[Antibiotic resistance: a public health priority in which everyone has a role to play!] / L'antibiorésistance : une priorité de santé publique, où chacun a un rôle à jouer !

Preserving the effectiveness of our antibiotics against pathogenic bacteria is a major public health issue, which is why the World Health Organization has made the fight against antibiotic resistance one of its ten priorities. The fight against antibiotic resistance must be implemented at international, national and local levels. Nurses, in close contact with patients, have a fundamental role to play in both pillars of the strategy implemented in France: in the prevention and control of infections, of course, but also in the proper use of antibiotics.

Updated mortality and causes of death in 2020-2021 in people with HIV: a multicenter study in France.

OBJECTIVE: The aim of this study was to assess updated mortality and causes of death in people with HIV (PWH) in France. DESIGN AND METHODS: We analyzed all deaths in PWH followed up between January 1, 2020, and December 31, 2021, in 11 hospitals in the Paris region. We described the characteristics and causes of death among deceased PWH, and evaluated the incidence of mortality and associated risk factors using a multivariate logistic regression. RESULTS: Of the 12 942 patients followed in 2020--2021, 202 deaths occurred. Mean annual incidence of death [95% confidence interval (95% CI)] was 7.8 per 1000 PWH (6.3-9.5). Forty-seven patients (23%) died from non-AIDS nonviral hepatitis (NANH)-related malignancies, 38 (19%) from non-AIDS infections (including 21 cases of COVID-19), 20 (10%) from AIDS, 19 (9%) from cardiovascular diseases (CVD), 17 (8.4%) from other causes, six (3%) from liver diseases, and five (2.5%) from suicides/violent deaths. The cause of death was unknown in 50 (24.7%) patients. Risks factors for death were age [adjusted odds ratio (aOR) 1.93; 1.66-2.25 by additional decade), AIDS history (2.23; 1.61-3.09), low CD4 + cell count (1.95; 1.36-2.78 for 200-500 cells/µl and 5.76; 3.65-9.08 for ≤200 versus > 500 cells/µl), and viral load more than 50 copies/ml (2.03; 1.33-3.08), both at last visit. CONCLUSION: NANH malignancies remained in 2020-2021 the first cause of death. COVID-19 accounted for more than half of the mortality related to non-AIDS infections over the period. Aging, AIDS history, and a poorer viro-immunological control were associated with death.

Safety and efficacy of switching to elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate in treatment-experienced people with HIV: a multicenter cohort study.

OBJECTIVES: We assessed the virologic efficacy of switching to co-formulated elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate (E/C/F/TDF) in patients with controlled HIV infection. METHODS: We conducted a retrospective multicenter observational cohort study including adult patients with controlled HIV-1 infection on any stable antiretroviral (ART) regimen, who switched to E/C/F/TDF. Success was measured by the proportion of patients with plasma viral load < 50 copies/ml at W48 using the FDA snapshot algorithm. We also assessed risk factors associated with virological failure (VF). RESULTS: 382 patients with HIV RNA < 50 copies/mL who switched to E/C/F/TDF were included in the study. Most patients (69.9%) were male, with median age 44 years (IQR 38-51), who had been on ART for a median of 7 years (IQR 4-13). Median CD4 count was 614/mm3 and 24.6% of the patients had a history of previous virological failure. The reasons for switching were simplification (67.0%) and tolerance issues (22.0%). At week 48, 314 (82.0% [95% CI 78.4-86.0]) patients had HIV RNA < 50 copies/mL, 13 (3.5% [95% CI 3.64-8.41]) experienced virological failure. Genotype at failure was available in 6/13 patients with detection of resistance-associated mutations to integrase inhibitors and NRTIs in 5/6 (83.3%) patients. We found no predictive factor associated with virological failure except for a borderline significance with the duration of viral suppression before the switch. Tolerability of E/C/F/TDF was good with 23/382 (6.0%) patients experiencing mild adverse reactions. CONCLUSION: In our cohort, switching well-suppressed patients to E/C/F/TDF resulted in few virologic failures and was well tolerated. However, resistance to integrase inhibitors emerged in patients with virological failure.

