Hélène Coignard-Biehler

Prevention of Infections During Primary Immunodeficiency

Because infectious diseases are a major source of morbidity and mortality in the majority of patients with primary immunodeficiencies (PIDs), the application of a prophylactic regimen is often necessary. However, because of the variety of PIDs and pathogens involved, and because evidence is scarce, practices are heterogeneous. To homogenize practices among centers, the French National Reference Center for PIDs aimed at elaborating recommendations for anti-infectious prophylaxis for the most common PIDs. 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 of PIDs and improving the outcome of patients with PIDs.

Efficacy of ertapenem in severe hidradenitis suppurativa: a pilot study in a cohort of 30 consecutive patients

OBJECTIVES Hidradenitis suppurativa (HS) is an inflammatory skin disease typically localized in the axillae and inguinal and perineal areas. In the absence of standardized medical treatment, severe HS patients present chronic suppurative lesions with polymicrobial anaerobic abscesses. Wide surgery is the cornerstone treatment of severe HS, but surgical indications are limited by the extent of lesions. Intravenous broad-spectrum antibiotics may help control HS, but their efficacy is not documented. This study was designed to assess the efficacy of a 6 week course of ertapenem (1 g daily) and of antibiotic consolidation treatments for 6 months (M6) in severe HS. PATIENTS AND METHODS Thirty consecutive patients with severe HS were retrospectively included in this study. The clinical severity of HS was assessed using the Sartorius score, which takes into account the number and severity of lesions. RESULTS The median (IQR) Sartorius score dropped from 49.5 (28-62) at baseline to 19.0 (12-28) after ertapenem (P < 10(-4)). Five patients were lost to follow-up thereafter. At M6 the Sartorius score further decreased for the 16 patients who received continuous consolidation treatments, since 59% of HS areas reached clinical remission at M6 (i.e. absence of any inflammatory symptoms, P < 10(-4)). Nine patients interrupted or received intermittent consolidation treatments due to poor observance or irregular follow-up. Their Sartorius score stopped improving or returned to baseline. No major adverse event occurred. CONCLUSIONS Ertapenem can dramatically improve severe HS. Consolidation treatments are needed to further improve HS and are mandatory to prevent relapses. Combined with surgery, optimized antibiotic treatments may be promising in severe HS.

The Microbiological Landscape of Anaerobic Infections in Hidradenitis Suppurativa: A Prospective Metagenomic Study

Background Hidradenitis suppurativa (HS) is a frequent and severe disease of the skin, characterized by recurrent or chronic skinfold suppurative lesions with a high impact on quality of life. Although considered inflammatory, antimicrobial treatments can improve or lead to clinical remission of HS, suggesting triggering microbial factors. Indeed, mixed anaerobic microbiota are associated with a majority of HS lesions. Our aim in this study was to characterize the landscape of anaerobic infections in HS using high-throughput sequencing. Methods We sampled and cultured 149 lesions and 175 unaffected control skinfold areas from 65 adult HS patients. The microbiome of 80 anaerobic lesions was compared to that of 88 control samples by 454 high-throughput sequencing after construction of 16S ribosomal RNA gene libraries. Results Bacterial cultures detected anaerobes in 83% of lesions vs 53% of control samples, combined with milleri group streptococci and actinomycetes in 33% and 26% of cases, respectively. High-throughput sequencing identified 43 taxa associated with HS lesions. Two gram-negative anaerobic rod taxa, Prevotella and Porphyromonas, predominated, contrasting with a reduced abundance of aerobic commensals. These rare taxa of normal skinfold microbiota were associated with lesions independently of gender, duration and familial history of HS, body mass index, and location. Two main additional taxa, Fusobacterium and Parvimonas, correlated with the clinical severity of HS. Conclusions In this study we reveal the high prevalence and particular landscape of mixed anaerobic infection in HS, paving the way for rationale targeted antimicrobial treatments.

Defective functions of polymorphonuclear neutrophils in patients with common variable immunodeficiency

Abstract Common variable immunodeficiency (CVID) is a heterogeneous antibody deficiency condition with alterations in T cell regulation and function, dendritic and B-cell compartment and represents the most frequent cause of symptomatic primary immunodeficiency. We addressed whether CVID is associated with abnormalities in the polymorphonuclear neutrophil (PMN) compartment, an important component of innate immunity and plays a key role in host defenses against invading microorganisms. We used flow cytometry to examine PMN phenotypic and functional abnormalities in CVID patients, using whole-blood conditions in order to avoid artifacts due to isolation procedures. We demonstrated that PMN from CVID patients displays, at resting state, a decreased expression of CD15, CD11b and CD16b, which might be related to an abnormality in neutrophil maturation. In addition, these neutrophils exhibit a decrease in degranulation, phagocytosis and reactive oxygen species production, as well as an increased death by apoptosis. These PMN abnormalities observed in CVID patients could result in an increased risk for recurrent bacterial infections.

