Deep cutaneous mycoses in kidney transplant recipients: Diagnostic and therapeutic challenges.

Deep cutaneous mycoses (DCMs) are rare infections that extend throughout the dermis and subcutis, often occurring after inoculation with pathogenic fungi. Trends toward a growing incidence have been observed that may be partially related to an increasing population of solid organ transplant patients. The aim of this study is to describe the diagnostics and the outcomes of DCM among kidney transplant recipients so as to optimize their management. We performed a retrospective review of cases of DCM occurring among kidney transplant recipients in our institution over 12 years. Twenty cases were included. Lesions were only located on the limbs and presented mainly as single (10/20, 50%) nodular lesions (15/20, 75%), with a mean size of 3 cm. Direct mycological examination was positive for 17 patients (17/20, 85%) and the cultures were consistently positive. Thirteen different fungal species were observed, including phaehyphomycetes (n = 8), hyalohyphomycetes (n = 3), dermatophytes (n = 1), and mucorale (n = 1). The (1-3) beta-D-glucan antigen (BDG) was also consistently detected in the serum (20/20, 100%). Systematic imaging did not reveal any distant infectious lesions, but locoregional extension was present in 11 patients (11/14, 79%). Nineteen patients received antifungal treatment (19/20, 95%) for a median duration of 3 months, with surgery for 10 (10/20, 50%). There is a great diversity of fungal species responsible for DCMs in kidney transplant recipients. The mycological documentation is necessary to adapt the antifungal treatment according to the sensitivity of the species. Serum BDG positivity is a potentially reliable and useful tool for diagnosis and follow-up.

Prevention and management of infectious and tropical diseases in kidney transplant recipients residing in European outermost and overseas territories.

BACKGROUND: The European Union encompasses 30 outermost and overseas countries and territories (OCTs). Despite a recent increasing activity of renal transplantation in these territories, many patients still undergo transplantation in continental Europe, with follow-up care coordinated between health professionals from both their transplant center and their home region. Each territory has its unique infectious epidemiology which must be known to ensure appropriate care for kidney transplant recipients (KTRs). AIMS: This paper proposes a pragmatic approach to optimize pre-transplant check-up and to provide an overview of the specific epidemiological features of each region. It offers practical algorithms to help practitioners in managing infected KTR living in these territories. This work advocates for increased collaborative research among European OCTs.

Initial empirical antibiotic therapy in kidney transplant recipients with pyelonephritis: A global survey of current practice and opinions across 19 countries on six continents.

BACKGROUND: Despite the burden of pyelonephritis after kidney transplantation, there is no consensus on initial empirical antibiotic management. METHODS: We surveyed clinicians throughout the world on their practice and opinions about the initial empirical therapy of post-transplant pyelonephritis, using clinical vignettes. A panel of experts from 19 countries on six continents designed this survey, and invited 2145 clinicians to participate. RESULTS: A total of 721 clinicians completed the survey (response rate: 34%). In the hypothetical case of a kidney transplant recipient admitted with pyelonephritis but not requiring intensive care, most respondents reported initiating either a 3rd-generation cephalosporin (37%) or piperacillin-tazobactam (21%) monotherapy. Several patient-level factors dictated the selection of broader-spectrum antibiotics, including having a recent urine culture showing growth of a resistant organism (85% for extended-spectrum ß-lactamase-producing organisms, 90% for carbapenemase-producing organisms, and 94% for Pseudomonas aeruginosa). Respondents attributed high importance to the appropriateness of empirical therapy, which 87% judged important to prevent mortality. Significant practice and opinion variations were observed between and within countries. CONCLUSION: High-quality studies are needed to guide the empirical management of post-transplant pyelonephritis. In particular, whether prior urine culture results should systematically be reviewed and considered remains to be determined. Studies are also needed to clarify the relationship between the appropriateness of initial empirical therapy and outcomes of post-transplant pyelonephritis.

Conversion From Intravenous In-Hospital Belatacept Injection to Subcutaneous Abatacept Injection in Kidney Transplant Recipients During the First COVID-19 Stay-at-Home Order in France.

