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Diphtheria is a re-emerging disease in resource-rich settings. We here report three cases of cutaneous diphtheria diagnosed and managed in our infectious disease department and discuss the determinants of its re-emergence. Migration, travel and vaccine scepticism are key factors not only for diphtheria re-emergence, but for the future of most preventable diseases.

We performed a single-centre retrospective study to evaluate the effectiveness of Toxoplasma gondii prevention strategies after allogeneic stem-cell transplantation. The charts of 138 allogeneic stem-cell recipients over a 4-year period were reviewed. Forty-nine percent of patients were not receiving optimal trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis at day +30, mainly due to persistent cytopenia. Six months after transplantation, the rate of toxoplasmosis reactivation was 11.6%, including nine cases of Toxoplasma infection and seven cases of Toxoplasma disease. Fifty-six percent of cases of reactivation occurred before day +30. Thirty-eight percent occurred in patients receiving atovaquone prophylaxis. In 57% of patients presenting with Toxoplasma disease, signs of disease were present at first evidence of Toxoplasma DNA in peripheral blood samples. This study illustrates the limitations inherent to currently used toxoplasmosis prevention strategies and argues for the use of a combined prophylactic and preemptive approach. After performing the initial study, we limited the use of atovaquone in favour of TMP-SMZ when possible, and implemented an early prevention strategy consisting of the introduction of prophylaxis starting on day of engraftment. Over the following 16 months, 88.9% of eligible Toxoplasma-seropositive patients were receiving TMP-SMZ at day +30, and the rate of early Toxoplasma reactivation was 1.5%.

The Bacillus Calmette-Guerin (BCG) is a life-attenuated form of Mycobacterium bovis widely used as immunotherapy for localized bladder cancer. Adverse reactions to intravesical BCG instillations are rare. We describe a 70-year-old man with a history of an aortobifemoral bypass graft, placement of a synthetic mesh for treatment of a ventral hernia and, most recently, superficial bladder cancer treated with BCG therapy. Ten months after his final intravesical BCG instillation, he complained of fever and asthenia. After 12 months of investigation, he was diagnosed with Mycobacterium bovis infection of his aortobifemoral bypass graft and abdominal mesh, with Streptococcus intermedius superinfection. The bypass graft was excised and replaced with an in situ arterial allograft, the abdominal mesh was removed, and treatment started with amoxicillin, isoniazid, rifampicin and ethambutol. Several additional vascular interventions were needed for allograft degradation, but 12 months after the final procedure, outcome was good. Among 35 cases of mycotic aneurysm reported after BCG therapy in the last 10 years, only one involved a vascular prosthesis. Surgical repair of such aneurysms using prosthetic grafts is commonly performed, associated with anti-mycobacterial treatment. Prognosis is poor with mortality of 14% (4/35) and a 26% rate of aneurysm recurrence under treatment (9/35).

Background Kaposi sarcoma (KS)–associated herpesvirus (KSHV) subtype depends mostly on patient origin. The current study aimed to assess KSHV diversity in a population of men who have sex with men (MSM) living in France. Methods The study included 264 patients. In 65 MSM, including 57 human immunodeficiency virus (HIV)–infected men with KS, multicentric Castleman disease, or primary effusion lymphoma and 8 HIV-uninfected men receiving HIV preexposure prophylaxis (PrEP), we performed KSHV typing with K1 open reading frame Sanger and KSHV whole-genome sequencing. In 199 other patients, we performed real-time polymerase chain reaction screening for the new variant. Results We found that 51% of KSHV-strains were subtype C (85% C3), and 33% were subtype A. Four patients with severe KSHV disease (2 with visceral KS, 1 with multicentric Castleman disease, and 1 with primary effusion lymphoma) and 1 asymptomatic PrEP user had a new variant resembling the Ugandan subtype F, but with different K1 open reading frame and KSHV whole-genome sequences and a different epidemiological context (MSM vs African population). Its prevalence was 4.5% in Caucasian MSM, and it was absent in other epidemiological groups. Conclusions Subtype C predominated among MSM living in France. The new F variant was identified in Caucasian MSM and associated with severe KSHV disease, suggesting that subtype F could be split into F1 and F2 variants. Careful screening for this variant may be required in MSM, given the severe clinical presentation of associated diseases.

