Salvage Therapy Including Foscarnet and Ibalizumab for Multidrug-Resistant Human Immunodeficiency Virus Type 2 Infection.

We evaluated Ibalizumab (IBA)-containing standardized optimized salvage regimen (with or without a 4-week foscarnet induction) in individuals harboring multidrug-resistant human immunodeficiency virus type 2 (HIV-2). Nine were included; 2 achieved virological suppression after foscarnet induction with a sustained suppression at Week 24 after IBA initiation, and an additional individual at Week 24 after Ibalizumab initiation.

Computerized Decision Support Systems Informing Community-Acquired Pneumonia Surveillance, France, 2017-2023.

We show the value of real-time data generated by a computerized decision support system in primary care in strengthening pneumonia surveillance. The system showed a 66% (95% CI 64%-67%) increase in community-acquired pneumonia from 2018 to 2023 for the population of France, 1 month before a national alert was issued.

Implementation of a Clinical Decision Support System for Antimicrobial Prescribing in Sub-Saharan Africa: Multisectoral Qualitative Study.

BACKGROUND: Suboptimal use of antimicrobials is a driver of antimicrobial resistance in West Africa. Clinical decision support systems (CDSSs) can facilitate access to updated and reliable recommendations. OBJECTIVE: This study aimed to assess contextual factors that could facilitate the implementation of a CDSS for antimicrobial prescribing in West Africa and Central Africa and to identify tailored implementation strategies. METHODS: This qualitative study was conducted through 21 semistructured individual interviews via videoconference with health care professionals between September and December 2020. Participants were recruited using purposive sampling in a transnational capacity-building network for hospital preparedness in West Africa. The interview guide included multiple constructs derived from the Consolidated Framework for Implementation Research. Interviews were transcribed, and data were analyzed using thematic analysis. RESULTS: The panel of participants included health practitioners (12/21, 57%), health actors trained in engineering (2/21, 10%), project managers (3/21, 14%), antimicrobial resistance research experts (2/21, 10%), a clinical microbiologist (1/21, 5%), and an anthropologist (1/21, 5%). Contextual factors influencing the implementation of eHealth tools existed at the individual, health care system, and national levels. At the individual level, the main challenge was to design a user-centered CDSS adapted to the prescriber's clinical routine and structural constraints. Most of the participants stated that the CDSS should not only target physicians in academic hospitals who can use their network to disseminate the tool but also general practitioners, primary care nurses, midwives, and other health care workers who are the main prescribers of antimicrobials in rural areas of West Africa. The heterogeneity in antimicrobial prescribing training among prescribers was a significant challenge to the use of a common CDSS. At the country level, weak pharmaceutical regulations, the lack of official guidelines for antimicrobial prescribing, limited access to clinical microbiology laboratories, self-medication, and disparity in health care coverage lead to inappropriate antimicrobial use and could limit the implementation and diffusion of CDSS for antimicrobial prescribing. Participants emphasized the importance of building a solid eHealth ecosystem in their countries by establishing academic partnerships, developing physician networks, and involving diverse stakeholders to address challenges. Additional implementation strategies included conducting a local needs assessment, identifying early adopters, promoting network weaving, using implementation advisers, and creating a learning collaborative. Participants noted that a CDSS for antimicrobial prescribing could be a powerful tool for the development and dissemination of official guidelines for infectious diseases in West Africa. CONCLUSIONS: These results suggest that a CDSS for antimicrobial prescribing adapted for nonspecialized prescribers could have a role in improving clinical decisions. They also confirm the relevance of adopting a cross-disciplinary approach with participants from different backgrounds to assess contextual factors, including social, political, and economic determinants.

Severe Scabies: A French Multi-centre Study Involving 95 Patients with Crusted and Profuse Disease and Review of the Literature.

