Vincent Le Moing

Preeminence of Staphylococcus aureus in Infective Endocarditis: A 1-Year Population-Based Survey

BACKGROUND Observational studies showed that the profile of infective endocarditis (IE) significantly changed over the past decades. However, most studies involved referral centers. We conducted a population-based study to control for this referral bias. The objective was to update the description of characteristics of IE in France and to compare the profile of community-acquired versus healthcare-associated IE. METHODS A prospective population-based observational study conducted in all medical facilities from 7 French regions (32% of French individuals aged ≥18 years) identified 497 adults with Duke-Li-definite IE who were first admitted to the hospital in 2008. Main measures included age-standardized and sex-standardized incidence of IE and multivariate Cox regression analysis for risk factors of in-hospital death. RESULTS The age-standardized and sex-standardized annual incidence of IE was 33.8 (95% confidence interval [CI], 30.8-36.9) cases per million inhabitants. The incidence was highest in men aged 75-79 years. A majority of patients had no previously known heart disease. Staphylococci were the most common causal agents, accounting for 36.2% of cases (Staphylococcus aureus, 26.6%; coagulase-negative staphylococci, 9.7%). Healthcare-associated IE represented 26.7% of all cases and exhibited a clinical pattern significantly different from that of community-acquired IE. S. aureus as the causal agent of IE was the most important factor associated with in-hospital death in community-acquired IE (hazard ratio [HR], 2.82 [95% CI, 1.72-4.61]) and the single factor in healthcare-associated IE (HR, 2.54 [95% CI, 1.33-4.85]). CONCLUSIONS S. aureus became both the leading cause and the most important prognostic factor of IE, and healthcare-associated IE appeared as a major subgroup of the disease.

The dynamic of Adherence to highly active antiretroviral therapy : Results from the French National APROCO cohort

Objectives: Our objective was to describe the evolution of adherence to highly active antiretroviral therapy (HAART) over a 20‐month period and its relationship with virologic success. Methods: Self‐reported adherence, clinical, and virologic data were collected 4 (M4), 12 (M12), and 20 (M20) months after initiation of a protease inhibitorcontaining regimen in the French APROCO cohort. At each visit, patients were classified as nonadherent, moderately, or highly adherent, and HIV plasma RNA was determined. Results: Among the 762 patients who were regularly followed until M20, the 436 patients who answered to all questionnaires, including adherence measurement, were selected for the analysis. The proportion of highly adherent patients was 55.7%, 62.2%, and 60.3% at M4, M12, and M20, respectively. A total of 137 patients (31.4%) was “always,” 225 (51.6%) “sometimes,” and 74 (17.0%) “never” “highly adherent” during follow‐up. After multiple adjustment for known baseline predictors, virologic success after 20 months of HAART was more likely achieved in patients who were always (odds ratio [OR] 95% confidence interval [CI], 3.02 [1.64‐5.58]) or sometimes (OR [95% CI], 2.15 [1.24‐3.74]) “highly adherent.” Conclusion: Adherence behavior is a dynamic process. Continued adherence was associated with better response to therapy and should be encouraged to reduce the risk of virologic failure.

Temporal Trends in Infective Endocarditis in the Context of Prophylaxis Guideline Modifications: Three Successive Population-Based Surveys

OBJECTIVES The goal of this study was to evaluate temporal trends in infective endocarditis (IE) incidence and clinical characteristics after 2002 French IE prophylaxis guideline modifications. BACKGROUND There are limited data on changes in the epidemiology of IE since recent guidelines recommended restricting the indications of antibiotic prophylaxis of IE. METHODS Three 1-year population-based surveys were conducted in 1991, 1999, and 2008 in 3 French regions totaling 11 million inhabitants age ≥20 years. We prospectively collected IE cases from all medical centers and analyzed age- and sex-standardized IE annual incidence trends. RESULTS Overall, 993 expert-validated IE cases were analyzed (323 in 1991; 331 in 1999; and 339 in 2008). IE incidence remained stable over time (95% confidence intervals given in parentheses/brackets): 35 (31 to 39), 33 (30 to 37), and 32 (28 to 35) cases per million in 1991, 1999, and 2008, respectively. Oral streptococci IE incidence did not increase either in the whole patient population (8.1 [6.4 to 10.1], 6.3 [4.8 to 8.1], and 6.3 [4.9 to 8.0] in 1991, 1999, and 2008, respectively) or in patients with pre-existing native valve disease. The increased incidence of Staphylococcus aureus IE (5.2 [3.9 to 6.8], 6.8 [5.3 to 8.6], and 8.2 [6.6 to 10.2]) was not significant in the whole patient population (p = 0.228) but was significant in the subgroup of patients without previously known native valve disease (1.6 [0.9 to 2.7], 3.7 [2.6 to 5.1], and 4.1 [3.0 to 5.6]; p = 0.012). CONCLUSIONS Scaling down antibiotic prophylaxis indications was not associated with an increased incidence of oral streptococcal IE. A focus on avoidance of S. aureus bacteremia in all patients, including those with no previously known valve disease, will be required to improve IE prevention.

