Antibiotic prescription patterns in patients with suspected urinary tract infections in Ecuador.

BACKGROUND: Urinary tract infections (UTI) are among the most common cause to prescribe antibiotics in primary care. Diagnosis is based on the presence of clinical symptoms in combination with the results of laboratory tests. Antibiotic therapy is the primary approach to the treatment of UTIs; however, some studies indicate that therapeutics in UTIs may be suboptimal, potentially leading to therapeutic failure and increased bacterial resistance. METHODS: This study aimed to analyze the antibiotic prescription patterns in adult patients with suspected UTIs and to evaluate the appropriateness of the antibiotic prescription. This is a cross-sectional study of patients treated in outpatient centers and in a second-level hospital of the Ministry of Public Health (MOPH) in a city in Ecuador during 2019. The International Classification of Disease Tenth Revision (ICD-10) was used for the selection of the acute UTI cases. The patients included in this study were those treated by family, emergency, and internal medicine physicians. RESULTS: We included a total of 507 patients in the analysis and 502 were prescribed antibiotics at first contact, constituting an immediate antibiotic prescription rate of 99.01%. Appropriate criteria for antibiotic prescription were met in 284 patients, representing an appropriate prescription rate of 56.02%. Less than 10% of patients with UTI had a urine culture. The most frequently prescribed antibiotics were alternative antibiotics (also known as second-line antibiotics), such as ciprofloxacin (50.39%) and cephalexin (23.55%). Factors associated with inappropriate antibiotic prescribing for UTIs were physician age over forty years, OR: 2.87 (95% CI, 1.65-5.12) p<0.0001, medical care by a general practitioner, OR: 1.89 (95% CI, 1.20-2.99) p = 0.006, not using point-of-care testing, OR: 1.96 (95% CI, 1.23-3.15) p = 0.005, and care at the first level of health, OR: 15.72 (95% CI, 8.57-30.88) p<0.0001. CONCLUSIONS: The results of our study indicate an appropriate prescription rate of 56.02%. Recommended antibiotics such as nitrofurantoin and fosfomycin for UTIs are underutilized. The odds for inappropriate antibiotic prescription were 15.72 times higher at the first level of care compared to the second. Effective strategies are needed to improve the diagnosis and treatment of UTIs.

[Health technology assessment in Ecuador's ministry of public health as a tool for drug purchasing from 2012 to 2015]. / La evaluación de tecnologías sanitarias en el Ministerio de Salud Pública de Ecuador como herramienta para la compra de medicamentos entre 2012 y 2015.

OBJECTIVE: Learn how the Ministry of Public Health (MSP, the Spanish acronym) of Ecuador uses health technology assessment (HTA) in decision-making on the purchase of drugs that are not on the National List of Essential Medicines (NLEM). METHODS: Information from databases of the Health Intelligence Directorate (DIS, the Spanish acronym) and the National Directorate of Drugs and Medical Devices (DNMDM, the Spanish acronym), was used to compare decisions made by both entities, to learn about the use and consistency of HTA reports in decisions on purchasing drugs not included in the NLEM. RESULTS: From 2012 to 2015, 227 reports were issued, of which 87 cover drugs; 36, devices; 29: medical procedures; 34: health programs; and 41: other medical technologies. The DNMDM requested 59 of the reports on drugs. There was 80% agreement in decisions made by the two directorates that participate in the process. CONCLUSIONS: The MSP, through the DIS, began using HTA in 2012. Given that the majority of reports evaluate drugs, it is essential that reports be prepared for other types of medical technologies and that they be prepared and used as widely as possible. Despite a high level of agreement in decisions, it is important to continue to improve the reports' scope and quality, and to monitor adoption and dissemination of authorized and funded technologies to learn the effectiveness and impact of HTA in Ecuador.

