Parte IV. Terapia antimicrobiana en pacientes con cáncer y receptores de trasplante de precursores hematopoyéticos / Antimicrobial therapy in cancer patients and hematopoietic stem cell transplantation receptors

Resumen Este documento incluye los recursos terapéuticos antiinfecciosos necesarios para pacientes inmunocomprometidos por terapia de cáncer o receptores de trasplante de precursores hematopoyéticos (TPH). Se aborda la terapia indicada para pacientes con las situaciones clínicas prevalentes en esta población y la terapia indicada para algunos microorganismos específicos. Según presentación clínica, se aborda el manejo de pacientes con: neutropenia febril sin foco, sepsis, infecciones del sistema nervioso central, neumonía, infecciones de piel y tejidos blandos, enterocolitis neutropénica e infección del tracto urinario. Se describe el arsenal terapéutico necesario, las dosis recomendadas y las precauciones especiales para el uso de antibacterianos, antivirales, antifúngicos y antiparasitarios en esta población, incluida la medición de concentraciones plasmáticas de ciertos fármacos en situaciones específicas.

This manuscript includes the antiinfective therapeutic resources for immunocompromised patients under chemotherapy by cancer or hematopoietic stem cells transplant (HSCT) receptors. The document presents the antimicrobial therapy indicated in the most prevalent clinical situations in this population and the primary and alternative therapy for some specific microorganisms. The clinical situations included in the analysis are: febrile neutropenia without focus, sepsis, infections of the central nervous system, pneumonia, skin and soft tissue infections, neutropenic enterocolitis and urinary tract infection. The therapeutic resources, recommended doses and special precautions for the use of antimicrobial recommended in bacterial, viral, fungal and parasitic infections in this population are described, including the measurement of plasma concentrations of certain drugs in specific situations.

Segurança e Benefício do Uso de Probióticos em Pacientes Submetidos ao TCTH: Revisão Integrativa / Safety and Benefit of Using Probiotics in Patients Undergoing HSCT: Integrative Review / Seguridad y Beneficio del Uso de Probióticos en Pacientes Sometidos al TCTH: Revisión Integradora

Introdução: O transplante de células-tronco hematopoiéticas (TCTH) é um dos potenciais tratamentos curativos utilizados para pacientes com doenças hematológicas e outras doenças imunes. Durante o transplante, o paciente é submetido ao condicionamento e a outros tratamentos, como radioterapia e quimioterapia, o que pode causar a perda da diversidade da microbiota intestinal. A manipulação da microbiota intestinal com probióticos vem sendo apontada como uma estratégia de prevenção de complicações nos pacientes submetidos ao TCTH. Objetivo: Identificar se há evidências científicas relacionadas à segurança e aos benefícios da utilização de probióticos em pacientes submetidos ao TCTH. Método: Revisão integrativa com base em estudos que abordassem o uso de probióticos para o caso específico de pacientes submetidos ao TCTH publicados entre 2000 a 2018. Resultados: Foram selecionados cinco estudos que atenderam aos critérios de inclusão e exclusão, com um total de 52 pacientes. A utilização de probióticos na prevenção e/ou tratamento da diarreia tem mostrado resultados positivos em pacientes com diarreia induzida por antibióticos ou por infecções bacterianas, porém os estudos ainda não destacam benefícios no uso de probióticos no caso específico de pacientes submetidos ao TCTH. Poucos estudos mostram o uso de probióticos para auxílio na melhora dos sintomas associados a infecções ou bacteremias em pacientes imunossuprimidos. Conclusão: O uso de probióticos na população submetida ao TCTH e em imunossuprimidos ainda é controverso, sendo necessários mais estudos que demonstrem os benefícios no uso dessa estratégia para esse público.

Introduction: Hematopoietic stem cell transplantation (HSCT) is one of the potential curative treatments used for patients with hematological and other immune diseases. During transplantation, the patient undergoes conditioning and other treatments, such as radiotherapy and chemotherapy, which may cause loss of the intestinal microbiota diversity. The manipulation of the intestinal microbiota with probiotics has been pointed out as a strategy to prevent complications in patients undergoing HSCT. Objective: To identify if there is scientific evidence related to the safety and benefits of the use of probiotics in patients submitted to HSCT. Method: Integrative review based on studies addressing the use of probiotics for the specific case of patients undergoing HSCT published between 2000 and 2018. Results: Five studies that met the inclusion and exclusion criteria were eligible, with a total of 52 patients. The use of probiotics in the prevention and/or treatment of diarrhea has shown positive results in patients with antibiotic-induced diarrhea or bacterial infections, but the studies do not yet emphasize the benefits of using probiotics in the specific case of patients submitted to HSCT. Few studies show the use of probiotics to help the improvement of the symptoms associated to infections or bacteremia in immunosuppressed patients. Conclusion: The use of probiotics in the population submitted to HSCT and immunosuppressed is still controversial, and further studies are necessary to demonstrate the benefits of using probiotics for this public.

