RESUMO
Transplant recipients are vulnerable to infections, including COVID-19, given their comorbidities and chronic immunosuppression. In this study, all hospitalized renal transplant recipients (RTR) with a positive nasal swab for Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2) seen consecutively between 03/01/2020 and 05/01/2020 at the Detroit Medical Center were included. Data on demographics, clinical presentation, laboratory findings, management, and outcomes were collected. Twenty-five patients were included, all African American (AA) and deceased-donor transplant recipients. The most common presenting symptom was dyspnea, followed by fever, cough and diarrhea. Multifocal opacities on initial chest x-ray were seen in 52% patients and 44% of patients had a presenting oxygen saturation of less than or equal to 94%. Four patients (16%) required transfer to the intensive care unit, one required intubation and one expired. COVID-19-infected RTR in this cohort had low mortality of 4% (n = 1). Despite multiple comorbidities and chronic immunosuppression, our cohort of African American RTR had favorable outcomes compared to other reports on COVID-19 in RTR.
Assuntos
Negro ou Afro-Americano , COVID-19/etnologia , Terapia de Imunossupressão/métodos , Unidades de Terapia Intensiva , Transplante de Rim , Falência Hepática/etnologia , Transplantados , Idoso , Comorbidade , Feminino , Humanos , Falência Hepática/cirurgia , Masculino , Michigan/epidemiologia , Pessoa de Meia-Idade , RNA Viral/análise , SARS-CoV-2/genéticaRESUMO
BACKGROUND: Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients. CMV cell-mediated immunity (CMV-CMI) as determined by a peptide-based enzyme-linked immunospot (ELISPOT) CMV assay may identify patients at risk for clinically significant CMV infection (CS-CMVi). METHODS: The CS-CMVi was defined as CMV viremia and/or disease necessitating antiviral therapy. CMV-CMI was characterized as high when the intermediate-early 1 (IE-1) antigen spot counts (SPCs) were >100 (cutoff 1) or when the IE-1 and phosphoprotein 65 antigen SPCs were both >100 SPCs per 250 000 cells (cutoff 2), and a low CMV-CMI when SPCs were below these thresholds. In this prospective multicenter study, we evaluated CMV-CMI every 2 weeks from the pretransplant period until 6 months posttransplantation in 241 allo-HCT recipients with positive CMV serostatus. The primary endpoint was CS-CMVi occurring within 2 weeks of the last measurement of CMV-CMI. RESULTS: CS-CMVi occurred in 70 allo-HCT recipients (29%). CMV-CMI was low in patients who experienced CS-CMVi (94%), whereas those who had a high CMV-CMI were less likely to have CS-CMVi (Pâ <â .0001). Patients with CS-CMVi had higher all-cause mortality (Pâ =â .007), especially those with low CMV-CMI (Pâ =â .035). On multivariable analysis, CMV-CMI, sex, race, antithymocyte globulin, and steroid use were independent predictors of CS-CMVi, and the time from transplant to engraftment was the only predictor of mortality. CONCLUSIONS: Measurement of CMV-CMI using a novel ELISPOT assay would be useful clinically to monitor allo-HCT recipients and distinguish between those at risk of developing CS-CMVi and requiring antiviral prophylaxis or therapy and those who are protected.
Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Antivirais/uso terapêutico , Citomegalovirus , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunidade Celular , Estudos ProspectivosRESUMO
Mucormycosis outbreaks have been linked to contaminated linen. We performed fungal cultures on freshly-laundered linens at 15 transplant and cancer hospitals. At 33% of hospitals, the linens were visibly unclean. At 20%, Mucorales were recovered from >10% of linens. Studies are needed to understand the clinical significance of our findings.
Assuntos
Roupas de Cama, Mesa e Banho/normas , Desinfecção , Serviço Hospitalar de Lavanderia , Mucorales/isolamento & purificação , Contaminação de Equipamentos , Humanos , Controle de Infecções , Têxteis , Estados UnidosRESUMO
Orolabial lymphogranuloma venereum was diagnosed for a man in Michigan, USA, who had sex with men, some infected with HIV. High index of suspicion for lymphogranuloma venereum led to accurate diagnosis, successful therapy, and description of an L2b variant with a unique genetic mutation.