Effect of Tocilizumab in Hospitalized Patients with Severe COVID-19 Pneumonia: A Case-Control Cohort Study.

Tocilizumab, an anti-interleukin-6 receptor, administrated during the right timeframe may be beneficial against coronavirus-disease-2019 (COVID-19) pneumonia. All patients admitted for severe COVID-19 pneumonia (SpO2 ≤ 96% despite O2-support ≥ 6 L/min) without invasive mechanical ventilation were included in a retrospective cohort study in a primary care hospital. The treatment effect of a single-dose, 400 mg, of tocilizumab was assessed by comparing those who received tocilizumab to those who did not. Selection bias was mitigated using three statistical methods. Primary outcome measure was a composite of mortality and ventilation at day 28. A total of 246 patients were included (106 were treated with tocilizumab). Overall, 105 (42.7%) patients presented the primary outcome, with 71 (28.9%) deaths during the 28-day follow-up. Propensity-score-matched 84 pairs of comparable patients. In the matched cohort (n = 168), tocilizumab was associated with fewer primary outcomes than the control group (hazard ratio (HR) = 0.49 (95% confidence interval (95%CI) = 0.3-0.81), p-value = 0.005). These results were similar in the overall cohort (n = 246), with Cox multivariable analysis yielding a protective association between tocilizumab and primary outcome (adjusted HR = 0.26 (95%CI = 0.135-0.51, p = 0.0001), confirmed by inverse probability score weighting (IPSW) analysis (p < 0.0001). Analyses on mortality only, with 28 days of follow-up, yielded similar results. In this study, tocilizumab 400 mg in a single-dose was associated with improved survival without mechanical ventilation in patients with severe COVID-19.

[Establishment and one-year evaluation of an internal medicine consultation in a maternity]. / Implantation et évaluation à un an d?une consultation de médecine interne dans une maternité.

OBJECTIVE: In the obstetric medicine movement and in response to requests for appointments in internal medicine by obstetricians and midwives, we created an internal medicine consultation within the maternity ward of our General Hospital, and provide feedback after 1 year. METHODS: This retrospective descriptive study took place at the Robert Ballanger Intercommunal Hospital Center in Aulnay-sous-Bois in Seine-Saint-Denis (France) between 3rd March 2016 and 9th March 2017, the first year of the internal medicine consultation, one afternoon every 15 days, in the maternity level 2b. RESULTS: Out of 121 appointments, 93 consultations were conducted for 63 patients. The main reasons were: thromboembolism (n=2), placental vascular disease (n=14), anemia (n=9), HIV infection (n=8), fetal deaths in utero (n=6), thrombocytopenia (n=6) and autoimmune biological abnormalities (n=3). Although none etiology was found for 16 patients (including 11 seen for placental vascular disease), a diagnosis was made in 75% of cases with a suitable therapeutic attitude. The diagnoses were varied: antiphospholipid syndrom, hypertension, but also discovery of a primary biliary cirrhosis, of a veritable pregnancy-induced immune thrombocytopenia induced by the pregnancy and of a lymphoma-associated on anemia. CONCLUSIONS: This consultation provides satisfaction in terms of interdisciplinary organization and collaboration. It appears useful to patients, leading to prevention advice, various diagnoses and sometimes long-term follow-up.

[Systemic lupus erythematosus: a French general hospital experience]. / Lupus systémique : quels patients et quelle prise en charge en Centre Hospitalier Général ?

