Increased Risk of Invasive Aspergillosis in Immunocompromised Patients With Persistent SARS-CoV-2 Viral Shedding >8 Weeks, Retrospective Case-control Study.

Background: Immunocompromised patients now represent the population most at risk for severe coronavirus disease 2019. Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral shedding was reported in these patients ranging from several weeks up to 9 months. We conducted a bicentric retrospective case-control study to identify risk and prognostic factors associated with persistent viral shedding in immunocompromised patients. Material and Methods: Symptomatic immunocompromised adults with persistent SARS-CoV-2 viral shedding >8 weeks were retrospectively included between 1 March 2020 and 24 April 2022 at 2 university hospitals in Paris, France, and matched with a control group consisting of symptomatic immunocompromised patients without persistent viral shedding. Results: Twenty-nine immunocompromised patients with persistent viral shedding were compared with 40 controls. In multivariate analysis, fever and lymphocytopenia (<0.5 G/L) were associated with an increased risk of persistent viral shedding (odds ratio [OR]: 3.3; 95% confidence interval [CI], 1.01-11.09) P = .048 and OR: 4.3; 95% CI, 1.2-14.7; P = .019, respectively). Unvaccinated patients had a 6-fold increased risk of persistent viral shedding (OR, 6.6; 95% CI, 1.7-25.1; P = .006). Patients with persistent viral shedding were at risk of hospitalization (OR: 4.8; 95 CI, 1.5-15.6; P = .008), invasive aspergillosis (OR: 10.17; 95 CI, 1.15-89.8; P = .037) and death (log-rank test <0.01). Conclusions: Vaccine coverage was protective against SARS-CoV-2 persistent viral shedding in immunocompromised patients. This new group of immunocompromised patients with SARS-CoV-2 persistent viral shedding is at risk of developing invasive aspergillosis and death and should therefore be systematically screened for this fungal infection for as long as the viral shedding persists.

Advances in antibacterial treatment of adults with high-risk febrile neutropenia.

BACKGROUND: High-risk febrile neutropenia (HR-FN) is a life-threatening complication in patients with haematological malignancies or receiving myelosuppressive chemotherapy. Since the last international guidelines were published over 10 years ago, there have been major advances in the understanding and management of HR-FN, including on antibiotic pharmacokinetics and discontinuation/de-escalation strategies. OBJECTIVES: Summarizing major advances in the field of antibacterial therapy in patients with HR-FN: empirical therapy, pharmacokinetics of antibiotics and antibiotic stewardship. SOURCES: Narrative review based on literature review from PubMed. We focused on studies published between 2010 and 2023 about the pharmacokinetics of antimicrobials, management of antimicrobial administration, and discontinuation/de-escalation strategies. We did not address antimicrobial prophylaxis, viral or fungal infections. CONTENT: Several high-quality publications have highlighted important modifications of antibiotic pharmacokinetics in HR-FN, with standard dosages exposing patients to underdosing. These recent clinical and population pharmacokinetics studies help improve management protocols with optimized initial dosing and infusion rules for ß-lactams, vancomycin, daptomycin and amikacin; they highlight the potential benefits of therapeutic drug monitoring. A growing body of evidence also shows that antibiotic discontinuation/de-escalation strategies are beneficial for bacterial ecology and patients' outcome. We further discuss methods and limitations for implementation of such protocols in haematology. IMPLICATIONS: We highlight recent information about the management of antibacterial therapy in HR-FN that might be considered in updated guidelines for HR-FN management.

Outcome of patients with cystic fibrosis colonized by Scedosporium and Lomentospora species: A longitudinal cohort study.

