Estudio de susceptibilidad a cefalosporinas de primera generación en enterobacterias aisladas de urocultivo, según criterios CLSI y EUCAST / Susceptibility to first-generation Cephalosporins in Enterobacteriaceae isolated from urine culture according to CLSI and EUCAST breakpoints

Resumen Actualmente se recomienda el uso de cefazolina para determinar la susceptibilidad a cefalosporinas orales de primera generación en cepas de enterobacterias en ITU no complicada. Nuestro objetivo fue establecer la susceptibilidad a cefalosporinas orales en cepas urinarias según puntos de corte para cefalotina o cefazolina y la correlación de susceptibilidad entre cefazolina y cefadroxilo. Se estudió la concordancia entre cefalotina y cefazolina en 52 cepas por método de Kirby-Bauer y Vitek XL. En Escherichia coli fue de 0% para VitekXL y 50% para Kirby-Bauer. La concordancia entre cefazolina y cefadroxilo fue 95,6%. En el laboratorio debiera usarse cefazolina para determinar susceptibilidad a cefalosporinas orales de primera generación. La concordancia entre cefazolina y cefadroxilo sugiere que cefazolina podría predecir susceptibilidad para cefadroxilo.

Currently, the use of cefazolin is recommended to determine the susceptibility to first-generation oral cephalosporins in strains of enterobacteria in uncomplicated UTI. We determined susceptibility differences to oral cephalosporins in urinary strains according to cefazolin or cefalotin breakpoints and the correlation of susceptibility between cefazolin and cefadroxil. We studied 52 strains with cefalotin and cefazolin by disk-diffusion and MIC (Kirby-Bauer and Vitek XL) and a subgroup by disk-diffusion for cefadroxil. Agreement among different methods was 100% for K. pneumoniae and Proteus spp. In Escherichia coli, agreement for Vitek and disk-diffusion were 0 and 50% respectively. Susceptibility to first generation cephalosporins in E. coli should be determined with cefazolin. Agreement between cefazolin and cefadroxil suggests that cefazolin could also predict the susceptibility of cefadroxil.

Determination of cefotaxime, cefoperazone, ceftazidime and cefadroxil using surface plasmon resonance band of silver nanoparticles

The aim of this work is to evaluate simple, sensitive, effective and validated procedures for the determination of cefotaxime, cefoperazone, ceftazidime and cefadroxil. In this study, the methods based on the ability of the cited drugs to reduce Ag+ ions to silver nanoparticles (Ag-NPs) in the presence of Polyvinyl Pyrrolidone (PVP) as a stabilizing agent producing very intense surface plasmon resonance peak of Ag-NPs (λmax. = 410-430 nm). The plasmon absorbance of the Ag-NPs allows the quantitative spectrophotometric determination of the cited drugs. The calibration curves are linear with concentration ranges of 0.4-3.2, 1-8, 0.5-4.0 and 1.5-9.0 µg/mL for cefotaxime, cefoperazone, ceftazidime and cefadroxil, respectively. Apparent molar absorptivity, detection and quantitative limits are calculated. Applications of the proposed methods to representative pharmaceutical formulations are successfully presented. The extracellular synthesis of nanoparticles is fast, and the method doesn't require various elaborate treatments and tedious extraction procedures.

Acné conglobata hemorrágico en un adulto joven. Caso clínico y revisión bibliográfica / Hemorrhagic conglobata acne in a young adult. Case report and bibliographic review

Se presenta un paciente adulto joven de 23 años de edad con acné conglobata hemorrágico, de 6 meses de evolución, luego de una limpieza facial. Presenta dolor facial, alza térmica, malestar general, edema y deformidad; además, depresión moderada. En estas lesiones se observa pústulas profundas y abscesos por confluencia de lesiones más pequeñas y se interconectan mediante fístulas; además, se acompañan de coágulos que drenan secreción hematopurulenta al inclinar la cabeza hacia abajo y adelante. Se diagnostica proceso infeccioso y aisla Stafilococcus aureus. Luego de realizar curaciones diarias, administrar antibiótico sistémico por vía oral y tratamiento de apoyo se logra una gran mejoría; además, se instaura tratamiento con isotreinoina durante 6 meses.AU

We present a young adult pacient of 23 years old with hemorrhagic conglobata acne, with six months of evolution after a facial cleansing, accompanied with pain, thermal rise, malaise, edema, face deformity and moderate depression. These lesions have deep postulas and abscesses that are formed by the confluence of smaller lesions and interconnected by fistulas as well as being accompanied by blood clots that drained hematopurulent secretion when tilting the head downward and forward. Infectious process is determined by isolating Staphylococcus Aureus. After daily cures, use of systemic antibiotics for oral vial and supportive treatment, it achieved a clinical improvement and begins a treatment based in isotretinoine by six months. AU

Nefronia en pediatría: dentro del espectro de las infecciones urinarias. Serie clínica y revisión de la literatura / Nephronia in pediatrics: part of the spectrum of upper urinary tract infections. Clinical cases and review of the literature

Nephronia or focal acute nephritis corresponds to a localized inflammatory non-liquefactive kidney infection which may involve parenchyma of one or more renal lobes. It has been suggested that nephronia is part of the spectrum of upper urinary tract infections between acute pyelonephritis and renal abscess. It is associated with a prolonged clinical course, higher levels of inflammatory markers and an increased risk of renal scarring, compared to pyelonephritis. Ultrasound plays a useful role. Nephronia is an under-diagnosed condition, thus, clinical suspicion is important for early diagnosis and appropriate treatment. We present three paediatric cases, and a review of the literature.

