RESUMO
A series of fused pyrroles were synthesized and tested for their in vivo anti-inflammatory activity. Among 14 examined derivatives, 5 derivatives (1b-e, g and 5b), showed a promising anti-inflammatory activity equivalent to reference anti-inflammatory drugs (indomethacin and ibuprofen). A molecular docking study was conducted to interpret the biological activities of the tested compounds. The docking results were complementary with the phase of the biological survey and confirmed the biological effects.
Assuntos
Anti-Inflamatórios/síntese química , Indóis/síntese química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Indóis/química , Indóis/farmacologia , Masculino , Simulação de Acoplamento Molecular , Ratos , Ratos Sprague-Dawley , Relação Estrutura-AtividadeRESUMO
Clostridium difficile infection (CDI) is one of the leading causes of hospital-acquired infections in recent times. Hematopoietic stem cell transplantation (HSCT) confers increased risk for CDI because of prolonged hospital stay, immunosuppression, the need to use broad-spectrum antibiotics and a complex interplay of preparative regimen and GvHD-induced gut mucosal damage. Our study evaluated risk factors (RF) for recurrent CDI in HSCT recipients given the ubiquity of traditional RF for CDI in this population. Of the 499 allogeneic HSCT recipients transplanted between 2005 and 2012, 61 (12%) developed CDI within 6 months before transplant or 2 years after transplant and were included in the analysis. Recurrent CDI occurred in 20 (33%) patients. One year incidence of CDI recurrence was 31%. Multivariable analyses identified the number of antecedent antibiotics other than those used to treat CDI as the only significant RF for recurrence (hazard ratio 1.96, 95% confidence interval 1.09-3.52, P=0.025). Most recurrences occurred within 6 months of the first CDI, and the recurrence of CDI was associated with a trend for increased risk of mortality. This prompts the need for further investigation into secondary prophylaxis to prevent recurrent CDI.
Assuntos
Infecções por Clostridium/etiologia , Infecção Hospitalar/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplantados , Adolescente , Adulto , Idoso , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Infecções por Clostridium/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Recidiva , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo , Adulto JovemRESUMO
Vancomycin-resistant enterococcus (VRE) is a well-known infectious complication among immunocompromised patients. We performed a retrospective analysis to identify risk factors for the development of VRE bacteremia (VRE-B) within 15 months after allogeneic hematopoietic cell transplantation (alloHCT) and to determine its prognostic importance for other post-transplant outcomes. Eight hundred consecutive adult patients who underwent alloHCT for hematologic diseases from 1997 to 2011 were included. Seventy-six (10%) developed VRE-B at a median of 46 days post transplant. Year of transplant, higher HCT comorbidity score, a diagnosis of ALL, unrelated donor and umbilical cord blood donor were all significant risk factors on multivariable analysis for the development of VRE-B. Sixty-seven (88%) died within a median of 1.1 months after VRE-B, but only four (6%) of these deaths were attributable to VRE. VRE-B was significantly associated with worse OS (hazard ratio 4.28, 95% confidence interval 3.23-5.66, P<0.001) in multivariable analysis. We conclude that the incidence of VRE-B after alloHCT has increased over time and is highly associated with mortality, although not usually attributable to VRE infection. Rather than being the cause, this may be a marker for a complicated post-transplant course. Strategies to further enhance immune reconstitution post transplant and strict adherence to infection prevention measures are warranted.
