Antistaphylococcal penicillins vs. cefazolin in the treatment of methicillin-susceptible Staphylococcus aureus infective endocarditis: a quasi-experimental monocentre study.

Whether cefazolin is as effective and safer than antistaphylococcal penicillins (ASPs) for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) is still debated in the absence of a randomized controlled trial. In this quasi-experimental study, we aimed to assess the effectiveness and safety of these two treatments in MSSA-IE, using the ASPs nationwide shortage in April 2016 as a unique opportunity to overcome the indication bias associated with observational studies. In this single-centre study, we compared patients with Duke-Li definite MSSA-IE treated with ASPs from January 2015 to March 2016 versus those treated with cefazolin from April 2016 to December 2018, when ASPs were not available. Effectiveness outcome was 90-day all-cause mortality. Safety outcomes included significant decrease in GFR and significant increase in serum liver enzymes. Logrank test was used to compare survival rates. Of 73 patients with MSSA-IE, 35 and 38 were treated with ASPs and cefazolin, respectively. Baseline patients' characteristics (demography, native or prosthetic valve IE, clinical characteristics, cardiac and septic complications) were similar between groups. Ninety-day all-cause mortality was 28.6% and 21.1%, in patients treated with ASPs and cefazolin, respectively (logrank p = 0.5727). There was no difference between groups for incident renal or liver toxicity events: acute kidney injury 45.7% vs. 44.7% (p = 0.933), increased ALT 5.7% vs. 13.2% (p = 0.432), bilirubin increase 5.7% vs. 10.5% (p = 0.676), in ASPs vs. cefazolin groups, respectively. In this quasi-experimental, effectiveness and safety did not statistically differ between ASPs and cefazolin for MSSA-IE treatment.

Multi-sectorial research is paramount for preventing and controlling emerging infectious diseases.

The social, economic and political consequences of emerging infectious disease (EID) may escape the sphere in which they first arise. In recent years, many EIDs have revealed the close links between human, animal and plant health, highlighting the need for multi-scale, multisectorial EID management. Human beings play a dual role in EID because they can promote their development through numerous human-environment interfaces and expanding international trade. On the other hand, their ability to analyze, interpret and act on the determinants of EID allows them to access the expertise necessary to control these EIDs. This expertise must be constantly adapted to remain relevant as the EID evolves, particularly in its virulence or transmission channels. Flexibility should become an inherent part of the expertise-based decision-making process even if it means going backwards. A certain degree of transparency and feedback to citizens is necessary for the acceptability of political decisions basing on expertise. A key step in the management of EID is the appropriate management of the early signal of infectious emergence. This step combines multidisciplinary skills allowing access to the best pathway for containing EID by implementing early countermeasures adapted to the situation. New digital technologies could significantly improve this early detection phase. Finally, experts have a fundamental role to play because they are located at the interface between operational actors and decision-makers, which allows multidirectional feedback, ideally in real time, between professional actors and decision makers. To combat current and future EIDs, expertise should be based on a multi-sectorial approach, promotion of collegiality and continuously adaptation to the evolving nature of EIDs.

A case report of fungemia due to Kodamaea ohmeri.

BACKGROUND: Kodamaea ohmeri is a yeast is frequently mistaken for Candida, which belongs to the same family. This micro-organism has been reported to cause life-threatening infections in humans. CASE PRESENTATION: A 81-year-old woman developed a severe fungemic pulmonary infection due to Kodamaea ohmeri that was identified from bronchoalveolar fluid and blood cultures, which is unusual in immunocompetent patients. Because K. ohmeri was first wrongly identified as Candida albicans, the patient inadequately received caspofungin, which was clinically ineffective, especially as the strain was resistant to echinocandins. Clinical cure was obtained after treatment was switched to voriconazole. CONCLUSIONS: An increasing number of serious infections due to K. ohmeri has been reported in the literature, but the correct identification of this micro-organism remains difficult.

Report of three imported cases of neurocysticercosis in Guadeloupe.

BACKGROUND: Neurocysticercosis is endemic in most countries of Central and South America but has rarely been described in the French West Indies. We aimed to better understand the clinical and radiological presentation of our cases. CASE PRESENTATION: We report three cases of neurocysticercosis in patients living in Guadeloupe, with different clinical and radiological presentations. CONCLUSION: Given the eventuality of autochtonous transmission, the diagnosis should be considered in all patients living in Guadeloupe presenting with seizures.

Characteristics and consequences of medical care interruptions in HIV-infected patients in France.

