RESUMEN
INTRODUCCIÓN: El amplio arsenal terapéutico destinado al tratamiento de las enfermedades infecciosas disponible en la actualidad hace imprescindible la realización de una selección rigurosa del agente antimicrobiano que se va a utilizar según una serie de criterios que permitan un uso adecuado de éstos. En primer lugar, habría que valorar la necesidad de instaurar un tratamiento antibiótico de acuerdo con los hallazgos clínicos del paciente. Una vez considerada esta necesidad, los criterios de selección del antimicrobiano más adecuado se deben hacer en función de los siguientes criterios: gravedad y estado general de base del paciente, consideración de los microorganismos más probables según el foco de la infección, el conocimiento del estado actual de resistencias de los posibles microorganismos implicados, la farmacocinética y la farmacodinámica de los antibióticos, los efectos secundarios y el coste de los antimicrobianos, la vía de administración y la duración del tratamiento. Las infecciones de piel y partes blandas están entre las infecciones más frecuentes en Pediatría. Los microorganismos implicados con mayor frecuencia son Staphylococcus aureus (S. aureus) y Streptococcus pyogenes (S. pyogenes). En ciertas situaciones deberá sospecharse que el S. aureus sea resistente a la meticilina (SARM). Las infecciones bacterianas de la piel pueden ocurrir a diferentes niveles de profundidad implicando la epidermis (impétigo), la dermis (ectima, erisipela) o el tejido celular subcutáneo (celulitis, abscesos subcutáneos), mientras que las infecciones de partes blandas se extenderán a mayor profundidad y afectarán a la fascia (fascitis necrotizante) o el músculo (piomiositis). El tratamiento antibiótico se debe iniciar de forma empírica cubriendo S. aureus y S. pyogenes y añadiendo un antibiótico con actividad inhibidora de la síntesis de toxinas cuando sea necesario. OBJETIVO: Evaluar rapidamente los parâmetros de eficácia, seguridade, costos y recomendaciones disponibles acerca del empleo de Dicloxacilina sódica para el tratamiento de personas con infecciones por gérmenes gram positivos, incluyendo estafilococos produtores de betalactamasa. METODOLOGÍA: Se realizo uma búsqueda bibliográfica en las principales bases de datos tales como PUBMED, LILACS, BRISA, COCHRANE, SCIELO, EMBASE, TRIPDATABASE como así también em sociedades científicas, agencias reguladoras, financiadores de salud y agencias de evaluación de tecnologias sanitárias. Se priorizó la inclusión de revisiones sistemáticas, ensayos clínicos controlados aleatorizados, evaluación de tecnologia sanitária y guias de práctica clínica. CONCLUSIONES: La Dicloxacilina, un antibiótico de la clase de las penicilinas, ha demostrado ser efectiva en el tratamiento de diversas infecciones bacterianas. Su eficacia radica en su capacidad para inhibir la síntesis de la pared celular bacteriana, lo que lleva a la muerte de las bacterias sensibles. Se utiliza comúnmente para tratar infecciones causadas por bacterias grampositivas, como Staphylococcus aureus, que son resistentes a la penicilina debido a la producción de la enzima beta-lactamasa. La Dicloxacilina es especialmente útil en el tratamiento de infecciones de la piel y tejidos blandos, como celulitis, forúnculos y abscesos, así como infecciones de heridas quirúrgicas y estafilococos en la piel. Alrededor del 5% de los pacientes tratados pueden esperar reacciones adversas. Los efectos adversos más comunes son náuseas, vómitos y diarrea. Como con otras penicilinas, se han producido reacciones de hipersensibilidad (inmediatas o tardías). La mayoría de estas son leves, sin embargo, se han reportado reacciones de hipersensibilidad graves, incluida la muerte (Aunque en extremo raras). Al costo aportado en solicitud, la tecnología tiene un impacto presupuestario mayor que los códigos disponibles actualmente en el Listado Oficial de Medicamentos (LOM). Actualmente con la concentración solicitada (250 mg/5 mL) existen 5 registros sanitarios activos, aunque su corta vida media obliga a administrarla con estrechos intervalos de dosificación (cada 6 horas) y el sabor de la solución oral es muy desagradable, lo que dificulta mucho el cumplimiento del tratamiento.