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The characteristics and outcomes of adult patients with respiratory syncytial virus (RSV) infection who require intensive care unit (ICU) admission are poorly defined. Although several studies in adults with RSV infection have been published in recent years, they did not focus specifically on critically ill patients. What are the characteristics and outcomes of adult ICU patients with RSV infection, and how do they compare to those of ICU patients with influenza infection? This retrospective, multicentre study in France and Belgium (17 sites) compared the characteristics and outcomes of adult ICU patients with RSV infection versus influenza infection between November 2011 and April 2018. Each patient with RSV infection was matched by institution and date of diagnosis with a patient with influenza infection. In-hospital mortality was compared between the two groups, with adjustment for prognostic factors in a multivariable model (sex, age, main underlying conditions, and concurrent bloodstream infection). Data from 618 patients (309 with RSV infection and 309 with influenza infection) were analysed. Patients with RSV infection were significantly more likely to have an underlying chronic respiratory condition (60.2% versus 40.1%, p<0.001) and to be immunocompromised (35% versus 26.2%, p=0.02) than patients with influenza infection. There were several differences in clinical signs and biological data at diagnosis between the groups. In-hospital mortality was not significantly different in the two groups (23.9% in the RSV group versus 25.6% in the influenza group, p=0.63), even after adjustment for prognostic factors in a multivariable model. Adult ICU patients with RSV infection differ from adult ICU patients with influenza in terms of comorbidities and characteristics at diagnosis. RSV infection was associated with high in-hospital mortality, approaching 25%. In multivariable analysis, RSV infection was associated with a similar odds of in-hospital death compared to i

Background: The characteristics and outcomes of adult patients with respiratory syncytial virus (RSV) infection who require ICU admission are poorly defined. Although several studies in adults with RSV infection have been published in recent years, they did not focus specifically on patients with critical illness. Research Question: What are the characteristics and outcomes of adult patients in the ICU with RSV infection and how do they compare with those of patients in the ICU with influenza infection? Study Design and Methods: This retrospective, multicenter study in France and Belgium (17 sites) compared the characteristics and outcomes of adult patients in the ICU with RSV infection vs those with influenza infection between November 2011 and April 2018. Each patient with RSV infection was matched by institution and date of diagnosis with a patient with influenza infection. In-hospital mortality was compared between the two groups, with adjustment for prognostic factors in a multivariate model (sex, age, main underlying conditions, and concurrent bloodstream infection). Results: Data from 618 patients (309 with RSV infection and 309 with influenza infection) were analyzed. Patients with RSV infection were significantly more likely to have an underlying chronic respiratory condition (60.2% vs 40.1%; P < .001) and to be immunocompromised (35% vs 26.2%; P = .02) than patients with influenza infection. Several differences in clinical signs and biological data at diagnosis were found between the groups. In-hospital mortality was not significantly different between the two groups (23.9% in the RSV group vs 25.6% in the influenza group; P = .63), even after adjustment for prognostic factors in a multivariate model. Interpretation: Adult patients in the ICU with RSV infection differ from adult patients in the ICU with influenza in terms of comorbidities and characteristics at diagnosis. RSV infection was associated with high in-hospital mortality, approaching 25%. In mul, SCOPUS: ar.j, info:eu-repo/semantics/published

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.

BACKGROUND: Little is known regarding the optimal management of nocardiosis among solid organ transplant (SOT) recipients. It is often suggested to avoid trimethoprim/sulfamethoxazole (TMP-SMX) monotherapy in heavily immunocompromised patients (such as SOT recipients) and/or in case of severe or disseminated nocardiosis. Our aim was to report our experience with TMP-SMX monotherapy in SOT recipients with nocardiosis. METHODS: Using data from a previously published European study, we assessed the incidence of adverse events in SOT recipients receiving TMP-SMX monotherapy and assessed its effectiveness. RESULTS: Thirty-one SOT recipients with nocardiosis were included, mostly kidney transplant recipients (20/31, 65%). Eleven (36%) had disseminated infection, and four (13%) had brain nocardiosis. Most patients had lung and/or pleural involvement (26/31, 84%). Daily dose of trimethoprim at initiation was 10 [6.4-14.8] mg/kg. The median estimated glomerular filtration rate at time of diagnosis of nocardiosis was 44 [30-62] ml/min/1.73 m². TMP-SMX was discontinued prematurely in one third of the patients (10/31, 32%, mostly for hematological toxicity [n = 3] or increased serum creatinine [n = 3]). Focusing on the 24 (77%) patients who completed at least 30 days of TMP-SMX monotherapy, 4 had late (>30 days) drug discontinuation, 1 experienced treatment failure, and 19 completed planned TMP-SMX monotherapy. Clinical outcome was favorable in these 19 patients, despite the fact that 8 (42%) had disseminated infection and 2 (11%) brain nocardiosis. Overall, all-cause 1-year mortality was 10% (3/31). CONCLUSIONS: TMP-SMX monotherapy appears to be effective for the treatment of most nocardiosis among SOT recipients. Interventional studies are needed to compare its safety and effectiveness with those of other regimens used to treat posttransplant nocardiosis.