Assuntos
Bacteriemia/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Adolescente , Adulto , Idoso , Bacteriemia/tratamento farmacológico , Bacteriemia/mortalidade , Enterococcus , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Análise de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Cytomegalovirus (CMV) is a common infection after myeloablative allogeneic hematopoietic stem cell transplant (M-alloHSCT). Achievement of complete donor T-cell chimerism (CDC-T) post transplant is a measure of immune reconstitution. We investigated the association between CDC-T post M-alloHSCT and the incidence of CMV viremia. METHODS: We retrospectively reviewed all CMV and chimerism results of 47 patients for the first 6 months post M-alloHSCT. CDC-T was analyzed as a time-varying covariate for association with post M-alloHSCT CMV viremia. RESULTS: CMV viremia occurred in 15 (32%) and CDC-T was achieved in 38 (81%) recipients within the first 6 months post M-alloHSCT. On univariable analysis, increased CMV viremia was seen among patients with CDC-T (hazard ratio 2.81 [P = 0.07, 95% confidence interval = 0.93-8.52]). A 30-day landmark analysis showed that the incidence of CMV viremia at 6 months (regardless of recipient CMV serostatus) was 50% among those who had achieved CDC-T by day 30, and 23% among those who had not (P = 0.06). CONCLUSION: We conclude that shorter time to CDC-T may be associated with higher risk of CMV viremia. If confirmed in a larger cohort, this might be a marker for risk stratification in the management of CMV in this population.
Assuntos
Quimerismo , Infecções por Citomegalovirus/epidemiologia , DNA/genética , Transplante de Células-Tronco Hematopoéticas , Linfócitos T , Condicionamento Pré-Transplante , Viremia/epidemiologia , Adolescente , Adulto , Idoso , Bussulfano/uso terapêutico , Estudos de Coortes , Ciclofosfamida/uso terapêutico , Ciclosporina/uso terapêutico , Infecções por Citomegalovirus/imunologia , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Incidência , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Agonistas Mieloablativos/uso terapêutico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Tacrolimo/uso terapêutico , Fatores de Tempo , Transplante Homólogo , Viremia/imunologia , Adulto JovemRESUMO
Invasive fusariosis (IF) has been associated with a poor prognosis. Although recent series have reported improved outcomes, the definition of optimal treatments remains controversial. The objective of this study was to evaluate changes in the outcome of IF. We retrospectively analysed 233 cases of IF from 11 countries, comparing demographics, clinical findings, treatment and outcome in two periods: 1985-2000 (period 1) and 2001-2011 (period 2). Most patients (92%) had haematological disease. Primary treatment with deoxycholate amphotericin B was more frequent in period 1 (63% vs. 30%, p <0.001), whereas voriconazole (32% vs. 2%, p <0.001) and combination therapies (18% vs. 1%, p <0.001) were more frequent in period 2. The 90-day probabilities of survival in periods 1 and 2 were 22% and 43%, respectively (p <0.001). In period 2, the 90-day probabilities of survival were 60% with voriconazole, 53% with a lipid formulation of amphotericin B, and 28% with deoxycholate amphotericin B (p 0.04). Variables associated with poor prognosis (death 90 days after the diagnosis of fusariosis) by multivariable analysis were: receipt of corticosteroids (hazard ratio (HR) 2.11, 95% CI 1.18-3.76, p 0.01), neutropenia at end of treatment (HR 2.70, 95% CI 1.57-4.65, p <0.001), and receipt of deoxycholate amphotericin B (HR 1.83, 95% CI 1.06-3.16, p 0.03). Treatment practices have changed over the last decade, with an increased use of voriconazole and combination therapies. There has been a 21% increase in survival rate in the last decade.
Assuntos
Antifúngicos/uso terapêutico , Fusariose/tratamento farmacológico , Fusariose/epidemiologia , Adolescente , Adulto , Idoso , Anfotericina B/uso terapêutico , Criança , Pré-Escolar , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Quimioterapia Combinada/métodos , Feminino , Fusariose/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Voriconazol/uso terapêutico , Adulto JovemRESUMO
We conducted a case-control study to describe the epidemiology and risk factors for infections requiring hospitalization in patients with myelodysplastic syndromes (MDS). Of 497 patients identified, 103 patients developed 201 episodes of infection. The probability of acquiring an infection 1 year from date of MDS diagnosis was 15% (95% confidence interval [CI] 12-18%). Patients developing infections had decreased survival compared to those who did not (P = 0.007). Significant risk factors for infection were higher risk MDS (hazard ratio [HR] = 2.7, 95% CI = 1.7-4.1, P < 0.0001), nadir absolute neutrophil count <500/mL (HR = 1.8, 95% CI = 1.2-2.7, P < 0.007), chronic obstructive pulmonary disease (HR = 2.6, 95% CI = 1.4-4.9, P < 0.003), history of other malignancy (HR 2.0, 95% CI = 1.3-3.1, P < 0.003), and autoimmune disease (HR 2.9, 95% CI = 1.4-6.0, P < 0.005). Age, nadir platelet count <20,000/mL, diabetes mellitus, and MDS treatment were not significant risk factors. Pneumonia was the most common infection, and bacteria the predominant pathogens.