The aim of this multi-centre French retrospective study was to identify severe, i.e. crusted and profuse, scabies patients. Records were retrieved from 22 Dermatology or Infectious Diseases departments in the Ile-de-France from January 2009 to January 2015 to characterize epidemiology, demography, diagnosis, contributing factors, treatment features, and outcomes in severe scabies. A total of 95 inpatients (57 crusted and 38 profuse) were included. A higher number of cases was observed among elderly patients (>75 years), mostly living in institutions. Thirteen patients (13.6%) reported a history of previously treated scabies. Sixty-three patients (66.3%) had been seen by a previous practitioner for the current episode (up to 8 previous visits). Initial misdiagnosis (e.g. eczema, prurigo, drug-related eruptions, psoriasis) was documented in 41 patients (43.1%). Fifty-eight patients (61%) had already received 1 or more previous treatments for their current episode. Forty percent received corticosteroids or acitretin for an initial diagnosis of eczema or psoriasis. Median time from the onset of symptoms to the diagnosis of severe scabies was 3 months (range 0.3-22). Itch was present in all patients at diagnosis. Most patients (n=84, 88.4%) had comorbidities. Diagnostic and therapeutic approaches varied. Complications occurred in 11.5% of cases. To date, there is no consensus for diagnosis and treatment, and future standardization of is required for optimal management.

Computerized decision support system (CDSS) use for surveillance of antimicrobial resistance in urinary tract infections in primary care.

BACKGROUND: Hospital-based surveillance of antimicrobial resistance may be irrelevant as a guide to antimicrobial use for urinary tract infections (UTIs) in primary care. OBJECTIVES: To highlight the value of online computerized decision support systems (CDSS) in providing information on the surveillance of antimicrobial resistance in community-acquired UTIs. METHODS: We collected the susceptibility profile for key antibiotics by type of UTI involving Escherichia coli from 2017 to 2020, using queries for UTI (Q-UTI) submitted to a French CDSS. We compared these results with those from the MedQual French surveillance system for community-acquired UTI and the European Antimicrobial Resistance Surveillance Network (EARS-NET) for invasive infections. RESULTS: We collected 43 591 Q-UTI, of which 10 192 (23%) involved E. coli: 40% cystitis, 32% male-UTI, and 27% pyelonephritis. Resistance was 41.3% (95% CI, 40.3%-42.2%) for amoxicillin, 16.6% (95% CI, 15.9%-17.3%) for fluoroquinolones, 6.6% (95% CI, 6.1%-7.0%) for third-generation cephalosporins (3GC), and 5.7% (95% CI, 5.2%-6.1%) for aminoglycosides. Resistance to amoxicillin was lower than that reported in MedQual (42.7%, P value = 0.004), and in EARS-NET (55.2%, P value < 0.001). For fluoroquinolones, resistance was higher than in MedQual (12.0%, P value < 0.001) and EARS-NET (15.8%, P value = 0.041). In complicated pyelonephritis and male UTI, fluoroquinolone resistance peaked at ∼20%. For 3GC, all UTI had higher resistance than in MedQual (3.5%, P value < 0.001), but lower than in EARS-NET (9.5%, P value < 0.001). Aminoglycoside resistance was not reported by MedQual, and was lower than in EARS-NET (7.1%, P value < 0.001). CONCLUSIONS: CDSS can inform prescribers in real-time about the ecology and surveillance of E. coli resistance in community-acquired UTI. In complicated upper UTIs, they can underline the risk of empirical use of fluoroquinolones and suggest preferential use of 3GC.

Novel mutations in antiviral multiresistant HSV-2 genital lesion: A case report.

HSV-2 antiviral resistance mainly occurs in immunocompromised patients and especially in HIV-positive individuals receiving long-term antiviral treatment. Those situations can be challenging as few alternatives are available for HSV infection management. To describe clinical and virological significance of two novel potential HSV-2 resistance mutations after treating an obese patient with a pseudotumoral genital HSV-related lesion. Consecutive different antiviral treatments were used: valacyclovir (VACV) then foscarnet (FOS) then topical cidofovir (CDV) and finally imiquimod. Under VACV, genotypic resistance testing revealed a novel mutation within viral thymidine kinase (TK, gene UL23) not previously reported but probably accounting for antiviral resistance: W89G, similar to W88R mutation reported in HSV-1 TK, known to be associated with ACV resistance for HSV-1. Under FOS, while initial mutations were still present, a second genotypic resistance testing performed on persisting lesions showed a novel mutation within viral DNA polymerase (DNA pol, gene UL30): C625R. All three antivirals used in this case are small molecules and pharmacokinetics of VACV, FOS, and CDV have not been evaluated in animals and there are very few studies in human. As small molecules are poorly bound to proteins and distribution volume is increased in obese patients, there is risk of underdosage. This mechanism is suspected to be involved in emergence of resistance mutation and further data is needed to adapt, closely to patient profile, antiviral dosage. This report describes a chronic HSV-2 genital lesion, with resistance to current antivirals and novel mutations within viral TK and DNA pol which may confer antiviral resistance.