La evaluación de tecnologías sanitarias en el Ministerio de Salud Pública de Ecuador como herramienta para la compra de medicamentos entre 2012 y 2015 / Health technology assessment in Ecuador’s ministry of public health as a tool for drug purchasing from 2012 to 2015

Objetivo. Conocer el uso de la evaluación de tecnologías sanitarias (ETS) en la toma de decisiones del Ministerio de Salud Pública (MSP) del Ecuador para la compra de medicamentos que no se encuentran en el Cuadro Nacional de Medicamentos Básicos (CNMB). Métodos. Con la información de las bases de datos de la Dirección de Inteligencia de la Salud (DIS) y la Dirección Nacional de Medicamentos y Dispositivos Médicos (DNMDM), se compararon las decisiones tomadas por ambas instancias, para conocer el uso y la congruencia de los informes de ETS en las decisiones de compra de los medicamentos no incluidos en el CNMB. Resultados. Entre 2012 y 2015, se han elaborado 227 informes, de los cuales 87 corresponden a medicamentos, 36 a dispositivos, 29 a procedimientos médicos, 34 a programas sanitarios, y 41 a otras tecnologías médicas. De los informes de medicamentos, 59 fueron solicitados por la DNM. La concordancia entre las decisiones tomadas por las dos direcciones que participan en el proceso alcanzó 80%. Conclusiones. La ETS se inició en el MSP en 2012 a través de la DIS. Considerando que la mayoría de informes evalúan medicamentos, es indispensable que se desarrollen informes para otros tipos de tecnologías médicas y que se difunda al máximo su desarrollo y uso. A pesar de que el nivel de concordancia entre las decisiones es elevado, es importante seguir mejorando el alcance y la calidad de los informes, así como monitorizar la incorporación y difusión de las tecnologías autorizadas y financiadas para conocer la efectividad y el impacto de la ETS en Ecuador.

Objective. Learn how the Ministry of Public Health (MSP, the Spanish acronym) of Ecuador uses health technology assessment (HTA) in decision-making on the purchase of drugs that are not on the National List of Essential Medicines (NLEM). Methods. Information from databases of the Health Intelligence Directorate (DIS, the Spanish acronym) and the National Directorate of Drugs and Medical Devices (DNMDM, the Spanish acronym), was used to compare decisions made by both entities, to learn about the use and consistency of HTA reports in decisions on purchasing drugs not included in the NLEM. Results. From 2012 to 2015, 227 reports were issued, of which 87 cover drugs; 36, devices; 29: medical procedures; 34: health programs; and 41: other medical technologies. The DNMDM requested 59 of the reports on drugs. There was 80% agreement in decisions made by the two directorates that participate in the process. Conclusions. The MSP, through the DIS, began using HTA in 2012. Given that the majority of reports evaluate drugs, it is essential that reports be prepared for other types of medical technologies and that they be prepared and used as widely as possible. Despite a high level of agreement in decisions, it is important to continue to improve the reports’ scope and quality, and to monitor adoption and dissemination of authorized and funded technologies to learn the effectiveness and impact of HTA in Ecuador.

Influence of genetic variants of CYP2D6, CYP2C9, CYP2C19 and CYP3A4 on antiepileptic drug metabolism in pediatric patients with refractory epilepsy.

BACKGROUND: Identified the polymorphisms of CYP2D6, CYP2C9, CYP2C19 and CYP3A4, within a rigorously selected population of pediatric patients with drug-resistant epilepsy. METHOD: The genomic DNA of 23 drug-resistant epilepsy patients and 7 patients with good responses were analyzed. Ten exons in these four genes were genotyped, and the drug concentrations in saliva and plasma were determined. RESULTS: The relevant SNPs with pharmacogenomics relations were CYP2D6*2 (rs16947) decreased your activity and CYP2D6*4 (rs1065852), CYP2C19*2 (rs4244285) and CYP3A4*1B (rs2740574) by association with poor metabolizer. The strongest risk factors were found in the AA genotype and allele of SNP rs3892097 from the CYP2D6 gene, followed by the alleles A and T of SNPs rs2740574 and rs2687116, respectively from CYP3A4. The most important concomitance was between homozygous genotype AA of rs3892097 and genotype AA of rs2740574 with 78.3% in drug-resistant epilepsy patients as compared to 14.3% in control patients. CONCLUSION: The results demonstrated the important role of the CYP 3A4*1B allelic variant as risk factor for developing drug resistance and CYP2D6, CYP2C19 SNPs and haplotypes may affect the response to antiepileptic drugs.

Epidemiology of Tropical Neglected Diseases in Ecuador in the Last 20 Years.

