RESUMEN
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.
Asunto(s)
Antibacterianos/administración & dosificación , Dicloxacilina/administración & dosificación , Microdiálisis/métodos , Staphylococcus aureus/efectos de los fármacos , Tejido Adiposo/metabolismo , Administración Intravenosa , Adulto , Antibacterianos/farmacocinética , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Dicloxacilina/farmacocinética , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Músculo Esquelético/metabolismo , Distribución TisularRESUMEN
We have previously shown that the phenothiazine, thioridazine, acts in synergy with the beta-lactam antibiotic, dicloxacillin, to kill methicillin-resistant Staphylococcus aureus. In this study, we investigated whether synergy by combining these two drugs could also be observed in vancomycin intermediate susceptible S. aureus (VISA) and methicillin-resistant Staphylococcus epidermidis (MRSE). Synergy was observed in three of four tested VISA strains, suggesting that the thickening of cell wall does not interfere with the effects of thioridazine. In S. epidermidis, no synergy was observed in all tested strains, suggesting that synergy by combining thioridazine and dicloxacillin is isolated to S. aureus species.
Asunto(s)
Antibacterianos/uso terapéutico , Dicloxacilina/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacos , Tioridazina/uso terapéutico , Antibacterianos/administración & dosificación , Dicloxacilina/administración & dosificación , Antagonistas de Dopamina/administración & dosificación , Antagonistas de Dopamina/uso terapéutico , Sinergismo Farmacológico , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/microbiología , Tioridazina/administración & dosificaciónRESUMEN
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 , MasculinoRESUMEN
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
Antibiotic treatment of Staphylococcus aureus infections is often problematic due to the slow response to therapy and the high frequency of infection recurrence. The intracellular persistence of staphylococci has been recognized and could offer a good explanation for these treatment difficulties. Knowledge of the interplay between intracellular antibiotic activity and the overall outcome of infection is therefore important. Several intracellular in vitro models have been developed, but few experimental animal models have been published. The mouse peritonitis/sepsis model was used as the basic in vivo model exploring a quantitative ex vivo extra- and intracellular differentiation assay. The intracellular presence of S. aureus was documented by electron microscopy. Five antibiotics, dicloxacillin, cefuroxime, gentamicin, azithromycin, and rifampin (rifampicin), were tested in the new in vivo model; and the model was able to distinguish between their extra- and intracellular effects. The intracellular effects of the five antibiotics could be ranked as follows as the mean change in the log(10) number of CFU/ml (Delta log(10) CFU/ml) between treated and untreated mice after 4 h of treatment: dicloxacillin (3.70 Delta log(10) CFU/ml) > cefuroxime (3.56 Delta log(10) CFU/ml) > rifampin (1.86 Delta log(10) CFU/ml) > gentamicin (0.61 Delta log(10) CFU/ml) > azithromycin (0.21 Delta log(10) CFU/ml). We could also show that the important factors during testing of intracellular activity in vivo are the size, number, and frequency of doses; the time of exposure; and the timing between the start of infection and treatment. A poor correlation between the intracellular accumulation of the antibiotics and the actual intracellular effect was found. This stresses the importance of performing experimental studies, like those with the new in vivo model described here, to measure actual intracellular activity instead of making predictions based on cellular pharmacokinetic and MICs.
