Association of depression and suicidal behaviour reporting with HIV integrase inhibitors: a global pharmacovigilance study.

OBJECTIVES: Concerns have been raised regarding neuropsychiatric adverse drug reactions of integrase inhibitors (INSTIs) in patients living with HIV. The aim of this study was to assess the risk of depression and suicidality reporting with INSTIs based on a global pharmacovigilance database. METHODS: Depression and suicidality cases in patients treated with INSTIs were identified within the WHO global database of individual case safety reports, VigiBase. Risk of depression and suicidality reporting with INSTIs compared with other ART was assessed using disproportionality analyses (case/non-case statistical approach). RESULTS: Of 19 991 410 reports over the study period, 124 184 reports concerned patients exposed to ART, including 22 661 patients exposed to an INSTI. Among patients treated with an INSTI, 547 cases of depression and 357 cases of suicidality were identified. Disproportionality analyses showed that depression [reporting OR (ROR) 3.6; 95% CI: 3.2-4.0] and suicidality (ROR 4.7; 95% CI: 4.1-5.4) were more reported with the use of INSTIs compared with other ART. Amongst INSTIs, depression reporting was significantly greater for bictegravir and dolutegravir, whereas suicidality reporting was significantly greater for dolutegravir only. CONCLUSIONS: Our findings suggest that depression and suicidality are adverse drug reactions of all INSTI agents, especially dolutegravir, which may occur within the first months of therapy.

Staphylococcus lugdunensis prosthetic joint infection: A multicentric cohort study.

OBJECTIVES: To describe Staphylococcus lugdunensis prosthetic joint infection (PJI) management and outcome. METHODS: Adults with proven S. lugdunensis PJI were included in a multicentric retrospective cohort. Determinants for failure were assessed by logistic regression and treatment failure-free survival curve analysis (Kaplan-Meier). RESULTS: One hundred and eleven patients were included (median age 72.4 [IQR, 62.7-79.4] years), with a knee (n = 71, 64.0%) or hip (n = 39, 35.1%) PJI considered as chronic in 77 (69.4%) cases. Surgical management consisted in debridement, antibiotic with implant retention (DAIR; n = 60, 54.1%), two-stage (n = 28, 25.2%) or one-stage (n = 15, 13.5%) exchange. Total duration of antimicrobial therapy was 13.1 (IQR, 11.8-16.9) weeks. After a median follow-up of 99.9 (IQR, 53.9-178.1) weeks, 22 (19.8%) S. lugdunensis-related treatment failures were observed. Independent determinants for outcome were diabetes (OR, 3.741; p = 0.036), sinus tract (OR, 3.846; p = 0.032), DAIR (OR, 3.749; p = 0.039) and rifampin-based regimen (OR, 0.319; p = 0.043). Twenty-four (40.0%) of the 60 DAIR-treated patients experienced treatment failure, with hip location (OR, 3.273; p = 0.048), delay from prosthesis implantation (OR, 1.012 per month; p = 0.019), pre-surgical CRP level >115 mg/L (OR, 4.800; p = 0.039) and mobile component exchange (OR, 0.302; p = 0.069) constituting additional determinants of outcome. CONCLUSIONS: Staphylococcus lugdunensis PJI are difficult-to-treat infections, with pivotal roles of an optimal surgical management.

Characteristics and Clinical Value of 18F-FDG PET/CT in the Management of Adult-Onset Still's Disease: 35 Cases.

While the diagnosis of adult-onset Still's disease (AOSD) involves the exclusion of differential diagnoses, the characteristics and value of 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography coupled with CT (PET/CT) in the management of AOSD remain poorly known. Our retrospective study included patients from four centers, fulfilling Yamaguchi or Fautrel criteria, who underwent a PET/CT during an active AOSD. Thirty-five patients were included. At the time of PET/CT, the Yamaguchi criteria were met in 23 of 29 evaluable cases. PET/CT showed bone marrow (74.3%), lymph node (74.3%), and splenic (48.6%) FDG uptake. Despite arthralgia or arthritis in most patients, joints were rarely the sites of 18F-FDG accumulation. The spatial distribution of 18F-FDG uptake was nonspecific, and its intensity could be similar to malignant disease. Lymph node or bone marrow biopsy was performed after PET/CT in 20 patients (57.1%). The intensity of bone marrow; splenic and lymph node hypermetabolism appeared to be correlated with disease activity. Abnormal PET/CT in the cervical lymph nodes and age ≥ 60 years seemed to be predictive factors for monocyclic evolution. The clinical value of PET/CT is not in direct diagnosis; but as an aid in excluding differential diagnoses by searching for their scintigraphic features and guiding biopsy.

First case of Abiotophia defectiva infectious endocarditis treated with a combination of amoxicillin and daptomycin.

Abiotophia defectiva (A. defectiva) infectious endocarditis (IE) is a serious disease that usually requires lengthy treatment with a combination of amoxicillin and gentamicin. Since severe nephrotoxicity can be associated with prolonged administration of gentamicin, the alternative use of daptomycin in combination with amoxicillin can be considered. We present the case of a 51-year-old man that presented an A. defectiva endocarditis on an aortic bicuspidy. Diagnosis of cirrhosis was made simultaneously, and therefore gentamicin was counter-indicated. A combination of amoxicillin 12 g per day and daptomycin 700 mg (10 mg/kg) was administrated, with resolution of clinical, biological and echographic abnormalities, and no relapse after 1 year. In our experience, amoxicillin with daptomycin could be an alternative in case of A. defectiva IE with counter-indication to aminoglycosides.

Histoplasmosis: An oral malignancy-like clinical picture.

