Serum and Salivary IgG and IgA Response After COVID-19 Messenger RNA Vaccination.

Importance: There is still considerable controversy in the literature regarding the capacity of intramuscular messenger RNA (mRNA) vaccination to induce a mucosal immune response. Objective: To compare serum and salivary IgG and IgA levels among mRNA-vaccinated individuals with or without previous SARS-CoV-2 infection. Design, Setting, and Participants: In this cohort study, SARS-CoV-2-naive participants and those with previous infection were consecutively included in the CoviCompare P and CoviCompare M mRNA vaccination trials and followed up to day 180 after vaccination with either the BNT162b2 (Pfizer-BioNTech) vaccine or the mRNA-1273 (Moderna) vaccine at the beginning of the COVID-19 vaccination campaign (from February 19 to June 8, 2021) in France. Data were analyzed from October 25, 2022, to July 13, 2023. Main Outcomes and Measures: An ultrasensitive digital enzyme-linked immunosorbent assay was used for the comparison of SARS-CoV-2 spike-specific serum and salivary IgG and IgA levels. Spike-specific secretory IgA level was also quantified at selected times. Results: A total of 427 individuals were included in 3 groups: participants with SARS-CoV-2 prior to vaccination who received 1 single dose of BNT162b2 (Pfizer-BioNTech) (n = 120) and SARS-CoV-2-naive individuals who received 2 doses of mRNA-1273 (Moderna) (n = 172) or 2 doses of BNT162b2 (Pfizer-BioNTech) (n = 135). The median age was 68 (IQR, 39-75) years, and 228 (53.4%) were men. SARS-CoV-2 spike-specific IgG saliva levels increased after 1 or 2 vaccine injections in individuals with previous infection and SARS-CoV-2-naive individuals. After vaccination, SARS-CoV-2-specific saliva IgA levels, normalized with respect to total IgA levels, were significantly higher in participants with previous infection, as compared with the most responsive mRNA-1273 (Moderna) recipients (median normalized levels, 155 × 10-5 vs 37 × 10-5 at day 29; 107 × 10-5 vs 54 × 10-5 at day 57; and 104 × 10-5 vs 70 × 10-5 at day 180 [P < .001]). In contrast, compared with day 1, spike-specific IgA levels in the BNT162b2-vaccinated SARS-CoV-2-naive group increased only at day 57 (36 × 10-5 vs 49 × 10-5 [P = .01]). Bona fide multimeric secretory IgA levels were significantly higher in individuals with previous infection compared with SARS-CoV-2-naive individuals after 2 antigenic stimulations (median optical density, 0.36 [IQR, 0.16-0.63] vs 0.16 [IQR, 0.10-0.22]; P < .001). Conclusions and Relevance: The findings of this cohort study suggest that mRNA vaccination was associated with mucosal immunity in individuals without prior SARS-CoV-2 infection, but at much lower levels than in previously infected individuals. Further studies are needed to determine the association between specific saliva IgA levels and prevention of infection or transmission.

Incidence of COVID-19 mRNA vaccine symptomatic breakthrough infections during Omicron circulation in adults with or without infection prior to vaccination.

OBJECTIVES: COVID-19 vaccine breakthrough infections were frequently reported during circulation of the Omicron variant. The ANRS|MIE CoviCompareP study investigated these infections in adults vaccinated and boosted with BNT162b2 [Pfizer-BioNTech] and with/without SARS-CoV-2 infection before vaccination. METHODS: In the first half of 2021, healthy adults (aged 18-45, 65-74 and 75 or older) received either one dose of BNT162b2 (n = 120) if they had a documented history of SARS-CoV-2 infection at least five months previously, or two doses (n = 147) if they had no history confirmed by negative serological tests. A first booster dose was administered at least 6 months after the primary vaccination, and a second booster dose, if any, was reported in the database. Neutralizing antibodies (NAbs) against the European (D614G) strain and the Omicron BA.1 variant were assessed up to 28 days after the first booster dose. A case-control analysis was performed for the 252 participants who were followed up in 2022, during the Omicron waves. RESULTS: From January to October 2022, 78/252 (31%) had a documented symptomatic breakthrough infection after full vaccination: 21/117 (18%) in those who had been infected before vaccination vs. 57/135 (42%) in those who had not. In a multivariate logistic regression model, factors associated with a lower risk of breakthrough infection were older age, a higher number of booster doses, and higher levels of Omicron BA.1 NAb titers in adults with infection before vaccination, but not in those without prior infection. CONCLUSION: Our results highlight the need to consider immune markers of protection in association with infection and vaccination history.