Assuntos
Infecções/epidemiologia , Síndromes Mielodisplásicas/epidemiologia , Neutrófilos , Doenças Autoimunes/epidemiologia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Hospitalização , Humanos , Contagem de Leucócitos , Masculino , Síndromes Mielodisplásicas/sangue , Neoplasias/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Hematopoietic stem cell transplant (HSCT) recipients have increased morbidity from respiratory viral infections. Pandemic influenza A - A(H1N1)/pdm09 - in 2009-2010 was associated with increased severity of illness in patients with underlying co-morbidities including HSCT, but the factors that contribute to severe disease in HSCT patients are not well characterized. METHODS: We conducted a multicenter review of microbiologically proven influenza A(H1N1)pdm09 in the HSCT population between April 2009 and April 2010 to determine factors that are associated with severe disease. RESULTS: We identified 37 adult patients (26 allogeneic and 11 autologous HSCT recipients). Median time from transplant to diagnosis was 411 days (range 4 days-14.9 years). Three cases were hospital acquired. Twenty-eight of 37 (75.7%) had confirmed A(H1N1)pdm09. Presumed viral lower respiratory tract infection was present in 12/37 (32.4%) patients. Antiviral therapy was given to 33/37 (89%) patients, primarily oseltamivir (n = 24) and oseltamivir before or after another antiviral (n = 8). Excluding those with nosocomial A(H1N1)pdm09, 18/34 (52.9%) were hospitalized and 6 (33%) required admission to an intensive care unit. Mortality within 30 and 60 days of symptom onset was 7/37 (18.9%) and 11/37 (29.7%), respectively. Factors associated with mortality included nosocomial acquisition (P = 0.023), receipt of mycophenolate mofetil (P = 0.001), or antilymphocyte antibody (P = 0.005) within the past 6 months, reduced-intensity conditioning (P = 0.027), and bacteremia (P = 0.021). CONCLUSIONS: A(H1N1)pdm09 infection was particularly severe in HSCT recipients, specifically among those receiving augmented immunosuppression for graft-versus-host disease. The high mortality of the nosocomial cases highlights the need for strict infection-control measures in hospitals during influenza outbreaks.
Assuntos
Antivirais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/epidemiologia , Pandemias , Adulto , Idoso , Infecção Hospitalar/complicações , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/epidemiologia , Hospitalização , Humanos , Controle de Infecções , Influenza Humana/complicações , Influenza Humana/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Oseltamivir/uso terapêutico , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
Human metapneumovirus (hMPV) infection can occur in all age groups with significant morbidity and mortality. Coinfection with influenza virus occurs mainly with influenza type A and all reported cases recovered completely. We report the case of a 61-year-old man who had hematopoietic stem cell transplant for myelodysplastic syndrome. He was admitted to hospital for septic shock and neutropenia, and blood culture was positive for Pseudomonas aeruginosa. He rapidly developed respiratory failure and required ventilator support. His respiratory culture grew P. aeruginosa and hMPV. His course was complicated by persistent shock requiring vasopressor support, and repeat nasopharyngeal swab was positive for influenza type B and hMPV. His condition rapidly deteriorated, his family elected comfort care, and the patient died shortly thereafter. Coinfection with hMPV and influenza virus type B may have a poor outcome and can be fatal, especially in immunocompromised patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Vírus da Influenza B/isolamento & purificação , Influenza Humana/complicações , Metapneumovirus/isolamento & purificação , Infecções por Paramyxoviridae/complicações , Coinfecção , Evolução Fatal , Humanos , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Infecções por Paramyxoviridae/microbiologia , Transplante HomólogoRESUMO
We report 2 cases of severe pneumonia due to the novel pandemic influenza A/H1N1 2009 in kidney transplant recipients. Our patients initially experienced influenza-like illness that rapidly progressed to severe pneumonia within 48 h. The patients became hypoxic and required non-invasive ventilation. The novel influenza A/H1N1 2009 was identified from their nasal swabs. These cases were treated successfully with a relatively high dose of oseltamivir, adjusted for their renal function. Clinical improvement was documented only after a week of antiviral therapy. Despite early antiviral treatment, we showed that morbidity following novel pandemic influenza A/H1N1 2009 infection is high among kidney transplant recipients.
