Olivier Lortholary

Université Paris-Sorbonne - Paris IV, Lutetia Parisorum, Île-de-France, France

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Publications (707)2728.82 Total impact

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    ABSTRACT: Antifungal prescription remains a challenge in pregnant women because of uncertainties regarding fetal toxicity and altered maternal pharmacokinetic parameters that may affect efficacy or increase maternal and fetal toxicity. We present updated data reviewing the available knowledge and current recommendations regarding antifungal prescription in pregnancy. Amphotericin B remains the first-choice parenteral drug in spite of its well-established toxicity. Topical drugs are used throughout pregnancy because of limited absorption. Recent data have clarified the teratogenic effect of high-dose fluconazole during the first trimester and provided reassuring cumulative data regarding its use at a single low dose in this key period. Recent data have also provided additional safety data on itraconazole and lipidic derivatives of amphotericin B. Regarding newer antifungal drugs, including posaconazole and echinocandins, clinical data are critically needed before considering prescription in pregnancy.
    Journal of Antimicrobial Chemotherapy 09/2014; 70(1). DOI:10.1093/jac/dku355 · 5.44 Impact Factor
  • Journal de Mycologie Médicale/Journal of Medical Mycology 09/2014; 24(3):e114. DOI:10.1016/j.mycmed.2014.06.012 · 0.40 Impact Factor
  • Journal de Mycologie Médicale/Journal of Medical Mycology 09/2014; 24(3):e113–e114. DOI:10.1016/j.mycmed.2014.06.011 · 0.40 Impact Factor
  • A. Paugam, T. Ancelle, O. Lortholary, S. Bretagne
    Journal de Mycologie Médicale/Journal of Medical Mycology 09/2014; 24(3):e115–e116. DOI:10.1016/j.mycmed.2014.06.016 · 0.40 Impact Factor
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    ABSTRACT: As infectious diseases are a major source of morbidity and mortality in the majority of patients with primary immunodeficiencies (PIDs), the application of prophylactic regimen is often necessary. However, because of the variety of PIDs and pathogens involved, and because evidence are scarce, practices are heterogeneous. The French National Reference Center for PIDs (CEREDIH) aimed at elaborating recommendations for anti-infectious prophylaxis for the most common PIDs, in order to homogenise practices among centers. We performed a literature review of infectious complications and prophylactic regimens associated with the most frequent PIDs. Then a working group including different specialists systematically debated, about chemoprophylaxis, immunotherapy, immunization and recommendations for patients. Grading of prophylaxis was done using strength of recommendations (decreasing from A to D) and evidence level (decreasing from I to III). These might help infectious diseases specialists in the management and improving the outcome of patients with PIDs.
    Clinical Infectious Diseases 08/2014; 59(10). DOI:10.1093/cid/ciu646 · 9.42 Impact Factor
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    ABSTRACT: To analyze trends in incidence and mortality of candidemia in intensive care units (ICUs) vs. non-ICU hospitalized patients and to determine risk factors for infection by specific species and for death.
    Intensive Care Medicine 08/2014; 40(9). DOI:10.1007/s00134-014-3408-3 · 5.54 Impact Factor
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    ABSTRACT: Rickettsia species are increasingly being recognized as a cause of infection among returning travelers. Murine typhus (MT) was mistakenly thought to have disappeared in the 1970s in Tunisia, yet recent serological data show that Rickettsia typhi, the causative agent of MT, still circulates in the Tunisian population. We report here a case of MT in a woman returning from Tunisia and hospitalized in France. Her presentation was nonspecific, with acute noneruptive fever. Diagnosis was confirmed by cross-adsorption and immunoblotting. Clinicians taking care of returning travelers with fever should be aware of MT, and know how to diagnose and treat it.
    Journal of Travel Medicine 08/2014; 22(1). DOI:10.1111/jtm.12154 · 1.53 Impact Factor
  • The Journal of Infectious Diseases 07/2014; DOI:10.1093/infdis/jiu412 · 5.78 Impact Factor
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    ABSTRACT: Solid organ transplant recipients are at risk for invasive fungal diseases, and are also exposed to healthcare-associated mucormycosis. Mainly causing localized cutaneous mucormycosis, Mucor irregularis infection is reported for the first time in a kidney-transplant recipient. A healthcare-associated origin was highly suspected in this case. We performed a literature review and highlight the characteristics of this very rare fungus.