La nefronia o nefritis focal aguda es una inflamación renal de etiología bacteriana sin licuefacción que típicamente involucra el parénquima de uno o más lóbulos renales. Dentro del espectro de las infecciones del tracto urinario, se ha planteado que podría ser una entidad intermedia entre la pielonefritis aguda y el absceso renal. Se asocia a un curso clínico más prolongado, mayores marcadores inflamatorios y mayor riesgo de cicatrices renales, al compararla con la pielonefritis. La ecografía renal juega un rol útil en el diagnóstico. Es una entidad subdiagnosticada; por lo que su sospecha es relevante para un diagnóstico oportuno y un tratamiento adecuado. Se presentan tres casos clínicos pediátricos y una revisión del tema.

Reconstrução mamária imediata com retalho do músculo grande dorsal e implante de silicone / Immediate breast reconstruction with latissimus dorsi flap and silicone implant

Introdução: O primeiro tratamento eficaz para o câncer de mama foi descrito em 1894. A partir das décadas de 60 e 70, cirurgias menos agressivas foram desenvolvidas, sem prejuízos oncológicos. Com evolução histórica semelhante, o retalho do músculo grande dorsal (RMGD) foi introduzido em 1906. Contudo, apenas 70 anos após sua primeira descrição, ele ganhou popularidade como uma opção para as reconstruções mamárias. Método: Estudo clínico retrospectivo realizado por meio da coleta de dados de 22 pacientes submetidas à reconstrução mamária imediata com emprego do RMGD associado a implante de silicone durante o período de fevereiro de 2012 a dezembro de 2013. Resultados: Não houve necrose do retalho de grande dorsal ou perda da reconstrução mamária nos casos estudados. Foram observados 10 casos (45%) de seroma em região dorsal, 3 casos (14%) de necrose parcial da pele da mastectomia e 3 casos (14%) de deiscência parcial da ferida operatória. Não foram evidenciados fatores de risco com significância estatística para as complicações apresentadas. Ocorreram 4 casos (18,18%) de alterações de cobertura do implante, com atrofia muscular e cutânea, e 2 casos (9,09%) de contratura capsular. Apenas um caso não foi associado à radioterapia. Contudo, não houve significância estatística em relação à radioterapia adjuvante e às complicações tardias apresentadas (p = 0,635). Conclusão: O RMGD associado ao implante de silicone é uma opção segura e confiável para a reconstrução mamária imediata após mastectomias.

Introduction: The first effective breast cancer treatment was described in 1894. Less aggressive surgeries were developed in the 1960s and 70s, without increased mortality due to cancer. With similar historical evolution, the latissimus dorsi muscle flap (LDMF) procedure was introduced in 1906. Seventy years after its first description, LDMF gained popularity as an option for breast reconstruction. Method: A retrospective clinical study was conducted using data obtained from 22 patients undergoing immediate breast reconstruction with LDMF and silicone implants between February 2012 and December 2013. Results: No latissimus dorsi flap necrosis or breast reconstruction losses were observed in this study. Ten cases (45%) of seroma were detected in the dorsal region, three cases (14%) of partial necrosis of the mastectomized skin, and three cases (14%) of partial surgical wound dehiscence. Statistical significant risk factors for the complications observed have not been emphasized. There were four cases (18.18%) of muscle and skin atrophy associated with implants, and two cases (9.09%) of capsular contracture. Only one case was not associated with radiotherapy. However, there were no statistically significant differences in adjuvant radiotherapy and late complications (p = 0.635). Conclusion: LDMF associated with silicone implants is a safe and reliable option for immediate breast reconstruction after mastectomies.

