RESUMO
BACKGROUND: Streptococcus pneumoniae is the leading cause of vaccine-preventable death in children <5 years of age globally. We determined incidence rates of invasive pneumococcal disease (IPD), clinical and chest X-ray-confirmed pneumonia (CXR+Pn), S. pneumoniae serotype distribution, and antimicrobial susceptibility in children in Goiânia, Brazil. METHODS: Prospective, population-based surveillance was conducted from May 2007 to May 2009 in children 28 days to <36 months of age presenting to all 33 pediatric healthcare services (outpatient departments, emergency rooms, hospitals) in Goiânia. Eligibility criteria were temperature ≥39.0 °C in the previous 24h and/or clinical suspicion of pneumonia or IPD. RESULTS: 14,509 subjects were enrolled. Median age was 14.0 months. S. pneumoniae was detected in 64 samples from 62 subjects: 58 (90.6%) blood; 4 (6.3%) cerebrospinal fluid; and 2 (3.1%) pleural fluid. Incidence rate of IPD (culture- and polymerase chain reaction-positive) for all children aged 28 days to <36 months was 57.5/100,000; overall incidence for culture-positive only was 54.9/100,000. Age stratification of culture-positive-only subjects found the highest rates were, 114.6/100,000 and 69.8/100,000, respectively, for the 6 months to <12 months and 12 months to <24 months age groups. The overall incidence of invasive pneumonia and pneumococcal meningitis was 37.2/100,000 and 5.3/100,000, respectively. The most common IPD serotypes were 14 (45.0%), 6B (13.3%), 18C (6.7%), and 23F (5.0%). Eight isolates (13.3%) were penicillin nonsusceptible. The cumulative percentages of serotypes included in 7-valent, 10-valent, and 13-valent pneumococcal conjugate vaccines were 78.3%, 80.0%, and 88.3%, respectively. The overall incidence of clinical pneumonia and CXR+Pn was, 9598/100,000 and 3428/100,000, respectively. CXR+Pn rates for hospitalized and non-hospitalized subjects were 1751/100,000 and 1677/100,000, respectively. CONCLUSIONS: The burden of IPD and pneumonia is considerable in children in a large Brazilian city, and is seen in hospitalized as well as ambulatory subjects. Vaccination with pneumococcal conjugate vaccines has the potential to decrease this burden.
Assuntos
Infecções Pneumocócicas/epidemiologia , Pneumonia Bacteriana/epidemiologia , Vigilância da População , Brasil/epidemiologia , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Masculino , Vacinas Pneumocócicas/administração & dosagem , Estudos ProspectivosRESUMO
BACKGROUND: Calcineurin inhibitor (CNI) and steroid (ST) withdrawal are strategies under investigation to reduce long-term toxicities associated with current immunosuppressive regimens. We conducted a single center, prospective trial comparing the efficacy and safety of CNI or ST withdrawal in kidney transplant recipients receiving sirolimus-based immunosuppressive regimen. METHODS: Forty-seven recipients of first renal transplant with non-HLA-identical living donors received sirolimus (SRL), tacrolimus (TAC), and ST without induction therapy and were randomized to undergo ST (TAC/SRL group, n = 24) or TAC (SRL/ST group, n = 21) withdrawal 3 months after transplantation. Primary efficacy and safety endpoints were the incidence of biopsy-confirmed acute rejection (BCAR) and renal function at 12 months. RESULTS: No differences were observed in the incidence of BCAR (4.2% vs. 9.5%), graft (95.8% vs. 95.6%), and patient (95.8% vs. 95.6%) survivals or in renal function (60 ± 11.5 vs. 63.4 ± 10.5 ml/min, P = 0.361). Higher mean cholesterol concentration was observed in the SRL/ST group (191.9 ± 63.3 vs. 241.6 ± 61.5 mg/dl, P = 0.019). Treatment discontinuation due to adverse events occurred in 12.5% of patients in TAC/SRL group and 21.7% in SRL/ST group. CONCLUSION: Within this short period of observation, our study was unable to detect any significant difference in major transplant outcomes comparing CNI and ST elimination strategies.