Introducción: El trasplante de células madre de las hematopoyéticas (TCTH) es uno de los posibles tratamientos curativos utilizados para pacientes con enfermedades hematológicas y otras enfermedades inmunes. Durante el transplante, el paciente es sometido al condicionamiento ya otros tratamientos, como radioterapia y quimioterapia, lo que puede causar la pérdida de la diversidad de la microbiota intestinal. La manipulación de la microbiota intestinal con probióticos viene siendo apuntada como una estrategia de prevención de complicaciones en los pacientes sometidos al TCTH. Objetivo: Identificar si hay evidencias científicas relacionadas con la seguridad y beneficios de la utilización de probióticos en pacientes sometidos al TCTH. Método: Revisión integradora basada em estúdios que abordan el uso de probióticos para el caso específico de pacientes sometidos a TCMH publicados entre 2000 y 2018. Resultados: Fueron elegibles 4 estudios que atendieron a los criterios de inclusión y exclusión, con un total de 52 pacientes. La utilización de probióticos en la prevención y/o tratamiento de la diarrea ha mostrado resultados positivos en pacientes con diarrea inducida por antibióticos o por infecciones bacterianas, pero los estudios aún no aportan beneficios en el uso de probióticos en pacientes sometidos al TCTH. Pocos estudios muestran infecciones o bacterias en pacientes inmunosuprimidos que utilizaron probióticos para ayudar en la mejora de los síntomas asociados al tratamiento. Conclusión: El uso de probióticos en la población sometida al TCTH e inmunosuprimidos aún es controvertido, siendo necesarios más estudios que comprueben los beneficios en el uso de probióticos para este público.

Evaluación de la indicación, consumo y costos de antifúngicos en un hospital pediátrico de Chile / Evaluation of the prescription, consumption and costs of antifungal drugs in a pediatric hospital in Chile

Resumen Introducción: El incremento de la enfermedad fúngica invasora (EFI) en pacientes inmunocomprometidos ha conducido a la frecuente prescripción de fármacos altamente activos pero de elevado costo económico. Objetivo: Caracterizar el uso de antifúngicos, evaluar su indicación y determinar consumo y costos asociados. Métodos: Estudio descriptivo, retrospectivo, desde enero de 2015 a abril de 2016. Auditoría de prescripciones y revisión de fichas clínicas; cada prescripción se clasificó de acuerdo a si correspondía a una EFI posible, probable o probada. Se calcularon consumos y costos de tratamientos. Resultados: Se auditaron 152 prescripciones de antifúngicos en 79 pacientes. El costo total de los medicamentos antifúngicos fue de US$ 714.413. El 52,1% del gasto (US $ 372.319) correspondió a indicaciones en EFI probada, 10,7% (US $ 76.377) EFI probable, 0.8% (US $ 5.638) no-EFI, 12,2% (US $ 87.459) EFI posibles y 1,5% (US $ 10.896) EFI descartada y 22,6% (US$ 161.723) fue profilaxis. El mayor consumo fue en indicaciones relacionadas a EFI probada con un DOT probada de 10,54 días, siendo anfotericina B liposomal y voriconazol iv los fármacos con mayor consumo con un DOTprobada AnBL de 3,15 y DOT probada voriconazol iv de 3,01. Conclusiones: El consumo de medicamentos antifúngicos genera altos costos correspondiente al 12% del presupuesto total de farmacia de nuestra institución. El gasto se asoció principalmente a indicaciones en EFI probadas, voriconazol y anfotericina B liposomal los con mayor consumo, lo que sumado a su alto costo y días prolongados de terapia generan un gran impacto en el presupuesto.

Background: The increase of invasive fungal disease (IFD) in immunocompromised patients has led to the frequent prescription of highly active antifungal drugs but with a high economic cost. Aim: To characterize the use of antifungals drugs, evaluate its prescription and determine consumption and associated costs. Methods: Retrospective descriptive study from January 2015 to April 2016. Audit of prescriptions and review of clinical files. Each prescription was classified according to whether it corresponded to a possible, probable or proven invasive fungal disease (IFD). Consumptions and treatment costs were calculated. Results: 152 antifungal prescriptions were audited in 79 patients. The total cost of antifungal medications was US $ 714,413. 52.1% of the expenditure (US $ 372,319) corresponded to indications in proven IFD, 10.7% (US $ 76,377) probable IFD, 0.8% (US $ 5,638) non-IFI, 12.2% (US $ 87,459) IFD possible and 1.5% (US $ 10,896) non-IFD and 22.6% (US $ 161,723) was prophylaxis. The highest consumption was in indications related to IFD tested with a proven DOT of 10.54 days, with liposomal amphotericin B and iv voriconazole the drugs with the highest consumption with a DOT probable_AnBL of 3.15 and DOT proven voriconazole iv of 3.01. Conclusions: The consumption of antifungal drug medications generates high costs at 12% of the total pharmacy budget of our institution. The expense was associated mainly with the indications in IFI tested the voriconazole and amphotericin B liposomal with the highest consumption which added to its high cost and prolonged days of general therapy a big impact in the budget.

