[Experience with daptomycin in a tertiary pediatric hospital]. / Experiencia con el uso de daptomicina en un hospital pediátrico de alta complejidad.

BACKGROUND: Vancomycin has been considered the treatment of choice especially for methicillin-resistant Staphylococcus aureus (MRSA) infections; but its poor tissue penetration, renal toxicity, and requiring of dosages monitoring, raises the need for new treatment alternatives such as daptomycin. AIMS: To analyze the safety and effectiveness of daptomycin in children. METHODS: Children with microbiologically documented infections treated with daptomycin were retrospectively included. RESULTS: The most frequent infections were endocarditis in 9 (32%), sepsis in 4 (14%), bacteremia in 7 (associated with catheter in 3) (25%), osteomyelitis in 3 (10%), peritonitis associated with dialysis in 3 (10%) and suppurative thrombophlebitis in 2 patients (p) (7%). Methicillin-resistant Staphylococcus aureus was the most common pathogen in 18 patients (64%). The indications for daptomycin were due to the failure of conventional treatment in 17 (61%), and the toxicity or intolerance to vancomycin in 11 patients (39%). The average duration of treatment was 19 days (95% ICR 7-42 days). Four patients (14%) completed outpatient treatment, 22 patients had a favorable response (79%). Adverse events were reported in 3 patients (2 creatinine-phosfo-kinase increase) and in one severe skin rash. CONCLUSIONS: Daptomycin demonstrated a favorable efficacy and safety in this pediatric population.

Experiencia con el uso de daptomicina en un hospital pediátrico de alta complejidad / Experience with daptomycin in a tertiary pediatric hospital

Resumen Introducción: Vancomicina ha sido considerada como el tratamiento de elección en especial para Staphylococcus aureus resistente a meticilina (SARM); pero su escasa penetración tisular, su toxicidad renal y el requerir monitoreo de su dosis, plantean la necesidad de nuevas alternativas de tratamiento, como daptomicina. Objetivos: Analizar la seguridad y efectividad de daptomicina en niños. Pacientes y Métodos: Se incluyeron, retrospectivamente, niños con infecciones microbiológicamente documentadas, tratados con daptomicina. Resultados: Las infecciones más frecuentes fueron endocarditis en 9 (32%), sepsis de la comunidad en 4 (14%), bacteriemia en 7 (asociada a catéter en 3) (25%), osteomielitis en 3 (10%), peritonitis asociada a diálisis en 3 (10%) y tromboflebitis supurativa en 2 pacientes (7%). Staphylococcus aureus resistente a meticilina fue el patógeno más común en 18 pacientes (64%), Daptomicina fue indicada por el fracaso del tratamiento convencional en 17 (61%), y la toxicidad o intolerancia a vancomicina en 11 pacientes (39%). La duración media de tratamiento fue de 19 días (RIC 95% 7-42 días). Cuatro pacientes (14%) completaron tratamiento ambulatorio. Tuvieron respuesta favorable 22 pacientes (79%) Se reportaron eventos adversos en tres pacientes: dos elevaciones de creatina-fosfocinasa) y una erupción cutánea grave. Conclusiones: Daptomicina demostró una eficacia y seguridad favorables en esta población pediátrica.

Abstract Background: Vancomycin has been considered the treatment of choice especially for methicillin-resistant Staphylococcus aureus (MRSA) infections; but its poor tissue penetration, renal toxicity, and requiring of dosages monitoring, raises the need for new treatment alternatives such as daptomycin. Aims: To analyze the safety and effectiveness of daptomycin in children. Methods: Children with microbiologically documented infections treated with daptomycin were retrospectively included. Results: The most frequent infections were endocarditis in 9 (32%), sepsis in 4 (14%), bacteremia in 7 (associated with catheter in 3) (25%), osteomyelitis in 3 (10%), peritonitis associated with dialysis in 3 (10%) and suppurative thrombophlebitis in 2 patients (p) (7%). Methicillin-resistant Staphylococcus aureus was the most common pathogen in 18 patients (64%). The indications for daptomycin were due to the failure of conventional treatment in 17 (61%), and the toxicity or intolerance to vancomycin in 11 patients (39%). The average duration of treatment was 19 days (95% ICR 7-42 days). Four patients (14%) completed outpatient treatment, 22 patients had a favorable response (79%). Adverse events were reported in 3 patients (2 creatinine-phosfo-kinase increase) and in one severe skin rash. Conclusions: Daptomycin demonstrated a favorable efficacy and safety in this pediatric population.

Medicinal cannabis in Latin America: History, current state of regulation, and the role of the pharmacist in a new clinical experience with cannabidiol oil.

