Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Infecciones por VIH/complicaciones , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Neoplasias Cutáneas/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Linfocitos T CD4-Positivos/inmunología , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , VIH/aislamiento & purificación , Infecciones por VIH/virología , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/virología , Humanos , Pronóstico , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/virología , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/virologíaRESUMEN
A 39-year-old male, who received a facial allograft (cytomegalovirus [CMV] donor-seropositive, recipient-seronegative), developed multidrug-resistant CMV infection despite valganciclovir prophylaxis (900 mg/day) 6 months post transplantation. Lower extremity weakness with upper and lower extremity paresthesias developed progressively 11 months post transplantation, coinciding with immune control of CMV. An axonal form of Guillain-Barré syndrome was diagnosed, based on electrophysiological evidence of a generalized, non-length-dependent, sensorimotor axonal polyneuropathy. Treatment with intravenous immunoglobulin led to complete recovery without recurrence after 6 months.
Asunto(s)
Infecciones por Citomegalovirus/complicaciones , Trasplante Facial/efectos adversos , Síndrome de Guillain-Barré/etiología , Inmunoglobulinas Intravenosas/uso terapéutico , Adulto , Antivirales/uso terapéutico , Citomegalovirus/efectos de los fármacos , Citomegalovirus/aislamiento & purificación , Farmacorresistencia Viral Múltiple , Ganciclovir/análogos & derivados , Ganciclovir/uso terapéutico , Humanos , Huésped Inmunocomprometido , Masculino , Factores de Tiempo , Valganciclovir , Carga Viral , ViremiaRESUMEN
Opportunistic infectious diseases in patients are variable and depend on the host as well as the type of immunosuppression. Cord blood transplant recipients appear to be particularly vulnerable to infectious complications. Sequential or concurrent opportunistic infectious diseases can be particularly difficult to manage and have increased mortality. We present a young patient, status post cord blood transplantation for acute myelogenous leukemia, who developed a large pulmonary mass-like infection with Aspergillus, cytomegalovirus, and Mycobacterium avium complex. Radiological, surgical, and pathological features are described.
Asunto(s)
Infecciones por Citomegalovirus/patología , Sangre Fetal/trasplante , Infección por Mycobacterium avium-intracellulare/diagnóstico por imagen , Infecciones Oportunistas/patología , Aspergilosis Pulmonar/patología , Adulto , Coinfección , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/diagnóstico por imagen , Resultado Fatal , Femenino , Humanos , Leucemia Mieloide Aguda/terapia , Infección por Mycobacterium avium-intracellulare/complicaciones , Infecciones Oportunistas/diagnóstico por imagen , Infecciones Oportunistas/microbiología , Aspergilosis Pulmonar/complicaciones , Enfisema Pulmonar/diagnóstico por imagen , Enfisema Pulmonar/microbiología , RadiografíaRESUMEN
We report on the management of the first full-face transplantation in a sensitized recipient with a positive preoperative crossmatch and subsequent antibody-mediated rejection (AMR). The recipient is a 45-year-old female who sustained extensive chemical burns, with residual poor function and high levels of circulating anti-HLA antibodies. With a clear immunosuppression plan and salvage options in place, a full-face allotransplant was performed using a crossmatch positive donor. Despite plasmapheresis alongside a standard induction regimen, clinical signs of rejection were noted on postoperative day 5 (POD5). Donor-specific antibody (DSA) titers rose with evidence of C4d deposits on biopsy. By POD19, biopsies showed Banff Grade III rejection. Combination therapy consisting of plasmapheresis, eculizumab, bortezomib and alemtuzumab decreased DSA levels, improved clinical exam, and by 6 months postop she had no histological signs of rejection. This case is the first to demonstrate evidence and management of AMR in face allotransplantation. Our findings lend support to the call for an update to the Banff classification of rejection in vascularized composite tissue allotransplantation (VCA) to include AMR, and for further studies to better classify the histology and mechanism of action of AMR in VCA.