To describe the consequences of medical care interruptions (MCIs) we selected patients with at least two medical encounters between January 2006 and June 2013 in the Dat'AIDS cohort. Patients with any time interval >15 months between two visits were defined as having a MCI, as opposed to uninterrupted follow-up (UFU). Patients' characteristics at the time of HIV diagnosis and at the censoring date were compared between groups. Cox proportional hazards models were built to assess the role of interruptions on survival (total and AIDS-free). Of 11 116 patients, 824 had at least one MCI. These patients were younger at the time of HIV diagnosis (30 vs. 33 years, P < 0·0001). MCI was less frequent in men having sex with men vs. heterosexual patients [odds ratio (OR) 0·81, 95% confidence interval (CI) 0·69-0·96)], and a centre effect was described. MCI was independently associated with AIDS (OR 2·54, 95% CI 2·10-3·09) and death (OR 2·65, 95% CI 1·94-3·61). At the censoring date, 52·2% of patients with at least one MCI had viral load below detection vs. 85·3% of the UFU group (P < 0·0001). In conclusion, MCIs were associated with patients' survival and with the proportion of viral loads below detection in our cohort, compromising individual and collective treatment benefits.

Penetration of daptomycin into bone and synovial fluid in joint replacement.

Daptomycin exhibits clinical activity in the treatment of infections with Gram-positive organisms, including infections due to methicillin-resistant Staphylococcus aureus. However, little is known about its penetration into bone and synovial fluid. The aim of our study was to assess the penetration of daptomycin into bone and synovial fluid after a single intravenous administration. This study was conducted in 16 patients who underwent knee or hip replacement and received a single intravenous dose of 8 mg of daptomycin per kg of body weight prior to surgery. Plasma daptomycin concentrations were measured 1 h after the end of daptomycin infusion and when bone fragments were removed. Daptomycin concentrations were also measured on bone fragments and synovial fluid collected at the same time during surgery. All samples were analyzed with a diode array-high-performance liquid chromatography (HPLC) method. After a single-dose intravenous infusion, bone daptomycin concentrations were above the MIC of daptomycin for Staphylococcus aureus in all subjects, and the median bone penetration percentage was 9.0% (interquartile range [IQR], 4.4 to 11.4). These results support the use of daptomycin in the treatment of Staphylococcus aureus bone and joint infections.

An undetectable polymerase chain reaction signal in routine HIV plasma viral load monitoring is associated with better virological outcomes in patients receiving highly active antiretroviral therapy.

OBJECTIVES: The aim of the study was to assess whether patients with undetectable viraemia [a negative polymerase chain reaction result (PCR(neg) )] and those with plasma viral load (PVL) < 40 HIV-1 RNA copies/mL but a detectable (positive) PCR signal (PCR(pos) ) had different outcomes in terms of the development of blips and virological failure (VF). METHODS: A multicentre observational database analysis was carried out. Data for patients whose highly active antiretroviral therapy (HAART) regime had been unchanged for ≥ 6 months by 1 January 2008, whose first two PVL measurements of 2008 were < 40 copies/mL and who had at least five PVL measurements between 1 January 2008 and 31 December 2010 were extracted from a multicentre observational database of 4928 patients receiving HAART. PVL assays used during this period had a detection threshold of 20 or 40 copies/mL. Undetectable PVL at baseline (BL PCR(neg) ) was defined as PCR(neg) at the first two PVL determinations of 2008. Multivariable Cox regression analysis was performed to investigate factors associated with the occurrence of blips and VF, defined as two consecutive PVL measurements > 40 copies/mL. RESULTS: Of the 1957 patients included in the study (mean age 47 years; median antiretroviral exposure 10.3 years), 1312 had BL PCR(neg) . Outcome events included 322 blips and 139 VFs, with incidence rates being significantly lower in patients with BL PCR(neg) than in those with BL PCR(pos) [13.0% vs. 23.4% (P < 0.0001) and 5.1% vs. 11.2% (P < 0.0001), respectively]. In multivariable analysis, BL PCR(neg) was associated with a reduced risk of blips [hazard ratio (HR) 0.58; 95% confidence interval (CI) 0.47-0.73; P < 0.0001] and VF (HR 0.44; 95% CI 0.31-0.62; P < 0.0001). CONCLUSIONS: Patients with PCR(neg) had better virological outcomes than those with PVL < 40 copies/mL but detectable viraemia. This suggests that the 'no-signal' information provided by currently commercially available HIV RNA quantification assays should be used routinely.

Streptococcus bovis/Streptococcus equinus complex fecal carriage, colorectal carcinoma, and infective endocarditis: a new appraisal of a complex connection.