    07/2014; 6. DOI:10.1016/j.mmcr.2014.07.005
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    ABSTRACT: To determine the epidemiology and trends of invasive fungal infections (IFIs) in France, we analyzed incidence, risk factors, and in-hospital death rates related to the most frequent IFIs registered in the national hospital discharge database during 2001-2010. The identified 35,876 IFI cases included candidemia (43.4%), Pneumocystis jirovecii pneumonia (26.1%), invasive aspergillosis (IA, 23.9%), cryptococcosis (5.2%), and mucormycosis (1.5%). The overall incidence was 5.9/100,000 cases/year and the mortality rate was 27.6%; both increased over the period (+1.5%, +2.9%/year, respectively). Incidences substantially increased for candidemia, IA, and mucormycosis. Pneumocystis jirovecii pneumonia incidence decreased among AIDS patients (-14.3%/year) but increased in non-HIV-infected patients (+13.3%/year). Candidemia and IA incidence was increased among patients with hematologic malignancies (>+4%/year) and those with chronic renal failure (>+10%/year). In-hospital deaths substantially increased in some groups, e.g., in those with hematologic malignancies. IFIs occur among a broad spectrum of non-HIV-infected patients and should be a major public health priority.
    Emerging infectious diseases 07/2014; 20(7):1163-1169. DOI:10.3201/eid2007.140087 · 7.33 Impact Factor
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    ABSTRACT: Background: Chronic granulomatous disease (CGD) is a rare phagocytic disorder that results in not only infections but also potentially severe inflammatory manifestations that can be difficult to diagnose and treat. Objective: To describe inflammatory manifestations in a single-center cohort of patients with CGD. Methods: Medical records of patients treated at Necker-Enfants Malades Hospital (Paris, France) between 1968 and 2009 and registered at the French National Reference Center for Primary Immunodeficiencies (CEREDIH) were retrospectively reviewed. Results: In a study population of 98 patients, a total of 221 inflammatory episodes were recorded in 68 individuals (69.4%). The incidence rate of inflammatory episodes was 0.15 per person-year (0.18 in patients with X-linked [XL] CGD and 0.08 in patients with autosomal-recessive [AR] CGD). The most commonly affected organs were the gastrointestinal tract (in 88.2% of the patients), lungs (26.4%), the urogenital tract (17.6%), and eyes (8.8%). Inflammation at other sites (the skin, central nervous system, and tympanum) and autoimmune manifestations (lupus, arthritis, etc) were recorded in 19.1% and 10.3% of the patients, respectively. Granuloma was found in 50% of the 44 histological analyses reviewed. The risk of inflammatory episodes was 2-fold higher in patients with XL-CGD than in patients with AR-CGD (relative risk, 2.22; 95% CI, 1.43-3.46). Conclusions: Patients with XL-CGD have a higher risk of developing inflammatory episodes than do patients with AR-CGD. Although the most commonly affected organ is the gastrointestinal tract, other sites can be involved, making the management of patients with CGD a complex, multidisciplinary task.
    Journal of Allergy and Clinical Immunology 06/2014; 134(3). DOI:10.1016/j.jaci.2014.04.014 · 11.25 Impact Factor
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    ABSTRACT: The objective of this investigation was to review the clinical manifestations, management, and outcome of osteoarticular infections caused by dimorphic fungi. We exhaustively reviewed reports of bone and joint infections caused by dimorphic fungi published between 1970 and 2012. Underlying conditions, microbiological features, histological characteristics, clinical manifestations, antifungal therapy, and outcome were analyzed in 222 evaluable cases. Among 222 proven cases (median age 41 years [interquartile range (IQR) 26-57]), 73 % had no predisposing condition. Histopathology performed in 128 (57 %) cases and culture in 170 confirmed diagnosis in 63 % and 98 % of the cases, respectively. Diagnosis was obtained from an extra-osteoarticular site in 16 cases. The median diagnostic time was 175 days (IQR 60-365). Sporothrix schenckii was the most frequent pathogen (n = 84), followed by Coccidioides immitis (n = 47), Blastomyces dermatitidis (n = 44), Histoplasma capsulatum (n = 18), Paracoccidioides brasiliensis (n = 16), and Penicillium marneffei (n = 13). Arthritis occurred in 87 (58 %) cases and osteomyelitis in 64 (42 %), including 19 vertebral osteomyelitis. Dissemination was reported in 123 (55 %) cases. Systemic antifungal agents were used in 216 (97 %) patients and in combination with surgery in 129 (60 %). Following the Infectious Diseases Society of America (IDSA) guidelines, a successful initial medical strategy was observed in 97/116 (84 %) evaluable cases. The overall mortality was 6 %, and was highest for P. marneffei (38.5 %). This study demonstrates that dimorphic osteoarticular infections have distinctive clinical presentations, occur predominantly in apparently immunocompetent patients, develop often during disseminated disease, and may require surgical intervention.