OBJECTIVE: Cannabis sativa was introduced in Latin America in the 16th century. Nevertheless, many years have elapsed, and scientific progress and the medicinal use of C sativa have been restricted by the national laws of the countries in the region. SUMMARY: In Argentina, the first law on medical cannabis, approved in 2017 (#17,350), establishes a regulatory framework for the medical use and scientific research of this plant and its derivatives. In 2018, the first clinical research protocol in Latin America was approved at Hospital de Pediatria Garrahan (Buenos Aires, Argentina) to evaluate the efficacy and safety of cannabidiol (CBD) oil for the treatment of pediatric patients with refractory epilepsy. In this context, the role of pharmacists in the health care system related to the study protocol and the medicinal use of CBD has evolved from dispensing to active participation in clinical follow-up and research protocols. CONCLUSION: Considering this experience, here we discuss the active role of the clinical pharmacist in the use of medicinal cannabis. Medicinal cannabis should be controlled in a legal framework based on clinical evidence, and the participation of the pharmacist in research and clinical protocols, as well as the dispensing and provision of information on the medicinal products should be emphasized in the clinical setting.

Eficacia y seguridad de ceftarolina fosamil en niños: revisión sistemática y metaanálisis / Safety and effectiveness of ceftaroline fosamil in children: a systematic review and meta-analysis

Introducción. La resistencia a los antibióticos plantea un problema de salud mundial cada vez mayor, por lo que la búsqueda de nuevos y más efectivos antibióticos es prioritaria. La ceftarolina tiene un amplio espectro de actividad contra cepas Gram-positivas clínicamente relevantes, que incluyen el Staphylococcus aureus meticilino resistente y cepas de Streptococcus pneumoniae resistentes, así como algunos patógenos Gram-negativos implicados en infecciones de piel y tejidos blandos o en la neumonía adquirida en la comunidad; es una potencial opción terapéutica. Se realizó una revisión sistemática que evaluó si la ceftarolina era más efectiva y segura que los comparadores. Material y métodos. Se realizó una búsqueda bibliográfica exhaustiva para identificar estudios clínicos experimentales que compararan la seguridad y eficacia de la ceftarolina con un comparador en la población pediátrica. El criterio de evaluación de eficacia fue la tasa de fracaso terapéutico y, para seguridad, la presencia de cualquier efecto adverso. Resultados. Se identificaron tres estudios, 2 de neumonía adquirida en la comunidad y uno de infecciones de piel y tejidos blandos. En ninguno, se detectó diferencia en el riesgo de fracaso terapéutico, RR 0,97 (0,54-1,73), ni en el criterio de seguridad, RR 0,79 (0,51-1,23). Conclusiones. La evidencia disponible sugiere que la ceftarolina podría ser una opción terapéutica válida en el tratamiento de las infecciones de piel y tejidos blandos o neumonía adquirida en la comunidad en pacientes pediátricos. No se encontraron trabajos de alta calidad de evidencia en otro tipo de infecciones o en pacientes admitidos en la Unidad de Cuidados Críticos.

Introduction. Antibiotic resistance is an increasingly growing health problem worldwide, so it is imperative to look for new, more effective antibiotics. Ceftaroline has a broad spectrum of activity against clinically relevant Grampositive strains, including methicillin-resistant Staphylococcus aureus and resistant Streptococcus pneumoniae strains, as well as Gram-negative pathogens implicated in skin and soft tissue infections or community-acquired pneumonia; it is therefore a potential therapeutic option. We conducted a systematic review to assess whether ceftaroline was safer and more effective than comparators. Material and methods. A comprehensive bibliographic search was done to identify experimental clinical trials that compared the safety and effectiveness of ceftaroline to a comparator in the pediatric population. The rate of therapeutic failure was used to determine the effectiveness, while the presence of any adverse event was considered for safety. Results. Three studies were identified: two in community-acquired pneumonia and one in skin and soft tissue infections. No study showed a difference in the risk for therapeutic failure, relative risk (RR): 0.97 (0.54-1.73), or safety criterion, RR: 0.79 (0.51-1.23). Conclusions. The available evidence suggests that ceftaroline may be a valid therapeutic option for the management of skin and soft tissue infections or community-acquired pneumonia in pediatric patients. No studies with a high-quality of evidence were observed in other types of infections or in patients admitted to the critical care unit.

Safety and effectiveness of ceftaroline fosamil in children: a systematic review and meta-analysis. / Eficacia y seguridad de ceftarolina fosamil en niños: revisión sistemática y metaanálisis.

