Clinical utility of a cytomegalovirus-specific T cell assay in assessing the risk of post-prophylaxis cytomegalovirus infection and post-treatment relapse.

INTRODUCTION: Cytomegalovirus (CMV) causes significant morbidity in solid organ transplant recipients (SOTR). Measuring cell-mediated immunity (CMI) may inform the risk of CMV infection after antiviral prophylaxis and predict relapse after CMV treatment. METHODS: We serially assessed CMV CMI using the QuantiFERON-CMV assay (QF-CMV; Qiagen, Germantown, MD) in two cohorts of SOTRs: during valganciclovir prophylaxis and during treatment of CMV viremia. Results of CMI were correlated with post-prophylaxis CMV infection and post-treatment relapse, respectively. RESULTS: Only one (4.2%) of 24 CMV D+/R- patients demonstrated positive QF-CMV by the end of valganciclovir prophylaxis. Four (16.6%) patients developed post-prophylaxis CMV infection; all four had undetectable QF-CMV at end of prophylaxis. Among 20 patients treated for CMV infection, 18 (90%) developed QF-CMV levels >.2 IU/mL by end of antiviral treatment and none developed CMV relapse. In contrast, the single patient who relapsed after completing treatment had a CMV CMI <.2 IU/ml (p = .0036). CONCLUSION: Since CMV D+/R- SOTRs are unlikely to develop adequate CMV CMI while receiving valganciclovir prophylaxis, the utility of CMV CMI monitoring for risk stratification during time of prophylaxis had limited value. Conversely, CMV CMI testing may be a useful marker of the risk of CMV relapse after antiviral treatment.

Prosthetic Joint Infections Due to Histoplasma capsulatum: A Report of 3 Cases.

Histoplasma capsulatum causes pneumonia and multisystemic disease in humans. Musculoskeletal involvement in histoplasmosis is most often tenosynovitis and rarely septic arthritis. Even more uncommon is the involvement of prosthetic joints. Here, we report a series of 3 cases of prosthetic joint failures caused by infection due to H capsulatum. Together with a review of 4 previously reported cases, we summarize host characteristics, clinical presentation, surgical approaches, antifungal management, and outcomes of this rare orthopedic joint infection.

Treatment of latent TB Infection and the risk of tuberculosis after solid organ transplantation: Comprehensive review.

BACKGROUND: Mycobacterium tuberculosis disease may occur after treatment of latent TB infection (LTBI). Prompted by a case of reactivation TB disease in a solid organ transplant (SOT) recipient who received LTBI treatment, we reviewed the literature to examine outcomes, adverse effects, resistance, and treatment choices of tuberculosis after LTBI therapy. METHODS: MEDLINE and Web of Science from inception to 5/2019 were reviewed using key words "latent tuberculosis infection" and "SOT" or "transplantation." The search yielded nine cases, 41 cohort studies and six randomized controlled trials (RCT). RESULTS: Cohort and RCT demonstrated significant reduction in TB disease among transplanted patients who received LTBI therapy; only 56/2651 (2.1%) SOT patients developed TB after LTBI therapy. Adverse drug reactions occurred in 149/1148 (12.9%) and 73/641 (11.4%) of cohort and RCT patients, respectively. Among liver recipients, 56/266 (21%) developed side effects, of which half (29/56, 51.8%) was INH-related. There was no reported INH resistance. CONCLUSIONS: Latent TB infection treatment is efficacious in SOT recipients at risk of TB disease. However, tuberculosis may still occur despite LTBI treatment. Hepatotoxicity associated with LTBI therapy is infrequent, although more commonly observed among liver recipients.

A Fatal Case of Disseminated Microsporidiosis Due to Anncaliia algerae in a Renal and Pancreas Allograft Recipient.

Microsporidiosis is an emerging opportunistic infection in immunocompromised patients. We report a case of fatal disseminated Anncaliia algerae infection in a profoundly immunosuppressed pancreas and kidney transplant recipient.

Unrecognized pre-transplant disseminated Coxiella burnetti infection diagnosed in a post-transplant heart-kidney recipient.

