Infection prevention for immunocompromised patients: A cross-translational multicentric survey of current organization in France.

OBJECTIVES: To evaluate current organization of infection prevention for immunocompromised patients (ICP) at a countrywide level. METHODS: Nationwide cross-sectional multicenter study based on an online survey disseminated in 2022 to physicians invested with preventive healthcare missions. RESULTS: A total of 341 physicians (96% graduates, 32% infectious disease specialists), participated in the survey, with a median age of 40 [35-51] years. On-site access to infection prevention consultations for ICP was reported by 30%, dedicated pre-travel consultations for ICPs by 29%, consultations for infection prevention in solid organ transplant candidates by 16% and return-to-work consultations for ICPs by 6%. Most participants (73%) were aware of nationwide vaccination guidelines for ICP, while 50% felt comfortable using them. Tools for infection prevention advice and ICP vaccination had been developed by 10%, while 89% would have appreciated access to tools developed by others. CONCLUSIONS: Infection prevention for ICPs remains neglected. Guidelines covering all fields of prevention for ICPs would be more than welcome.

Adults at risk of pneumococcal disease in France.

BACKGROUND: Immunocompromised patients and those with certain underlying medical conditions are at risk of pneumococcal disease, but in France their vaccine coverage is largely unknown. We aimed to assess the number of adult patients eligible for pneumococcal vaccination in France. METHODS: We conducted an annual cross-sectional study based on retrospective data from the French National Health Data System. Over 2014-2018, we included all adults continuously affiliated to the General health insurance scheme (covering 76% of the population), at risk of pneumococcal disease. Patients were identified with published or newly developed algorithms using diagnoses and reimbursements for hospital stays, medical procedures, and specific treatments, laboratory tests, or medical devices. RESULTS: On January 1, 2018, we identified 4,045,021 at-risk patients (11% increase since 2014). Mean age was 66.1years (55.1% were aged≥65), 51% were men, and 18% had at least two conditions. Of these, 3,634,594 had a chronic medical condition (including 2,617,921 patients treated for diabetes, 616,003 for chronic respiratory disease, 424,223 for heart failure, and 285,214 for chronic liver disease) and 570,035 were immunocompromised (of these, 191,527 were treated with immunosuppressive drugs or biotherapy, 152,255 with chemotherapy for cancer, and 100,604 for HIV). CONCLUSION: These published or newly developed algorithms - which can be used to address other public health issues - identified more than 4 million adults eligible for pneumococcal vaccination in the main health insurance scheme (10% of the studied adult population). This is a first step towards ensuring patients get vaccinated as part of their chronic condition management.

COVID-19 vaccines: Frequently asked questions and updated answers.

At the end of December 2019, China notified the World Health Organization about a viral pneumonia epidemic soon to be named COVID-19, of which the infectious agent, SARS-CoV-2, was rapidly identified. Less than one year later, published phase 3 clinical trials underlined the effectiveness of vaccines utilizing hitherto unusual technology consisting in injection of the messenger RNA (m-RNA) of a viral protein. In the meantime, numerous clinical trials had failed to identify a maximally effective antiviral treatment, and mass vaccination came to be considered as the strategy most likely to put an end to the pandemic. The objective of this text is to address and hopefully answer the questions being put forward by healthcare professionals on the different anti-SARS-CoV-2 vaccines as regards their development, their modes of action, their effectiveness, their limits, and their utilization in different situations; we are proposing a report on both today's state of knowledge, and the 14 February 2021 recommendations of the French health authorities.

Prolonged suppressive antibiotic therapy for prosthetic joint infection in the elderly: a national multicentre cohort study.

During prosthetic joint infection (PJI), optimal surgical management with exchange of the device is sometimes impossible, especially in the elderly population. Thus, prolonged suppressive antibiotic therapy (PSAT) is the only option to prevent acute sepsis, but little is known about this strategy. We aimed to describe the characteristics, outcome and tolerance of PSAT in elderly patients with PJI. We performed a national cross-sectional cohort study of patients >75 years old and treated with PSAT for PJI. We evaluated the occurrence of events, which were defined as: (i) local or systemic progression of the infection (failure), (ii) death and (iii) discontinuation or switch of PSAT. A total of 136 patients were included, with a median age of 83 years [interquartile range (IQR) 81-88]. The predominant pathogen involved was Staphylococcus (62.1%) (Staphylococcus aureus in 41.7%). A single antimicrobial drug was prescribed in 96 cases (70.6%). There were 46 (33.8%) patients with an event: 25 (18%) with an adverse drug reaction leading to definitive discontinuation or switch of PSAT, 8 (5.9%) with progression of sepsis and 13 died (9.6%). Among patients under follow-up, the survival rate without an event at 2 years was 61% [95% confidence interval (CI): 51;74]. In the multivariate Cox analysis, patients with higher World Health Organization (WHO) score had an increased risk of an event [hazard ratio (HR) = 1.5, p = 0.014], whereas patients treated with beta-lactams are associated with less risk of events occurring (HR = 0.5, p = 0.048). In our cohort, PSAT could be an effective and safe option for PJI in the elderly.