Assuntos
Anti-Inflamatórios/administração & dosagem , Inibidores de Calcineurina , Rejeição de Enxerto/patologia , Imunossupressores/administração & dosagem , Transplante de Rim , Adolescente , Adulto , Idoso , Anti-Inflamatórios/efeitos adversos , Biópsia , Quimioterapia Combinada/efeitos adversos , Feminino , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão/efeitos adversos , Terapia de Imunossupressão/métodos , Imunossupressores/efeitos adversos , Estimativa de Kaplan-Meier , Transplante de Rim/imunologia , Transplante de Rim/patologia , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Adulto JovemRESUMO
AIM: This study was designed to identify optimal therapeutic sirolimus (SRL) concentrations in black kidney transplant recipients on reduced cyclosporine (CsA) exposure and prednisone. METHODS: Seventy patients (64 living/six deceased) received CsA (8-10 mg/kg/d), prednisone, and 15 mg loading dose followed by 5-mg fixed doses of SRL till day 7 when they were randomized to maintain SRL trough concentrations (high-performance liquid chromatography) of 8-12 (GI = 34) or 15-20 (GII = 36) ng/mL. RESULTS: Mean CsA concentrations were 109 +/- 53 vs. 89 +/- 41 ng/mL and 75 +/- 54 vs. 60 +/- 35 ng/mL (ns) at 2 and 6 months. Accordingly, mean SRL trough concentrations were 12.4 +/- 6.1 vs. 20.0 +/- 9.5 ng/mL (p < 0.001) and 10.8 +/- 5.8 vs. 18.0 +/- 6.1 ng/mL (p < 0.001). The incidence of biopsy-proven acute rejection [13% (GI: 18% vs. GII: 8%, ns)], graft loss or death was 16% (GI: 21% vs. GII: 11%, ns]. There were no deaths and three graft losses (GI = 1; GII = 2). Creatinine clearance was higher in GI (64.5 +/- 17 vs. 54.4 +/- 14.7 mL/min, p = 0.011). The incidence of post-transplant diabetes mellitus was 13% and no CMV disease was observed. CONCLUSION: In black recipients of primarily living renal allograft donors reduced CsA exposure and SRL concentration-controlled regimens produced low incidences of acute rejection, post-transplant diabetes mellitus and CMV disease, with no significant impairment in graft function.
Assuntos
Negro ou Afro-Americano , Ciclosporina/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Transplante de Rim , Sirolimo/administração & dosagem , Adulto , Biópsia , Cromatografia Líquida de Alta Pressão , Ciclosporina/farmacocinética , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/farmacocinética , Rejeição de Enxerto/sangue , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Imunossupressores/farmacocinética , Falência Renal Crônica/etnologia , Falência Renal Crônica/cirurgia , Masculino , Prednisona/administração & dosagem , Prednisona/farmacocinética , Estudos Prospectivos , Sirolimo/farmacocinética , Fatores de Tempo , Transplante Homólogo , Resultado do TratamentoRESUMO
The need to adapt optimal conditions of sirolimus blood level monitoring in laboratories led us to optimize an high-performance liquid chromatography-ultraviolet method and compare the elution performances using the mobile phase A, 68% MeOH/2% acetonitrile (ACN)/30% H(2)O and mobile phase B, 30% MeOH/42% ACN/28% H(2)O. Samples were assayed with 1-chlorobutane, redissolved in MeOH/water and injected onto a C-18 column at 50 degrees C. The assay achieved sensitivity of 2.5-150 ng/ml (CV = 10.6%) and recovery of 92-103.6%. The intra- and interassay precisions ranged from 3.3% to 13% and from 5.9% to 15% for quality controls of 7.5, 60 and 120 ng/ml. The mobile phase A was unable to elute and recover sirolimus and internal standard in the expected retention time and concentration. Under our working conditions, the assay was precise, accurate and sensible, stressing the importance of establishing for the best working conditions according to the staff and demands of the laboratory.
