High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France

BACKGROUND: Influenza-like illness (ILI) may be caused by a variety of pathogens. Clinical observations are of little help to recognise myxovirus infection and implement appropriate prevention measures. The limited use of molecular tools underestimates the role of other common pathogens. OBJECTIVES: During the early weeks of the 2009-2010 flu pandemic, a clinical and virological survey was conducted in adult and paediatric patients with ILI referred to two French University hospitals in Paris and Tours. Aims were to investigate the different pathogens involved in ILI and describe the associated symptoms. METHODS: H1N1v pandemic influenza diagnosis was performed with real time RT-PCR assay. Other viral aetiologies were investigated by the molecular multiplex assay RespiFinder19®. Clinical data were collected prospectively by physicians using a standard questionnaire. RESULTS: From week 35 to 44, endonasal swabs were collected in 413 patients. Overall, 68 samples (16.5%) were positive for H1N1v. In 13 of them, other respiratory pathogens were also detected. Among H1N1v negative samples, 213 (61.9%) were positive for various respiratory agents, 190 in single infections and 23 in mixed infections. The most prevalent viruses in H1N1v negative single infections were rhinovirus (62.6%), followed by parainfluenza viruses (24.2%) and adenovirus (5.3%). 70.6% of H1N1v cases were identified in patients under 40 years and none after 65 years. There was no difference between clinical symptoms observed in patients infected with H1N1v or with other pathogens. CONCLUSION: Our results highlight the high frequency of non-influenza viruses involved in ILI during the pre-epidemic period of a flu alert and the lack of specific clinical signs associated with influenza infections. Rapid diagnostic screening of a large panel of respiratory pathogens may be critical to define and survey the epidemic situation and to provide critical information for patient management

Antibiotics for asymptomatic bacteriuria in kidney transplant recipients

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, and identified three on-going studies. Overall, incidence of symptomatic UTI varied between 19% and 31% in the groups not treated for asymptomatic bacteriuria. Antibiotic treatment had uncertain effects on preventing symptomatic UTI (2 studies, 200 participants: RR 0.86, 95% CI 0.51 to 1.45). Risk for selecting multidrug-resistant organisms was uncertain with antibiotic treatment (1 study, 112 participants: RR 1.21, 95% CI 0.60 to 2.41). Persistence of asymptomatic bacteriuria was high regardless of treatment. Antibiotics also have uncertain effects on other important patient and graft outcomes, for instance on all-cause mortality (1 study, 112 participants: RR 2.23, 95% CI 0.21 to 23.86), graft loss (1 study, 112 participants: RR 1.11, 95% CI 0.07 to 17.36), acute rejection (1 study, 112 participants: RR 0.93, 95% CI 0.44 to 1.97), hospitalisation for UTI (1 study, 112 participants: RR 0.74, 95% CI 0.13 to 4.27), graft function (2 studies, 200 participants, MD in serum creatinine concentration -0.06 mg/dL, 95% CI -0.19 to 0.08) and adverse reactions (1 study, 112 participants: no severe adverse event attributable to the antibiotic treatment). Evidence quality was low for all outcomes. Authors' conclusions: Currently, there is insufficient evidence to support routinely treating kidney transplant recipients with antibiotics in case of asymptomatic bacteriuria after transplantation, but data are scarce. Further studies assessing routine antibiotic treatment would inform practice and we await the results of three ongoing randomised studies, which may help resolve existing uncertainties.SCOPUS: re.jinfo:eu-repo/semantics/publishe

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

International audienceInvasive 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

Mucor irregularis-associated cutaneous mucormycosis: Case report and review

Solid organ transplant recipients are at risk for invasive fungal diseases, and are also exposed to healthcare-associated mucormycosis. Mainly causing localized cutaneous mucormycosis, Mucor irregularis infection is reported for the first time in a kidney-transplant recipient. A healthcare-associated origin was highly suspected in this case. We performed a literature review and highlight the characteristics of this very rare fungus

Prevalence of asymptomatic bacteriuria among kidney transplant recipients beyond two months post-transplant : a multicenter, prospective, cross-sectional study

BackgroundDuring 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.MethodsTo 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.ResultsWe 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.ConclusionsAmong kidney transplant recipients who are beyond the second month post-transplant, the prevalence of asymptomatic bacteriuria is low. Further studies are needed to ascertain the cost-effectiveness of a screen-and-treat strategy for asymptomatic bacteriuria in this population

Prospective evaluation of serum beta-glucan in patients with invasive fungal diseases

International audienceObjectives : The incidence of invasive fungal diseases (IFD) is currently increasing as a consequence of the growing population of immunocompromised patients. A key to IFD prognosis relies on early diagnosis, allowing early initiation of antifungal therapy. Over past years, the detection of the fungal (1-3)-β-D-glucan (BG) antigen has been increasingly used as an early IFD marker. However, different studies evaluating the performances of the BG assay in different target populations found contradictory results. In the present study, we assessed BG serum concentrations (Fungitell®, Associates of Cape Cod) in patients with documented IFD at time of diagnosis (TOD) and during antifungal treatment. Methods : We included 118 adults and 23 children with candidemia, invasive aspergillosis (IA) or rare IFD. Patients with two concomitant IFD or a possible cause of false-positive BG results were excluded. For candidemia and IA, serial sera were prospectively collected. The first serum was sampled respectively within [-3;+7] or [-7;+7] days toward mycological diagnosis. The follow-up period was of 2 and 6 months, respectively. Patients with rare IFD were included when at least one BG dosage was available within [-7;+15] days toward diagnosis. Whenever possible, a BG follow-up was performed until the IFD was controlled. Results: Thirty-three patients with candidemia and 31 with IA (28 probable and 3 proven IA) were included. They were patients with hematological diseases, solid organ transplant or patients hospitalized in ICU. Serum BG at TOD was negative in 44% of patients with candidemia and 52% with IA. No correlation was observed between negative BG at TOD and particular Candida species, catheter use, IA type, category of patients or recent administration of antifungals. Overall, for 18% and 14% of patients with candidemia and IA, BG remained not detected during the entire follow-up period. Among patients with candidemia or IA who had positive BG at TOD, >80% reached their peak value within the subsequent 2 weeks. Afterwards, the decrease of BG concentrations was rapid (half-concentration 3 weeks) in 20%, while 30% had persistently high BG. Thirty-three percent of patients with IA had a rapid decrease (half-concentration in 2 months). Regarding rare IFD, we included 77 patients with 26 different infections. While some IFD (scedosporiosis or cryptococcosis) had variable patterns toward BG at TOD, other were associated in all our cases with negative BG (fusariosis, microsporidiosis) or moderate to high (≥ 200 pg/ml) BG (hepatosplenic candidiasis, eumycotic mycetoma, subcutaneous phaehypho- or dermatophytomycosis, trichosporonosis). Conclusion: Altogether, our results offer valuable information for the clinical use of BG assay in various IFD and highlight the high percentage of patients with documented IFD, mainly candidemia and IA, for whom BG are negative at TOD

Acquired Flucytosine Resistance during Combination Therapy with Caspofungin and Flucytosine for Candida glabrata Cystitis

International audienceTreatment of Candida glabrata cystitis remains a therapeutic challenge, and an antifungal combination using flucytosine is one option. We describe two patients with refractory C. glabrata cystitis who failed flucytosine combined with caspofungin with early-acquired high-level resistance to flucytosine due to nonsense mutations in the FUR1 gene. Rapidly acquired flucytosine resistance with microbiological failure should discourage combination of caspofungin and flucytosine during urinary candidiasis