Invasive pulmonary aspergillosis following human metapneumovirus infection in solid-organ transplant recipients: Another virus to add to the list.

There is increasing recognition that respiratory viral infections such as influenza, respiratory syncytial virus, parainfluenza virus, adenovirus, and SARS-CoV-2 can promote the development of invasive fungal pulmonary coinfections, particularly invasive aspergillosis, both in immunocompetent and immunocompromised patients. To date, there are no case reports exploring the role of human metapneumovirus as a risk factor for fungal coinfection. Below, we describe the case of a 63-year-old woman who received a kidney transplant and developed invasive pulmonary aspergillosis after a human metapneumovirus infection and discuss the possible phenomena that could favor this association.

Histoplasma capsulatum tenosynovitis: An unusual presentation in a kidney transplant recipient.

Histoplasmosis is an expected endemic mycosis in solid organ transplant recipients and occurs as a primary infection, reactivation, or, rarely, acquired from an infected allograft. Reactivation is favored by maintenance immunosuppression or anti-rejection therapy, which facilitates the appearance of disseminated forms as well as unusual presentations. We present the case of a 66-year-old woman with isolated tenosynovitis due to Histoplasma capsulatum 25 years after a kidney transplant.

Association between inappropriate empirical antimicrobial therapy and mortality in gram-negative bloodstream infections in patients with febrile neutropenia and hematological malignancy.

BACKGROUND AND OBJECTIVE: Inappropriate initial antimicrobial therapy has been associated with high mortality in patients with gram-negative bacilli bloodstream infections during febrile neutropenia following chemotherapy for hematological malignancies. The aim of this study is to determine this association in our hospital. METHODS: A single center, retrospective, cohort study of bloodstream infection due to gram-negative bacilli and febrile neutropenia was conducted. Clinical characteristics, microbiological etiology, antimicrobial resistance profile, empirical and targeted antibiotic therapy, intensive care unit admission, persistent bacteremia and mortality were analyzed. RESULTS: Of the 171 episodes of bloodstream infection due to gram-negative bacilli, empirical antimicrobial therapy was inappropriate in 43 episodes (25.1 %). There was a significant difference in mortality at 7 and 30 days between patients who received appropriate versus inappropriate empirical treatment (4.6 % versus 13.9 %, p = 0.04; 15.6 % versus 32.5 %, p = 0.016). Inappropriate empirical treatment (RR, 2.97 [95 % CI, 1.01-8.74]), shock at the time of febrile neutropenia diagnosis (RR, 6.5 [95 % CI, 1.83-23.05]) carbapenem-resistant microorganism (RR, 3.73 [95 % CI, 1.14-12.24]) and persistent bacteremia (RR, 84.6 [95 % CI, 11.3-629.4]) were associated with an increased mortality at 7 and 30 days. In the multivariate analysis, shock (RR, 4.85 [95 % CI, 2.10-11.65]) and persistent bacteremia was independently associated with increased 30-day mortality, but inappropriate empirical antimicrobial therapy was not an independent prognostic determinant (RR, 1.66 [0.53-4.82]). CONCLUSION: Shock at the time of febrile neutropenia diagnosis contributes to mortality in patients with gram-negative bacilli bloodstream infection, in this scenario, appropriate empirical antimicrobial therapy should be encouraged.

Anti-GM-CSF Neutralizing Autoantibodies in Colombian Patients with Disseminated Cryptococcosis.

BACKGROUND: Cryptococcosis is a potentially life-threatening fungal disease caused by encapsulated yeasts of the genus Cryptococcus, mostly C. neoformans or C. gattii. Cryptococcal meningitis is the most frequent clinical manifestation in humans. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been discovered in otherwise healthy adult patients with cryptococcal meningitis, mostly caused by C. gattii. We hypothesized that three Colombian patients with cryptococcal meningitis caused by C. neoformans in two of them would carry high plasma levels of neutralizing auto-Abs against GM-CSF. METHODS: We reviewed medical and laboratory records, performed immunological evaluations, and tested for anti-cytokine auto-Abs three previously healthy HIV-negative adults with disseminated cryptococcosis. RESULTS: Peripheral blood leukocyte subset levels and serum immunoglobulin concentrations were within the normal ranges. We detected high levels of neutralizing auto-Abs against GM-CSF in the plasma of all three patients. CONCLUSIONS: We report three Colombian patients with disseminated cryptococcosis associated with neutralizing auto-Abs against GM-CSF. Further studies should evaluate the genetic contribution to anti-GM-CSF autoantibody production and the role of the GM-CSF signaling pathway in the immune response to Cryptococcus spp.