Farmacocinética de posaconazol en la profilaxis y tratamiento de la infección fúngica invasora en niños inmunocomprometidos en un hospital pediátrico / Pharmacokinetics of posaconazol in the prophylaxis and treatment of invasive fungal infection in immunocompromised children in a pediatric hospital

Resumen Introducción En pediatría no existe consenso en la dosificación de posaconazol (PSC) para profilaxis y tratamiento de la infección fúngica invasora (IFI), usándose la medición de concentraciones plasmáticas (CPs) del fármaco. Objetivo Describir la experiencia de monitoreo de las CPs de PSC en niños inmunocomprometidos con IFI y determinar si las dosis recomendadas alcanzan CPs efectivas en profilaxis (≥ 0,7 µg/mL) y tratamiento (≥ 1,25 µg/mL). Método Análisis retrospectivo en niños que recibieron PSC suspensión como profilaxis o tratamiento entre enero de 2012 y octubre de 2016, en las unidades de Oncología y Trasplante de Médula Ósea del Hospital Calvo Mackenna. Resultados 78 CPs en seis pacientes (4 indicaciones de profilaxis y 4 tratamientos) fueron revisados. La mediana de dosis de PSC fue de 12,5 y 18,8 mg/kg/d para profilaxis y tratamiento, respectivamente, resultando CP mediana de 0,97 y 1,8 μg/mL, respectivamente. En profilaxis, se registraron 40/67 (60%) con CP ≥ 0,70 μg/mL recibiendo una mediana de dosis de 12,5 mg/kg/d. Mientras que para el tratamiento: 5/11 (46%), presentaron CP ≥ 1,25 μg/mL, recibiendo una mediana de dosis de 18 mg/kg/d. Conclusión Nuestros resultados se ajustan a lo recomendado para la dosificación de PSC, pero evidencian una necesidad de realizar una monitorización individualizada para mantener adecuadas CPs.

Background There is no consensus on the optimal dosage use of posaconazole (PSC) for invasive fungal infection (IFI) in pediatric patients and normally it is adjusted with drug levels (DLs) ≥ 0.7 μg/ml and ≥ 1.25 μg/ml for prophylaxis and treatment, respectively. Objective To describe the experience of monitoring DLs of PSC in immunocompromised pediatric patients with IFI and to determine if the recommended doses reach CP effective in prophylaxis (≥ 0.7 μg/mL) and treatment (≥ 1.25 μg/mL). Method A retrospective analysis in children who received PSC from January 2012 to October 2016, in the Oncology and Bone Marrow Transplant units at Hospital Calvo Mackenna was done Six patients with 78 DLs were reviewed (4 prophylaxis and 4 treatment). Median PSC dose was 12.5 and 18.8 mg/kg/d for prophylaxis and treatment, resulting in mean DLs of 0.97 and 1.8 μg/mL respectively. In prophylaxis 40/67 (60%) were recorded with DLs ≥ 0.70 μg/mL receiving a median dose of 12.5 mg/kg/d. While for treatment: 5/11 (46%) presented DLs ≥ 1.25 μg/mL, receiving a median dose of 18 mg/kg/d. Conclusion Our results are in line with the recommended for PSC dosage, but individualized monitoring is required to maintain adequate DLs.

Use of transfer factor in immunosuppressed surgical patients / Avaliação do uso de fator de transferência na resposta imunológica de pacientes cirúrgicos imunodeprimidos

ABSTRACT Objective : to evaluate the action of Transfer Factor on the immune response of patients with malignant neoplasm submitted to surgery, chemotherapy and radiotherapy. Method: we analyzed the variations of leukocytes, total lymphocytes, T-lymphocytes and CD4 counts in 60 patients submitted to immunostimulation with a single, daily dose of 0.5mg sublingual Transfer Factor, started simultaneously with chemotherapy and/or radiotherapy. Results: there were statistically significant increases in the counts of all cell lines studied, more pronounced after 12 months of use of the medication. Conclusion: the Transfer Factor restored immune response and showed no side effects.

