Ruxandra Moroti

Correlation between inflammatory biomarkers and metabolic disorders in HIV infected patients undergoing antiretroviral therapy

Correlation between inflammatory biomarkers and metabolic disorders in HIV infected patients undergoing antiretroviral therapy Raluca Mihăilescu, Victoria Aramă, Cătălin Tiliscan, Daniela Munteanu, Viorica Leoveanu, Mihaela Rădulescu, Adriana Hristea, Cristina Popescu, Ruxandra Moroti, Violeta Molagic, Raluca Năstase, Loredana Benea, Ana Maria Tudor, Mihai Lazăr, Anca-Ruxandra Negru, Irina Lăpădat, Ligia Ionescu, Mirela Cernat, Georgeta Jugănaru, Doina Cristea, Adriana Manea, Adrian Streinu-Cercel, Daniela Adriana Ion, Sorin Ștefan Aramă

Triazole-resistant Aspergillus fumigatus harbouring G54 mutation: Is it de novo or environmentally acquired?

Triazole resistance in Aspergillus fumigatus develops in patients with chronic lung diseases receiving long-term azole therapy or by environmental selection of resistant A. fumigatus. Here we report for the first time the isolation of triazole-resistant A. fumigatus (TRAF) harbouring the G54E mutation from environmental samples in India, Romania and Tanzania. This mutation in the cyp51A azole target gene of A. fumigatus is so far considered as de novo occurring in patients due to prolonged exposure to azoles. A total of 81 soil and woody debris samples from India, Romania and Tanzania were processed for detection of TRAF and determination of their susceptibility to medical triazoles and fungicides. cyp51A sequencing and real-time PCR were performed for detection of mutations. The isolates were genotyped by microsatellite typing. Overall, 25% of samples (20/81) from India, Romania and Tanzania harboured TRAF. Of the 20 samples harbouring TRAF, a single resistance mechanism, the G54E mutation, was found in 16 samples from three countries. This mechanism was responsible for 46.4% of resistant isolates from Tanzania, 30.4% from Romania and 20.0% from India. The G54E isolates revealed high MICs of itraconazole and posaconazole and were cross-resistant to agricultural fungicides. The majority of the Romanian and Tanzanian G54E isolates had an identical genotype. The present report describes the genetic heterogeneity of TRAF strains harbouring the G54E mutation in the environment of India, Romania and Tanzania. It may be anticipated that long-term exposure of A. fumigatus to fungicides may induce selection of G54 mutants in the environment.

Gut microbiota and its complex role. The experience of the National Institute for Infectious Diseases “Prof. Dr. Matei Balş” in fecal bacteriotherapy for Clostridium difficile infection

Gut microbiota and its complex role. The experience of the National Institute for Infectious Diseases “Prof. Dr. Matei Bals” in fecal bacteriotherapy for Clostridium difficile infection Cătălin Apostolescu, Ruxandra Moroti, Violeta Molagic, Valeriu Gheorghiță, Daniela Tălăpan, Mona Popoiu, Smaranda Botea, Alexandru Rafila, Marilena Palaghiță, Anca Budulac, Lavinia Ivănescu, Mirela Trifan, Gheorghiță Ciobanu, Adrian Streinu-Cercel

Toxoplasmosis: a rare cause of IRIS in HIV infected patients. Case series

Results Three patients, one male and 2 women, aged 55 years old, respectively 41 and 42 year-old, all 3 diagnosed concomitantly with HIV infection (as very late presenters) and cerebral toxoplasmosis, with a CD4 count of 6, 6 and 7/cmm respectively, viral loads (VL) of 254,000, 57,000 and 156,000 copies/mL respectively, and CSF viral load below the plasmatic VL in all 3 cases. We recorded minimal abnormalities of CSF analysis regarding the number of cells and biochemical exams; all had positive PCR for Toxoplasma gondii in the CSF and positive serology (IgG). All 3 had intracerebral lesions (abscesses) and all were biopsied at the neurosurgery department for diagnostic purpose before knowing their HIV-positive status. They received high doses of oral trimethoprim/sulfamethoxazole (T/S) for toxoplasmosis and antiretroviral therapy in the first 2 weeks after the diagnosis. They repeated cerebral imagery (MRI) after 3 weeks of T/S and had no regression of the size of lesions (although with the decreasing of perilesional edema) and new lesions, in two cases without having corresponding symptoms; in all 3 cases the CD4 count increased in the first month more than 100%. The search for another cause for the augmentation of their brain lesions was negative. Maintaining the same medication, the next imagery exams showed improvement in 2 out of 3 cases, in which the outcome was favorable with almost complete neurological recovery. In the remaining case the evolution was unfavorable (death).