Predictors of virological rebound in HIV-1-infected patients initiating a protease inhibitor-containing regimen.

Objective To study the predictors of virological rebound in patients having early virological response to protease inhibitor (PI)-containing regimen. Design and methods APROCO cohort study prospectively enrolled 1283 HIV-infected patients starting a PI-containing regimen in 1997–1999. Adherence to therapy was measured with self-administered questionnaires after 4 months of therapy (M4). Virological rebound was defined as a viral load (VL) > 500 copies/ml in patients having early virological response, defined as a VL < 500 copies/ml at M4. Predictors of time to virological rebound were studied with multivariate proportional hazards model. Results During a median follow-up of 20 months, virological rebound was observed in 32% of the 830 patients with early virological response. Virological rebound was more frequent when patients had received previous antiretroviral treatment [adjusted hazards ratio (HR) = 2.4;P < 0.0001], were younger (HR = 1.4 per each 10 years younger;P < 0.0001), had baseline CD4 cell count < 500 × 106/l (HR = 2.3;P < 0.001), had higher baseline VL (HR = 1.4 per each log10 copies/ml higher;P < 0.001), reported low adherence to therapy at M4 (HR = 2.1;P < 0.001) or had stopped PI at M4 (HR = 1.7;P = 0.04). Conclusion Initiation of treatment at a stage of preserved immunity is associated with a more durable virological response under protease inhibitor. Every effort should be made to monitor and strengthen adherence to therapy, even in patients having early virological response.

Hepatitis B or Hepatitis C Virus Infection Is a Risk Factor for Severe Hepatic Cytolysis after Initiation of a Protease Inhibitor-Containing Antiretroviral Regimen in Human Immunodeficiency Virus-Infected Patients

ABSTRACT In a cohort of 1,047 human immunodeficiency virus type 1-infected patients started on protease inhibitors (PIs), the incidence of severe hepatic cytolysis (alanine aminotransferase concentration five times or more above the upper limit of the normal level ≥ 5N) was 5% patient-years after a mean follow-up of 5 months. Only positivity for hepatitis C virus antibodies (hazard ratio [HR], 7.95;P < 10−3) or hepatitis B virus surface antigen (HR, 6.67; P < 10−3) was associated with severe cytolysis. Before starting patients on PIs, assessment of liver enzyme levels and viral coinfections is necessary.

The impact of valve surgery on short- and long-term mortality in left-sided infective endocarditis: do differences in methodological approaches explain previous conflicting results?

AIMS The aim of this study was to evaluate the effect of valve surgery (VS) in infective endocarditis (IE) on 5-year mortality and to evaluate whether conflicting results reported by previous studies could be due to differences in their methodological approaches. METHODS AND RESULTS Four hundred and forty-nine patients with a definite left-sided IE were selected from a prospective, population-based study. Association between VS and 5-year mortality was examined with a Cox model. To determine the impact of different methodological approaches, we also analysed the relationship between VS and mortality in our database, according to each method used in the five previous studies. Valve surgery was performed in 240 patients (53%). It was associated with an increase in short-term mortality [within the first 14 post-operative days; adjusted hazard ratio (HR), 3.69; 95% confidence interval (CI), 2.17-6.25; P<0.0001] and a decrease in long-term mortality (adjusted HR, 0.55; 95% CI, 0.35-0.87; P=0.01). At least 188 days of follow-up were required for VS to provide an overall survival advantage. When applying each studys method to our database, we obtained results similar to those reported. CONCLUSION Previous conflicting results appear to be related to differences in statistical methods. When using appropriate models, we found that VS was significantly associated with reduced long-term mortality.

Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial.