Patients with hematological malignancies and COVID-19 display a high mortality rate. In such patients, immunosuppression due to underlying disease and previous specific treatment impairs humoral response, limiting viral clearance. Thus, COVID-19 convalescent plasma (CCP) therapy appears to be a promising approach through the transfer of neutralizing antibodies specific to SARS-CoV-2.Our study reports the effect of CCP in a cohort of patients with hematological malignancies and COVID-19 between 1 May 2020 and 1 April 2021. Overall, 112 hospitalized patients with severe COVID-19 (83 B-cell neoplasm, 19 plasma cell neoplasm, and 10 myeloid neoplasm) were included. The overall survival of the whole cohort was 65% [56–74.9] and 77.5% [68.5–87.7] for patients with B-cell neoplasm. Prior anti-CD20 monoclonal antibodies therapy was associated with better overall survival whereas age, high blood pressure, and COVID-19 severity were associated with a poor outcome after CCP transfusion. A retrospective analysis in the subgroup of COVID-19 patients with B-cell neoplasm treated with CCP (n=81) was compared to a similar group of patients (n=120) treated only with standard of care. An inverse probability of treatment weighting (IPTW) approach, performed to limit confusion and immortality bias, revealed a decreased mortality of 63% (95% CI=31%–80%) in the main analysis and 50% (95% CI=28%–66%) in the overall population of the CCP-treated group of patients with similar findings in the other sensitivity analyses.Convalescent plasma may be beneficial in COVID-19 patients with B-cell neoplasm who are unable to mount a humoral immune response. Comparing CCP to other passive immunotherapy approaches such as anti-SARS-CoV-2 monoclonal antibodies is warranted. Funding Information: This study was funded by Sorbonne University, Paris, France. Declaration of Interests: None to declare. Ethics Approval Statement: Patients gave their written informed consent for the retrospective data collection, and ethical clearance was obtained from the French Infectious Diseases Society (IRB number: 00011642)

Purpose To report the case 47-year-old patient presenting with severe maculopathy associated with long-term ritonavir treatment. Methods Observational case report of one patient and literature review. Results A 47 year-old Caucasian man presented with progressive bilateral vision loss for the past 5 years. His medical history included Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) coinfection since 1992. He was treated by highly active antiretroviral therapy for 24 years including 4 years of didanosine treatment and 18 years of ritonavir treatment. Bilateral extensive macular atrophy with foveal sparing on the left eye and absence of midperipheral/peripheral retina involvement was confirmed on multimodal imaging and functional testing including swept-source OCT angiography and electroretinography. Conclusion Ritonavir associated maculopathy is a scarcely described medication-associated retinopathy. In this case, an extensive macular atrophy (with complete loss of photoreceptor, RPE and choriocapillaris layers) and subsequent cone-rod dysfunction appeared after 18 years of ritonavir exposure., We describe the case of a patient 47 year-old HIV patient presenting with bilateral symmetric macular atrophy. Both multimodal imaging, functional testing of the retina and history of drug exposure are consistent with ritonavir associated maculopathy.

International audience; Design: Current international guidelines recommend either boosted protease inhibitor (PI/r)-based or integrase inhibitors (INSTI)-based regimens during primary HIV infection (PHI), even though the latter have only demonstrated their superiority at the chronic stage. We compared the effectiveness of INSTI-based versus PI/r-based combined antiretroviral therapy (cART) initiated during PHI.Methods: This study was conducted among patients who initiated cART between 2013 and 2017, using data from the ANRS-PRIMO cohort and the Dat’AIDS study. Cumulative proportions of patients reaching viral suppression (HIV-1 RNA

International audience; Background - Increasing incidence of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-positive men having sex with men (MSM) has been described in recent years. Phylogenetic analyses of acute HCV infections were undertaken to characterize the dynamics during the epidemic in Paris, and associated sexually transmitted infections (STIs) were evaluated. Methods - Sanger sequencing of polymerase gene was performed. Maximum likelihood phylogenies were reconstructed using FastTree 2.1 under a GTR+CAT model. Transmission chains were defined as clades with a branch probability ≥0.80 and intraclade genetic distances

International audience; Background: The incidence of Chlamydia trachomatis (Ct) urethritis has been increasing for the past 10 years. There is little data regarding the screening of Ct infection in asymptomatic men in France, despite the national recommendation to screen at-risk asymptomatic men under 30 attending Sexually Transmitted Infections (STI) clinics. Recent data from the French surveillance network Rénachla show indeed that systematic screening is still focused on women. The objective of our study was to determine the prevalence and risk factors for Ct infection in asymptomatic men under 30 attending an STI clinic located in Paris, France.Methods: We performed a cross-sectional study between April 4, and December 31, 2016 in the database of the software DIAMM Client V8 used in our STI clinic. We extracted the demographic characteristics, sexual behavior and result of STI screening of all asymptomatic men who had consulted and given their consent for the use of their personal data. Those data were collected in usual care through a standardized questionnaire filled in during an appointment with a trained physician. STI screening was performed using PCR kit CT/NG Abbott Realtime® on first void urines. For MSM, a rectal swab was also collected. Risk factors for Ct infection were analyzed by univariate and multivariate modeling using STATA software 8.2.Results: Among 872 men who had attended the clinic, 647 were included and 37 (5.7, 95% CI 4.2 to 7.8) were positive for Ct in urine. In univariate analysis, men who had unprotected sex in the last 6 weeks (OR 2.40 (95%CI 1.16 to 4.94), p = 0.02), and those who had an infected partner (OR 7.6 (95%CI 3.03 to 20), p = 0.0001) were more likely to be infected. In the multivariate analysis having an infected partner was the only risk factor (OR 11.1(95% CI 3.7 to 33.3), p = 0.0001) that remained significant.Conclusion: Prevalence of Ct infection is high among asymptomatic men of 30 years or less attending our urban STI clinic especially among those with an infected partner. The Ct screening among this population associated with partner notification, as recommended by the French national guidelines, should be more widely implemented.

