Uncommon case of Mycobacterium bovis brain abscess complicated by suppurative fistula, and review of the literature. / Caso insólito de absceso cerebral por Mycobacterium bovis complicado con fístula supurativa y revisión de la bibliografía.

INTRODUCTION: Mycobacterium bovis is an infrequent cause of central nervous system tuberculosis in Spain, with few cases described in the literature. Since compulsory pasteurization of milk and implementation of eradication programs on infected cattle, human sporadic illness with this organism has dramatically declined in developed countries. CASE REPORT: A 71-year-old immunocompromised male, who presented a calvarial lytic lesion. A craniotomy for the total resection of the lesion was performed and the microbiology results were positive for M. bovis, therefore antituberculous therapy was initiated. Despite of the correct treatment, the patient developed a tuberculous abscess that required an aggressive surgical management followed by a suppurative fistula. Based on the treatment of tuberculous lymphadenitis, we decided to perform a conservative management with antituberculous therapy (isoniazid + rifampicin + ethambutol + moxifloxacin + steroids during 12 months) and avoided new surgical cleanings of the surgical bed obtaining a good response and a good clinical evolution. CONCLUSIONS: As far as we know, this is the first case reported of a suppurative fistula after the resection of a cerebral abscess caused by M. bovis, therefore, there is no report in the literature about the treatment of this complication.

TITLE: Caso insólito de absceso cerebral por Mycobacterium bovis complicado con fístula supurativa y revisión de la bibliografía.Introducción. Mycobacterium bovis es una causa infrecuente de tuberculosis del sistema nervioso central en España, del cual existen pocos casos descritos en la bibliografía. Desde la pasteurización obligatoria de la leche y la implementación de programas de erradicación del ganado infectado, la enfermedad esporádica humana con este organismo ha disminuido drásticamente en los países desarrollados. Caso clínico. Varón inmunoafectado de 71 años, que presentaba una lesión lítica esporádica en la calota. Se realizó una craneotomía de la lesión y los resultados de microbiología fueron positivos para M. bovis, por lo que se inició tratamiento con terapia antituberculosa. A pesar del tratamiento correcto, el paciente desarrolló un absceso tuberculoso, que requirió un tratamiento quirúrgico agresivo, seguido de una complicación con una fístula supurativa. Sobre la base del tratamiento descrito para la linfadenitis tuberculosa, se decidió realizar un tratamiento conservador de la fístula supurativa, sin realizar nuevas limpiezas del lecho quirúrgico, y mantener de manera prolongada la terapia antituberculosa (isoniacida + rifampicina + etambutol + moxifloxacino + esteroides durante 12 meses), con lo que presentó una buena evolución clínica. Conclusiones. Hasta la fecha, éste es el primer caso descrito de una fístula supurativa después de la resección de un absceso cerebral causado por M. bovis, por lo que no existe en la bibliografía artículo alguno que describa el tratamiento adecuado de esta complicación.

Regular monitoring of cytomegalovirus-specific cell-mediated immunity in intermediate-risk kidney transplant recipients: predictive value of the immediate post-transplant assessment.

OBJECTIVE: Previous studies on monitoring of post-transplant cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) are limited by single-centre designs and disparate risk categories. We aimed to assess the clinical value of a regular monitoring strategy in a large multicentre cohort of intermediate-risk kidney transplant (KT) recipients. METHODS: We recruited 124 CMV-seropositive KT recipients with no T-cell-depleting induction pre-emptively managed at four Spanish institutions. CMV-specific interferon-γ-producing CD4+ and CD8+ T cells were counted through the first post-transplant year by intracellular cytokine staining after stimulation with pp65 and immediate early-1 peptides (mean of six measurements per patient). The primary outcome was the occurrence of any CMV event (asymptomatic infection and/or disease). Optimal cut-off values for CMV-specific T cells were calculated at baseline and day 15. RESULTS: Twelve-month cumulative incidence of CMV infection and/or disease was 47.6%. Patients with pre-transplant CMV-specific CD8+ T-cell count <1.0 cells/µL had greater risk of CMV events (adjusted hazard ratio (aHR) 2.84; p 0.054). When the CMI assessment was performed in the immediate post-transplant period (day 15), the presence of <2.0 CD8+ T cells/µL (aHR 2.18; p 0.034) or <1.0 CD4+ T cells/µL (aHR 2.43; p 0.016) also predicted the subsequent development of a CMV event. In addition, lower counts of CMV-specific CD4+ (but not CD8+) T cells at days 60 and 180 were associated with a higher incidence of late-onset events. CONCLUSIONS: Monitoring for CMV-specific CMI in intermediate-risk KT recipients must be regular to reflect dynamic changes in overall immunosuppression and individual susceptibility. The early assessment at post-transplant day 15 remains particularly informative.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [I]: anti-tumor necrosis factor-α agents).

BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting tumour necrosis factor-α (TNF-α) and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT: Preclinical and clinical evidence indicate that anti-TNF-α therapy (infliximab, adalimumab, golimumab, certolizumab pegol and etanercept) is associated with a two-to four-fold increase in the risk of active tuberculosis and other granulomatous conditions (mostly resulting from the reactivation of a latent infection). In addition, it may lead to the occurrence of other serious infections (bacterial, fungal, opportunistic and certain viral infections). These associated risks seem to be lower for etanercept than other agents. Screening for latent tuberculosis infection should be performed before starting anti-TNF-α therapy, followed by anti-tuberculosis therapy if appropriate. Screening for chronic hepatitis B virus (HBV) infection is also recommended, and antiviral prophylaxis may be warranted for hepatitis B surface antigen-positive individuals. No benefit is expected from the use of antibacterial, anti-Pneumocystis or antifungal prophylaxis. Pneumococcal and age-appropriate antiviral vaccinations (i.e. influenza) should be administered. Live-virus vaccines (i.e. varicella-zoster virus or measles-mumps-rubella) may be contraindicated in people receiving anti-TNF-α therapy, although additional data are needed before definitive recommendations can be made. IMPLICATIONS: Prevention measures should be implemented to reduce the risk of latent tuberculosis or HBV reactivation among individuals receiving anti-TNF-α therapy.

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.

Comparison of the clinical course of Clostridium difficile infection in glutamate dehydrogenase-positive toxin-negative patients diagnosed by PCR to those with a positive toxin test.

OBJECTIVES: To evaluate the potential role of PCR-based assays in the over-diagnosis of Clostridium difficile infection (CDI) by using a validated diagnostic algorithm in daily clinical practice. METHODS: We performed a retrospective cohort study evaluating all C. difficile-positive stool samples identified at our institution during a 12-month period, to compare outcomes and recurrence rates between patients with a positive enzyme immunoassay (EIA) for both glutamate dehydrogenase (GDH) and toxin A/B ('toxin-positive group'), with those with GDH-positive, toxin-negative samples in whom the diagnosis was made by a positive PCR-based assay ('toxin-/PCR+ group'). Medical records were reviewed by two independent investigators blinded to the mode of diagnosis. RESULTS: We analysed 231 first CDI episodes (106 (45.8 %) in the 'toxin-positive group' and 125 (54.1%) in the 'toxin-/PCR+ group'). Both groups had similar baseline characteristics. Patients in the 'toxin-positive group' presented more frequently with a severe/severe complicated form than those in the 'toxin-/PCR+ group' (36 (33.9%) versus 24 (19.2%); p 0.011) and had more recurrences (27 (25.5%) versus 9 (7.2%); p 0.001). Diagnosis of CDI based on a GDH/toxin-positive EIA independently predicted severe/severe-complicated course (adjusted OR 2.11; 95% CI 1.06-4.22; p 0.033) and recurrence (adjusted OR 3.79; 95% CI 1.65-8.69; p 0.002). There were no differences in all-cause mortality (12.3% versus 12.0%; p 0.95) or CDI-attributable mortality (4.7% versus 4.8%; p 0.93). CONCLUSIONS: Toxin-positive patients were more likely to have severe-complicated forms of CDI and recurrences. Nevertheless, CDI-related complications may still occasionally occur among toxin-negative patients diagnosed by PCR, which stresses the need for individualized clinical evaluation.

Pathogen-related factors affecting outcome of catheter-related bacteremia due to methicillin-susceptible Staphylococcus aureus in a Spanish multicenter study.