Scedosporium and Lomentospora species rank second among the filamentous fungi colonizing the airways of cystic fibrosis (CF) patients. These fungi could be responsible for allergic bronchopulmonary mycosis (ABPM) and bronchitis before lung transplantation and invasive infections after. However, their role in CF lung disease is debated. This study aimed to identify clinical or environmental factors associated with an airway colonization by Scedosporium/Lomentospora species in patients with CF over a period of 7 years. A longitudinal cohort study was conducted from 2008 to 2014 in the CF reference centre in Lyon, France, to compare the characteristics of patients with Scedosporium/Lomentospora colonized and non-colonized patients. During the study period, 283 patients completed the clinical and microbiological follow-up. The analysis revealed that a higher number and duration of hospitalizations, an increased number of courses of parenteral antibiotic therapy, a history of ABPA, and treatment by itraconazole were significantly associated with an airway colonization by Scedosporium/Lomentospora species. The rate of decline of forced expiratory volume in the first second was not statistically different between colonized and non-colonized patients. This study provides evidence that patients colonized by Scedosporium/Lomentospora species require more medical care than non-colonized patients. Additional care could be in part explained by the management of Scedosporium/Lomentospora-related diseases such as ABPM or bronchitis. However, we did not demonstrate a faster rate of decline of respiratory function or body mass index in colonized patients, suggesting, as previously reported, that colonization of the airways by these fungi does not play a significant role in the progression of CF disease.

This prospective study did not demonstrate a faster rate of decline of respiratory function or body mass index in cystic fibrosis (CF) patients colonized by Scedosporium/Lomentospora species compared to non-colonized patients, suggesting that these fungi do not play a significant role in the progression of CF disease.

COVID-19 outbreak in vaccinated patients from a haemodialysis unit: antibody titres as a marker of protection from infection.

BACKGROUND: Patients on maintenance haemodialysis (HD) have an increased risk of severe coronavirus disease 2019 (COVID-19) and a reduced response to vaccines. Data are needed to identify immune correlates of protection in this population. METHODS: Following a COVID-19 outbreak among vaccinated patients in a HD unit, clinical data and serological response to BNT162b2 vaccine were retrospectively recorded. RESULTS: Among 53 patients present in the dialysis room, 14 were infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (COVID_Pos) and 39 were not. Compared with uninfected patients, COVID_Pos patients more frequently had additional causes of immunosuppression (50% versus 21%; P = .046) and were more often scheduled on the Monday-Wednesday-Friday (MWF) shift (86% versus 39%; P = .002). Moreover, COVID_Pos had lower anti-spike (S) immunoglobulin G (IgG) titres than uninfected patients {median 24 BAU/mL [interquartile range (IQR) 3-1163] versus 435 [99-2555]; P = .001} and lower neutralization titres [median 108 (IQR 17-224) versus 2483 (481-43 908); P = .007]. Anti-S and neutralization antibody titres are correlated (r = 0.92, P < .001). In multivariable analysis, an MWF schedule {odds ratio [OR] 10.74 [95% confidence interval (CI) 1.9-93.5], P = .014} and anti-S IgG titres 1 month before the outbreak [<205 BAU/mL: OR 0.046 (95% CI 0.002-0.29), P = .006] were independently associated with COVID-19 infection. None of the patients with anti-S IgG >284 BAU/mL got infected. Ten of 14 COVID_Pos patients were treated with casirivimab and imdevimab. No patient developed severe disease. CONCLUSIONS: Anti-S IgG titre measured prior to exposure correlates to protection from SARS-CoV-2 infection in HD patients. BNT162b2 vaccination alone or in combination with monoclonal antibodies prevented severe COVID-19.

Impact of public health measures on the post-COVID-19 respiratory syncytial virus epidemics in France.