Background Whether active therapy with beta-lactam/beta-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. Methods We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. Results Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count <= 500 cells/mu L at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. Conclusions Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).

SCOPUS: le.j, info:eu-repo/semantics/published

Background: Little is known regarding the optimal management of nocardiosis among solid organ transplant (SOT) recipients. It is often suggested to avoid trimethoprim/sulfamethoxazole (TMP-SMX) monotherapy in heavily immunocompromised patients (such as SOT recipients) and/or in case of severe or disseminated nocardiosis. Our aim was to report our experience with TMP-SMX monotherapy in SOT recipients with nocardiosis. Methods: Using data from a previously published European study, we assessed the incidence of adverse events in SOT recipients receiving TMP-SMX monotherapy and assessed its effectiveness. Results: Thirty-one SOT recipients with nocardiosis were included, mostly kidney transplant recipients (20/31, 65%). Eleven (36%) had disseminated infection, and four (13%) had brain nocardiosis. Most patients had lung and/or pleural involvement (26/31, 84%). Daily dose of trimethoprim at initiation was 10 [6.4-14.8] mg/kg. The median estimated glomerular filtration rate at time of diagnosis of nocardiosis was 44 [30-62] ml/min/1.73 m². TMP-SMX was discontinued prematurely in one third of the patients (10/31, 32%, mostly for hematological toxicity [n = 3] or increased serum creatinine [n = 3]). Focusing on the 24 (77%) patients who completed at least 30 days of TMP-SMX monotherapy, 4 had late (>30 days) drug discontinuation, 1 experienced treatment failure, and 19 completed planned TMP-SMX monotherapy. Clinical outcome was favorable in these 19 patients, despite the fact that 8 (42%) had disseminated infection and 2 (11%) brain nocardiosis. Overall, all-cause 1-year mortality was 10% (3/31). Conclusions: TMP-SMX monotherapy appears to be effective for the treatment of most nocardiosis among SOT recipients. Interventional studies are needed to compare its safety and effectiveness with those of other regimens used to treat posttransplant nocardiosis., SCOPUS: ar.j, DecretOANoAutActif, info:eu-repo/semantics/published

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.

Dear Editors, Nocardiosis is a rare but potentially severe bacterial opportunistic infection that may occur after solid organ transplantation (SOT), typically among thoracic transplant recipients and/or in recipients with a high degree of immunosuppression due to anti-rejection therapy [1]. However, nocardiosis may also occur late after transplantation among minimally immunosuppressed patients, suggesting that additional risk factors exist [1]. Recently, autoantibodies against granulocyte macrophage colony-stimulating factor (GM-CSF) have been identified among five previously healthy patients with disseminated nocardiosis [2]. These autoantibodies likely promote nocardiosis by reducing neutrophil and macrophage activation, phagocytosis, and bactericidal activity [2]. We hypothesized that anti-GM-CSF autoantibodies might be involved in post-SOT nocardiosis, especially in patients who apparently have a relatively low degree of immunosuppression. [...]

SCOPUS: le.j, DecretOANoAutActif, info:eu-repo/semantics/published

Many transplant physicians screen for and treat asymptomatic bacteriuria (ASB) during post-kidney-transplant surveillance. We investigated whether antibiotics are effective in reducing the occurrence of symptomatic urinary tract infection (UTI) in kidney transplant recipients with ASB., SCOPUS: ar.j, info:eu-repo/semantics/published