Introduction: Antibiotic resistance is an increasingly growing health problem worldwide, so it is imperative to look for new, more effective antibiotics. Ceftaroline has a broad spectrum of activity against clinically relevant Grampositive strains, including methicillin-resistant Staphylococcus aureus and resistant Streptococcus pneumoniae strains, as well as Gram-negative pathogens implicated in skin and soft tissue infections or community-acquired pneumonia; it is therefore a potential therapeutic option. We conducted a systematic review to assess whether ceftaroline was safer and more effective than comparators. Material and methods: A comprehensive bibliographic search was done to identify experimental clinical trials that compared the safety and effectiveness of ceftaroline to a comparator in the pediatric population. The rate of therapeutic failure was used to determine the effectiveness, while the presence of any adverse event was considered for safety. Results: Three studies were identified: two in community-acquired pneumonia and one in skin and soft tissue infections. No study showed a difference in the risk for therapeutic failure, relative risk (RR): 0.97 (0.54-1.73), or safety criterion, RR: 0.79 (0.51-1.23). Conclusions: The available evidence suggests that ceftaroline may be a valid therapeutic option for the management of skin and soft tissue infections or community-acquired pneumonia in pediatric patients. No studies with a high-quality of evidence were observed in other types of infections or in patients admitted to the critical care unit.

Introducción. La resistencia a los antibióticos plantea un problema de salud mundial cada vez mayor, por lo que la búsqueda de nuevos y más efectivos antibióticos es prioritaria. La ceftarolina tiene un amplio espectro de actividad contra cepas Gram-positivas clínicamente relevantes, que incluyen el Staphylococcus aureus meticilino resistente y cepas de Streptococcus pneumoniae resistentes, así como algunos patógenos Gram-negativos implicados en infecciones de piel y tejidos blandos o en la neumonía adquirida en la comunidad; es una potencial opción terapéutica. Se realizó una revisión sistemática que evaluó si la ceftarolina era más efectiva y segura que los comparadores. Material y métodos. Se realizó una búsqueda bibliográfica exhaustiva para identificar estudios clínicos experimentales que compararan la seguridad y eficacia de la ceftarolina con un comparador en la población pediátrica. El criterio de evaluación de eficacia fue la tasa de fracaso terapéutico y, para seguridad, la presencia de cualquier efecto adverso. Resultados. Se identificaron tres estudios, 2 de neumonía adquirida en la comunidad y uno de infecciones de piel y tejidos blandos. En ninguno, se detectó diferencia en el riesgo de fracaso terapéutico, RR 0,97 (0,54-1,73), ni en el criterio de seguridad, RR 0,79 (0,51-1,23). Conclusiones. La evidencia disponible sugiere que la ceftarolina podría ser una opción terapéutica válida en el tratamiento de las infecciones de piel y tejidos blandos o neumonía adquirida en la comunidad en pacientes pediátricos. No se encontraron trabajos de alta calidad de evidencia en otro tipo de infecciones o en pacientes admitidos en la Unidad de Cuidados Críticos.

Efficacy and safety of ceftaroline: systematic review and meta-analysis.

BACKGROUND: Resistance to antibiotics is steadily increasing. Ceftaroline has a broad spectrum of activity against clinically relevant gram-positive strains including methicillin-resistant Staphylococcus aureus. OBJECTIVES: This systematic review was conducted to evaluate whether ceftaroline is effective and safe, leading to a lower rate of treatment failures than comparators. MATERIAL AND METHODS: Studies were included if they were comparing the efficacy and safety of ceftaroline with other antibiotics. DATA SOURCES: Using the search terms 'ceftaroline' or 'ceftaroline fosamil', a search strategy was developed. The efficacy endpoint was the rate of treatment failure, while the safety endpoint was the incidence of adverse events. Heterogeneity bias was estimated using the Q-test, and publication bias was estimated using Egger's test. Null hypothesis was rejected if p value was less than 0.05. RESULTS: Only 10 studies were included. SYNTHESIS OF RESULTS: The risk of treatment failure was significantly lower for ceftaroline than for comparators, and cumulative meta-analysis showed that the effect size was relevant and precise. Pooled risk ratio was 0.79 (95% confidence interval = 0.65-0.95). The rates of adverse events were similar among the studies, and there were no statistically significant differences between groups. For this endpoint, there was a significant heterogeneity among studies (p = 0.03). Pooled risk ratio for adverse events was 0.98 (95% confidence interval = 0.87-1.10), without a statistical difference. DISCUSSION: The risk of treatment failure was significantly lower for ceftaroline than comparators, while the rate of adverse events was similar. To the best of our knowledge, this is the first systematic review on the efficacy and safety of ceftaroline including children and adults. A limitation is that no randomized controlled trials were found in non-complicated skin- and soft-tissue infection and non-community-acquired pneumonia infections; only few cases with methicillin-resistant Staphylococcus aureus isolations and no patients admitted to the intensive care unit were evaluated. INTERPRETATION: Ceftaroline may be an option of treatment in complicated skin- and soft-tissue infection and community-acquired pneumonia.

Efficacy and safety of daptomycin: systematic review and meta-analysis.

