Ageing with HIV: do comorbidities and polymedication drive treatment optimization?

OBJECTIVES: The aim of the study was to describe the ageing HIV-infected population (> 50 years old) and their current antiretroviral therapy (ART), comorbidities and coprescriptions in France in 2013 and to compare them to the younger population. METHODS: A retrospective analysis of a prospectively collected database was performed. The characteristics of patients receiving ART as well as their current ART and their numbers of comorbidities and comedications at the censoring date (1 July 2013) were compared between patients ageing with HIV infection, patients who seroconverted while ageing, and younger patients. RESULTS: We compared 10 318 ageing patients [median age 56 years; 25% interquartile range (IQR) 53-62 years] with 13 302 younger patients (median age 42 years; 25% IQR 36-47 years). The ageing patients were more frequently male than the younger patients (77 vs. 65%). Among the ageing patients, 7025 were diagnosed with HIV infection before 2000 and represented a distinct group, the 'experienced ageing' group, by comparison with the 'recently diagnosed ageing' group. Triple therapy containing a boosted protease inhibitor was used in 28.2% of the patients (vs. 39% and 36% of the younger and "recently diagnosed ageing" groups, respectively); a nonnucleoside reverse transcriptase inhibitor in 27% (vs. 33% and 38%, respectively), an integrase strand transfer inhibitor (INSTI) in 9% (vs. 7% and 9%, respectively), and another regimen (fewer or more than three drugs) in 35.8% (vs. 21% and 16.5%, respectively). "Experienced ageing" patients typically had one or more comorbidities (62.1%) and were receiving at least one comedication (71%). Central nervous system (CNS) agents (prescribed in 44.6% of the "experienced ageing" patients) and antilipidaemics (in 44.2%) were the most frequently prescribed comedications. INSTIs were used in 23% of the population and were used significantly more often in patients with comorbidities and coprescriptions. For all comparisons, P < 0.0001. CONCLUSIONS: In ageing HIV-infected patients, especially those with a long history of HIV infection, comorbidities and coprescriptions are highly prevalent.

Comparative risk of failure of ABC/3TC or TDF/FTC based first-line regimens in patients with a high viral load.

OBJECTIVES: To compare the efficacy, in current clinical practice, of first regimens containing abacavir with lamivudine (ABC/3TC) or tenofovir with emtricitabine (TDF/FTC) in patients with baseline viral load ≥100,000 HIV-1 RNA copies/mL. METHODS: Using a prospective cohort, we selected all patients starting a first HIV regimen based either on ABC/3TC or on TDF/FTC. The propensity score (PS) method was used to limit the indication bias due to the observational nature of the data. Adjusting and weighting methods via PS were used to compare the effectiveness of a first regimen containing ABC/3TC or TDF/FTC. The primary outcome was treatment failure by month 12 (M12). RESULTS: Overall, 2781 patients started an antiretroviral (ARV) regimen with ABC/3TC or TDF/FTC each in combination with efavirenz, boosted atazanavir or boosted darunavir. Among the 2472 uncensored patients before M12, 962 (39%) had a baseline viral load ≥100,000 copies/mL of whom 294 were in treatment failure at or before M12. Our analyses showed no difference between ABC/3TC and TDF/FTC in the risk of treatment failure at M12 in patients starting an ARV regimen with a high viral load (≥100,000 copies/mL). CONCLUSIONS: Using a large prospectively collected cohort of patients seeking care in France, we found no evidence that ABC/3TC based regimens led to more failures than TDF/FTC based ones in patients with high baseline viral loads.

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.

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.

The social representations of diagnosing Lyme disease.

Social science studies on the controversy surrounding Lyme disease (LD) focused on the opposition between the "mainstream" and biomedical approach on one side and the "Lyme-literate" one on the other side, the latter claiming the existence of the chronic form of LD. The qualitative and exploratory study 'C18-48 Quali-Explo-PIQTIQ' (2019) investigated the social representations of LD in patients bitten by a tick. Twenty-four semi-structured interviews were conducted in three French medical units. Thematic and patient trajectory analyses were performed. Our results showed that, after the tick bite, some patients presented an "illness without disease" condition, characterised by uncertainty. In some cases, they consulted "Lyme-literate" health providers and received a diagnosis of chronic LD. This diagnosis was obtained by prescribing unassessed biological testing, providing an objective result and clinical categorisation. Unlike literature on the "Lyme-literate" approach, this diagnostic procedure involved some biomedical operations.