Asunto(s)
Trasplante Facial , Rechazo de Injerto/inmunología , Aloinjertos , Femenino , Humanos , Inmunidad Celular , Persona de Mediana EdadRESUMEN
BK virus (BKV), a ubiquitous human polyomavirus, usually does not cause disease in healthy individuals. BKV reactivation and disease can occur in immunosuppressed individuals, such as those who have undergone renal transplantation or hematopoietic cell transplantation (HCT). Clinical manifestations of BKV disease include graft dysfunction and failure in renal transplant recipients; HCT recipients frequently experience hematuria, cystitis, hemorrhagic cystitis (HC), and renal dysfunction. Studies of HCT patients have identified several risk factors for the development of BKV disease including myeloablative conditioning, acute graft-versus-host disease, and undergoing an umbilical cord blood (uCB) HCT. Although these risk factors indicate that alterations in the immune system are necessary for BKV pathogenesis in HCT patients, few studies have examined the interactions between host immune responses and viral reactivation in BKV disease. Specifically, having BKV immunoglobulin-G before HCT does not protect against BKV infection and disease after HCT. A limited number of studies have demonstrated BKV-specific cytotoxic T cells in healthy adults as well as in post-HCT patients who had experienced HC. New areas of research are required for a better understanding of this emerging infectious disease post HCT, including prospective studies examining BK viruria, viremia, and their relationship with clinical disease, a detailed analysis of urothelial histopathology, and laboratory evaluation of systemic and local cellular and humoral immune responses to BKV in patients receiving HCT from different sources, including uCB and haploidentical donors.
Asunto(s)
Virus BK , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Riñón/efectos adversos , Infecciones por Polyomavirus/transmisión , Infecciones Tumorales por Virus/transmisión , Adulto , Humanos , Infecciones por Polyomavirus/inmunología , Infecciones por Polyomavirus/virología , Infecciones Tumorales por Virus/inmunología , Infecciones Tumorales por Virus/virologíaRESUMEN
Parainfluenza infection is a cause of significant morbidity and mortality in allogeneic hematopoietic stem cell transplant (HSCT) patients. DAS181 is a novel antiviral agent with activity against influenza and parainfluenza. We report the first 2 cases, to our knowledge, of successful DAS181 use in ventilated HSCT patients with severe parainfluenza lung disease.
Asunto(s)
Antivirales/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas , Huésped Inmunocomprometido , Inmunosupresores/uso terapéutico , Infecciones por Paramyxoviridae/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Proteínas Recombinantes de Fusión/uso terapéutico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Paramyxoviridae/complicaciones , Infecciones por Paramyxoviridae/inmunología , Neumonía Viral/complicaciones , Neumonía Viral/inmunología , Prednisona/uso terapéutico , Respiración Artificial , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Sirolimus/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Data on the incidence, timing, and risk factors for herpes zoster (HZ) in heart transplant (HT) recipients are limited. METHODS: We determined HZ incidence rates and actuarial estimates of time to first HZ episode in 314 HT recipients at our institution from 1995 to 2010. We developed Cox models to assess potential risk factors for HZ in HT. RESULTS: Median age at HT was 54 (range, 17-71) years; 237 (76%) were male. There were 60 episodes of HZ in 51 patients, with an overall incidence rate of 31.6 cases (95% confidence interval [CI], 23.5-41.6)/1000 person-years. Although most cases occurred during the first post-HT year, cumulative HZ incidence was 0.078 at 1, 0.15 at 5, and 0.20 at 10 years. Many patients had substantial HZ morbidity, including 14% with HZ ophthalmicus and 45% with post-herpetic neuralgia. Adjusting for age, gender, and acute cellular rejection episodes, exposure to mycophenolate mofetil (MMF) was an independent risk factor for HZ (adjusted hazard ratio [HR] 2.18; 95% CI, 1.20-3.96; P = 0.01), while ganciclovir-based cytomegalovirus prophylaxis reduced HZ risk (adjusted HR 0.09; 95% CI, 0.01-0.71; P = 0.02). Although age and female gender increased HZ risk, the magnitude of their effect was not statistically significant in Cox models. CONCLUSIONS: HZ is common and morbid after HT, particularly with MMF exposure. Ganciclovir prophylaxis is effective in reducing the short-term risk of HZ, but the steady incidence of cases for years post HT makes long-term HZ prevention challenging. Augmenting varicella zoster virus immunity post HT with vaccines warrants further exploration.
