Xavier Argemi

Impact of malnutrition and social determinants on survival of HIV-infected adults starting antiretroviral therapy in resource-limited settings.

Objectives:Determining the impact of malnutrition, anaemia and social determinants on survival once starting antiretroviral therapy (ART) in a cohort of HIV-infected adults in a rural HIV care centre in Sihanoukville, Cambodia. Methods:Retrospective and descriptive cohort study of adults starting ART between December 2004 and July 2009. We used the Kaplan–Meier and Cox regression survival analyses to identify predictors of death. Results:Out of 1002 patients, 49.7% were men; median age was 40; median time of follow-up was 2.4 years and 10.4% died during the follow-up. At baseline, median CD4 cell count was 83 cells/&mgr;l, 79.9% were at WHO stage III or IV. In multivariate analysis, malnutrition appeared to be a strong and independent risk factor of death; 11.2% had a BMI less than 16 kg/m2 and hazard ratio was 6.97 [95% confidence interval (CI), 3.51–13.89], 21.5% had a BMI between 16 and 18 kg/m2 and hazard ratio was 2.88 (95% CI, 1.42–5.82), 30.8% had a BMI between 18 and 20 kg/m2 and hazard ratio was 2.18 (95% CI, 1.09–4.36). Severe anaemia (haemoglobin ⩽8.4 g/dl) and CD4 cell count below 100 cells/&mgr;l also predicted mortality, hazard ratio were 2.25 (95% CI, 1.02–4.34) and 2.29 (95% CI, 1.01–2.97), respectively. Social determinants were not significantly associated with death in univariate analysis. Conclusion:Malnutrition and anaemia are strong and independent prognostic factors at the time of starting ART. Nutritional cares are essential for the clinical success of HIV programs started in developing countries.

Implementation of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry in Routine Clinical Laboratories Improves Identification of Coagulase-Negative Staphylococci and Reveals the Pathogenic Role of Staphylococcus lugdunensis

ABSTRACT The use of matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) for staphylococcal identification is now considered routine in laboratories compared with the conventional phenotypical methods previously used. We verified its microbiological relevance for identifying the main species of coagulase-negative staphylococci (CoNS) by randomly selecting 50 isolates. From 1 January 2007 to 31 August 2008, 12,479 staphylococci were isolated with phenotypic methods, of which 4,594 were identified as Staphylococcus aureus and 7,885 were coagulase negative staphylococci. Using MALDI-TOF MS from 1 January 2011 to 31 August 2012, 14,913 staphylococci were identified, with 5,066 as S. aureus and 9,847 as CoNS. MALDI-TOF MS allowed the identification of approximately 85% of the CoNS strains, whereas only 14% of the CoNS strains were identified to the species level with phenotypic methods because they were often considered contaminants. Furthermore, the use of MALDI-TOF MS revealed the occurrence of recently characterized Staphylococcus species, such as S. pettenkoferi, S. condimenti, and S. piscifermentans. Microbiological relevance analysis further revealed that some species displayed a high rate of microbiological significance, i.e., 40% of the S. lugdunensis strains included in the analysis were associated with infection risk. This retrospective microbiological study confirms the role of MALDI-TOF MS in clinical settings for the identification of staphylococci with clinical consequences. The species distribution reveals the occurrence of the recently identified species S. pettenkoferi and putative virulent species, including S. lugdunensis.

Pathogenic features of clinically significant coagulase-negative staphylococci in hospital and community infections in Benin.

In West Africa, very little consideration has been given to coagulase negative Staphylococci (CNS). Herein, we describe the features contributing to the pathogenicity of 99 clinically-significant independent CNS isolates associated with infections encountered at the National Teaching Hospital Center of Cotonou (Benin). The pathogenic potentials of nosocomial strains were compared with community strains. S. haemolyticus (44%), S. epidermidis (22%) and S. hominis (7%) were the most frequently isolated while bacteremia (66.7%) and urinary tract infections (24.2%) were the most commonly encountered infections. Most strains were resistant to multiple antibiotics, including penicillin (92%), fosfomycin (81%), methicillin (74%) and trimethoprim-sulfamethoxazole (72%). The most frequently isolated species were also the most frequently resistant to methicillin: S. hominis (100%), S. haemolyticus (93%) and S. epidermidis (67%). Screening of toxic functions or toxin presence revealed hemolytic potential in 25% of strains in over 50% of human erythrocytes in 1h. Twenty-six percent of strains exhibited protease activity with low (5%), moderate (10%) and high activity (11%), while 25% of strains displayed esterase activity. Three percent of strain supernatants were able to lyse 100% of human polymorphonuclear cells after 30min. Polymerase chain reaction and latex agglutination methods revealed staphylococcal enterotoxin C gene expression in 9% of S. epidermidis. A majority of hospital-associated CNS strains (68%) had at least one important virulence feature, compared with only 32% for community-acquired strains. The present investigation confirms that these microorganisms can be virulent, at least in some individual cases, possibly through genetic transfer from S. aureus.

