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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

Background During routine post-kidney transplant care, most European transplant physicians screen patients for asymptomatic bacteriuria. The usefulness of this strategy is debated. To make screening cost-effective, asymptomatic bacteriuria should be prevalent enough to justify the expense, and antibiotics should improve patient outcomes significantly if asymptomatic bacteriuria is detected. Regrettably, the prevalence of asymptomatic bacteriuria among kidney transplant recipients is not well defined. Methods To determine the prevalence of asymptomatic bacteriuria among kidney transplant recipients, we did a cross-sectional study among kidney transplant recipients undergoing routine surveillance in three outpatient transplant clinics in Belgium and France. We excluded patients who were in the first two months post-transplantation and/or had a urinary catheter. Asymptomatic participants who had a urine culture with one organism isolated at .105 CFU/mL were asked to provide a confirmatory urine specimen. Asymptomatic bacteriuria was defined per Infectious Diseases Society of America guidelines. Results We screened 500 consecutive kidney transplant recipients. Overall, the prevalence of asymptomatic bacteriuria was 3.4% (17/500 patients). It was similarly low among kidney transplant recipients who were between 2 and 12 months after transplantation (1.3%, 1/76 patients) and those who were farther after transplantation (3.8%, 16/424 patients: P = 0.49). Asymptomatic bacteriuria was significantly associated with female gender (risk ratio 3.7, 95% CI 1.3-10.3, p = 0.007) and older age (mean age: 61 ± 12 years [bacteriuric participants], versus 53 ± 15 years [non-bacteriuric participants], p = 0.03). One participant's colistin-resistant Escherichia coli isolate carried the globally disseminated mcr-1 gene. Conclusions Among kidney transplant recipients who are beyond the second month post-transplant, the prevalence of asymptomatic bacteriuria is low. Further studies are need, SCOPUS: ar.j, info:eu-repo/semantics/published

Urinary tract infection is the most common infection among kidney transplant recipients (KTRs). Many transplant physicians fear that host compromise will allow low-virulence strains to cause pyelonephritis in KTRs, so they often treat asymptomatic bacteriuria with antibiotics. Identification of the host/microbe factors that determine the clinical presentation (i.e. pyelonephritis versus asymptomatic bacteriuria) once an Escherichia coli strain enters a KTRs bladder could inform management decisions., info:eu-repo/semantics/published

Background Transplant recipients are at risk of pulmonary nocardiosis, a life-threatening opportunistic infection caused by Nocardia species. Given the limitations of conventional diagnostic techniques (i.e. microscopy and culture), a polymerase chain reaction (PCR)-based assay was developed to detect Nocardia spp. on clinical samples. While this test is increasingly being used by transplant physicians, its performance characteristics are not well documented. We evaluated the performance characteristics of this test on bronchoalveolar lavage (BAL) fluid samples from lung transplant recipients (LTRs). Methods We prospectively included all BAL samples from LTRs undergoing bronchoscopy at our institution between December 2016 and June 2017 (either surveillance or clinically-indicated bronchoscopies). Presence of microbial pathogens was assessed using techniques available locally (including microscopy and 10-day culture for Nocardia). BAL samples were also sent to the French Nocardiosis Observatory (Lyon, France) for the Nocardia PCR-based assay. Transplant physicians and patients were blinded to the Nocardia PCR results. Results We included 29 BAL samples from 21 patients (18 surveillance and 11 clinically-indicated bronchoscopies). Nocardiosis was not diagnosed in any of these patients by conventional techniques. However, Nocardia PCR was positive in five BAL samples from five of the patients (24%, 95% confidence interval: 11–45%); four were asymptomatic and undergoing surveillance bronchoscopy, and one was symptomatic and was later diagnosed with influenza virus infection. None of the five PCR-positive patients died or were diagnosed with nocardiosis during the median follow-up of 21 months after the index bronchoscopy (range: 20–23 months). Conclusions In this prospective study, Nocardia PCR was positive on BAL fluid from one fourth of the LTRs. Nocardia PCR-based assays should be used with caution on respiratory samples from LTRs because of the possible detection o, SCOPUS: ar.j, info:eu-repo/semantics/published

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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. We combined WGS and epidemiological data to analyze an outbreak of NDM-producing K. pneumoniae that occurred in two Belgian hospitals situated about 50 miles apart. We characterized 74 NDM-producing K. pneumoniae isolates [Hospital A (n=9); Hospital B (n=24) and 41 contemporary isolates from 15 other Belgian hospitals] using pulsed-field gel electrophoresis and WGS. A K. pneumoniae ST716 clone was identified as being responsible for the outbreak with 9/9 strains from Hospital A and 20/24 strains from Hospital B sharing a unique pulsotype and being clustered together on WGS (compared with 1/41 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 one 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. 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.