The first COVID-19 stay-at-home order came into effect in France on 17 March 2020. Immunocompromised patients were asked to isolate themselves, and outpatient clinic visits were dramatically reduced. In order to avoid visits to the hospital by belatacept-treated kidney transplant recipients (KTRs) during the initial period of the pandemic, we promptly converted 176 KTRs at two French transplant centers from once-monthly 5 mg/kg in-hospital belatacept infusion to once-weekly 125 mg subcutaneous abatacept injection. At the end of follow-up (3 months), 171 (97.16%) KTRs survived with a functioning graft, 2 (1.14%) had died, and 3 (1.70%) had experienced graft loss. Two patients (1.1%) experienced acute T cell-mediated rejection. Nineteen patients (10.80%) discontinued abatacept; 47% of the KTRs found the use of abatacept less restrictive than belatacept, and 38% would have preferred to continue abatacept. Mean eGFR remained stable compared to baseline. Seven patients (3.9%) had COVID-19; among these, two developed severe symptoms but survived. Only one patient had a de novo DSA. Side effects of abatacept injection were uncommon and non-severe. Our study reports for the first time in a large cohort that once-weekly injection of abatacept appears to be feasible and safe in KTRs previously treated with belatacept.

Severe relapse of SARS-CoV-2 infection in a kidney transplant recipient with negative nasopharyngeal SARS-CoV-2 RT-PCR after rituximab.

Immunocompromised patients may experience prolonged viral shedding after their initial SARS-CoV-2 infection, however, symptomatic relapses after remission currently remain rare. We herein describe a severe COVID-19 relapse case of a kidney transplant recipient (KTR) following rituximab therapy, 3 months after a moderate COVID-19 infection, despite viral clearance after recovery of the first episode. During the clinical relapse, the diagnosis was established on a broncho-alveolar lavage specimen (BAL) by RT-PCR. The infectivity of the BAL sample was confirmed on a cell culture assay. Whole genome sequencing confirmed the presence of an identical stain (Clade 20A). However, it had an acquired G142D mutation and a larger deletion of 3-amino-acids at position 143-145. These mutations located within the N-terminal domain are suggested to play a role in viral entry. The diagnosis of a COVID-19 relapse should be considered in the setting of unexplained persistent fever and/or respiratory symptoms in KTRs (especially for those after rituximab therapy), even in patients with previous negative naso-pharyngeal SARS-CoV-2 PCR.

Increased incidence and unusual presentations of CMV disease in kidney transplant recipients after conversion to belatacept.

Belatacept may increase cytomegalovirus (CMV) disease risk after conversion from CNI-based therapy. We analyzed CMV disease characteristics after belatacept conversion. Propensity score matching was used to compare CMV disease incidence in belatacept- and CNI-treated kidney transplant recipients (KTRs). CMV disease characteristics and risk factors under belatacept were analyzed. In total, 223 KTRs (median age [IQR] 59.2 years [45.4-68.5]) were converted to belatacept (median of 11.5 months [2.5-37.0] post-transplantation); 40/223 (17.9%) developed CMV disease. Independent risk factors included increased age (p = .0164), D+/R- CMV serostatus (p = .0220), and low eGFR at conversion (p = .0355). Among 181 belatacept-treated patients matched to 181 controls, 32/181 (17.7%) experienced CMV disease (vs. 5/181 controls [2.8%]). CMV disease cumulative incidences were 6.33 and 0.91/100 person-years (p-y) in belatacept and control groups, respectively. CMV disease risk was particularly high in elderly patients (converted >70 years) and those with eGFR <30 ml/min; cumulative incidences were 18.4 and 5.2/100 p-y, respectively. CMV diseases under belatacept were atypical, with late-onset disease (24/40 patients [60%]), high CMV seropositivity (27/40, 67%), increased severe and tissue-invasive disease rates (gastrointestinal involvement in 32/40 [80%]) and life-threatening diseases (4/40 [10%]). These findings should stimulate further research to secure the use of belatacept as a valuable rescue therapy in KTRs.