Late delivery of antibiotics: a new proxy for antimicrobial stewardship?

OBJECTIVES: To analyse the time elapsed between the prescription of antibiotics and their pick-up at the pharmacy and identify their determinants. METHODS: We used the National Health Insurance reimbursement databases on antibiotics delivery in 2021 in La Manche, Western France. Delayed delivery was defined as the time between prescription and antibiotic pick-up of >24 hours. RESULTS: We enrolled 207 250 prescriptions, of whom 18 728 (9.0%) collected their antibiotics at the community pharmacy >24 hours after prescription. Independent factors associated with delayed delivery were age >15 years (15-64 years: OR, 2.08 [1.98-2.19]; p < 0.001 and >65 years OR, 3.27 [3.09-3.46]; p < 0.001), male sex (OR, 00.77 [0.75-0.80]; p < 0.001), low income (OR, 1.08 [1.02-1.15]; p = 0.013), chronic diseases (OR, 1.29 [1.25-1.34]; p < 0.001), prescription during the weekend (OR, 1.49 [1.43-1.56]; p < 0.001), summer season (OR, 1.11 [1.07-1.16]; p < 0.001), lock-down period (OR, 4.15 [3.80-4.53]; p < 0.001), and distance from the patient home to his general practitioner office and the pharmacy >10 km (OR, 1.17 [1.13-1.21]; p < 0.001). DISCUSSION: The delayed delivery of antibiotics after prescription is not uncommon, especially in elderly patients, those with low income or chronic diseases, in case of weekend prescriptions, summer season and when the pharmacy is > 10 km away from the patient's home and his general practitioner office. If confirmed, this potential indicator of unnecessary prescriptions, readily available in some databases, may be used to target antimicrobial stewardship programmes and monitor the effect of interventions.

Yellow fever vaccine-associated neurologic and viscerotropic disease: a 10-year case series of the French National Reference Center for Arboviruses with clinical and immunological insights.

BACKGROUND: Immunization against the Yellow fever virus (YFV) with the 17D live-attenuated vaccine is the most effective way to prevent the disease. However, unexpected severe adverse events can occur. They consist in a neurological impairment - neurological disease (YEL-AND), a YF-like illness - viscerotropic disease (YEL-AVD) or anaphylaxis. In this article, we describe the epidemiology, clinical and biological features of YEL-AND and YEL-AVD cases reported to the French National Reference Center for Arboviruses (NRCA) in the past 10 years. METHODS: We conducted a national, retrospective study using the database of the NRCA from June 2012 to June 2022. All patients whose biological samples were sent to the NRCA for detection of YFV by serology and/or RT-qPCR for a suspected vaccine-associated adverse event were included. We collected data by reading medical records and conducted complementary neuro-immunological analysis, followed by a search for autoimmunity against type-1-interferon when samples were available at the NRCA. RESULTS: There were 10 cases of YEL-AND and 2 cases of YEL-AVD reported to the NRCA in the past 10 years, which represented an overall incidence of 0.6 for 100 000 doses. A total of 6/12 cases were previously healthy patients (50%, mean age 31 years), and 4/12 cases had cardiovascular co-morbidities (42%, mean age 56 years). The majority of YEL-AND had a favourable outcome at 6 months of follow up. One YEL-AVD patient passed. In secondary analyses, we evidenced a significant blood cerebrospinal fluid (CSF) barrier dysfunction, without intrathecal synthesis of immunoglobulin and without argument for a neuron damage. We further detected a significant rate of anti-type-1alpha interferon antibodies in 3/10 tested patients (2 YEL-AND and 1 YEL-AVD). CONCLUSION: YEL-AND and YEL-AVD are rare events that can underlie defect in the innate immunity of apparently healthy or mild co-morbid subjects. Outcome was generally favourable in the YEL-AND cases of our series, but still life-threatening or even fatal in the YEL-AVD cases.

Interest in the combination of antimicrobial therapy for orthopaedic device-related infections due to Enterococcus spp.