Asunto(s)
Cardiomiopatías/cirugía , Rechazo de Injerto/prevención & control , Cardiopatías Congénitas/cirugía , Trasplante de Corazón , Herpes Zóster/epidemiología , Inmunosupresores/uso terapéutico , Ácido Micofenólico/análogos & derivados , Neuralgia Posherpética/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Antivirales/uso terapéutico , Estudios de Cohortes , Infecciones por Citomegalovirus/prevención & control , Femenino , Ganciclovir/uso terapéutico , Herpes Zóster/inmunología , Herpes Zóster Oftálmico/epidemiología , Humanos , Huésped Inmunocomprometido , Incidencia , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Adulto JovenRESUMEN
We reviewed medical records of all patients (n = 4) who underwent facial composite tissue allotransplantation (FCTA) at our center between April 2009 and May 2011; data were censored in June 2012. We searched for FCTA publications and reviewed them for infectious complications and prophylaxis strategies. Three patients received full and one partial FCTA at our institution. Two recipients were cytomegalovirus (CMV) Donor (D)+/Recipient (R)- and two CMV D+/R+. Perioperative prophylaxis included vancomycin, cefazolin and micafungin and was adjusted based on peritransplant cultures. Additional prophylaxis included trimethoprim-sulfamethoxazole and valganciclovir. Two recipients developed surgical site infection and two developed pneumonia early after transplantation. Both CMV D+/R- recipients developed CMV disease after discontinuation of prophylaxis, recovered with valganciclovir treatment and did not experience subsequent rejection. Other posttransplant infections included bacterial parotitis, polymicrobial bacteremia, invasive dermatophyte infection and Clostridium difficile-associated diarrhea. Nine publications described infectious complications in another 9 FCTA recipients. Early posttransplant infections were similar to those observed in our cohort and included pulmonary, surgical-site and catheter-associated infections. CMV was the most frequently described opportunist. In conclusion, infections following FCTA were related to anatomical, technical and donor/recipient factors. CMV disease occurred in D+/R- recipients after prophylaxis, but was not associated with rejection.
Asunto(s)
Infecciones por Citomegalovirus/etiología , Cara/cirugía , Rechazo de Injerto/etiología , Complicaciones Posoperatorias , Infección de la Herida Quirúrgica/etiología , Trasplante de Tejidos/efectos adversos , Adulto , Antiinfecciosos/uso terapéutico , Infecciones Relacionadas con Catéteres/tratamiento farmacológico , Infecciones Relacionadas con Catéteres/etiología , Citomegalovirus , Infecciones por Citomegalovirus/tratamiento farmacológico , Femenino , Rechazo de Injerto/tratamiento farmacológico , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Neumonía/tratamiento farmacológico , Neumonía/etiología , Pronóstico , Infección de la Herida Quirúrgica/tratamiento farmacológico , Trasplante Homólogo , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoRESUMEN
BACKGROUND: A recent randomized trial demonstrated that 1 year of antiviral prophylaxis for cytomegalovirus (CMV) after lung transplantation is superior to 3 months of treatment for prevention of CMV disease. However, it is uncertain if a shorter duration of prophylaxis might result in a similar rate of CMV disease among select lung transplant (LT) recipients who are at lower risk for CMV disease, based on baseline donor (D) and recipient (R) CMV serologies. METHODS: We retrospectively assessed incidence, cumulative probability, and predictors of CMV disease and viremia in LT recipients transplanted between July 2004 and December 2009 at our center, where antiviral CMV prophylaxis for 6-12 months is standard. RESULTS: Of 129 LT recipients, 94 were at risk for CMV infection based on donor CMV seropositivity (D+) or recipient seropositivity (R+); 14 developed CMV disease (14.9%): 11 with CMV syndrome, 2 with pneumonitis, and 1 with gastrointestinal disease by the end of follow-up (October 2010); 17 developed asymptomatic CMV viremia (18.1%). The cumulative probability of CMV disease was 17.4% 18 months after transplantation. CMV D+/R- recipients who routinely received 1 year of prophylaxis were more likely to develop CMV disease compared with D+/R+ or D-/R+ recipients, who routinely received 6 months of prophylaxis (12/45 vs. 2/25 vs. 0/24, P = 0.005). Recipients who stopped CMV prophylaxis before 12 months (in D+/R- recipients) and 6 months (in R+ recipients) tended to develop CMV disease more than those who did not (9/39 vs. 3/41, P = 0.06). CONCLUSIONS: On a 6-month CMV prophylaxis protocol, few R+ recipients developed CMV disease in this cohort. In contrast, despite a 12-month prophylaxis protocol, D+/R- LT recipients remained at highest risk for CMV disease.