Objectives: Systemic lupus erythematosus (SLE) is a disease requiring long-term follow-up. Most studies published in the literature concerned teaching hospitals. We wanted to study a population of SLE patients, their follow-up and therapeutic modalities in a general hospital in order to evaluate professional practices.Methods: We performed a descriptive and retrospective study with SLE patients followed at Centre Hospitalier Intercommunal Robert Ballanger in Aulnay sous Bois (Seine Saint-Denis) between March 2013 and March 2015.Results: Thirty-nine patients were included with various forms of the disease: 77% presented arthritis, 67% had skin involvement, 44% had haematological disorders, 26% had serosal involvement, 13% had kidney involvement, 13% had neuropsychiatric disorders, 8% had digestive tract involvement and 2% had myocarditis. Thirty-five patients were treated with hydroxychloroquine and 12 were treated with immunosuppressive or biotherapy. Patients were seen 3 or 4 times a year as outpatients; 19 were hospitalized at least once in conventional wards and 27 were admitted at least once to a day hospital. Advice from a teaching hospital colleague was required for 6 patients, but only one patient was permanently followed in another hospital.Conclusion: Our patients had similar clinical features to those reported in large series, except for a lower prevalence of renal injuries. Therapeutic management was in accordance with guidelines, with frequent discussion with teaching hospitals. We identified measures to improve our follow-up?: more cardiovascular prevention, more vaccinations and adjustment of hydroxychloroquine monitoring.

Effect of early syphilis infection on plasma viral load and CD4 cell count in human immunodeficiency virus-infected men: results from the FHDH-ANRS CO4 cohort.

BACKGROUND: Concomitant syphilis and human immunodeficiency virus (HIV) infection is increasingly frequent in industrialized countries. METHODS: From a large hospital cohort of HIV-infected patients followed up in the Paris area between 1998 and 2006, we examined the effect of early syphilis on plasma HIV-1 RNA levels and CD4 cell counts. We compared 282 HIV-1-infected men diagnosed as having incident primary or secondary syphilis with 1233 syphilis-free men matched for age (±5 years), sexual orientation, participating center, length of follow-up (±6 months), and immunologic and virologic status before the date of syphilis diagnosis (index date). Increase in viral load (VL) (plasma HIV-1 RNA) of at least 0.5 log or a rise to greater than 500 copies/mL in patients with previously controlled VL during the 6 months after the index date was analyzed, as were CD4 cell count variations and CD4 slope after the index date. RESULTS: During the 6 months after the index date, VL increase was observed in 77 men with syphilis (27.3%) and in 205 syphilis-free men (16.6%) (adjusted odds ratio [aOR], 1.87; 95% CI, 1.40-2.49). Even in men with a VL of less than 500 copies/mL undergoing antiretroviral therapy, syphilis was associated with a higher risk of VL increase (aOR, 1.52; 95% CI, 1.02-2.26). The CD4 cell count decreased significantly (mean, -28/µL) compared with the syphilis-free group during the syphilis episode (P = .001) but returned to previous levels thereafter. CONCLUSIONS: In HIV-infected men, syphilis was associated with a slight and transient decrease in the CD4 cell count and with an increase in VL, which implies that syphilis may increase the risk of HIV transmission, even in patients receiving antiretroviral therapy and with a VL of less than 500 copies/mL.

Quality of travel health advice in a French travel medicine and vaccine center: a prospective observational study.

BACKGROUND: The number of international trips undertaken by French citizens is rising and we wished to assess the appropriateness of advices given to travelers in a vaccine and travel medicine center in France. METHODS: We conducted a 3-month prospective study in one center in Paris where prescriptions and advice to travelers are given by trained physicians in travel medicine who have access to a computerized decision support system (Edisan). A questionnaire was used to record trip characteristics, patients' demographics, and prescriptions. Main outcome measure was the adequacy of prescriptions for malaria prophylaxis, yellow fever, and hepatitis A vaccines to French guidelines. RESULTS: A total of 730 subjects were enrolled in this study, with a median age of 28 years. Travel destinations were sub-Saharan Africa (58%), Asia (21%), and South America (18%). Among the 608 patients (83%) traveling to malaria-endemic areas, malaria prophylaxis was in accordance with guidelines in 578/608 patients (95.1%, 95% CI: 93-96.5), and doxycycline was the regimen of choice (48%). Inappropriate malaria prophylaxis was given to eight patients, one of whom developed plasmodium falciparum malaria. All 413 patients (100%, 95% CI: 99-100) traveling to yellow fever-endemic areas who needed vaccination were correctly vaccinated. However, three patients received yellow fever vaccination without indication. Also, 442 of 454 patients (97.4%, 95% CI: 95.4-98.5) eligible to receive hepatitis A vaccination were immunized. CONCLUSION: Appropriate advice for malaria prophylaxis, yellow fever, and hepatitis A vaccinations was provided in a travel medicine and vaccine center where trained physicians used a computerized decision support system. Even in this setting, however, errors can occur and professional practices should be regularly assessed to improve health care.