INTRODUCTION: The objective of this study was to evaluate the management of orthopaedic device-related infections (ODRIs) due to Enterococcus spp. MATERIALS AND METHODS: We performed a retrospective cohort study in a French tertiary university hospital. Patients with prosthetic joint- or osteosynthesis-associated infections caused by enterococci from 2013 to 2020 were included. Patients who died within 5 days after surgery; who were in palliative care; or who had osteosynthesis of the hand, foot or vertebra were excluded. RESULTS: Thirty-six patients were included, with 24 in the arthroplasty group and 12 in the osteosynthesis material group. Most infections were polymicrobial (63.9%, n = 23). Debridement, antibiotics and implant retention (DAIR) was performed in 30.6% (n = 11), withdrawal of material in 16.7% (n = 6), one-stage exchange in 30.6% (n = 11) and two-stage exchange in 22.2% of cases (n = 8). The antibiotic regimen was amoxicillin in 41.6% (n = 15), rifampicin in 27.8% (n = 10), linezolid in 25% (n = 9) and/or fluoroquinolones in 30.6% (n = 11). Clinical success at 1 year was 67% (18/27). The only variable statistically associated with a decreased risk of clinical failure was a duration of antibiotic therapy of 12 weeks (p = 0.04). Patients with a lower body mass index and age tended to decrease the risk of clinical failure (p = 0.05 and 0.06 respectively). CONCLUSIONS: The management of enterococcal ODRIs is complex, and ODRI patients are at high risk for relapse. In our small study, a better outcome was not demonstrated for patients with combination therapy and rifampicin use. Further studies are needed to improve the medico-surgical strategy for treating these infections.

Neutralizing antibodies against SARS-CoV-2 variants following mRNA booster vaccination in adults older than 65 years.

Immune response induced by COVID-19 vaccine booster against delta and omicron variants was assessed in 65 adults (65-84 years old) early aftesr a first booster dose. An increase in SARS-CoV-2 neutralizing antibodies was shown in individuals not previously infected without evidence of an age-related effect, with lower increase in those infected before a single dose of primary vaccination. Of note, humoral response was observed only starting from the 5th day after the boost.

Mycobacterium genavense Infections in Immunocompromised Patients Without HIV: Case Series of Solid Organ Transplant Patients and Literature Review.

Background: Mycobacterium genavense infection is rare and can occur in immunocompromised patients without human immunodeficiency virus (HIV). Methods: We describe 2 cases of M genavense infection in solid organ transplant (SOT) recipients, and we performed a literature review of immunocompromised patients without HIV. Results: Fifty-two cases are reported. Predisposing factors were receipt of SOT (40.4%) and autoimmune disease (36.5%). Infection was disseminated in 86.5% of cases. Organs involved were lymph nodes (72.3%), gastrointestinal tract (56.5%), lung (35.5%), and bone marrow (28.8%). Most patients were treated with at least 3 antimycobacterial agents (98%), with a clinical cure achieved in 54.9%. In multivariate analysis, lack for cure was associated with age of the time infection (odds ratio [OR], 15.81 [95% confidence interval {CI}, 2.92-152.93]; P = .011) and positive bone marrow culture (OR, 1.05 [95% CI, 1.01-1.12]; P = .042). Conclusions: Mycobacterium genavense infection is a rare and generally disseminated disease with a poor prognosis. Optimal treatment regimen and its duration remain to be defined.

Yersinia enterocolitica endocarditis on aortic bioprosthesis: A case report.

Yersinia enterocolitica is a Gram-negative bacillus and an unusual cause of endocarditis. We report the first case of a 74-year-old woman who developed a Yersinia enterocolitica endocarditis on an aortic bioprosthesis. Case of a 74-year-old woman with chronic hepatitis C who developed a Yersinia enterocolitica endocarditis on an aortic bioprosthesis in the weeks following an infective diarrhea with bacteremia. The patient was cured without surgery using ceftriaxone followed by oral fluoroquinolone according to the antimicrobial sensitivity testing (AST) results. Y. enterocolitica is a very rare cause of endocarditis and iron overload and chronic hepatitis C have been reported as predisposing conditions. The pathogenicity and virulence of the various serotypes of Y. enterocolitica are discussed.

Association between Following the ESCMID Guidelines for the Management of Candidemia and Mortality: A Retrospective Cohort Study.