HIV-associated histoplasmosis is mainly misdiagnosed for granulomatous diseases, such as tuberculosis. Nonetheless, malignancy-like lesions have been reported sporadically in HIV-infected patients. Although the main reported lesions are erosive or ulcerated, here a rare case of oral tumor is reported. This case raises the awareness of this presentation, and the importance of accurate identification in the laboratory. Performing systematic specific stains for fungal elements and culture on tissue samples ensures accurate differential diagnosis.

Long-term outcome of critically ill adult patients with acute epiglottitis.

BACKGROUND: Acute epiglottitis is a potentially life threatening disease, with a growing incidence in the adult population. Its long-term outcome after Intensive Care Unit (ICU) hospitalization has rarely been studied. METHODOLOGY AND PRINCIPAL FINDINGS: Thirty-four adult patients admitted for acute epiglottitis were included in this retrospective multicentric study. The mean age was 44 ± 12 years (sex ratio: 5.8). Sixteen patients (47%) had a history of smoking while 8 (24%) had no previous medical history. The average time of disease progression before ICU was 2.6 ± 3.6 days. The main reasons for hospitalization were continuous monitoring (17 cases, 50%) and acute respiratory distress (10 cases, 29%). Microbiological documentation could be made in 9 cases (26%), with Streptococcus spp. present in 7 cases (21%). Organ failure at ICU admission occurred in 8 cases (24%). Thirteen patients (38%) required respiratory assistance during ICU stay; 9 (26%) required surgery. Two patients (6%) died following hypoxemic cardiac arrest. Five patients (15%) had sequelae at 1 year. Patients requiring respiratory assistance had a longer duration of symptoms and more frequent anti inflammatory use before ICU admission and sequelae at 1 year (p < 0.05 versus non-ventilated patients). After logistic regression analysis, only exposure to anti-inflammatory drugs before admission was independently associated with airway intervention (OR, 4.96; 95% CI, 1.06-23.16). CONCLUSIONS AND SIGNIFICANCE: The profile of the cases consisted of young smoking men with little comorbidity. Streptococcus spp. infection represented the main etiology. Outcome was favorable if early respiratory tract protection could be performed in good conditions. Morbidity and sequelae were greater in patients requiring airway intervention.

Clonal complex 398 methicillin susceptible Staphylococcus aureus: a frequent unspecialized human pathogen with specific phenotypic and genotypic characteristics.

Clonal complex 398 livestok-associated-MRSA (CC398 LA-MRSA) clone is described as a major animal pathogen that can also colonize and infect humans. CC398 methicillin susceptible Staphylococcus aureus (CC398 MSSA) is less described. We identified 126 CC398 MSSA strains of human origin within 6380 S. aureus isolates gathered between 2009 and 2011, from the French National Reference Centre for Staphylococci. They were characterized using antimicrobial susceptibility testing, spa typing, DNA microarrays (Identibac S. aureus Genotyping ®, Alere), CC398-specific sequence PCR, ermT (encoding macrolides résistance) PCR. Fifty-three CC398 LA-MRSA collected from French pigs and veal were used as comparators, and phylogenetic relations between human CC398 MSSA and animal CC398 MRSA populations were explored on the basis of spa-typing and DNA microarrays. CC398 MSSA were able to induce a large spectrum of infections (especially skin, bloodstream, and pneumonias). The prevalence rate of this clone was high in MSSA population, i.e., 24.7% in a local prospective study on nasal colonization, and 7.5% in a national prospective study on infective endocarditis. CC398 MSSA isolates were frequently (89%) erythromycin resistant, due to the presence of the ermT gene, a gene not detected in erythromycin resistant CC398 LA-MRSA strains. Expression of staphylococcal complement inhibitor (scn) and the chemotaxis inhibitory protein (chp), was also specific to this population. The CC398 MRSA signature included also a panel of antibiotic resistance genes, especially a type IV or V cassette mec and tetM. CC398 MSSA and CC398 LA-MRSA populations were closely related based on spa-typing and DNA microarrays, with the MRSA strains forming the most derived lineage in phylogenic trees. Both MSSA and MRSA populations may come from common ancestors, which would have evolved in the settings of different selective pressures, explaining the acquisition of ermT, chp and scn for MSSA, and antibiotic resistance genes for MRSA.

Major West Indies MRSA clones in human beings: do they travel with their hosts?

BACKGROUND: Descriptions of the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) have seldom been produced in the Caribbean, which is a major tourism destination. MATERIALS AND METHODS: Using DNA microarrays and spa typing, we characterized 85 MRSA isolates from human skin and soft-tissue infections from five different islands. RESULTS: In the French West Indies (n = 72), the most frequently isolated clones were the same clones that are specifically isolated from mainland France [Lyon (n = 35) and Geraldine (n = 11) clones], whereas the clones that were most frequently isolated from the other islands (n = 13) corresponded with clones that have a worldwide endemic spread [Vienna/Hungarian/Brazilian (n = 5), Panton Valentine leukocidin-positive USA300 (n = 4), New York/Japan (n = 2), and pediatric (n = 1) clones]. CONCLUSION: The distribution of the major MRSA clones in the French (Guadeloupe and Martinique) and non-French West Indies (Jamaica, Trinidad, and Tobago) is different, and the clones most closely resemble those found in the home countries of the travelers who visit the islands most frequently. The distribution might be affected by tourist migration, which is specific to each island.

Genome analysis of Staphylococcus aureus ST291, a double locus variant of ST398, reveals a distinct genetic lineage.

Staphylococcus aureus ST291 has been reported as a homologue recombinant double locus variant of the livestock associated S. aureus ST398. However, whole genome sequencing show that ST291 is a unique genetic lineage with highly variable content within its accessory genome compared to both human and livestock associated genome sequenced CC398s.