RESUMEN
BACKGROUND & OBJECTIVES: The emergence of resistance to fluoroquinolones in enteric fever despite the pathogen being susceptible by in vitro laboratory results, led to repeated changes in Clinical and Laboratory Standard Institute (CLSI) guidelines for this class of antibiotics to have specific and sensitive interpretative criteria. In 2015, CLSI added pefloxacin disk diffusion criteria as a surrogate marker for fluoroquinolone susceptibility. This study was carried out to evaluate the use of pefloxacin as a surrogate marker for ciprofloxacin, ofloxacin and levofloxacin susceptibility in clinical isolates of Salmonella Typhi and S. Paratyphi A. METHODS: A total of 412 strains of S. Typhi and S. Paratyphi A were studied for pefloxacin disk diffusion test as a surrogate marker for susceptibility to ciprofloxacin, ofloxacin and levofloxacin as per CLSI and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Molecular mechanisms of resistance to fluoroquinolones were also determined and correlated with pefloxacin susceptibility breakpoints. RESULTS: Of the total 412 strains, 34 were susceptible to ciprofloxacin and 33 each to levofloxacin and ofloxacin using CLSI minimum inhibitory concentration (MIC) breakpoints. There was a positive correlation between MICs with correlation coefficients 0.917, 0.896 and 0.958 for the association between ciprofloxacin and ofloxacin, ciprofloxacin and levofloxacin and ofloxacin and levofloxacin, respectively (P <0.001). The sensitivity, specificity and positive predictive value of pefloxacin as a surrogate marker using ciprofloxacin MIC as a gold standard were 100, 99.5 and 94.4 per cent, while 100, 99.2 and 91.7 per cent taking ofloxacin and levofloxacin MIC as gold standard. Mutations in target genes correlated with the pefloxacin susceptibility results. INTERPRETATION & CONCLUSIONS: Our results showed that pefloxacin served as a good surrogate marker for the detection of susceptibility to ciprofloxacin, ofloxacin and levofloxacin in S. Typhi and S. Paratyphi A. Further studies are required to confirm these findings.
Asunto(s)
Farmacorresistencia Bacteriana/genética , Fiebre Paratifoidea/tratamiento farmacológico , Pefloxacina/administración & dosificación , Salmonella enterica/efectos de los fármacos , Antibacterianos/administración & dosificación , Biomarcadores , Farmacorresistencia Bacteriana/efectos de los fármacos , Humanos , Mutación , Fiebre Paratifoidea/microbiología , Fiebre Paratifoidea/patología , Salmonella enterica/patogenicidad , Salmonella paratyphi A/efectos de los fármacos , Salmonella paratyphi A/patogenicidadRESUMEN
Knowledge of the uncertainty in model parameters is essential for decision-making in drug development. Contrarily to other aspects of nonlinear mixed effects models (NLMEM), scrutiny towards assumptions around parameter uncertainty is low, and no diagnostic exists to judge whether the estimated uncertainty is appropriate. This work aims at introducing a diagnostic capable of assessing the appropriateness of a given parameter uncertainty distribution. The new diagnostic was applied to case bootstrap examples in order to investigate for which dataset sizes case bootstrap is appropriate for NLMEM. The proposed diagnostic is a plot comparing the distribution of differences in objective function values (dOFV) of the proposed uncertainty distribution to a theoretical Chi square distribution with degrees of freedom equal to the number of estimated model parameters. The uncertainty distribution was deemed appropriate if its dOFV distribution was overlaid with or below the theoretical distribution. The diagnostic was applied to the bootstrap of two real data and two simulated data examples, featuring pharmacokinetic and pharmacodynamic models and datasets of 20-200 individuals with between 2 and 5 observations on average per individual. In the real data examples, the diagnostic indicated that case bootstrap was unsuitable for NLMEM analyses with around 70 individuals. A measure of parameter-specific "effective" sample size was proposed as a potentially better indicator of bootstrap adequacy than overall sample size. In the simulation examples, bootstrap confidence intervals were shown to underestimate inter-individual variability at low sample sizes. The proposed diagnostic proved a relevant tool for assessing the appropriateness of a given parameter uncertainty distribution and as such it should be routinely used.