Antiretroviral therapy initiation in France: adherence to national guidelines and outcome.

OBJECTIVES AND METHODS: Retrospective study of all patients who started antiretroviral therapy (ART) in 2007 in a single center in Paris, with baseline characteristics and 1-year outcome, to assess adherence to national guidelines. RESULTS: We analyzed 118 patients. Time of ART initiation was in agreement with the guidelines for only 64 (54.2%) patients. Fifty patients (42%) started ART with AIDS or a CD4 count <200 cells/mm(3). In all, 62 (52%) and 47 patients (40%) received a combination of 2 nucleoside analogues with efavirenz (EFV) and 1 ritonavir-boosted protease inhibitor (PI/r), respectively. Treatment regimens were in accordance with the guidelines for 114 patients (97%). At 1 year, 16 patients (13.5%) were lost to follow-up, only 5 (4.9%) experienced HIV disease progression or death, but 19 (18.6%) required hospitalization. Antiretroviral therapy was changed in 21 patients (21%). Ten patients (8.4%) experienced virologic failure. CONCLUSION: Antiretroviral therapy was in agreement with guidelines for the choice of combination but was often initiated too late.

Severe acute renal failure in an HIV-infected patient after only 2 weeks of tenofovir-based antiretroviral therapy.

We report a 46-year-old man who has sex with men (MSM) patient, of Scottish descent, who had no history of arterial hypertension, diabetes, or illicit drug use, was hepatitis C virus (HCV) negative but underwent right nephrectomy for urothelial tumor in 2006. Before starting antiretroviral therapy, he had a CD4 cell count of 316/mm(3) and plasma HIV RNA level was 1,020,537 copies per milliliter. He developed acute renal failure only 2 weeks after introduction of tenofovir-based antiretroviral therapy and then required 3 months of hemodialysis. After the end of hemodialysis, antiviral therapy was resumed with abacavir (300 mg×2/day), lamivudine (300 mg every day), and lopinavir/ritonavir (400/100 mg twice daily). Renal biopsy revealed severe and diffuse toxic acute tubular necrosis Two years after tenofovir discontinuation, the patient's renal function remained subnormal. Although severe renal toxicity due to tenofovir is rare, patients receiving tenofovir must be monitored closely for renal dysfunction especially during the first weeks of tenofovir therapy.

Aspergillus-related myositis: a case report and review of the literature.

OBJECTIVES: Infectious myositis can be a life-threatening condition. We describe the clinical presentation, diagnosis, treatment, and outcome of a patient with Aspergillus-related myositis and review the relevant literature on Aspergillus-related myositis. METHODS: We report on a patient with acquired immunodeficiency syndrome who presented with Aspergillus myo-fasciitis, which was unusual because of its relapsing-remitting course and favorable outcome. We analyze the clinical features, diagnosis, and treatment of 9 additional patients identified through a PubMed literature review between 1964 and early 2010. RESULTS: A 64-year-old human immunodeficiency virus positive African woman was hospitalized for a relapsing-remitting history of bilateral myo-fasciitis for more than 15 years. She had already undergone 3 previous muscle biopsies without definite diagnosis. A computed tomographic scan-guided biopsy revealed numerous septae hyphae with focal necrosis. Cultures yielded Aspergillus flavus as the underlying pathogen and the diagnosis of Aspergillus-related myo-fasciitis was finally made. On reviewing the literature, only 9 other cases have been described. However, no similar case with such a chronic and favorable course was reported. CONCLUSIONS: As compared with the reported cases in the literature, our case is unusual because of its relapsing-remitting course for more than 15 years and favorable outcome. Our case emphasizes the difficulty of the diagnosis, and the importance of early and appropriate management of this rare myositis, which should be systematically evoked in patients with immune deficiency.

JC virus variant associated with cerebellar atrophy in a patient with AIDS.