Weak antibody response to three doses of mRNA vaccine in kidney transplant recipients treated with belatacept.

Poor responses to mRNA COVID-19 vaccine have been reported after 2 vaccine injections in kidney transplant recipients (KTRs) treated with belatacept. We analyzed the humoral response in belatacept-treated KTRs without a history of SARS-CoV-2 infection who received three injections of BNT162b2-mRNA COVID-19 vaccine. We also investigated vaccine immunogenicity in belatacept-treated KTRs with prior COVID-19 and characterized symptomatic COVID-19 infections after the vaccine in belatacept-treated KTRs. Among the 62 belatacept-treated KTRs (36 [58%] males), the median age (63.5 years IQR [51-72]), without COVID-19 history, only four patients (6.4%) developed anti-SARS-CoV-2 IgG with low antibody titers (median 209, IQR [20-409] AU/ml). 71% were treated with mycophenolic acid and 100% with steroids in association with belatacept. In contrast, in all the 5 KTRs with prior COVID-19 history, mRNA vaccine induced a strong antibody response with high antibody titers (median 10 769 AU/ml, IQR [6410-20 069]) after two injections. Seroprevalence after three-vaccine doses in 35 non-belatacept-treated KTRs was 37.1%. Twelve KTRs developed symptomatic COVID-19 after vaccination, including severe forms (50% of mortality). Breakthrough COVID-19 occurred in 5% of fully vaccinated patients. Administration of a third dose of BNT162b2 mRNA COVID-19 vaccine did not improve immunogenicity in KTRs treated with belatacept without prior COVID-19. Other strategies aiming to improve patient protection are needed.

COVID-19 severity in kidney transplant recipients is similar to nontransplant patients with similar comorbidities.

Higher rates of severe COVID-19 have been reported in kidney transplant recipients (KTRs) compared to nontransplant patients. We aimed to determine if poorer outcomes were specifically related to chronic immunosuppression or underlying comorbidities. We used a 1:1 propensity score-matching method to compare survival and severe disease-free survival (defined as death and/or need for intensive care unit [ICU]) incidence in hospitalized KTRs and nontransplant control patients between February 26 and May 22, 2020. Patients were matched for risk factors of severe COVID-19: age, sex, body mass index, diabetes mellitus, preexisting cardiopathy, chronic lung disease, and basal renal function. We included 100 KTRs (median age [interquartile range (IQR)]) 64.7 years (55.3-73.1) in three French transplant centers. After a median follow-up of 13 days (7-30), transfer to ICU was required for 34 patients (34%) and death occurred in 26 patients (26%). Overall, 43 patients (43%) developed a severe disease during a median follow-up of 8.5 days (2-14). Propensity score matching to a large French cohort of 2017 patients hospitalized in 24 centers, revealed that survival was similar between KTRs and matched nontransplant patients with respective 30-day survival of 62.9% and 71% (p = .38) and severe disease-free 30-day survival of 50.6% and 47.5% (p = .91). These findings suggest that severity of COVID-19 in KTRs is related to their associated comorbidities and not to chronic immunosuppression.

Safety and efficacy of fumagillin for the treatment of intestinal microsporidiosis. A French prospective cohort study.

BACKGROUND: Intestinal microsporidiosis due to Enterocytozoon bieneusi is a cause of chronic diarrhoea in immunocompromised patients. Fumagillin has been approved in France for its treatment. OBJECTIVES: To investigate the efficacy and safety of fumagillin in a real-life setting. METHODS: As required by the French Medicine Agency, all patients receiving fumagillin were enrolled in a prospective study to evaluate its efficacy and safety. Stool examination with identification of E. bieneusi by PCR was performed at baseline, end of treatment and monthly thereafter for 6 months. Safety was monitored up to 6 months and full blood counts were monitored up to 42 days after treatment initiation. The primary endpoint was safety. Parasite clearance and relapses were secondary endpoints. RESULTS: From 2007 to 2018, 166 patients received fumagillin, including 6 children. Patients were transplant recipients (84%), HIV-infected patients (13%) or had another cause of immunosuppression (5%). Serious adverse events were reported in 41 patients (25%), mainly thrombocytopenia (15%) and neutropenia (5%), with two haemorrhagic events leading to one death. Severe thrombocytopenia (<50 G/L) developed in 50 patients (29.6%), neutropenia (<1 G/L) in 20 patients (11.8%) and severe anaemia (<8 g/dL) in 21 patients (12.4%). At the end of treatment, 94% of patients with available stool examination (n = 132) had no spores detected. Among 99 patients with available follow-up after the end of treatment, three parasite relapses were documented. CONCLUSIONS: E. bieneusi microsporidiosis was mainly diagnosed in transplant recipients. Fumagillin was associated with haematological toxicity but showed high efficacy with a low relapse rate.