BACKGROUND: The aim of this study was to assess whether daptomycin is safer and more efficacious than comparators for the treatment of serious infection caused by gram-positive microorganisms. METHODS: Electronic databases (Medline, EMBASE, the Cochrane Central Register of Controlled Trials and clinical registered trials) were searched to identify randomized controlled trials (RCTs) that assessed the efficacy and safety of daptomycin versus therapy with any other antibiotic comparator. Two reviewers independently applied selection criteria, performed a quality assessment and extracted the data. Heterogeneity was assessed, and a random-effects or fixed-effects model, when appropriate, was used for estimates of risk ratio (RR). The primary outcome assessed was the risk of clinical treatment failure among the intention-to-treat population and the presence of any treatment related adverse event (AEs). RESULTS: A total of seven trials fulfilled the inclusion criteria. Daptomycin treatment failure rates were no different to comparator regimens (RR = 0.96; CI 95% 0.86-1.06). No significantly different treatment related AEs were identified when comparing groups (RR = 0.91; CI 95% 0.83-1.01). CONCLUSIONS: No significant differences in treatment failure rates and safety were found using daptomycin or any of the comparators treatment.

Uso de posaconazol en niños: experiencia en un hospital pediátrico de alta complejidad / Use of posaconazole in children: Experience in a tertiary pediatric hospital

La información sobre el uso de posaconazol en niños es escasa. Se realizó este estudio descriptivo retrospectivo entre agosto de 2010 y marzo de 2017 para evaluar las características clínicas, microbiológicas y la evolución de los pacientes tratados con posaconazol. Se incluyeron 16 niños. Mediana de edad: 161 meses (rango intercuartílico -RIC- 69-173 m). Todos tenían enfermedad subyacente y presentaban infección fúngica invasiva probada. Los aislamientos más frecuentes fueron Mucor spp. y Aspergillus spp. La dosis media de posaconazol fue 600 mg/día (400-800 mg/día) y la mediana de duración del tratamiento, 223 días (RIC 48-632). Diez pacientes presentaron efectos adversos, pero solo uno requirió suspensión del antifúngico debido a alteraciones hidroelectrolíticas.

There is limited information on the use of posaconazole in children. This retrospective and descriptive study was conducted to evaluate the clinical, microbiological characteristics and evolution of patients treated with posaconazole between August 2010 and March 2017. We included 16 children. Median age: 161 months (interquartile range -IQR-69-173m). All had underlying disease and a proven invasive fungal infection. The most frequent isolated were Mucor spp. and Aspergillus spp. The mean posaconazole dose was 600 mg /day (400-800 mg/day) and the median duration of treatment was 223 days (IQR 48-632). Ten patients had adverse effects, but only one required suspension of the antifungal treatment due to hydroelectrolytic disorders.

[Use of posaconazole in children: Experience in a tertiary pediatric hospital]. / Uso de posaconazol en niños: experiencia en un hospital pediátrico de alta complejidad.

There is limited information on the use of posaconazole in children. This retrospective and descriptive study was conducted to evaluate the clinical, microbiological characteristics and evolution of patients treated with posaconazole between August 2010 and March 2017. We included 16 children. Median age: 161 months (interquartile range -IQR- 69-173 m). All had underlying disease and a proven invasive fungal infection. The most frequent isolated were Mucor spp. and Aspergillus spp. The mean posaconazole dose was 600 mg/day (400-800 mg/day) and the median duration of treatment was 223 days (IQR 48-632). Ten patients had adverse effects, but only one required suspension of the antifungal treatment due to hydroelectrolytic disorders.

La información sobre el uso de posaconazol en niños es escasa. Se realizó este estudio descriptivo retrospectivo entre agosto de 2010 y marzo de 2017 para evaluar las características clínicas, microbiológicas y la evolución de los pacientes tratados con posaconazol. Se incluyeron 16 niños. Mediana de edad: 161 meses (rango intercuartílico ­RIC­ 69-173 m). Todos tenían enfermedad subyacente y presentaban infección fúngica invasiva probada. Los aislamientos más frecuentes fueron Mucor spp. y Aspergillus spp. La dosis media de posaconazol fue 600 mg/ día (400-800 mg/día) y la mediana de duración del tratamiento, 223 días (RIC 48-632). Diez pacientes presentaron efectos adversos, pero solo uno requirió suspensión del antifúngico debido a alteraciones hidroelectrolíticas.

Efficacy and safety of voriconazole in immunocompromised patients: systematic review and meta-analysis.