[Endobronchial ultrasonography (EBUS) for the internist]. / Écho-endoscopie bronchique (EBUS) pour l'interniste.

Endobronchial ultrasonography (EBUS) is a recent mini-invasive technique allowing transbronchial needle aspiration (TBNA) of mediastinal lymph nodes as well as peribronchial lesions. EBUS was initially developed for lung cancer mediastinal staging. Over the years, indications for EBUS have been progressively extended to the scope of inflammatory disorders, mediastinal lymphomas, and infectious diseases. Particularly in immunosuppressed patients, including HIV-infected patients, EBUS allows the diagnosis of several diseases that involve the mediastinum, avoiding invasive surgical explorations such as mediastinoscopy or thoracoscopy. This review aims at discussing the technical aspects, and specifies indications, results, and limits of EBUS for the internist.

Low immunogenicity of quadrivalent meningococcal vaccines in solid organ transplant recipients.

Immunization against meningococcal disease is recommended for solid organ transplant (SOT) recipients at high risk for meningococcal disease or travelling to an endemic country. However, the immunogenicity of meningococcal vaccines has not been studied in this population. We analyzed the immune response of quadrivalent (against Neisseria meningitidis serogroups A, C, Y, and W) polysaccharidic non-conjugate and conjugate meningococcal vaccines in kidney- and liver-transplant patients using bactericidal assays against the targeted serogroups. Upon vaccination with a non-conjugate (n = 5) or a conjugate vaccine (n = 10), respectively, 40% and 50% of patients were able to mount an immune response, achieving at least the threshold correlated with protection defined as human serum bactericidal antibody titers of ≥4. Responders showed only partial and low responses (titers ≤64), thus predicting a rapid decline in bactericidal response. Only 1 patient developed a booster response to preexisting immunity. Our data argue for the need of additional measures for SOT recipients, when they are at risk of meningococcal disease.

Survey of French physician practices in treatment and control of transmission of smear-positive tuberculosis.

OBJECTIVES: To evaluate isolation practices and management of sputum smear-positive tuberculosis (TB) in France. METHODS: A survey was conducted using a questionnaire e-mailed in 2011 and 2012 to physicians of the French Society of Infectious Diseases, the French Respiratory Society and the French National Society of Internal Medicine. RESULTS: Of 311 responders, a quarter stated they treated more than 25 TB cases per year. A total of 87.8% declared they routinely used a four-drug regimen in the initial intensive phase. Of the 311 physicians who responded, 31.9% removed isolation precautions after three negative acid-fast bacilli (AFB) sputum results, 19.0% after 15 days of treatment and 34.1% only in case of clinical improvement. According to 71% of the responders, discharge from hospital despite positive AFB sputum smear results was 'possible'. A routine AFB sputum smear was performed after 2 months of treatment by only 21% of the responders. CONCLUSION: Despite recent national guidelines, the management of isolation precautions for sputum smear-positive TB remains heterogeneous, and a significant proportion of physicians use a three-drug regimen. Further efforts should be made to implement TB guidelines, mainly by raising awareness through national scientific institutions, but also by obtaining better evidence.

Worsening pneumonitis due to a pharmacokinetic drug-drug interaction between everolimus and voriconazole in a renal transplant patient.

WHAT IS KNOWN AND OBJECTIVE: Azole antifungals, prescribed prophylactically to avoid severe infections in immunosuppressed organ transplant recipients, can interact with drug substrates of CYP3A4. We report serious adverse effects due to interaction between orally administered voriconazole and everolimus in a renal transplant recipient. CASE DESCRIPTION: Despite reduction of the dose of everolimus by a third, the blood trough concentration of everolimus increased considerably in a kidney transplant recipient upon oral administration of voriconazole. Everolimus was then discontinued. Pneumonia secondary to pulmonary aspergillosis worsened, possibly due to the excessive immunosuppression. WHAT IS NEW AND CONCLUSION: Orally administered voriconazole inhibits intestinal and hepatic cytochrome P450-3A4 activity and thereby reduces everolimus metabolism. An 80% decrease in dose or discontinuation of everolimus is required when concomitant voriconazole is introduced. Daily blood monitoring of everolimus is warranted until a steady state of concentrations is reached.