Breakthrough Invasive Sinusitis by Hormographiella aspergillata in a Neutropenic Patient Receiving Voriconazole Therapy: A Case Report and Review of Breakthrough H. aspergillata Infections.

Breakthrough invasive infections occurs during the use of antifungals both in prophylaxis and therapy, it favors the emergence of new pathogens in the fungal landscape. Hormographiella aspergillata is considered a rare but emerging pathogen in the era of broad-spectrum antifungal use in patients with hematological malignancies. Here, we present a case report of invasive sinusitis due to Hormographiella aspergillata, manifesting as a breakthrough infection in a patient with severe aplastic anemia under treatment with voriconazole for invasive pulmonary aspergilosis. Also, we make a review of H. aspergillata breakthrough infections published in the literature.

Posaconazole versus voriconazole for primary treatment of invasive aspergillosis: a phase 3, randomised, controlled, non-inferiority trial.

BACKGROUND: Voriconazole has been recommended as primary treatment for patients with invasive aspergillosis. Intravenous and tablet formulations of posaconazole that have improved systemic absorption could be an effective alternative to voriconazole. We aimed to assess non-inferiority of posaconazole to voriconazole for the primary treatment of invasive aspergillosis. METHODS: We did a randomised, prospective, double-blind, double-dummy, controlled trial comparing posaconazole (intravenous or oral posaconazole 300 mg twice on day 1, followed by 300 mg once a day for days 2-84) with voriconazole (6 mg/kg intravenous or 300 mg oral twice on day 1 followed by 4 mg/kg intravenously or 200 mg orally twice a day for days 2-84) for 12 weeks or less in the primary treatment of invasive aspergillosis. Participants were from 91 study sites in 26 countries, were aged 13 years or older, weighed at least 40 kg, and met criteria for proven, probable, or possible fungal disease. Participants were randomly assigned (1:1) via a computer-generated randomisation schedule with stratification by risk status. The primary endpoint was cumulative all-cause mortality up until day 42 in the intention-to-treat (ITT) population (defined as randomly assigned participants who received ≥1 dose of study drug), with a 10% non-inferiority margin. The ITT population was also evaluated for safety. This study is registered with ClinicalTrials.gov, NCT01782131, and EudraCT, 2011-003938-14. FINDINGS: Between Oct 25, 2013, and Sept 10, 2019, of 653 individuals assessed for eligibility, 575 ITT participants were randomly assigned and received one or more doses of study drug (n=288 [50%] posaconazole, n=287 [50%] voriconazole). Mortality up until day 42 was 15% (44 of 288) in the posaconazole group and 21% (59 of 287) in the voriconazole group (treatment difference -5·3% [95% CI -11·6 to 1·0]; p<0·0001). Mortality up until day 42 in the full-analysis-set subpopulation (ITT participants with proven or probable invasive aspergillosis) supported this conclusion: 31 (19%) of 163 participants in the posaconazole group and 32 (19%) of 171 participants in the voriconazole group (treatment difference 0·3% [95% CI -8·2 to 8·8]). The most frequently reported treatment-related adverse events (incidence >3%) were increased aspartate aminotransferase (AST) or alanine aminotransferase (ALT), nausea, hypokalaemia, and vomiting in the posaconazole group and increased ALT, AST, or alkaline phosphatase, hallucination, increased γ-glutamyltransferase peptidase, nausea, and blurred vision in the voriconazole group. The overall incidence of treatment-related adverse event rates in the ITT population was 30% for posaconazole and 40% for voriconazole (treatment difference -10·2% [95% CI -17·9 to -2·4]). INTERPRETATION: Posaconazole was non-inferior to voriconazole for all-cause mortality up until day 42 in participants with invasive aspergillosis. Posaconazole was well tolerated, and participants had fewer treatment-related adverse events than in the voriconazole group. This study supports the use of posaconazole as a first-line treatment for the condition. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co, Inc.

Multifocal skeletal tuberculosis with mycobacteremia after kidney transplantation: A case report.