    European Journal of Clinical Microbiology 06/2014; 33(12). DOI:10.1007/s10096-014-2149-0 · 2.54 Impact Factor
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    ABSTRACT: Amphotericin B is a powerful polyene antifungal drug used for treating systemic fungal infections and is usually administered for a short period. Side effects after prolonged use are unknown in humans. Here we report the case of a 28-year-old man suffering from chronic granulomatous disease (CGD), treated for invasive cerebral aspergillosis with liposomal amphotericin B (L-AmB) for a very long time (8 consecutive years). We describe the efficacy and safety of this treatment in the long term. Aspergillosis was kept under control as long as L-AmB therapy was maintained, but relapsed when the dose was reduced. No overt renal toxicity was noted. The patient gradually developed hepatosplenomegaly and pancytopenia. Abnormalities of bone marrow were similar to the sea-blue histiocyte syndrome. Liver biopsy showed images of nodular regenerative hyperplasia related to CGD as well as a histiocytic storage disease. We discuss the very prolonged use of L-AmB leading to the development of a lysosomal storage disease.
    International journal of antimicrobial agents 06/2014; 43(6). DOI:10.1016/j.ijantimicag.2014.02.015 · 4.26 Impact Factor
  • La Revue de Médecine Interne 06/2014; 35:A46. DOI:10.1016/j.revmed.2014.03.042 · 1.32 Impact Factor
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    ABSTRACT: Management of primary immune thrombocytopenia (ITP) has changed, and clinical practice broadens the use of thrombopoietin receptor agonists and anti-CD20 antibody as options for second-line therapy, as alternative to splenectomy. Splenectomy remains a successful, definitive curative treatment. The purpose of this review about the complications of the splenectomy, in the context of ITP, is to increase the awareness of clinicians towards the preventive measures, which are often not correctly applied.
    La Revue de Médecine Interne 06/2014; 35(6):382–387. DOI:10.1016/j.revmed.2013.11.002 · 1.32 Impact Factor
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    ABSTRACT: The incidence of varicella is low in pregnant women, and estimated around 1/1000 pregnancies. Vaccination is the cornerstone of prevention, but is contraindicated during pregnancy. Varicella is more severe in pregnant women. The risk of viral pneumonia is not increased, but VZV-associated pneumonia is usually more severe in pregnant women. Infection between 0–20 WG is associated with a 2 % risk of congenital varicella syndrome. Infection between D-5 and D + 2 of delivery is associated with high risk of severe neonatal infection. Non-immune pregnant women with significant exposure to VZV require post-exposure prophylaxis with specific anti-VZV immunoglobulins that should be administered ideally within 4 days post-exposure and maximum within 10 days of exposure. Anti-VZV immunoglobulins are available in France in the context of an approved expanded access to an investigational new drug. Pregnant women with varicella should receive within 24 hours antiviral treatment based either on valaciclovir or, in case of severe infection, intravenous aciclovir. Both drugs were shown safe during pregnancy, even during the first trimester. Neonates born from mothers who developed varicella between D-5 and D +2 of delivery should also receive as soon as possible specific anti-VZV immunoglobulins.
