Clostridium difficile infection is associated with graft loss in solid organ transplant recipients.

Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case-control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched 2 control subjects per case by age at transplantation, sex, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred fifty-eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38-0.58), with the highest rate in lung (1.48, 95% CI 0.93-2.24). In multivariable analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29-6.19) and antibiotic treatments (HR 4.51, 95% CI 2.03-10.0) during the preceding 3 months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI posttransplantation had an increased risk of graft loss (HR 2.24, 95% CI 1.15-4.37; P = .02). These findings may help to improve the management of SOT recipients.

Preventive Strategies Against Cytomegalovirus and Incidence of α-Herpesvirus Infections in Solid Organ Transplant Recipients: A Nationwide Cohort Study.

We assessed the impact of antiviral preventive strategies on the incidence of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections in a nationwide cohort of transplant recipients. Risk factors for the development of HSV or VZV infection were assessed by Cox proportional hazards regression. We included 2781 patients (56% kidney, 20% liver, 10% lung, 7.3% heart, 6.7% others). Overall, 1264 (45%) patients received antiviral prophylaxis (ganciclovir or valganciclovir, n = 1145; acyclovir or valacyclovir, n = 138). Incidence of HSV and VZV infections was 28.9 and 12.1 cases, respectively, per 1000 person-years. Incidence of HSV and VZV infections at 1 year after transplant was 4.6% (95% confidence interval [CI] 3.5-5.8) in patients receiving antiviral prophylaxis versus 12.3% (95% CI 10.7-14) in patients without prophylaxis; this was observed particularly for HSV infections (3% [95% CI 2.2-4] versus 9.8% [95% CI 8.4-11.4], respectively). A lower rate of HSV and VZV infections was also seen in donor or recipient cytomegalovirus-positive patients receiving ganciclovir or valganciclovir prophylaxis compared with a preemptive approach. Female sex (hazard ratio [HR] 1.663, p = 0.001), HSV seropositivity (HR 5.198, p < 0.001), previous episodes of rejection (HR 1.95, p = 0.004), and use of a preemptive approach (HR 2.841, p = 0.017) were significantly associated with a higher risk of HSV infection. Although HSV and VZV infections were common after transplantation, antiviral prophylaxis significantly reduced symptomatic HSV infections.

Lymphocytic choriomeningitis virus infection induced by percutaneous exposure.

We report a case of acquired lymphocytic choriomeningitis virus (LCMV) infection due to an accidental percutaneous inoculation of LCMV at work. The injured worker developed a flu-like syndrome, followed by pericarditis and meningoencephalitis. Seroconversion was confirmed by ELISA. The patient made a complete recovery. We review measures undertaken to prevent a similar event and propose a follow-up protocol in the event of accidental LCMV exposure.

CSF lactate for accurate diagnosis of community-acquired bacterial meningitis.

CSF lactate measurement is recommended when nosocomial meningitis is suspected, but its value in community-acquired bacterial meningitis is controversial. We evaluated the diagnostic performance of lactate and other CSF parameters in a prospective cohort of adult patients with acute meningitis. Diagnostic accuracy of lactate and other CSF parameters in patients with microbiologically documented episodes was assessed by receiver operating characteristic (ROC) curves. The cut-offs with the best diagnostic performance were determined. Forty-five of 61 patients (74%) had a documented bacterial (n = 18; S. pneumoniae, 11; N. meningitidis, 5; other, 2) or viral (n = 27 enterovirus, 21; VZV, 3; other, 3) etiology. CSF parameters were significantly different in bacterial vs. viral meningitis, respectively (p < 0.001 for all comparisons): white cell count (median 1333 vs. 143/mm(3)), proteins (median 4115 vs. 829 mg/l), CSF/blood glucose ratio (median 0.1 vs. 0.52), lactate (median 13 vs. 2.3 mmol/l). ROC curve analysis showed that CSF lactate had the highest accuracy for discriminating bacterial from viral meningitis, with a cutoff set at 3.5 mmol/l providing 100% sensitivity, specificity, PPV, NPV, and efficiency. CSF lactate had the best accuracy for discriminating bacterial from viral meningitis and should be included in the initial diagnostic workup of this condition.