Asunto(s)
Antibacterianos/farmacología , Peritonitis , Sepsis , Infecciones Estafilocócicas , Staphylococcus aureus/efectos de los fármacos , Animales , Animales no Consanguíneos , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Recuento de Colonia Microbiana , Dicloxacilina/administración & dosificación , Dicloxacilina/farmacocinética , Dicloxacilina/farmacología , Dicloxacilina/uso terapéutico , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , Peritoneo/citología , Peritoneo/efectos de los fármacos , Peritoneo/microbiología , Peritonitis/tratamiento farmacológico , Peritonitis/microbiología , Rifampin/administración & dosificación , Rifampin/farmacocinética , Rifampin/farmacología , Rifampin/uso terapéutico , Sepsis/tratamiento farmacológico , Sepsis/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Resultado del TratamientoRESUMEN
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
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: Dicloxacillin, a semisynthetic isoxazolyl penicillin, exhibits antimicrobial activity against a wide variety of Gram-positive bacteria, as well as stability against penicillinases and low level of toxicity. The objective of this study was to obtain optimal dosing regimen of oral administration of dicloxacillin by analyzing the pharmacokinetic (PK) index in healthy volunteers and in vitro antibacterial activity by using Monte Carlo simulation. MATERIALS AND METHODS: A total of 867 clinical isolates from community-onset infections were collected from 31 secondary hospitals in People's Republic of China. The minimum inhibitory concentration (MIC) values of dicloxacillin were determined by the agar dilution method. Based on the MICs and the PK parameters of different dosage regimens, Monte Carlo simulation was performed to simulate the PK/pharmacodynamic indices of 250 mg once-daily (qd), 500 mg qd, 1,000 mg qd, 2,000 mg qd, 250 mg every 6 hours (q6h), and 500 mg q6h, respectively. The probability of target attainment was estimated at each MIC value, and the cumulative fraction of response (CFR) was calculated to evaluate the efficacy of these regimens. RESULTS: Dicloxacillin showed poor antibacterial activity against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Resistance to dicloxacillin was observed in 7.5% of coagulase-negative Staphylococcus (CNS) isolates and 9.2% of other Streptococcus isolates, whereas 1.5% of methicillin-sensitive Staphylococcus aureus (MSSA) was resistant to dicloxacillin. Multiple-dose regimens could obtain higher CFR than single-dose regimens against H. influenza and S. pneumoniae. However, all dosing regimens against MSSA achieved CFR ≥$90%. Meanwhile, dosing regimen of 2,000 mg qd, 250 mg q6h, and 500 mg q6h could achieve >90% of CFR for CNS. For other Streptococcus isolates, multiple-dose regimens achieved CFR ≥90%. CONCLUSION: Dicloxacillin has a significant antibacterial activity against MSSA, CNS, and other Streptococcus isolates. The simulation results suggest that dicloxacillin 250 mg q6h and 500 mg q6h dosing regimens may be recommended for clinical applications, especially for community-onset infections.
Asunto(s)
Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Dicloxacilina/administración & dosificación , Dicloxacilina/farmacocinética , Administración Oral , Bacterias/efectos de los fármacos , Infecciones Comunitarias Adquiridas/microbiología , Simulación por Computador , Farmacorresistencia Bacteriana , Voluntarios Sanos , Humanos , Pruebas de Sensibilidad Microbiana , Método de MontecarloRESUMEN
Biofilms of Staphylococcus epidermidis and Candida spp. are two of the most frequent factors of infections associated with the use of indwelling medical devices. Several strategies have been proposed and/or developed to prevent infection. The aim of this study was to compare the effect of sub-inhibitory concentrations of anti-microbial agents on biofilm formation. Biofilms of three strains of S. epidermidis and two of both Candida albicans and Candida dubliniensis were formed in the presence of three antibiotics and two antifungal agents respectively. Based on the control samples, the percentage of biofilm formation inhibition by the different agents was determined and compared. The results showed that the influence of the antibacterial and antifungal agents tested is strain dependent, with the effect of the different agents also varying among strains, even though they have the same mechanism of action.