Clinical usefulness of 18F–FDG PET/CT for initial staging and assessment of treatment efficacy in patients with lymph node tuberculosis

INTRODUCTION Few studies have evaluated the promising role of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (PET) and PET/computed tomography FDG PET/CT in evaluating and monitoring treatment response in patients with lymph node tuberculosis (LNTB). The aim of this clinical investigation was to assess the clinical usefulness of FDG PET/CT for initial tuberculosis staging and to determine the prognostic value of the decrease of 18F-FDG uptake during antibiotic treatment in LNTB patients. METHODS We retrospectively reviewed 18 cases of LNTB admitted at a single center from 2004 to 2014. Medical records of patients who underwent two FDG PET/CT (>6 months interval), at initial staging and at the end of therapy were reviewed to determine the impact of FDG PET/CT on initial management of LNTB and response to therapy. Statistical analysis was performed using linear mixed-effects model. RESULTS Thirteen cases of disseminated LNTB and five cases of localized LNTB were included in the study. Initial FDG PET/CT allowed guided biopsy for initial diagnosis in 5 patients and identified unknown extra-LN TB sites in 9 patients. Visual analysis follow-up of FDG PET/CT showed a complete metabolic response in 9/18 patients (all of whom were cured), a partial response in 7/18 (5 of whom were cured) and no response in 2/18 (all of whom were not cured). The semi-quantitative evaluation of 18F-FDG intensity decrease based on the maximum standardized uptake value (SUVmax), compared to targeted estimated decrease allowed to predict correctly a complete response to treatment in 14/18 cases. CONCLUSION FDG PET/CT allows an accurate pre-therapeutic mapping of LNTB and helps for early TB confirmation. The SUVmax follow up is a potential tool for monitoring the treatment response.

Whole-Genome Sequencing of Seven Strains of Staphylococcus lugdunensis Allows Identification of Mobile Genetic Elements

Coagulase negative staphylococci are normal inhabitant of the human skin flora that account for an increasing number of infections, particularly hospital-acquired infections. Staphylococcus lugdunensis has emerged as a most virulent species causing various infections with clinical characteristics close to what clinicians usually observe with Staphylococcus aureus and both bacteria share more than 70% of their genome. Virulence of S. aureus relies on a large repertoire of virulence factors, many of which are encoded on mobile genetic elements. S. lugdunensis also bears various putative virulence genes but only one complete genome with extensive analysis has been published with one prophage sequence (φSL2) and a unique plasmid was previously described. In this study, we performed de novo sequencing, whole genome assembly and annotation of seven strains of S. lugdunensis from VISLISI clinical trial. We searched for the presence of virulence genes and mobile genetics elements using bioinformatics tools. We identified four new prophages, named φSL2 to φSL4, belonging to the Siphoviridae class and five plasmids, named pVISLISI_1 to pVISLISI_5. Three plasmids are homologous to known plasmids that include, amongst others, one S. aureus plasmid. The two other plasmids were not described previously. This study provides a new context for the study of S. lugdunensis virulence suggesting the occurrence of several genetic recombination’ with other staphylococci.

Campylobacter fetus infection in three rheumatoid arthritis patients treated with rituximab

Campylobacter fetus osteoarticular or prosthetic material infection or cellulitis has been rarely described, mainly in immunocompromised patients. Among these cases, only two patients had inflammatory systemic diseases treated with rituximab (RTX).1 We report three patients with rheumatoid arthritis (RA) treated with RTX who developed osteoarticular or cutaneous infection due to C fetus . The patients were aged 71, 53 and 80 years with disease durations of 24, 13 and 19 years, respectively. All patients had a history of diabetes. Patients 1 and 3 had hypertensive cardiomyopathy, while patient 2 suffered from chronic obstructive pulmonary disease (COPD) and patient 3 from bronchiolitis obliterans organising pneumonia. All patients were co-treated with corticosteroids (10 mg/day) and disease-modifying antirheumatic …

A new hot spot for tick-borne encephalitis (TBE): A marked increase of TBE cases in France in 2016