D-01: DIHosp – Motifs d’hospitalisation en urgence de patients porteurs de déficits immunitaires héréditaires

Introduction – objectifs Recenser les motifs d’hospitalisation en urgence de patients enfants et adultes porteurs d’un deficit immunitaire hereditaire (DIH). Materiels et methodes Etude nationale observationnelle multicentrique prospective (octobre 2010-novembre 2011). Signalement des hospitalisations au CEREDIH (Centre de Reference DIH), recueil de donnees et analyse par le CEREDIH et le comite de pilotage de l’etude. Resultats Cent-trente-sept patients (73 adultes > 15 ans (53 %)) ont ete hospitalises 200 fois. La mediane d’hospitalisation est de 1/patient (1 a 5). Quarante- deux pourcent des patients avaient un deficit B, 15 % un deficit T, 15 % un deficit de la phagocytose, 7 % un syndrome de dysregulation immunitaire, 17 % un DIH specifique (Syndromes hyperIgE, de DiGeorge, de Wiskott- Aldrich, Dyskeratose Congenitale…). Les antecedents etaient : 68,6 % d’infection severe, 30 % d’auto-immunite, 24 % de bronchiectasies, 18 % de port de catheter central, 13 % de splenectomie, 12 % greffes de cellules souches hematopoietiques. Les principaux diagnostics des 200 hospitalisations etaient : infections (78,7 %), cytopenies (6,5 %), evenement non-infectieux pulmonaire (3,5 %). 57,5 % et 36,5 % des cas avaient une guerison complete de l’episode et guerison avec sequelles respectivement. Le deces est survenu dans 12 cas (5 enfants et 7 adultes), de cause infectieuse pour 9 dont 4 chocs septiques. Conclusion Les resultats preliminaires de cette etude mettent en evidence la forte incidence des complications infectieuses chez ces patients. La mortalite associee dans cette population de patients est notable (8,8 %). Les analyses sont en cours afin d’identifier les facteurs de risque de complications severes au sein des DIH.

COL4-04 Les pratiques de prévention des infections chez les patients splénectomisés, en médecine hospitalière et médecine de ville

Introduction On compte 500 000 patients aspleniques en France ce qui represente une population importante que le medecin generaliste doit savoir prendre en charge. L’asplenie confere a ces patients une susceptibilite aux infections par les germes encapsules et les agents intra-erythrocytaires. Ces infections sont souvent des septicemies ou meningites d’evolution fulminante et sont appelees OPSI ( overwhelming post splenectomy infections ). Les recommandations en termes de prevention de ces infections sont codifiees depuis longtemps, mais l’incidence des OPSI reste elevee avec une mortalite importante. Objectif Etudier les pratiques de prevention des infections en medecine hospitaliere et liberale pour savoir si elles sont en adequation avec les recommandations. Patients et methodes Les dossiers de patients splenectomises entre 2000 et 2005 ont ete analyses, avec un recueil dans les dossiers hospitaliers et par questionnaire telephonique aupres des medecins traitants. Les donnees recoltees etaient les caracteristiques demographiques, les vaccinations et antibioprophylaxie administrees, et la survenue eventuelle d’un evenement infectieux. Resultats 154 dossiers ont ete analyses a l’hopital et 46 en ville. La couverture vaccinale anti- pneumococcique est bonne avec des resultats de 70,6 % a l’hopital et 82,3 % en ville. La vaccination contre le meningocoque et l’haemophilus est mediocre avec respectivement 24 % et 44 % de couverture vaccinale a l’hopital. Concernant l’antibioprophylaxie, les resultats sont similaires a ceux de la litterature, autour de 70 % de prescription. L’incidence des infections graves de 8,4 % est importante et liee a la grande representation de patients d’hematologie dans notre population. Conclusion Les pratiques de prevention des infections chez les splenectomises sont partiellement connues des medecins hospitaliers et des medecins traitants, avec notamment des lacunes dans la vaccination contre le meningocoque et l’haemophilus