    La Presse Médicale 06/2014; DOI:10.1016/j.lpm.2014.04.001 · 1.17 Impact Factor
  • Médecine et Maladies Infectieuses 06/2014; 44(6):91. DOI:10.1016/S0399-077X(14)70321-X · 0.91 Impact Factor
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    ABSTRACT: The incidence of varicella is low in pregnant women, and estimated around 1/1000 pregnancies. Vaccination is the cornerstone of prevention, but is contraindicated during pregnancy. Varicella is more severe in pregnant women. The risk of viral pneumonia is not increased, but VZV-associated pneumonia is usually more severe in pregnant women. Infection between 0-20 WG is associated with a 2 % risk of congenital varicella syndrome. Infection between D-5 and D+2 of delivery is associated with high risk of severe neonatal infection. Non-immune pregnant women with significant exposure to VZV require post-exposure prophylaxis with specific anti-VZV immunoglobulins that should be administered ideally within 4 days post-exposure and maximum within 10 days of exposure. Anti-VZV immunoglobulins are available in France in the context of an approved expanded access to an investigational new drug. Pregnant women with varicella should receive within 24hours antiviral treatment based either on valaciclovir or, in case of severe infection, intravenous aciclovir. Both drugs were shown safe during pregnancy, even during the first trimester. Neonates born from mothers who developed varicella between D-5 and D+2 of delivery should also receive as soon as possible specific anti-VZV immunoglobulins.
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    ABSTRACT: Objective: Patients coinfected with HIV and Mycobacterium tuberculosis frequently experience a paradoxical worsening of tuberculosis (TB) symptoms early after the initiation of combination antiretroviral therapy (cART). This immune reconstitution inflammatory syndrome (TB-IRIS) can lead to significant morbidity and needs to be distinguished from TB recurrence due to ineffective treatment. We investigated whether plasma biomarkers could predict the occurrence of TB-IRIS. Design: ANRS 129 BKVIR is a single-arm multicentre trial that enrolled 69 cART-naive HIV-1-infected patients treated for TB. The patients received once-daily tenofovir/emtricitabine/efavirenz first-line regimen. TB-IRIS cases (IRIS+) were validated by an Event Review Committee. Methods: A panel of 26 plasma biomarkers was monitored longitudinally for 24 weeks from cART initiation onward, using multiplexed assays and high-sensitivity ELISA. Statistical analyses of biomarkers were adjusted for test multiplicity. Results: One-third of patients (n = 23) experienced TB-IRIS. The inflammatory cytokines and chemokines interleukin (IL)-6, IL-8, interferon-gamma-induced protein 10 (IP-10), and tumour necrosis factor-alpha (TNF-alpha) showed increased plasma levels at week 4 in IRIS-positive (IRIS+) patients (P < 0.05 for each biomarker). The soluble IL-2 receptor sCD25, which is released upon CD4(+) T-cell activation, was significantly increased at week 0 in IRIS+ patients (P< 0.05), and remained elevated throughout follow-up. IL-7, a key homeostatic cytokine for CD4(+) T-cells, showed a trend for higher values in the TB-IRIS group. Both sCD25 and IL-7 baseline levels were independently associated with a shorter time to TB-IRIS occurrence (P = 0.005 and P = 0.02, respectively). Conclusion: These findings support a role for CD4(+) T-cell activation prior to massive inflammation in the development of TB-IRIS. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
    AIDS (London, England) 05/2014; 28(11). DOI:10.1097/QAD.0000000000000311 · 6.56 Impact Factor
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    ABSTRACT: Background Yeasts, mostly Candida, are important causes of bloodstream infections (BSI), responsible for significant mortality and morbidity among hospitalized patients. The epidemiology and species distribution vary from different regions. The goals of this study were to report the current epidemiology of Candida BSI in a Shanghai Teaching Hospital and estimate the impact of appropriate antifungal therapy on the outcome. Methods From January 2008 to December 2012, all consecutive patients who developed Candida BSI at Ruijin University Hospital were enrolled. Underlying diseases, clinical severity, species distribution, antifungal therapy and its impact on the outcome were analyzed. Results A total of 121 episodes of Candida BSI were identified, with an incidence of 0.32 episodes/1,000 admissions (0.21 in 2008 and 0.42 in 2012) The proportion of candidemia caused by non-albicans species (62.8%), including C. parapsilosis (19.8%), C. tropicalis (14.9%), C. glabrata (7.4%), C. guilliermondii (5.8%), C. sake (5.0%) was higher than that of candidemia caused by C. albicans (37.2%). The overall crude 28-day mortality was 28.1% and significantly reduced with appropriate empiric antifungal therapy administered within 5 days (P = 0.006). Advanced age (OR 1.04; P = 0.014), neutropenia < 500/mm3 (OR 17.44; P < 0.001) were independent risk factors for 28-day mortality, while appropriate empiric antifungal therapy (OR 0.369; P = 0.035) was protective against 28-day mortality. Conclusion The epidemiology of candidemia in Shanghai differed from that observed in Western countries. Appropriate empiric antifungal therapy influenced the short-term survival.