Description of an outbreak of hemorrhagic fever with renal syndrome in the southern Jura Mountains, France, in 2021.

OBJECTIVE: The aim of our study was to describe the 2021 Hemorrhagic Fever with Renal Syndrome (HFRS) outbreak in the southern Jura Mountains. PATIENTS AND METHODS: We included all laboratory-confirmed cases of HFRS reported between April and September 2021 in the three local hospitals. RESULTS: A total of 90 patients were enrolled in the study: 73 hospitalized and 17 non-hospitalized patients. Transient myopia was only reported in non-hospitalized patients. Forty (44.4 %) patients underwent medical imaging before hantavirus diagnosis. Twenty-one patients (28.8 %) had a plasma creatinine level > 353.6 µmol/L, no patient developed severe metabolic disorder. Only one patient was dialyzed. A pacemaker was implanted before diagnosis of HFRS due to severe bradycardia in one patient. Sudden death was reported in one patient. CONCLUSION: This hantavirus epidemic led to numerous hospitalizations, one dialysis treatment, and one death. Early diagnosis by rapid test could avoid unnecessary investigations.

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.

Electrostatic wipes as simple and reliable methods for influenza virus airborne detection.

The performance of an in-house protocol for virus detection on commercialized electrostatic wipes (EWs) was assessed experimentally by impregnating them with suspensions of cytomegalovirus, adenovirus, and influenza virus, and by determining the recovery efficiency, repeatability, and detection limit of the protocol. The protocol was sensitive enough to detect 4 log10 gene copies of virus. At room temperature, influenza RNA was stable on EWs for at least four days. When EWs were placed high in 32 influenza-infected patients' rooms, influenza RNA was detectable in 75% (N = 24) of EWs, suggesting that EWs are simple and reliable methods for influenza virus airborne detection.

Number, type and cost of microbiological tests during HIV Pre-Exposure Prophylaxis: The experience of a French hospital.

BACKGROUND: Microbiological tests are required for individuals on HIV Pre-Exposure Prophylaxis (PrEP), but their real-life numbers, types and cost are poorly described. METHODS: Number, type, and results of microbiological tests performed in a Besançon Hospital-associated laboratory, France, from 2016 to 2019, in the setting of PrEP consultations were retrospectively collected. Costs were estimated by the current reimbursement rate set by the French national protection system. RESULTS: 756 consultations for PrEP initiation or follow-up of 135 persons were performed over 4 years. Among 3434 tests performed in the institution-associated laboratory, 1083 and 2351 were virological and bacteriological tests, respectively. Serology was predominant in virology (98% of virological tests), with HIV, HCV, and HBV screening as the 3 more frequent assays, whereas molecular biology was predominant in bacteriology (63.1% of bacteriological tests) with N. gonorrhoeae and C. trachomatis screening as leader assays. Agar-based culture accounted for 1% of bacterial tests. The global cost of microbiological tests was 45,983.20 euros, corresponding to a mean cost of 60.80 euros per consultation. Virological and bacteriological tests accounted for 37.7% and 62.3% of this budget, respectively. No seroconversion was observed for HIV or HCV. N. gonorrhoeae and C. trachomatis were detected at least once in 39.3% and 22.4% of individuals, respectively, with 15% of symptomatic episodes in both cases. Active syphilis infection was detected in 15.4% of individuals. CONCLUSIONS: Since numerous microbiological tests are required during PrEP, the availability of specific technical platforms should not be neglected by centers wishing to set up PrEP consultations.

Functional signs in patients consulting for presumed Lyme borreliosis.