Suscetibilidade antimicrobiana de Staphylococcus spp: isolados de cães com pioderma superficial / Antimicrobial susceptibility of Staphylococcus spp: isolated from canine superficial pyoderma

Foram obtidas 154 amostras de lesões cutâneas de cães com pioderma superficial atendidos no Serviço de Dermatologia Veterinária do Hospital Veterinário Universitário (HVU) da Universidade Federal de Santa Maria (UFSM), com o objetivo de determinar a suscetibilidade antimicrobiana de isolados de Staphylococcus spp. e avaliar a presença de multirresistência. Após isolamento e identificação, as cepas foram submetidas ao teste de sensibilidade aos antimicrobianos, cujos resultados evidenciaram menores percentuais de resistência à associação amoxicilina e ácido clavulânico (1,9 por cento), cefadroxil (1,9 por cento), cefalexina (1,9 por cento) e vancomicina (0,6 por cento). Os maiores percentuais de resistência foram frente à amoxicilina (60,4 por cento) e penicilina G (60,4 por cento). A multirresistência foi detectada em 23,4 por cento e a resistência à meticilina em 5,8 por cento das amostras. Pode-se concluir que os isolados de Staphylococcus spp. apresentam elevada suscetibilidade aos antimicrobianos comumente utilizados no tratamento dos piodermas superficiais em cães atendidos no HVU-UFSM, como a cefalexina e a amoxicilina associada ao ácido clavulânico, confirmando a eleição desses fármacos para o tratamento de cães com esta afecção. A suscetibilidade diminuída das cepas frente às fluoroquinolonas, também recomendadas pela literatura para o tratamento de pioderma, permite sugerir que estes fármacos não devem mais ser considerados na seleção empírica. A identificação de Staphylococcus spp. multirresistentes na população canina estudada justifica análises bacteriológicas periódicas e regionais de lesões cutâneas de cães com pioderma superficial, a fim de minimizar a seleção de bactérias resistentes, possíveis falhas terapêuticas e também motiva a antimicrobianoterapia prudente.

A total of 154 samples of skin lesions were obtained from dogs with superficial pyoderma that were assisted by the Veterinary Dermatology Service at the University Veterinary Hospital (HVU), Universidade Federal de Santa Maria (UFSM), aiming to determine the antimicrobial susceptibility of Staphylococcus spp. isolates and evaluate the presence of multidrug resistance profile. After bacterial isolation and identification, the strains were tested for antimicrobial susceptibility, and the results showed lower percentages of resistance to the amoxicillin and clavulanic acid association (1.9 percent), cefadroxil (1.9 percent), cephalexin (1.9 percent) and vancomycin (0.6 percent). The highest percentages were towards amoxicillin (60.4 percent) and penicillin G (60.4 percent). The multidrug resistance was detected in 23.4 percent and the methicillin resistance in 5.8 percent of the samples. It may be concluded that the Staphylococcus spp. isolates present high susceptibility to key antimicrobials used in the treatment of superficial pyodermas in dogs at the HVU-UFSM, such as cephalexin and the amoxicillin and clavulanic acid association, confirming the preference for these drugs when treating dogs with this disorder. The susceptibility of the strains to fluoroquinolones, also recommended in the literature for the treatment of pyodermas, allows suggesting that such drugs should not be considered in the empirical selection. The identification of multidrug-resistant Staphylococcus spp. in the studied canine population justifies periodic and regional bacteriological tests of skin lesions in dogs with superficial pyoderma, possible therapeutic failures and also motivates wise use of antimicrobial therapy.

Profilaxis antimicrobiana en cirugía ortopédica: cefazolina vs cefadroxilo IV / Antimicrobial prophylaxis in orthopedic surgery: cefazolina vs cefadroxilo IV

Toda intervención quirúrgica está expuesta a infectarse. La necesidad de profilaxis antimicrobiana en cirugía ortopédica para casos quirúrgicos agudos o electivas de cirugías limpias ha sido establecida como procedimiento de rutina. En Cirugía Ortopédica y Traumatología cuando se requiere el uso de implantes metálicos con el fin de realizar osteosíntesis o sustitución de las superficies articulares, aumenta el riesgo de infección, por tratarse de materiales extraños que son introducidos en el organismo. En estos casos la antibióticoterapia preventiva es de primordial importancia. Se realizó un estudio de profilaxis antimicrobiana, multicéntrico, aleatorizado, prospectivo, doble ciego, comparativo de grupos paralelos, con el fin de evaluar la eficacia de Cefadroxilo I.V. Vs. Cefazolina I.V. como antibióticos profilácticos mediante la determinación del número de pacientes infectados en cirugía de fracturas cerradas en la cuales se colocó material de síntesis. Se completaron 58 pacientes, 34 en el grupo de cefadroxilo y 24 en el grupo de cefazolina, al inicio los grupos fueron similares en cuanto a edad, sexo, tipo de fractura, tiempo de intervención, tiempo entre la fractura y la intervención.Más pacientes en el grupo de cefadroxilo tenían el tiempo máximo autorizado entre la fractura y la intervención (p: 0,07). Se presentó en el grupo de cefadroxilo una infección de la herida operatoria y un caso de eritema leve que cedió con tratamiento oral con cefadroxilo, sin diferencias entre los grupos.Hubo tres casos de eventos adversos, reacción anafiláctica a las 48 horas en el grupo de cefazolina que ameritó finalización de protocolo y hematoma en miembro inferior derecho y, en el grupo de cefadroxilo, una elevación discreta de enzimas hepáticas. La respuesta terapéutica de profilaxis antimicrobianano mostró diferencia entre los grupos. El cefadroxilo es tan eficaz como la cefazolina para la profilaxis antimicrobiana en pacientes con fracturas...