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por Citomegalovirus/prevención & control , Trasplante de Pulmón , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: The incidence of infection with non-tuberculous mycobacteria (NTM) after lung transplant is insufficiently defined. Data on the impact of NTM infection on lung transplant survival are conflicting. METHODS: To quantify the incidence and outcomes of colonization and disease with NTM in patients after lung transplantation, the medical records, chest imaging, and microbiology data of 237 consecutive lung transplant recipients between 1990 and 2005 were reviewed. American Thoracic Society (ATS)/Infectious Diseases Society of America and Centers for Disease Control criteria were used to define pulmonary NTM disease and NTM surgical-site infections (SSI), respectively. Incidence rates for NTM colonization and disease were calculated. Comparisons of median survival were done using the log-rank test. RESULTS: NTM were isolated from 53 of 237 patients (22.4%) after lung transplantation over a median of 25.2 months of follow-up. The incidence rate of NTM isolation was 9.0/100 person-years (95% confidence interval [CI), 6.8-11.8), and the incidence rate of NTM disease was 1.1/100 person-years (95% CI 0.49-2.2). The most common NTM isolated was Mycobacterium avium complex (69.8%), followed by Mycobacterium abscessus (9.4%), and Mycobacterium gordonae (7.5%). Among these 53 patients, only 2 patients met ATS criteria for pulmonary disease and received treatment for M. avium. One patient had recurrent colonization after treatment, the other one was cured. Four of the 53 patients developed SSI, 3 caused by M. abscessus and 1 caused by Mycobacterium chelonae. Three of these patients had persistent infection requiring chronic suppressive therapy and one died from progressive disseminated disease. A total of 47 (89%) patients who met microbiologic but not radiographic criteria for pulmonary infection were not treated and were found to have only transient colonization. Median survival after transplantation was not different between patients with transient colonization who did not receive treatment and those who never had NTM isolated. CONCLUSION: Episodic isolation of NTM from lung transplant recipients is common. Most isolates occur among asymptomatic patients and are transient. Rapidly growing NTM can cause significant SSI, which may be difficult to cure. NTM disease rate is higher among lung transplant recipients than in the general population. In this cohort, NTM isolation was not associated with increased post-transplantation mortality.
Asunto(s)
Trasplante de Pulmón/efectos adversos , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Mycobacterium/aislamiento & purificación , Infecciones del Sistema Respiratorio/epidemiología , Infección de la Herida Quirúrgica/epidemiología , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Mycobacterium/clasificación , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/mortalidad , Complejo Mycobacterium avium/aislamiento & purificación , Micobacterias no Tuberculosas/aislamiento & purificación , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/mortalidad , Infección de la Herida Quirúrgica/microbiología , Infección de la Herida Quirúrgica/mortalidad , Adulto JovenRESUMEN
The kinetics of serum (1 â 3)-ß-d-glucan (BG) following the diagnosis of invasive fungal disease and administration of antifungal therapy are poorly characterized. It is unknown whether early BG changes have prognostic implications. We assessed the post-diagnostic kinetics of BG in patients with an initial serum BG ≥80 pg/mL and at least one additional post-diagnostic BG value in the setting of invasive aspergillosis (IA, n=69), invasive candidiasis (IC, n=40), or Pneumocystis jirovecii pneumonia (PCP, n = 18), treated with antifungal therapy. Clinical failure of antifungal therapy and mortality were assessed at 6 and 12 weeks, and Cox modelling was used to assess the hazard of initial BG and change in BG at 1 or 2 weeks for these outcomes. In patients with at least two BG values, median initial BG was >500 pg/mL (interquartile range (IQR) 168 to >500; range 80 to >500) in IA, 136 pg/mL (IQR 88 to >500; range 31 to >500) in IC and >500 pg/mL (IQR 235 to >500; range 86 to >500) in PCP. In patients with at least two BG values through to 1 week after diagnosis, overall 1-week decline in BG was 0 pg/mL (IQR 0-53) in IA, 0 (IQR - 65 to 12) in IC and 17 (IQR 0-82) in PCP. Most patients with BG values through 6 and 12 weeks had persistent levels >80 pg/mL. Initial BG and the early trajectory of BG were not predictive of 6-week or 12-week clinical failure or mortality. Whereas BG eventually declines in patients with IA, IC and PCP, it lacks prognostic value within a clinically meaningful time frame.