Factors influencing posaconazole plasmatic concentrations in patients presenting with acute myeloid leukemia.

PURPOSE: The effectiveness of posaconazole (PSZ) prophylaxis on invasive fungal infections, in patients presenting with acute myeloid leukemia (AML), seems to be correlated to its blood plasma concentration. Our goal was to identify the risk factors for underdosing. PATIENTS AND METHODS: We retrospectively reviewed the records of patients treated for AML treated with PSZ, during a 2-year period. Assays<500ng/mL were considered as under dosed. RESULTS: Fifty-nine assays (43 patients) were performed during induction (n=22) or consolidation (n=37) chemotherapy. PSZ treatment was initiated within a median of 3 days before neutropenia with a first assay performed at 8 days (3-28). The median PSZ blood plasma concentration was 375ng/mL (<200-1900). Forty-one (69%) treatment were maintained until the end of neutropenia. One patient presented with candidemia, 9 with possible invasive aspergillosis, without any significant association with underdosing. The univariate analysis showed that co-administration of proton pump inhibitors (PPIs) (P=0.01) and cause of hospitalization (induction chemotherapy vs consolidation, P=0.008) were associated with underdosing, contrary to feeding difficulties (P=0.07) and digestive disorders (P=0.5). The multivariate analysis confirmed the impact of PPI use (P=0.01) and the cause of hospitalization (P=0.003). CONCLUSION: This study highlights the major impact of PPI administration on PSZ blood plasma levels and stresses the risk of non-effective prophylaxis during induction treatment of AML.

Persistence of yellow fever vaccine-induced antibodies after solid organ transplantation.

Immunization using live attenuated vaccines represents a contra-indication after solid organ transplantation (SOT): consequently, transplant candidates planning to travel in countries where yellow fever is endemic should be vaccinated prior to transplantation. The persistence of yellow fever vaccine-induced antibodies after transplantation has not been studied yet. We measured yellow-fever neutralizing antibodies in 53 SOT recipients vaccinated prior to transplantation (including 29 kidney recipients and 18 liver recipients). All but one (98%) had protective titers of antibodies after a median duration of 3 years (min.: 0.8, max.: 21) after transplantation. The median antibody level was 40 U/L (interquartile range: 40-80). For the 46 patients with a known or estimated date of vaccination, yellow-fever antibodies were still detectable after a median time of 13 years (range: 2-32 years) post-immunization. Our data suggest there is long-term persistence of antibodies to yellow fever in SOT recipients who have been vaccinated prior to transplantation.

Generic drug prescriptions following hospital discharge: a prospective study in France.

AIMS: Systematic generic prescription at discharge could reduce confusion on drug-name usage, decrease commercial influence on medicine, and reduce drug-related expenditures. This study aimed to analyze generic drug prescriptions at discharge from hospital and to estimate the potential savings associated with a total substitution policy (substitution of every substitutable drug for its cheapest generic counterpart). METHODS: Drug prescriptions before admission and at discharge of all patients from three medical units of a university hospital were prospectively collected for five weeks without informing prescribers. RESULTS: Prescriptions from 85 patients were analyzed. On admission, 68 patients (80%) received 413 drugs; 141 were substitutable brand-name drugs and 23 (16%), which were directly prescribed as generics. At discharge, 488 drugs were prescribed to the 85 patients; 180 were substitutable drugs but only 5 (2.8%) were written as generics on prescription pads, a decrease of 78% (p<0.0001) compared to admission. In average, generics were 18% less expensive than brand-name drugs. Some common therapeutic classes offered even greater price difference, such as proton-pump inhibitors (42%), statins (32%), or antihypertensive agents (28%). Potential savings from a total substitution policy at discharge were estimated to €1512 per 1000 patients per week; for lifetime drugs, savings amounted to €18,960 per 1000 patients per year. CONCLUSIONS: Very few drugs are written as generics on medical forms at discharge in France. Hospital practitioners should be encouraged to prescribe generics, particularly in chronic diseases. A broad generic prescription policy at hospital discharge would result in substantial savings for health insurance.