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.

Epidemiological and clinical study of microsporidiosis in French kidney transplant recipients from 2005 to 2019: TRANS-SPORE registry.

INTRODUCTION: Microsporidiosis is an emerging opportunistic infection in renal transplantation (RT) recipients. We aimed to describe its clinical presentation and treatment. MATERIALS AND METHODS: We collected microsporidiosis cases identified in RT recipients between 2005 and 2019 in six French centers from the Crystal, Divat and Astre prospective databases. RESULTS: We report 68 RT recipients with intestinal microsporidiosis; the patients were predominantly male (61.8%), with a median age of 58 (46-69) years. Infection occurred at a median time of 3 (0.8-6.8) years posttransplant. Only Enterocytozoon bieneusi was found. Microsporidiosis manifested as diarrhea (98.5% of patients) with weight loss (72.1%) and acute renal injury (57.4%) without inflammatory biological parameters. The therapeutic approaches were no treatment (N = 9), reduction of the immunosuppressive regimen (∆IS) (N = 22), fumagillin alone (N = 9), fumagillin and ∆IS (N = 19), and albendazole or nitazoxanide and ∆IS (N = 9). Overall clinical remission was observed in 60 patients (88.2%). We observed no acute kidney rejection, renal transplant failure, or death within 6 months after microsporidiosis. CONCLUSION: E. bieneusi is an underestimated opportunistic pathogen in RT recipients, and infection with E. bieneusi leads to diarrhea with important dehydration and acute renal injury. The treatment is based on the reduction of the immunosuppressive regimen and the administration of fumagillin if available.

Ribavirin for Hepatitis E Virus Infection After Organ Transplantation: A Large European Retrospective Multicenter Study.

BACKGROUND: Ribavirin is currently recommended for treating chronic hepatitis E virus (HEV) infection. This retrospective European multicenter study aimed to assess the sustained virological response (SVR) in a large cohort of solid organ transplant (SOT) recipients with chronic HEV infection treated with ribavirin monotherapy (N = 255), to identify the predictive factors for SVR, and to evaluate the impact of HEV RNA mutations on virological response. METHODS: Data from 255 SOT recipients with chronic HEV infection from 30 European centers were analyzed. Ribavirin was given at the median dose of 600 (range, 29-1200) mg/day (mean, 8.6 ± 3.6 mg/kg/day) for a median duration of 3 (range, 0.25-18) months. RESULTS: After a first course of ribavirin, the SVR rate was 81.2%. It increased to 89.8% when some patients were offered a second course of ribavirin. An increased lymphocyte count at the initiation of therapy was a predictive factor for SVR, while poor hematological tolerance of ribavirin requiring its dose reduction (28%) and blood transfusion (15.7%) were associated with more relapse after ribavirin cessation. Pretreatment HEV polymerase mutations and de novo mutations under ribavirin did not have a negative impact on HEV clearance. Anemia was the main adverse event. CONCLUSIONS: This large-scale retrospective study confirms that ribavirin is highly efficient for treating chronic HEV infection in SOT recipients and shows that the predominant HEV RNA polymerase mutations found in this study do not affect the rate of HEV clearance.This large-scale retrospective study that included 255 solid organ transplant recipients confirms that ribavirin is highly efficient for treating chronic hepatitis E virus (HEV) infection and shows that HEV RNA polymerase mutations do not play a role in HEV clearance.