KIR-associated protection from CMV replication requires pre-existing immunity: a prospective study in solid organ transplant recipients.

Previous studies have associated activating Killer cell Immunoglobulin-like Receptor (KIR) genes with protection from cytomegalovirus (CMV) replication after organ transplantation. Whether KIR-associated protection is operating in the context of primary infection, re-activation, or both, remains unknown. Here we correlated KIR genotype and CMV serostatus at the time of transplantation with rates of CMV viremia in 517 heart (n=57), kidney (n=223), liver (n=165) or lung (n=72) allograft recipients reported to the Swiss Transplant Cohort Study. Across the entire cohort we found B haplotypes-which in contrast to A haplotypes may contain multiple activating KIR genes-to be protective in the most immunosuppressed patients (receiving anti-thymocyte globulin induction and intensive maintenance immunosuppression) (hazard ratio after adjustment for covariates 0.46, 95% confidence interval 0.29-0.75, P=0.002). Notably, a significant protection was detected only in recipients who were CMV-seropositive at the time of transplantation (HR 0.45, 95% CI 0.26-0.77, P=0.004), but not in CMV seronegative recipients (HR 0.59, 95% CI 0.22-1.53, P=0.28). These data indicate a prominent role for KIR-and presumably natural killer (NK) cells-in the control of CMV replication in CMV seropositive organ transplant recipients treated with intense immunosuppression.

Epstein-Barr virus-related post-transplant lymphoproliferative disorder in solid organ transplant recipients.

Epstein-Barr virus (EBV) contributes to the pathogenesis of post-transplant lymphoproliferative disease (PTLD) in more than 70% of cases. EBV DNAemia surveillance has been reported to assist in the prevention and treatment of PTLD in hematopoietic stem-cell transplantation (HSCT) recipients. Derived from experience in HSCT and taking into account that PCR-based EBV monitoring techniques are currently available in most solid organ transplant (SOT) centres, there is a great interest in EBV surveillance and prevention of PTLD in SOT recipients. In the present document we have tried to address from a practical perspective different important topics regarding the prevention and management of EBV-related PTLD in SOT. To this end, available information on SOT was analysed and combined with potentially useful data from HSCT and expert observations. The document is therefore structured according to different specific questions, each of them culminating in a consensus opinion of the panel of European experts, grading the answers according to internationally recognized levels of evidence. The addressed issues were grouped under the following topics. (i) Timing and epidemiological data of PTLD. Prophylaxis guided by clinical risk factors of early and late PTLD in SOT. (ii) Relationship of EBV DNAemia load monitoring and the development of PTLD in solid organ transplant recipients. (iii) Monitoring of EBV DNAemia after SOT. Which population should be monitored? What is the optimal timing of the monitoring? (iv) Management of SOT recipients with persistent and/or increasing EBV DNAemia.

Impact of enterococcal colonization and infection in solid organ transplantation recipients from the Swiss transplant cohort study.

BACKGROUND: The burden of enterococcal infections has increased over the last decades with vancomycin-resistant enterococci (VRE) being a major health problem. Solid organ transplantation is considered as a risk factor. However, little is known about the relevance of enterococci in solid organ transplantation recipients in areas with a low VRE prevalence. METHODS: We examined the epidemiology of enterococcal events in patients followed in the Swiss Transplant Cohort Study between May 2008 and September 2011 and analyzed risk factors for infection, aminopenicillin resistance, treatment, and outcome. RESULTS: Of the 1234 patients, 255 (20.7%) suffered from 392 enterococcal events (185 [47.2%] infections, 205 [52.3%] colonizations, and 2 events with missing clinical information). Only 2 isolates were VRE. The highest infection rates were found early after liver transplantation (0.24/person-year) consisting in 58.6% of Enterococcus faecium. The highest colonization rates were documented in lung transplant recipients (0.33/person-year), with 46.5% E. faecium. Age, prophylaxis with a betalactam antibiotic, and liver transplantation were significantly associated with infection. Previous antibiotic treatment, intensive care unit stay, and lung transplantation were associated with aminopenicillin resistance. Only 4/205 (2%) colonization events led to an infection. Adequate treatment did not affect microbiological clearance rates. Overall mortality was 8%; no deaths were attributable to enterococcal events. CONCLUSIONS: Enterococcal colonizations and infections are frequent in transplant recipients. Progression from colonization to infection is rare. Therefore, antibiotic treatment should be used restrictively in colonization. No increased mortality because of enterococcal infection was noted.