Asunto(s)
Descubrimiento de Drogas/estadística & datos numéricos , Modelos Estadísticos , Dinámicas no Lineales , Pefloxacina/farmacocinética , Fenobarbital/farmacocinética , Incertidumbre , Simulación por Computador , Humanos , Modelos Biológicos , Pefloxacina/administración & dosificación , Fenobarbital/administración & dosificaciónRESUMEN
Taking parameter uncertainty into account is key to make drug development decisions such as testing whether trial endpoints meet defined criteria. Currently used methods for assessing parameter uncertainty in NLMEM have limitations, and there is a lack of diagnostics for when these limitations occur. In this work, a method based on sampling importance resampling (SIR) is proposed, which has the advantage of being free of distributional assumptions and does not require repeated parameter estimation. To perform SIR, a high number of parameter vectors are simulated from a given proposal uncertainty distribution. Their likelihood given the true uncertainty is then approximated by the ratio between the likelihood of the data given each vector and the likelihood of each vector given the proposal distribution, called the importance ratio. Non-parametric uncertainty distributions are obtained by resampling parameter vectors according to probabilities proportional to their importance ratios. Two simulation examples and three real data examples were used to define how SIR should be performed with NLMEM and to investigate the performance of the method. The simulation examples showed that SIR was able to recover the true parameter uncertainty. The real data examples showed that parameter 95 % confidence intervals (CI) obtained with SIR, the covariance matrix, bootstrap and log-likelihood profiling were generally in agreement when 95 % CI were symmetric. For parameters showing asymmetric 95 % CI, SIR 95 % CI provided a close agreement with log-likelihood profiling but often differed from bootstrap 95 % CI which had been shown to be suboptimal for the chosen examples. This work also provides guidance towards the SIR workflow, i.e.,which proposal distribution to choose and how many parameter vectors to sample when performing SIR, using diagnostics developed for this purpose. SIR is a promising approach for assessing parameter uncertainty as it is applicable in many situations where other methods for assessing parameter uncertainty fail, such as in the presence of small datasets, highly nonlinear models or meta-analysis.
Asunto(s)
Imidazoles/farmacocinética , Modelos Biológicos , Dinámicas no Lineales , Pefloxacina/farmacocinética , Fenobarbital/farmacocinética , Incertidumbre , Administración Oral , Algoritmos , Simulación por Computador , Intervalos de Confianza , Humanos , Imidazoles/administración & dosificación , Inyecciones Intravenosas , Modelos Estadísticos , Pefloxacina/administración & dosificación , Fenobarbital/administración & dosificación , Programas InformáticosRESUMEN
BACKGROUND: The purpose of the current study is to evaluate the effects of systemic ornidazole (SO) and systemic and local compound ornidazole and pefloxacin mesylate (SCOPM/LCOMP) on the inflammatory response associated with rat experimental chronic periodontitis (ECP) in sites with subgingival debridement. MATERIAL/METHODS: Periodontitis was induced in male Sprague-Dawley rats by placing a thin steel ligature around the upper first molars and inoculating them with Porphyromonas gingivalis 381. After the successful induction of the rat ECP, the periodontitis rats were randomly divided into 3 different combined treatment groups: (A) SO with scaling and root planing (SRP); (B) SCOMP with SRP; and (C) LCOMP with SRP. After 2 weeks the effects of the treatments were evaluated based on gingivitis, plaque index, probing pocket depth, aspartate aminotransferase, alveolar bone loss, and hematoxylin-eosin staining of the region around the first molars. RESULTS: After treatment, comparison with ECP was performed. The mean percentage reductions of SBI in SO, SCOPM, and LCOPM were 27.73%, 33.61%, and 58.82%, respectively. Those of PI were 33.20%, 42.80%, and 60.00%; those of PPD were 48.66%, 55.70%, and 72.48%; those of GCF-AST were 41.64%, 49.03%, and 66.42%; and those of ABL were 41.19%, 43.63%, and 54.47%, respectively. The inflammatory score of H&E showed median scores of 2.5, 1.75, 1.63, and 0.95 for ECP, SO, SCOMP, and LCOMP, respectively. All 3 treatment groups exhibited significantly reduced inflammation indicators (P<0.05). Of the 3, group C was the most effective (P<0.05). CONCLUSIONS: Although all the combined treatment groups responded to therapy with significant resolution of the infection, adjunctive LCOMP therapy is more effective for periodontitis.