Asymptomatic bacteriuria and urinary tract infections in kidney transplant recipients.

PURPOSE OF REVIEW: Urinary tract infection (UTI) is the most common infection in kidney transplant recipients (KTRs). Several elements increase the risk of UTI and/or modify its clinical presentation among KTRs (e.g. immunosuppressive therapy, kidney allograft denervation, and use of urinary catheters). Also, KTRs may have UTIs because of difficult-to-identify and/or difficult-to-treat organisms. We provide an overview of the current knowledge regarding bacterial UTIs in KTRs, with a focus on recent findings. RECENT FINDINGS: There is accumulating evidence from clinical trials that screening for and treating asymptomatic bacteriuria is not beneficial in most KTRs (i.e. those who are ≥1-2 months posttransplant and do not have a urinary catheter). These patients have a point-prevalence of asymptomatic bacteriuria of only 3% and treating asymptomatic bacteriuria probably does not improve their outcomes. There is no clinical trial evidence to guide the management of symptomatic UTI in KTRs. Several important clinical questions remain unanswered, especially regarding the management of posttransplant pyelonephritis and the prevention of UTI in KTRs. SUMMARY: Despite its frequency and associated morbidity, UTI after kidney transplantation is an understudied infection. In an era of increasing antimicrobial resistance and limited resources, further research is needed to ensure optimal use of antimicrobials in KTRs with UTI.

Central nervous system complications in adult cystinosis patients.

Little is known about the long-term progression of adult nephropathic cystinosis patients. Our objective was to study central nervous system complications in cystinosis patients in the era of early cysteamine treatment, using advanced neuroimaging techniques. Neurological examination and multimodal brain 3 Tesla MRI were performed in 21 adult cystinosis patients, including 18 infantile cystinosis patients, 20 controls matched for age and renal function, and 12 healthy controls. Differences in gray matter volume and rest cerebral blood flow (CBF) using arterial spin labeling sequence were investigated using whole-brain voxel-based approach. Median age was 33.8 years (18.7-65.8). Seven patients (38.9%) presented with at least one central nervous system clinical abnormality: two (11.1%) with seizures, three (16.7%) with memory defects, five (27.8%) with cognitive defect, and one (5.5%) with stroke-like episode. These patients had a worse compliance to treatment (compliance score 2 vs 1, P = .03) and received a lower median cysteamine dose (0.9 g/day vs 2.1 g/day, P = .02). Among patients with infantile cystinosis, 13 (72.2%) showed cortical atrophy, which was absent in controls, but it was not correlated with symptoms. Cystinosis patients showed a significant gray matter decrease in the middle frontal gyrus compared with healthy controls and a significant negative correlation between the cystine blood level and rest CBF was observed in the right superior frontal gyrus, a region associated with executive function. Compliance to cysteamine treatment is a major concern in these adult patients and could have an impact on the development of neurological and cognitive complications.

Long-term outcome of methylmalonic aciduria after kidney, liver, or combined liver-kidney transplantation: The French experience.

Organ transplantation is discussed in methylmalonic aciduria (MMA) for renal failure, and poor quality of life and neurological outcome. We retrospectively evaluated 23 French MMA patients after kidney (KT), liver-kidney (LKT), and liver transplantation (LT). Two patients died, one after LKT, one of hepatoblastoma after KT. One graft was lost early after KT. Of 18 evaluable patients, 12 previously on dialysis, 8 underwent KT (mean 12.5 years), 8 LKT (mean 7 years), and 2 LT (7 and 2.5 years). At a median follow-up of 7.3 (KT), 2.3 (LKT), and 1.0 years (LT), no metabolic decompensation occurred except in 1 KT. Plasma and urine MMA levels dramatically decreased, more after LKT. Protein intake was increased more significantly after LKT than KT. Enteral nutrition was stopped in 7/8 LKT, 1/8 KT. Early complications were frequent after LKT. Neurological disorders occurred in four LKT, reversible in one. Five years after KT, four patients had renal failure. The metabolic outcomes were much better after LKT than KT. LKT in MMA is difficult but improves the quality of life. KT will be rarely indicated. We need more long-term data to indicate early LT, in the hope to delay renal failure and prevent neurodevelopmental complications.