Asunto(s)
Antifúngicos/uso terapéutico , Aspergilosis/diagnóstico , Candidiasis Invasiva/diagnóstico , Neumonía por Pneumocystis/diagnóstico , beta-Glucanos/sangre , Adulto , Anciano , Anciano de 80 o más Años , Antígenos Fúngicos/sangre , Aspergilosis/tratamiento farmacológico , Aspergilosis/microbiología , Aspergilosis/mortalidad , Aspergillus/clasificación , Aspergillus/efectos de los fármacos , Candida/clasificación , Candida/efectos de los fármacos , Candidiasis Invasiva/tratamiento farmacológico , Candidiasis Invasiva/microbiología , Candidiasis Invasiva/mortalidad , Causas de Muerte , Femenino , Humanos , Cinética , Masculino , Persona de Mediana Edad , Pneumocystis carinii/efectos de los fármacos , Neumonía por Pneumocystis/tratamiento farmacológico , Neumonía por Pneumocystis/microbiología , Neumonía por Pneumocystis/mortalidad , Pronóstico , Proteoglicanos , Insuficiencia del Tratamiento , Adulto JovenRESUMEN
Parainfluenza virus (PIV) infections can cause serious respiratory infections and death in immunocompromised patients. No antiviral agents have proven efficacy against PIV, and therapy generally consists of supportive care. DAS181, a novel sialidase fusion protein that temporarily disables airway epithelial PIV receptors by enzymatic removal of sialic acid moieties, has been shown to inhibit infection with PIV strains in vitro and in an animal model. We describe here the clinical course of 2 immunocompromised patients with PIV-3 infection, one with a history of lung transplantation and the other neutropenic after autologous hematopoietic stem cell transplantation for multiple myeloma. Both patients had substantial clinical improvement in respiratory and systemic symptoms after a 5-day DAS181 treatment course, although the clinical improvement in the autologous stem cell transplantation patient also paralleled neutrophil engraftment.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Pulmón/efectos adversos , Virus de la Parainfluenza 3 Humana/efectos de los fármacos , Infecciones por Paramyxoviridae/tratamiento farmacológico , Proteínas Recombinantes de Fusión/uso terapéutico , Trasplante Homólogo/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Virus de la Parainfluenza 3 Humana/genética , Virus de la Parainfluenza 3 Humana/aislamiento & purificación , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/virología , Resultado del TratamientoRESUMEN
Phaeohyphomycosis is an increasingly recognized cause of brain abscess in both immunocompetent and immunocompromised hosts. We report a case of cerebral phaeohyphomycosis in a 55-year-old male heart transplant recipient caused by Bipolaris spicifera. We review the literature regarding the pathogenesis, epidemiology, diagnosis, and management of infections with dematiaceous fungi.