OBJECTIVES: The objective of this study was to evaluate the association between ESCMID adherence and 30-day mortality in candidemia. METHODS: We performed a retrospective cohort study in two French tertiary-care hospitals. All patients with at least one positive blood culture (BC) for Candida spp. between January 2013 and December 2019 were included. An adherent case was defined as a candidemia case for which the treatment fulfilled a bundle of defined criteria based on the latest ESCMID recommendations. We explored factors associated with adherence to ESCMID recommendations in an unadjusted model, and we used a propensity score method to address potential channeling biases with regard to 30-day mortality. RESULTS: During the study period, 165 cases of candidemia were included. Among the ESCMID criteria, funduscopic examination was not performed in 45% and neither was echocardiography in 31%, while the ESCMID criteria were fully implemented in 44 cases (27%). In the propensity score analysis, the all-cause 30-day mortality rate was significantly lower among adherent cases (3.4/36.6, 9%) than among nonadherent cases (42.4/119.5, 36%) (OR = 5.3 95% CI [1.6-17.1]). CONCLUSIONS: In our study, adherence to the bundle of criteria for candidemia management was associated with increased survival, supporting additional efforts to implement these recommendations.

Reactogenicity among health care workers following a BNT162b2 or mRNA-1273 second dose after priming with a ChAdOx1 nCOV-19 vaccine.

OBJECTIVES: In March 2021, French authorities recommended a heterologous second dose of the mRNA vaccine for persons aged <55 years, with administration 9 to 12 weeks after the first dose of ChAdOx1 nCoV-19. This recommendation was despite a lack of data on the reactogenicity and safety of the regimen. Since then, several studies have shown an acceptable short-term safety profile of ChAdOx1 nCoV-19 and BNT162b2 heterologous vaccination, although some transient increased reactogenicity has been described. METHODS: We performed a single-centre prospective observational cohort study among health care workers (HCWs) at a tertiary care hospital to assess the reactogenicity of the BNT162b2 and mRNA-1273 vaccines administered as a second dose in participants primed with ChAdOx1 nCoV-19. RESULTS: Among 1184 HCWs, 356 (30%) agreed to participate. Of the participants, 32.3% were male, and the mean age was 35 years (standard deviation: 10.1 years). Of the participants, 229 received BNT162b2 and 127 received mRNA-1273. A systemic reaction was observed in 130 of 229 (56.8%) and 100 of 127 (78.7%) HCWs, respectively. Injection site reactions were generally limited (grade 1 or 2 in 163 of 229 (97.6%) and 90 of 127 (85.7 %) HCWs, respectively). After adjustment for age, sex, and HCW role, receiving the mRNA-1273 vaccine was associated with higher reactogenicity with more grade 3 side effects (adjusted OR (aOR): 3.34; 95% CI, 1.91-5.85), more systemic symptoms (aOR: 2.82; 95% CI, 1.69-4.7), and not being able to work (aOR: 8.35; 95% CI, 3.78-18.44) compared with receiving the BNT162b2 vaccine. DISCUSSION: Among patients receiving the mRNA1273 vaccine as a second dose, our study confirms good tolerance of the heterologous schedule with a higher risk of short-term side effects in comparison with patients receiving the BNT162b2 vaccine.

Medicosurgical management of deep wound infections after thoracolumbar instrumentation: risk factors of poor outcomes.

BACKGROUND: Surgical site infection (SSI) after thoracolumbar osteosynthesis is a common complication. Its management relies on surgical revision and antibiotic therapy, but treatment failure is not uncommon. The aim of our study was to assess the frequency of SSI management failure and its risk factors. METHODS: A retrospective study of patients hospitalized from 2011 to 2019 at the University Hospital of Caen was carried out. The infection rate and the time to onset of failure were assessed over a minimum follow-up of 1 year. Treatment failure was defined as the occurrence of a new intervention in the spine in the year following the end of antibiotic therapy, the establishment of long-term suppressive antibiotic therapy, or death from any cause within 1 year of the end of antibiotic therapy. We compared the treatment failure group with the treatment success group to determine risk factors for treatment failure. RESULTS: A total of 2881 patients underwent surgery during the study period, and 92 developed an SSI, corresponding to an SSI rate of 3.19%. Thirty-six percent of the patients with an SSI presented treatment failure. The median time to failure was 31 days. On multivariate analysis, diabetes mellitus was identified as a risk factor for treatment failure, whereas prolonged postoperative drainage for 4 to 5 days was a protective factor. CONCLUSIONS: The number of failures was significant, and failure occurred mainly during the early phase. To decrease the risk of treatment failure, prolonged duration of postoperative drainage seems to be helpful. Additionally, as diabetes is a risk factor for treatment failure, good control of glycemia in these patients might impact their outcomes.