Although extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae have become a worldwide public health concern, little is known regarding the clinical course of colonized or infected individuals. Our objective was to characterize the determinants of fatal outcomes related to ESBL-producing microorganisms at a large hospital in Paris, France. In 2012–2013, all consecutive patients with clinical samples testing positive for ESBL-producing Enterobacteriaceae at Saint-Antoine Hospital were identified. Patient clinical data were obtained at hospital entry, while information on intensive care unit (ICU) admissions and death were prospectively collected. Risk-factors for fatal 1-year outcomes were assessed using logistic regression. In total, 643/4684 (13%) ESBL-positive samples were observed, corresponding to 516 episodes (n = 206, 40% treated) among 330 patients. Most episodes were nosocomial-related (n = 347/516, 67%) involving Escherichia coli (n = 232/516, 45%) or Klebsiella pneumoniae (n = 164/516, 32%). Empirical antibiotic therapy was adequate in 89/206 (43%) infections, while the median length of hospital stay was 30 days [interquartile range (IQR) = 11–55] and 39/201 (19%) were admitted to the ICU. Overall, 104/241 patients (43%) with available data died within 1 year. In the multivariable analysis, 1-year death was associated with age >80 years (p = 0.01), concomitant comorbidity (p = 0.001), nosocomial-acquired infection (p = 0.002), and being infected rather than colonized (p < 0.001). In this series of patients with identified samples of ESBL-producing Enterobacteriaceae, hospital burden was large and 1-year mortality rates high. Understanding which patients in this setting would benefit from broad-spectrum empirical antibiotic therapy should be further examined.

International audience; Introduction : Extra-gastro-intestinal tract manifestations associated with Clostridium difficile infection (CDI), including reactive arthritis (ReA), are uncommon.Method : We report a case of ReA associated with a relapse of CDI in a 46-year-old woman. A toxigenic C. difficile strain was isolated from stools and characterized as PCR-ribotype 014/020/077. We conducted a comprehensive literature review of ReA associated with CDI (ReA-CDI). Diagnostic criteria for ReA-CDI were: (i) evidence of aseptic synovitis (confirmed by culture) developing during or immediately after colitis, (ii) presence of a toxigenic C. difficile strain in stool samples, and (iii) absence of other causes of colitis and arthritis.Results : Forty-nine cases of ReA-CDI (excluding the present report) have already been described since 1976. Of these reports, Mean age of patients was 38 years (SD: 18.5), 46% were male, and 68% had HLA B27 genotype. Sixty-nine percent of patients received a β-lactamin treatment before CDI. ReA-CDI occurred a median 10 days (range 0–55 days) after CDI. Outcome was favorable in 90% of patients and oral non anti-inflammatory drugs were required for 55%.Conclusion : ReA-CDI remains uncommon. Compared to the general population, it is more likely observed in younger patients with HLA B27-positive genotype.

Objectives Boosted PIs are commonly prescribed in patients presenting with advanced HIV infection. We assessed the efficacy and tolerability of once-daily ritonavir-boosted atazanavir or darunavir plus two NRTIs in HIV-1-infected ART-naive patients with severe immunosuppression, targeting at least an 85% success rate at week 48. Methods This 48 week, open-label, non-comparative, randomized, multicentre trial included ART-naive patients with CD4 cell counts 1000 copies/mL and without genotypic mutations conferring resistance to the study drugs. Patients were randomized (1:1) to receive once-daily atazanavir/ritonavir (300/100 mg) or darunavir/ritonavir (800/100 mg) plus tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine. The primary endpoint was treatment success, defined as plasma HIV-1 RNA ≤50 copies/mL at week 48 and no permanent PI/ritonavir discontinuation. The study was registered with ClinicalTrials.gov (NCT01928407). Results One hundred and twenty patients were enrolled: 77% were men, 30% were born in Africa and 39% had AIDS. The median baseline CD4 and plasma HIV-RNA values were 69 cells/mm(3) and 5.4 log10 copies/mL. All but four patients received tenofovir disoproxil fumarate/emtricitabine. The week 48 treatment success rate was 66% (95% CI 54%-78%) with atazanavir/ritonavir and 80% (95% CI 68%-89%) with darunavir/ritonavir. The median CD4 cell count increased similarly in the two groups (Δweek 48 to week 0: +194 cells/mm(3)). Adverse events occurred in 23 and 18 patients, respectively. Conclusions Despite good adherence, neither study regimen reached the predefined objective, suggesting a need for more potent regimens for patients with advanced HIV infection.