Asunto(s)
Antibacterianos/administración & dosificación , Antifúngicos/administración & dosificación , Biopelículas/efectos de los fármacos , Candida/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacos , Anfotericina B/administración & dosificación , Cefazolina/administración & dosificación , Dicloxacilina/administración & dosificación , Fluconazol/administración & dosificación , Humanos , Vancomicina/administración & dosificaciónRESUMEN
BACKGROUND: Dicloxacillin, a semisynthetic isoxazolyl penicillin antibiotic, has antimicrobial activity against a wide variety of gram-positive bacteria including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumonia, Streptococcus epidermidis, Streptococcus viridans, Streptococcus agalactiae, and Neisseria meningitidis. The objective of this study was to evaluate the safety and pharmacokinetic profile of dicloxacillin after single and multiple oral dose in healthy Chinese volunteers. METHODS: A single-center, open-label, randomized, two-phase study was conducted in 16 subjects. In the single-dose phase, subjects were randomly assigned to receive single doses of 0.25, 0.5, 1.0, and 2.0 g of dicloxacillin sodium capsule in a 4-way crossover design with a 5-day washout period between administrations. In the multiple-dose phase, subjects were assigned to receive 0.25 or 0.5 g every 6 hours for 3 days in a 2-way crossover design. Plasma and urine pharmacokinetic samples were assayed by a validated high-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated and analyzed statistically. Safety assessments were conducted throughout the study. RESULTS: Following a single oral dose of 0.25-2.0 g dicloxacillin sodium, the maximum plasma drug concentration (Cmax) and the corresponding values for the area under the concentration- time curve from 0 to 10 hours (AUC0-10 h) increased in a dose-proportional manner. The mean elimination half-life (t1/2) was in the range of 1.38-1.71 hours. Dicloxacillin was excreted in its unchanged form via the kidney, with no tendency of accumulation, and varied from 38.65% to 50.10%. No appreciable accumulation of drug occurred with multiple oral doses of dicloxacillin. No serious adverse events were reported. Adverse events were generally mild. CONCLUSION: Dicloxacillin was safe and well tolerated in the volunteers and displayed linear increases in the Cmax and AUC0-10 h values.
Asunto(s)
Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Dicloxacilina/administración & dosificación , Dicloxacilina/farmacocinética , Administración Oral , Adolescente , Adulto , Antibacterianos/efectos adversos , Antibacterianos/sangre , Antibacterianos/orina , Área Bajo la Curva , Pueblo Asiatico , China , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Dicloxacilina/efectos adversos , Dicloxacilina/sangre , Dicloxacilina/orina , Esquema de Medicación , Femenino , Semivida , Voluntarios Sanos , Humanos , Modelos Lineales , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Modelos Biológicos , Eliminación Renal , Espectrometría de Masas en Tándem , Adulto JovenRESUMEN
Differences in the elimination, distribution, and absorption of dicloxacillin and cloxacillin were studied in a group of healthy individuals with the use of a 2-compartment model. In patients on chronic intermittent hemodialysis, only dicloxacillin was investigated and the results were compared with data obtained in earlier studies on cloxacillin and flucloxacillin. In healthy volunteers the bioavailability after oral administration of 2 gm dicloxacillin or 2 gm cloxacillin amounted to 48.8% and 36.9% of the dose, respectively, when calculated from the area under the serum concentration-time curve, and to 74.1% and 48.5%, respectively, when calculated from the urinary excretion. Individual variation in bioavailability after oral administration was slightly lower for docloxacillin than for cloxacillin. The higher serum concentrations of dicloxacillin, as compared with cloxacillin, are also attributable to slower (renal) elimination (T 1/2: 42 and 33 min, respectively). Analysis of serum concentrations after intravenous administration of 1 and 2 gm dicloxacillin to healthy subjects revealed concentration-dependent kinetics with respect ot renal elimination. In hemodialysis patients the elimination rate of dicloxacillin (T 1/2: 129 min) corresponds with the extrarenal elimination rate in healthy subjects. The bioavailability after oral administration of 1 gm in patients is good (75.9% of the dose).
Asunto(s)
Cloxacilina/metabolismo , Dicloxacilina/metabolismo , Diálisis Renal , Administración Oral , Adulto , Disponibilidad Biológica , Cloxacilina/administración & dosificación , Dicloxacilina/administración & dosificación , Femenino , Semivida , Humanos , Inyecciones Intravenosas , Enfermedades Renales/metabolismo , Cinética , Masculino , Persona de Mediana Edad , Modelos BiológicosRESUMEN
Elephantiasis nostras (EN) is a clinical entity that usually presents as a persistent swelling of the lower extremities. It has been related to recurrent lymphangitis of bacterial origin that causes a fibrosis and thickening of both epidermal and connective tissue. Although very rare, EN has been previously reported in the lips. This is the first case reported in the oral medicine literature that describes EN involving the lips. We describe the clinical features and a differential diagnosis of the lip lesions and a treatment protocol to which this patient has responded. A diagnosis of EN should be entertained in patients with chronically edematous, scaling lip lesions.