Valvular and infection-associated risk factors as criteria to guide the use of echocardiography in patients with native joint infections.

BACKGROUND: Native joint and bone infections (NJBI) are associated with infective endocarditis (IE) in 15% of cases. There are no studies analyzing the use of cardiac imaging in cases of NJBI. The objective of this study was to identify factors associated with echocardiography suggestive of IE in patients with NJBI. METHODS: This medical records review was conducted in patients hospitalized for NJBI between 2007 and 2017 in Rheumatology and Infectious Diseases departments of 2 university hospitals. Patients included had a microbiologically proven NJBI during their hospitalization. RESULTS: In this cohort of 546 patients, median age 66 years, echocardiography was suggestive of IE in 66 (12%). In multivariate analysis, factors associated with echocardiography suggestive of IE were 2 or more positive blood cultures (OR 11.55 (CI95% 3.24-74.20)), cardiac conditions with a high risk of IE (OR 7.34 (CI95% 2.95-18.61)), unknown heart murmur (OR 4.59 (CI95% 1.79-11.74)), multifocal infection (OR 2.26 (CI95% 1.21-4.23)) and an infection due to S. bovis (OR 3.52 (CI95% 1.26-9.79)). The factor associated with the absence of an echocardiography evocative of IE was infection due to unconventional bacteria for IE (OR 0.13 (CI95% 0.01-0.76)). According to the factors associated with echocardiography evocative of IE, we propose the Normandy score based on three kinds of data: cardiac condition, bacterial strain and NJBI mechanism. Echocardiography should be realized when this score, whose negative predictive value is 100% CI95% (98-100%) for prescription of echocardiography, is more than zero. CONCLUSIONS: A score based on valvular condition, bacterial strain and NJBI mechanism could guide clinicians in prescribing echocardiography during NJBI with an excellent negative predictive value.

Tolerance of BNT162b2 mRNA COVI-19 vaccine in patients with a medical history of COVID-19 disease: A case control study.

INTRODUCTION: Studies evaluating BNT162b2 mRNA Covid-19 vaccine safety excluded subjects with a previous history of COVID-19 infection. The aim of our study was to focus on the tolerance of this vaccine this population. METHODS: An anonymous self-reporting survey related to safety and tolerance of vaccine was completed by subjects 21 to 28 days after the first vaccine dose in two vaccination centers. RESULTS: Subjects with prior COVID-19 disease history (n = 61) had higher systemic reactions than subjects without any previous history (n = 1987) (45.9% vs 29.7%, p = 0.01). Asthenia, headache and fever were significantly more frequent in COVID-19 + group than negative group (25.6% vs 15.2% p = 0.045, 19.7% vs 9.3% p = 0.01, 6.5% vs 0.9% p = 0.003 respectively). Grade of severity was higher in COVID-19 + than in COVID-19 - group (p = 0.03). CONCLUSION: Our study confirms a higher risk of side effects in patients with preexisting SARS-CoV-2 disease but with a good overall tolerance.

Effect of Tenofovir Disoproxil Fumarate and Emtricitabine on nasopharyngeal SARS-CoV-2 viral load burden amongst outpatients with COVID-19: A pilot, randomized, open-label phase 2 trial.