A computerized decision support system (CDSS) for antibiotic prescription in primary care-Antibioclic: implementation, adoption and sustainable use in the era of extended antimicrobial resistance.

OBJECTIVES: To describe the implementation and use of a computerized decision support system (CDSS) for antibiotic prescription in primary care in France (Antibioclic). The CDSS targets 37 infectious diseases and has been freely available on a website since 2011. METHODS: Description and implementation of the architecture of a CDSS for antibiotic prescription in general practice. Analysis of the queries made between 2012 and 2018 on the CDSS by GPs. Analysis of two cross-sectional studies of users in 2014 and 2019. RESULTS: The number of queries increased from a median of 796/day [IQR, 578-989] in 2012 to 11 125/day [5592-12 505] in 2018. Unique users increased from 414/day [245-494] in 2012 to 5365/day [2891-5769] in 2018. Time taken to make a query was 2 min [1.9-2.1]. Among 3 542 347 queries in 2018, 78% were for adults. Six situations accounted for ≥50% of queries: cystitis; acute otitis media; acute sinusitis; community-acquired pneumonia; sore throat; and pyelonephritis. Queries concerned pathologies for which antibiotic prescription was necessary (64%), was conditional on additional clinical steps (34%) or was not recommended (2%). Most users (81%) were GPs, with median age of 38 years [31-52] and 58% were female. Among the 4016 GPs who responded to the surveys, the vast majority (96%) reported using the CDSS during the consultation, with 24% systematically using Antibioclic to initiate an antibiotic course and 93% having followed the CDSS recommendation for the latest prescription. Most GPs were comfortable using the CDSS in front of a patient. CONCLUSIONS: Antibioclic has been adopted and is widely used in primary care in France. Its interoperability could allow its adaptation and implementation in other countries.

Paving the Way for the Implementation of a Decision Support System for Antibiotic Prescribing in Primary Care in West Africa: Preimplementation and Co-Design Workshop With Physicians.

BACKGROUND: Suboptimal use of antibiotics is a driver of antimicrobial resistance (AMR). Clinical decision support systems (CDSS) can assist prescribers with rapid access to up-to-date information. In low- and middle-income countries (LMIC), the introduction of CDSS for antibiotic prescribing could have a measurable impact. However, interventions to implement them are challenging because of cultural and structural constraints, and their adoption and sustainability in routine clinical care are often limited. Preimplementation research is needed to ensure relevant adaptation and fit within the context of primary care in West Africa. OBJECTIVE: This study examined the requirements for a CDSS adapted to the context of primary care in West Africa, to analyze the barriers and facilitators of its implementation and adaptation, and to ensure co-designed solutions for its adaptation and sustainable use. METHODS: We organized a workshop in Burkina Faso in June 2019 with 47 health care professionals representing 9 West African countries and 6 medical specialties. The workshop began with a presentation of Antibioclic, a publicly funded CDSS for antibiotic prescribing in primary care that provides personalized antibiotic recommendations for 37 infectious diseases. Antibioclic is freely available on the web and as a smartphone app (iOS, Android). The presentation was followed by a roundtable discussion and completion of a questionnaire with open-ended questions by participants. Qualitative data were analyzed using thematic analysis. RESULTS: Most of the participants had access to a smartphone during their clinical consultations (35/47, 74%), but only 49% (23/47) had access to a computer and none used CDSS for antibiotic prescribing. The participants considered that CDSS could have a number of benefits including updating the knowledge of practitioners on antibiotic prescribing, improving clinical care and reducing AMR, encouraging the establishment of national guidelines, and developing surveillance capabilities in primary care. The most frequently mentioned contextual barrier to implementing a CDSS was the potential risk of increasing self-medication in West Africa, where antibiotics can be bought without a prescription. The need for the CDSS to be tailored to the local epidemiology of infectious diseases and AMR was highlighted along with the availability of diagnostic tests and antibiotics using national guidelines where available. Participants endorsed co-design involving all stakeholders, including nurses, midwives, and pharmacists, as central to any introduction of CDSS. A phased approach was suggested by initiating and evaluating CDSS at a pilot site, followed by dissemination using professional networks and social media. The lack of widespread internet access and computers could be circumvented by a mobile app with an offline mode. CONCLUSIONS: Our study provides valuable information for the development and implementation of a CDSS for antibiotic prescribing among primary care prescribers in LMICs and may, in turn, contribute to improving antibiotic use, clinical outcomes and decreasing AMR.