Even with appropriate clinical management, complicated methicillin-susceptible Staphylococcus aureus (MSSA) catheter-related bacteremia (CRB) is frequent. We investigated the influence of molecular characteristics of MSSA strains on the risk of complicated bacteremia (CB) in MSSA-CRB. A multicenter prospective study was conducted in Spain between 2011 and 2014 on MSSA-CRB. Optimized protocol-guided clinical management was required. CB included endocarditis, septic thrombophlebitis, persistent bacteremia and/or end-organ hematogenous spread. Molecular typing, agr functionality and DNA microarray analysis of virulence factors were performed in all MSSA isolates. Out of 83 MSSA-CRB episodes included, 26 (31.3%) developed CB. MSSA isolates belonged to 16 clonal complexes (CCs), with CC30 (32.5%), CC5 (15.7%) and CC45 (13.3) being the most common. Comparison between MSSA isolates in episodes with or without CB revealed no differences regarding agr type and functionality. However, our results showed that CC15 and the presence of genes like cna, chp and cap8 were associated with the development of CB. The multivariate analysis highlighted that the presence of cna (Hazard ratio 2.9; 95% CI 1.14-7.6) was associated with the development of CB. Our results suggest that particular CCs and specific genes may influence the outcome of MSSA-CRB.

Significance of the isolation of Staphylococcus aureus from a central venous catheter tip in the absence of concomitant bacteremia: a clinical approach.

The optimal approach following the isolation of Staphylococcus aureus from an intravascular catheter tip in the absence of concomitant bacteremia remains unclear. We aimed to determine the rate of delayed complications in these patients. We performed a retrospective observational study (during the period 2002-2012) including patients with a catheter tip culture yielding S. aureus. Patients were followed up for ≥6 months. The primary endpoint was the occurrence of delayed staphylococcal complications (either bacteremia and/or metastatic distant infections). A total of 113 patients were included (75 % male, median age 61 years): 46 and 67 with negative and positive blood cultures, respectively. We found a lower rate of delayed staphylococcal complications in cases with no bacteremia within 48 h since catheter removal than in cases of confirmed S. aureus catheter-related bacteremia (0.0 % vs. 25.4 %; p-value < 0.001). In the group without bacteremia, there was a subgroup of 15 patients (32.6 %) who did not receive antimicrobial treatment. Again, delayed complications occurred less commonly in this subgroup of patients without bacteremia (0.0 % vs. 25.4 %; p-value = 0.033). In contrast to patients with S. aureus catheter-related bacteremia, no delayed infectious complications were observed in patients with an isolated catheter tip culture yielding S. aureus and negative blood cultures within 48 h of catheter removal. Futures studies are needed to assess if the therapeutic approach could be different for this group of patients.

Progressive increase of resistance in Enterobacteriaceae urinary isolates from kidney transplant recipients over the past decade: narrowing of the therapeutic options.

BACKGROUND: Antibiotic resistance is an emerging phenomenon in kidney transplantation (KT). METHODS: We compared species distribution and antimicrobial susceptibility patterns in 1052 isolates from urine cultures obtained in 2 different cohorts of kidney transplant recipients in a single center (Cohort A: 189 patients undergoing KT between January 2002 and December 2004 [336 isolates]; Cohort B: 115 patients undergoing KT between January 2011 and December 2013 [716 isolates]). RESULTS: Asymptomatic bacteriuria accounted for most of the isolates (86.9% in Cohort A and 92.3% in Cohort B). Klebsiella pneumoniae (9.5% vs. 15.6%), Pseudomonas aeruginosa (1.8% vs. 7.9%), and Enterobacter cloacae (0.6% vs. 3.1%) were significantly more common in Cohort B. The isolation of K. pneumoniae in Cohort B was associated with the occurrence of acute pyelonephritis (9.8% of all K. pneumoniae isolates vs. 2.8% of the remaining uropathogens; P = 0.001). Non-susceptibility rates among Enterobacteriaceae in Cohort B were higher for every class of antibiotics (P ≤ 0.003) with the exception of fosfomycin. Compared to Cohort A, significant increases were seen in isolates from Cohort B for multidrug-resistant (MDR) (43.9% vs. 67.8%, respectively; P = 0.001), extended-spectrum beta-lactamase (ESBL)-producing (6.6% vs. 26.1%; P = 0.001), and carbapenemase-producing Enterobacteriaceae strains (0.0% vs. 5.0%; P = 0.001). Such differences were mostly attributable to K. pneumoniae (as 54.5% and 13.4% of isolates in Cohort B were ESBL-producing and carbapenemase-producing, respectively). MDR isolates were responsible for 69.1% of episodes of symptomatic urinary tract infection in Cohort B. CONCLUSION: The increase in resistance rates among Enterobacteriaceae uropathogens is significant and may have an effect on KT programs.

Post-transplant monitoring of NK cell counts as a simple approach to predict the occurrence of opportunistic infection in liver transplant recipients.