Assuntos
Antivirais/uso terapêutico , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/tratamento farmacológico , Transplante de Rim , Oseltamivir/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Antivirais/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Oseltamivir/administração & dosagem , Transplante , Resultado do TratamentoRESUMO
Vancomycin-resistant enterococcal (VRE) infection is a growing threat. We studied the incidence, risk factors, and clinical course of early-onset VRE bacteremia in allogeneic hematopoietic stem cell transplant recipients. We carried out a chart review of 281 allogeneic hematopoietic stem cell transplant recipients from 1997-2003, including preparative regimen, diagnosis, status of disease, graft-versus-host disease prophylaxis, antimicrobial therapy, and survival. VRE bacteremia developed in 12/281 (4.3%) recipients; 10 (3.6%) were within 21 days of transplant. Diagnoses were acute leukemia (7), NHL (2), and MDS (1). In all, 70% had refractory/relapsed disease; 30% were in remission. In total, 50% had circulating blasts. Nine of 10 had matched unrelated donors (7/9 with CD8+ T-cell depletion). The average time to positive VRE cultures was 15 days; average WBC was 0.05, and 80% had concomitant infections. Despite treatment, all patients died within 73 days of VRE bacteremia. Intra-abdominal complications were common. Causes of death included bacterial or fungal infection, multiorgan failure, VOD, ARDS, and relapse. A total of 60% of patients engrafted neutrophils, but none engrafted platelets. Early VRE bacteremia after allogeneic bone marrow transplant is associated with a rapidly deteriorating clinical course, although not always directly due to VRE. Early VRE may be a marker for the critical condition of these high-risk patients at the time of transplant.
Assuntos
Bacteriemia/etiologia , Transplante de Medula Óssea/efeitos adversos , Enterococcus faecalis/isolamento & purificação , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Causas de Morte , Progressão da Doença , Resistência a Medicamentos , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Estudos Retrospectivos , Transplante Homólogo , Vancomicina/farmacologiaRESUMO
Engraftment syndrome (ES) following autologous hematopoietic stem cell transplantation (AHSCT) is characterized by fever and rash. In January 2002, we instituted steroid prophylaxis for ES from day +4 to +14. This study was conducted to assess whether this practice increased the risk of infection. In total, 194 consecutive patients were reviewed, 111 did not receive steroid prophylaxis (group A), and 83 did (group B). Initial antimicrobial prophylaxis was the same in both groups. There were no significant differences between groups in age, gender, race, prior radiation therapy, number of prior chemotherapy regimens, disease status at transplant, mobilization regimen, days of leukopheresis, CD34(+) cell dose, and days to platelet and neutrophil engraftment. Group B had significantly fewer patients with non-Hodgkin's lymphoma and multiple myeloma, shorter median duration from diagnosis to transplant, lower risk of ES, and shorter mean length of hospital stay. The incidence of early and late microbiologically confirmed infections was not significantly different between groups. Types of infections and types of organisms identified were similar in both groups. Hospital readmission rates were similar in both groups. Steroid prophylaxis significantly decreases the risk of ES following AHSCT, and is associated with shortened hospitalization, without increasing risk of infection.
Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias/terapia , Esteroides/administração & dosagem , Adolescente , Adulto , Idoso , Infecções Bacterianas/etiologia , Infecções Bacterianas/prevenção & controle , Estudos de Casos e Controles , Feminino , Doença Enxerto-Hospedeiro/complicações , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/etiologia , Micoses/prevenção & controle , Transplante Autólogo , Viroses/etiologia , Viroses/prevenção & controleRESUMO
Ganciclovir-resistant cytomegalovirus (CMV) infection is an emerging problem in transplant recipients. Foscarnet resistance and cidofovir resistance have also been described, but no previous reports have suggested treatment regimens for patients with CMV refractory to all three of these drugs. Leflunomide, an immunosuppressive drug used in rheumatoid arthritis and in rejection in solid-organ transplantation, has been reported to have novel anti-CMV activity. However, its clinical utility in CMV treatment has not been described previously. We report an allogeneic bone marrow transplant recipient who developed CMV infection refractory to sequential therapy with ganciclovir, foscarnet, and cidofovir. The patient was ultimately treated with a combination of leflunomide and foscarnet. Both phenotypic and genotypic virologic analysis was performed on sequential CMV isolates. The patient's high CMV-DNA viral load became undetectable on leflunomide and foscarnet, but the patient, who had severe graft-versus-host disease (GVHD) of the liver, expired with progressive liver failure and other complications. We concluded that leflunomide is a new immunosuppressive agent with anti-CMV activity, which may be useful in the treatment of multiresistant CMV. However, the toxicity profile of leflunomide in patients with underlying GVHD remains to be defined.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Infecções por Citomegalovirus/tratamento farmacológico , Isoxazóis/uso terapêutico , Terapia de Salvação/métodos , Farmacorresistência Viral , Quimioterapia Combinada , Evolução Fatal , Feminino , Foscarnet/uso terapêutico , Doença Enxerto-Hospedeiro , Humanos , Imunossupressores/uso terapêutico , Leflunomida , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Falência Hepática , Pessoa de Meia-Idade , Transplante Homólogo , Carga Viral/métodosRESUMO
BACKGROUND: Previous studies suggest that zinc salts may be effective in treating the common cold. Since rhinovirus infections occur primarily in the nasal cavity, an attempt to arrest the infection at the portal of entry seems logical. AIM: To assess the ability of zinc nasal gel to shorten the duration and reduce the severity of the common cold in healthy adults. STUDY DESIGN: Randomized, double blind, placebo-controlled study. METHODS: Of 1087 patients screened by telephone, 80 patients were enrolled, all presenting within 24-48 h of the onset of illness. They received one dose per nostril of a nasal gel spray containing either 33 mmol/l zincum gluconicum, or an identical placebo four times daily until their symptoms resolved, for a maximum of 10 days. RESULTS: Median duration of cold symptoms in the zinc group was significantly shorter than in the placebo group (median [IQR] 4.3 days [2.5-5.5] vs. 6 days [5-8.5], p=0.002). Nasal drainage, nasal congestion, hoarseness, and sore throat were the symptoms most affected. Significant reduction of total symptom scores started from the second day of the study. Adverse effects (mainly nasal stinging) were similar in both groups. DISCUSSION: Zincum gluconicum nasal gel shortens duration and reduces symptom severity of the common cold in healthy adults, when started within 24-48 h of the onset of illness.
Assuntos
Resfriado Comum/tratamento farmacológico , Gluconatos/uso terapêutico , Zinco/uso terapêutico , Administração Intranasal , Adulto , Método Duplo-Cego , Feminino , Géis , Humanos , Masculino , Cooperação do Paciente , Fatores de Tempo , Resultado do Tratamento , Zinco/efeitos adversosRESUMO
High-dose etoposide (2 g/m(2)) plus G-CSF is a very effective regimen for peripheral blood progenitor cell (PBPC) mobilization. Unfortunately, neutropenia is common. The infectious complications associated with high-dose etoposide have not been previously described. After noting a high incidence of hospitalizations for neutropenic fever, we began a vigorous prophylactic antibiotic regimen for patients receiving high-dose etoposide plus G-CSF, attempting to reduce infectious complications. Ninety-eight patients underwent etoposide mobilization between December 1997 and June 2000. Three chronological patient groups received: (1) no specific antibiotic prophylaxis (n = 44); (2) vancomycin i.v., cefepime i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27); and (3) vancomycin i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27). The patients not receiving antibiotic prophylaxis had a 68% incidence of hospitalization for neutropenic fever. In the patients receiving prophylaxis, the incidence was reduced to 26% and 15% respectively, for an overall incidence of 20% (P < 0.001 for comparison between prophylaxed and unprophylaxed groups). We conclude that etoposide mobilization is associated with a significant incidence of neutropenic fever, which can be substantially reduced by a vigorous antimicrobial prophylactic program.
