José Tiago Silva

Aspergillus tracheobronchitis: report of 8 cases and review of the literature.

AbstractAspergillus tracheobronchitis (AT) is an infrequent but severe form of invasive pulmonary aspergillosis in which the fungal infection is entirely or predominantly confined to the tracheobronchial tree. We reviewed 8 cases of AT diagnosed in our tertiary care center during an 18-year period, as well as 148 cases previously reported in the English literature from 1985 to July 2011. The demographic, clinical, imaging, bronchoscopic, and outcome characteristics of every eligible patient were excerpted, and predictors of inhospital mortality were identified by logistic regression. Solid organ transplantation (SOT) (44.2%), hematologic malignancy (21.2%), neutropenia (18.7%), and chronic obstructive pulmonary disease (15.4%) were the most common underlying conditions reported. Most cases occurred in patients receiving long-term corticosteroid treatment (71.8%) or chemotherapy (25.0%). Fever and respiratory complaints (cough, dyspnea, stridor, or wheezing) were the most frequent symptoms; one-third of patients developed acute respiratory distress at presentation, and 15.1% were asymptomatic at the time of diagnosis. Initial imaging studies were not informative in 47.4% of the cases. Aspergillus fumigatus was the predominant species (74.4%). The pseudomembranous form was the most commonly observed (31.9% of cases) and was more frequent in neutropenic patients (p = 0.007), whereas ulcerative AT (31.2%) was associated with SOT (p = 0.001). The most frequent antifungal monotherapy regimens were amphotericin B deoxycholate (23.1%) and itraconazole (18.6%), whereas combined therapy was administered in 35.9% of the cases. Overall inhospital mortality was 39.1%, with neutropenia (odds ratio [OR], 20.47; p < 0.001) and acute respiratory distress at presentation (OR, 9.54; p = 0.002) as independent prognostic factors. Our pooled analysis of the literature shows that AT remains a rare opportunistic infection with a nonspecific presentation and a variable course depending on the nature of the predisposing factor.

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.

Caspofungin versus fluconazole as prophylaxis of invasive fungal infection in high‐risk liver transplantation recipients: A propensity score analysis

Targeted prophylaxis has proven to be an efficient strategy in liver transplantation recipients (LTRs). The aim of this study was to compare the effectiveness and safety of caspofungin with that of fluconazole in high‐risk (HR) LTRs. Caspofungin and fluconazole were compared in a multicenter, retrospective, cohort study in HR‐LTRs in Spain. Outcomes were assessed at 180 days after transplantation. A propensity score approach was applied. During the study period (2005‐2012), we analyzed 195 HR‐LTRs from 9 hospitals. By type of prophylaxis, 97 patients received caspofungin and 98 received fluconazole. Of a total of 17 (8.7%) global invasive fungal infections (IFIs), breakthrough IFIs accounted for 11 (5.6%) and invasive aspergillosis (IA) accounted for 6 (3.1%). By univariate analysis, no differences were observed in the prevention of global IFIs. However, caspofungin was associated with a significant reduction in the rate of breakthrough IFIs (2.1% versus 9.2%, P = 0.04). In patients requiring dialysis (n = 62), caspofungin significantly reduced the frequency of breakthrough IFIs (P = 0.03). The propensity score analysis confirmed a significant reduction in the frequency of IA in patients receiving caspofungin (absolute risk reduction, 0.06; 95% confidence interval [CI], 0.001‐0.11; P = 0.044). Linear regression analysis revealed a significant decrease in blood alanine aminotransferase levels and a significant increase in bilirubin levels after administration of caspofungin. Caspofungin and fluconazole have similar efficacy for the prevention of global IFIs in HR‐LTRs in this observational, multicenter cohort study. However, caspofungin was associated with a significant reduction of breakthrough IFIs and, after adjusting for confounders, caspofungin was associated with a lower rate of IA. This benefit is probably more favorable in patients on dialysis. Caspofungin is safe in HR‐LTRs, although bilirubin levels may be increased.

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

Monitoring of peripheral blood lymphocyte subpopulation (PBLS) counts might be useful for estimating the risk of infection after liver transplantation (LT).

Experience with leflunomide as treatment and as secondary prophylaxis for cytomegalovirus infection in lung transplant recipients: A case series and review of the literature

Data concerning the use of leflunomide—a drug approved for rheumatoid arthritis with in vitro anticytomegalovirus (CMV) activity—in lung transplant (LT) recipients are scarce.