[1] Las Guías Clínicas de Pediatria consideran tanto Cefadroxilo y Dicloxacilina como opciones para infecciones de la piel y tejidos blancos, y en otras alternativas terapéuticas se consideran Amoxicilina + Ácido clavulánico, Clindamicina y Claritromicina. Para el tratamiento de infecciones causadas por bacterias productoras de penicilinasa, neumococos del grupo A-beta, estreptococos hemolíticos y cepas de estafilococos resistentes a la penicilina G, se pueden considerar varias opciones terapéuticas. Algunas de estas opciones incluyen: Antibióticos antiestafilocócicos: Entre ellos se incluyen la oxacilina, la meticilina, la nafcilina y doxiciclina. Estos antibióticos son resistentes a la acción de la penicilinasa, una enzima producida por las bacterias estafilococos que inactiva la penicilina. Son eficaces contra infecciones causadas por estafilococos resistentes a la penicilina y a la meticilina. Cefalosporinas de primera generación, como la cefalexina y la cefadroxilo, pueden ser una opción de tratamiento para infecciones causadas por estafilococos productores de penicilinasa, neumococos del grupo A-beta, estreptococos hemolíticos y algunas cepas de estreptococos resistentes a la penicilina G. Estas cefalosporinas tienen actividad contra una amplia variedad de bacterias grampositivas y algunas gramnegativas, y son especialmente útiles en infecciones leves a moderadas de la piel y tejidos blandos, infecciones del tracto urinario y faringitis estreptocócica. Cefalosporinas de segunda generación: Las cefalosporinas como la cefuroxima, la cefaclor y la cefprozil pueden ser efectivas contra estreptococos y algunos tipos de estafilococos resistentes a la penicilina. Sin embargo, su eficacia contra cepas productoras de penicilinasa puede ser limitada. Macrólidos: Los macrólidos como la eritromicina, la claritromicina y la azitromicina pueden ser útiles en el tratamiento de infecciones causadas por estreptococos y neumococos. Sin embargo, algunos estafilococos pueden desarrollar resistencia a estos antibióticos, por lo que su uso puede ser limitado en infecciones estafilocócicas graves. Vancomicina: La vancomicina es un antibiótico que se utiliza para tratar infecciones causadas por estafilococos resistentes a la meticilina y otros microorganismos grampositivos. Es un agente de reserva que se reserva para infecciones graves o resistentes a otros antibióticos. En el LOM, se encuentra al menos un representante de casi todos los grupos de antibióticos mencionados, con formulaciones pediátricas disponibles en jarabe o suspensión (Cefadroxilo, Claritromicina, Amoxicilina + ácido clavulánico). En los casos en que no se dispone de estas formulaciones, como con la doxiciclina para niños mayores de 8 años o clindamicina, se pueden emplear las presentaciones en tabletas o cápsulas. Además, algunas formulaciones endovenosas, como la clindamicina, oxacilina e incluso la vancomicina, están disponibles para su uso en casos que lo requieran.
Asunto(s)
Humanos , Intoxicación Alimentaria Estafilocócica/tratamiento farmacológico , Dicloxacilina/uso terapéutico , Bacterias Grampositivas/efectos de los fármacos , Anticuerpos Monoclonales/efectos adversos , Evaluación en Salud , EficaciaRESUMEN
BACKGROUND: While standard blood tests are often sufficient for an anaemia workup, sometimes more invasive diagnostic testing is required to exclude rare conditions. CASE PRESENTATION: A man in his forties contacted his general practitioner because of increasing functional dyspnoea. He had completed a course of dicloxacillin a few months previously for a skin abscess on his abdomen. Bloodwork revealed severe anaemia (haemoglobin 5.4 g/dL), which required transfusion. Subsequent testing excluded iron and vitamin deficiency anaemia, haemolysis and malignancy. Initial bone marrow biopsy was of suboptimal quality. However, repeat tissue sample supported a diagnosis of pure red cell aplasia. The patient improved with ciclosporin treatment, which was gradually tapered. INTERPRETATION: Pure red cell aplasia should be considered in patients with new onset isolated anaemia with severe reticulocytopenia. Diagnosis depends on obtaining representative tissue from bone marrow biopsy. It is difficult to conclude for this patient whether the aetiology of his pure red cell aplasia was idiopathic or secondary to recent dicloxacillin use.