Nocardiosis is an opportunistic infection caused by Nocardia species (spp.), which are Gram-positive branching filamentous bacteria. In a recent issue of Biology of Blood and Marrow Transplantation, Molina et al. [1] studied the relationship between Pneumocystis jirovecii pneumonia (PJP) prophylaxis and Nocardia infections in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Molina et al. [1] performed a retrospective study of nocardiosis among HSCT recipients at the University of California, Los Angeles (UCLA), Medical Center between 2000 and 2017 [...]

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

Background: Asymptomatic bacteriuria, defined as bacteriuria without signs or symptoms of urinary tract infection (UTI), occurs in 17% to 51% of kidney transplant recipients and is thought to increase the risk for a subsequent UTI. No consensus exists on the role of antibiotics for asymptomatic bacteriuria in kidney transplantation. Objectives: To assess the benefits and harms of treating asymptomatic bacteriuria in kidney transplant recipients with antimicrobial agents to prevent symptomatic UTI, all-cause mortality and the indirect effects of UTI (acute rejection, graft loss, worsening of graft function). Search methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 1 September 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. Selection criteria: All randomised controlled trials (RCTs) and quasi-RCTs in any language assessing treatment of asymptomatic bacteriuria in kidney transplant recipients at any time-point after transplantation. Data collection and analysis: Two authors independently determined study eligibility, assessed quality and extracted data. Primary outcomes were incidence of symptomatic UTI and incidence of antimicrobial resistance. Other outcomes included incidences of all-cause mortality, graft loss, graft rejection, graft function, hospitalisation for UTI, adverse reactions to antimicrobial agents and relapse or persistence of asymptomatic bacteriuria. We expressed dichotomous outcomes as absolute risk difference (RD) or risk ratio (RR) with 95% confidence intervals (CI) and continuous data as mean differences (MD) with 95% CI. Data were pooled using the random effects model. Main results: We included two studies (212 participants) comparing antibiotics versus no treatment, SCOPUS: re.j, info:eu-repo/semantics/published

Objectives: To assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT). Methods: We performed a multinational case-control study that retrospectively recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy. Results: We identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p <0.001) within the 6 months prior to the onset of late IPA. After multivariate adjustment, previous occurrence of IRE (OR 19.26; 95% CI 2.07–179.46; p 0.009) was identified as an independent risk factor for late IPA. Conclusion: More than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND: Solid organ transplant (SOT) recipients are at risk of nocardiosis, a rare opportunistic bacterial infection, but prognosis and outcome of these patients are poorly defined. Our objectives were to identify factors associated with 1-year mortality after nocardiosis and describe the outcome of patients receiving short-course antibiotics (≤120 days). METHODS: We analyzed data from a multicenter European case-control study that included 117 SOT recipients with nocardiosis diagnosed between 2000 and 2014. Factors associated with 1-year all-cause mortality were identified using multivariable conditional logistic regression. RESULTS: One-year mortality was 10-fold higher in patients with nocardiosis (16.2%, 19/117) than in control transplant recipients (1.3%, 3/233, P < .001). A history of tumor (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.8), invasive fungal infection (OR, 1.3; 95% CI, 1.1-1.5), and donor age (OR, 1.0046; 95% CI, 1.0007-1.0083) were independently associated with 1-year mortality. Acute rejection in the year before nocardiosis was associated with improved survival (OR, 0.85; 95% CI, 0.73-0.98). Seventeen patients received short-course antibiotics (median duration 56 [24-120] days) with a 1-year success rate (cured and surviving) of 88% and a 5.9% risk of relapse (median follow-up 49 [6-136] months). CONCLUSIONS: One-year mortality was 10-fold higher in SOT patients with nocardiosis than in those without. Four factors, largely reflecting general medical condition rather than severity and/or management of nocardiosis, were independently associated with 1-year mortality. Patients who received short-course antibiotic treatment had good outcomes, suggesting that this may be a strategy for further study.

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

Cytomegalovirus (CMV) pneumonitis occurs frequently among solid organ transplant recipients and is classically associated with significant viral replication in both blood and bronchoalveolar lavage (BAL) samples. We present a case of a 64-year-old lung transplant recipient who presented with CMV pneumonitis that was diagnosed based on the association of viral inclusion in the BAL sample, rapid response to ganciclovir, and absence of other infectious etiology. Surprisingly, we observed very low or undetectable viral load both in blood and BAL samples. Diagnosis of CMV pneumonitis should rely on the association of clinical, pathological, radiological, and microbiological signs, while quantitative nucleic acid amplification testing should be interpreted with caution.