Assuntos
Imunossupressores/sangue , Sirolimo/sangue , Cromatografia Líquida de Alta Pressão , Humanos , Raios UltravioletaRESUMO
BACKGROUND: The ability of sirolimus (SRL), in combination with reduced exposure of cyclosporine, was investigated to prevent acute rejection and associated side effects. METHODS: Between June 1999 and February 2000, 70 recipients of primary one-haplotype living-related donor renal allografts were randomized to receive SRL (2 mg/d) or azathioprine (AZA) (2 mg/kg/d) combined with cyclosporine and prednisone. The primary end-point was a composite of first occurrence of biopsy-confirmed acute rejection, graft loss, or death during the first 3 months after transplantation. RESULTS: From week 4 to month 12, SRL patients received lower cyclosporine (week 4: 364 mg/d vs. 455 mg/d, p = 0.004; month 12: 195 mg/d vs. 255 mg/d, p = 0.038) doses and showed lower cyclosporine concentrations (week 4: 247 ng/mL vs. 309 ng/mL, p = 0.04; month 12: 143 ng/mL vs. 188 ng/mL, p = 0.045). Compared with AZA, SRL patients showed reduced 3-month primary end point (0% vs. 17.1%, p = 0.025), and reduced incidence of biopsy-confirmed acute rejection at 3 months (0% vs. 14.3%, p = 0.01) but not at 12 months (11.4% vs. 14.3%, NS). Mean creatinine at 12 months were not different (1.8 +/- 0.6 vs. 1.6 +/- 0.6, p = 0.23). Hyperlipidemia was the only adverse event more frequent among SRL patients (49% vs. 17%, p = 0.01). There were no differences in infections and no malignancies in both groups. CONCLUSIONS: The combination of 2 mg fixed doses of SRL, reduced cyclosporine exposure and prednisone was associated with a low incidence of acute rejection and did not result in significantly impaired graft function compared with patients receiving AZA, standard doses of cyclosporine and prednisone.
Assuntos
Azatioprina/uso terapêutico , Ciclosporina/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Prednisona/uso terapêutico , Sirolimo/uso terapêutico , Adulto , Azatioprina/administração & dosagem , Azatioprina/efeitos adversos , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Lipídeos/sangue , Masculino , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Prospectivos , Segurança , Sirolimo/administração & dosagem , Sirolimo/efeitos adversosRESUMO
BACKGROUND: Different HPLC methods have been developed and used to determined sirolimus blood concentrations. These methods show different performance characteristics, mostly related to peak interference, recovery, assay sensitivity, and turnaround times. OBJECTIVE: We adapted, improved, and validated an HPLC method with UV detection for measurement of sirolimus in whole blood clinical samples. METHODS: The standards, quality controls, or patient samples (0.25 or 0.5 mL) and internal standard (desmethoxysirolimus) were extracted with 1-chlorobutane. After evaporation, the extract was reconstituted in a 70% acetonitrile/water mixture and analyzed onto a reverse-phase C18 column at 50 degrees C under a flow rate of 1.0 mL/min in the HPLC system. Ultraviolet detection was performed at 278 nm, with sensitivity setting of 0.010 AUFS. Identification of peaks of interest was by retention time; quantification of sirolimus was based on a peak area ratio. RESULTS: Analytic recovery ranging from 96 to 120% (CV = 3.7 to 16.8%; bias = -4.2 to 16.7%) was observed throughout the assay's linear range (2.5-150.0 ng/mL). The lower limit of quantification for both sample volumes (0.25 or 0.5 mL) was 2.5 ng/mL (CV = 12 and 15%, bias = -1.2 and 4%, respectively). The intra- and interassay imprecision ranged from 6.2 to 14.4% and from 9.1 to 18.6%, with bias ranging from 1.3 to 12.9% and -1.8% to 7.1, for quality control levels of 3, 10, and 20 ng/mL. Whole blood and extracted samples are stable at room temperature and at 4 and -20 degrees C for 1 week and 3 days, respectively. Chromatograms showed good separation free of interfering peaks. A set of 45 samples can be extracted in 2 h, allowing results within 24 h. CONCLUSION: This HPLC-UV method shows good and reproducible performance, satisfying all requirements of an assay designated to be applied in therapeutic drug monitoring strategies after organ transplantation.