RESUMO Objetivo: avaliar a ação do Fator de Transferência na resposta imunológica de pacientes portadores de neoplasia maligna submetidos à cirurgia, quimioterapia e radioterapia. Método: análise das variações dos valores dos leucócitos, linfócitos totais, linfócitos T e CD4 em 60 pacientes submetidos à imunoestimulação com Fator de Transferência administrado em dose única de 0,5mg por via sublingual, diariamente e iniciada simultaneamente à quimioterapia e/ou radioterapia. Resultados: houve um aumento no número de todas as linhagens celulares estudadas que foi mais acentuada após 12 meses de uso da medicação. A análise estatística realizada com o software Graph Pad Instat, testadas pelo método Kolmogorov and Smirnov, mostrou que os resultados foram significativos. Conclusão: o Fator de Transferência restabeleceu a resposta imune e não apresentou efeitos colaterais.

Prophylactic effect of Bovine lactoferrin against acute toxoplasmosis in immunocompetent and immunosuppressed mice

This study evaluated the immune-potentiating effect of administrating bovine Lactoferrin [LF] to immunocompetent [IC] and immunosuppressed [IS] mice prior to infection with tachyzoites of T. gondii RH strain. Mice were IS with cyclophosphamide. LF was given in seven of them as oral doses on alternate days. Immunological and parasitological assessments showed that LF induced statistical significance comparable resistance against acute toxoplasmosis in IC and IS mice. This was verified by elevated splenic CD4[+] T lymphocytes, reduced tachyzoites' viability and infectivity, with diminished parasite burdens. So, mice mortality declined and their survival was prolonged. This indicated that LF have prophylactic efficacy against human toxoplasmosis in risky persons with alleviating immune balance

Update in the treatment of cutaneous leishmaniasis

Cutaneous leishmaniasis [CL] is still a major health problem in many countries including Saudi Arabia. Patients with CL are seen, not only by dermatologists, but also by pediatricians and community physicians. Knowledge of available treatment options is essential. A literature review utilizing PubMed on Cochrane evidence-based library was undertaken in the last five years. Several medication and therapeutic modalities are currently in use, though the gold standard remains systemic antimonials. Drug resistance and serious side effects preclude the use of available medications. Newer therapies like liposomal amphotericin B, miltefosine and pentamidine are being used; while it is hoped that other drugs like imiquimod, tamoxifen, PDT and pentamidine structural analogs being tested would offer better efficacy, easier administration and lower toxicity. After decades of little advance in the treatment of leishmaniasis, there are now several options with newer compounds and combinations of these

Comparison of different techniques for the diagnosis of parasitic infections among leukemic children

Acute lymphocytic leukemia [ALL] is a worldwide problem, and it is more prevalent in children. As the chemotherapy is taken, the host defenses are altered and the patient becomes more liable to infection. This study aimed at determining the frequency of parasitic infections among children with ALL in relation to controls, and to evaluate the different techniques used in the diagnosis of these infections. The study was carried out in Alexandria University Children's Hospital at El-Shatby during one year. The study included 117 children with ALL, and same number of immunocompetent children as a control group. Stool, urine, cerebrospinal fluid [CSF], and blood samples were collected and prepared to be examined by different techniques. The overall percentages of parasitic infections were 90.6% and 58.1% among leukemic children and controls, respectively. Microsporidiosis was the most prevalent infection, and Cryptosporidium parvum was the most common coccidial infection. Microsporidium was the only parasite detected in the CSF of leukemic children. The best technique was modified Ziehl Neelsen to detect coccidia, Trichrome stain for protozoa and Quick-Hot Gram-chromotrope stain for microsporidial infection. There was a high percentage of parasitic infections among Jeukemic children, and the results indicate that the combination of many techniques is more likely to be effective in the diagnosis of these infections

Adenoviral Pneumonia During Etanercept Treatment in a Patient with Rheumatoid Arthritis

Inhibitors of tumor necrosis factor-alpha (TNF-alpha) have been approved for treating rheumatoid arthritis. As one of the biological response modifiers, etanercept has also been used in the treatment of psoriatic arthritis and inflammatory bowel disease. While etanercept is effective, certain infectious complications, such as tuberculosis, fungus, and cytomegalovirus, have been reported. We report the first Korean case of adenoviral pneumonia in a 55-year-old female who developed disseminated adenoviral infection following etanercept treatment, which resolved after anti-TNF-alpha discontinuation.

Infection prophylaxis in the myelosuppresed patient with cancer

The present prospective study included 29 patients attending the Paediatric Unit of Kasr El-Aini Center of Radiation Oncology and Nuclear Medicine. Eligible patients were randomly allocated to receive or not to receive oral prophylactic antibiotics as well as miconazole [2%] oral gel. Incidence of infection was higher among the control group [77.8%] than the antibiotic group [61%]. However, the difference was not statistically significant. On the other hand, more patients among the control group [86%] significantly developed oral moniliasis than those among the antibiotic group [55.5%] [P = 0.001]