Since the beginning of the COVID-19 pandemic, other respiratory illnesses decreased worldwide. This study described the consequences of public health measures on respiratory syncytial virus (RSV) severe infections in France, where an interseasonal resurgence of RSV occurred recently. All patients admitted to Necker Hospital (Paris) between August 2018 and April 2021 with a diagnosis of RSV-associated acute lung respiratory infection (ALRI) were enrolled. Characteristics of subjects with RSV-associated ALRI in 2020/2021 were compared to those infected during the two previous outbreaks. Overall, 664 inpatients were diagnosed with RSV-associated ALRI: 229, 183, and 252 during the 2018/2019, 2019/2020, and 2020/2021 outbreaks, respectively. During autumn 2020, a national lockdown began in France but schools remained open. A 3-month delayed RSV epidemic occurred at the end of this lockdown. Compared to previous outbreaks, the 2020/2021 epidemics involved more children aged 6 to 11 months (25.8% versus 13.1%, p < 0.0001), but less infants aged < 6 months (41.3% versus 56.6%, p < 0.0001) and less adults (0.0 versus 2.7%, p < 0.0001). Shorter length of stay at hospital, less frequent requirement of admission to intensive care unit, use of non-invasive ventilation, and/or high-flow nasal oxygen were observed in 2020/2021 than during previous epidemics (p < 0.0001). Delayed RSV outbreak was associated with more hospitalizations for ALRI, higher age of pediatric inpatients, but milder median clinical phenotype. Reinforced public health measures (even while keeping nurseries and schools open with mandatory face masks since six years of age) could impact, at least transiently, the burden of RSV-related hospitalizations.

Case Report: Cerebrovascular Events Associated With Bacterial and SARS-CoV-2 Infections in an Adolescent.

Neurologic manifestations associated with Covid-19 are increasingly reported, especially stroke and acute cerebrovascular events. Beyond cardiovascular risk factors associated with age, some young adults without medical or cardiovascular history had stroke as a presenting feature of Covid-19. Suggested stroke mechanisms in this setting are inflammatory storm, subsequent hypercoagulability, and vasculitis. To date, a handful of pediatric stroke cases associated with Covid-19 have been reported, either with a cardioembolic mechanism or a focal cerebral arteriopathy. We report the case of an adolescent who presented with febrile meningism and stupor. Clinical, biological, and radiological features favored the diagnosis of Lemierre syndrome (LS), with Fusobacterium necrophorum infection (sphenoid sinusitis and meningitis) and intracranial vasculitis. The patient had concurrent SARS-CoV-2 infection. Despite medical and surgical antimicrobial treatment, stroke prevention, and venous thrombosis prevention, he presented with severe cerebrovascular complications. Venous thrombosis and stroke were observed, with an extension of intracranial vasculitis, and lead to death. As both F. necrophorum and SARS-CoV-2 enhance inflammation, coagulation, and activate endothelial cells, we discuss how this coinfection may have potentiated and aggravated the usual course of LS. The potentiation by SARS-CoV-2 of vascular and thrombotic effects of a bacterial infection may represent an underreported cerebrovascular injury mechanism in Covid-19 patients. These findings emphasize the variety of mechanisms underlying stroke in this disease. Moreover, in the setting of SARS-CoV-2 pandemic, we discuss in what extent sanitary measures, namely, lockdown and fear to attend medical facilities, may have delayed diagnosis and influenced outcomes. This case also emphasizes the role of clinical assessment and the limits of telemedicine for acute neurological condition diagnosis.

Systematic Booster after Rabies Pre-Exposure Prophylaxis to Alleviate Rabies Antibody Monitoring in Individuals at Risk of Occupational Exposure.

Pre-exposure rabies prophylaxis (PrEP) is recommended for people at frequent or increased risk of professional exposure to lyssavirus (including rabies virus). PrEP provides protection against unrecognized exposure. After the primary vaccination, one's immune response against rabies may decline over time. We aimed to evaluate the immune response to rabies in individuals immunized for occupational reasons before and after a booster dose of the rabies vaccine. With this aim, we retrospectively documented factors associated with an inadequate response in individuals vaccinated for occupational purposes. Our findings analyzed data from 498 vaccinated individuals and found that 17.2% of participants had an inadequate antibody titration documented after their primary vaccination without the booster, while inadequate response after an additional booster of the vaccine was evidenced in 0.5% of tested participants. This study showed that a single booster dose of vaccine after PrEP conferred a high and long-term immune response in nearly all individuals except for rare, low responders. A systematic rabies booster after primary vaccination may result in alleviating the monitoring strategy of post-PrEP antibody titers among exposed professionals.