Asunto(s)
Elefantiasis/patología , Enfermedades de los Labios/patología , Adulto , Antibacterianos/uso terapéutico , Antipruriginosos/uso terapéutico , Infecciones Bacterianas , Clindamicina/uso terapéutico , Tejido Conectivo/patología , Diagnóstico Diferencial , Dicloxacilina/administración & dosificación , Dicloxacilina/uso terapéutico , Doxepina/uso terapéutico , Quimioterapia Combinada/uso terapéutico , Edema/patología , Elefantiasis/tratamiento farmacológico , Epidermis/patología , Eritema/patología , Eritromicina/uso terapéutico , Femenino , Fibrosis , Estudios de Seguimiento , Humanos , Enfermedades de los Labios/tratamiento farmacológico , Linfangitis/microbiología , Penicilinas/uso terapéutico , RecurrenciaRESUMEN
Debate continues concerning proper management of peritonsillar abscess (PA). We studied 189 children (mean age, 9 years) admitted in our department during the last 7 years with the diagnosis of PA. Management consisted of incision and drainage (performed in 92.5% of the children without general anaesthesia) and antibiotic therapy intravenously. There was resolution without complications in the overwhelming majority of the cases. After the initial episode, we further followed up 101 children. The recurrence rate was 15.8%. Forty-seven percent of the recurrences occurred 1 month after the children had been discharged. Probably some of these second PA should be considered as persistent and not as recurrent. Therefore, we propose that after their discharge, the children must take oral antibiotics (resistant to beta-lactamase) for more than 10 days. Cultures were taken from 58 cases. The predominant bacterial isolates were Streptococcus spp. (55%), anaerobes spp. (12%) and Staphylococcus aureus (6%). To our knowledge, this is the first survey that addresses exclusively a pediatric population and suggests that incision and drainage without general anaesthesia is an applicable and effective management in children with PA. Moreover, we believe that peritonsillar abscess is no longer a strong indication for tonsillectomy due to the relatively low rate of recurrence. We recommend close follow-up, mainly for the first months after the initial episode.
Asunto(s)
Absceso Peritonsilar/cirugía , Adolescente , Amoxicilina/administración & dosificación , Amoxicilina/uso terapéutico , Bacterias Anaerobias , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/cirugía , Niño , Preescolar , Protocolos Clínicos , Terapia Combinada , Dicloxacilina/administración & dosificación , Dicloxacilina/uso terapéutico , Drenaje , Femenino , Estudios de Seguimiento , Humanos , Lactante , Inyecciones Intravenosas , Masculino , Absceso Peritonsilar/tratamiento farmacológico , Recurrencia , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/cirugía , Infecciones Estreptocócicas/tratamiento farmacológico , Infecciones Estreptocócicas/cirugía , Tonsilitis/tratamiento farmacológico , Tonsilitis/cirugíaRESUMEN
Rabbits were given dicloxacillin subconjunctively. Very high levels of the drug were recovered from the aqueous humor. Soon after injection, corneal opacification, epithelial sloughing and conjunctival necrosis were noted clinically. The globes were studied histopathologically.
Asunto(s)
Opacidad de la Córnea/inducido químicamente , Dicloxacilina/toxicidad , Animales , Conjuntiva/patología , Córnea/patología , Opacidad de la Córnea/patología , Dicloxacilina/administración & dosificación , Epitelio/patología , Femenino , Humanos , Inyecciones , Masculino , Necrosis , ConejosRESUMEN
Nine men with ten episodes of staphylococcal endocarditis with valvular vegetation (except one) were treated with intravenous cloxacillin for an average of 10 days and followed by oral cloxacillin or dicloxacillin, both with probenecid, for a total duration of 4 wks. Monitoring of serum bactericidal titers (SBT) showed similar values between the two routes of therapy. All patients were bacteriologically and clinically cured. However, there were 3 recurrences, 2 were drug abusers. One nonabuser had the same staphylococcal species 8 months later. All survived the second episode. This preliminary study supports the contention that intravenous followed by oral therapy for staphylococcal endocarditis may be a viable and a more economical form of therapy.