Fusarium ramigenum , a novel human opportunist in a patient with common variable immunodeficiency and cellular immune defects: case report

BackgroundFusarium species are ubiquitous environmental fungi that occasionally provoke serious invasive infections in immunocompromised hosts. Among Fusarium species, Fusarium ramigenum, belonging to the Fusarium fujikuroi species complex, has thus far never been found to cause human infections. Here we describe the first case of invasive fusariosis caused by Fusarium ramigenum in a human and also identify immunological deficiencies that most likely contributed to invasiveness.Case presentationA 32-year-old Caucasian male with a seemingly insignificant medical history of mild respiratory illness during the preceding two years, developed invasive pulmonary fusariosis. Detailed immunological assessment revealed the presence of common variable immunodeficiency, complicated by a severe impairment of the capacity of T-cells to produce both gamma-interferon and interleukin-17. In-depth microbiological assessment identified the novel human opportunistic pathogen Fusarium ramigenum as cause of the infection.ConclusionThis report demonstrated that an opportunistic invasive fungal infection may indicate an underlying cellular immune impairment of the host. The unexpected invasive infection with Fusarium ramigenum in this case unmasked a complex combined humoral and cellular immunological deficiency.

Molecular determinants of resistance in Escherichia coli-ST131 isolated blood stream infections

Background During the past years an E coli clonal lineage ST131 has emerged explosively, causing predominantly communityonset antimicrobial resistant infections. E coli ST131 has been shown to harbor a number of virulence and resistance genes and is now recognized for its ability to cause potentially severe infections in many parts of the developing world, implying public health measures in attempt to control infection.

HIV-associated Burkitt lymphoma with bone marrow and cerebral invasion in a patient with history of Plasmodium falciparum infection

HIV infected patients are more likely to develop non-Hodgkin lymphoma (NHL). Burkitt lymphoma (BL) is a highly aggressive NHL, associated with immunosuppression, especially with HIV. According to WHO classification there are three clinical types of BL: endemic, sporadic and immunosuppression-associated. Sporadic lymphoma was described especially in children (40% of child lymphomas in USA and EU). Two cofactors seem to be associated with BL: Ebstein Barr virus (EBV) and Plasmodium falciparum (PF) infection. PF and EBV are well-known co-factors in the pathogenesis of BL, but the mechanisms of interaction remain unclear. We present a 51 year-old male, who developed lymphadenopathy, prolonged fever, weight loss, splenomegaly and seizure. The patient was admitted to a Hematology University Hospital. After lymph node biopsy he was diagnosed with BL. A specimen of bone marrow from the right iliac crest showed gross invasion by Burkitt tumor cells. The patient tested positive for HIV and he was referred to the National Institute of Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest. According to CDC Classification System for HIV Infection the patient had AIDS (C3 stage with a CD4 count of 39/cmm) and a high HIV viral load (500,262 copies/mL). The patient’s medical history revealed Plasmodium falciparum malaria 4 years ago, while he was living in South America. Epidemiological data revealed more than 200 sexual partners in the last two years. At admission to our hospital he had pancytopenia: white blood cells 1400/cmm, with 600 neutrophils and 600 lymphocytes, hemoglobin 9.6 g/dL and platelet count 25,000/cmm. The patient was tested for EBV infection and high titer of anti-VCA antibodies was found. ART was initiated with TDF-FTC-lopinavir/r with good virological outcome (after 6 weeks of therapy the viral load was 383 copies/mL). Cerebral MRI showed diffuse lymphomatous invasion. After 3 weeks of ART the patient was referred to Hematology Hospital where chemotherapy was started. Post-chemotherapy the pancytopenia was more severe: white blood cells – 200/cmm with CD4 count – 10/cmm, platelets – 15,000/cmm and hemoglobin – 7.9 g/dL. The BL response after chemotherapy was poor and the patient died two months after the diagnosis, despite the good virological outcome. We present a rare case of NHL in a HIV-infected patient, with multiple co-factors for BL: HIV infection, EBV infection and Plasmodium falciparum infection. The prognostic in AIDS depends on the comorbidities’ outcome.