Background The incidence of nosocomial infections due to carbapenem-resistant Klebsiella pneumoniae is increasing worldwide. Whole-genome sequencing (WGS) can help elucidate the transmission route of nosocomial pathogens. Methods We combined WGS and epidemiological data to analyze an outbreak of New Delhi metallo-β-lactamase (NDM)-producing K. pneumoniae that occurred in 2 Belgian hospitals situated about 50 miles apart. We characterized 74 NDM-producing K. pneumoniae isolates (9 from hospital A, 24 from hospital B, and 41 contemporary isolates from 15 other Belgian hospitals) using pulsed-field gel electrophoresis and WGS. Results A K. pneumoniae sequence type 716 clone was identified as being responsible for the outbreak with all 9 strains from hospital A and 20 of 24 from hospital B sharing a unique pulsotype and being clustered together at WGS (compared with 1 of 41 isolates from other Belgian hospitals). We identified the outpatient clinic of hospital B as the probable bridging site between the hospitals after combining epidemiological, phylogenetic, and resistome data. We also identified the patient who probably caused the transmission. In fact, all but 1 strain from hospital A carried a Tn1331-like transposon, whereas none of the hospital B isolates did. The patient from hospital A who did not have the Tn1331-like transposon was treated at the outpatient clinic of hospital B on the same day as the first NDM-producing K. pneumoniae-positive patient from hospital B. Conclusions The results from our WGS-guided investigation highlight the importance of implementing adequate infection control measures in outpatient settings, especially when healthcare delivery moves from acute care facilities to outpatient clinics., SCOPUS: ar.j, info:eu-repo/semantics/published

Background Scedosporium species and Lomentospora prolificans (S/L) are the second most common causes of invasive mold infections following Aspergillus in lung transplant recipients. Methods We assessed the current practices on management of S/L colonization/infection of the lower respiratory tract before and after lung transplantation in a large number of lung transplant centers through an international practice survey from October 2016 to March 2017. Results A total of 51 respondents from 45 lung transplant centers (17 countries, 4 continents) answered the survey (response rate 58%). S/L colonization was estimated to be detected in candidates by 48% of centers. Only 18% of the centers used a specific medium to detect S/L colonization. Scedosporium spp. colonization was a contraindication to transplantation in 10% of centers whereas L prolificans was a contraindication in 31%; 22% of centers declared having had 1-5 recipients infected with S/L in the past 5 years. Conclusions This survey gives an overview of the current practices regarding S/L colonization and infection in lung transplant centers worldwide and underscores the need of S/L culture procedure standardization before implementing prospective studies.

INTRODUCTION : La nocardiose est une infection opportuniste grave qui touche de 0,04 à 3,5 % des greffés d’organe solide. Le cotrimoxazole (CMZ) en monothérapie semble être une option thérapeutique intéressante, compte tenu de son large spectre anti-Nocardia et de sa bonne diffusion tissulaire. L’objectif de notre étude était de décrire l’expérience clinique du CMZ en monothérapie chez les patients greffés d’organe solides présentant une infection à Nocardia. MATÉRIELS ET MÉTHODES : Nous avons analysé les données d’une étude multinationale rétrospective cas-témoins déjà publiée qui avait inclus 117 cas de nocardiose diagnostiquées entre 2000 et 2014. Tous les patients traités par CMZ dans les 15 jours suivant le diagnostic de nocardiose étaient éligibles, à condition d’avoir eu moins de 5 jours d’association avec d’autres antibiotiques (cohorte A). Parmi eux, la cohorte B comprenait tous les patients ayant reçu plus de 30 jours de CMZ en monothérapie. Pour chaque patient éligible, un questionnaire a été envoyé aux investigateurs pour recueillir des données supplémentaires. RÉSULTATS : Trente patients ont été inclus dans la cohorte A. La plupart présentait une nocardiose pulmonaire/pleurale (n = 25/30, 83 %). Onze patients (36 %) présentaient une nocardiose disséminée ou une atteinte cutanée et 4/30 (13 %) avaient une atteinte cérébrale. Les organes transplantés étaient majoritairement le rein (20/30, 66 %) et le cœur (5/30, 17 %). Nocardia farcinica (11/26, 42 %) était la plus fréquemment retrouvée. Parmi les 19 patients de la cohorte A pour lesquels le formulaire complémentaire a été retourné, : une insuffisance rénale aiguë ou une hyperkaliémie ont été observées chez 12/19 (63 %) et 7/19 (37 %) des patients. Dans 9/19 cas, le CMZ a été interrompu en raison d’une toxicité et un patient était décédé un jour après avoir commencé le CMZ. Chez un patient, le CMZ a été arrêté en raison d’un échec thérapeutique avec aggravation de l’atteinte pulmonaire après 4 mois de mo