The proportion of group D streptococcal infective endocarditis (IE) (predominantly due to Streptococcus gallolyticus) and the incidence of colorectal cancer are higher in France than in most European countries. We assumed that this could be explained by a high group D streptococci (GDS) fecal carriage rate. The aims of this study were to re-assess the GDS fecal carriage rate in France and its relationship with colorectal cancer. Consecutive adult subjects who were to undergo a complete colonoscopy were invited to participate. GDS were searched in subjects' stools before their colonoscopy using biomolecular techniques. Colonoscopic findings were sorted into four subgroups: normal colonoscopy, non-tumoral lesions, benign tumors, and premalignant/malignant tumors. GDS fecal carriages were calculated overall and in each subgroup and compared. The data from 259 subjects were analyzed. GDS were identified in the feces of 12 subjects, with the following distribution: S. lutetiensis (n = 9), S. pasteurianus (n = 2), and S. gallolyticus (n = 1). This accounted for an overall GDS fecal carriage rate of 4.6 %. The GDS fecal carriage rate was 6 % in case of normal colonoscopy, 1.3 % in case of non-tumoral lesions, 3.2 % in case of benign tumors, and 11 % in case of premalignant/malignant tumors. These four percentages were not statistically different. The GDS fecal carriage rate was lower than expected, which did not confirm our working hypothesis. Most strains belonged to S. bovis biotype II, while S. gallolyticus was found only once. These findings suggest that different GDS play different roles in the etiopathogenesis of IE and colorectal cancer.

Infant neurodevelopment and behavior in Guadeloupe after lead exposure and Zika maternal infection during pregnancy.

BACKGROUND: Prenatal lead exposure is known to have neurotoxic effects on the developing fetus, while some viral infections may have a tropism for the central nervous system. Our objective was to study whether the effects of prenatal lead exposure on infant development and behaviors at 18 months of age are modified by the occurrence of a maternal infection to Zika virus (ZIKV) during pregnancy. METHODS: During the ZIKV epidemic in Guadeloupe in 2016 a cohort of pregnant women was set up. Blood samples (pregnancy, childbirth and cord) (n = 297) enabled us to measure blood lead levels aimed to determine prenatal lead exposure and the likelihood of maternal infection during pregnancy (ZIKV status + vs -). The 18 months "Ages and Stages Questionnaire" (ASQ) was used to generate scores for global development, fine and gross motor skills, communication, problem solving, and personal-social skills. The questions from a longitudinal cohort study conducted in Canada (Québec) were used to generate hyperactivity, opposition, inattention and physical aggression scores. Associations were tested by multivariate linear regressions. RESULTS: Prenatal lead exposure was associated with delays in neurodevelopment at 18 months, reflected by lower scores in ASQ totals, and in the fine motor and problem-solving domains. Some of these associations appeared to be sex-specific, observed almost exclusively in boys (ASQ total, fine motor and personal-social scores). Prenatal lead exposure was not associated with behavioral scores. ZIKV infection during pregnancy was associated with a lower fine motor ASQ score, and higher scores for hyperactivity, opposition and physical aggression. Significant interaction between prenatal lead exposure and ZIKV status was observed with a lower personal-social score in ZIKV (-) only, and for hyperactivity and inattention scores, though some of these interactions (ASQ personal-social score, inattention score) were no longer significant when children with microcephaly were excluded from the analyses. DISCUSSION/CONCLUSION: Our study confirms previous findings of associations between prenatal exposure to lead at low levels and adverse neurodevelopmental outcomes during infancy and the particular vulnerability of boys. It suggests associations between ZIKV infection during pregnancy and adverse effects on a number of neurodevelopmental functions (fine motor function) and behaviors (opposition, hyperactivity), that need to be confirmed at later age. There is no strong evidence of interaction between ZIKV infection and lead exposure but both prenatal risk factors may affect fine motor function.

Infective endocarditis prophylaxis: moving from dental prophylaxis to global prevention?

Infective endocarditis (IE) is an infectious disease which mainly affects elderly patients. Staphylococcus aureus is the main microorganism and IE, which used to be associated with a previously known heart disease, is now associated with healthcare procedures. For a long time, it was thought necessary to prevent IE with antibiotics before starting many invasive procedures. But in the last few years, there has been a change, with a drastic limitation on the situations in which antibiotic prophylaxis is required. Epidemiological studies emphasize changes in the profile of IE, which is moving from a streptococcal disease in patients with previously known heart disease to a staphylococcal healthcare-associated disease in elderly patients suffering from many comorbidities or having intracardiac devices. These changes should lead us to question the validity of our current management of antibiotic prophylaxis. There are already recommendations from the American Heart Association (AHA) for the prevention of implantable cardiovascular electronic device implantation, but apart from this particular situation, should we not extend prophylaxis to more comprehensive prevention in patients who have comorbidities? To find an answer, we need to acquire more data on the pathophysiology of IE while continuing epidemiological surveillance of the disease.