Any operation is exposed to infection. The need for antimicrobial prophylaxis in orthopedic surgery for acute or elective surgical cases of clean surgery is established as a routine procedure. Orthopedic Surgery when required the use of metallic implants in order to perform internal fixation or replacement of the articular surfaces, increases the risk of infection because they are foreign materials are introduced into the body. In these cases, preventive antibiotic therapy is very important. We performed a study of antimicrobialprophylaxis multicenter, randomized, prospective, double-blind, parallel group comparison in order to evaluate the effectiveness of Cefadroxil IV vs. Cefazolin I.V. as prophylactic antibiotics by determining the number of infected patients after fracture surgery in which synthetic material was placed. Fifty eigth patients were completed, 34 in the cefadroxil group and 24 in the cefazolin group, at the beginning the groups were similar in age, sex, fracture type, operative time, time between fracture and surgery. More patients in the cefadroxil group had the maximum allo-wable time between the fracture and surgery. (P: 0.07). In the cefadroxil group we found a wound infection and one case of mild erythema which resolved with oral treatment with cefadroxil, without differences between groups. There were three cases of adverse events, anaphylactic reaction to cefazolin at 48 h in the group that required finalization of protocol and hematoma in right leg and in the cefadroxil group, a moderate increase in liver enzymes. The therapeutic response of antimicrobial prophylaxis showed no difference between groups. Cefadroxil is as effective as cefazolin for antimicrobial prophylaxis in patients with fractures that warrant placement of synthetic material

Nefritis aguda focal: caso clínico / Focal acute nephritis: a case report

Focal acute nephritis (FAN) or acute lobar nephronia is a rare clinical picture characterized by an infection localized in the kidney, with an inflammatory mass without liquefaction. Of variable clinical manifestations, diagnosis is achieved through CT scanning. Histologically, unlike acute pyelonephritis, it does not present a diffuse infíltrate. Objective: Case report of FAN in a pediatric patient. Case Report: Ten year old male complaining of abdominal pain, presents painful percussion in the right lumbar fossa. Urinary analysis and culture were negative, renal sonogram was negative. Abdominal CT sean showed múltiple hypodense renal foci. He responded well to cephotaxim, being discharged in the third day of hospitalization with completion of treatment as outpatient. Differential diagnosis with Acute Pyelonephritis is very important, as it requires controlled and opportune treatment to prevent renal absceses. Diagnosis of this pathology must be pursued despite a normal UA.

La nefritis aguda focal o nefronia lobar aguda constituye un cuadro poco común caracterizado por una infección localizada en el riñon, la que corresponde a una masa inflamatoria sin licuefacción. Posee una clínica variable, siendo la tomograña computada (TAC) la prueba más sensible y específica para el diagnóstico de esta enfermedad. Esta patología se diferencia histológicamente de la pielonefritis aguda por no presentar un infiltrado inflamatorio difuso. Objetivo: presentar un caso de nefronia aguda multifocal en un paciente pediátrico. Caso clínico: Escolar de 10 años que consultó por dolor abdominal, al examen destacaba la presencia de percusión dolorosa en fosa lumbar. Los exámenes de orina y urocultivo fueron negativos. Al ingreso no se detectó cambios renales ecográficamente evidenciables. Se realizó un TAC de abdomen que mostraba múltiples focos renales hipodensos. Respondió favorablemente a terapia antibiótica con cefotaxima siendo dado de alta al tercer día, completando terapia en forma ambulatoria. La diferenciación de este cuadro de otros procesos renales como la pielonefritis aguda (PNA) es muy importante, ya que precisa un tratamiento oportuno y controlado por el riesgo de evolucionar a absceso renal. El diagnóstico de esta patología debe ser buscado a pesar de contar con exámenes de orina negativos.

Utilidad del cefadroxilo en leishmaniosis tegumentaria americana con infecciones piógenas sobreagregadas / Use of cefadroxil for american tegumentary leishmaniosis with intercurrent pyogenic infections

La leishmaniosis tegumentaria americana es un problema de salud en el medio rural venezolano. Las úlceras leishmánicas tienden a infectarse secundariamente por bacterias piógenas. Se evaluaron 41 pacientes con la enfermedad que recibieron cefadroxilo oral previo a la toma de segmentos de piel del borde de las úlceras para la demostración microscópica de Leishmania spp. La mayoría de los pacientes eran adultos masculinos y provenían del medio rural del estado Miranda, con una úlcera única localizada en los miembros inferiores. El diagnóstico inmunoserológico se efectuó por leishmanina y anticuerpos fluorescentes y el de certeza por visualización de amastigotes en frotis coloreados. Los resultados inmunoserológicos fueron positivos en todos los pacientes, mientras que el parásito se observó en 51 por ciento de los frotis coloreados con Giemsa. Una semana postratamiento antimicrobiano, los pacientes presentaban mejoría de las infecciones sobreagregadas y también progreso en la visualización del parásito por disminución de la carga bacteriana. Los pacientes fueron tratados con antimoniato de meglumina intramuscular en series de 10 días, con reposo intermedio. Respondieron adecuadamente, las lesiones cicatrizaron y los nódulos satelitales acompañantes desaparecieron. Se concluye que el cefadroxilo es útil para tratar las infecciones piógenas secundarias asociadas en LTA y aumentar la sensibilidad para observar los parásitos en piel. La leishmaniosis considerada como enfermedad emergente, motiva la búsqueda de alternativas terapéuticas adecuadas