Solid organ transplant recipients have a higher risk of active Mycobacterium tuberculosis infection (TB) compared to the general population. Recognized risk factors are immunosuppressant use, graft dysfunction, diabetes mellitus, liver disease caused by the hepatitis C virus, and co-infections by other opportunists. Most of the active TB cases reported in solid organ transplant recipients occur in kidney transplant patients, especially if they come from M tuberculosis-endemic areas. Extrapulmonary and disseminated TB are among the wide spectrum of clinical presentations found, but the lungs are the most common organ affected. Disseminated disease occurs in up to a third of the affected population, however, multifocal osteoarticular TB with mycobacteremia is unusual. We report the case of a kidney transplant patient with disseminated M tuberculosis infection, who presented with multifocal skeletal TB.

Successful treatment of thrombotic microangiopathy associated with dengue infection: A case report and literature review.

Dengue infection has been associated with multiple renal complications, including glomerulonephritis, acute tubular necrosis, tubulointerstitial nephritis, and thrombotic microangiopathy (TMA), this last one being a rare complication of dengue, with only a few reported cases. TMA associated with dengue can be explained by an alteration in the activity of the enzyme ADAMTS13, leading to thrombotic thrombocytopenic purpura; or it can be secondary to direct or indirect endothelial injury by the virus, which leads to hemolytic uremic syndrome. Here, we present a case of severe TMA, not related to ADAMTS13, which was clearly associated with dengue infection.

Pharmacokinetic and Exposure Response Analysis of the Double-Blind Randomized Study of Posaconazole and Voriconazole for Treatment of Invasive Aspergillosis.

BACKGROUND AND OBJECTIVE: A double-blind phase 3 study was conducted to compare posaconazole 300 mg intravenously (IV)/300 mg orally once daily (twice daily day 1) with voriconazole 4 mg/kg IV twice daily/200 mg orally twice daily (6 mg/kg day 1) for treatment of invasive aspergillosis. This analysis was conducted to summarize the pharmacokinetics and exposure-response relationships of posaconazole and voriconazole using plasma trough concentration (Ctrough) as a surrogate for exposure from the double-blind phase 3 study. METHODS: The pharmacokinetic evaluable population included all intention-to-treat (ITT) participants with at least one plasma concentration during the treatment period. Treatment blinding was maintained without therapeutic drug monitoring. Ctrough sampling occurred throughout treatment; efficacy and safety were evaluated using quartiles determined by mean Ctrough concentrations. Exposure efficacy variables included day 42 all-cause mortality (primary study endpoint) and global clinical response. Exposure safety variables included all adverse events and treatment-related adverse events. RESULTS: The pharmacokinetic analysis population included 506 of 575 ITT participants (437 with Ctrough concentrations: 228 posaconazole, 209 voriconazole). No trend was seen across quartiles of posaconazole Ctrough for the key efficacy endpoint of all-cause mortality through day 42. Participants in the highest quartile of voriconazole Ctrough had higher all-cause mortality through day 42 than participants in the lower three quartiles of voriconazole Ctrough. Similar findings were observed for global clinical response and Ctrough. No clear exposure safety trend by quartile was seen for posaconazole or voriconazole. CONCLUSIONS: A strong exposure-response relationship was not observed across the range of exposure from the administered doses and formulations for posaconazole or voriconazole. TRIAL REGISTRATION: NCT01782131; registered January 30, 2013.

Brain abscess caused by Cladophialophora bantiana after renal allograft loss: A case report / Absceso cerebral por Cladophialophora bantiana en un paciente con trasplante renal: reporte de un caso

Cerebral feohifomycosis are severe infections caused by dematiaceous fungi. Cladophialophora bantiana is one of the most commonly isolated species; it has central nervous system tropism and it often manifests as a brain abscess in immunocompetent patients. In immunocompromised patients, it can lead to brain abscesses and disseminated infections. Despite the availability of broad-spectrum antifungal drugs, it is a must to perform surgical management, in addition to drug therapy. However, mortality is high. The diagnostic approach must be invasive to establish a timely diagnosis and direct treatment based on culture and susceptibility tests. We report a case of brain abscess caused by C. bantiana in an immunosuppressed patient who was treated with surgical resection and voriconazole with an adequate response to therapy and without neurological sequels.