INTRODUCTION: Little is known about the functional symptoms associated with Lyme borreliosis (LB) in Europe. We aimed to assess functional symptoms associated with presumed LB and to compare patients with and without confirmed LB. MATERIALS AND METHODS: We performed a retrospective monocenter study. Patients consulting for presumed LB were included. RESULTS: Between November 2015 and June 2018, 355patients were included (mean age: 51years, 52% of women) of which 48had LB: erythema migrans (42%), early disseminated LB (50%; 35% of neuroborreliosis cases), and late disseminated LB (8%). The most frequently reported functional symptoms were neuropathic pain (23%), arthralgia (23%), and asthenia (17%). Other functional symptoms were rare (≤10%). Three hundred and seven (86%) patients did not have LB. Patients with confirmed LB reported fewer functional symptoms than patients without LB (1.8 (±1.7) vs. 3.6 (±2.5), P<0.001) with a shorter duration of symptoms (< 3 months in 48% vs. 16% of cases, P<0.001). They less often reported asthenia (17% vs. 59%, P<0.001), widespread pain (10% vs. 31%, P=0.003), myalgia (10% vs. 32%, P=0.002), memory disorders (4% vs. 16%, P=0.03), irritability (2% vs. 23%, P±0.001), and sadness (0% vs. 16%, P=0.003). CONCLUSION: In patients consulting for presumed LB, patients diagnosed with LB had fewer and shorter functional symptoms than patients without LB.

Does type of immunosupression influence the course of Covid-19 infection?

Coronavirus disease 19 (Covid-19) is a new emerging virus responsible for pandemic and death. High blood pressure, diabetes, obesity have been described as poor prognosis factors. Few data have been reported in patient with immunocompromised status (solid tumor, hematological malignancy, rheumatoid conditions or organ transplant). We evaluated the characteristics of patients, including the outcome, with immunodepression hospitalized in Besancon University hospital (East of France). We wanted to identify if a type of immunosupression influences the course of Covid-19. In a cohort of 80 patients with immunosupression (42 solid tumors, 20 hematological malignancy and 18 non neoplastic immunosupression), poor outcomes (Intensive care unit hospitalization and or deaths) was frequent (38%) and tended to be more frequent in patients with hematological malignancy.

Time to blood culture positivity: An independent predictor of infective endocarditis and mortality in patients with Staphylococcus aureus bacteraemia.

OBJECTIVES: Time to blood culture positivity (TTP), a routinely available parameter in automated blood culture systems, may be a proxy for infectious burden in patients with bloodstream infections. We aimed to study the association between TTP and infective endocarditis (IE), or death, in patients with Staphylococcus aureus bacteraemia. METHODS: VIRSTA is a multicentre prospective cohort study that included all adult patients with S. aureus bacteraemia in eight university hospitals in France (2009-2011). We analysed data from four centres which collected data on TTP. Regression models were used to study the association between TTP and definite IE (Duke-Li criteria), and 30 day-mortality. RESULTS: We included 587 patients with S. aureus bacteraemia: mean age was 65.3 ± 16.3 years, 420 out of 587 patients (71.6%) were male, 121 out of 587 (20.6%) died, and 42 out of 587 (7.2%) had definite IE. Median TTP of first positive blood culture was 13.7 h (interquartile range 9.9-18). On multivariate analysis, 30-day mortality was associated with TTP ≤13.7 h (74/295 (25.1%) vs. 47/292 (16.1%), p 0.02), as well as old age, McCabe score, methicillin resistance, stroke, pneumonia, and C-reactive protein. TTP was also independently associated with IE, but with a U-shape curve: IE was more common in the first (TTP <10 h, 17/148, 11.5%), and the last (TTP ≥18 h, 8/146, 5.5%) quartiles of TTP, p 0.002. CONCLUSIONS: TTP provides reliable information in patients with S. aureus bacteraemia, on the risk of IE, and prognosis, with short TTP being an independent predictor of death. These data, readily available at no cost, may be used to identify patients who require specific attention.

Lyme borreliosis and other tick-borne diseases. Guidelines from the French scientific societies (II). Biological diagnosis, treatment, persistent symptoms after documented or suspected Lyme borreliosis.

The serodiagnosis of Lyme borreliosis is based on a two-tier strategy: a screening test using an immunoenzymatic technique (ELISA), followed if positive by a confirmatory test with a western blot technique for its better specificity. Lyme serology has poor sensitivity (30-40%) for erythema migrans and should not be performed. The seroconversion occurs after approximately 6 weeks, with IgG detection (sensitivity and specificity both>90%). Serological follow-up is not recommended as therapeutic success is defined by clinical criteria only. For neuroborreliosis, it is recommended to simultaneously perform ELISA tests in samples of blood and cerebrospinal fluid to test for intrathecal synthesis of Lyme antibodies. Given the continuum between early localized and disseminated borreliosis, and the efficacy of doxycycline for the treatment of neuroborreliosis, doxycycline is preferred as the first-line regimen of erythema migrans (duration, 14 days; alternative: amoxicillin) and neuroborreliosis (duration, 14 days if early, 21 days if late; alternative: ceftriaxone). Treatment of articular manifestations of Lyme borreliosis is based on doxycycline, ceftriaxone, or amoxicillin for 28 days. Patients with persistent symptoms after appropriate treatment of Lyme borreliosis should not be prescribed repeated or prolonged antibacterial treatment. Some patients present with persistent and pleomorphic symptoms after documented or suspected Lyme borreliosis. Another condition is eventually diagnosed in 80% of them.