Nocardiosis is a rare, life-threatening opportunistic infection, affecting 0.04% to 3.5% of patients after solid organ transplant (SOT). The aim of this study was to identify risk factors for Nocardia infection after SOT and to describe the presentation of nocardiosis in these patients. We performed a retrospective case-control study of adult patients diagnosed with nocardiosis after SOT between 2000 and 2014 in 36 European (France, Belgium, Switzerland, the Netherlands, Spain) centers. Two control subjects per case were matched by institution, transplant date, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors for nocardiosis. One hundred and seventeen cases of nocardiosis and 234 control patients were included. Nocardiosis occurred at a median of 17.5 (range, 2-244) months after transplant. In multivariable analysis, high calcineurin inhibitor trough levels in the month before diagnosis (odds ratio [OR], 6.11; 95% confidence interval [CI], 2.58-14.51), use of tacrolimus (OR, 2.65; 95% CI, 1.17-6.00) and corticosteroid dose (OR, 1.12; 95% CI, 1.03-1.22) at the time of diagnosis, patient age (OR, 1.04; 95% CI, 1.02-1.07), and length of stay in the intensive care unit after SOT (OR, 1.04; 95% CI, 1.00-1.09) were independently associated with development of nocardiosis; low-dose cotrimoxazole prophylaxis was not found to prevent nocardiosis. Nocardia farcinica was more frequently associated with brain, skin, and subcutaneous tissue infections than were other Nocardia species. Among the 30 cases with central nervous system nocardiosis, 13 (43.3%) had no neurological symptoms. We identified 5 risk factors for nocardiosis after SOT. Low-dose cotrimoxazole was not found to prevent Nocardia infection. These findings may help improve management of transplant recipients.

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

The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy., 0, SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published

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

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case–control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09–90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08–10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04–339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63–456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group., 0, SCOPUS: ar.j, FLWIN, SCOPUS: ar.j, info:eu-repo/semantics/published

Cytomegalovirus (CMV) pneumonitis occurs frequently among solid organ transplant recipients and is classically associated with significant viral replication in both blood and bronchoalveolar lavage (BAL) samples. We present a case of a 64-year-old lung transplant recipient who presented with CMV pneumonitis that was diagnosed based on the association of viral inclusion in the BAL sample, rapid response to ganciclovir, and absence of other infectious etiology. Surprisingly, we observed very low or undetectable viral load both in blood and BAL samples. Diagnosis of CMV pneumonitis should rely on the association of clinical, pathological, radiological, and microbiological signs, while quantitative nucleic acid amplification testing should be interpreted with caution., SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published

Nocardiosis is a rare, life-threatening opportunistic infection, affecting 0.04% to 3.5% of patients after solid organ transplant (SOT). The aim of this study was to identify risk factors for Nocardia infection after SOT and to describe the presentation of nocardiosis in these patients., SCOPUS: ar.j, info:eu-repo/semantics/published

Background Therapeutic drug monitoring of mycophenolic acid (MPA) is usually performed with a limited sampling strategy (LSS), which relies on a limited number of blood samples and subsequent extrapolation of the global exposure to MPA. LSS is usually performed successfully with mycophenolate mofetil (MMF), but data on enteric-coated mycophenolate sodium (EC-MPS) are scarce. Here, we evaluated the feasibility of 6-h LSS therapeutic drug monitoring with EC-MPS compared with MMF monitoring among kidney transplant recipients. Methods Sixty-two patients who received EC-MPS during the first 6 months of transplantation were compared with a matched group of 64 MMF-treated kidney transplant recipients. The area under the curve (AUC) was computed by LSS using multiple concentration time points (0, 1, 2, 3 and 6 h post-dose) and a trapezoidal rule. Patients had MPA therapeutic drug monitoring performed on two occasions, one within 2 weeks and the second after 3-4 months of transplantation. Results EC-MPS monitoring and MMF therapeutic drug monitoring were not interpretable in 34.5% (n = 40/116) and 1.8% (n = 2/112) of patients, respectively {relative risk [RR] 19.3 [95% confidence interval (CI) 4.8-78.0]; P < 0.0001}. The main cause of abnormal EC-MPS therapeutic drug monitoring was delayed absorption of both the previous evening and the morning dose, resulting in MPA plasma levels before the next morning dose being higher than MPA plasma levels measured at 1, 2 and 3 h after taking EC-MPS. Cyclosporin in association with MMF significantly increased the risk of low AUC values (<30 mg h/L) in comparison with tacrolimus [55% (n = 11/20) and 10% (n = 9/88), respectively; RR 5.4 (95% CI 2.6-11.2); P < 0.0001]. Conclusions The risk of therapeutic drug monitoring failure with EC-MPS is >30% during the first 6 months of renal transplantation. Delayed pharmacokinetics was the main reason. In contrast, the risk of therapeutic drug monitoring failure was substantially lower with MMF., SCOPUS: ar.j, info:eu-repo/semantics/published

http://www.thelancet.com/protocol-reviews/14PRT-5447, info:eu-repo/semantics/published

Hyponatremia occurring as a result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common and potentially lethal complication in critically ill patients. Urea, by inducing renal water excretion and promoting sodium (Na) retention, has been well described as a treatment for chronic SIADH. However, there are limited data on its use for the treatment of SIADH as encountered in patients admitted to the intensive care unit (ICU). We assessed the effects of urea administration for treatment of SIADH in ICU patients., Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published