Asunto(s)
Ascomicetos/aislamiento & purificación , Absceso Encefálico/microbiología , Feohifomicosis Cerebral/microbiología , Trasplante de Corazón/efectos adversos , Micosis/microbiología , Antifúngicos/uso terapéutico , Ascomicetos/clasificación , Ascomicetos/efectos de los fármacos , Absceso Encefálico/diagnóstico por imagen , Absceso Encefálico/tratamiento farmacológico , Feohifomicosis Cerebral/diagnóstico por imagen , Feohifomicosis Cerebral/tratamiento farmacológico , Humanos , Huésped Inmunocomprometido , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Micosis/diagnóstico por imagen , Micosis/tratamiento farmacológico , Pirimidinas/uso terapéutico , Radiografía , Resultado del Tratamiento , Triazoles/uso terapéutico , VoriconazolRESUMEN
BACKGROUND: Despite advances in cytomegalovirus (CMV) prophylaxis and therapy, some transplant recipients still develop refractory CMV infections. Maribavir (MBV), an investigational benzimidazole antiviral agent, acts by a mechanism different from that of existing anti-CMV drugs. Previous Phase I and II studies have demonstrated a favorable safety profile for MBV, but its utility in treatment of complex CMV syndromes is unknown. METHODS: Between June and December 2008, MBV was released for use under individual emergency investigational new drug applications requested by treating physicians and approved by the US Food and Drug Administration and local institutional review boards. Six patients (5 solid organ transplant recipients and 1 hematopoietic stem cell transplant recipient) who had failed to respond to other therapies and/or had known ganciclovir-resistant CMV were treated with MBV at a starting oral dose of 400 mg twice daily. RESULTS: Patients were treated for a median of 207 days (range, 15-376). Four of 6 patients had no detectable CMV DNAemia within 6 weeks of starting MBV therapy. One patient, who had an initial viral load of 1.8 million copies/mL, developed MBV resistance mutations. One patient, who had low serum levels of MBV, had persistent CMV DNAemia and viruria without developing genotypic or phenotypic resistance to MBV. One patient cleared CMV DNAemia, but died of pneumonia and multiorgan failure. No significant adverse effects attributable to MBV were observed. CONCLUSIONS: MBV deserves further systematic evaluation as treatment for CMV infection that is resistant and/or refractory to standard therapies, but its optimal dose, duration of therapy, and use in combinations versus as a single agent have yet to be determined.
Asunto(s)
Antivirales/administración & dosificación , Bencimidazoles/administración & dosificación , Infecciones por Citomegalovirus/tratamiento farmacológico , Farmacorresistencia Viral , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Órganos/efectos adversos , Ribonucleósidos/administración & dosificación , Adolescente , Adulto , Anciano , Antivirales/efectos adversos , Antivirales/farmacología , Antivirales/uso terapéutico , Bencimidazoles/efectos adversos , Bencimidazoles/farmacología , Bencimidazoles/uso terapéutico , Citomegalovirus/efectos de los fármacos , Citomegalovirus/genética , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/virología , Femenino , Ganciclovir/farmacología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Ribonucleósidos/efectos adversos , Ribonucleósidos/farmacología , Ribonucleósidos/uso terapéutico , Resultado del TratamientoRESUMEN
We describe a woman with relapsed acute myelogenous leukemia after allogeneic stem cell transplantation who developed disseminated Geotrichum candidum infection during chemotherapy-induced neutropenia. The isolate was susceptible to voriconazole, amphotericin B, and micafungin in vitro. We review the literature regarding invasive infections with G. candidum, which predominantly affect immunocompromised hosts, and discuss potential therapies for this rare pathogen.
Asunto(s)
Geotricosis/microbiología , Geotrichum , Leucemia Mieloide Aguda/complicaciones , Trasplante de Células Madre/efectos adversos , Trasplante Homólogo/efectos adversos , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Cateterismo Venoso Central/efectos adversos , Femenino , Geotricosis/diagnóstico , Geotricosis/tratamiento farmacológico , Geotrichum/clasificación , Geotrichum/efectos de los fármacos , Humanos , Persona de Mediana Edad , RecurrenciaRESUMEN
BACKGROUND: Acute limbic encephalitis has been reported in the setting of treatment-related immunosuppression and attributed to human herpesvirus-6 (HHV6) infection. Clinical and laboratory features of the syndrome, however, have not been well characterized. METHODS: We describe the clinical, EEG, MRI, and laboratory features of nine patients with acute limbic encephalitis after allogeneic hematopoietic stem cell transplantation (HSCT). To explore the relationship between HHV6 and this syndrome, we reviewed available CSF HHV6 PCR results from all HSCT patients seen at our center from March 17, 2003, through March 31, 2005. RESULTS: Patients displayed a consistent and distinctive clinical syndrome featuring anterograde amnesia, the syndrome of inappropriate antidiuretic hormone secretion, mild CSF pleocytosis, and temporal EEG abnormalities, often reflecting clinical or subclinical seizures. MRI showed hyperintensities within the uncus, amygdala, entorhinal area, and hippocampus on T2, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI) sequences. CSF PCR assays for HHV6 were positive in six of nine patients on initial lumbar puncture. All patients were treated with foscarnet or ganciclovir. Cognitive recovery varied among long-term survivors. The one brain autopsy showed limbic gliosis and profound neuronal loss in amygdala and hippocampus. Among 27 HSCT patients with CSF tested for HHV6 over a 2-year period, positive results occurred only in patients with clinical limbic encephalitis. CONCLUSIONS: Patients undergoing allogeneic hematopoietic stem cell transplantation are at risk for post-transplant acute limbic encephalitis (PALE), a distinct neurologic syndrome. Treatment considerations should include aggressive seizure control and, possibly, antiviral therapy. PALE can be associated with the CSF presence of human herpesvirus-6, but the pathogenic role of the virus requires further exploration.