Lyme borreliosis and other tick-borne diseases. Guidelines from the French Scientific Societies (I): prevention, epidemiology, diagnosis.

Lyme borreliosis is transmitted en France by the tick Ixodes ricinus, endemic in metropolitan France. In the absence of vaccine licensed for use in humans, primary prevention mostly relies on mechanical protection (clothes covering most parts of the body) that may be completed by chemical protection (repulsives). Secondary prevention relies on early detection of ticks after exposure, and mechanical extraction. There is currently no situation in France when prophylactic antibiotics would be recommended. The incidence of Lyme borreliosis in France, estimated through a network of general practitioners (réseau Sentinelles), and nationwide coding system for hospital stays, has not significantly changed between 2009 and 2017, with a mean incidence estimated at 53 cases/100,000 inhabitants/year, leading to 1.3 hospital admission/100,000 inhabitants/year. Other tick-borne diseases are much more seldom in France: tick-borne encephalitis (around 20 cases/year), spotted-fever rickettsiosis (primarily mediterranean spotted fever, around 10 cases/year), tularemia (50-100 cases/year, of which 20% are transmitted by ticks), human granulocytic anaplasmosis (<10 cases/year), and babesiosis (<5 cases/year). The main circumstances of diagnosis for Lyme borreliosis are cutaneous manifestations (primarily erythema migrans, much more rarely borrelial lymphocytoma and atrophic chronic acrodermatitis), neurological (<15% of cases, mostly meningoradiculitis and cranial nerve palsy, especially facial nerve) and rheumatologic (mostly knee monoarthritis, with recurrences). Cardiac and ophtalmologic manifestations are very rarely encountered.

Characteristics and regional variations of group D streptococcal endocarditis in France.

The proportion of infective endocarditis (IE) caused by group D streptococci (GDS; formerly Streptococcus bovis) increased markedly in France, to account for 25% of all cases of IE by 1999. In an attempt to explain this phenomenon, a comparative analysis of GDS and oral streptococci (OS) causing IE was performed. This study was based on data collected from a large cross-sectional population-based survey that was conducted in 1999. In total, 559 cases of definite IE were recorded, of which 142 involved GDS and 79 involved OS. Patients with GDS IE were older (62.7 vs. 56.6 years, p 0.01) and had a history of valve disease less frequently than did patients with OS IE (33.8% vs. 67.1%, p <0.0001). At-risk procedures for IE were performed less frequently in patients with GDS than in patients with OS (14.8% vs. 24.1%, p 0.08), but co-morbidities were more frequent in the GDS group (59.9% vs. 32.9%, p 0.0001). Diabetes, colon diseases and cirrhosis were also more frequent in the GDS group (p 0.006, p <0.0001 and p 0.08, respectively). Rural residents accounted for 31.0% of the GDS group, but for only 15.2% of the OS group (p 0.001). Likewise, the proportion of GDS IE was higher in regions with mixed (urban and rural) populations (Franche-Comté 81.8%, Marne 68.7%, Lorraine 70.3% and Rhône-Alpes 65.3%) than in exclusively urban regions (Paris and Ile de France 58.0%). Further investigations are required to elucidate the link in France between the incidence of GDS IE, rural residency and nutritional factors.

Clonal complex 398 methicillin-susceptible Staphylococcus aureus bloodstream infections are associated with high mortality.