BACKGROUND: Tenofovir and emtricitabine interfere with the SARS CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). Several cohorts reported that people treated by tenofovir disoproxil fumarate and emtricitabine are less likely to develop SARS CoV-2 infection and related severe COVID-19. METHODS: We conducted a pilot randomized, open-label, controlled, phase 2 trial at two hospitals in France. Eligible patients were consecutive outpatients (aged ≥18 years) with RT-PCR-confirmed SARS-CoV-2 infection and an interval from symptom onset to enrolment of 7 days or less. Patients were randomly assigned in a 1:1 ratio to receive oral tenofovir disoproxil fumarate and emtricitabine (2 pills on day 1 followed by 1 pill per day on days 2-7) or the standard of care. The primary and secondary endpoints were SARS-CoV-2 viral clearance from baseline assessed by cycle threshold (Ct) RT-PCR on nasopharyngeal swab collected at day 4 and day 7, respectively. A higher Ct corresponds to a lower SARS CoV-2 viral burden. Other endpoints were the time to recovery and the number of adverse events. This trial is registered with ClinicalTrials.gov, NCT04685512. FINDINGS: From November, 20th 2020 to March, 19th 2021, 60 patients were enrolled and randomly assigned to a treatment group (30 to tenofovir disoproxil fumarate and emtricitabine and 30 to standard of care). The median number of days from symptom onset to inclusion was 4 days (IQR 3-5) in both groups. Amongst patients who received tenofovir disoproxil fumarate, the difference from standard of care in the increase in Ct RT-PCR from baseline was 2.3 (95% confidence interval [-0.6 to 5.2], p = 0.13) at day 4 and 2.9 (95% CI [0.1 to 5.2], p = 0.044) at day 7. At day 7, 6/30 in the tenofovir disoproxil fumarate and emtricitabine group and 3/30 in the standard of care group reported no COVID-related symptoms. Adverse events included 11 cases of gastrointestinal side effects (grade ≤ 2), three of which leaded to drug discontinuation. Three patients had COVID-19 related hospitalisation, no participant died. INTERPRETATION: In this pilot study of outpatients adult with recent non-severe COVID-19, tenofovir disoproxil fumarate plus emtricitabine appeared to accelerate the natural clearance of nasopharyngeal SARS-CoV-2 viral burden. These findings support the conduct of larger trials of tenofovir-based therapies for the prevention and early treatment of COVID-19. FUNDING: No external funding.

Forgiveness of Dolutegravir-Based Triple Therapy Compared With Older Antiretroviral Regimens: A Prospective Multicenter Cohort of Adherence Patterns and HIV-RNA Replication.

BACKGROUND: For many people with HIV (PWH), taking antiretroviral therapy (ARV) every day is difficult. METHODS: Average adherence (Av-Adh) and log-transformed treatment interruption (TI) to ARV were prospectively measured over 6 months using electronic drug monitoring (EDM) in several cohorts of PWH. Multivariate linear regression models including baseline confounders explored the influence of EDM-defined adherence (R 2) on 6-month log10 HIV-RNA. Multivariate logistic regression models were used to compare the risk of HIV-RNA detection (VR) within subgroups stratified by lower (≤95%) and higher (>95%) Av-Adh. RESULTS: Three hundred ninety-nine PWH were analyzed with different ARVs: dolutegravir (n = 102), raltegravir (n = 90), boosted PI (bPI; n = 107), and NNRTI (n = 100). In the dolutegravir group, the influence of adherence pattern measures on R 2 for HIV-RNA levels was marginal (+2%). Av-Adh, TI, and Av-Adh × TI increased the R 2 for HIV-RNA levels by 54% and 40% in the raltegravir and bPI treatment groups, respectively. TI increased the R 2 for HIV-RNA levels by 36% in the NNRTI treatment group. Compared with the dolutegravir-based regimen, the risk of VR was significantly increased for raltegravir (adjusted odds ratio [aOR], 45.6; 95% CI, 4.5-462.1; P = .001), NNRTIs (aOR, 24.8; 95% CI, 2.7-228.4; P = .005), and bPIs (aOR, 28.3; 95% CI, 3.4-239.4; P = .002) in PWH with Av-Adh ≤95%. Among PWH with >95% Av-Adh, there were no significant differences in the risk of VR among the different ARVs. CONCLUSIONS: These findings support the concept that dolutegravir in combination with 2 other active ARVs achieves greater virological suppression than older ARVs, including raltegravir, NNRTI, and bPI, among PWH with lower adherence.

Case Report: Leishmania and HIV Co-Diagnosis: How to Understand Medical History?