BACKGROUND Duration of treatment for patients with vertebral osteomyelitis is mainly based on expert recommendation rather than evidence. We aimed to establish whether 6 weeks of antibiotic treatment is non-inferior to 12 weeks in patients with pyogenic vertebral osteomyelitis. METHODS In this open-label, non-inferiority, randomised controlled trial, we enrolled patients aged 18 years or older with microbiologically confirmed pyogenic vertebral osteomyelitis and typical radiological features from 71 medical care centres across France. Patients were randomly assigned to either 6 weeks or 12 weeks of antibiotic treatment (physicians choice in accordance with French guidelines) by a computer-generated randomisation list of permuted blocks, stratified by centre. The primary endpoint was the proportion of patients who were classified as cured at 1 year by a masked independent validation committee, analysed by intention to treat. Non-inferiority would be declared if the proportion of cured patients assigned to 6 weeks of treatment was not less than the proportion of cured patients assigned to 12 weeks of treatment, within statistical variability, by an absolute margin of 10%. This trial is registered with EudraCT, number 2006-000951-18, and Clinical Trials.gov, number NCT00764114. FINDINGS Between Nov 15, 2006, and March 15, 2011, 359 patients were randomly assigned, of whom six in the 6-week group and two in the 12-week group were excluded after randomisation. 176 patients assigned to the 6-week treatment regimen and 175 to the 12-week treatment regimen were analysed by intention to treat. 160 (90·9%) of 176 patients in the 6-week group and 159 (90·9%) of 175 of those in the 12-week group met the criteria for clinical cure. The difference between the groups (0·05%, 95% CI -6·2 to 6·3) showed the non-inferiority of the 6-week regimen when compared with the 12-week regimen. 50 patients in the 6-week group and 51 in the 12-week group had adverse events, the most common being death (14 [8%] in the 6-week group vs 12 [7%] in the 12-week group), antibiotic intolerance (12 [7%] vs 9 [5%]), cardiorespiratory failure (7 [4%] vs 12 [7%]), and neurological complications (7 [4%] vs 3 [2%]). INTERPRETATION 6 weeks of antibiotic treatment is not inferior to 12 weeks of antibiotic treatment with respect to the proportion of patients with pyogenic vertebral osteomyelitis cured at 1 year, which suggests that the standard antibiotic treatment duration for patients with this disease could be reduced to 6 weeks. FUNDING French Ministry of Health.

Ten-year incidence and risk factors of bone fractures in a cohort of treated HIV1-infected adults.

In the ANRS CO8 APROCO-COPILOTE cohort of patients treated with combination antiretroviral therapy since 1997–1999, the incidence density of bone fractures was 3.3 for 1000 patient-years [95% confidence interval (CI) = 2.0–4.6]. The rate was 2.9-fold (95% CI = 1.3–6.5) higher among patients with excessive alcohol consumption and 3.6-fold (95% CI = 1.6–8.1) higher in those with hepatitis C virus (HCV) coinfection. Specific monitoring of HCV/HIV-coinfected patients and active promotion of alcohol cessation should be recommended for the prevention of bone fractures.

Clinical, biologic, and behavioral Predictors of early immunologic and virologic response in HIV-infected patients initiating protease inhibitors

Summary: Predictors of virologic (plasma HIV RNA viral load [VL] <500 copies/ml) and immunologic (rise in CD4+ cell count >50 cells/mm3) response after 4 months of therapy (M4) were studied in 750 HIV‐1‐infected patients prospectively enrolled at the initiation of a protease inhibitor (PI)‐containing regimen. A virologic response was observed in 80% of patients, and an immunologic response was observed in 64%. Sixty‐two percent of patients self‐reported full adherence to therapy at 1 month of therapy (M1) and M4. In multivariate analysis, a virologic response was more frequent in fully adherent patients (odds ratio [OR] = 2.0; p = .001). An immunologic response was associated with age <36 years (OR = 1.4; p = .03), baseline VL (OR = 1.5 per 1 log10 copies/ml higher; p < .01), decrease in VL at M1 (OR = 1.5 per 1 log10 copies/ml decrease; p < .01), baseline total lymphocyte count (OR = 1.7 per 50% lower; p < .001), and baseline CD4+ cell percentage ≥ 20% (OR = 1.9; p < .001) but not with adherence to therapy. Full adherence seems to be a major predictor of a virologic response to P1‐containing triple therapy. An immunologic response may be possible despite incomplete adherence, at least early in therapy.

Zika virus infections in three travellers returning from South America and the Caribbean respectively, to Montpellier, France, December 2015 to January 2016.

We report three unrelated cases of Zika virus infection in patients returning from Martinique, Brazil and Colombia respectively, to Montpellier, France. They developed symptoms compatible with a mosquito-borne disease, and serological and molecular investigations indicated a recent Zika virus infection. Considering the recent warning for the likely teratogenicity of Zika virus and the presence of competent mosquito vectors in southern France, these cases highlight the need for awareness of physicians and laboratories in Europe.