Incidence and outcomes of respiratory viral infections in lung transplant recipients: a prospective study.

BACKGROUND: The incidence and outcomes of respiratory viral infections in lung transplant recipients (LTR) are not well defined. The objective of this prospective study conducted from June 2008 to March 2011 was to characterise the incidence and outcomes of viral respiratory infections in LTR. METHODS: Patients were seen in three contexts: study-specific screenings covering all seasons; routine post-transplantation follow-up; and emergency visits. Nasopharyngeal specimens were collected systematically and bronchoalveolar lavage (BAL) was performed when clinically indicated. All specimens underwent testing with a wide panel of molecular assays targeting respiratory viruses. RESULTS: One hundred and twelve LTR had 903 encounters: 570 (63%) were screening visits, 124 (14%) were routine post-transplantation follow-up and 209 (23%) were emergency visits. Respiratory viruses were identified in 174 encounters, 34 of these via BAL. The incidence of infection was 0.83 per patient-year (95% CI 0.45 to 1.52). The viral infection rates upon screening, routine and emergency visits were 14%, 15% and 34%, respectively (p<0.001). Picornavirus was identified most frequently in nasopharyngeal (85/140; 60.7%) and BAL specimens (20/34; 59%). Asymptomatic viral carriage, mainly of picornaviruses, was found at 10% of screening visits. Infections were associated with transient lung function loss and high calcineurin inhibitor blood levels. The hospitalisation rate was 50% (95% CI 30% to 70.9%) for influenza and parainfluenza and 16.9% (95% CI 11.2% to 23.9%) for other viruses. Acute rejection was not associated with viral infection (OR 0.4, 95% CI 0.1 to 1.3). CONCLUSIONS: There is a high incidence of viral infection in LTR; asymptomatic carriage is rare. Viral infections contribute significantly to this population's respiratory symptomatology. No temporal association was observed between infection and acute rejection.

Impact of antiviral preventive strategies on the incidence and outcomes of cytomegalovirus disease in solid organ transplant recipients.

We assessed the impact of antiviral prophylaxis and preemptive therapy on the incidence and outcomes of cytomegalovirus (CMV) disease in a nationwide prospective cohort of solid organ transplant recipients. Risk factors associated with CMV disease and graft failure-free survival were analyzed using Cox regression models. One thousand two hundred thirty-nine patients transplanted from May 2008 until March 2011 were included; 466 (38%) patients received CMV prophylaxis and 522 (42%) patients were managed preemptively. Overall incidence of CMV disease was 6.05% and was linked to CMV serostatus (D+/R- vs. R+, hazard ratio [HR] 5.36 [95% CI 3.14-9.14], p < 0.001). No difference in the incidence of CMV disease was observed in patients receiving antiviral prophylaxis as compared to the preemptive approach (HR 1.16 [95% CI 0.63-2.17], p = 0.63). CMV disease was not associated with a lower graft failure-free survival (HR 1.27 [95% CI 0.64-2.53], p = 0.50). Nevertheless, patients followed by the preemptive approach had an inferior graft failure-free survival after a median of 1.05 years of follow-up (HR 1.63 [95% CI 1.01-2.64], p = 0.044). The incidence of CMV disease in this cohort was low and not influenced by the preventive strategy used. However, patients on CMV prophylaxis were more likely to be free from graft failure.