Baseline graft status is a critical predictor of kidney graft failure after diarrhoea.

BACKGROUND: Diarrhoea is one of the most frequent complications after kidney transplantation (KT). Non-infectious diarrhoea has been associated with reduced graft survival in kidney transplant recipients. However, the risk factors for renal allograft loss following diarrhoea remain largely unknown. METHODS: Between January 2010 and August 2011, 195 consecutive KT recipients who underwent standardized microbiological workups for diarrhoea at a single centre were enrolled in this retrospective study. RESULTS: An enteric pathogen was readily identified in 91 patients (47%), while extensive microbiological investigations failed to find any pathogen in the other 104. Norovirus was the leading cause of diarrhoea in these patients, accounting for 30% of the total diarrhoea episodes. The baseline characteristics were remarkably similar between non-infectious and infectious diarrhoea patients, with the exception that the non-infectious group had significantly lower graft function before diarrhoea (P = 0.039). Infectious diarrhoea was associated with a longer duration of symptoms (P = 0.001) and higher rates of acute kidney injury (P = 0.029) and hospitalization (P < 0.001) than non-infectious diarrhoea. However, the non-infectious group had lower death-censored graft survival than the infectious group (Gehan-Wilcoxon test, P = 0.038). Multivariate analysis retained three independent predictors of graft failure after diarrhoea: diarrhoea occurring ≥5 years after KT [hazard ratio (HR) 4.82; P < 0.001], re-transplantation (HR 2.38; P = 0.001) and baseline estimated glomerular filtration rate <30 mL/min/1.73 m2 (HR 11.02; P < 0.001). CONCLUSION: Our study shows that pre-existing conditions (re-transplantation, chronic graft dysfunction and late occurrence) determine the primary functional long-term consequences of post-transplant diarrhoea.

No clinical benefit of rapid versus gradual tapering of immunosuppression to treat sustained BK virus viremia after kidney transplantation: a single-center experience.

Immunosuppressive drug tapering is currently the recommended treatment of BK virus (BKV) viremia after kidney transplantation; however, its exact modalities remain unclear. We retrospectively compared two consecutive strategies in 111 patients with sustained viremia: a gradual monitoring/tapering group (GT, n = 57) before 2012 and a rapid monitoring/tapering group (RT, n = 54) after 2012. At viremia diagnosis, the dose of mycophenolic acid (MPA) and tacrolimus levels (T0 ) were similar among patient groups. However, following onset, the dose of MPA at 1 month (P = 0.002) and 3 months (P = 0.005) and Tac T0 at 1 month (P = 0.030) and 3 months (P = 0.006) were lower in the RT group. This rapid minimization shortened BKV viremia (P < 0.001) and resulted in a better protection of graft function in patients with confirmed BKV-associated nephropathy (P = 0.033) without impacting 5-year graft survival. Survival without rejection was similar (P = 0.571), but the RT group had increased the development of de novo donor-specific antibodies (dnDSAs; P < 0.001). Multivariate Cox analysis identified basiliximab versus Thymoglobulin® induction [hazard ratio (HR), 3.090; P = 0.001] and the RT strategy (HR, 6.021; P = 0.002) as independently associated with dnDSAs. Compared to a gradual tapering, rapid immunosuppression tapering to treat sustained BKV viremia does not improve medium-term clinical outcome but increases the risk of developing dnDSAs.

Failure of voriconazole therapy due to acquired azole resistance in Aspergillus fumigatus in a kidney transplant recipient with chronic necrotizing aspergillosis.