To the best of our knowledge, we report the first case of pre-transplant unrecognized disseminated Coxiella burnetii infection, unmasked in the post-transplant period leading to both heart and kidney allograft dysfunction. A 59 year old man with a history of simultaneous heart-kidney transplantation due to end stage heart failure from severe aortic regurgitation (AR) and cryoglobulinemic immune complex mediated concentric necrotizing glomerulonephritis (GN), presents with a history of intermittent fevers and fatigue. Prior to transplantation he was treated for multiple episodes of culture negative endocarditis requiring bio-prosthetic valve replacement. Evaluation of fever included a transesophageal echocardiogram (TEE) that revealed a large hyperechoic mass on the anterior mitral leaflet with perforation, severe mitral regurgitation and moderate AR. Blood cultures were negative at that time. Owing to development of allograft mitral and aortic valve insufficiency, he underwent allograft bio-prosthetic mitral valve (MV) replacement and aortic valvuloplasty 2 years following his transplantation. Pathologic examination of the allograft mitral valve demonstrated fibrinopurulent exudate with degenerating bacterial organisms, consistent with vegetation and myxoid degenerative changes. Due to a high suspicion for native heart C. burnetii prosthetic valve endocarditis prior to transplantation, we re-evaluated the native explanted heart histopathology, as well as the explanted allograft MV. Cardiac allograft and native MV were positive for C. burnetii by real-time PCR. C. burnetii serology was consistent with persistent infection as well.

Anti-infective chemoprophylaxis after solid-organ transplantation.

INTRODUCTION: Solid organ transplant (SOT) recipients are at high risk of opportunistic infections due to bacterial, viral, fungal, and parasitic pathogens. Anti-infective prophylaxis is a time-tested proven strategy for the prevention of these infections after SOT. Areas covered: The current recommendations for the prevention of surgical site infections, herpes simplex, cytomegalovirus, invasive fungal infections, and selected parasitic diseases are highlighted. Recent peer-reviewed publications on the prevention of infection after SOT were reviewed and their significance was discussed in the context of the current recommendations for preventing infectious complications. Expert commentary: The authors comment on the current approaches to infection prevention in transplant recipients, and discuss how these recommendations are implemented in their clinical practice. Notable findings published during the past year were highlighted, and their clinical significance was interpreted in the context of current recommendations. The evolution of diagnostic and immunologic assays was emphasized, with focus on their potential role in optimizing the current antimicrobial approaches to infection prevention after SOT.

Prolonged shedding of pandemic influenza A (H1N1) 2009 virus in a pancreas-after-kidney transplant recipient.

Prolonged shedding of influenza virus has been reported in immunocompromised patients. Delayed viral clearance may contribute to antiviral resistance and nosocomial transmission. We report a case of a pancreas-after-kidney transplant recipient who had detectable pandemic influenza A virus for 12 months. Pyrosequencing analysis detected the H275Y mutation, which is associated with resistance to oseltamivir.

Misidentification of Neosartorya pseudofischeri as Aspergillus fumigatus in a lung transplant patient.

We present a case of disseminated Neosartorya pseudofischeri infection in a bilateral lung transplant patient with cystic fibrosis. The organism was originally misidentified from respiratory specimens as Aspergillus fumigatus using colonial and microscopic morphology. DNA sequencing subsequently identified the organism correctly as N. pseudofischeri.

Gordonia bacteremia.

Gordonia species are ubiquitous aerobic actinomycetes that rarely cause infection in humans. We report the second known case of Gordonia otitidis catheter-related bacteremia in an immunocompromised patient and review four additional cases of Gordonia bacteremia seen at our institution over the past 14 years. In addition, the existing literature on Gordonia infections is reviewed.

Fluoride excess and periostitis in transplant patients receiving long-term voriconazole therapy.

BACKGROUND: We describe a heart transplant patient with painful periostitis and exostoses who was receiving long-term therapy with voriconazole, which is a fluoride-containing medication. Elevated plasma and bone fluoride levels were identified. Discontinuation of voriconazole therapy led to improvement in pain and reduced fluoride and alkaline phosphatase levels. METHODS: To determine whether voriconazole is a cause of fluoride excess, we measured plasma fluoride levels in 10 adult post-transplant patients who had received voriconazole for at least 6 months and 10 post-transplant patients who did not receive voriconazole. To assess the effect of renal insufficiency on fluoride levels in subjects receiving voriconazole, half were recruited on the basis of a serum creatinine level of ≥1.4 mg/dL on their most recent measurement, whereas the other 5 subjects receiving voriconazole had serum creatinine levels <1.4 mg/dL. All control subjects had serum creatinine levels of ≥1.4 mg/dL. Patients were excluded from the study if they received a fluorinated pharmaceutical other than voriconazole. RESULTS: All subjects who received voriconazole had elevated plasma fluoride levels, and no subjects in the control group had elevated levels (14.32 µmol/L ± 6.41 vs 2.54 ± 0.67 µmol/L; P<.001). Renal function was not predictive of fluoride levels. Plasma fluoride levels remained significantly higher in the voriconazole group after adjusting for calcineurin inhibitor levels and doses. Half of the voriconazole group subjects had evidence of periostitis, including exostoses in 2 patients. Discontinuation of voriconazole therapy in patients with periostitis resulted in improvement of pain and a reduction in alkaline phosphatase and fluoride levels. CONCLUSIONS: Voriconazole is associated with painful periostitis, exostoses, and fluoride excess in post-transplant patients with long-term voriconazole use.