BACKGROUND: Tropical and zoonotic diseases are major problems in developing countries like Ecuador. Poorly designed houses, the high proportion of isolated indigenous population and under developed infrastructure represent a fertile environment for vectors to proliferate. Control campaigns in Ecuador over the years have had varying success, depending on the disease and vectors targeted. AIMS: In our study we analyse the current situation of some neglected diseases in Ecuador and the efficiency of the control campaigns (by measuring changes in numbers of cases reported) that the Ecuadorian government has been running to limit the spread of these infectious and parasitic diseases. RESULTS: Our study reveals that Brucellosis, Chagas Disease, Rabies and Onchocerciasis have been controlled, but small outbreaks are still detected in endemic areas. Leptospirosis and Echinococcosis have been increasing steadily in recent years in Ecuador since the first records. The same increase has been reported world-wide also. Better diagnosis has resulted in a higher number of cases being identified, particularly with regard to the linking of outdoor activities and contact with farm animals as contributing vectors. Improvements in diagnosis are due to regular professional training, implementation of automatized systems, establishing diagnosis protocols and the creation of an epidemiological vigilance network that acts as soon as a case is reported. CONCLUSION: Control campaigns performed in Ecuador have been successful in recent years, although natural phenomena limit their efficiency. Leptospirosis and Echinococcosis infections remain a growing problem in Ecuador as it is worldwide.

MDR-1 and MRP2 Gene Polymorphisms in Mexican Epileptic Pediatric Patients with Complex Partial Seizures.

Although the Pgp efflux transport protein is overexpressed in resected tissue of patients with epilepsy, the presence of polymorphisms in MDR1/ABCB1 and MRP2/ABCC2 in patients with antiepileptic-drugs resistant epilepsy (ADR) is controversial. The aim of this study was to perform an exploratory study to identify nucleotide changes and search new and reported mutations in patients with ADR and patients with good response (CTR) to antiepileptic drugs (AEDs) in a rigorously selected population. We analyzed 22 samples In Material and Methods, from drug-resistant patients with epilepsy and 7 samples from patients with good response to AEDs. Genomic DNA was obtained from leukocytes. Eleven exons in both genes were genotyped. The concentration of drugs in saliva and plasma was determined. The concentration of valproic acid in saliva was lower in ADR than in CRT. In ABCB1, five reported SNPs and five unreported nucleotide changes were identified; rs2229109 (GA) and rs2032582 (AT and AG) were found only in the ADR. Of six SNPs associated with the ABCC2 that were found in the study population, rs3740066 (TT) and 66744T > A (TG) were found only in the ADR. The strongest risk factor in the ABCB1 gene was identified as the TA genotype of rs2032582, whereas for the ABCC2 gene the strongest risk factor was the T allele of rs3740066. The screening of SNPs in ACBC1 and ABCC2 indicates that the Mexican patients with epilepsy in this study display frequently reported ABCC1 polymorphisms; however, in the study subjects with a higher risk factor for drug resistance, new nucleotide changes were found in the ABCC2 gene. Thus, the population of Mexican patients with AED-resistant epilepsy (ADR) used in this study exhibits genetic variability with respect to those reported in other study populations; however, it is necessary to explore this polymorphism in a larger population of patients with ADR.

Genetic polymorphisms associated with antiepileptic metabolism.

Several factors, including pharmacogenetics, contribute to inter-individual variability in drug response. Many antiepileptic drugs (AEDs) are metabolized by a variety of enzymatic reactions, and the cytochrome P450 (CYP) family has attracted considerable attention. Some of the CYPs exist as genetic (allelic) variants, which may also affect the plasma concentrations or drug exposure. Regarding the metabolism of AEDs, the polymorphic CYP2C9 and CYP2C19 are of particular interest. There have been recent advances in discovering factors such as these, especially those underlying the risk of medication toxicity. This review summarizes the evidence about whether such polymorphisms affect the clinical action of AEDs to facilitate future studies on the pharmacogenetics of epilepsy. We performed Key Words searches in the public databases PubMed, Medscape, and Rxlisty, Pharm GKB for genetic polymorphisms and the NCBI website for the nomenclature of alleles of CYP450, finding that CYP2D6, CYP2C9, CYP3A4, and CYP2D19 were involved in the metabolism of most antiepileptic drugs, given the allele frequency in the population and the associated variability in the clinical response.