Invasive aspergillosis (IA) affects the lungs and disseminates mostly in patients with neutropenia and/or patients who are receiving immunosuppressive and steroid therapies. Despite progress in the diagnosis of and therapy for IA, it is still characterized by a high mortality rate. Currently, voriconazole is considered as the standard therapy for IA. Over recent years, triazole-resistant Aspergillus fumigatus isolates have emerged in the environment due to the use of fungicidal agricultural products, with the risk of developing IA related to a resistant isolate. However, resistance may also develop in patients who are undergoing long-term triazole therapy, particularly in the setting of chronic forms of pulmonary aspergillosis. Herein we describe a kidney transplant recipient who failed to respond to voriconazole therapy due to acquired resistance secondary to the appearance of a de novo mutation (Y121F) in the cyp51A gene during chronic necrotizing pulmonary aspergillosis. The infecting isolate acquired voriconazole resistance in 8 months despite plasma concentrations within the recommended range of the drug, necessitating lobectomy in association with a new antifungal strategy consisting of liposomal amphotericin and caspofungin with a good outcome over 36 months.

Clinical Assessment of a Nocardia PCR-Based Assay for Diagnosis of Nocardiosis.

The diagnosis of nocardiosis, a severe opportunistic infection, is challenging. We assessed the specificity and sensitivity of a 16S rRNA Nocardia PCR-based assay performed on clinical samples. In this multicenter study (January 2014 to April 2015), patients who were admitted to three hospitals and had an underlying condition favoring nocardiosis, clinical and radiological signs consistent with nocardiosis, and a Nocardia PCR assay result for a clinical sample were included. Patients were classified as negative control (NC) (negative Nocardia culture results and proven alternative diagnosis or improvement at 6 months without anti-Nocardia treatment), positive control (PC) (positive Nocardia culture results), or probable nocardiosis (positive Nocardia PCR results, negative Nocardia culture results, and no alternative diagnosis). Sixty-eight patients were included; 47 were classified as NC, 8 as PC, and 13 as probable nocardiosis. PCR results were negative for 35/47 NC patients (74%). For the 12 NC patients with positive PCR results, the PCR assay had been performed with respiratory samples. These NC patients had chronic bronchopulmonary disease more frequently than did the NC patients with negative PCR results (8/12 patients [67%] versus 11/35 patients [31%]; P = 0.044). PCR results were positive for 7/8 PC patients (88%). There were 13 cases of probable nocardiosis, diagnosed solely using the PCR results; 9 of those patients (69%) had lung involvement (consolidation or nodule). Nocardia PCR testing had a specificity of 74% and a sensitivity of 88% for the diagnosis of nocardiosis. Nocardia PCR testing may be helpful for the diagnosis of nocardiosis in immunocompromised patients but interpretation of PCR results from respiratory samples is difficult, because the PCR assay may also detect colonization.

Diagnosis and management of asymptomatic bacteriuria in kidney transplant recipients: a survey of current practice in Europe.

Background: Asymptomatic bacteriuria is frequent in kidney transplant recipients (KTRs). However, there is no consensus on diagnosis or management. We conducted a European survey to explore current practice related to the diagnosis and management of asymptomatic bacteriuria in adult KTRs. Methods: A panel of experts from the European Renal Association-European Dialysis Transplant Association/Developing Education Science and Care for Renal Transplantation in European States working group and the European Study Group for Infections in Compromised Hosts of the European Society of Clinical Microbiology and Infectious Diseases designed this cross-sectional, questionnaire-based, self-administered survey. Invitations to participate were e-mailed to European physicians involved in the care of KTRs. Results: Two hundred and forty-four participants from 138 institutions in 25 countries answered the survey (response rate 30%). Most participants [72% (176/244)] said they always screen for asymptomatic bacteriuria in KTRs. Six per cent (15/240) reported never treating asymptomatic bacteriuria with antibiotics. When antimicrobial treatment was used, 24% of the participants (53/224) said they would start with empirical antibiotics. For an episode of asymptomatic bacteriuria caused by a fully susceptible microorganism and despite no contraindications, a majority of participants (121/223) said they would use a fluoroquinolone (n = 56), amoxicillin/clavulanic acid (n = 38) or oral cephalosporins (n = 27). Conclusions: Screening for and treating asymptomatic bacteriuria are common in KTRs despite uncertainties around the benefits and harms. In an era of antimicrobial resistance, further studies are needed to address the diagnosis and management of asymptomatic bacteriuria in these patients.