Stewardship program on carbapenem prescriptions in a tertiary hospital for adults and children in France: a cohort study.

Antimicrobial stewardship programs aim at reducing the overuse of broad-spectrum antibiotics such as carbapenems, but their impact remains unclear. We compared the use of carbapenems between paediatric and adult subjects admitted to a French tertiary hospital and described the intervention of an antibiotic stewardship team (AST). As part of AST routine activity, all adult and paediatric patients receiving carbapenems are identified in real time using a computer-generated alert system and reviewed by the AST. Data associated with carbapenem prescriptions were extracted for 2 years (2014-2015) and were compared between paediatric and adult wards. Prescription appropriateness (i.e. no clinically suitable narrower spectrum alternative to carbapenem for de-escalation) and AST intervention were analysed. In total, 775 carbapenem prescriptions for 291 children and 262 adults were included. Most patients (95%) had a comordity and 52% had known recent carriage of extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBLE). Most carbapenem prescriptions came from intensive care units (n = 269, 35%) and were initiated for urinary tract (n = 200, 27%), sepsis (n = 181, 25%), and lung (n = 153, 21%) infections. Carbapenems were initiated empirically in 537 (70%) cases, and an organism was isolated in 523 (67%) cases. Among the isolated organisms, 47% (n = 246) were ESBLE and 90% (n = 468) were susceptible to carbapenems, but an alternative existed in 61% (n = 320) of cases according to antibiotic susceptibility testing. Among prescriptions reviewed by the AST, 39% (n = 255) were considered non-appropriate and led to either antibiotic discontinuation (n = 47, 7%) or de-escalation (n = 208, 32%). Non-appropriate prescriptions were more frequent in paediatric wards (p = 0.01) and in microbiologically documented infections (p = 0.013), and less observed in immunocompromised patients (p = 0.009) or with a known ESBLE carriage (p < 0.001). Tailored stewardship programs are essential to better control carbapenem use and subsequent antimicrobial resistance.

Comparing Dynamics and Determinants of Severe Acute Respiratory Syndrome Coronavirus 2 Transmissions Among Healthcare Workers of Adult and Pediatric Settings in Central Paris.

BACKGROUND: Healthcare workers (HCWs) have paid a heavy toll during the coronavirus disease 2019 (COVID-19) outbreak. Routes of transmission remain to be fully understood. METHODS: This prospective study compared a 1500-bed adult and 600-bed pediatric setting of a tertiary-care university hospital located in central Paris. From 24 February until 10 April 2020, all symptomatic HCWs were screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a nasopharyngeal swab. HCWs screened positive were questioned on their profession, symptoms, and occupational and nonoccupational exposures to SARS-CoV-2. RESULTS: Among 1344 HCWs tested, 373 were positive (28%) and 336 (90%) corresponding questionnaires were completed. Three hospitalizations and no deaths were reported. Most HCWs (70%) had patient-facing occupational activities (22% in COVID-19 dedicated units). The total number of HCW cases peaked on 23 March, then decreased slowly, concomitantly with a continuous increase of compliance to preventive measures (including universal medical masking and personal protective equipment [PPE] for direct care to COVID-19 patients). Attack rates were of 3.2% and 2.3% in the adult and pediatric settings, respectively (P = .0022). In the adult setting, HCWs more frequently reported exposure to COVID-19 patients without PPE (25% vs 15%, P = .046). Report of contacts with children attending out-of-home care facilities dramatically decreased over the study period. CONCLUSIONS: Universal masking, reinforcement of hand hygiene, and PPE with medical masks for patients' care allowed protection of HCWs and containment of the outbreak. Residual transmissions were related to persistent exposures with undiagnosed patients or colleagues and not to contacts with children attending out-of-home care facilities.

Circumstances of Human-Bat interactions and risk of lyssavirus transmission in metropolitan France.