Appropriateness of intended antibiotic prescribing using clinical case vignettes in primary care, and related factors.

BACKGROUND: Factors associated with the appropriateness of antibiotic prescribing in primary care have been poorly explored. In particular, the impact of computerised decision-support systems (CDSS) remains unknown. OBJECTIVES: We aim at investigating the uptake of CDSS and its association with physician characteristics and professional activity. METHODS: Since May 2022, users of a CDSS for antibiotic prescribing in primary care in France have been invited, when registering, to complete three case vignettes assessing clinical situations frequently encountered in general practice and identified as at risk of antibiotic misuse. Appropriateness of antibiotic prescribing was defined as the rate of answers in line with the current guidelines, computed by individuals and by specific questions. Physician's characteristics associated with individual appropriate antibiotic prescribing (< 50%, 50-75% and > 75% appropriateness) were identified by multivariate ordinal logistic regression. RESULTS: In June 2023, 60,067 physicians had registered on the CDSS. Among the 13,851 physicians who answered all case vignettes, the median individual appropriateness level of antibiotic prescribing was 77.8% [Interquartile range, 66.7%-88.9%], and was < 50% for 1,353 physicians (10%). In the multivariate analysis, physicians' characteristics associated with appropriateness were prior use of the CDSS (OR = 1.71, 95% CI 1.56-1.87), being a general practitioner vs. other specialist (OR = 1.34, 95% CI 1.20-1.49), working in primary care (OR = 1.14, 95% CI 1.02-1.27), mentoring students (OR = 1.12, 95% CI 1.04-1.21) age (OR = 0.69 per 10 years increase, 95% CI 0.67-0.71). CONCLUSION: Individual appropriateness for antibiotic prescribing was high among CDSS users, with a higher rate in young general practitioners, previously using the system. CDSS could improve antibiotic prescribing in primary care.

Individual appropriateness for antibiotic prescribing is high among CDSS users.CDSS use could passively improve antibiotic prescribing in primary care.Factors associated with appropriateness for antibiotic prescribing for primary care diseases are: prior use of CDSS, general practice speciality vs. other specialities, younger age and mentoring of students.

Enterococcal endocarditis management and relapses.

Introduction: Enterococcus faecalis is the third micro-organism causing endocarditis and is associated with a significant relapse rate. The objective of this study was to describe the management of patients with Enterococcus faecalis endocarditis (EE) and its implication for relapses. Methods: We conducted a monocentric, retrospective analysis of all patients hospitalized for EE including endocarditis or infection of cardiac implantable electronic device defined by the modified ESC 2015 Duke criteria in a referral centre in Paris, France. Results: Between October 2016, and September 2022, 54 patients with EE were included, mostly men (n = 40, 74%) with a median age of 75 [68-80] years. A high risk for infective endocarditis (IE) was found in 42 patients (78%), including 14 (26%) previous histories of IE, and 32 (59%) histories of valvular cardiac surgery. The aortic valve was the most frequently affected (n = 36, 67%). Combination therapy was mainly amoxicillin-ceftriaxone during all the curative antibiotic therapy duration (n = 31, 57%). Surgery was indicated for 40 patients (74%), but only 27 (50%) were operated on, mainly due to their frailty. Among the 17 deaths (32%), six (11%) happened during the first hospitalization for EE. A suppressive antibiotic treatment was initiated in 15 (29%) patients, mostly because of not performing surgery. During the 6-year study period an EE relapse occurred in three (6%) patients. Conclusions: EE is a worrying disease associated with a high risk of relapse and significant mortality. Suppressive antibiotic therapy could be a key treatment to limit the occurrence of relapses.