BACKGROUND: Voriconazole is a second-generation triazole. It has excellent bioavailability and broad antifungal spectrum; thus, it is an attractive option for patients at high risk of invasive fungal infections (IFIs). Comparing efficacy and safety of voriconazole with other antifungals in prophylaxis or treatment of IFIs would be useful to draw conclusions regarding prevention and therapeutics of these infections. AIM: To assess efficacy and safety of voriconazole compared with other options as prophylaxis or treatment of IFIs in haematology-oncology patients. MATERIALS AND METHODS: A literature search was performed in MEDLINE database using the search term 'voriconazole' and completed with manual search. STUDY SELECTION: Randomized controlled trials (RCTs) comparing voriconazole with other antifungal agents or placebo. DATA EXTRACTION: Seven studies fulfilled the eligibility criteria. RESULTS: Five studies compared voriconazole to another comparator as prophylaxis of IFIs and two as treatment. Pooled results showed that voriconazole was more effective than the comparator (RR = 1.17; 95%CI = 1.01-1.34), but heterogeneity was significant (Q test 32.7; p = .00001). Sub-analysis according to prophylaxis showed RR = 1.17; 95%CI = 1.00-1.37; while as treatment, RR = 1.23; 95%CI = 0.68-2.22. Risk of adverse events was not different from that observed for the comparator (RR = 1.06, 95%CI = 0.66-1.72) though significant heterogeneity was detected (p < .01). CONCLUSIONS: Voriconazole was as effective and safe as comparators, probably better as prophylaxis than as treatment, but limitations due to variability in the sample size of studies, differences in the age of patients, and heterogeneity between studies' outcome measures indicate the need for further research.

Anidulafungina en niños: experiencia de un hospital pediátrico de tercer nivel en Argentina / Ánidulafungin in children: Experience in a tertiary care children's hospital in Argentina

La experiencia con anidulafungina en el tratamiento de infecciones fúngicas invasivas en pediatría es escasa. Se presenta nuestra experiencia en 55 niños. La anidulafungina se administró por vía intravenosa en la dosis de carga de 3 mg/kg en una sola dosis diaria, seguida de 1,5 mg/kg cada 24 h durante una media de 14 días (rango, 7-22 d.). La mediana de edad de los pacientes fue de 114 meses (rango intercuartíhco, 32168 m.). Todos los pacientes tenían enfermedades subyacentes. En los trasplantados de médula ósea, la diferencia entre el valor inicial y al final de la administración del fármaco en el recuento de glóbulos blancos, valores de transaminasas y función renal no fue significativo. Ninguno de los pacientes tuvo eventos adversos o murió por causas relacionadas con anidulafungina. La anidulafungina podría ser una opción para la profilaxis o el tratamiento de las infecciones fúngicas invasivas en pediatría, aunque se requieren estudios metodológicamente sólidos para probarlo.

The experience using anidulafungin for the treatment of invasive fungal infections in pediatrics is limited. In this article, we describe our experience in 55 children. Anidulafungin was administered intravenously at a loading dose of 3 mg/kg once daily, followed by 1.5 mg/kg every 24 hours over a mean period of 14 days (range: 7-22 days). Patients' median age was 114 months old (interquartile range: 32-168 months old). All patients had underlying diseases. Among patients with bone marrow transplant, the difference in white blood cell count, transaminase levels, and renal function at baseline and at the end of anidulafungin administration was not significant. No adverse events were reported and no patient died from an anidulafungin-related cause. Anidulafungin may be considered an alternative for the prophylaxis or treatment of invasive fungal infections in pediatrics but methodologically robust studies are needed to confirm this.

Anidulafungin in children: Experience in a tertiary care children's hospital in Argentina. / Anidulafungina en niños: experiencia de un hospital pediátrico de tercer nivel en Argentina.

The experience using anidulafungin for the treatment of invasive fungal infections in pediatrics is limited. In this article, we describe our experience in 55 children. Anidulafungin was administered intravenously at a loading dose of 3 mg/kg once daily, followed by 1.5 mg/kg every 24 hours over a mean period of 14 days (range: 7-22 days). Patients' median age was 114 months old (interquartile range: 32-168 months old). All patients had underlying diseases. Among patients with bone marrow transplant, the difference in white blood cell count, transaminase levels, and renal function at baseline and at the end of anidulafungin administration was not significant. No adverse events were reported and no patient died from an anidulafungin-related cause. Anidulafungin may be considered an alternative for the prophylaxis or treatment of invasive fungal infections in pediatrics but methodologically robust studies are needed to confirm this.

La experiencia con anidulafungina en el tratamiento de infecciones fúngicas invasivas en pediatría es escasa. Se presenta nuestra experiencia en 55 niños. La anidulafungina se administró por vía intravenosa en la dosis de carga de 3 mg/kg en una sola dosis diaria, seguida de 1,5 mg/kg cada 24 h durante una media de 14 días (rango, 7-22 d.). La mediana de edad de los pacientes fue de 114 meses (rango intercuartílico, 32-168 m.). Todos los pacientes tenían enfermedades subyacentes. En los trasplantados de médula ósea, la diferencia entre el valor inicial y al final de la administración del fármaco en el recuento de glóbulos blancos, valores de transaminasas y función renal no fue significativo. Ninguno de los pacientes tuvo eventos adversos o murió por causas relacionadas con anidulafungina. La anidulafungina podría ser una opción para la profilaxis o el tratamiento de las infecciones fúngicas invasivas en pediatría, aunque se requieren estudios metodológicamente sólidos para probarlo.