Background: There is no consensus on the optimal management of immunosuppression during bacterial infections among solid organ transplant recipients. Methods: A multicenter, cross-sectional survey, of high-volume kidney and liver transplant centers across US and Europe. Structured questionnaires including six multiple-choice questions concerning the management of immunosuppression during infection were distributed among 381 centers. Results: A total of 124 (33%) centers fully completed the questionnaire: 67 liver, 57 kidney centers. Participating centers reported heterogenous approaches to immunosuppression management for all types of immunosuppressive drugs. Notably, kidney centers reported similar frequencies of either discontinuation (19%), continuation (19%), or dose reduction (17.5%) of antimetabolites; discontinuation only for life-threatening infection (17.5%) or case by case decisions (27%). Calcineurin inhibitors (CNI) management was heterogenous mostly among liver centers, with 8% discontinuing the CNI, 18% continuing, and 22% reducing dose. Heterogenous approaches to management of steroids and inhibitors of the mammalian target of rapamycin were also demonstrated. Conclusions: Immunosuppression management during bacterial infection is heterogenous in US and European centers. Immunosupression reduction (ISR) during infection is a common practice, though supported by limited evidence. Demonstrating high heterogeneity in the approach to ISR, together with the equivocal results of clinical studies, support consideration of an interventional clinical trial., SCOPUS: ar.j, DecretOANoAutActif, info:eu-repo/semantics/published

Dans le domaine des maladies infectieuses, l’épidémiologie clinique utilise les principes de l’épidémiologie pour répondre à des questions cliniques relatives aux infections survenant chez nos patients, constituant ainsi le socle de l’« evidence-based medicine ». L’épidémiologie moléculaire consiste quant à elle à étudier une infection en fonction des caractéristiques moléculaires du pathogène et/ou de l’hôte. Mes collègues et moi- même avons combiné épidémiologies clinique et moléculaire afin de clarifier la pertinence de notre pratique historique de dépistage et traitement de la bactériurie asymptomatique chez les patients transplantés de rein.Plusieurs travaux d’épidémiologie clinique ont été conduits. Dans une enquête de pratique européenne, nous avons constaté que la bactériurie asymptomatique était fréquemment dépistée et traitée par antibiotiques chez les transplantés de rein. Dans une revue systématique et méta-analyse Cochrane, nous n’avons cependant pas identifié de preuves en faveur du traitement antibiotique de la bactériurie asymptomatique chez ces patients. Les preuves disponibles étant peu nombreuses et de faible qualité, nous avons réalisé un essai clinique randomisé multicentrique comparant antibiotiques et abstention thérapeutique chez les transplantés de rein ayant un épisode de bactériurie asymptomatique après les deux premiers mois post-greffe. Dans cet essai, l’antibiothérapie n’a pas réduit significativement l’incidence des infections urinaires symptomatiques. Enfin, dans une étude transversale multicentrique, nous avons observé que la prévalence de la bactériurie asymptomatique était basse chez les transplantés de rein après les deux premiers mois post-greffe (environ 3%). L’ensemble de nos travaux plaide contre une politique systématique de dépistage et traitement de la bactériurie asymptomatique chez les patients transplantés de rein, après les deux premiers mois post-greffe.L’épidémiologie moléculaire a été utilisée afin d’identifier les c, In the field of infectious diseases, clinical epidemiology can be defined as the application of principles of epidemiology to conduct studies that answer clinical questions related to infections; it serves as the basic science of evidence-based medicine. Molecular epidemiology can be defined as the study of an infection in relation to the molecular characteristics of the causative microorganism and/or the host. My colleagues and I combined clinical and molecular epidemiology studies to determine the usefulness of a screen-and-treat strategy for asymptomatic bacteriuria among kidney transplant recipients.Clinical epidemiology was used to directly evaluate the practice of screening for and treating asymptomatic bacteriuria among kidney transplant recipients. In a survey of practice across Europe, we found that asymptomatic bacteriuria was frequently screened for and treated by kidney transplant physicians. However, a Cochrane systematic review and meta-analysis found no evidence to support the routine treatment of asymptomatic bacteriuria in kidney transplant recipients. Because data were scarce and of low-quality, we performed a pragmatic, multicenter randomized trial to compare antibiotic versus no antibiotic therapy in kidney transplant recipients who have asymptomatic bacteriuria beyond the second month post-transplant. In this trial, antibiotics did not significantly reduce the incidence of symptomatic urinary tract infection. Moreover, in a multicenter, cross-sectional study, the prevalence of asymptomatic bacteriuria was lower than expected in kidney transplant recipients. Specifically, only around 3% of screened kidney transplant recipients had asymptomatic bacteriuria beyond two months post-transplant. Taken together, our clinical epidemiology studies do not support the effectiveness of a screen-and-treat strategy for asymptomatic bacteriuria in kidney transplant recipients who are beyond two months post-transplant.Molecular epidemiology was used to identify, Doctorat en Sciences médicales (Médecine), info:eu-repo/semantics/nonPublished