Assuntos
Doenças Labiais/diagnóstico , Doenças Labiais/microbiologia , Linfogranuloma Venéreo/diagnóstico , Linfogranuloma Venéreo/microbiologia , Adulto , Coinfecção , Infecções por HIV , Homossexualidade Masculina , Humanos , Linfogranuloma Venéreo/transmissão , Masculino , Úlcera/microbiologiaRESUMO
Herpes zoster (HZ) can have a substantial impact on quality of life (QoL). The vaccine efficacy (VE) of a recombinant zoster vaccine (RZV) was 68.2% (95% confidence interval [CI], 55.6% to 77.5%) in a phase 3 study in adult autologous hematopoietic stem cell transplant (HSCT) recipients (NCT01610414). Herein, we report the impact of RZV on patients' QoL. Autologous HSCT recipients were randomized 1:1 to receive 2 doses of RZV or placebo, given 1 to 2 months apart. QoL was measured by the Short Form Survey-36 and Euro-QoL-5 Dimension at baseline, 1 month, and 1 year postdose 2 and during suspected HZ episodes with the Zoster Brief Pain Inventory (ZBPI). The RZV impact on ZBPI burden of illness and burden of interference scores was estimated. The 2 scores were calculated from the area under the curve (days 0 to 182) of the ZBPI worst pain and ZBPI activities of daily living scores, respectively, assuming a score of 0 for patients not having a confirmed HZ episode. The ZBPI maximum worst pain score was significantly lower in the RZV than placebo group (mean: 5.8 versus 7.1, Pâ¯=â¯.011). Consequently, the VE estimates for HZ burden of illness (82.5%; 95% CI, 73.6 to 91.4) and burden of interference (82.8%; 95% CI, 73.3 to 92.3) were higher than the HZ VE estimate (ie, 68.2%). RZV showed significantly better QoL scores than placebo 1 week following rash onset among patients with confirmed HZ. In addition to reducing the risk of HZ and its complications, RZV significantly reduced the impact of HZ on patients' QoL in those who developed breakthrough disease.
Assuntos
Vacina contra Varicela/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3 , Qualidade de Vida , Adulto , Idoso , Autoenxertos , Vacina contra Varicela/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversosRESUMO
Fungal endophthalmitis remains a significant cause of vision impairment and blindness. Moreover, the prognosis is poor, in part due to delay in diagnosis and to limited availability of effective antifungal agents with good ocular penetration. Thus, it is imperative to evaluate the therapeutic efficacy in fungal endophthalmitis of newer antifungal agents. In this study, we assessed the efficacy of isavuconazole in treating Aspergillus fumigatus endophthalmitis in an exogenous mouse model of the disease. Briefly, endophthalmitis was induced by intravitreal (IVT) injection of A. fumigatus spores into immunocompetent C57BL/6 (B6) mouse eyes. Mice were randomized into five groups that received isavuconazole via (i) oral gavage, (ii) IVT injections, (iii) intravenous injection, (iv) IVT injection followed by oral gavage, and (v) IVT injection followed by intravenous injection. Our data showed that isavuconazole treatment via all routes reduced fungal burden in A. fumigatus-infected eyes. This coincided with the preservation of retinal structural integrity (histology analysis) and retinal function (electroretinography [ERG] analysis), resulting in significantly improved disease outcome. Furthermore, isavuconazole treatment reduced the levels of inflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin 1ß [IL-1ß], and IL-6) and cellular infiltration in the eyes. Notably, oral administration of isavuconazole was as effective in ameliorating endophthalmitis as intravitreal injection of the drug. Collectively, our study demonstrates that isavuconazole is effective in treating A. fumigatus endophthalmitis in mice, indicating its potential use in human ocular infections.