Las feohifomicosis cerebrales son infecciones graves causadas por mohos dematiáceos, entre los cuales Cladophialophora bantiana es una de las especies más comúnmente aislada. Esta tiene tropismo por el sistema nervioso central y frecuentemente produce abscesos cerebrales en pacientes inmunocompetentes; además, en los inmunocomprometidos también puede ocasionar infección diseminada. Pese a la disponibilidad de medicamentos antifúngicos de amplio espectro, a menudo se requiere también la intervención quirúrgica; de todas maneras, la mortalidad es elevada. El diagnóstico debe hacerse interviniendo para tomar la muestra y hacer el cultivo y las pruebas de sensibilidad. Se presenta aquí el caso de un paciente con trasplante renal que presentó un absceso cerebral por C. bantiana, el cual se extrajo mediante resección quirúrgica. El paciente recibió tratamiento con voriconazol, con adecuada respuesta, mejoría y sin secuelas neurológicas.

[Severe hypoxemic respiratory failure caused by Pneumocystis jirovecii in a late kidney transplant recipient].

Pneumonia caused by Pneumocystis jirovecii is an uncommon infection in kidney transplant patients that can have an acute and rapid progression to respiratory failure and death. The period of greatest risk occurs in the first six months after the transplant, and it relates to the high doses of immunosuppression drugs required by patients. However, it may occur late, associated with the suspension of prophylaxis with trimethoprim-sulfamethoxazole.We present two cases of renal transplant patients who had severe hypoxemic respiratory failure due to P. jirovecii six years after transplantation. In addition to steroids, they received treatment with trimethoprim-sulfamethoxazole. One patient died, while the other had clinical recovery, with preservation of the renal graft function.

Tiroiditis subaguda y tirotoxicosis posterior a vacuna contra SARS-CoV-2: reporte de 2 casos / Subacute thyroiditis and thyrotoxicosis after SARS-CoV-2 vaccine: report of 2 cases

La enfermedad por coronavirus SARS-CoV-2 que surgió en el año 2019 (COVID-19), ha obligado al rápido desarrollo de vacunas para prevenir su propagación e intentar controlar la pandemia. Dentro de las vacunas desarrolladas, las primeras en ser aprobadas con una tecnología nueva en el campo de la vacunación, fueron las vacunas basadas en ARNm (ácido ribonucleico mensajero), que lograron tasas de efectividad cercanas al 95 % para la prevención de la enfermedad COVID-19 grave. Los eventos adversos comunes son reacciones locales leves, pero ha habido varios informes de pacientes que desarrollaron tiroiditis subaguda y disfunción tiroidea después de recibir la vacuna contra SARS-CoV-2. Este artículo presenta dos casos de tiroiditis subaguda poco después de recibir la vacuna contra COVID-19

The SARS-CoV-2 coronavirus disease which emerged in 2019 (COVID-19), has forced the rapid development of vaccines to prevent the spread of infection and attempt to control the pandemic. Among the vaccines developed, one of the first to be approved with a new technology in the field of vaccination, was the mRNA (messenger ribonucleic acid) vaccine, with rates of effectiveness close to 95% for the prevention of severe COVID-19 disease. Common adverse events are mild local reactions, but there have been some reports of patients developing sub-acute thyroiditis and thyroid dysfunction after receiving the SARS-CoV-2 vaccine. This article presents two case reports of subacute thyroiditis shortly after receiving the COVID-19 vaccine

Trasplante renal en pacientes con infección por el virus de la inmunodeficiencia humana: revisión de la literatura / Renal transplantation in patients with human immunodeficiency virus infection: a literature review

Resumen El trasplante renal es el tratamiento de elección en la enfermedad renal crónica terminal porque mejora la calidad de vida y la supervivencia de los pacientes al compararlo con la diálisis. Sin embargo, para mantener un injerto funcional y evitar el rechazo es necesario el uso de inmunosupresión potente durante toda la vida del injerto, lo cual puede tener como complicaciones una mayor susceptibilidad a presentar infecciones, desarrollo de cáncer, alteraciones metabólicas y problemas cardiovasculares. Los pacientes infectados con el virus de la inmunodeficiencia humana tienen alto riesgo de desarrollar enfermedad renal crónica terminal por múltiples causas. En el siglo pasado, el trasplante renal se consideraba contraindicado para estos pacientes. No obstante, hoy en día el trasplante renal se considera una opción terapéutica para pacientes adecuadamente seleccionados y con protocolos de manejo bien establecidos. Reportándose supervivencia reportadas del injerto y del paciente a tres años de 88,2 % y 82,6 % respectivamente. Este artículo de revisión tiene como objetivo revisar la experiencia mundial existente en el manejo de los pacientes trasplantados renal con infección por VIH.