OBJECTIVES Tick-borne encephalitis virus (TBEV) is a zoonotic agent causing severe encephalitis. In 2016, in Northeastern France, we faced a TBEV infection increase, leading to a warning from the Regional Health Agency. Here, we report the confirmed TBE cases diagnosed between January 2013 and December 2016, with particular emphasis on the year 2016. METHODS A total of 1643 blood and cerebrospinal fluid (CSF) samples from everywhere in France, corresponding to 1460 patients, were prospectively tested for anti-TBEV-specific IgM and IgG antibodies by ELISA. Additional 39 blood and CSF samples from patients with suspected Lyme neuroborreliosis were retrospectively investigated. RESULTS The TBEV seropositivity rate was estimated to 5.89% and 54 patients were diagnosed as TBE-confirmed cases. A significant increase in TBE cases was observed during the year 2016 with 29 confirmed cases, instead of a mean of eight cases during the three previous years (p=0.0006). Six imported cases and 48 autochthonous cases, located in the Alsace region (n=43) and in the Alpine region (n=5) were reported. Forty-six patients experienced neurological impairment. Nine patients showed an incomplete recovery at last follow-up (from 15days to eight months post-infection). TBE diagnosis was performed earlier for patients taken in charge in the Alsace region than those hospitalized elsewhere in France (p=0.0087). Among the 39 patients with suspected Lyme neuroborreliosis retrospectively investigated, one showed a TBEV recent infection. CONCLUSION The TBE increase that occurred in France in 2016 highlights the need to improve our knowledge about the true burden of TBEV infection and subsequent long-term outcomes.

Is Staphylococcus lugdunensis Significant in Clinical Samples

ABSTRACT The implication of coagulase-negative staphylococci in human diseases is a major issue, particularly in hospital settings wherein these species often act as opportunistic pathogens. In addition, some coagulase-negative staphylococci such as S. lugdunensis have emerged as pathogenic bacteria, implicated in severe infections, particularly, osteoarticular infections, foreign-body-associated infections, bacteremia, and endocarditis. In vitro studies have shown the presence of several putative virulence factors such as adhesion factors, biofilm production, and proteolytic factors that might explain clinical manifestations. Taken together, the clinical and microbiological data might change the way clinicians and microbiologists look at S. lugdunensis in clinical samples.

In vitro activity of daptomycin against Enterococcus faecalis under various conditions of growth-phases, inoculum and pH.

Enterococcus faecalis (E. faecalis) has become a major leading cause of nosocomial endocarditis. Treatment of such infections remains problematic and new therapeutic options are needed. Nine E. faecalis strains were tested: six obtained from patients presenting endocarditis, one with isolated bacteremia, and two reference strains. Antibiotics included daptomycin, alone or in combination, linezolid, tigecycline, rifampicin, gentamicin, teicoplanin, ceftriaxone and amoxicillin. Time-kill studies included colony counts at 1, 4 and 24 h of incubation. Significant bactericidal activity was defined as a decrease of ≥3log10CFU/ml after 24 h of incubation. Antibiotics were tested at a low (106 CFU/ml) and high (109 CFU/ml) inoculum, against exponential- and stationary-phase bacteria. We also performed time kill studies of chemically growth arrested E. faecalis. Various pH conditions were used during the tests. In exponential growth phase and with a low inoculum, daptomycin alone at 60 µg/ml and the combination amoxicillin-gentamicin both achieved a 4-log10 reduction in one hour on all strains. In exponential growth phase with a high inoculum, daptomycin alone was bactericidal at a concentration of 120 µg/ml. All the combinations tested with this drug were indifferent. In stationary phase with a high inoculum daptomycin remained bactericidal but exhibited a pH dependent activity and slower kill rates. All combinations that did not include daptomycin were not bactericidal in conditions of high inoculum, whatever the growth phase. The results indicate that daptomycin is the only antibiotic that may be able of overcoming the effects of growth phase and high inoculum.

Kinetics of biofilm formation by Staphylococcus lugdunensis strains in bone and joint infections

OBJECTIVE To describe the clinical presentation and 1-year follow-up of patients with bone and joint infections (BJIs) caused by Staphylococcus lugdunensis and evaluate its biofilm-forming capacities. PATIENTS AND METHODS Overall, 28 patients with BJIs from VISLISI clinical trials were included. We evaluated 1-year clinical follow-up and analyzed biofilm production kinetics of the 28 strains using the BioFilm Ring Test®. RESULTS Of all patients, 12 had osteoarticular infections without material and 16 had prosthetic joint infections, of which 9 underwent a 1-stage revision procedure. At the 1-year follow-up, all patients were cured but needed a surgical intervention. Diabetes affected 46.4% of all patients. Of all, 20 strains (71.4%) started biofilm formation within 2 h, but all strains started the formation after 4 h experiment, and 25 strains (89.3%) reached a maximum after 6 h. CONCLUSIONS This study describes the clinical and surgical management of BJIs caused by S. lugdunensis and shows that 1-stage prosthesis exchange procedures may be efficient. Further, It shows that biofilm production by this strain was not marginal and directly impacted clinical and surgical management.