Cutaneous leishmaniosis of the New World (CLNW) is a health problem in rural areas of Venezuela. Patients with muco-cutaneous ulcers tend to present intercurrent infections of the lesions by pyogenic bacteria. After removing skin specimens from the ulcer borders for microscopic demonstration of Leishmania spp amastigotes, forty-one patients with the disease, being treated with cefadroxil per os were studied. Most of the patients came from rural Miranda state, were male adults and had one ulcer on a lower limb. Confirmatory diagnosis was made using the Montenegro test, or Leishmanin immunoserology (IFAT) and demonstration of the presence of parasites in the skin samples. All the patients were positive for the Leishmanin test, while parasites were observed in 51 percent of the skin smears colored by the Giemsa procedure. After a week of treatment with cefadroxil, bacterial infections were reduced and a decrease in bacterial load was also noted when visualizing the parasite from the skin smears. Patients were treated with intramuscular antimony meglumine for 10-day periods with an intervening rest period. All patients responded adequately to the meglumine antileishmania treatment; the lesions healed and accompanying tributary lymph nodes disappeared. Conclusion: Cefadroxil is a suitable antibiotic for treating intercurrent pyogenic infections in cases of tegumentary leishmaniosis. Since leishmaniosis is considered an emerging disease, a search for appropriate, alternative therapies is required

Estudio multicéntrico, abierto y prospectivo con cefadroxilo de pacientes con infecciones en tejidos blandos, residentes en grandes ciudades de la Argentina / Multicentric, open and prospective trial related to the adhesion to the treatment with cefadroxil of patients with infections of soft tissues living in peripheric and/or marginal areas of large cities of the Argentine Republic

Desde las últimas décadas se observa un incrmento cada vez mayor de resistencia microbiana a los quimioterápicos ocasionada por malas prescripciones, falta de adherencia al tratamiento, automedicación, entre otros. El cefadroxilo, comparte las cualidades de la cefalexina, pero además las concentraciones séricas y urinarias mas sostenidas permiten el tratamiento de infecciones con una a dos dosis diarias. Dicha particularidad farmacocinética otorga un beneficio para el paciente que permite asegurar la adherencia al tratamiento.

Avaliação de diferentes cronogramas de coletas de amostras biológicas em estudos de bioequivalência e análise da influência de teor de fármaco sobre os resultados destes estudos / Evaluation of the effects on different doses and sampling schedules on the assessment of bioequivalence

Os estudos de bioequivalência são realizados em humanos, por meio da administração dos medicamentos em estudo pela mesma via extravascular, sob condições experimentais padronizadas, seguida pela determinação das concentrações plasmáticas do fármaco em função do tempo. Nestes estudos considera-se que curvas estatisticamente semelhantes de decaimento sanguíneo de fármacos produzem o mesmo resultado em termos de eficácia e segurança. A partir das curvas de concentração em função do tempo obtidas, determinam-se os parâmetros farmacocinéticos Cmax, tmax e ASC. A bioequivalência entre dois produtos é estabelecida por meio do IC 90%, que deve estar entre 80 a 125% para os parâmetros farmacocinéticos Cmax e ASC. O cronograma de coleta de amostras biológicas é um dos aspectos mais críticos no planejamento de estudos de bioequivalência, pois este afeta diretamente a determinação dos parâmetros farmacocinéticos utilizados na avaliação da bioequivalência. Outro aspecto importante relacionado a este tipo de estudo é a diferença de teor entre os produtos a serem submetidos ao estudo de bioequivalência, que segundo a legislação brasileira vigente, deve ser menor ou igual a 5%. Neste trabalho foram avaliados diferentes cronogramas de coleta de amostras sangue, avaliando-se o impacto destes no resultado final de um estudo de bioequivalência e, além disso, a influência da diferença de teor de fármaco entre dois produtos que levaria à bioinequivalência também foi investigada. Para tanto simulações matemáticas e um estudo in vivo foram conduzidos. O fármaco modelo escolhido foi a cefadroxila, por apresentar características farmacocinéticas e farmacodinâmicas ideais. O programa Microsoft Office Excel 2003 foi utilizado para simular as concentrações plasmáticas e determinar o IC 90%. As simulações foram feitas por meio de dois modelos: modelo baseado em máximos e mínimos de parâmetros farmacocinéticos, e modelo baseado em coeficientes de variação intra e inter-individuais do fármaco. Dez diferentes doses, entre -10% a 20% da dose referência, e 6 cronogramas de coleta foram avaliados. O estudo in vivo foi realizado com quatro doses diferentes de cefadroxila. A bioequivalência entre as doses e em diferentes cronogramas de coleta foi avaliada em 24 voluntários sadios do sexo masculino. Os voluntários receberam as quatro doses do estudo em desenho cruzado, em quatro períodos e quatro seqüências, com washout de 7 dias entre as doses. As concentrações plasmáticas de cefadroxila, até 8 horas após a administração, foram determinadas por cromatografia líquida de alta eficiência com detecção DAD. Os parâmetros farmacocinéticos tmax, Cmax e AUC0-t foram determinados nas diferentes doses e cronogramas de coleta, sendo que o critério para estabelecer-se a bioequivalência foi baseada nos resultados do IC 90% dos parâmetros farmacocinéticos Cmax e AUC0-t. Os resultados obtidos nas simulações mostraram boa correlação com os dados reais obtidos a partir de estudos in vivo. As simulações baseadas em coeficientes de variação intra e inter-individuais descreveram melhor os resultados observados no estudo in vivo. De acordo com os resultados obtidos no estudo in vivo pode-se concluir que cronogramas de coletas com menos amostras são tão eficientes quanto cronogramas de coletas com mais amostras, desde que o tempo de tmax esteja incluído. Em relação ao teor de fármaco, concluiu-se que dois produtos com diferença de teor menor ou igual a 11% ainda são bioequivalentes e que diferença maior ou igual a 14% resultam em bioinequivalência. Observou-se ainda que o parâmetro farmacocinético ASC0-t é mais sensível que Cmax para detectar diferenças