[Vaccinations for the traveling adult solid organ transplant recipient (excluding hematopoietic stem cell transplant recipients)]. / Vaccinations du voyageur adulte transplanté d'organes (à l'exclusion des receveurs de cellules souches hématopoïétiques).

Progress in transplantation technique has offered a growing number of solid organ transplant recipients the opportunity to travel to tropical and low-income countries. The issue of vaccine-preventable diseases is a challenging question in immunocompromised patients including those with solid organ transplant. Since the response to vaccines is weakened in case of chronic organ failure, candidates should be vaccinated early in the course of the disease. Clinicians should implement a vaccinal strategy until the patient is scheduled for transplantation and monitor its efficacy by serological assays. Live attenuated vaccines (such as yellow fever, measles-mumps-rubella, or chicken pox) are contra-indicated in solid organ transplant recipients and, when indicated, should be administered prior to transplantation, particularly in foreign-born patients highly likely to visit friends and relatives in endemic areas. Vaccinations for transplant recipients considering international travel should be realized according to the risk of acquiring vaccine-preventable diseases but also on both tolerance and immune response which are affected by degree and duration of immunosuppression, comorbidities, and type of organ transplanted. Routine and specific vaccinations for solid organ transplant recipients, as well as travel-related vaccination (such as hepatitis A, typhoid, meningococcal meningitis, rabies, tick-born encephalitis, Japanese encephalitis, and cholera) should be considered during a specific pretravel medical consultation. However, vaccination should be avoided in the 6 months following transplantation when patients are usually receiving the highest doses of immunosuppressive drugs. In this comprehensive review, we provide vaccination schedules based on published studies and guidelines for vaccination of solid organ transplant recipients.

[The infection theory in atherosclerosis]. / Théorie infectieuse de l'athérosclérose.

Atherosclerosis displays all the features of a chronic inflammatory process. Aggressions that ignite and fuel atherosclerotic inflammation warrant keen attention. Infection is a potential clue, implying microbes with certain discrete characteristics: a wide epidemiologic distribution, a tropism for the arterial wall, and an aptitude for persistence, latency and recurrence. The infectious theory has built up from the pioneering observations of Fabricant et al. (1978) on the arterial lesions provoked by Marek's disease herpesvirus in chicken. So far one virus (cytomegalovirus) and two bacteria (Chlamydia pneumoniae and Helicobacter pylori) have been implicated in human atherosclerosis, based upon experimental, sero-epidemiologic, or pathologic evidence. None of these potential contributions has yet been established beyond reasonable doubt. However, grounded on the suspicion about C. pneumoniae, provocative therapeutic evidence has added recently: according to two pilot studies, treatment with macrolide antibiotics appear to improve the prognosis of coronary artery disease in both its chronic and acute forms. If ongoing larger-scale studies confirm these preliminary results, a novel era will open in our capacity for explaining, treating and preventing atherosclerosis. An infectious aetiology of atherosclerosis is now to be considered earnestly, and is already being submitted to more intensive clinical and experimental investigation.

[The bacteriology of tuberculosis and non-tuberculosis mycobacterial infections]. / Bactériologie de la tuberculose et des infections à mycobactéries non tuberculeuses.

Changing incidence and nature of mycobacterial infections subsequent to the historical regression of tuberculosis and the acquired human immunodeficiency syndrome (AIDS) epidemic, as well as the development of new technical tools for molecular biology, have profoundly modified the methods used for the bacteriological diagnosis of mycobacteria infections. Although microscopic search for acid-fast bacilli, culture and antibiotic resistance tests on Löwenstein-Jensen medium remain the reference methods, more rapid and sophisticated methods are now available. Culture on radiolabeled media using the Bactec system has shortened the delay for positive culture and interpretable antibiotic sensitivity tests. Molecular techniques allow: 1) rapid identification of the most frequently isolated mycobacteria strains, including the most frequent laboratory contaminant M. gordonae, with genome probes; 2) genome typing of M. tuberculosis strains to trace interhuman transmission, detect recurrence or exogenous reinfection or demonstrate laboratory contamination; 3) rapid detection of rifampicin resistance; and 4) direct detection of M. tuberculosis and M. avium in pathological specimens. The role of mycobacteria in the environment causing opportunistic infections, atypical mycobacteria or non-tuberculosis mycobacteria (NTM), particularly the aviaire complex, has grown considerably. Isolation and identification relies on methods used to detect bacilli as well as blood cultures and analysis of fecal matter. NTM are naturally resistant to most of the antituberculosis antibiotics but are sometimes sensitive to aminoglycosides, fluoroquinolones or new macrolides.