Within the last decade, methicillin-resistant Staphylococcus aureus belonging to clonal complex 398 (CC398) has become a worldwide threat associated with livestock. More recently, methicillin-susceptible S. aureus (MSSA) belonging to CC398 have been increasingly reported as a cause of invasive infections in patients without livestock contact. We investigated risk factors associated with CC398 bloodstream infections (BSIs) compared with non-CC398 BSIs with a case-control study in a French university Hospital. From January 2010 to December 2014, nonduplicate Staphylococcus aureus (SA) isolates responsible for BSIs in adult patient were typed to identify those belonging to CC398. Each adult patient with a CC398 SA BSI (cases) was matched with 2 non-CC398 SA BSI controls randomly selected on the basis of the time at risk, the unit of hospitalization and susceptibility to methicillin. We retrospectively extracted the clinical information from electronic medical records and used conditional logistic regression for univariate and multivariate analyses. We identified 67 CC398 isolates among the 770 SA responsible for BSI in adult patients. All CC398 isolates were susceptible to methicillin. The proportion of CC398 among MSSA increased steadily from 4.6% in 2010 to 15.1% in 2013 and then stabilized at 13.8% in 2014. Factors significantly associated with CC398 MSSA BSIs were healthcare-associated infection (odds ratio (OR) 3.02, 95% confidence interval (CI) 1.19-7.63), history of neurologic disease (OR 2.51, 95% CI 1.13-5.65) and 30-day mortality (OR 2.44, 95% CI 1.23-4.85).

Appropriateness of aminoglycoside prescriptions in a French university hospital.

INTRODUCTION: Aminoglycosides are a major class of antibiotics. Their use is particularly interesting in the treatment of severe infections but their toxicity is well known. They are mostly prescribed combined with other agents and as first-line treatments. We aimed to assess the appropriateness of aminoglycoside prescriptions in a French university hospital on the basis of the latest French recommendations published in 2011. METHOD: We conducted a prospective study between January 17th and February 4th, 2014 to assess prescription modalities of aminoglycosides on the basis of the following criteria: indication, duration of treatment, dosing schedule, administration modalities, and drug level monitoring. Prescriptions were then compared to the 2011 national guidelines. RESULTS: A total of 68 consecutive prescriptions were analyzed and only 47.8% complied with guidelines. Most physicians complied with recommendations, particularly with the indication for severe infections (95.6%), the administration of a single daily dose (92.6%), and the slow intravenous infusion (30minutes) administration (84%). However, physicians tended to prescribe lower doses than recommended (40.3%), especially to patients presenting with renal insufficiency, and drug level monitoring was not optimal. CONCLUSION: Although new and accurate national recommendations were recently published, aminoglycoside prescription is still not optimal, in particular for dosing and plasma concentration monitoring.

Factors associated with 12 week case-fatality in Staphylococcus aureus bacteraemia: a prospective cohort study.

Staphylococcus aureus bacteraemia (SAB) is a frequent and deadly disease. Given the lack of a randomized trial, optimal first-line antibiotic treatment is still debated. Our aim was to identify prognostic factors in SAB patients and to analyse the impact of first-line antibiotics. The VIRSTA prospective cohort study was conducted in eight tertiary care centres in France. Consecutive incident adults in whom a blood culture drawn in participating centres grew S. aureus between April 2009 and October 2011 were prospectively followed for 12 weeks. Factors associated with 12-week case-fatality were identified by multivariate logistic regression. We enrolled 2091 patients and analysed survival in 1972 (median age 67.8 years, interquartile range 55.5-78.9; females 692/1972, 35.1%). SAB was nosocomial or healthcare-related in 1372/1972 (69.6%) of cases and the primary focus was unknown in 414/1972 (21.0%) of cases. Week 12 case-fatality rate was 671/1972 (34.0%). The main independent prognostic factors on multivariate analysis were age (adjusted OR by 10-year increment 1.56; 95% CI 1.44-1.69), septic shock (OR 5.11; 95% CI 3.84-6.80), metastatic cancer (OR 4.28; 95% CI 2.88-6.38), and unknown primary focus (OR 2.62; 95% CI 2.02-3.41). In the 1538 patients with methicillin-sensitive S. aureus (MSSA) bacteraemia, first-line empiric antistaphylococcal penicillins (OR 0.40; 95% CI 0.17-0.95) and vancomycin (OR 0.37; 95% CI 0.17-0.83), alone or combined with an aminoglycoside, were associated with better outcome compared with other antibiotics. There are few modifiable prognostic factors for SAB. Initiating empiric antibiotics with antistaphylococcal penicillins or vancomycin may be associated with better outcome in MSSA bacteraemia.