Bioequivalence studies are designed to compare the in vivo performance of different formulations of the same drug or different drug products by a randomized crossover study. Pharmacokinetic parameters are obtained from the drug concentration-time profile in blood, serum, or plasma. The most frequently used pharmacokinetic parameters are area under the plasma or blood concentration-time curve (AUC), maximum concentration (Cmax) and time to achieve maximum concentration (tmax). Bioequivalence is concluded if the average bioavailability of the test formulation is within (80%, 125%) that of the reference formulation, with a certain assurance, that is, an equivalence criterion of 80% to 125% for assessment of bioequivalence based on the ratio of average bioavailability is employed. The logarithmic transformation is used for AUC and Cmax. Accuracy in measuring pharmacokinetics parameters directly affects accuracy of bioequivalence tests. Since the number of blood samples per patient is limited, sampling points should be chosen such that the time concentration profile is adequately defined so as to allow the calculation of relevant parameters. According to guidelines proposed by the National Agency of Sanitary Vigilance of Brazil (ANVISA), bioequivalence studies can be conducted only if the difference in drug content between the reference and test product is less than or equal to 5%. The goals of this study are to evaluate the influence of differences in amount of active moiety present in the formulation and possibility of reducing the number of sampling points in bioequivalence studies and to discuss the impact of these parameters in bioequivalence conclusions. For these approaches, simulations and an in vivo study were done. The drug selected was cefadroxil. Cefadroxil presents ideal pharmacokinetics and pharmacodynamics characteristics for this kind of study, such as high bioavailability, low intra and intersubject variability, short elimination rate and wide therapeutic range. Microsoft Office Excel 2003 software was used to simulate drug concentration-time profiles for different doses and several sampling schedules, and to determine 90% confidence interval. Simulations were done by two models: a) based on assumed maximum and minimum pharmacokinetic parameters values; b) based on assumed intra and intersubject variability. Ten different doses, ranging from -10% to 20% of the reference dose, and six sampling schedules were evaluated. The in vivo study was performed with four different cefadroxil doses. Their relative bioavailability were evaluated in 24 healthy volunteers who received a single oral dose of each preparation. An open, randomized clinical trial designed as four-periods and four sequences crossover with 7-days washout between doses was employed. Plasma samples for assessments of their cefadroxil concentration by HPLC-DAD were obtained over 8 h after administration. Pharmacokinetics parameters tmax, Cmax and AUC0-t were evaluated using different doses and sampling schedules. For the purpose of bioequivalence analysis Cmax and AUC0-t were considered. For each schedule, to claim bioequivalence in average bioavailability, a 90% confidence interval was constructed for ratio of average between test and reference products and compared with (80%, 125%) limits. If the constructed confidence interval falls within the limits, then the two formulations are considered bioequivalent. The results obtained by simulate time-concentration profiles, showed good correlation with real data. Comparing the results obtained through in vivo study and the two simulations models, the simulations based in intra and intersubject variability was more predictive. In conclusion, no significant differences were found between sampling schedules evaluated, since the sampling time around tmax were maintained in sampling schedules. Bioinequivalence was observed when the difference between cefadroxil doses was higher than 14%. The parameter AUC0-t was more sensitive than Cmax to detect differences