Assuntos
Antibioticoprofilaxia/métodos , Quimioterapia Combinada/uso terapêutico , Etoposídeo/efeitos adversos , Febre/prevenção & controle , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Neutropenia/prevenção & controle , Assistência Ambulatorial , Cefepima , Cefalosporinas/efeitos adversos , Ciprofloxacina/administração & dosagem , Claritromicina/administração & dosagem , Coleta de Dados , Etoposídeo/administração & dosagem , Feminino , Febre/induzido quimicamente , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Infecções Oportunistas/prevenção & controle , Vancomicina/administração & dosagemRESUMO
BACKGROUND: Ganciclovir-resistant (GCV-R) cytomegalovirus (CMV) is now being reported with increasing frequency in solid organ transplant recipients. OBJECTIVE: To describe the clinical characteristics and outcomes of all solid organ transplant patients with GCV-R CMV seen between 1990 and 2000 at a single center. METHODS: Patients with clinically suspected GCV resistance had viral isolates subjected to phenotypic analysis by plaque reduction assay, and also genotypic analysis. Medical records of the 13 patients with GCV-R CMV were reviewed for demographic, microbiologic, clinical, and pathologic data. RESULTS: Thirteen patients were identified, including 5 kidney, 1 heart, and 7 lung transplant recipients. All but one patient (92%) were CMV donor seropositive, recipient negative (D+/R-), and 11/13 (85%) had tissue-invasive CMV. CMV viremia was recurrent in 9/13 (69%); in 2 others, the first CMV episode was fatal. Overall, 9/13 (69%) of patients have died, all of CMV or its complications. Of the 10 who received foscarnet, only one survived. All patients had received GCV-based prophylactic regimens; 8/13 patients (62%) had received CMV hyperimmune globulin (CMVIG) as part of prophylaxis, 6/13 (46%) had received oral ganciclovir, and 5/13 (38%) had received intermittent (3 x/week) IV ganciclovir for prophylaxis. CONCLUSIONS: GCV-R CMV is associated with CMV D+/R- status, tissue-invasive disease, and high mortality even with foscarnet therapy. Exposure to less than fully therapeutic levels of GCV, in the form of oral or intermittent IV GCV, is common. The use of CMVIG in prophylaxis does not appear to prevent resistance. Further work remains to be done to elucidate the risk factors and optimal mode of prophylaxis and treatment for GCV-R CMV.
Assuntos
Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/uso terapêutico , Transplante de Órgãos/efeitos adversos , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/terapia , Farmacorresistência Viral , Quimioterapia Combinada , Feminino , Foscarnet/farmacologia , Foscarnet/uso terapêutico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Nonmyeloablative peripheral blood stem cell transplantation (PBSCT) is a novel therapeutic strategy for patients with malignant and non-malignant hematologic diseases. Infectious complications of this procedure have not been previously well described. Data on 12 patients transplanted at a tertiary care center were collected prospectively and verified retrospectively. Neutropenia developed in a third of patients, lasting for a median of 5 days. All patients developed some degree of graft-versus-host disease, as intended. Most patients achieved full chimerism by week 5. Bacterial infections occurred in two patients (17%). Cytomegalovirus (CMV) viremia occurred in five patients (42%) at a median of 80 days; none had received CMV prophylaxis. Viremia was associated with fever and fatigue in three patients, possible gastrointestinal involvement in one patient and was asymptomatic in one patient. All viremic patients responded to intravenous ganciclovir therapy. No fungal infections were documented. No patients died as a result of infection. The incidence of CMV viremia in our patients was high, but the incidence of invasive disease due to CMV was low. The best strategy to prevent CMV in patients undergoing nonmyeloablative PBSCT remains to be determined, but strategies employed in traditional allogeneic bone marrow transplantation should be considered in these patients.