Asunto(s)
Anemia , Neoplasias , Aplasia Pura de Células Rojas , Humanos , Masculino , Anemia/etiología , Anemia/complicaciones , Médula Ósea , Dicloxacilina , Neoplasias/complicaciones , Aplasia Pura de Células Rojas/diagnóstico , Aplasia Pura de Células Rojas/etiología , AdultoRESUMEN
The aim of this study was to investigate the transfer of residues of five ß-lactam antibiotics (ampicillin, penicillin G, cloxacillin, dicloxacillin and cephalexin) and two tetracyclines (tetracycline and oxytetracycline) in the processing of cheese and whey powder, evaluating the effect of the processes and the final concentration in each product generated. Raw milk was fortified at two concentration levels with the seven antibiotics. The first concentration level (C1) was chosen according to the maximum residue limit (MRL) of each antibiotic (ampicillin and penicillin G: 4 µg kg-1; cloxacillin and dicloxacillin: 30 µg kg-1; cephalexin, tetracycline and oxytetracycline: 100 µg kg-1). The second concentration level (C2) was spiked as follows according to each antibiotic: 0.5 MRL (cloxacillin, dicloxacillin, cephalexin), 0.1 MRL (tetracycline and oxytetracycline) and 3 MRL (ampicillin and penicillin G). The antibiotics were analyzed by LC-MS/MS. No ampicillin or penicillin G residues were found in cheese or whey powder, although they were detected in whey at concentrations similar to those added to raw milk. Cephalexin was mostly distributed in whey between 82% and 96%, being the antibiotic that presented the highest concentration in whey powder (784 ± 98 µg kg-1) when milk was spiked at the MRL. The whey distribution of cloxacillin and dicloxacillin ranged from 57% to 59% for cloxacillin and from 46% to 48% for dicloxacillin, and both concentrated in whey powder. Tetracyclines were the antibiotics that concentrated in cheese, with retentions between 75% and 80% for oxytetracycline and between 83% and 87% for tetracycline. The distribution of antibiotics in the dissimilar stages of the cheese and whey powder production processes, as well as their concentration in the final products, depend on each type of antibiotic. Knowledge of the transfer of antibiotic residues during the process and final disposal is an input for the risk assessment of their consumption.
Asunto(s)
Queso , Residuos de Medicamentos , Oxitetraciclina , Animales , Leche/química , beta-Lactamas/análisis , Tetraciclina/análisis , Polvos/análisis , Queso/análisis , Oxitetraciclina/análisis , Suero Lácteo/química , Dicloxacilina/análisis , Cromatografía Liquida , Espectrometría de Masas en Tándem , Antibacterianos/análisis , Tetraciclinas/análisis , Cloxacilina , Ampicilina , Cefalexina , Residuos de Medicamentos/análisisRESUMEN
AIMS: Dicloxacillin is used to treat staphylococcal infections and we have previously shown that dicloxacillin is an inducer of cytochrome P450 enzymes (CYPs). Here, we employed a translational approach to investigate the effect of a treatment with dicloxacillin on warfarin efficacy in Danish registries. Furthermore, we assessed dicloxacillin as an inducer of CYPs in vitro. METHODS: We conducted a register-based study and analysed international normalized ratio (INR) levels in chronic warfarin users before and after short- and long-term use of dicloxacillin (n = 1023) and flucloxacillin (n = 123). Induction of CYPs were investigated in a novel liver model of 3D spheroid primary human hepatocytes at the level of mRNA, and protein and enzyme activity. RESULTS: Short- and long-term dicloxacillin treatments decreased INR levels by -0.65 (95% confidence interval [CI]: -0.57 to -0.74) and -0.76 (95% CI: -0.50 to -1.02), respectively. More than 90% of individuals experienced subtherapeutic INR levels (below 2) after long-term dicloxacillin treatment. Flucloxacillin decreased INR levels by -0.37 (95% CI: -0.14 to -0.60). In 3D spheroid primary human hepatocytes, the maximal induction of CYP3A4 mRNA, protein and enzyme activity by dicloxacillin were 4.9-, 2.9- and 2.4-fold, respectively. Dicloxacillin also induced CYP2C9 mRNA by 1.7-fold. CONCLUSION: Dicloxacillin induces CYPs and reduces the clinical efficacy of warfarin in patients. This effect is substantially exacerbated during long-term treatment with dicloxacillin. The in vitro results corroborated this drug-drug interaction and correlated to the clinical findings. Caution is warranted for warfarin patients that initiate dicloxacillin or flucloxacillin, especially for a long-term treatment of endocarditis.
Asunto(s)
Dicloxacilina , Warfarina , Humanos , Warfarina/efectos adversos , Dicloxacilina/farmacología , Anticoagulantes/efectos adversos , Floxacilina/farmacología , Relación Normalizada Internacional , Sistema Enzimático del Citocromo P-450/genética , Hepatocitos , Interacciones FarmacológicasRESUMEN
BACKGROUND: In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs). METHODS: Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated. RESULTS: A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%-100%. For moxifloxacin and rifampicin, the PTAs were 71%-100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%-17%.Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics. CONCLUSIONS: For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis.