Tuberculosis and Transplantation

Mycobacterium tuberculosis is a major opportunistic pathogen in transplant recipients. Compared to that in the general population, the frequency of tuberculosis (TB) is 10 to 40 times higher in hematopoietic stem cell transplant (HSCT) recipients and 20 to 74 times higher in solid-organ transplant (SOT) recipients. Transplant recipients with TB are also more likely to develop disseminated disease, have longer time to definitive diagnosis, require more invasive diagnostic procedures, and experience greater anti-TB treatment-related toxicity than the general population. Specific risk factors for TB in SOT recipients include previous exposure to M. tuberculosis (positive tuberculin skin tests and/or residual TB lesions in pretransplant chest X ray) and the intensity of immunosuppression (use of antilymphocyte antibodies, type of basal immunosuppression, and intensification of immunosuppressive therapy for allograft rejection). Risk factors in HSCT recipients are allogeneic transplantation from an unrelated donor; chronic graft-versus-host disease treated with corticosteroids; unrelated or mismatched allograft; pretransplant conditioning using total body irradiation, busulfan, or cyclophosphamide; and type and stage of primary hematological disorder. Transplant recipients with evidence of prior exposure to M. tuberculosis should receive treatment appropriate for latent TB infection. Optimal management of active TB disease is particularly challenging due to significant drug interactions between the anti-TB agents and the immunosuppressive therapy. In this chapter, we address the epidemiology, clinical presentation, diagnostic considerations, and management strategies for TB in SOT and HSCT recipients.

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.

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

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.

Fosfomycin for the Treatment of Asymptomatic Bacteriuria and Cystitis in Kidney Transplantation: new uses of an old antibiotiotic in the era of multidrug-resistance

Background The number of urinary tract infections (UTI) caused by multidrug-resistant (MDR) Gram-negative bacilli (GNB) in kidney transplant recipients (KTR) is increasing. Fosfomycin could be a suitable alternative, especially when other effective oral antibiotics are absent. Materials and Methods We performed a retrospective study including 14 Spanish hospitals. KTR treated with oral fosfomycin for cystitis or asymptomatic bacteriuria (AB) between 2005 and 2017 were included. Patients that concomitantly received another active antibiotic were excluded. We defined “clinical cure” of patients with cystitis as the remission of UTI symptoms at the end of treatment. Results A total of 326 KTR (42% males) developed 353 episodes of UTI (40.5% cystitis and 59.5% AB) treated with fosfomycin (11.9% of cases after the failure of a previous antibiotic treatment). 79 recipients (22.4%) had a urinary catheter (double J stent [14.4%]; urethral catheter [9.6%]). 333 episodes were produced by a GNB (94.3%), 57.0% were identified as MDR (16.5% extended-spectrum &bgr;-lactamase (ESBL)-producing Enterobacteriaceae; 3.3% of carbapenemase-producing bacilli). Gram-positive cocci accounted for 20 UTI (5.7%), especially Enterococcus spp. (12 episodes [60.0%]). A median dose of 2 g daily of fosfomycin (IQR: 1.5-3) was prescribed, for a median of 7 days (IQR: 3-9). There was clinical cure in 119 KTR (83.8%) treated for cystitis. Only 56 of these recipients had a urine culture performed within the first two weeks after stopping fosfomycin; in 44 (78.6%) it was sterile. In the case of AB, 99 KTR (48.3%) had a urine culture performed within the first two weeks after stopping fosfomycin; it was sterile in 50 (50.5%). No serious adverse events related to fosfomycin were reported. Conclusion Fosfomycin appears to be safe and effective for the treatment of cystitis and AB in KTR. Its availability is especially important for the treatment of infections produced by MDR bacteria with poor alternative antibiotic options. Countries in which oral fosfomycin is not available should consider its commercialization. On behalf of the Spanish Network for Research in Infectious Diseases (REIPI) and the Group for the Study of Infection in Transplantation of the Spanish Society of Infectious Diseases and Clinical Microbiology (GESITRA-SEIMC).

Vitamin D deficiency and infection risk in kidney transplant recipients: A single-center cohort study

Recent studies have reported an increased susceptibility to infection among vitamin D‐deficient kidney transplant (KT) recipients, although methodological concerns remain.