Daptomycin > 6 mg/kg/day as salvage therapy in patients with complex bone and joint infection: cohort study in a regional reference center

Background: Even if daptomycin does not have approval for the treatment of bone and joint infections (BJI), the Infectious Diseases Society of America guidelines propose this antibiotic as alternative therapy for prosthetic joint infection. The recommended dose is 6 mg/kg/d, whereas recent data support the use of higher doses in these patients.Methods: We performed a cohort study including consecutive patients that have received daptomycin >6 mg/kg/d for complex BJI between 2011 and 2013 in a French regional reference center. Factors associated with treatment failure were determined on univariate Cox analysis and Kaplan-Meier curves.Results: Forty-three patients (age, 61 ± 17 years) received a mean dose of 8 ± 0.9 mg/kg/d daptomycin, for a mean 81 ± 59 days (range, 6-303 days). Most had chronic (n = 37, 86 %) implant-associated (n = 37, 86 %) BJI caused by coagulasenegative staphylococci (n = 32, 74 %). A severe adverse event (SAE) occurred in 6 patients (14 %), including 2 cases of eosinophilic pneumonia, concomitant with daptomycin Cmin >24 mg/L. Outcome was favorable in 30 (77 %) of the 39 clinically assessable patients. Predictors for treatment failure were age, non-optimal surgery and daptomycin withdrawal for SAE.Conclusions: Prolonged high-dose daptomycin therapy was effective in patients with complex BJI. However, optimal surgery remains the cornerstone of medico-surgical strategy; and a higher incidence of eosinophilic pneumonia than expected was recorded

Physiopathologie de l infection à Legionella pneumophila dans un modèle expérimental murin

To progress in the understanding of L. pneumophila infection, we investigated host-pathogen interaction in vitro through lung epithelial cell cultures and in vivo through an A/J murine model focusing on two aspects: the studies of alveolar-capillary barrier injury and lung inflammatory response. Three parts have been developed: 1) a study of the mechanisms leading to L. pneumophila attachment to respiratory epithelia; 2) a study of virulence factor type IV secretion system (Dot/Icm system) involvement in L. pneumophila pathogenesis; 3) a primary characterization of mucosal innate response. The main results of this work are : -in vitro, the zinc ion is an important co-factor of L. pneumophila adherence to alveolar type II pneumocytes via a protein adhesin. -In vivo, sulphated saccharide heparin co-instilled intratracheally with L. pneumophila challenge has a protective effect on the alveolar-capillary barrier and prevents bacterial dissemination. It tends to confirm the competitive inhibition by heparin of L. pneumophila attachment to lung epithelium in vivo, and point to the possible involvement of a heparan-sulfate adhesin in L. pneumophila binding to pneumocytes. -In vivo, L. pneumophila Dot/Icm system of serogroup 1 strains Lens and Paris is central to pathogenesis and is associated with the development of acute lung injury, lung bacterial replication and systemic spread. -In vivo, at 4 and 48 hours post-infection by L. pneumophila both gene expressions of lung -defensins mBD-1 and mBD-3 were detected in a constitutive and inducible way respectively. However, the absence of ccl20 gene expression was observed, a key chemokine for dendritic cells recruitment after bacterial infectionLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Emerging infectious agents

International audienceEmergence of many emerging or re-emerging infectious diseases have occurred over the past decade, some of which are major public threat. SARS, MERS-CoV, highly pathogenic avian influenza A(H5N1), Ebola virus disease have raised concerns because of their virulence, their mortality, and/or their modality of transmission, or their impact on maternofoetal transmission (Zika virus). The witness of these emergences have conducted health authorities to have policies and plans and to imagine new organizations for health systems in order to identify any case of highly communicable virulent disease for immediate isolation, and adequate management

Imported cutaneous larva migrans by a 31-year-old French woman after a travel in Gabon

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Orbital granuloma: a rare manifestation of extrapulmonary tuberculosis

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Necrotic sore throat, tender lymphadenopathies, hepatitis and activated lymphocytes in circulating blood as a clinical presentation of severe infectious mononucleosis

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Daptomycin-induced eosinophilic pneumonia

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