The impact of invasive fungal diseases on survival after lung transplantation.

BACKGROUND: Recipients of lung transplants are at high risk of infectious complications. We investigated the epidemiology of infections after lung transplantation and determined their impact on survival. METHODS: We retrospectively reviewed the medical records of patients who underwent lung transplantation at Mayo Clinic (Rochester) during 1990-2005. Survival analyses were performed using Kaplan-Meier estimation and Cox proportional hazard modeling. RESULTS: Sixty-nine lung transplants were performed during the 16-yr study period. The mean (+/-SD) patient age was 50.5 +/- 9.7 yr; 45% were male. During the mean (+/-SD) follow-up period of 1188 (+/-1288) d, the cumulative percentage of patients with infections were: bacteria (52%), cytomegalovirus (CMV) (49%), other viruses (32%), fungi (19%), mycobacteria (7%), and Pneumocystis jiroveci (1%). The median survival time after lung transplantation was 5.02 yr. Kaplan-Meier estimation of one-, three-, and five-yr survival was 80%, 61%, and 50%, respectively. Overall, 37 (54%) patients died due to graft rejection and failure (35%), invasive fungal diseases (16%), post-transplant lymphoproliferative disorder and other malignancies (14%), cardiovascular diseases (5%), CMV disease (3%), bacterial infection (3%), or other causes (24%). Survival analysis using Kaplan-Meier estimation showed that invasive fungal disease (Aspergillus sp., n = 9, Candida sp., n = 2, Alternaria sp., n = 1, Rhizopus sp., n = 1, and/or Mucor sp., n = 1) was significantly associated with mortality (p = 0.0104). After adjusting for age and graft rejection, invasive fungal disease remains a significant predictor of mortality (p = 0.0262). CONCLUSION: Invasive fungal disease is significantly associated with all-cause mortality after lung transplantation. An aggressive antifungal preventive strategy may lead to improved survival after lung transplantation.

Emergence of drug-resistant cytomegalovirus in the era of valganciclovir prophylaxis: therapeutic implications and outcomes.

BACKGROUND: Valganciclovir prophylaxis is reportedly associated with a low incidence of ganciclovir-resistant cytomegalovirus (CMV). We assessed the incidence, clinical features, and outcome of drug-resistant CMV among solid organ transplant patients who received valganciclovir prophylaxis. METHODS: The medical records of all CMV D+/R- kidney, pancreas, liver, and heart recipients were screened for CMV disease, and the clinical course and outcomes of patients with drug-resistant CMV were reviewed. RESULTS: During a four-yr-study period, a total of 225 CMV D+/R- transplant patients received valganciclovir prophylaxis for a median of 92 d. Sixty-five (29%) of the 225 patients developed delayed-onset primary CMV disease, including nine (14%) suspected to have drug-resistant virus. Four (6.2%) had confirmed UL97 or UL54 mutations. All except one patient manifested gastrointestinal tissue-invasive disease. Together with reduction in immunosuppression, intravenous foscarnet with or without CMV hyperimmunoglobulin was the most common treatment. Drug-associated nephrotoxicity was commonly observed and resulted in allograft loss in two patients. During the mean follow-up of 2.2 yr, allograft loss and mortality occurred in two of four patients with proven and in three of five patients with clinically suspected drug-resistant CMV. CONCLUSIONS: Cytomegalovirus disease because of clinically suspected or genotypically confirmed drug-resistant CMV is not uncommon in CMV D+/R- solid organ transplant patients who received valganciclovir prophylaxis. Because of its significant morbidity and mortality, an optimized strategy of CMV prevention is warranted to reduce the negative impact of drug-resistant CMV on the successful outcome of organ transplantation.

Disseminated coccidioidomycosis in a liver transplant recipient with negative serology: use of polymerase chain reaction.

Coccidioidomycosis has been previously described in recipients of solid organ transplantation, especially in patients who have lived in or have visited areas endemic for Coccidioides spp. We present a case of coccidioidomycosis in a liver transplant recipient with several unique aspects, including negative serology and positive polymerase chain reaction results.