BACKGROUND: Monitoring of peripheral blood lymphocyte subpopulation (PBLS) counts might be useful for estimating the risk of infection after liver transplantation (LT). METHODS: We prospectively measured total lymphocyte and PBLS counts at baseline and post-transplant months 1 and 6 in 92 LT recipients. PBLS were enumerated by single-platform 6-color flow cytometry technology. Areas under receiver operating characteristic (ROC) curves were used to evaluate the accuracy of different PBLS for predicting cytomegalovirus (CMV) disease and overall opportunistic infection (OI). Adjusted hazard ratios (aHRs) for both outcomes were estimated by Cox regression. RESULTS: After a median follow-up of 730.0 days, 29 patients (31.5%) developed 38 episodes of OI (including 22 episodes of CMV disease). The counts of CD3(+) , CD4(+) , and CD8(+) T cells, and CD56(+) CD16(+) natural killer (NK) cells at month 1 were significantly lower in patients subsequently developing OI. The NK cell count was the best predictive parameter (area under ROC curve for predicting CMV disease: 0.78; P-value = 0.001). Patients with an NK cell count <0.050 × 10(3) cells/µL had higher cumulative incidences of CMV disease (P-value = 0.001) and overall OI (P-value <0.001). In the multivariate models, an NK cell count <0.050 × 10(3) cells/µL at month 1 post transplantation remained as an independent risk factor for CMV disease (aHR: 5.54; P-value = 0.003) and overall OI (aHR: 7.56; P-value <0.001). CONCLUSION: Post-transplant kinetics of NK cell counts may be used as a simple and affordable proxy to the cell-mediated immunity status in LT recipients and to their associated risk of OI.

Management of cytomegalovirus infection in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

Cytomegalovirus (CMV) infection remains a major complication of solid organ transplantation. Because of management of CMV is variable among transplant centers, in 2011 the Spanish Transplantation Infection Study Group (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) developed consensus guidelines for the prevention and treatment of CMV infection in solid organ transplant recipients. Since then, new publications have clarified or questioned the aspects covered in the previous document. For that reason, a panel of experts revised the evidence on CMV management, including immunological monitoring, diagnostics, prevention, vaccines, indirect effects, treatment, drug resistance, immunotherapy, investigational drugs, and pediatric issues. This document summarizes the recommendations.

Detection of Epstein-Barr virus DNAemia after lung transplantation and its potential relationship with the development of post-transplant complications.

BACKGROUND: Recent studies suggest that Epstein-Barr virus DNAemia (EBVd) may act as a surrogate marker of post-transplant immunosuppression. This hypothesis has not been tested so far in lung transplant (LT) recipients. METHODS: We included 63 patients undergoing lung transplantation at our center between October 2008 and May 2013. Whole blood EBVd was systematically assessed by real-time polymerase chain reaction assay on a quarterly basis. The occurrence of late complications (overall and opportunistic infection [OI] and chronic lung allograft dysfunction [CLAD]) was analyzed according to the detection of EBVd within the first 6 months post transplantation. RESULTS: Any EBVd was detected in 30 (47.6%) patients. Peak EBVd was higher in patients with late overall infection (2.23 vs. 1.73 log10 copies/mL; P = 0.026) and late OI (2.39 vs. 1.74 log10 copies/mL; P = 0.004). The areas under receiver operating characteristic curves for predicting both events were 0.806 and 0.871 respectively. The presence of an EBVd ≥2 log10 copies/mL during the first 6 months post transplantation was associated with a higher risk of late OI (adjusted hazard ratio [aHR] 7.92; 95% confidence interval [CI] 2.10-29.85; P = 0.002). Patients with detectable EBVd during the first 6 months also had lower CLAD-free survival (P = 0.035), although this association did not remain statistically significant in the multivariate analysis (aHR 1.26; 95% CI 0.87-5.29; P = 0.099). CONCLUSIONS: Although preliminary in nature, our results suggest that the detection of EBVd within the first 6 months after transplantation is associated with the subsequent occurrence of late OI in LT recipients.

Should Asymptomatic Bacteriuria Be Systematically Treated in Kidney Transplant Recipients? Results From a Randomized Controlled Trial.