Public health issues and health rendezvous for migrants from conflict zones in Ukraine: A French practice guideline.

Given the number of people leaving the war zone in Ukraine and arriving in France, the French high council for public health (HCSP) has drawn up a number of recommendations. The experts have taken into account the vulnerability of migrant populations, which is exacerbated by (a) promiscuity that increases the risk of exposure to infectious agents; (b) the psychological consequences of conflict, family separation and exile; (c) prevalence in Ukraine of communicable diseases such as (possibly multi-resistant) tuberculosis, HIV and HCV; (d) low vaccination coverage (risk of circulation of poliovirus) and (e) the risk of spreading infectious diseases (Covid-19, measles…). Consequently, experts recommend that priority be given to: (i) Initial (immediate) reception, which will help to provide emergency care and to assess immediate needs (psychological disorders, risk of medication breakdown and risk of infection); (ii) Other priority measures (vaccination catch-up, including vaccination against SARS-CoV-2 and mandatory vaccination for children's entry into school, screening for post-traumatic stress disorder and tuberculosis) must be implemented as soon as feasible. At this stage, it is imperative: To ensure coordination and access to information throughout the country, by providing medico-social support (opening of social rights and access to care); To digitize medical data for the purposes of traceability; To use professional interpreting and/or health facilitators, or else, if necessary, digital translation tools. (iii) Finally, experts stress the need for vigilance in terms of management, conservation of social rights and continuity of care after the initial period, and organization of a "health rendezvous" within four months of a migrant's entering the country.

Environmental risk factors for haemorrhagic fever with renal syndrome in a French new epidemic area.

In France, haemorrhagic fever with renal syndrome (HFRS) is endemic along the Belgian border. However, this rodent-borne zoonosis caused by the Puumala virus has recently spread south to the Franche-Comté region. We investigated the space-time distribution of HFRS and evaluated the influence of environmental factors that drive the hantavirus reservoir abundance and/or the disease transmission in this area. A scan test clearly indicated space-time clustering, highlighting a single-year (2005) epidemic in the southern part of the region, preceded by a heat-wave 2 years earlier. A Bayesian regression approach showed an association between a variable reflecting biomass (normalized difference vegetation index) and HFRS incidence. The reasons why HFRS cases recently emerged remain largely unknown, and climate parameters alone do not reliably predict outbreaks. Concerted efforts that combine reservoir monitoring, surveillance, and investigation of human cases are warranted to better understand the epidemiological patterns of HFRS in this area.

A decision tree to help determine the best timing and antiretroviral strategy in HIV-infected patients.

Optimal antiretroviral strategies for HIV-infected patients still need to be established. To this end a decision tree including different antiretroviral strategies that could be adopted for HIV-infected patients was built. A 10-year follow-up was simulated by using transitional probabilities estimated from a large cohort using a time-homogeneous Markov model. The desired outcome was for patients to maintain a CD4 cell count of >500 cells/mm3 without experiencing AIDS or death. For patients with a baseline HIV viral load ≥5 log10 copies/ml, boosted protease inhibitor-based immediate highly active antiretroviral therapy (HAART) allowed them to spend 12% more time with CD4 ≥500/mm3 than did delayed HAART (6·40 vs. 5·69 and 5·57 vs. 4·90 years for baseline CD4 ≥500 and 350-499/mm3, respectively). In patients with a baseline HIV viral load ≤3·5 log10 copies/ml, delayed HAART performed better than immediate HAART (6·43 vs. 6·26 and 5·95 vs. 5·18 for baseline CD4 ≥500 and 350-499/mm3, respectively). Immediate HAART is beneficial in patients with a baseline HIV viral load 5 log10 copies/ml, whereas deferred HAART appears to be the best option for patients with CD4 ≥350/mm3 and baseline HIV viral load <3·5 log10 copies/ml.

[Regional audit on fluoroquinolones usage in the hospital and the community: are these antibiotics over-used?]. / Audit régional de l'usage des fluoroquinolones à l'hôpital et en ville : y a-t-il une surconsommation de ces antibiotiques ?