Background: Assessing the satisfaction of patients about the health care they have received is relatively common nowadays. In France, the satisfaction questionnaire, I-Satis, is deployed in each institution admitting inpatients. Internet self-completion and telephone interview are the two modes of administration for collecting inpatient satisfaction that have never been compared in a multicenter randomized experiment involving a substantial number of patients. Objective: The objective of this study was to compare two modes of survey administration for collecting inpatient satisfaction: Internet self-completion and telephone interview. Methods: In the multicenter SENTIPAT (acronym for the concept of sentinel patients, ie, patients who would voluntarily report their health evolution on a dedicated website) randomized controlled trial, patients who were discharged from the hospital to home and had an Internet connection at home were enrolled between February 2013 and September 2014. They were randomized to either self-complete a set of questionnaires using a dedicated website or to provide answers to the same questionnaires administered during a telephone interview. As recommended by French authorities, the analysis of I-Satis satisfaction questionnaire involved all inpatients with a length of stay (LOS), including at least two nights. Participation rates, questionnaire consistency (measured using Cronbach alpha coefficient), and satisfaction scores were compared in the two groups. Results: A total of 1680 eligible patients were randomized to the Internet group (n=840) or the telephone group (n=840). The analysis of I-Satis concerned 392 and 389 patients fulfilling the minimum LOS required in the Internet and telephone group, respectively. There were 39.3% (154/392) and 88.4% (344/389) responders in the Internet and telephone group, respectively (P

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 26 fevrier 2014

Summary There has been a major paradigm shift in the management of HIV infected patients, with earlier initiation of antiretroviral treatment and lifelong exposure to drugs for which long-term safety issues must be faced by clinicians. Within the past 5 years, new drugs from both previously established and novel therapeutic classes have been released that tend to be safer and more efficient than their former combinations. Although hepatotoxicity was one of the most common side effects from initial antiretrovirals, phase II/III safety data regarding liver tolerance from more recent drugs are reassuring. However, data on the long-term exposure to these therapeutic options are needed, and a handful of case reports are emerging, reporting rare but potentially life-threatening adverse hepatic events in patients with hepatitis co-infection or taking other hepatotoxic drugs.

The outcome of bacterial bloodstream infections during pregnancy has greatly improved over the last few decades. However, there are no recent data on the characteristics of bacteremia in pregnant women. The aim of this study was to describe clinical and microbiological features of bacteremia and to assess maternal and fetal outcome. This retrospective study was conducted in the obstetrics departments of five teaching hospitals in Paris, France, from 2005 to 2009. The incidence of bacteremia was 0.3%. The most common sources of bacteremia were chorioamnionitis (47%) and the most common pathogen isolated was Escherichia coli. Empirical antimicrobial therapy was inappropriate in 29% of bacteremia cases, mostly (65%) when secondary to infection with an aminopenicillin-resistant microorganism. Bacteremia during pregnancy was associated with a 10% fetal mortality. Bacteremia during pregnancy is a rare occurrence, but it is associated with an unexpectedly poor fetal outcome and a high mortality rate.

A rapid and accurate diagnosis of Clostridium difficile infection (CDI) is essential for patient management and implementation of infection control measures. During a prospective time-series study, we compared the impact of three different diagnostic strategies on patient care. Each strategy was tested during a 3-month period: P1 (diagnosis based on the stool cytotoxicity assay and the toxigenic culture), P2 (diagnosis based on PCR) and P3 (two-step algorithm based on glutamate dehydrogenase detection followed by nucleic acid amplification test). The following criteria were used to assess the quality of patient management: (i) time for result reporting, (ii) frequency of repeat testing within 7 days, (iii) time elapsed between stool collection and beginning of treatment for patients with CDI, and (iv) frequency of empirical treatment for patients without CDI. Of 1122 stool samples (P1 n = 359, P2 n = 374, P3 n = 389), 36 (10.0%), 47 (12.3%) and 48 (12.3%) were positive for C. difficile during P1, P2 and P3, respectively. The time for reporting of a positive or a negative result was significantly shorter and the frequency of redundant stool samples within 7 days was lower during P2 and P3 than during P1. Patients with CDI were specifically treated with vancomycin or metronidazole earlier during P2 and P3 than patients from P1 (0.5 ± 0.5 days and 1.0 ± 1.8 days vs. 2.0 ± 1.7 days). The empirical therapy among patients without CDI decreased from 13.6% during P1 to 6.4% during P2 and 5.6% during P3. A rapid CDI diagnosis impacts positively on patient care.