Asunto(s)
Quimioterapia Combinada/administración & dosificación , Endocarditis Bacteriana/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Cloxacilina/administración & dosificación , Dicloxacilina/administración & dosificación , Esquema de Medicación , Femenino , Gentamicinas/administración & dosificación , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Probenecid/administración & dosificación , Staphylococcus aureus/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacosRESUMEN
In vitro enzymatic degradation rate of ampicillin (AB-PC) in urine of patients with complicated urinary tract infection and its protective effect of dicloxacillin (MDI-PC) was studied using a specific fluorometric assay for aminobenzylpenicilloic acid (AB-PA), which is converted from AB-PC by bacterial beta-lactamase. The results showed that average degradation rate of AB-PC in the urine of 10 patients were 12.2%, 21.5%, 34.3% and 48.2% at 15, 30, 60 and 120 minutes, respectively. While MDI-PC prevented the enzymatic transformation of AB-PC in such urinary samples and the average degradation rates at 15, 30, 60 and 120 minutes were considerably reduced to 7.7%, 12.2%, 21.6% and 32.8%, respectively. In vivo urinary excretion rate of AB-PA was compared between a total of 5 patients and 4 healthy volunteers after oral administration of 250 mg AB-PC. It was found that the patients excreted 9.1%, 10.7% and 12.7% of total dose at 0 approximately to 2 hours, 2 approximately to 4 hours, 4 approximately to 6 hours, respectively, while the average excretion rates in healthy volunteers were 1.54%, 2.88% and 7.94%, respectively. In 4 patients cross-over administration study, the combined dose of AB-PC and MDI-PC has been proved to clearly decrease the urinary excretion rate of AB-PA in 2 cases, but there was no significant difference in the average rate between the single and the combined dose.
Asunto(s)
Ampicilina/orina , Dicloxacilina/farmacología , Infecciones Urinarias/orina , Ampicilina/administración & dosificación , Ampicilina/metabolismo , Biotransformación , Dicloxacilina/administración & dosificación , Humanos , Infecciones Urinarias/metabolismo , beta-Lactamasas/orinaRESUMEN
BACKGROUND: Infections of arterial vascular grafts are among the most dreaded complications in vascular surgery. Infection in a thoracic aorta graft poses particular challenges. Depending on the local anatomy, extraanatomic bypass, otherwise the cornerstone in the management of infected vascular grafts, is usually impossible. MATERIAL AND METHODS: We present a case report on a patient with an infected thoracic aorta graft and discuss the choice of antibiotics for long-term suppressive therapy. RESULTS: In the course of the 52 months since the insertion of the aortic graft, the patient experienced eight serious episodes of staphylococcal septicaemia, with Staphylococcus aureus in blood culture on each occasion. A combination therapy of three orally administered anti-staphylococcal antibiotics has kept him free from recurrent septic episodes over the last 25 months, with a good quality of life and without signs of systemic infection. INTERPRETATION: Life-long antibiotic suppressive therapy for infected thoracic aorta graft offers the prospect of long-term survival with a good quality of life, even when there are recurrent serious septic complications. The choice of antibiotics should take into account the feasibility of the proposed treatment; parenteral antibiotics are not a realistic option in the long run. The antibiotics should be well absorbed after oral administration, have a high intrinsic activity against the offending pathogen, and be given at intervals leading to inhibitory blood concentrations throughout most of the day. In our patient, a triple combination therapy was necessary.