Summary Kidney transplantation is the recommended treatment for end-stage chronic kidney disease, improving patients' quality of life and survival compared to dialysis. Nevertheless, to keep a functional graft and avoid rejection, strong immunosuppression is required during the graft's lifetime, which can lead to complications such as increased susceptibility to infections, development of cancer, metabolic changes and cardiovascular problems. Patients infected with the human immunodeficiency virus are at high risk of developing end-stage renal disease. Previous this century, kidney transplantation was considered contraindicated for these patients group. However nowadays, kidney transplantation is a therapeutic option for well-selected patients and with well-established treatment protocols. Several studies reported a three-year graft survival rate of 88,2% and patient survival of 82,6%. In this article, we present an overview of the worldwide experience with the treatment of kidney transplant patients with HIV infection.

Absceso cerebral por Cladophialophora bantiana en un paciente con trasplante renal: reporte de un caso / Brain abscess caused by Cladophialophora bantiana after renal allograft loss: A case report

Resumen Las feohifomicosis cerebrales son infecciones graves causadas por mohos dematiáceos, entre los cuales Cladophialophora bantiana es una de las especies más comúnmente aislada. Esta tiene tropismo por el sistema nervioso central y frecuentemente produce abscesos cerebrales en pacientes inmunocompetentes; además, en los inmunocomprometidos también puede ocasionar infección diseminada. Pese a la disponibilidad de medicamentos antifúngicos de amplio espectro, a menudo se requiere también la intervención quirúrgica; de todas maneras, la mortalidad es elevada. El diagnóstico debe hacerse interviniendo para tomar la muestra y hacer el cultivo y las pruebas de sensibilidad. Se presenta aquí el caso de un paciente con trasplante renal que presentó un absceso cerebral por C. bantiana, el cual se extrajo mediante resección quirúrgica. El paciente recibió tratamiento con voriconazol, con adecuada respuesta, mejoría y sin secuelas neurológicas.

Abstract Cerebral feohifomycosis are severe infections caused by dematiaceous fungi. Cladophialophora bantiana is one of the most commonly isolated species; it has central nervous system tropism and it often manifests as a brain abscess in immunocompetent patients. In immunocompromised patients, it can lead to brain abscesses and disseminated infections. Despite the availability of broad-spectrum antifungal drugs, it is a must to perform surgical management, in addition to drug therapy. However, mortality is high. The diagnostic approach must be invasive to establish a timely diagnosis and direct treatment based on culture and susceptibility tests. We report a case of brain abscess caused by C. bantiana in an immunosuppressed patient who was treated with surgical resection and voriconazole with an adequate response to therapy and without neurological sequels.

Insuficiencia respiratoria hipoxémica grave por Pneumocystis jirovecii después de trasplante renal / Severe hypoxemic respiratory failure caused by Pneumocystis jirovecii in a late kidney transplant recipient

Resumen La neumonitis por Pneumocystis jirovecii es una infección infrecuente en pacientes con trasplante de riñón, que se presenta de forma aguda y puede progresar rápidamente hasta la insuficiencia respiratoria y la muerte. El período de mayor riesgo es el de los primeros seis meses después del trasplante, y se asocia con las altas dosis de medicamentos inmunosupresores que reciben los pacientes. La condición también puede presentarse de manera tardía, asociada con la suspensión de la profilaxis con trimetoprim-sulfametoxazol. Se reportan dos casos de pacientes con trasplante renal que presentaron insuficiencia respiratoria hipoxémica grave por P. jirovecii pasados seis años del trasplante, y que fueron tratados con trimetoprim-sulfametoxazol y esteroides. Uno de los pacientes murió y el otro se recuperó sin que hubiera efectos en la función del injerto renal.

Abstract Pneumonia caused by Pneumocystis jirovecii is an uncommon infection in kidney transplant patients that can have an acute and rapid progression to respiratory failure and death. The period of greatest risk occurs in the first six months after the transplant, and it relates to the high doses of immunosuppression drugs required by patients. However, it may occur late, associated with the suspension of prophylaxis with trimethoprim-sulfamethoxazole. We present two cases of renal transplant patients who had severe hypoxemic respiratory failure due to P. jirovecii six years after transplantation. In addition to steroids, they received treatment with trimethoprim-sulfamethoxazole. One patient died, while the other had clinical recovery, with preservation of the renal graft function.