Assuntos
Aspergillus fumigatus/efeitos dos fármacos , Endoftalmite/tratamento farmacológico , Infecções Oculares Fúngicas/tratamento farmacológico , Nitrilas/farmacologia , Piridinas/farmacologia , Triazóis/farmacologia , Animais , Antifúngicos/farmacologia , Aspergilose/tratamento farmacológico , Modelos Animais de Doenças , Eletrorretinografia/métodos , Injeções Intravítreas/métodos , Camundongos , Camundongos Endogâmicos C57BL , Retina/microbiologia , Corpo Vítreo/microbiologiaRESUMO
Neutropenia is linked to the development of invasive candidiasis/candidaemia, for which micafungin has demonstrated efficacy, but evidence in patients with neutropenia is limited. The aim of this study was to evaluate the efficacy of micafungin for the treatment of invasive candidiasis/candidaemia in patients with neutropenia (<500 neutrophils/µL) and without neutropenia. This pooled, post hoc analysis of 2 Phase 3 trials compared micafungin 100 mg/d (adults) and 2 mg/kg/d (paediatrics) with L-AmB 3 mg/kg/d (NCT00106288) and micafungin 100 mg/d and 150 mg/d with caspofungin 70 mg/d followed by 50 mg/d (adults) (NCT00105144); treatment duration 2-4 weeks (≤8 weeks for chronic disseminated candidiasis). Effects of neutropenia duration and Candida spp. on efficacy outcomes (treatment success, clinical and mycological response) were examined. Of 685 patients, 77 had neutropenia. The most common infection in patients with/without neutropenia was due to C. tropicalis (31/77) and C. albicans (295/608) respectively. Overall success was numerically lower in patients with vs without neutropenia (63.6% vs 72.9%). Clinical and mycological response was similar between groups. Neutropenia duration or Candida spp. did not impact micafungin's overall success rate. This analysis supports evidence that micafungin is effective against invasive candidiasis/candidaemia in patients with neutropenia, irrespective of neutropenia duration or Candida spp., although overall success may be lower than in patients without neutropenia.
Assuntos
Antifúngicos/uso terapêutico , Candidemia/tratamento farmacológico , Candidíase Invasiva/tratamento farmacológico , Equinocandinas/uso terapêutico , Lipopeptídeos/uso terapêutico , Neutropenia/microbiologia , Adolescente , Adulto , Antifúngicos/administração & dosagem , Candida/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Candida tropicalis/efeitos dos fármacos , Candida tropicalis/isolamento & purificação , Candidemia/complicações , Candidemia/microbiologia , Candidíase/complicações , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Candidíase Invasiva/complicações , Candidíase Invasiva/microbiologia , Caspofungina , Equinocandinas/administração & dosagem , Equinocandinas/efeitos adversos , Feminino , Humanos , Lipopeptídeos/administração & dosagem , Lipopeptídeos/efeitos adversos , Masculino , Micafungina , Pessoa de Meia-Idade , Neutropenia/complicações , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Although fluoroquinolone prophylaxis is frequently utilized in autologous hematopoietic stem cell transplant (AHSCT) patients, its impact on morbidity and mortality is uncertain. This study investigates the role of quinolone prophylaxis after AHSCT in recent years. METHODS: We conducted a retrospective review of 291 consecutive adult patients who underwent AHSCT for malignant disorders, between June 2013 and January 2015. Outcomes were compared between patients who received norfloxacin prophylaxis and those who did not. The endpoints were mortality during prophylaxis and at 100 days after transplant, frequency of ICU admissions, and incidence and type of bacteremia. RESULTS: Of 291 patients, 252 patients received norfloxacin prophylaxis and 39 patients did not. The mortality during prophylaxis and at 100 days as well as the median number of days of hospitalization following AHSCT did not differ between the two groups. No differences were noted in the frequency of ICU admission, incidence of septic shock, and duration of ICU stay. Patients who did not receive prophylaxis had a significantly higher rate of neutropenic fever (97%) than patients who received prophylaxis (77%) (p = 0.005). The patients with prophylaxis demonstrated a significantly higher rate of gram-positive bacteremia as compared to those without prophylaxis (p = 0.002). Frequency of Clostridium difficile infection was similar during and post-prophylaxis. More antibiotic use was noted among patients without prophylaxis [97%; median 9 (range, 5-24) days] compared to patients with prophylaxis [79%; median 7 (range, 3-36) days, p = 0.04]. CONCLUSION: Although fluoroquinolone prophylaxis reduced the incidence of neutropenic fever and antibiotic use in AHSCT, it did not alter mortality or morbidity.