Since the elimination of dog and terrestrial wild animal rabies, bat exposures remain the only source of autochthonous lyssavirus transmission to humans in Western Europe. European bats have already been found infected with several lyssaviruses, and human-bat interactions represent a risk of viral transmission and fatal encephalitis for humans. In this study, we aim to better characterize exposures to bats in metropolitan France from 2003 to 2016 and to identify circumstances associated with exposures to lyssavirus-positive bats. Two complementary sources of data were analysed: 1/ data associated with bats responsible for human exposure received for Lyssavirus testing by the French National Reference Centre for Rabies (NRCR); and 2/ data pertaining to individuals seeking medical care through the French Anti-Rabies Clinics network after contact with a bat. From 2003 to 2016, 425 bats originating from metropolitan France were submitted to the NRCR and 16 (4%) were found positive with a lyssavirus (EBLV-1b was diagnosed in 9 bats, EBLV-1a in 6 and BBLV in one specimen). The two factors associated with bat positivity in our study were the female sex and the bat belonging to the E. serotinus species. During the same study period, 1718 individuals sought care at an Anti-Rabies Clinic after exposure to a bat resulting in an estimated incidence of human-bat interactions of 1.96 per 106 person-years. The two most frequent circumstances of exposure were handling or bites. Interactions mostly involved one adult human being and one live and non-sick-looking bat. Our study provides new insights about circumstances of human-bat interactions and may be helpful to target prevention interventions to improve the awareness of the population of the risk of lyssavirus transmission.

Epidemiology of rabies cases among international travellers, 2013-2019: A retrospective analysis of published reports.

BACKGROUND: Sixty cases of rabies in international travellers from 1990 to 2012 were previously reviewed. We present here an update of rabies cases in international travellers from 2013 to 2019. METHODS: We systematically reviewed the existing literature and collected 23 cases of rabies in individuals who crossed an international border between the time of infection and diagnosis, or who were infected following expatriation or migration. RESULTS: Most cases were in male adult travellers and diagnosed in Europe and the Middle East, with most exposures in Asia or in Africa. Migrants originating from rabies-endemic low-and-middle income countries and their descendants accounted for two thirds of cases. Other cases were in tourists, business travellers and expatriates. Median travel duration (excluding migration trip) was 60 days (range 7-240 days). Most cases were due to dog bites and most common clinical presentation was furious rabies. In most patients (74%), no rabies post-exposure prophylaxis (RPEP) was administered before rabies symptoms appeared. Other patients received incomplete RPEP series. CONCLUSION: Rabies should be suspected in any patient with encephalitis or paralysis who travelled to, or migrated from a rabies-endemic country. Comprehensive information about a rabies risk should be given to travellers to rabies endemic countries, notably migrants visiting friends and relatives.

Immune response to rabies post-exposure prophylaxis in patients with non-HIV secondary immunodeficiencies.

BACKGROUND: This study sought to determine the proportion of individuals with non-HIV secondary immunodeficiencies presenting inadequate antibody titers after rabies post-exposure prophylaxis (PEP) and to identify variables associated with inadequate response. METHODS: A retrospective review of the records of immunocompromised patients having received a full course of PEP after a rabies exposure and having been tested for post-PPE antibody titers in two French Antirabies Clinics, between 2013 and 2018, was conducted. Antibody titers < 0.5 EU/ml (ELISA) were classified as inadequate. RESULTS: A total of 28 individuals were included, 6 had inadequate post-PPE titers. None of the tested variable was independently associated with inadequate titers. CONCLUSIONS: Inadequate response was unpredictable and not explained either by the characteristics of patients or by the PEP regimen they received. These findings support the WHO recommendation to systematically assess post-PEP response in immunocompromised patients to detect non-responders, who might require an additional dose.

Devastating Gynecological Infections in Women with STAT3 Deficiency.

We provide the first description of a series of 9 severe gynecological infections (mastitis and pelvic cellulitis) occurring in the French national cohort of women with STAT3 deficiency. Each episode had unique features in terms of clinical presentation, microbial documentation, location, treatment duration, and related persistent esthetic damage.