Clinical characteristics and outcomes of respiratory syncytial virus-associated ARF in immunocompetent patients: A seven-year experience at a tertiary hospital in France.

BACKGROUND: Respiratory syncytial virus (RSV) is widely recognized as a cause of acute respiratory failure in infants and immunocompromised patients. However, RSV can also contribute to acute respiratory failure in adults, particularly among the elderly population. The objective of this study was to analyze the clinical characteristics and outcomes of immunocompetent adults hospitalized for RSV infection. METHODS: This retrospective study included all immunocompetent adult patients consecutively admitted to a tertiary care hospital with RSV-related acute respiratory failure over a seven-year period (2016-2023). Diagnosis of RSV infection was made through nasal swabs or pulmonary samples, with multiplex reverse transcription polymerase chain reaction (RT-PCR). Patients were eligible for inclusion if they required supplemental oxygen therapy for at least 48 h. RESULTS: One hundred and four patients met the inclusion criteria. Median age [IQR] was 77 years [67-85]. Ninety-seven patients had at least one comorbidity (97/104, 93%). At the time of RSV diagnosis, 67 patients (67/104, 64%) experienced acute decompensation of a pre-existing chronic comorbidity. Antibiotics were started in 80% (77/104) of patients; however, only 16 patients had a confirmed diagnosis of bacterial superinfection. Twenty-six patients needed ventilatory support (26/104, 25%) and 21 were admitted to the intensive care unit (21/104, 20%). The median duration of oxygen therapy [IQR] was 6 days [3-9], while the median hospital length of stay [IQR] was 11 days [6-15]. The overall mortality rate within 1 month of hospital admission was 13% (14/104). The sole variables associated with one-month mortality were age and maximum oxygen flow during hospitalization. CONCLUSION: RSV-associated acute respiratory failure affected elderly individuals with multiple comorbidities and was associated with prolonged hospitalization and a high mortality rate.

Investigating infectious outcomes in adult patients undergoing solid organ transplantation: A retrospective single-center experience, Paris, France.

OBJECTIVES: This study described the demographic characteristics, clinical presentation, treatment, and outcomes of solid organ transplant recipients who were admitted to our center for infection. It also determined factors associated with a poor outcome, and compares early and late period infections. METHODS: In this retrospective observational study, conducted at a tertiary care center in France between October 2017 and March 2019, infectious outcomes of patients with solid organ transplant where studied. RESULTS: A total of 104 patients were included with 158 hospitalizations for infection. Among these 104 patients, 71 (68%) were men. The median age was 59 years old. The most common symptoms on admission were fever (66%) and chills (31%). Lower respiratory tract infections were the most common diagnosis (71/158 hospitalizations). Urinary tract infections were frequently seen in kidney transplant recipients (25/60 hospitalizations). One or more infectious agents were isolated for 113 hospitalizations (72%): 70 bacteria, 36 viruses and 10 fungi, with predominance of gram-negative bacilli (53 cases) of which 13 were multidrug-resistant. The most frequently used antibiotics were third generation cephalosporins (40 cases), followed by piperacillin-tazobactam (26 cases). We note that 25 infections (16%) occurred during the first 6 months (early post-transplant period). Patients admitted during the early post-transplant period were more often on immunosuppressive treatment with prednisone (25/25 VS 106/133) (p = 0.01), mycophenolic acid (22/25 VS 86/133) (p = 0.03), presented for an urinary tract infection (10/25 VS 25/133) (p = 0.04) or a bacterial infection (17/25 VS 53/133) (p = 0.01). Patients with later infection had more comorbidities (57/83 VS 9/21) (p = 0.03), cancer (19/83 VS 0/21) (p = 0.04) or were on treatment with everolimus (46/133 VS 0/25) (p = 0.001). During 31 hospitalizations (20%), patients presented with a serious infection requiring intensive care (n = 26; 16%) or leading to death (n = 7; 4%). Bacteremia, pulmonary and cardiac complications were the main risk factors associated with poor outcome. CONCLUSION: Infections pose a significant challenge in the care of solid organ transplant patients, particularly those with comorbidities and intensive immunosuppression. This underscores the crucial importance of continuous surveillance and epidemiologic monitoring within this patient population.