Metabolic syndrome, insulin resistance and the risk of cardiovascular disease in HIV patients undergoing antiretroviral therapy

We enrolled 103 patients, including 60 males (58.3%) and 43 females (41.7%). The mean age was 32.3±13.3 years (range: 13-65 years). The median Framingham score was 1.2% (IQR=5.8%). Most patients (81.63%) had a low CVR (below 10%) and 18.37% had Framingham score values above 10%. MS and IR prevalences were 16.9% and 61.2%, respectively. CVR in the general population is primarily dependent on age. This observation was valid for our group: the median age was 24 years in people with low CVR, compared with 50 years for those with Framingham score above 10% (p=0.000). None of the antiretroviral drug classes significantly influenced CVR.

Characteristics of Kaposi sarcoma in HIV-infected patients

Objective: to describe clinical and laboratory characteristics; to assess predictors for death in HIV-infected patients with Kaposi sarcoma (KS). We performed a retrospective study of HIV-infected patients diagnosed with KS in one infectious diseases hospital in Romania, between January 2008-November 2013. KS diagnosis was established on physical examination, skin biopsy, and for visceral involvement upper gastrointestinal endoscopy, bronchoscopy and computed tomography. KS was staged according to the AIDS Clinical Trials Group (ACTG) [1] and the Mitsuyasu classification system [2]. We identified 27 HIV-infected patients with KS. The median age was 42 years (IQR 34-52) and 18 (67%) were male. The median CD4 count at HIV diagnosis was 195 cells/cmm (IQR 55-313), while at KS diagnosis the median CD4 count was 101 cells/cmm (IQR 41-270). Eighteen (67%) patients had a CD4 count <200 cells/cmm. The median HIV viral load at the time of KS diagnosis was 120,000 copies/mL (IQR 316-328,522). HIV infection was diagnosed before KS in 19 patients (70%), with a median time between HIV and KS diagnosis of 7 months (IQR 0-58). The most frequent KS localization was the lower limb in 16 (59%) patients and 7 (26%) patients had disseminated KS. Oral, gastrointestinal and pulmonary involvements were seen in 10 (37%), 4 (15%) and 3 (11%) patients respectively. Concomitant opportunistic infections were diagnosed in 20 (74%), while other malignancies in 3 (12%) patients. According to the ACTG classification 16 (59%) patients had poor risk KS. Fifteen (56%), 6 (22%), 1 (4%) and 5 (18%) were in stage 1, 2, 3 and 4, respectively according to the Mitsuyasu classification. Six (22%) patients received specific KS treatment: three local radiotherapy and three systemic therapy (two with interferon; one with liposomal doxorubicin). The overall mortality was 41% with a median duration between KS diagnosis and death of 6 months (IQR 2-15). Gastrointestinal involvement (p=0.019), poor-risk KS in ACTG classification (p<0.001) and stage IV Mitsuyasu (p=0.006) were associated with death in univariate analysis. The mortality rate in this study was high, due to poor immunological status, extended KS and high incidence of opportunistic infections, but also due to the lack of specific systemic treatment.

Clinical and epidemiologic features of community versus hospital-acquired Clostridium difficile infection

Methods We enrolled all CDI patients admitted to the Adults III department of the National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest, between January – July 2014. Stool culture, toxin EIA and Cepheid Gene Xpert C. difficile test were used for CDI diagnosis. The subjects were divided into two groups: CA-CDI patients (Group 1) and HA-CDI patients (Group 2). Our objective was to describe the clinical, epidemiologic features and outcome of CA-CDI compared to hospital-associated CDIs (HA-CDI) including the ATLAS bedside severity scoring system. Statistical analyses were performed using SPSS Statistics package v.17.