The indication for antimicrobial treatment of asymptomatic bacteriuria (AB) after kidney transplantation (KT) remains controversial. Between January 2011 and December 2013, 112 KT recipients that developed one episode or more of AB beyond the second month after transplantation were included in this open-label trial. Participants were randomized (1:1 ratio) to the treatment group (systematic antimicrobial therapy for all episodes of AB occurring ≤24 mo after transplantation [53 patients]) or control group (no antimicrobial therapy [59 patients]). Systematic screening for AB was performed similarly in both groups. The primary outcome was the occurrence of acute pyelonephritis at 24-mo follow-up. Secondary outcomes included lower urinary tract infection, acute rejection, Clostridium difficile infection, colonization or infection by multidrug-resistant bacteria, graft function and all-cause mortality. There were no differences in the primary outcome in the intention-to-treat population (7.5% [4 of 53] in the treatment group vs. 8.4% [5 of 59] in the control group; odds ratio [OR] 0.88, 95% confidence interval [CI] 0.22-3.47) or the per-protocol population (3.8% [1 of 26] in the treatment group vs. 8.0% [4 of 50] in the control group; OR 0.46, 95% CI 0.05-4.34). Moreover, we found no differences in any of the secondary outcomes. In conclusion, systematic screening and treatment of AB beyond the second month after transplantation provided no apparent benefit among KT recipients (NCT02373085).

Infectious Complications Following Small Bowel Transplantation.

Microbiological spectrum and outcome of infectious complications following small bowel transplantation (SBT) have not been thoroughly characterized. We performed a retrospective analysis of all patients undergoing SBT from 2004 to 2013 in Spain. Sixty-nine patients underwent a total of 87 SBT procedures (65 pediatric, 22 adult). The median follow-up was 867 days. Overall, 81 transplant patients (93.1%) developed 263 episodes of infection (incidence rate: 2.81 episodes per 1000 transplant-days), with no significant differences between adult and pediatric populations. Most infections were bacterial (47.5%). Despite universal prophylaxis, 22 transplant patients (25.3%) developed cytomegalovirus disease, mainly in the form of enteritis. Specifically, 54 episodes of opportunistic infection (OI) occurred in 35 transplant patients. Infection was the major cause of mortality (17 of 24 deaths). Multivariate analysis identified retransplantation (hazard ratio [HR]: 2.21; 95% confidence interval [CI]: 1.02-4.80; p = 0.046) and posttransplant renal replacement therapy (RRT; HR: 4.19; 95% CI: 1.40-12.60; p = 0.011) as risk factors for OI. RRT was also a risk factor for invasive fungal disease (IFD; HR: 24.90; 95% CI: 5.35-115.91; p < 0.001). In conclusion, infection is the most frequent complication and the leading cause of death following SBT. Posttransplant RRT and retransplantation identify those recipients at high risk for developing OI and IFD.

Effect of long-term prophylaxis in the development of cytomegalovirus-specific T-cell immunity in D+/R- solid organ transplant recipients.

BACKGROUND: This study aimed to characterize the dynamics of acquisition of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) in CMV donor positive/recipient negative solid organ transplant (SOT) patients receiving long-term antiviral prophylaxis, and to determine whether development of CMI confers protection against CMV disease. METHODS: A prospective multicenter study was conducted in Spain from September 2009 to September 2012. Whole blood specimens were prospectively collected at 30, 90, 120, 200, and 365 days after SOT, and CMI was determined by enumeration of CMV pp65 and IE-1-specific CD69(+) /interferon-γ-producing CD8(+) and CD4(+) T cells by flow cytometry for intracellular cytokine staining. As part of a simultaneous clinical trial, patients received either early prophylaxis (in the first 3 days after transplantation) in the first period of the study or delayed prophylaxis (initiated at day 14) during the second period of the study. The impact of the dynamics of acquisition of CMV-specific CMI on the incidence of CMV disease was evaluated by Kaplan-Meier survival analysis. RESULTS: A total of 95 SOT recipients were recruited. CMV infection and disease occurred in 38 (40%) and 26 (27.4%) patients, respectively. The proportion of patients achieving any detectable CMV-specific CMI response at each of the different monitoring points was higher in liver transplant recipients, as compared to kidney or heart transplant recipients. The presence of any detectable response at day 120 or 200 was protective against the development of CMV disease (positive predictive values 92% and 93%, respectively). CONCLUSIONS: The rate of acquisition of CMV-specific CMI in SOT recipients undergoing antiviral prophylaxis differed significantly between different SOT populations. Patients developing any detectable CMI response were protected against the occurrence of CMV disease.

Risk factors for metastatic osteoarticular infections after a long follow-up of patients with Staphylococcus aureus bacteraemia.