The human polyomavirus JC virus (JCV) is the agent of progressive multifocal leukoencephalopathy (PML). It has also recently been involved in cerebellar atrophy. Factors involved in this entity are elusive. We present a case of a human immunodeficiency virus (HIV)-infected patient with PML and cerebellar atrophy. In addition to a compartmentalization of JCV strains between urine, cerebrospinal fluid, and cerebellum, specific rearrangements in the JCV regulatory region were observed in the cerebellum, resulting in alterations of transcription factor binding sites. Our data underline the importance of searching for JCV in HIV-infected patients with cerebellar disorders and suggest that mutations in the regulatory region may be involved in cerebellar degeneration.

Incidence and risk factors of thrombocytopenia in patients receiving intermittent antiretroviral therapy: a substudy of the ANRS 106-window trial.

BACKGROUND: Incidence and risk factors for thrombocytopenia in patients discontinuing highly active antiretroviral therapy (HAART) have not been fully investigated. METHODS: Well-suppressed patients on HAART were randomized to continuous (CT) or intermittent therapy (IT) for 96 weeks. Incidence of thrombocytopenia (<150 x 10(3) platelets/mm(3)) was assessed and multivariate analysis performed to identify baseline predictors. Correlations were assessed between platelet, CD4, CD8 T-cell counts, and viral load after treatment interruption. RESULTS: Three hundred ninety-one patients were included, with a median baseline platelet count of 243,000/mm(3). The incidence of thrombocytopenia at week 96 was significantly higher in the IT versus the CT arm (25.4% versus 9.8%, respectively, P < 0.001) and median time to thrombocytopenia was 9 weeks. In multivariate analysis, the IT strategy: odds ratio (OR) = 4.1 (2.1-7.9; P < 0.0001), a history of thrombocytopenia: OR = 11.9 (2.4-57.9; P = 0.002), and a low baseline platelet count: OR = 3.4 (2.3-5.1; P < 0.0001) were associated with an increased risk of thrombocytopenia. Also, after treatment interruption, changes from baseline in platelet counts were correlated with changes in CD4 T-cell counts and plasma HIV RNA levels (P < 0.001 for both). CONCLUSIONS: Intermittent therapy is associated with a high incidence of thrombocytopenia, especially among patients with low platelet counts and a history of thrombocytopenia.

In vitro susceptibility of various genotypic strains of Toxoplasma gondii to pyrimethamine, sulfadiazine, and atovaquone.

Sulfadiazine, pyrimethamine, and atovaquone are widely used for the treatment of severe toxoplasmosis. Their in vitro activities have been almost exclusively demonstrated on laboratory strains belonging to genotype I. We determined the in vitro activities of these drugs against 17 strains of Toxoplasma gondii belonging to various genotypes and examined the correlations among 50% inhibitory concentrations (IC50s), growth kinetics, strain genotypes, and mutations on drug target genes. Growth kinetics were determined in THP-1 cell cultures using real-time PCR. IC50s were determined in MRC-5 cell cultures using a T. gondii-specific enzyme-linked immunosorbent assay performed on cultures. Mutations in dihydrofolate reductase (DHFR), dihydropteroate synthase (DHPS), and cytochrome b genes were determined by sequencing. Pyrimethamine IC50s ranged between 0.07 and 0.39 mg/liter, with no correlation with the strain genotype but a significant correlation with growth kinetics. Several mutations found on the DHFR gene were not linked to lower susceptibility. Atovaquone IC50s were in a narrow range of concentrations (mean, 0.06 +/- 0.02 mg/liter); no mutation was found on the cytochrome b gene. IC50s for sulfadiazine ranged between 3 and 18.9 mg/liter for 13 strains and were >50 mg/liter for three strains. High IC50s were not correlated to strain genotypes or growth kinetics. A new mutation of the DHPS gene was demonstrated in one of these strains. In conclusion, we found variability in the susceptibilities of T. gondii strains to pyrimethamine and atovaquone, with no evidence of drug resistance. A higher variability was found for sulfadiazine, with a possible resistance of three strains. No relationship was found between drug susceptibility and strain genotype.