Eficacia y seguridad de la caspofungina en pediatría: revisión sistemática y metaanálisis / Efficacy and safety of caspofungin in children: systematic review and meta-analysis

Las infecciones fúngicas invasivas son una importante causa de morbimortalidad en pediatría. La caspofungina es una equinocandina utilizada como alternativa en la prevención y/o tratamiento de ciertas infecciones fúngicas invasivas en niños, aunque con poca evidencia sobre su eficacia y seguridad en comparación con el tratamiento habitual. Objetivos. Evaluar la eficacia y seguridad de la caspofungina comparada con otros antifúngicos en la prevención y/o tratamiento de infecciones fúngicas invasivas en pediatría. Material y métodos. La estrategia de búsqueda inicial tuvo como objetivo identificar estudios controlados aleatorizados de aceptable calidad metodológica (escala de Jadad > 3) mediante la palabra clave "caspofungin" realizados en pacientes de entre los 0 y los 18 años. Resultados. Solo 3 publicaciones cumplieron los criterios de inclusión. De ellas, 2 fueron en población pediátrica y una en neonatal. No se documentó una mayor incidencia de efectos adversos para la caspofungina y su eficacia no se diferenció de otros antifúngicos (RR típico 1,47; IC 95%: 0,78-2,79). Conclusiones. Esta revisión sistemática sugiere que la caspofungina podría considerarse como una alternativa para su indicación en pediatría en la prevención y tratamiento de las infecciones fúngicas invasivas. Sin embargo, dado el pequeño número de publicaciones existentes, se requieren más estudios para alcanzar conclusiones definitivas.

Invasive fungal infections are a significant cause of morbidity and mortality in children. Caspofungin is an echinocandin used as an alternative treatment in the prevention and/or treatment of certain invasive fungal infections in children, although compared to the standard treatment there is little evidence on its efficacy and safety. Objectives. To evaluate the efficacy and safety of caspofungin compared with other antifungal drugs for the prevention and/or treatment of invasive fungal infections in children. Material and methods. The objective of the initial search strategy was to identify randomized controlled studies of acceptable methodological quality (Jadad scale >3), through the key word "caspofungin", conducted in patients with an age range from 0 to 18 years old. Results. Only 3 publications met the inclusion criteria. Two of them were studies conducted in children and one in newborn infants. A higher incidence of adverse events was not documented for caspofungin and its efficacy was not different from that of other antifungal drugs (typical RR 1.47; CI 95%: 0.78-2.79). Conclusions. This systematic review suggests that caspofungin could be considered as an alternative drug in children for the prevention and treatment of invasive fungal infections. However, given the small number of existing publications, more studies are required to reach definite conclusions.

Efficacy and safety of caspofungin in children: systematic review and meta-analysis. / Eficacia y seguridad de la caspofungina en pediatria: revision sistematica y metaanalisis.

INTRODUCTION: Invasive fungal infections are a significant cause of morbidity and mortality in children. Caspofungin is an echinocandin used as an alternative treatment in the prevention and/or treatment of certain invasive fungal infections in children, although compared to the standard treatment there is little evidence on its efficacy and safety. OBJECTIVE: To evaluate the efficacy and safety of caspofungin compared with other antifungal drugs for the prevention and/or treatment of invasive fungal infections in children. MATERIALS AND METHODS: The objective of the initial search strategy was to identify randomized controlled studies of acceptable methodological quality (Jadad scale >3), through the key word "caspofungin", conducted in patients with an age range from 0 to 18 years old. RESULTS: The objective of the initial search strategy was to identify randomized controlled studies of acceptable methodological quality (Jadad scale >3), through the key word "caspofungin", conducted in patients with an age range from 0 to 18 years old. CONCLUSIONS: This systematic review suggests that caspofungin could be considered as an alternative drug in children for the prevention and treatment of invasive fungal infections. However, given the small number of existing publications, more studies are required to reach definite conclusions.