Asunto(s)
Endocarditis Bacteriana , Endocarditis , Humanos , Rifampin/uso terapéutico , Dicloxacilina/uso terapéutico , Linezolid/uso terapéutico , Moxifloxacino/uso terapéutico , Antibacterianos/farmacología , Endocarditis/tratamiento farmacológico , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis Bacteriana/microbiología , Amoxicilina , Pruebas de Sensibilidad MicrobianaRESUMEN
From October 2022 through January 2023, nine patients with NDM-5/OXA-48-carbapenemase-producing Enterobacter hormaechei ST79 were detected in Denmark and subsequently one patient in Iceland. There were no nosocomial links between patients, but they had all been treated with dicloxacillin capsules. An NDM-5/OXA-48-carbapenemase-producing E. hormaechei ST79, identical to patient isolates, was cultured from the surface of dicloxacillin capsules in Denmark, strongly implicating them as the source of the outbreak. Special attention is required to detect the outbreak strain in the microbiology laboratory.
Asunto(s)
Dicloxacilina , Brotes de Enfermedades , Humanos , Islandia/epidemiología , Dinamarca/epidemiologíaRESUMEN
INTRODUCTION: Recent evidence has shown that oral antibiotic therapy is not inferior to IV antibiotic therapy in the treatment of complicated Staphylococcus aureus infections. Therefore, oral antibiotic therapy is now frequently prescribed in clinical practice due to cost benefit, ease of administration, decreased complication rate, and lack of need for IV access. In vitro susceptibility testing for ß-lactam oral antibiotics is not routinely performed as the guidelines provided by the Clinical and Laboratory Standards Institute (CLSI) recommend using oxacillin and cefoxitin as surrogate markers. Hence, oral antibiotic susceptibilities for cephalexin and dicloxacillin are not reported and implied based on oxacillin and cefoxitin. The objective of the current study was to determine whether susceptibilities among S. aureus isolates are predictable when comparing commonly used IV and oral beta-lactams. METHODS: Cefazolin, cephalexin, dicloxacillin, and oxacillin broth microdilution minimum inhibitory concentrations (MICs) were determined for 100 clinical isolates of methicillin-sensitive S. aureus by broth microdilution following CLSI guidelines. RESULTS: Among these isolates, median MICs for cephalexin were eight-fold higher than cefazolin MICs and median MICs for dicloxacillin were four-fold less than oxacillin MICs. Ten percent of more strains studied had a major or very major error in its susceptibility reporting when cephalexin was compared to its surrogate marker oxacillin. DISCUSSIONS/CONCLUSIONS: The variations in MICs observed compounded with the dosing and pharmacokinetic differences of oral versus IV ß-lactam suggests that establishing breakpoints for oral ß-lactam antibiotics is necessary to ensure adequate therapy is selected for the treatment of complex S. aureus infections.
Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Cefoxitina/farmacología , Cefoxitina/uso terapéutico , beta-Lactamas/farmacología , beta-Lactamas/uso terapéutico , Cefazolina/farmacología , Cefazolina/uso terapéutico , Staphylococcus aureus , Dicloxacilina/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Oxacilina/farmacología , Oxacilina/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Cefalexina/farmacología , Cefalexina/uso terapéutico , Monobactamas/uso terapéuticoRESUMEN
BACKGROUND: Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient's treatment journey leading to biologic therapy is unclear. OBJECTIVES: To examine treatment patterns and duration of systemic treatment use in patients with HS preceding biologic therapy. METHODS: We identified all patients with HS receiving treatment with biologics in the Danish National Patient Registry from 2010 to 2018 and extracted their entire prescription history of specific systemic treatments from the Danish National Prescription Registry since its inception in 1995. The patients' treatment journeys are graphically displayed through Sankey diagrams and box plots generated to show temporal distributions. Descriptive patient characteristics were presented as frequencies with percentages for categorical variables and as means with SDs or medians with interquartile ranges (IQRs) for continuous variables. RESULTS: A total of 225 patients with HS were included. Patients had most frequently been treated with penicillin (n = 214; 95·1%), dicloxacillin (n = 194; 86·2%), tetracycline (n = 145; 64·4%) and rifampicin/clindamycin (n = 111; 49·3%), as well as the retinoids isotretinoin and acitretin, and dapsone. Prior to biologic therapy, patients received a mean of 4·0 (SD 1·3) different systemic therapies, across a mean of 16·9 (SD 11·3) different treatment series. The mean time from first systemic therapy until biologic therapy was initiated was 15·3 (SD 5·1) years [8·2 (SD 5·9) years when excluding penicillin and dicloxacillin]. CONCLUSIONS: Patients with HS who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS. Delay in the initiation of biologic therapy may represent a missed opportunity to prevent disease progression. What is already known about this topic? The treatment journey leading to biologic therapy in patients with HS has not previously been investigated. What does this study add? Our data from 225 patients with HS illustrate that patients who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS.