Assuntos
Antibacterianos/uso terapêutico , Fluoroquinolonas/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Clostridium difficile is a leading cause of infectious diarrhea in hematopoietic stem cell transplant (HSCT) recipients. Asymptomatic colonization of the gastrointestinal tract occurs before development of C. difficile infection (CDI). This prospective study examines the rates, risk factors, and outcomes of colonization with toxigenic and nontoxigenic strains of C. difficile in HSCT patients. This 18-month study was conducted in the HSCT unit at the Karmanos Cancer Center and Wayne State University in Detroit. Stool samples from the patients who consented for the study were taken at admission and weekly until discharge. Anaerobic culture for C. difficile and identification of toxigenic strains by PCR were performed on the stool samples. Demographic information and clinical and laboratory data were collected. Of the 150 patients included in the study, 29% were colonized with C. difficile at admission; 12% with a toxigenic strain and 17% with a nontoxigenic strain. Over a 90-day follow-up, 12 of 44 (26%) patients colonized with any C. difficile strain at admission developed CDI compared with 13 of 106 (12%) of patients not colonized (odds ratio [OR], 2.70; 95% confidence interval [95% CI], 1.11 to 6.48; P = .025). Eleven of 18 (61%) patients colonized with the toxigenic strain and 1 of 26 (4%) of those colonized with nontoxigenic strain developed CDI (OR, 39.30; 95% CI, 4.30 to 359.0; P < .001) at a median of 12 days. On univariate and multivariate analyses, none of the traditional factors associated with high risk for C. difficile colonization or CDI were found to be significant. Recurrent CDI occurred in 28% of cases. Asymptomatic colonization with C. difficile at admission was high in our HSCT population. Colonization with toxigenic C. difficile was predictive of CDI, whereas colonization with a nontoxigenic C. difficile appeared protective. These findings may have implications for infection control strategies and for novel approaches for the prevention and preemptive treatment of CDI in the HSCT patient population.
Assuntos
Clostridioides difficile , Diarreia , Enterocolite Pseudomembranosa , Adulto , Idoso , Aloenxertos , Clostridioides difficile/genética , Clostridioides difficile/isolamento & purificação , Clostridioides difficile/patogenicidade , Diarreia/etiologia , Diarreia/genética , Diarreia/microbiologia , Enterocolite Pseudomembranosa/etiologia , Enterocolite Pseudomembranosa/genética , Enterocolite Pseudomembranosa/microbiologia , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Antifungal prophylaxis with a new oral tablet formulation of posaconazole may be beneficial to patients at high risk for invasive fungal disease. A two-part (Phase 1B/3) study evaluated posaconazole tablet pharmacokinetics (PK) and safety. METHODS: Patients with neutropenia following chemotherapy for haematological malignancy or recipients of allogeneic HSCT receiving prophylaxis or treatment for graft-versus-host disease received 300 mg posaconazole (as tablets) once daily (twice daily on day 1) for up to 28 days without regard to food intake. Weekly trough PK sampling was performed during therapy, and a subset of patients had sampling on days 1 and 8. Cmin-evaluable subjects received ≥6 days of dosing, and were compliant with specified sampling timepoints. Steady-state PK parameters, safety, clinical failure and survival to day 65 were assessed. ClinicalTrials.gov, NCT01777763; EU Clinical Trials Register, EUDRA-CT 2008-006684-36. RESULTS: Two hundred and ten patients received 300 mg posaconazole (as tablets) once daily. Among Cmin-evaluable subjects (nâ=â186), steady-state mean Cmin was 1720 ng/mL (rangeâ=â210-9140). Steady-state Cmin was ≥700 ng/mL in 90% of subjects with 5% (10 of 186) <500 ng/mL and 5% (10 of 186) 500-700 ng/mL. Six (3%) patients had steady-state Cmin ≥3750 ng/mL. One patient (<1%) had an invasive fungal infection. The most common treatment-related adverse events were nausea (11%) and diarrhoea (8%). There was no increase in adverse event frequency with higher posaconazole exposure. CONCLUSIONS: In patients at high risk for invasive fungal disease, 300 mg posaconazole (as tablets) once daily was well tolerated and demonstrated a safety profile similar to that reported for posaconazole oral suspension: most patients (99%) achieved steady-state pCavg exposures >500 ng/mL and only one patient (<1%) had a pCavg <500 ng/mL.
Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Quimioprevenção/métodos , Fungemia/prevenção & controle , Comprimidos/administração & dosagem , Triazóis/administração & dosagem , Triazóis/farmacocinética , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/efeitos adversos , Quimioprevenção/efeitos adversos , Feminino , Neoplasias Hematológicas/complicações , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Plasma/química , Análise de Sobrevida , Comprimidos/efeitos adversos , Triazóis/efeitos adversos , Adulto JovemRESUMO
The incidence of cytomegalovirus (CMV) reactivation/disease after autologous stem cell transplant (ASCT) is much lower than that after allogeneic stem cell transplantation. With the recent use of rituximab during cancer chemotherapy or conditioning regimens prior to transplantation, there has been an increasing concern of opportunistic infections including CMV. In the present study, we reviewed the patients undergoing ASCT from December 2007 to December 2013 to identify those developing CMV reactivation/disease. Out of the 978 patients who underwent ASCT at the Karmanos Cancer Institute, 239 patients were tested for symptomatic CMV reactivation based on clinical suspicion. Of the tested patients, 7/239 (2.9 %) were documented to have CMV reactivation within 90 days of ASCT. The median time to develop CMV viremia was 32 days from transplantation. Of the 239 patients tested, CMV viremia was detected in 3 out of 72 patients who received rituximab as compared to 4 out of 167 patients who did not. Three of these seven viremic patients were treated with anti-viral drugs; viremia resolved in all patients at a median of 24 days. Three patients were found to develop other bacterial and/or fungal infections following CMV viremia. Two of the seven patients died during 1-year follow-up, due to primary disease progression or Candida sepsis. None of the patients developed proven tissue-invasive CMV disease. The study did not evaluate the incidence of asymptomatic CMV infection/reactivation. Despite prior publications based on limited data, rituximab does not appear to contribute to an increased frequency of symptomatic CMV reactivation following ASCT.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/isolamento & purificação , Neoplasias/terapia , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Idoso , Terapia Combinada , Citomegalovirus/genética , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/virologia , DNA Viral/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/classificação , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Rituximab/administração & dosagem , Transplante Autólogo , Viremia/diagnóstico , Viremia/virologia , Ativação Viral , Adulto JovemRESUMO
Voriconazole use has increased since the drug's introduction in 2002, and new and unique adverse effects are emerging as patients undergo prolonged therapy. Most concerning is the increased risk of cutaneous malignancies, primarily squamous cell carcinoma (SCC); this risk is duration dependent and the associated malignancies tend to be more aggressive and multifocal. Voriconazole is also associated with phototoxicity (which may be a precursor to malignancy), periostitis, hallucinations and encephalopathy, peripheral neuropathy, alopecia, nail changes, hyponatremia, and other adverse effects. Some toxicities (neuropsychiatric and gastrointestinal including hepatic) are seen in clear association with supratherapeutic serum voriconazole levels; thus, careful monitoring of voriconazole levels is a critical component of safe drug use. Guidelines for screening for adverse effects after long-term voriconazole use may be beneficial and need to be established.