INTRODUCCIÓN: Las infecciones fúngicas invasivas son una importante causa de morbimortalidad en pediatría. La caspofungina es una equinocandina utilizada como alternativa en la prevención y/o tratamiento de ciertas infecciones fúngicas invasivas en niños, aunque con poca evidencia sobre su eficacia y seguridad en comparación con el tratamiento habitual. OBJETIVO: Evaluar la eficacia y seguridad de la caspofungina comparada con otros antifúngicos en la prevención y/o tratamiento de infecciones fúngicas invasivas en pediatría. MATERIAL Y MÉTODOS: La estrategia de búsqueda inicial tuvo como objetivo identificar estudios controlados aleatorizados de aceptable calidad metodológica (escala de Jadad 〉 3) mediante la palabra clave "caspofungin" realizados en pacientes de entre los 0 y los 18 años. RESULTADOS: Solo 3 publicaciones cumplieron los criterios de inclusión. De ellas, 2 fueron en población pediátrica y una en neonatal. No se documentó una mayor incidencia de efectos adversos para la caspofungina y su eficacia no se diferenció de otros antifúngicos (RR típico 1,47; IC 95%: 0,78-2,79). CONCLUSIONES: Esta revisión sistemática sugiere que la caspofungina podría considerarse como una alternativa para su indicación en pediatría en la prevención y tratamiento de las infecciones fúngicas invasivas. Sin embargo, dado el pequeño número de publicaciones existentes, se requieren más estudios para alcanzar conclusiones definitivas.

Is Trimethoprim-Sulfamethoxazole a Valid Alternative in the Management of Infections in Children in the Era of Community-Acquired Methicillin-Resistant Staphylococcus aureus? A Comprehensive Systematic Review.

Objective. To evaluate the use of TMP-SMX compared with other options available for the treatment of children with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections. Data Sources. The following databases were searched: Medline and PreMedline (OivdSP interface); Excerpta Medica Database (EMBASE; Elsevier interface); Cumulative Index to the Nursing and Allied Health Literature (CINAHL; EbscoHost interface); Sciences Citation Index Expanded (SCI-EXPANDED; Web of Science interface); Cochrane Library (Wiley interface); Scopus (Elsevier interface), and DARE, HTA (CRD interface). The search strategy was the one developed by SIGN to identify randomized clinical trials and systematic reviews. Also, we conducted a hand review of all reference lists of included studies. No language or data limits were added. The last search was done on October 1, 2015. Main key words were trimethoprim or trimethoprim-sulfamethoxazole combination and Staphylococcus aureus. Study Selection. Only randomized controlled trials comparing TMP-SMX versus any other antibiotic as the first-line treatment in CA-MRSA infections in children were included. Articles were reviewed by 2 reviewers, and in case of discrepancy, the final decision was made by the study coordinator. Data Extraction. Only 27 out of 364 articles identified were randomized controlled trials and only 4 fulfilled the eligibility criteria (Jadad score >3). Data Synthesis. Evidence found only referred to use of TMP-SMX in soft tissue infections. Heterogeneity among studies precluded meta-analysis. Conclusions. Available evidence is not conclusive to promote or refuse TMP-SMX as first-line treatment in CA-MRSA infections in children. Additional well-designed studies are required to fsurther elucidate this issue.

Deoxycholate amphotericin B and nephrotoxicity in the pediatric setting.

Since the introduction of amphotericin B as an antifungal agent, the morbidity and mortality of pediatric patients with mycotic infections have increased, primarily because of the increased immunocompromised patients. Despite the fact that deoxycholate amphotericin B was once the primary drug used for mycotic infections, its administration to children older than neonates is currently controversial because of its nephrotoxic effects. Three lipid-associated formulations have been developed and have reportedly shown similar efficacy and fewer nephrotoxic effects in adults than conventional amphotericin B, but the conclusions from comparative studies in children evaluating the nephrotoxicity risks of the 4 agents are controversial. Nevertheless, guidelines favor liposomal or lipid complex amphotericin B when polyene antifungal therapy is recommended in this age group. However, high acquisition costs often preclude their prescription in economically poor regions. Thus, physicians must consider all of these factors when determining the most cost-effective polyene antifungal treatment for their pediatric patients. This is particularly pertinent in developing countries where resources are scarce. Adjuvant sodium supplementation has been reported to be effective in protecting kidney function in extremely low birth weight infants prescribed deoxycholate amphotericin B. Further pharmacokinetic and pharmacodynamic studies of the drug in children could also provide information for rational dosing regimens designed to decrease nephrotoxicity. Conventional amphotericin B, with appropriate kidney protective measures, still plays a role in the treatment of empiric invasive mycotic infections in most pediatric patients. Liposomal and lipid complex amphotericin B should be reserved for those receiving long-term nephrotoxic agents or with altered renal function or disease. Antifungal susceptibility, renal compromise and the clinical status of the patient should determine treatment for culture-proven infections. Under the current cost limitations, undertaking and evaluating low-cost, kidney-sparing, deoxycholate amphotericin B treatments for children should be a primary concern.

[Advantages and drawbacks of amphotericin formulations in children: literature review]. / Ventajas y desventajas de los distintos tipos de anfotericina en pediatría: revisión de la bibliografía.

