazole were compared in non-neutropenic cancer patients with oropharyngeal candidiasis. Of 279 patients who were randomised between the two treatment groups, 252 patients were considered to be eligible (126 in each group). The clinical cure rate was 74% for fluconazole and 62% for itraconazole (P=0.04, 95% Confidence Interval (CI): 0.5-23.3%). The mycological cure rate was 80% for fluconazole and 68% for itraconazole (P=0.03, 95% CI: 1.2-22.6%). The safety and tolerance profile of both drugs were comparable. This study has shown that in patients with cancer and oropharyngeal candidiasis, fluconazole has a significantly better clinical and mycological cure rate compared with itraconazole.
    No preview · Article · Jul 2004 · European Journal of Cancer
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    ABSTRACT: In this paper we review evidence in favor of a protective role for antibodies directed at the lipopolysaccharide (LPS) core region of Gram-negative bacilli. It will be shown that, given the right animal model, polyclonal antisera raised against O-antigen lacking, rough mutant strains, can be shown to protect animals against lethal sepsis due to a variety a bacterial species. Evidence for a protective role obtained from clinical studies will also be discussed. It will be stressed how difficult it is to prove that the antibodies directed against the LPS-core, and not other proteins present in the polyclonal anti-rough strain antisera, were responsible for the observed protective effects. The solution to some of these problems is the production of monoclonal antibodies (Mabs). We will discuss the findings that purified anti-core Mabs may give false-positive outcomes of protection studies, due to the induction of tolerance by small amounts of contaminating endotoxin, present in the antibody preparation. The need to administer the Mab therapeutically instead of prophylactically to the test animals, will be stressed. It will be shown how we succeeded in determining the epitope-specificities of several anti-core antibodies. It will be shown also that use of Elisa alone for characterization of anti-core Mabs may lead to false conclusions concerning epitope specificities. We will prove that synthetic KDO-(=ketodeoxycctanate) and lipid A-containing antigens are indispensable tools for thorough characterization of Mabs. Using this methodology we were able to discriminate between specific antigen-antibody interactions, and the ability of some Mabs to bind “non-specifically” to hydrophobic surfaces. The relationship between epitope specificity and protective effects of anti-core Mabs will be described. Finally, we will demonstrate that a KDO-specific Mabs is capable of protecting mice against lethal sepsis; in other words, it will be shown conclusively that Mabs to defined epitopes in LPS core region are cross-protective.
    No preview · Article · Feb 2004 · Acta Biotechnologica

  • No preview · Article · Jan 2004

  • No preview · Article · Apr 2003 · Clinical Science
  • Martin Llewelyn · J Cohen

    No preview · Article · Feb 2001 · Intensive Care Medicine
  • M Llewelyn · J Cohen

    No preview · Article · Feb 2001 · Current clinical topics in infectious diseases
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    Shiranee Sriskandan · Jonathan Cohen
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    ABSTRACT: A retrospective analysis of 7 patients with streptococcal toxic shock revealed isolated prolongation of the activated partial thromboplastin time, which returned to normal during recovery. Levels of factor XII were reduced in 2 patients who had single factor assays performed, consistent with activation of the kallikrein-kinin system. We speculate that bradykinin release following activation of the kallikrein-kinin system in streptococcal toxic shock may underlie the features of pain, capillary leaking, and severe hypotension characteristic of this syndrome.
    Preview · Article · Jul 2000 · Clinical Infectious Diseases

  • No preview · Article · Nov 1999 · Shock
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    ABSTRACT: The effect of growth phase on expression of virulence-associated factors was studied by Northern hybridization in an M1T1 clinical isolate of Streptococcus pyogenes. Expression of M protein, C5a peptidase, and capsule was maximal in the exponential phase of growth, while streptococcal pyrogenic exotoxins A and B and mitogenic factor were maximally expressed in later phases of growth.
    Full-text · Article · Nov 1999 · Infection and Immunity