Asunto(s)
Productos Biológicos , Hidradenitis Supurativa , Acitretina/uso terapéutico , Antibacterianos/uso terapéutico , Factores Biológicos/uso terapéutico , Productos Biológicos/uso terapéutico , Clindamicina , Dapsona/uso terapéutico , Dicloxacilina/uso terapéutico , Utilización de Medicamentos , Hidradenitis Supurativa/tratamiento farmacológico , Humanos , Isotretinoína/uso terapéutico , Rifampin/uso terapéutico , Tetraciclinas/uso terapéuticoRESUMEN
Background: Dicloxacillin is a beta-lactam antibiotic that is commonly used in the treatment of lactational mastitis in breastfeeding women. Although penicillins have long been considered safe for breastfeeding mothers and their infants, there is almost no data on the transfer of dicloxacillin into human breast milk despite the fact that it is commonly used for mastitis. Case Report: This study determined the drug concentration-time profile of dicloxacillin in milk samples collected from three lactating mothers consuming 500 mg dicloxacillin taken every 6 hours for treatment of mastitis. Milk levels were measured using liquid chromatography mass spectrometry. The maximum concentration of dicloxacillin in milk was 67.6 ng/mL. The relative infant dose (RID) was calculated to be 0.03%. This value is well below the theoretical level of concern of 10%. Discussion: The limited transfer of dicloxacillin into human milk is probably explained by the high plasma protein binding of dicloxacillin and its subsequent poor penetration into human milk. Conclusion: In this case series, the level of dicloxacillin in milk was found to be very low, and the RID to be only 0.03% of the maternal dose. Although the levels detected were low, dicloxacillin does transfer into breast milk. Caution should be exercised in infants with hypersensitivity to penicillins.
Asunto(s)
Antibacterianos/administración & dosificación , Lactancia Materna , Dicloxacilina/administración & dosificación , Mastitis/tratamiento farmacológico , Leche Humana/metabolismo , Animales , Antibacterianos/uso terapéutico , Cromatografía Liquida , Dicloxacilina/uso terapéutico , Femenino , Humanos , Lactante , Lactancia/metabolismo , Lactancia/fisiología , Espectrometría de Masas , Leche Humana/químicaRESUMEN
An 85-year-old man with a background of transfusion-dependent chronic myelomonocytic leukaemia and chronic kidney disease stage III presented with symptomatic anaemia, acute kidney injury, sepsis and high anion gap metabolic acidosis (HAGMA). Initial treatment with intravenous antibiotics and blood transfusion was complicated by transfusion-associated circulatory overload, necessitating diuresis and non-invasive ventilation. Despite gradual clinical improvement, the patient's HAGMA persisted, and no cause was identified on urine testing or renal ultrasound. As the patient was on long-term dicloxacillin for infective endocarditis prophylaxis and regular paracetamol, pyroglutamic acidosis (PGA) (5-oxoproline acidosis) was considered. This was later confirmed with elevated serum levels, and the HAGMA resolved following cessation of these medications. Although considered an uncommon cause of HAGMA, PGA is likely also under-recognised, and to our knowledge, this may be the second reported case in the context of dicloxacillin.
Asunto(s)
Acetaminofén/efectos adversos , Acidosis/inducido químicamente , Dicloxacilina/efectos adversos , Acetaminofén/administración & dosificación , Equilibrio Ácido-Base , Anciano de 80 o más Años , Analgésicos no Narcóticos/efectos adversos , Antibacterianos/efectos adversos , Diagnóstico Diferencial , Dicloxacilina/administración & dosificación , Endocarditis/prevención & control , Humanos , MasculinoAsunto(s)
Fibrilación Atrial , Isquemia Encefálica , Embolia , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Anticoagulantes/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Dicloxacilina , Embolia/etiología , Floxacilina , Válvulas Cardíacas , Humanos , Warfarina/efectos adversosRESUMEN
The antibiotics dicloxacillin and flucloxacillin induce cytochrome P450-dependent metabolism of warfarin. We explored the influence of these drug-drug interactions on the clinical effectiveness of warfarin therapy due to atrial fibrillation or heart valve replacement. Using the population-based Danish registers, we performed a propensity-score matched cohort study including around 50,000 episodes of dicloxacillin/flucloxacillin matched to phenoxymethylpenicillin and to no antibiotic, respectively. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) by comparing 21-day (days 7-28) risks of ischemic stroke/systemic embolism (SE) following initiation of each exposure. When compared with phenoxymethylpenicillin, dicloxacillin/flucloxacillin was associated with an HR of ischemic stroke/SE of 2.09 (95% CI 1.51-2.90; strongest for dicloxacillin (HR 2.17; 95% CI 1.56-3.02)). Use of an untreated comparator strengthened the association (HR 2.84; 95% CI 1.97-4.09). Dicloxacillin should be used with caution in patients receiving warfarin. This may also apply to flucloxacillin; however, more data on the risks associated with flucloxacillin exposure during warfarin therapy are needed.