Fungal infections have increased in morbidity, and the range of fungal species causing disease in humans has expanded, mainly due to the rise in number of immunocompromised patients. Amphotericin B is a broad spectrum antifungal agent that has been the standard therapy for many life-threatening mycoses for the past 50 years. However, the use of this drug is commonly associated with infusion related events (such as chills, fever, headache, nausea, vomiting), and most significantly to dose limiting nephrotoxicity. Three lipid formulations that increase the therapeutic index have been approved for use. However, questions regarding dose, cost-effectiveness and indications exist in the pediatric setting. Although no high quality evidence studies in children comparing the four types of amphotericin in culture-positive fungal infections currently exist, all four preparations are believed to have similar effectiveness. High drug costs limit the use of lipid formulations; however, renal toxic side effects should be taken into account when costs are considered.

Ventajas y desventajas de los distintos tipos de anfotericina en pediatría: revisión de la bibliografía / Advantages and drawbacks of amphotericin formulations in children: literature review

Las infecciones fúngicas han aumentado últimamente y el espectro de especies se ha modificado, en especial por el aumento del número de pacientes inmunocomprometidos. La anfotericina B es un antimicótico de amplio espectro; ha sido, durante los últimos 50 años, el fármaco de elección para el tratamiento antifúngico empírico y frente al aislamiento de hongos sensibles. Sin embargo, su uso se asocia con efectos adversos como fiebre, escalofríos, náuseas y vómitos (dependientes de la infusión) y, más significativamente, con nefrotoxicidad. Existen en la actualidad tres presentaciones farmacéuticas con lípidos que aumentan el índice terapéutico. A pesar de su uso extenso, existen aún interrogantes acerca de las dosis óptimas y costos que justifiquen su empleo en la edad pediátrica. No hay trabajos de alta calidad de evidencia sobre infecciones fúngicas documentadas en pediatría que comparen las cuatro presentaciones farmacéuticas disponibles. No obstante, pareciera que todas tienen similar eficacia. Los elevados costos de las anfotericinas asociadas a lípidos limitan su uso; sin embargo, la reducción de costos asociados a la menor nefrotoxicidad debería considerarsecuando se analizan los aspectos económicos de su indicación

Ventajas y desventajas de los distintos tipos de anfotericina en pediatría: revisión de la bibliografía / Advantages and drawbacks of amphotericin formulations in children: literature review

Las infecciones fúngicas han aumentado últimamente y el espectro de especies se ha modificado, en especial por el aumento del número de pacientes inmunocomprometidos. La anfotericina B es un antimicótico de amplio espectro; ha sido, durante los últimos 50 años, el fármaco de elección para el tratamiento antifúngico empírico y frente al aislamiento de hongos sensibles. Sin embargo, su uso se asocia con efectos adversos como fiebre, escalofríos, náuseas y vómitos (dependientes de la infusión) y, más significativamente, con nefrotoxicidad. Existen en la actualidad tres presentaciones farmacéuticas con lípidos que aumentan el índice terapéutico. A pesar de su uso extenso, existen aún interrogantes acerca de las dosis óptimas y costos que justifiquen su empleo en la edad pediátrica. No hay trabajos de alta calidad de evidencia sobre infecciones fúngicas documentadas en pediatría que comparen las cuatro presentaciones farmacéuticas disponibles. No obstante, pareciera que todas tienen similar eficacia. Los elevados costos de las anfotericinas asociadas a lípidos limitan su uso; sin embargo, la reducción de costos asociados a la menor nefrotoxicidad debería considerarsecuando se analizan los aspectos económicos de su indicación (AU)

Ventajas y desventajas de los distintos tipos de anfotericina en pediatría: revisión de la bibliografía / Advantages and drawbacks of amphotericin formulations in children: literature review

Las infecciones fúngicas han aumentado últimamente y el espectro de especies se ha modificado, en especial por el aumento del número de pacientes inmunocomprometidos. La anfotericina B es un antimicótico de amplio espectro; ha sido, durante los últimos 50 años, el fármaco de elección para el tratamiento antifúngico empírico y frente al aislamiento de hongos sensibles. Sin embargo, su uso se asocia con efectos adversos como fiebre, escalofríos, náuseas y vómitos (dependientes de la infusión) y, más significativamente, con nefrotoxicidad. Existen en la actualidad tres presentaciones farmacéuticas con lípidos que aumentan el índice terapéutico. A pesar de su uso extenso, existen aún interrogantes acerca de las dosis óptimas y costos que justifiquen su empleo en la edad pediátrica. No hay trabajos de alta calidad de evidencia sobre infecciones fúngicas documentadas en pediatría que comparen las cuatro presentaciones farmacéuticas disponibles. No obstante, pareciera que todas tienen similar eficacia. Los elevados costos de las anfotericinas asociadas a lípidos limitan su uso; sin embargo, la reducción de costos asociados a la menor nefrotoxicidad debería considerarsecuando se analizan los aspectos económicos de su indicación (AU)