AIM OF THE STUDY: The ecological impact of an over-use or a mis-use of fluoroquinolones (FQs) appears of great importance according to published data. With the objective to set up a regional antibiotic stewardship program, we conducted a regional audit on FQs usage. MATERIAL AND METHODS: [corrected] Ninety general practionners and 15 health care facilities participated to this prospective study. Overall, 511 prescriptions were evaluated (276 from hospital physicians and 235 [46%] from general practionners). The compliance of FQs prescription with national recommendations and with a regional referential was assessed. This regional referential was established in order to preserve FQs. RESULTS: Only 14,3% of the prescriptions complied with the regional referential, even if the choice of FQs were in accordance with national recommendations in 56,8% of the prescriptions. Urinary tract infections (mostly non-complicated) were the most common indication for FQs prescription. CONCLUSION: Analysis of FQs prescriptions shows that there is a significant potential for FQs preservation in Franche-Comté.

Evaluation of a web-based self-reporting method for monitoring international passengers returning from an area of emerging infection.

OBJECTIVES: Emerging infectious diseases are a public health issue of international concern. Identifying methods to limit their expansion is essential. We assessed the feasibility of a screening strategy in which each traveler would actively participate in the screening process after an intercontinental flight by reporting their own health status via a web-based self-administered questionnaire. PATIENTS AND METHODS: In 2015 and 2017, we invited passengers arriving at or departing from Pointe-à-Pitre international airport to answer an online health questionnaire during the four days following their arrival from or at Paris-Orly international airport. SPIRE 1 was intended for passengers arriving at Pointe-à-Pitre and was conceived as a pilot study. SPIRE 2 was an improved version of SPIRE 1 and consisted in three parts, which permitted to further assess the benefits of pre-flight request and email follow-up. Endpoints were the connection rates and response rates to online health questionnaire. RESULTS: For SPIRE 1, 4/1038 travelers (0.4%) completed the two steps of the online health questionnaire. In SPIRE 2, response rates ranged from 3/1059 (0.3%) to 19/819 (2.3%). Response rates were significantly better when passengers were approached before their flight. CONCLUSIONS: The yield of an online health questionnaire was unexpectedly low.

Community-acquired bacterial meningitis in adults: in-hospital prognosis, long-term disability and determinants of outcome in a multicentre prospective cohort.

OBJECTIVES: To identify factors associated with unfavourable in-hospital outcome (death or disability) in adults with community-acquired bacterial meningitis (CABM). METHODS: In a prospective multicentre cohort study (COMBAT; February 2013 to July 2015), all consecutive cases of CABM in the 69 participating centres in France were enrolled and followed up for 12 months. Factors associated with unfavourable outcome were identified by logistic regression and long-term disability was analysed. RESULTS: Among the 533 individuals enrolled, (Streptococcus pneumoniae 53.8% (280/520 isolates identified), Neisseria meningitidis 21.3% (111/520), others 24.9% (129/520)), case fatality rate was 16.9% (90/533) and unfavourable outcome occurred in 45.0% (225/500). Factors independently associated with unfavourable outcome were: age >70 years (adjusted odds ratio (aOR) 4.64; 95% CI 1.93-11.15), male gender (aOR 2.11; 95% CI 1.25-3.57), chronic renal failure (aOR 6.65; 95% CI 1.57-28.12), purpura fulminans (aOR 4.37; 95% CI 1.38-13.81), localized neurological signs (aOR 3.72; 95% CI 2.29-6.05), disseminated intravascular coagulation (aOR 3.19; 95% CI 1.16-8.79), cerebrospinal fluid (CSF) white-cell count <1500 cells/µL (aOR 2.40; 95% CI 1.42-4.03), CSF glucose concentration (0.1-2.5 g/L: aOR 1.92; 95% CI 1.01-3.67; <0.1 g/L: aOR 2.24; 95% CI 1.01-4.97), elevated CSF protein concentration (aOR 1.09; 95% CI 1.03-1.17), time interval between hospitalization and lumbar puncture >1 day (aOR 2.94; 95% CI 1.32-6.54), and S. pneumoniae meningitis (aOR 4.99; 95% CI 1.98-12.56), or meningitis other than N. meningitidis (aOR 4.54; 95% CI 1.68-12.27). At 12 months, 26.7% (74/277) had hearing loss, 32.8% (87/265) depressive symptoms, 31.0% (86/277) persistent headache, and 53.4% had a physical health-related quality of life (142/266) <25th centile of the distribution of the score in the general French population (p < 0.0001). CONCLUSIONS: The burden of CABM (death, disability, depression, impaired quality of life and hearing loss) is high. Identification of cases from the first symptoms may improve prognosis. CLINICALTRIAL: Gov identification number: NCT01730690.

International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass.

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.