GABAergic alterations in neocortex of patients with pharmacoresistant temporal lobe epilepsy can explain the comorbidity of anxiety and depression: the potential impact of clinical factors.

Temporal lobe epilepsy (TLE) is a chronic neurodegenerative disease with a high prevalence of psychiatric disorders. Temporal neocortex contributes to either seizure propagation or generation in TLE, a situation that has been associated with alterations of the γ-amino-butyric acid (GABA) system. On the other hand, an impaired neurotransmission mediated by GABA in temporal neocortex has also been involved with the pathophysiology of psychiatric disorders. In spite of these situations, the role of the necortical GABA system in the comorbidity of TLE and mood disorders has not been investigated. The present study was designed to identify alterations in the GABA system such as binding to GABAA and GABAB receptors and benzodiazepine site, the tissue content of GABA and the expression of the mRNA encoding the α1-6, ß1-3, and γ GABAA subunits, in the temporal neocortex of surgically treated patients with TLE with and without anxiety, and/or depression. Neocortex of patients with TLE and comorbid anxiety and/or depression showed increased expression of the mRNA encoding the γ2-subunit, reduced GABAB-induced G-protein activation in spite of elevated GABAB binding, and lower tissue content of GABA when compared to autopsy controls. Some of these changes significantly correlated with seizure frequency and duration of epilepsy. The results obtained suggest a dysfunction of the GABAergic neurotransmission in temporal neocortex of patients with TLE and comorbid anxiety and/or depression that could be also influenced by clinical factors such as seizure frequency and duration of illness.

Mecanismos de neurodegeneración en la epilepsia del lóbulo temporal / Mechanisms of neurodegeneration in temporal lobe epilepsy

Epilepsy affects 1 and 2 percent of the worldwide population, while temporal lobe epilepsy (TLE) covers 40 percent of all epilepsy cases. Controversy in defining epilepsy as a neurodegenerative disease exists because, no there is enough evidence to show seizures and status epilepticus (SE) as cause for irreversible neuronal damage. Epileptogenic insult at the beginning of the disease produces an acute and delayed neuronal death, resulting in gliosis, but also triggers compensatory processes such as angiogenesis, cell proliferation and reorganization of extracellular matrix as receptors, channels and drug transporter proteins. In neurogenesis and axonal regrowth, the age of onset is crucial for the formation of abnormal neurons and aberrant circuits as a result of seizures; approximately 30 percent begin in the temporal lobe. These disturbances continue in parallel or sequentially during the course of epilepsy, which implies a great challenge in the search of new treatments...

La epilepsia es una enfermedad que afecta entre el 1 al 2 por ciento de la población mundial, siendo la epilepsia del lóbulo temporal (ELT) la que abarca el 40 por ciento de todos los casos de epilepsia. La controversia en definir a la epilepsia como una enfermedad neurodegenerativa, se debe a que no hay pruebas suficientes que demuestren como las convulsiones y el estado de mal epiléptico (SE) provocan un daño neuronal irreversible. El insulto epileptógenico presente al inicio de la enfermedad genera la muerte neuronal aguda y tardía, para dar lugar a la gliosis; pero también se desencadenan procesos compensatorios como la angiogénesis, la proliferación celular y una reorganización tanto de la matriz extracelular como de los receptores, canales y proteínas transportadoras de fármacos. En el caso de la neurogénesis y recrecimiento axonal, la edad de inicio es determinante para la formación de neuronas anormales y circuitos aberrantes como consecuencia de las convulsiones, dónde aproximadamente un 30 por ciento comienzan en el lóbulo temporal. Estas alteraciones se continúan en paralelo o de forma secuencia! durante la evolución de la epilepsia, lo que implica un gran desafío en la búsqueda de nuevos tratamientos...