[Neuroborreliosis, tick-borne encephalitis and neurosyphilis]. / Neuroborréliose, méningo-encéphalite verno-estivale et neurosyphilis.

Infections affecting frequently the nervous system include Lyme disease, tick-borne encephalitis and syphilis. These three most dreaded neuro-infectious diseases observed in Switzerland are discussed, based on diagnostic criteria, screening testing, and treatments modalities. Neuroborreliosis and neurosyphilis are bacterial infectious diseases treatable by antibiotics, whereas the treatment of tick-borne encephalitis, a viral disease, is only based on preventive vaccination.

Neonatal herpes simplex virus infections in Switzerland: results of a 6-year national prospective surveillance study.

A large variation in neonatal herpes incidence is observed in USA and Europe. Better knowledge of neonatal herpes epidemiology is important to inform local prevention strategies. Between 2002 and 2008, the Swiss Paediatric Surveillance Unit reported prospectively proven neonatal herpes simplex virus infections. During the study period seven cases were declared, for an incidence of 1.6/100,000 (95% CI 0.64-3.28/100,000) live births. This is one of the lowest incidences of neonatal herpes reported.

Upper and lower respiratory tract viral infections and acute graft rejection in lung transplant recipients.

BACKGROUND: Lung transplant recipients are frequently exposed to respiratory viruses and are particularly at risk for severe complications. The aim of this study was to assess the association among the presence of a respiratory virus detected by molecular assays in bronchoalveolar lavage (BAL) fluid, respiratory symptoms, and acute rejection in adult lung transplant recipients. METHODS: Upper (nasopharyngeal swab) and lower (BAL) respiratory tract specimens from 77 lung transplant recipients enrolled in a cohort study and undergoing bronchoscopy with BAL and transbronchial biopsies were screened using 17 different polymerase chain reaction-based assays. RESULTS: BAL fluid and biopsy specimens from 343 bronchoscopic procedures performed in 77 patients were analyzed. We also compared paired nasopharyngeal and BAL fluid specimens collected in a subgroup of 283 cases. The overall viral positivity rate was 29.3% in the upper respiratory tract specimens and 17.2% in the BAL samples (P < .001). We observed a significant association between the presence of respiratory symptoms and positive viral detection in the lower respiratory tract (P = .012). Conversely, acute rejection was not associated with the presence of viral infection (odds ratio, 0.41; 95% confidence interval, 0.20-0.88). The recovery of lung function was significantly slower when acute rejection and viral infection were both present. CONCLUSIONS: A temporal relationship exists between acute respiratory symptoms and positive viral nucleic acid detection in BAL fluid from lung transplant recipients. We provide evidence suggesting that respiratory viruses are not associated with acute graft rejection during the acute phase of infection.

Comparison of a multiplexed bead-based assay with an immunofluorescence and an enzyme-immuno assay for the assessment of Epstein-Barr virus serologic status.

We have compared a multiplexed bead-based assay (BBA) with an enzyme immunoassay (EIA) and immunofluorescence assay (IFA) for the assessment of the Epstein-Barr virus (EBV) serostatus. Three hundred and ninety-three sera, classified according to IFA results as seronegative (n=100), acute infection (n=100), past infection (n=100) and indeterminate (n=93), were tested by BBA and EIA. Overall, the three methods gave similar results with a relatively high (75.2%) concordance with the consensus interpretation of the serostatus. The most significant discordances were: (i) 58 samples had uninterpretable results for BBA, in majority due to the detection of non-antigen specific antibody binding by control beads. (ii) almost half the samples positive for anti-Epstein-Barr nuclear antigen (EBNA) IgG by BBA or EIA were negative by IFA. Among the latter, only a minority had a history of immunocompromise or treatment, or detectable anti-early antigen antibody. This discrepancy probably reflects a poor sensitivity of IFA for anti-EBNA IgG detection. EIA and BBA had a similar performance and had substantial practical advantages over IFA with respect to testing for EBV serostatus.