Asunto(s)
Encefalitis por Herpes Simple/virología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpesvirus Humano 6/inmunología , Encefalitis Límbica/virología , Complicaciones Posoperatorias/virología , Adulto , Amnesia Anterógrada/inmunología , Amnesia Anterógrada/fisiopatología , Amnesia Anterógrada/virología , Amígdala del Cerebelo/patología , Amígdala del Cerebelo/fisiopatología , Antivirales/uso terapéutico , Diabetes Insípida/inmunología , Diabetes Insípida/fisiopatología , Diabetes Insípida/virología , Encefalitis por Herpes Simple/inmunología , Encefalitis por Herpes Simple/fisiopatología , Epilepsia del Lóbulo Temporal/inmunología , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/virología , Hipocampo/patología , Hipocampo/fisiopatología , Humanos , Encefalitis Límbica/inmunología , Encefalitis Límbica/fisiopatología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/inmunología , Complicaciones Posoperatorias/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: Nebulized amphotericin B deoxycholate (AmBd) has been used to prevent invasive pulmonary aspergillosis after lung transplantation. METHODS: In this retrospective study we compared the safety and tolerability of nebulized AmBd and nebulized liposomal amphotericin B (L-AmB) in 38 consecutive lung transplant recipients. Progress notes, medication administration records, microbiology, and pulmonary function reports were reviewed. Histologic sections from lung tissue were examined. Plasma amphotericin B levels were measured. RESULTS: A total of 1206 doses of AmBd and 1149 doses of L-AmB were administered. Eighteen patients received AmBd only, 11 received L-AmB only, and 9 received the medications sequentially. The total number of complaints vs. the number of doses administered was 1.0% for AmBd-treated patients and 1.2% for L-AmB-treated patients. No differences were observed between the treatment groups on lung biopsy specimens. Plasma amphotericin B levels were <0.2-0.9 microg/mL in AmBd-treated patients and <0.2 microg/mL in L-AmB-treated patients. CONCLUSIONS: In lung transplant recipients, both inhaled AmBd and L-AmB were safe and well tolerated over a large number of medication exposures.
Asunto(s)
Anfotericina B/administración & dosificación , Antifúngicos/administración & dosificación , Ácido Desoxicólico/administración & dosificación , Trasplante de Pulmón/efectos adversos , Micosis/tratamiento farmacológico , Aerosoles , Anfotericina B/efectos adversos , Anfotericina B/sangre , Química Farmacéutica , Ácido Desoxicólico/efectos adversos , Ácido Desoxicólico/sangre , Combinación de Medicamentos , Farmacorresistencia Fúngica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
We describe 2 patients who developed prolonged QTc interval on electrocardiogram while being treated with voriconazole. The first patient had undergone induction chemotherapy for acute myelogenous leukemia, and her course had been complicated by invasive aspergillosis and an acute cardiomyopathy. She developed torsades de pointes 3 weeks after starting voriconazole therapy. She was re-challenged with voriconazole without recurrent QTc prolongation or cardiac dysfunction. The second patient had a significantly prolonged QTc interval while on voriconazole therapy. We recommend careful monitoring for QTc prolongation and arrhythmia in patients who are receiving voriconazole, particularly those who have significant electrolyte disturbances, are on concomitant QT prolonging medications, have heart failure such as from a dilated cardiomyopathy, or have recently received anthracycline-based chemotherapy. The potential for synergistic cardiotoxicity must be carefully considered.