We aimed to identify risk factors associated with the development of haematogenous metastatic osteoarticular infection (MOI) after an episode of Staphylococcus aureus bacteraemia (SAB). We followed 198 patients with SAB during a median of 68.9 months. Nine (4.54%) developed an MOI (median: 6.77 months) after SAB. Factors associated with MOI were the presence of joint prosthesis (hazard ratio 17.56; 95% CI 4.48-68.85) and osteoporosis (hazard ratio 8.46; 95% CI 1.9-37.57). MOI is a common complication after SAB and is related to high morbidity and mortality. Patients with previous osteoarticular disease are at the greatest risk of developing this complication.

Effect of delaying prophylaxis against CMV in D+/R- solid organ transplant recipients in the development of CMV-specific cellular immunity and occurrence of late CMV disease.

OBJECTIVES: Evaluate the protective effect against late CMV disease of delaying antiviral prophylaxis initiation in D+/R- patients receiving solid organ transplant (SOT). METHODS: Prospective multicenter study in D+/R- SOT recipients in Spain (Sept/09-Sept/12). Whole blood specimens were prospectively collected after Tx for CMV-specific cell-mediated immunity (CMI) determination. Two prophylaxis strategies were compared: early prophylaxis (EP; starting within the first 3 days after Tx) and delayed prophylaxis (DP; starting 14 days after Tx). Risk factors for the occurrence of CMV disease were determined by survival analysis and proportional risk Cox regression models. RESULTS: We included 95 patients (50 EP V 45 DP). Twenty six patients (27.4%) developed CMV disease: 32.7% EP vs. 20% DP; (p = 0.2). No cases of CMV disease were reported previously to beginning delayed prophylaxis. The percentage of individuals with detectable CMI response was higher in patients with DP although differences did not reach statistic significance (42% vs 29.6% at day 200 after Tx; p = 0.4). There was a clear trend towards less end-organ CMV disease in patients receiving DP (18.2% EP vs 5% DP; p = 0.09) and DP was the only protective factor in the multivariate analysis (HR: 0.26; CI: 0.05-1.2; p = 0.09). CONCLUSIONS: A 14-day delay in CMV prophylaxis in D+/R- SOT recipients is safe and may reduce the incidence of late CMV end-organ disease although correlation of this effect with CMI responses was not complete.

Mycobacterium abscessus pulmonary infection complicated with vertebral osteomyelitis in a heart transplant recipient: case report and literature review.

Infections produced by Mycobacterium abscessus are emerging in immunosuppressed patients, such as solid organ transplant recipients. We report the first case, to our knowledge, of a vertebral osteomyelitis caused by M. abscessus in a heart transplant recipient, and review the risk factors, manifestations, and therapeutic approaches to this uncommon disease.

Current preventive strategies and management of Epstein-Barr virus-related post-transplant lymphoproliferative disease in solid organ transplantation in Europe. Results of the ESGICH Questionnaire-based Cross-sectional Survey.

There is limited clinical evidence on the utility of the monitoring of Epstein-Barr virus (EBV) DNAemia in the pre-emptive management of post-transplant lymphoproliferative disease (PTLD) in solid organ transplant (SOT) recipients. We investigated current preventive measures against EBV-related PTLD through a web-based questionnaire sent to 669 SOT programmes in 35 European countries. This study was performed on behalf of the ESGICH study group from the European Society of Clinical Microbiology and Infectious Diseases. A total of 71 SOT programmes from 15 European countries participated in the study. EBV serostatus of the recipient is routinely obtained in 69/71 centres (97%) and 64 (90%) have access to EBV DNAemia assays. EBV monitoring is routinely used in 85.9% of the programmes and 77.4% reported performing pre-emptive treatment for patients with significant EBV DNAemia levels. Pre-emptive treatment for EBV DNAemia included reduction of immunosuppression in 50.9%, switch to mammalian target of rapamycin inhibitors in 30.9%, and use of rituximab in 14.5% of programmes. Imaging by whole-body 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) is used in 60.9% of centres to rule out PTLD and complemented computer tomography is used in 50%. In 10.9% of centres, FDG-PET is included in the first-line diagnostic workup in patients with high-risk EBV DNAemia. Despite the lack of definitive evidence, EBV load measurements are frequently used in Europe to guide diagnostic workup and pre-emptive reduction of immunosuppression. We need prospective and controlled studies to define the impact of EBV monitoring in reducing the risk of PTLD in SOT recipients.