Contributions and challenges of community pharmacists during the COVID-19 pandemic: a qualitative study.

BACKGROUND: Healthcare services across the world have been deeply impacted by the COVID-19 pandemic. In primary care, community pharmacists have had an important role in the frontline healthcare response to the pandemic. OBJECTIVES: This study aimed to explore the experiences, contributions and perceived challenges of community pharmacists regarding the provision of healthcare services during the COVID-19 pandemic. METHODS: Semi-structured qualitative interviews were conducted with community pharmacists in France. Participants were recruited through a professional organization of pharmacists combined with a snowballing technique. Interviews were transcribed and then analyzed using thematic analysis. RESULTS: A total of 16 community pharmacists participated in the interviews. Study participants described providing a range of novel services in response to the pandemic on top of continuing their usual services. All participants described providing preventative services to reduce and mitigate the spread of SARS-CoV-2, such as education on hygiene and social distancing, delivery of face masks and hand sanitizer and adjusting pharmacy premises. Most respondents also described being involved in SARS-CoV-2 detection through screening and performing antigen testing in pharmacies. Participants reported being actively involved in COVID-19 vaccination by educating the general public about vaccines, facilitating their distribution to general practitioners as well as administering vaccines. Over half the respondents described rapidly changing guidelines and service users' anxiety as challenges to the provision of healthcare services during the pandemic. CONCLUSIONS: This study suggests that community pharmacists have significantly contributed to the response to the COVID-19 pandemic by ensuring continuity of pharmaceutical services and providing novel screening, testing and vaccination services. Their roles and responsibilities during the COVID-19 health crisis indicate that they can play an important role in the management of emerging infectious diseases.

Congenital Leishmaniasis in a Newborn Infant Whose Mother was Coinfected With Leishmaniasis and HIV.

In utero transmission of Leishmania infantum is the putative mechanism of congenital leishmaniasis. However, this hypothesis is based on limited research. In addition, the consequences for infant newborn development remain to be clarified by additional data. We report here the occurrence, specific management, and monitoring of congenital leishmaniasis in a newborn infant whose mother was coinfected with leishmaniasis and human immunodeficiency virus; transplacental transmission, confirmed by overt clinical disease at birth, was documented, which provides, to our knowledge, the first evidence of hepatic and neurologic impairment in an infant with congenital visceral leishmaniasis.

SARS-COV2 infection in 30 HIV-infected patients followed-up in a French University Hospital.

INTRODUCTION: An acute respiratory disease caused by a novel coronavirus (SARSCOV2) is spreading from China since January 2020. Surprisingly, few cases of Covid-19 have been reported in people living with HIV (PLWHIV). METHODS: Here we present a series of 30 PLWHIV diagnosed for SARS-COV2 infection. The principal outcome was to describe clinical characteristics of this population. RESULTS: Eighteen (60%) patients were men, 10/30 (33,3%) women and 2/30 (6,7%) transgender women. Median age was 53,7 years (range 30-80 years) and 23/30 patients (76,7%) were born in a foreign country (out of France). The most common comorbidities were cardiovascular disease (11/30, 36,7%), hypertension (11/30, 36,7%), diabetes (9/30,30%) obesity (7/30, 23%) and chronic renal disease (5/30, 16,7%). Twenty (66,7%) patients presented overweight. Five patients (16,7%) had a Charlson comorbidity (Quan et al., 2011) score ≥3. Twenty-seven (90%) patients were virologically suppressed.CD4 count was >500cell/mm 3 in 23/30 (76,6%) patients. An antiviral treatment for SARS-COV2 was administered, in addition to HIV treatment, in 5/30 patients (16,3%). Twenty-four patients (80%) recovered from covid-19, 3/30 (10%) required invasive mechanical ventilation, 2/30 (6,7%) patients died and 4/30 (13,3%) patients were still hospitalized. CONCLUSIONS: Most of the patients were virologically suppressed with CD4>500 mm3. Risk factors were the same as those described in other SARS-COV2 series, suggesting that HIV infection is probably not an independent risk factor for covid-19.