In vitro activity of cefadroxil, cephalexin, cefatrizine and cefpirome in presence of essential and trace elements

Evidences supporting the introduction of metallic elements in several biological processes are rapidly accumulating. Likewise, many drugs possess modified toxicological and pharmacological properties when in the form of metal complexes. In order to ascertain the role of various essential and trace element complexation on the antibacterial activity of various cephalosporins, the synergistic or antagonistic behavior of cefadroxil, cephalexin, cefatrizine and cefpirome in presence of essential and trace elements has been studied and compared with the parent drug. The essential and trace elements comprised of magnesium, calcium, chromium, manganese, ferric, cobalt, nickel, copper, zinc and cadmium in the form of their chloride. These studies were carried out by observing the minimum inhibitory concentration [MIC] using agar dilution method and compared with the MIC'S of the standard cephalosporins against various species of Gram [+] and Gram [-] microorganisms such as Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis, Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella typhi and Shigella dysenteriae. Different dilutions of cephalosporins and salts of essential and trace elements were used in these studies. The ratio of the drug and metal salts was 1:1 and the reactions were carried out at two different temperatures as 37°C and 60°C in order to study the complex formation. The aim of our study was on one hand to evaluate the changes in microbiological activity of the standard cephalosporins after in vitro metal interactions to study the synergetic or antagonistic behavior of the later through the difference in MICs values of these cephalosporins and on the other hand to access the bioassay directed extent of drug metal complexations. Our investigation reveal that interaction of above cephalosporins with essential and trace elements cause antagonistic effect in many cases which was shown by decrease in antimicrobial activity of cephalosporins and MIC values were increased

Extracción de amblyomma cajennense (fabricius, 1787) de un caso de otoacariasis humana en el Estado Sucre-Venezuela / Extraction of amblyomma cajennense (fabricius, 1787) a case of human otoacariasis in the State Sucre-Venezuela

El ingreso accidental de insectos y otros artrópodos en el canal auditivo es una etiología común de los cuerpos extraños en otorrinolaringología. La infestación humana con especies del genero Amblyomma es infrecuentemente reportada. Se reporta el caso de un paciente masculino de 7 años de edad, natural y procedente de Tunapuy, Municipio Libertador, Estado Sucre, cuya madre refiere la introducción de un "insecto" en el oído derecho en horas de la madrugada. El paciente presentó dolor de moderada a fuerte intensidad en el oído derecho. Al evaluarse el canal auditivo por otoscopia se evidenció la presencia de una garrapata de <5 mm de largo, la cual fue extraída con pinzas, posterior a la colocación directa de xilocaína al 2 por ciento en el canal auditivo. No se observaron signos de lesión significativa, inflamación o supuración. Se le indicó profilaxis antimicrobiana con cefadroxilo 30 mg/Kg/d bid vo, así como nimesulide 5 mg/kg/d bid vo, ambos por 5 días. El paciente fue reevaluado a los 14 días, no presentando sintomatología alguna, ni signos de enfermedad local o sistémica. Posteriormente la garrapata aislada del oído fue identificada taxonómicamente según las claves de Hoogstraal y Jones, como Amblyomma cajennense. Esta garrapata se ha descrito aislada de diversos hospedadores mamíferos, incluyendo al humano; reportándose en los Estados Amazonas, Anzoátegui, Apure, Bolívar, Carabobo, Falcón, Guárico, Lara, Miranda, Yaracuy y Zulia. De acuerdo a la revisión realizada, éste es el primer reporte de su descripción en el Estado Sucre.

Evaluación comparativa de la eficacia y tolerabilidad del cefadroxilo vs oxacilina en el tratamiento de las infecciones de piel y tejidos blandos / Comparative evaluation of the effectiveness an tolerability of the cafadroxil vs oxacillin in the treatment of the skin infections and soft fabrics