  • No preview · Article · Jul 1999 · Journal of Infection
  • S Sriskandan · J Cohen
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    ABSTRACT: This article has reviewed the mechanisms by which gram-positive bacteria lead to septic shock, with regard to bacterial structure and toxicology and the host responses elicited both in animal models and in the clinical setting. Gram-positive organisms are better suited to invade host tissues and elicit, in general, a brisker phagocytic response than gram-negative organisms. The lack of endotoxin in the outer cell wall is compensated for by the presence of exposed peptidoglycan and a range of other toxic secreted products. It appears that cell wall components of gram-positive bacteria may signal via the same receptor as gram-negative endotoxin, although the type of signal and coreceptor may differ. Both animal and clinical data suggest that, unlike endotoxin-mediated shock, gram-positive infection produces a modest TNF response only and does not respond well to anti-TNF therapies. This leads one to conclude that the mechanisms leading to shock in gram-positive infection may be multifactorial and perhaps more difficult to treat. A thorough review of gram-positive mechanisms of sepsis is hampered by a lack of basic research in this field. Understanding of gram-negative bacterial structure and the regulation of virulence genes is at an advanced stage, yet the molecular tools to analyse virulence factors in the gram-positive genome have only recently become available. There is a paucity of good animal models of gram-positive infection and a lack of microbiologic data from some of the major trials in sepsis that might have given greater insight into the mechanisms leading to shock in various infections.
    No preview · Article · Jul 1999 · Infectious Disease Clinics of North America
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    ABSTRACT: The EORTC Invasive Fungal Infections Cooperative Group (IFICG) conducted a prospective survey by questionnaire of all cases of invasive aspergillosis (IA) in cancer patients to ascertain current diagnostic and therapeutic approaches. All members of the IFICG were asked prospectively to complete a detailed questionnaire for each IA case identified in their institution over a 12-month period. One hundred and thirty questionnaires were returned. All cases were independently evaluated (DWD & JC) and 123 were eligible. Cases came from 20 hospitals in eight countries and the number of cases per institution varied from 1-21. Acute myeloid leukaemia (AML) (60, 49%), acute lymphoblastic leukaemia (ALL) (21, 17%) and lymphoma (11, 9%) were the most frequent underlying diseases, and 16 (12%) patients had received an allogeneic bone marrow transplant. Pulmonary involvement was present in 87%, infection of sinuses/nose in 16% and brain in 8%. The chest radiograph was initially normal in 9% of those with primary pulmonary disease. The diagnosis was confirmed in 50%, probable in 31% and possible in 19%. The evidence for IA was on the basis of clinical and radiological features alone in 28%, with culture or histology in another 31% and 9%, respectively, and with both culture and histology in 29%. In three (2%) patients with diagnosis was based on culture or histology alone. Treatment was given to 120 patients (98%)-amphotericin B 75%, lipid-associated amphotericin B 36%, itraconazole 40%, flucytosine 12%, growth factors 33%, lobectomy 5%. At 3 months after diagnosis or first suspicion of IA, 44 (36%) patients were alive and 79 (64%) dead. Outcome was best in those with AML (30% death and 46% with a complete antifungal response or cure). Growth factors (mostly granulocyte colony stimulating factor) appeared not to influence outcome (P = 0.99). IA remains a considerable diagnostic and therapeutic challenge. No single diagnostic procedure was universally successful and a multifaceted approach including surgery is necessary. There was no discernable difference in outcome between initial therapy with amphotericin B, itraconazole or lipid-associated amphotericin B, although numbers are limited and the study was retrospective.
    No preview · Article · Oct 1998 · Journal of Infection
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    ABSTRACT: ???Objectives:the EORTC Invasive Fungal Infections Cooperative Group (IFICG) conducted a prospective survey by questionnaire of all cases of invasive aspergillosis (IA) in cancer patients to ascertain current diagnostic and therapeutic approaches.Methods:all members of the IFICG were asked prospectively to complete a detailed questionnaire for each IA case identified in their institution over a 12-month period.Results:one hundred and thirty questionnaires were returned. All cases were independently evaluated (DWD & JC) and 123 were eligible. Cases came from 20 hospitals in eight countries and the number of cases per institution varied from 1–21. Acute myeloid leukaemia (AMI) (60, 49%), acute lymphoblastic leukaemia (ALL) (21, 17%) and lymphoma (11, 9%) were the most frequent underlying diseases, and 16 (12%) patients had received an allogeneic bone marrow transplant. Pulmonary involvement was present in 87%, infection of sinuses/nose in 16% and brain in 8%. The chest radiograph was initially