    BMC Infectious Diseases 05/2014; 14(1):241. DOI:10.1186/1471-2334-14-241 · 2.56 Impact Factor

Publication Stats

17k Citations
2,728.82 Total Impact Points

Institutions

  • 2014–2015
    • Université Paris-Sorbonne - Paris IV
      Lutetia Parisorum, Île-de-France, France
  • 2006–2015
    • Assistance Publique – Hôpitaux de Paris
      • Department of Radiology
      Lutetia Parisorum, Île-de-France, France
    • Université Victor Segalen Bordeaux 2
      Burdeos, Aquitaine, France
    • Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine)
      Lutetia Parisorum, Île-de-France, France
  • 2005–2015
    • Université René Descartes - Paris 5
      • • Faculté de Médecine
      • • Faculty of medicine
      Lutetia Parisorum, Île-de-France, France
    • Hôpital Jean-Verdier – Hôpitaux Universitaires Paris-Seine-Saint-Denis
      Bondy, Île-de-France, France
    • Universidad Pontificia Bolivariana
      Medellín, Antioquia, Colombia
    • Baylor University
      Waco, Texas, United States
  • 2004–2015
    • Hôpital Universitaire Necker
      Lutetia Parisorum, Île-de-France, France
    • Washington University in St. Louis
      San Luis, Missouri, United States
    • Deaconess Hospital Group Croix Saint - Simon
      Lutetia Parisorum, Île-de-France, France
  • 2008–2014
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
    • Université de Versailles Saint-Quentin
      Versailles, Île-de-France, France
    • Centre hospitalier Gustave Dron
      Tourcoing, Nord-Pas-de-Calais, France
    • Sikkim Manipal Institute of Technology
      Rungpo, Sikkim, India
    • Association Française pour la Recherche sur l'Hidrosadénite
      Lutetia Parisorum, Île-de-France, France
    • Groupe Hospitalier Saint Vincent
      Strasburg, Alsace, France
  • 1993–2014
    • Institut Pasteur
      Lutetia Parisorum, Île-de-France, France
  • 2013
    • Statens Serum Institut
      København, Capital Region, Denmark
    • Hospital for Special Surgery
      New York City, New York, United States
  • 2012
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      Torrance, California, United States
    • University of Houston
      • College of Pharmacy
      Houston, TX, United States
  • 2011
    • CHRU de Strasbourg
      Strasburg, Alsace, France
  • 2010
    • Centrum kardiovaskulární a transplantační chirurgie
      Brünn, South Moravian, Czech Republic
    • University College Dublin
      Dublin, Leinster, Ireland
    • University of Rochester
      • Division of Infectious Diseases
      Rochester, New York, United States
  • 2009
    • Institut de veille sanitaire
      • Department of Infectious Diseases
      Charenton-le-Pont, Ile-de-France, France
    • St George's, University of London
      • Center for Infection and Immunity Research
      Londinium, England, United Kingdom
    • Hôpital Saint-Vincent-de-Paul – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France
  • 2008–2009
    • University of Pittsburgh
      • Division of Infectious Diseases
      Pittsburgh, Pennsylvania, United States
  • 2007
    • Hôpital Cochin (Hôpitaux Universitaires Paris Centre)
      Lutetia Parisorum, Île-de-France, France
    • University of Cologne
      • Department of Internal Medicine
      Köln, North Rhine-Westphalia, Germany
  • 1995–2005
    • Université Paris 13 Nord
      Île-de-France, France
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
  • 2002
    • National Institutes of Health
      Maryland, United States
    • European Organisation for Research and Treatment of Cancer
      Bruxelles, Brussels Capital, Belgium
  • 2000–2002
    • Hôpital Raymond-Poincaré – Hôpitaux universitaires Paris Ile-de-France Ouest
      Île-de-France, France
    • The University of Manchester
      Manchester, England, United Kingdom
  • 1993–1994
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
  • 1992
    • Institut Curie
      Lutetia Parisorum, Île-de-France, France