Assuntos
Antifúngicos/efeitos adversos , Voriconazol/efeitos adversos , Adulto , Alopecia/induzido quimicamente , Antifúngicos/uso terapêutico , Arritmias Cardíacas/induzido quimicamente , Carcinoma de Células Escamosas/induzido quimicamente , Relação Dose-Resposta a Droga , Esquema de Medicação , Monitoramento de Medicamentos , Neoplasias de Cabeça e Pescoço/induzido quimicamente , Humanos , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Masculino , Doenças da Unha/induzido quimicamente , Doenças do Sistema Nervoso/induzido quimicamente , Periostite/induzido quimicamente , Neoplasias Cutâneas/induzido quimicamente , Carcinoma de Células Escamosas de Cabeça e Pescoço , Voriconazol/uso terapêuticoAssuntos
Proteínas de Bactérias/genética , Escherichia coli/genética , Klebsiella pneumoniae/genética , beta-Lactamases/genética , Adulto , Carbapenêmicos/farmacologia , Escherichia coli/isolamento & purificação , Genes Bacterianos , Humanos , Klebsiella pneumoniae/isolamento & purificação , Masculino , Técnicas de Diagnóstico Molecular/métodos , Mutação , Reação em Cadeia da PolimeraseRESUMO
Recent match results from the National Resident Matching Program for the subspecialty of infectious diseases show an ongoing decline in the number of fellowship positions filled, and, more important, in the number of applicants, particularly from the pool of international medical graduates. The main reasons for this declining application rate are unclear; in the absence of hard data, we present our viewpoint on this issue. Difficulties in securing visas for permanent residency in the United States, perception of a limited job market, and the explosive growth in the number of hospitalist positions may be important contributing factors. Infectious Diseases Society of America members need to focus on medical students and medical residents in their formative years. We present potential solutions to this problem of declining interest in the field of infectious diseases.
Assuntos
Infectologia/estatística & dados numéricos , Bolsas de Estudo , Humanos , Medicina , Estados Unidos , Recursos HumanosRESUMO
Posaconazole tablets, a new oral formulation of posaconazole, can be effective when given as antifungal prophylaxis to neutropenic patients at high risk for invasive fungal infection (e.g., those with acute myelogenous leukemia or myelodysplastic syndrome). Such effectiveness might be specifically important to patients with poor oral intake because of nausea, vomiting, or chemotherapy-associated mucositis. This was a prospective, global study in high-risk patients to characterize the pharmacokinetics and safety profile of posaconazole tablets and to identify the dose of posaconazole tablets that would provide exposure within a predefined range of exposures (steady-state average concentration [area under the concentration-time curve/24 h] of ≥500 ng/ml and ≤2,500 ng/ml in >90% of patients). The study evaluated two sequential dosing cohorts: 200 mg posaconazole once daily (n = 20) and 300 mg posaconazole once daily (n = 34) (both cohorts had a twice-daily loading dose on day 1) taken without regard to food intake during the neutropenic period for ≤28 days. The exposure target was reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking 200 mg posaconazole once daily and in 31 of 32 (97%) patients taking 300 mg posaconazole once daily; 300 mg posaconazole once daily achieved the desired exposure target. Posaconazole tablets were generally well tolerated in high-risk neutropenic patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01777763.).
Assuntos
Antifúngicos/uso terapêutico , Micoses/prevenção & controle , Neutropenia/microbiologia , Triazóis/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Antifúngicos/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Comprimidos/administração & dosagem , Comprimidos/efeitos adversos , Comprimidos/farmacocinética , Comprimidos/uso terapêutico , Triazóis/administração & dosagem , Triazóis/farmacocinéticaRESUMO
Piperacillin-tazobactam (PTZ) is known to cause false-positive results in the Platelia Aspergillus enzyme-linked immunoassay (EIA), due to contamination with galactomannan (GM). We tested 32 lots of PTZ and 27 serum specimens from patients receiving PTZ. GM was not detected in the lots of PTZ; one serum specimen (3.7%) was positive. PTZ formulations commonly used in the United States today appear to be a rare cause for false-positive GM results.