Asunto(s)
Aorta Torácica/cirugía , Aortitis/tratamiento farmacológico , Prótesis Vascular/efectos adversos , Clindamicina/administración & dosificación , Dicloxacilina/administración & dosificación , Quimioterapia Combinada/administración & dosificación , Complicaciones Posoperatorias/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Sepsis/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Administración Oral , Anciano , Aorta Torácica/microbiología , Aortitis/microbiología , Aortitis/cirugía , Humanos , Masculino , Complicaciones Posoperatorias/microbiología , Infecciones Relacionadas con Prótesis/microbiología , Recurrencia , Sepsis/microbiología , Factores de TiempoRESUMEN
This is an observational retrospective study. Our goal is to describe the local dermonecrotic reaction occurring after a spider bite in eleven pediatric patients. In seven (63.7%), the spider was identified as Loxosceles reclusa, and in four, bites were presumptive. The main symptoms and signs were pain, erythema, swelling, blisters, and vasculitis in five patients. There was a significant relationship between the time of onset before the treatment and the severity of the lesions (63.4 hours in the severe cases vs 14.4 hours in the mild cases, p < 0.05), as well the time spent in the emergency room (50 hours vs 10 hours respectively, p < 0.05). Treatment with dapsone, 1 mg/kg/24 h, and/or paracetamol and dicloxacillin was successful; one case required surgical treatment. No systemic loxoscelism occurred in this patient.
Asunto(s)
Piel/patología , Picaduras de Arañas/diagnóstico , Acetaminofén/administración & dosificación , Analgésicos no Narcóticos/administración & dosificación , Antiinflamatorios no Esteroideos/administración & dosificación , Niño , Dapsona/administración & dosificación , Dicloxacilina/administración & dosificación , Quimioterapia Combinada , Humanos , Necrosis , Penicilinas/administración & dosificación , Estudios Retrospectivos , Picaduras de Arañas/tratamiento farmacológico , Picaduras de Arañas/patologíaRESUMEN
In a double-blind test it was shown the efficacy of topical fusidic acid in comparison with oral dicloxacillin, in patients with skin infection by Staphylococcus aureus or/and Streptococcus pyogenes. In the experimental group, 16 patients from 20 received 2% topical fusidic acid in cream and reacted well in a shorter period of time than 17 from a group of 20 that had 500 mg. of dicloxacillin orally twice a day.
Asunto(s)
Dicloxacilina/uso terapéutico , Ácido Fusídico/uso terapéutico , Enfermedades Cutáneas Infecciosas/tratamiento farmacológico , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico , Administración Oral , Administración Tópica , Adolescente , Adulto , Dicloxacilina/administración & dosificación , Dicloxacilina/efectos adversos , Femenino , Ácido Fusídico/administración & dosificación , Ácido Fusídico/efectos adversos , Humanos , Masculino , Staphylococcus aureus , Streptococcus pyogenesRESUMEN
The shortage of drugs active against meticillin-resistant Staphylococcus aureus (MRSA) is a growing clinical problem. In vitro studies indicate that the phenothiazine thioridazine (TZ) might enhance the activity of the ß-lactam antibiotic dicloxacillin (DCX) to a level where MRSA is killed, but experiments in simple animal models have not been performed. In the present study, we introduced Caenorhabditis elegans infected by S. aureus as an in vivo model to test the effect of TZ as a helper drug in combination with DCX. Because TZ is an anthelmintic, initial experiments were carried out to define the thresholds of toxicity, determined by larval development, and induction of stress-response markers. No measurable effects were seen at concentrations of less than 64 mg TZ l(-1). Seven different MRSA strains were tested for pathogenicity against C. elegans, and the most virulent strain (ATCC 33591) was selected for further analyses. In a final experiment, full-grown C. elegans were exposed to the test strain for 3 days and subsequently treated with 8 mg DCX l(-1) and 8 mg TZ l(-1) for 2 days. This resulted in a 14-fold reduction in the intestinal MRSA load as compared with untreated controls. Each drug alone resulted in a two- to threefold reduction in MRSA load. In conclusion, C. elegans can be used as a simple model to test synergy between DCX and TZ against MRSA. The previously demonstrated in vitro synergy can be reproduced in vivo.