normal in 9% of those with primary pulmonary disease. The diagnosis was confirmed in 50%, probable in 31% and possible in 19%. The evidence for IA was on the basis of clinical and radiological features alone in 28%, with culture or histology in another 31% and 9%, respectively, and with both culture and histology in 29%. In three (2%) patients the diagnosis was based on culture or histology alone. Treatment was given to 120 patients (98%) — amphotericin B 75%, lipid-associated amphotericin B 36%, itraconazole 40%, flucytosine 12%, growth factors 33%, lobectomy 5%. At 3 months after diagnosis or first suspicion of IA, 44 (36%) patients were alive and 79 (64%) dead. Outcome was best in those with AML (30% death and 46% with a complete antifungal response or cure). Growth factors (mostly granulocyte colony stimulating factor) appeared not to influence outcome (P = 0.99).Conclusion:IA remains a considerable diagnostic and therapeutic challenge. No single diagnostic procedure was universally successful and a multifaceted approach including surgery is necessary. There was no discernable difference in outcome between initial therapy with amphotericin B, itraconazole or lipid-associated amphotericin B, although numbers are limited and the study was retrospective.
    No preview · Article · Sep 1998 · Journal of Infection
  • J Cohen · T J Evans · J Spink
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    ABSTRACT: NO is an important mediator in sepsis. It has been unequivocally established that it is the major determinant in the vasodilatation and consequent hypotension in experimental animals following the administration of LPS. It is cytotoxic, particularly in combination with superoxide anions, and exerts negative inotropic and chronotropic effects on the heart. The exact role that these functions play in sepsis, however, remain unclear. Similarly, its immunomodulatory and cerebral effects, although potentially important, remain of uncertain significance in sepsis. Regulation of such a pivotal molecule is clearly extremely important: the data described here show that not only is this regulation extremely complex, but it appears to vary in different cell types. The implication of this finding for future clinical work is clear. NO production is not all bad: in some circumstances, it may be desirable to differentially regulate iNOS activity such that production is restricted in some cell types but not in others. The work described here begins to offer the possibility of identifying new molecular targets which allow this kind of differential regulation.
    No preview · Article · Feb 1998 · Progress in clinical and biological research
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    ABSTRACT: The treatment of deep fungal infection in haematological malignancy remains controversial due to the limited number of antifungal agents available and problems over their spectrum and dose-limiting side-effects. Difficulties in diagnosis mean that most treatments are begun empirically; amphotericin B remains the drug of choice. Emerging resistance may limit the usefulness of fluconazole and other azoles in some areas. Lipid preparations of amphotericin B have reduced the toxicity of this agent, but some issues of dosage and efficacy remain. Adjunctive treatments aimed at augmenting the host response to infection may have a role to play in deep fungal infection.
    No preview · Article · Dec 1997 · Journal of Antimicrobial Chemotherapy
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    S Sriskandan · A McKee · L Hall · J Cohen
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    ABSTRACT: We have tested the ability of Streptococcus pyogenes to produce streptococcal pyrogenic exotoxin A (SPEA) and superantigenic activity in the presence of sub-inhibitory concentrations of ampicillin and clindamycin. After 6 h of culture, SPEA production by S. pyogenes was higher in broths containing ampicillin (715.7 +/- 296.4 pg/10(6) cfu) than in broths containing clindamycin (167.1 +/- 31.9 pg/10(6) cfu), a difference that was not significant (P = 0.25). Promitogenic activity of bacterial supernatants was also greater in ampicillin-treated cultures (467.5 +/- 17.2 ccpm/10(6) cfu) than in clindamycin-treated cultures (169.2 +/- 8.9 ccpm/10(6) cfu), a difference that was highly significant (P = 0.0001). The data support the use of clindamycin in the treatment of streptococcal toxic shock-like syndrome, in order to inhibit superantigen synthesis.
    Preview · Article · Sep 1997 · Journal of Antimicrobial Chemotherapy

Publication Stats

4k Citations
713.99 Total Impact Points

Institutions

  • 2009-2014
    • University of Sussex
      • Brighton and Sussex Medical School
      Brighton, England, United Kingdom
  • 2013
    • Brighton and Sussex Medical School
      Brighton, England, United Kingdom
  • 1982-2004
    • Ealing, Hammersmith & West London College
      Londinium, England, United Kingdom
  • 2001
    • Imperial College London
      • Department of Infectious Disease Epidemiology
      London, ENG, United Kingdom
  • 1996-1998
    • The Royal Orthopaedic Hospital NHS Foundation Trust
      Birmingham, England, United Kingdom
  • 1993
    • Royal United Hospital Bath NHS Trust
      Bath, England, United Kingdom