[Characteristics of the cholera epidemic of 1998 in Ecuador during El Niño]. / Características de la epidemia de cólera de 1998 en Ecuador, durante el fenómeno de "El Niño"

OBJECTIVE: To describe the outbreak of cholera that occurred in Ecuador in 1998 during the El Nino weather phenomenon, to present data on the resistance of the circulating strains of Vibrio cholerae to antimicrobial drugs, and to describe the preventive measures taken by health authorities in order to reduce the impact of the disease. METHODS: The epidemiological data came from three sources: 1) the registry of the National Bureau of Epidemiology of the Ministry of Public Health of Ecuador, 2) the registry of the National Institute of Hygiene and Tropical Medicine, and 3) the final report of the Training Program for the Fight against Cholera and Diarrheal Diseases. Isolation, identification, and serotyping was done of V. cholerae in the feces samples from 10% of the suspected cholera cases that were identified between 1 January and 31 December 1998. The suspected cases were defined by the sudden appearance of watery diarrhea, with or without dehydration, in epidemic areas. The strains that were isolated were submitted to a standard antibiogram by the diffusion method, in which the following antibiotics were tested: amoxicillin, tetracycline, trimethoprimsulfamethoxazole, vibriostatic compound O/129, nalidixic acid, erythromycin, norfloxacin, ciprofloxacin, gentamycin, chloramphenicol, and colistin. RESULTS: In 1998 there were 3 755 cases reported in 17 of the 21 provinces of the country. This corresponds to an incidence rate of 53.96 per 100 000 population. Thirty seven patients died, for a case fatality rate of 0.97%. A total of 301 strains of V. cholerae were isolated in the 637 suspected-cholera samples that were processed; all corresponded to V. cholerae O1, El Tor, subtype Ogawa. All of the strains were sensitive to tetracycline and to quinolones; 5.6% of the strains were resistant to erythromycin. The only strain resistant to amoxicillin was multiresistant. Officials in Ecuador implemented a series of preventive measures, and the surveillance system was strengthened in order to reduce the impact of the disease. CONCLUSIONS: The preventive measures helped to reduce the impact of the 1998 cholera epidemic in Ecuador, in terms of both incidence and the case fatality rate. Given the overall sensitivity of the strains to the antimicrobial drugs, there is no reason to change the current treatment regimens in the country. Taking into account the frequency of natural disasters in Ecuador and the relation that they have to the reappearance of cholera, interventions should be designed that make it possible to prevent and control the reappearance of the disease and its spread to the most vulnerable provinces of the central Sierra mountainous region and the eastern part of the country.

Características de la epidemia de cólera de 1998 en Ecuador, durante el fenómeno de "El Niño" / Characteristics of the cholera epidemic of 1998 in Ecuador during El Niño

Objetivos. Caracterizar el brote de cólera ocurrido en Ecuador en 1998 durante el fenómeno de "El Niño", presentar los datos sobre la resistencia de las cepas circulantes de Vibrio cholerae a los antimicrobianos y describir las medidas preventivas tomadas por las autoridades sanitarias para reducir el impacto de la enfermedad. Métodos. Los datos epidemiológicos provienen de los registros de la Dirección Nacional de Epidemiología del Ministerio de Salud Pública de Ecuador y del Instituto Nacional de Higiene y Medicina Tropical, y el informe final del Programa de Formación para la Lucha contra el Cólera y las Enfermedades Diarreicas (PROCED ALA 93/25). Se procedió a aislar, identificar y serotipificar V. cholerae en las muestras de heces de 10 por ciento de los pacientes con posible cólera identificados entre el 1 de enero y el 31 de diciembre de 1998. Los casos sospechados se definieron por la aparición súbita de diarrea acuosa, con o sin deshidratación, en zonas epidémicas. Las cepas aisladas se sometieron a un antibiograma estándar por el método de difusión, en el que se probaron los siguientes antibióticos: amoxicilina, tetraciclina, sulfametoxazol con trimetoprim, compuesto vibriostático O/129, ácido nalidíxico, eritromicina, norfloxacino, ciprofloxacino, gentamicina, cloranfenicol y colistina. Resultados. En 1998 se notificaron 3 755 casos en 17 de las 21 provincias del país, lo que corresponde a una tasa de incidencia de 53,96 por 100 000 habitantes. Treinta y siete pacientes fallecieron, lo cual supone una tasa de letalidad del 0,97 por ciento. Se aislaron 301 cepas de V. cholerae en las 637 muestras con sospechosa de cólera que se procesaron; todas correspondieron a V. cholerae O:1, El Tor, subtipo Ogawa. La totalidad de las cepas fueron sensibles a la tetraciclina y a las quinolonas, y 5,6 por ciento resistentes a la eritromicina. La única cepa resistente a la amoxicilina fue multirresistente. Las autoridades nacionales pusieron en práctica una serie de medidas preventivas en la comunidad y se fortaleció el sistema de vigilancia para reducir el impacto de la enfermedad. Conclusiones. Las medidas preventivas contribuyeron a reducir el impacto de la nueva epidemia de cólera en el Ecuador, tanto en términos de letalidad como de incidencia