Assuntos
Antibacterianos/uso terapêutico , Aspergilose/diagnóstico , Aspergillus/isolamento & purificação , Testes Diagnósticos de Rotina/métodos , Reações Falso-Positivas , Mananas/sangue , Soro/química , Idoso de 80 Anos ou mais , Antibacterianos/química , Contaminação de Medicamentos , Feminino , Galactose/análogos & derivados , Humanos , Técnicas Imunoenzimáticas/métodos , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/química , Ácido Penicilânico/uso terapêutico , Piperacilina/química , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Estados UnidosRESUMO
INTRODUCTION: Cytomegalovirus (CMV) remains a serious opportunistic infection in hematopoietic cell transplant (HCT) and solid-organ transplant (SOT) recipients. Traditional anti-CMV drugs are limited by toxicities and the development of resistance. Letermovir and maribavir are newly approved antivirals for the prevention and treatment of CMV. AREAS COVERED: Prior reviews have discussed use of letermovir for prevention of CMV after HCT and maribavir for resistant or refractory (R/R) CMV post HCT or SOT. Subsequent data have expanded their use including letermovir for primary CMV prophylaxis in high-risk renal transplant recipients and new recommendations for extending prophylaxis through day + 200 in certain HCT patients. Data on the use of maribavir for first asymptomatic CMV infection post-HCT has also been published. This review compares the pharmacology of anti-CMV agents and discusses the updated literature of these new drugs in the prevention and treatment of CMV. EXPERT OPINION: Letermovir and maribavir are much needed tools that spare toxicities of ganciclovir, foscarnet, and cidofovir. High cost is a challenge preventing their integration into clinical practice in resource-limited countries. Transplant centers need to exercise restraint in overuse to avoid resistance, particularly in the setting of high viral loads.
Assuntos
Antivirais , Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Transplante de Órgãos , Humanos , Acetatos/uso terapêutico , Acetatos/efeitos adversos , Acetatos/farmacologia , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Antivirais/farmacologia , Benzimidazóis/uso terapêutico , Benzimidazóis/efeitos adversos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/prevenção & controle , Diclororribofuranosilbenzimidazol/análogos & derivados , Farmacorresistência Viral , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções Oportunistas/prevenção & controle , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/virologia , Transplante de Órgãos/efeitos adversos , Quinazolinas/uso terapêutico , Quinazolinas/farmacologia , Ribonucleosídeos/uso terapêutico , Ribonucleosídeos/farmacologia , Carga Viral/efeitos dos fármacosRESUMO
Chimeric antigen receptor (CAR) T-cell therapy has emerged as a novel therapeutic option for hematologic malignancies. Human immunodeficiency virus (HIV) nucleic acid amplification tests (NAATs) amplifying 5' long terminal repeat and gag genes cross-react with lentiviral vector-based CAR T-cell products. Cross-reactivity between CAR T-cell products and HIV NAATs may lead to false-positive test results.
RESUMO
Background: Acyclovir-resistant mucocutaneous herpes simplex virus (HSV) infection is an uncommon problem typically seen in immunocompromised hosts. Systemic treatment options are limited. The performance of foscarnet and its toxicities in this population are poorly characterized. Methods: This was a multicenter retrospective study of adults treated with foscarnet for HSV infection between January 2012 and December 2017. Relevant data were collected including demographics, baseline conditions, previous anti-HSV medications, concomitant medications, HSV outcomes, and adverse events. Acyclovir-resistant HSV infection was defined based on genotypic or phenotypic testing results; refractory infection was defined as infection not improving after 5 days of treatment-dosed antiviral therapy in those not tested for resistance. Results: Twenty-nine patients had 31 episodes of HSV (15/18 resistant; among episodes without resistance testing, 7/10 refractory; 3 not evaluable) treated with foscarnet. All patients were immunocompromised including 19 (66%) with hematologic malignancy and 9 (31%) with HIV. Median duration of foscarnet was 16 days (range, 6-85 days). Fifteen episodes (48%) healed by the end of or after foscarnet. Median time to healing among those with resolution was 38 days (range, 9-1088 days). At least 1 adverse event during therapy was reported in 26 (84%) treatment episodes including 23 (74%) that were considered drug related. Common adverse events were electrolyte disturbance (20 [65%]) and kidney dysfunction (13 [42%]). Foscarnet was discontinued in 10 episodes (32%) due to an adverse event, including 6 due to kidney dysfunction. Conclusions: Among 31 episodes of HSV treated with foscarnet, only half resolved with treatment, and adverse events were common.