Adverse reactions to antimicrobials in pediatric patients admitted to a tertiary hospital: a cohort study.

BACKGROUND: Antimicrobials are widely used in hospitals and are often associated with adverse drug reactions (ADRs). The objective of this study was to determine the incidence of ADRs caused by antimicrobials and classify them according to the type of reaction, the class of antimicrobials used, causality, severity and avoidability. METHODS: A prospective cohort study was carried out with paediatric patients for 6 months. Causality was verified using the Naranjo and Liverpool algorithms, the severity was verified with the adapted scale of Hartwig and the avoidability was verified with the Liverpool Avoidability Assessment Tool. RESULTS: A total of 303 patients were followed, and 18.2% (55/303) of them had one or more ADRs during the hospital stay. Just over half of the patients (28/55) had diarrhea. The most used antimicrobials were beta-lactams and second-generation cephalosporins. Suspicions were classified mainly as possible 78.6% (55/70) according to the Naranjo algorithm, and as probable 48.6% (34/70) according to the Liverpool algorithm. The antimicrobial most involved with ADRs was cefepime. The risk of manifesting ADR was greater with the use of some antimicrobials such as clindamycin (relative risk (RR) 3.0, CI 1.67 to 5.4), as well as with the increase in hospitalisation days (OR 1.022, CI 1.008 to 1.036) and in the number of antimicrobials prescribed (OR 1.649, CI 1.360 to 2.001). CONCLUSION: ADRs were observed in approximately one-fifth of patients and were mostly gastrointestinal, moderate, unavoidable and with variable causality, depending on the algorithm used.

Effect of conversion from calcineurin inhibitors to everolimus on hepatitis C viremia in adult kidney transplant recipients / Efeitos da conversão de inibidores da calcineurina para Everolimo na viremia por hepatite C em receptores adultos de transplantes renais

ABSTRACT Introduction: Currently, there is no specific immunosuppressive protocol for hepatitis C (HCV)-positive renal transplants recipients. Thus, the aim of this study was to evaluate the conversion effect to everolimus (EVR) on HCV in adult kidney recipients. Method: This is an exploratory single-center, prospective, randomized, open label controlled trial with renal allograft recipients with HCV-positive serology. Participants were randomized for conversion to EVR or maintenance of calcineurin inhibitors. Results: Thirty patients were randomized and 28 were followed-up for 12 months (conversion group, Group 1 =15 and control group, Group 2 =13). RT-PCR HCV levels reported in log values were comparable in both groups and among patients in the same group. The statistical analysis showed no interaction effect between time and group (p value G*M= 0.852), overtime intra-groups (p-value M=0.889) and between group (p-value G=0.286). Group 1 showed a higher incidence of dyslipidemia (p=0.03) and proteinuria events (p=0.01), while no difference was observed in the incidence of anemia (p=0.17), new onset of post-transplant diabetes mellitus (p=1.00) or urinary tract infection (p=0.60). The mean eGFR was similar in both groups. Conclusion: Our study did not show viral load decrease after conversion to EVR with maintenance of antiproliferative therapy.

RESUMO Introdução: Atualmente não há um protocolo imunossupressor específico para os receptores de transplantes renais portadores de hepatite C (HCV). Assim, o objetivo deste estudo foi avaliar o efeito da conversão a Everolimo (EVR) na HCV em receptores adultos de transplantes renais. Método: Trata-se de um estudo unicêntrico, prospectivo, randomizado, exploratório, controlado, aberto em receptores de aloenxertos renais com sorologia positiva para HCV. Os participantes foram randomizados para conversão a EVR ou manutenção dos inibidores da calcineurina. Resultados: Trinta pacientes foram randomizados e 28 foram acompanhados por um período de 12 meses (grupo de conversão, Grupo 1 = 15 e grupo controle, Grupo 2 =13). Níveis de RT-PCR HCV descritos em valores logarítmicos foram comparáveis entre os grupos e entre pacientes em um mesmo grupo. A análise estatística não mostrou efeitos de interação entre tempo e grupo (valor p G*M= 0,852), ao longo do tempo em cada grupo (valor p M=0,889) e entre grupos (valor p G=0,286). O Grupo 1 apresentou uma maior incidência de eventos de dislipidemia (p=0,03) e proteinúria (p=0,01); não houve diferença na incidência de anemia (p=0,17), diabetes mellitus de início pós-transplante (p=1,00) ou infecção do trato urinário (p=0,60). A TFGe média foi semelhante nos dois grupos. Conclusão: Nosso estudo não mostrou redução da carga viral após conversão a EVR com manutenção do tratamento antiproliferativo.

Effect of conversion from calcineurin inhibitors to everolimus on hepatitis C viremia in adult kidney transplant recipients.

INTRODUCTION: Currently, there is no specific immunosuppressive protocol for hepatitis C (HCV)-positive renal transplants recipients. Thus, the aim of this study was to evaluate the conversion effect to everolimus (EVR) on HCV in adult kidney recipients. METHOD: This is an exploratory single-center, prospective, randomized, open label controlled trial with renal allograft recipients with HCV-positive serology. Participants were randomized for conversion to EVR or maintenance of calcineurin inhibitors. RESULTS: Thirty patients were randomized and 28 were followed-up for 12 months (conversion group, Group 1 =15 and control group, Group 2 =13). RT-PCR HCV levels reported in log values were comparable in both groups and among patients in the same group. The statistical analysis showed no interaction effect between time and group (p value G*M= 0.852), overtime intra-groups (p-value M=0.889) and between group (p-value G=0.286). Group 1 showed a higher incidence of dyslipidemia (p=0.03) and proteinuria events (p=0.01), while no difference was observed in the incidence of anemia (p=0.17), new onset of post-transplant diabetes mellitus (p=1.00) or urinary tract infection (p=0.60). The mean eGFR was similar in both groups. CONCLUSION: Our study did not show viral load decrease after conversion to EVR with maintenance of antiproliferative therapy.

Clinical evaluation of a dried blood spot method for determination of mycophenolic acid in renal transplant patients.

OBJECTIVES: The aim of this study is to evaluate the clinical application of dried blood spots (DBS) sampling in renal transplant patients under mycophenolic acid (MPA) immunosuppression, comparing measurements performed in paired plasma and DBS samples. DESIGN AND METHODS: 77 paired DBS and plasma samples were obtained from 19 renal transplant patients. MPA was measured in both matrices by HPLC-DAD. Estimated plasma concentrations (EPC) were calculated from DBS concentrations (DC) using the formula EPC=DC/[1-(Hct/100)], using either individual or mean hematocrit (Hct). Agreement between methods was evaluated using Passing-Bablok regression and Bland-Altman difference plots. RESULTS: MPA concentrations in DBS were in mean 60.7% of those measured in plasma. EPC calculated from DBS and patient's individual Hct presented a high correlation with blood plasma (r=0.9862), and comparable absolute values (slope 1.0563 and intercept -0.0739), being in mean 102.2% of the measured plasma concentrations. EPC can also be calculated with the mean Hct of the group of patients, with similar results. CONCLUSIONS: DBS sampling can be used for TDM of MPA in a clinical setting, employing conventional HPLC equipment, presenting similar results to plasma samples after a proper mathematical treatment. Moreover, due to its intrinsic stability and handling safety, DBS sampling can be considered a useful alternative especially in developing countries where sample logistics could be a major difficulty.