Asunto(s)
Fibrilación Atrial/tratamiento farmacológico , Dicloxacilina/farmacología , Floxacilina/farmacología , Implantación de Prótesis de Válvulas Cardíacas/métodos , Warfarina/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Anticoagulantes/administración & dosificación , Anticoagulantes/farmacocinética , Anticoagulantes/farmacología , Fibrilación Atrial/complicaciones , Isquemia Encefálica/epidemiología , Isquemia Encefálica/etiología , Isquemia Encefálica/prevención & control , Estudios de Cohortes , Interacciones Farmacológicas , Embolia/epidemiología , Embolia/etiología , Embolia/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Penicilina V/farmacología , Sistema de Registros , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Warfarina/farmacocinética , Warfarina/farmacología , Adulto JovenRESUMEN
One of the greatest disturbing global health problems is antibiotic-resistant bacterial infections, which have rendered numerous currently used antibiotics ineffective. Thus, the feasibility of chitosan-coated deformable liposomes (C-Lips) containing dicloxacillin (DLX) were evaluated for their efficacy against methicillin-resistant Staphylococcus aureus (MRSA) strains, which are resistant to beta lactam antibiotics. DLX-loaded liposomes (DLX-Lip) were prepared by a lipid film hydration method and then chitosan (CS) coated (C-DLX-Lip) by the electrostatic deposition method. Both DLX-Lips and C-DLX-Lips showed a particle size distribution with a nano-range and a narrow polydispersity index (PDI). After CS coating, the zeta potential was shifted from negative to positive value. The DLX entrapment efficiency (EE) and drug loading (DL) were 62% and 5.6% for C-DLX-Lips compared to 38% and 3.1% for DLX-Lip, respectively. The in vitro release profile of C-DLX-Lips possessed a slow release behavior. Moreover, the DLX-Lips and C-DLX-Lips demonstrated an enhanced anti-MRSA activity. These results revealed that DLX-Lips and C-DLX-Lips may serve as promising carriers for DLX to increase the efficacy against MRSA, which offers considerably clinical value for long-term use of DLX.
Asunto(s)
Antibacterianos/administración & dosificación , Dicloxacilina/administración & dosificación , Sistemas de Liberación de Medicamentos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Materiales Biocompatibles/administración & dosificación , Quitosano/administración & dosificación , Liposomas , Resistencia a la Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Tamaño de la PartículaRESUMEN
Patients with a durable, continuous flow left ventricular assist device (CF-LVAD) require anticoagulation with warfarin to prevent thromboembolic events. Driveline infections (DLIs) are a common CF-LVAD complication. A common pathogen implicated in DLI is oxacillin-sensitive Staphylococcus aureus (OSSA), which is effectively treated by oral dicloxacillin. Previous published experiences have observed a significant drug interaction between dicloxacillin and warfarin resulting in decreased international normalized ratio (INR) and increased warfarin dosing requirements. We sought to analyze the effect of dicloxacillin on INR and warfarin dose when used for DLI in our CF-LVAD program. Five of 106 patients having received an CF-LVAD at our institution met the inclusion criteria for this case series. These patients required a mean 51.8% (standard deviation of 29.8%) weekly warfarin dose increase to restore INR to the therapeutic range after the addition of dicloxacillin. Three of the five patients subsequently had their dicloxacillin discontinued, with a mean decrease in weekly warfarin dose of 30.6% (standard deviation of 19.1%). In our experience, when coalesced with prior published reports, an empiric warfarin dose increase of 25% to 33% is reasonable upon initiation of dicloxacillin and an empiric warfarin dose reduction of 10% to 15% is recommended upon discontinuation of dicloxacillin. Close INR follow-up is warranted during and after dicloxacillin treatment.