We report a case of a severe visceral leishmaniasis revealing an HIV-1 infection presenting as an acute primary infection. A young French man living in Paris with history of unprotected sex with a recent male partner and recent travel in Greece was admitted in our Infectious Diseases Department, presenting with acute febrile psychotic disorder, and positive HIV-1 serology with high viral load, very low CD4+ T-cells count and a western blot pattern suggesting an acute infection. The psychotic disorder was finally related to hemophagocytic lymphohistiocytosis diagnosed on bone marrow aspiration, supposedly secondary to HIV acute primary infection. The progressive worsening of pancytopenia despite antiretroviral treatment and the persistence of fever, chills and sweat led to the diagnosis of visceral leishmaniasis through bone marrow biopsy and leishmanial serology. He was treated with intravenous liposomal amphotericin B with quick improvement. We discuss the way HIV infection and visceral leishmaniasis may have interact to lead to the clinical presentation of our patient.

Tenofovir disoproxil fumarate and emtricitabine maintenance strategy in virologically controlled adults with low HIV-1 DNA: 48 week results from a randomized, open-label, non-inferiority trial.

OBJECTIVES: Low HIV reservoirs may be associated with viral suppression under a lower number of antiretroviral drugs. We investigated tenofovir disoproxil fumarate/emtricitabine as a maintenance strategy in people living with HIV (PLHIV) with low HIV-DNA. METHODS: TRULIGHT (NCT02302547) was a multicentre, open-label, randomized trial comparing a simplification to tenofovir disoproxil fumarate/emtricitabine versus a triple regimen continuation (tenofovir disoproxil fumarate/emtricitabine with a third agent, control arm) in virologically suppressed adults with HIV-DNA <2.7 log10 copies/106 PBMCs and no prior virological failure (VF). The primary endpoint (non-inferiority margin 12%) was the percentage of participants with a plasma viral load (pVL) <50 copies/mL in ITT (Snapshot approach) and PP analyses at Week 48 (W48). RESULTS: Of the 326 participants screened, 223 (68%) were randomized to the tenofovir disoproxil fumarate/emtricitabine arm (n = 113) or control arm (n = 110). At W48, the tenofovir disoproxil fumarate/emtricitabine and control arms maintained a pVL < 50 copies/mL in 100/113 (88.5%) and 100/110 (90.9%) participants, respectively (ITT difference 2.4%, 95% CI -5.9 to 10.7; PP difference 3.4%, 95% CI -4.2 to 11.0). Six VFs occurred in the tenofovir disoproxil fumarate/emtricitabine arm (two with emerging mutations M184V and K65R) versus two in the control arm (ITT difference 3.5%, 95% CI -1.9 to 9.4). All VFs were resuppressed after treatment modification. CONCLUSIONS: Although non-inferiority was shown, simplification to tenofovir disoproxil fumarate/emtricitabine should not be used for most PLHIV because of a low risk of VF with resistance.

General practitioners' clinical practice on the management of cystitis in Normandy, France: A clinical vignettes-based study.

RATIONALE, AIMS, AND OBJECTIVES: The objective was to measure the quality of clinical practice for the management of cystitis in adult women in general practice by collaborating with quality circles and the regional centre for antibiotic counsel. METHOD: This descriptive cross-sectional study was performed in 2018 in Normandy, France. A questionnaire composed of clinical vignettes was used to evaluate practices of general practitioners (GPs) with regard to cystitis classified into four categories: simple, at risk of complication, recurrent, and caused by multidrug-resistant bacteria. The 2017 French Infectious Diseases Society's guidelines were used as a reference. RESULTS: A total of 142 GPs participated in the study (45.5% of the solicited). Fosfomycin-trometamol and pivmecillinam were cited as first-line treatments for simple cystitis by 134 (94%) and 38 (27%) participants, respectively. For at risk of complication cystitis, the treatments cited were cefixime by 64 participants (45%), ofloxacin by 50 (35%), pivmecillinam by 49 (35%), fosfomycin-trometamol by 38 (27%), nitrofurantoin by 36 (25%), and amoxicillin-clavulanic acid by 28 (20%). Mean compliance rates were 85% for simple cystitis, 39% for at risk of complication cystitis, 60% for recurrent cystitis and 14% for cystitis caused by multidrug-resistant bacteria. Two criteria had less than 10% of the compliant answers: comprehensive knowledge of cystitis complication risk factors (9%) and positivity thresholds of urine cultures (10%). CONCLUSIONS: In this study, diagnostic means, follow-up testing, and simple cystitis treatment (with fosfomycin predominantly mentioned) were broadly compliant. The use of critical antibiotics was too frequent for at risk of complication cystitis. There may be a need to improve the knowledge of professionals on antibiotic resistance and appropriate antibiotic use.