Comparar la eficacia y tolerabilidad del cefadroxilo contra la oxacilina en el tratamiento de las infecciones de piel y tejidos blandos. Realizamos un estudio controlado aleatorizado, simple ciego, de grupos en paralelo, en donde se incluyeron un total de 98 pacientes divididos al azar en dos grupos para recibir cefadroxilo (47 pacientes) y oxacilina (51 pacientes). Se practicó examen clínico basal que incluyó evaluación local de la lesión con escala de inflamación estandarizada a 15 puntos, temperatura corporal y contaje leucocitario. Esta evaluación se repitió a las 48 horas, al 4to día y 10 de ser necesario. En la comparación de efectividad se consideraron parámetros de curación clínica y fracaso terapéutico, además de modificaciones en el score de inflamación, temperatura y contaje blando. Se comprobó curación definitiva en 95 por ciento de los casos con cefadroxilo, que fue superior al grupo tratado con oxacilina que presentó curación en el 86 por ciento. El fracaso terapéutico fue de 4 por ciento con cefadroxilo y 18 por ciento en el grupo de la oxacilina. La comparación intragrupal del día 0 Vs día 2 y día 0 Vs día 4, demostraron una reducción significativa en la escala de inflamación de los dos grupos de tratamiento. Ambos tratamientos lograron una mejoría clínica significativa del cuadro inflamatorio en 4 a 5 días, permitiendo el paso del tratamiento de la vía parenteral a la oral en ese lapso. La curación definitiva fue lograda en un promedio de 8 días. La temperatura corporal en ambos grupos descendió significativamente luego de 48 horas de tratamiento. El contaje blando mostró descenso notable y sostenido en los grupos, alcanzando significación en los días 2 y 4 de tratamiento. Solo dos pacientes en cada grupo fueron retirados por efectos adversos (cefadroxilo 4 por ciento y oxacilina 5 por ciento). El cefadroxilo fue más efectivo que la oxacilina en el tratamiento de infecciones leves a moderadas de piel y partes blandas, bajo los rangos de dosis planteadas para los medicamentos en estudio. Oxacilina mostró mayor porcentaje de fracaso en comparación al cefadroxilo. Sin embargo, los pacientes alcanzaron curación clínica con oxacilina, lo realizaron en un lapso de tiempo más corto. El cefadroxilo y la oxacilina fueron medicamentos seguros en el tratamiento de infecciones de piel y partes blandas, mostrando una proporción comparable y aceptable de efectos adversos

A Simple and Sensitive Assay for Cefepime in Human Plasma Using High Performance Liquid Chromatography

A simple and sensitive assay method was developed for cefepime in human plasma using high performance liquid chromatography (HPLC). Cefepime and cefadroxil (the internal standard) were extracted from heparinized human plasma by simple deproteination with perchloric acid. The extract was injected into an Atlantis dC18 column (250 X 4.6 mm; particle size 5micrometer, Waters) and the column was eluted with methanol and 0.01 M dihydrogen phosphate at pH 3.0 (15 : 85 v : v) as a mobile phase at a flow rate of 0.7 mL/min. Linearity was confirmed for the range 0.25 to 200 micro L/mL and the limit of quantitation was 0.25 micro L/mL. The retention times were 10.2 min and 13.4 min for cefepime and cefadroxil, respectively. This method was successfully applied to a pharmacokinetic study of cefepime in plasma from bone marrow transplant patients.

Evaluación de la sensibilidad in vitro al cefadroxilo y cefradina en Venezuela (1990-2000) / Evaluation of the sensibility in vitro to cephadroxyl and cefradine in Venezuela

En este estudio retrospectivo realizado en Venezuelase analizó la evolución, desde el año 1990 al año 2000, de los índices de sensibilidad de staphylococcus aureus, estreptococos beta hemolíticos del grupo A y streptococcus pneumoniae a cefadroxilo y cefradina, cefalosporinas de primera generación, mediante antibiogramas utilizando discos de papel impregnados con antibiótico. Los datos de cefadroxilo y cefradina se obtuvieron por inferencia de acuerdo a los criterios de la NCCLS (National Commitee for Clinical Laboratory Standards) del año 2001. Noventa por ciento de las cepas de staphylococcus aureus, 100 por ciento de las estreptococcus beta hemolíticos del grupo A y 78 por ciento de las de streptococcus pneumoniae fueron sensibles a ambos antibióticos. Concluimos que, con base en los estudios de tejidos blandos y faringoamigdalitis estreptocóccica; nuestros resultados coinciden con reportes internacionales.

Effect of co-administration of piperine on pharmacokinetics of beta-lactam antibiotics in rats.

Co-administration of piperine, an alkaloid isolated from Piper nigrum L. enhanced bioavailability of beta lactam antibiotics, amoxycillin trihydrate and cefotaxime sodium significantly in rats. The improved bioavailability is reflected in various pharmacokinetic parameters viz. tmax, Cmax, t(1/2) and AUC, of these antibiotics. The increased bioavailability could be attributed to the effect of piperine on microsomal metabolising enzymes or enzymes system.

A case of bronchial asthma due to cefadroxil in a housewife / 천식및알레르기

Cephalosporins are the most important -lactams that induce IgE-mediated reactions. Also, cephalosporins have been known as a causative agent for occupational asthma in pharmaceutical workers. To our knowledge, this is the first report of cephalosporin-induced bronchial asthma in a housewife with no history of occupational exposure. We experienced a 30-year old female who had developed shortness of breath, coughing and itching sensation of the skin since 3 years ago whenever she handled drug powder for upper respiratory infections (URI) prescribed for her two sons with bronchial asthma. She had handled drug powder for 7 years because her sons had experienced frequent URI. Skin prick test with cefadroxil (10mg/ml) and cefaclor (10mg/ml) showed positive reactions. Bronchial challenge test with cefadroxil showed immediate asthmatic reaction, and bronchial challenge with cefaclor showed immediate urticaria and angioedema without significant fall in FEV1. We confirmed cefadroxil-induced bronchial asthma sensitized by intermittent inhalation in a non-occupational setting.