Asunto(s)
Anticoagulantes/administración & dosificación , Dicloxacilina/farmacología , Corazón Auxiliar/efectos adversos , Warfarina/administración & dosificación , Anciano , Femenino , Humanos , Infecciones , Masculino , Persona de Mediana EdadRESUMEN
Staphylococcus aureus has developed resistance towards the most commonly used anti-staphylococcal antibiotics. Therefore, there is an urgent need to find new treatment opportunities. A new approach relies on the use of helper compounds, which are able to potentiate the effect of antibiotics. A well-studied helper compound is thioridazine, which potentiates the effect of the ß-lactam antibiotic dicloxacillin against Methicillin-resistant Staphylococcus aureus (MRSA). In order to identify thioridazine's mechanism of action and how it potentiates the effect of dicloxacillin, we generated thioridazine resistant strains of MRSA USA300 by serial passage experiments. Selected strains were whole-genome sequenced to find mutations causing thioridazine resistance. Genes observed to be mutated were attempted deleted in MRSA USA300. The cls gene encoding a cardiolipin synthase important for synthesis of the membrane lipid cardiolipin was found to be mutated in thioridazine resistant strains. Deletion of this gene resulted in a two-fold increased Minimum inhibitory concentrations (MIC) value for thioridazine compared to the wild type and decreased susceptibility similar to the thioridazine resistant strains. Since cardiolipin likely plays a role in resistance towards thioridazine, it might also be important for the mechanism of action behind the potentiating effect of thioridazine. TDZ is known to intercalate into the membrane and we show here that TDZ can depolarize the plasma membrane. However, our results indicate that the membrane potential reducing effect of TDZ is independent of the resistance mechanism.
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana/fisiología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/metabolismo , Tioridazina/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Cardiolipinas/metabolismo , Dicloxacilina/farmacología , Farmacorresistencia Bacteriana/genética , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Mutación , Filogenia , Transferasas (Grupos de Otros Fosfatos Sustitutos)/genética , Transferasas (Grupos de Otros Fosfatos Sustitutos)/metabolismo , Secuenciación Completa del GenomaRESUMEN
The antibiotic dicloxacillin has been shown to induce drug-metabolizing CYP enzymes to a clinically relevant extent. In this study, we investigated whether the use of dicloxacillin confers an increased risk of unwanted pregnancy among oral contraceptive users. The study population comprised Danish women falling pregnant (1997-2015) during oral contraceptive use, defined as having filled a prescription for an oral contraceptive within 120 days both before and after the estimated date of conception. Data were analysed using a case-crossover approach. For each woman, we assessed the use of dicloxacillin preceding the date of conception and during 10 previous control periods and estimated the odds ratio for such unintended pregnancies associated with the use of dicloxacillin. Among 364 women using dicloxacillin prior to conception, 40 (11%) were exposed to dicloxacillin at the time of conception, yielding an odds ratio (OR) associating use of dicloxacillin to unintended pregnancy of 1.18 (95% CI 0.84-1.65). Supplementary and sensitivity analyses generally returned similar estimates, except for a slightly increased risk among users of progestogen-only oral contraceptives (OR 1.83, 95% CI 0.63-5.34). Analysis of other antibiotics as negative controls yielded results close to unity (ORs ranging from 0.83 to 1.13). In conclusion, our study found no evidence for an increased risk of oral contraceptive failure when using dicloxacillin. However, acknowledging study limitations, we suggest the use of supplementary barrier methods during treatment with dicloxacillin, until our findings are confirmed in further studies.
Asunto(s)
Antibacterianos/efectos adversos , Anticonceptivos Orales/administración & dosificación , Dicloxacilina/efectos adversos , Embarazo no Deseado , Adulto , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Estudios Cruzados , Dinamarca , Dicloxacilina/administración & dosificación , Dicloxacilina/farmacología , Interacciones Farmacológicas , Femenino , Humanos , Embarazo , Embarazo no Planeado , Riesgo , Adulto JovenRESUMEN
BACKGROUND: A new series of 13 piperazinyl flavone derivatives has been synthesized and examined for their in vitro antiradical and antioxidant activities in response to the pharmacy industry's increasing demand for new non-toxic anti-inflammatory and anticancer drugs. METHOD: Their antioxidant activity was evaluated by the reactive oxygen species (ROS) scavenging assays, 2,2-diphenyl-1-picrylhydrazyl free radical (DPPHâ¢) and 2,2'-azino-bis(3- ethylbenzothiazoline-6-sulphonic acid) radical cation (ABTS+â¢) scavenging assays, and the ferric reducing antioxidant potency (TAC) method, and was compared to known positive controls, herbal infusions, and penicillins. Chemiluminescence, spectrophotometry, electron spin resonance (ESR) and 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) as the spin trap were the measurement techniques. RESULT: It was seen that synthesized compounds have a wide spectrum of antioxidant property. Some of the test compounds proved to be extremely efficient scavengers of H2O2 exhibiting, in some cases, EC50 of about 2 µM. The values of antioxidant status (TAS) were in the range of 49 ± 3.9 to 1283 ± 51.3 µM TE/g (TE = Trolox equivalent) and were lower than that of butylated hydroxytoluene (BHT) (1304 ± 43.2 µM TE/g) and green tea (1356 ± 40.0 µM TE/g), but for several synthesized compounds, they were higher than chamomille infusion and penicillins. Ferric reducing antioxidant powers (TAC) for the piperazinyl flavone derivatives were in the range 7 ± 0.5 to 104 ± 0.6 µM TE/g and were weaker than that of BHT (217 ± 5.3 µM TR/g ). CONCLUSION: Carboxylic or hydroxamic acid substituted piperazinyl flavones are potentially active as antioxidants, thus may be suggested as pharmacologically interesting ones.