Características de la epidemia de cólera de 1998 en Ecuador, durante el fenómeno de El Niño

Objetivos: Caracterizar el brote de cólera ocurrido en Ecuador en 1998 durante el fenómeno de "El Niño", presentar los datos sobre la resistencia de las cepas circulantes de Vibrio cholerae a los antimicrobianos y describir las medidas preventivas tomadas por las autoridades sanitarias para reducir el impacto de la enfermedad. Métodos: los datos epidemiológicos provienen de los registros de la Dirección Nacional de Epidemiología del Ministerio de Salud Pública de Ecuador y del Instituto Nacional de Higiene y Medicina Tropical y el informe final del Programa de Formación para la Lucha contra el Cólera y las Enfermedades Diarreicas (PROCED ALA 93/25). Se procedió a aislar, identificar y serotipificar V. cholerae en las muestras de heces de 10

de los pacientes con posible cólera identificados entre el 1 de enero y el 31 de diciembre de 1998. Los casos sospechados se definieron por la aparición súbita de diarrea acuosa, con o sin deshidratación, en zonas epidémicas. Las cepas aisladas se sometieron a un antibiograma estándar por el método de difusión, en el que se probaron los siguientes antibióticos: amoxicilina, tetraciclina, sulfametoxazol con trimetoprim, compuesto vibriostático 0/129, ácido nalidíxico, eritromicina, norfloxacino, ciprofloxacino, gentamicina, cloranfenicol y colistina. Resultados: En 1998 se notificaron 3755 caos en 17 de las 21 provincias del país, lo que corresponde a una tasa de incidencia de 53,96 por 100000 habitantes. Treinta y siete pacientes fallecieron, lo cual supone una tasa de letalidad del 0,97

. Se aislaron 301 cepas de V.cholerae en las 637 muestras con sospechosa de cólera que se procesaron; todas correspondieron a V.cholerae 0:1, El Tor, subtipo Ogawa. La totalidad de las cepas fueron sensibles a la tetraciclina y a las quinolonas, y 5,6

resistentes a la eritromicina. La única cepa resistente a la amoxicilina fue multirresistente. Las autoridades nacionales pusieron en práctica una serie de medidas preventivas en la comunidad y se fortaleció el sistema de vigilancia para reducir el impacto de la enfermedad. Conclusiones: Las medidas preventivas contribuyeron a reducir el impacto de la nueva epidemia de cólera en el Ecuador, tanto en términos de letalidad como de incidencia. En vista de la sensibilidad global de las cepas a los antimicrobianos, no se justifica cambiar los esquemas de tratamiento vigentes en la región. Teniendo en cuenta la frecuencia de los desastres naturales en este país y su relación con la reaparición del cólera, es recomendable diseñar intervenciones que permitan prevenir y controlar la reaparición de la enfermedad y su extensión hacia las provincias más vulerables de la Sierra y el Oriente(AU)

Producción y caracterización de anticuerpos monoclonales específicos para la toxina de vibrio cholerae 01: informe preliminar

El vibrio cholerae es el agente causal de la enfermedad del cólera. El serotipo 01 puede ser subdividido en los biotipos el tor y clásico. En el diagnóstico de la enfermedad del cólera se utilizan kits comerciales con el uso de anticuerpos monoclonales (AM), éstos existen a nivel mundial, pero el país no cuenta todavía con un centro de elaboración y mantenimiento de producción de AM, por lo que se propuso la creación de un centro de elaboración de anticuerpos monoclonales. En este informe preliminar mencionamos la producción y caracterización de AM contra la toxina colérica (TC) para lo que se utilizó como antígeno el extracto total del V. cholerae 01 (AC). La purificación se realizó mediante cromatografía de afinidad...