Asunto(s)
Flavonas/farmacología , Depuradores de Radicales Libres/farmacología , Piperazinas/farmacología , Ácido Ascórbico/farmacología , Hidroxitolueno Butilado/farmacología , Camellia sinensis , Dicloxacilina/farmacología , Flavonas/síntesis química , Flavonas/química , Depuradores de Radicales Libres/síntesis química , Depuradores de Radicales Libres/química , Matricaria , Penicilina G/farmacología , Piperazinas/síntesis química , Piperazinas/química , Extractos Vegetales/farmacología , Relación Estructura-Actividad , Tés de HierbasRESUMEN
Two accurate, precise and sensitive high-performance thin layer chromatography (HPTLC) and high-performance liquid chromatography (HPLC) methods were developed for assay of ampicillin (AMP) and dicloxacillin (DX) in the presence of their impurity, 6-aminopenicillanic acid (APA). Method (A) is HPTLC method; using silica gel HPTLC F254 plates as a stationary phase with methanol: chloroform: acetic acid (1:9: 0.2, by volume) as a developing system. All the bands were scanned at 220 nm. Method (B) is reversed phase- HPLC which depended on isocratic elution using C18 column and mobile phase consisting of acetonitrile: water (60:40, v/v), pH adjusted to 4 with orthophosphoric acid, at a flow rate of 1 mL min-1 and ultraviolet detection at 240 nm. The proposed methods were validated as per ICH guidelines and their linearity was evident in the ranges of 0.5-2 µg band-1, 0.4-2 µg band-1 and 0.2-1.2 µg band-1 for method (A) and 5-40 µg mL-1, 5-40 µg mL-1 and 2-16 µg mL-1 for method (B) for AMP, DX and APA, respectively. The proposed methods were successfully used for assay of AMP and DX in pure form and in pharmaceutical formulation where no interference from the excipients was detected.
Asunto(s)
Ampicilina/análisis , Cromatografía Líquida de Alta Presión/métodos , Cromatografía en Capa Delgada/métodos , Dicloxacilina/análisis , Ácido Penicilánico/análogos & derivados , Ampicilina/química , Dicloxacilina/química , Contaminación de Medicamentos , Límite de Detección , Modelos Lineales , Ácido Penicilánico/análisis , Ácido Penicilánico/química , Reproducibilidad de los ResultadosRESUMEN
AIMS: The most common pathogen to cause postoperative infections in Denmark is Staphylococcus aureus. Despite using prophylactic antibiotics, infections are still seen. Whether the tissue concentration is above the minimal inhibitory concentration (MIC) for the pathogen is unknown. Thus, the concentration of dicloxacillin in muscle and adipose tissue was measured after intravenous administration, in healthy men. METHODS: MIC for dicloxacillin against S. aureus was determined using the broth macrodilution method. A microdialysis (MD) catheter was placed in the subcutaneous tissue of the abdomen and in the lateral vastus muscle of the thigh of six healthy male volunteers. They were given 2 g dicloxacillin intravenously. Samples from blood and MD fluid were collected. The unbound dicloxacillin was isolated from plasma. Samples were analysed with high performance liquid chromatography (HPLC). RESULTS: The maximum concentration was reached in muscle tissue after 0.5 h and in adipose tissue after 0.8 h. AUC0-6h for the dicloxacillin concentration in adipose tissue was significantly lower when compared to the unbound dicloxacillin concentration in plasma. The dicloxacillin concentration was above the MIC for sensitive S. aureus for a minimum of 2.3 h and a median of 4.1 h in muscle tissue and a minimum of 1.8 h and a median of 3.2 h in adipose tissue. CONCLUSIONS: The unbound dicloxacillin concentration in adipose and muscle tissue remained above the MIC for sensitive S. aureus, for a period sufficient for many orthopaedic procedures. Whether this is true in patients with compromised circulation remains to be investigated.