Asunto(s)
Ornidazol/uso terapéutico , Pefloxacina/uso terapéutico , Periodontitis/tratamiento farmacológico , Animales , Masculino , Ornidazol/administración & dosificación , Pefloxacina/administración & dosificación , Periodontitis/microbiología , Porphyromonas gingivalis/patogenicidad , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: This study investigated the effects of salmonella infection and its chemotherapy on lipid metabolism in tissues of rats infected orally with Salmonella typhimurium and treated intraperitoneally with pefloxacin and amoxillin. METHODS: Animals were infected with Salmonella enterica serovar Typhimurium strain TA 98. After salmonellosis was confirmed, they were divided into 7 groups of 5 animals each. While one group served as infected control group, three groups were treated with amoxillin (7.14 mg/kg body weight, 8 hourly) and the remaining three groups with pefloxacin (5.71 mg/kg body weight, 12 hourly) for 5 and 10 days respectively. Uninfected control animals received 0.1 ml of vehicle. Rats were sacrificed 24h after 5 and 10 days of antibiotic treatment and 5 days after discontinuation of antibiotic treatment. Their corresponding controls were also sacrificed at the same time point. Blood and tissue lipids were then evaluated. RESULTS: Salmonella infection resulted in dyslipidemia characterised by increased concentrations of free fatty acids (FFA) in plasma and erythrocyte, as well as enhanced cholesterogenesis, hypertriglyceridemia and phospholipidosis in plasma, low density lipoprotein-very low density lipoprotein (LDL-VLDL), erythrocytes, erythrocyte ghost and the organs. The antibiotics reversed the dyslipidemia but not totally. A significant correlation was observed between fecal bacterial load and plasma cholesterol (r=0.456, p<0.01), plasma triacyglycerols (r=0.485, p<0.01), plasma phospholipid (r=0.414, p<0.05), plasma free fatty acids (r=0.485, p<0.01), liver phospholipid (r=0.459, p<0.01) and brain phospholipid (r=0.343, p<0.05). CONCLUSION: The findings of this study suggest that salmonella infection in rats and its therapy with pefloxacin and amoxillin perturb lipid metabolism and this perturbation is characterised by cholesterogenesis.
Asunto(s)
Amoxicilina/administración & dosificación , Dislipidemias/etiología , Pefloxacina/administración & dosificación , Salmonelosis Animal/complicaciones , Salmonelosis Animal/tratamiento farmacológico , Salmonella typhimurium , Animales , Antibacterianos/administración & dosificación , Colesterol/sangre , Quimioterapia Combinada , Dislipidemias/tratamiento farmacológico , Dislipidemias/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Lípidos/sangre , Masculino , Fosfolípidos/sangre , Ratas , Salmonelosis Animal/metabolismo , Distribución Tisular , Triglicéridos/sangreRESUMEN
The pharmacokinetics of orally administered pefloxacin were studied to evaluate the bio-enhancing effect of the herbal bio-enhancer, trikatu, in mountain Gaddi goats (n = 6). The findings of the study revealed a decreased plasma concentration (p > 0.05) of pefloxacin following trikatu administration during the absorption phase (10, 15, 20 min post pefloxacin administration). In contrast, the plasma concentrations of pefloxacin were significantly higher at 4, 6, 8 and 12 h (during the elimination phase) of the pefloxacin administration. The findings of the investigation revealed higher values for the area under the curve, the area under the first moment of the plasma drug concentration time curve, the mean residential time, the total duration of pharmacological action and bioavailability. Trikatu treatment, however, significantly reduced the elimination half life (t 1/2 beta) and zero time intercept of the elimination phase. The apparent volume of distribution based on the total area under the plasma drug concentration curve [(Vd(area)] and the apparent volume of distribution based on the zero time plasma concentration intercept of the elimination phase [Vd(B)] were significantly higher in trikatu treated animals indicating a better penetration of the drug. Based on the MIC of 0.8 microg/ml of pefloxacin, a priming dose of 6.0 mg/kg and a maintenance dose of 2.21 mg/kg is required to be administered at 8 h intervals. For practical purposes in goats this would mean a priming dose of 6 mg/kg and a maintenance dose of 2 mg/kg given by the oral route, to be repeated at 8 h intervals.
Asunto(s)
Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Cabras/metabolismo , Pefloxacina/administración & dosificación , Pefloxacina/farmacocinética , Fitoterapia/veterinaria , Extractos Vegetales/farmacología , Administración Oral , Animales , Antibacterianos/sangre , Disponibilidad Biológica , Estudios Cruzados , Zingiber officinale , Interacciones de Hierba-Droga , Pefloxacina/sangre , Piper , Piper nigrumRESUMEN
BACKGROUND: Schnitzler syndrome is characterized by chronic urticarial rash and monoclonal IgM gammopathy and is sometimes associated with periodic fever, arthralgias, and bone pain. Current treatment is unsatisfactory. OBSERVATIONS: Eleven patients with Schnitzler syndrome were treated with oral pefloxacin mesylate (800 mg/d). In 10 patients, we observed a dramatic and sustained improvement of urticarial and systemic manifestations. Corticosteroid therapy could be stopped or reduced in 6 patients. In 9 patients, pefloxacin was administered for more than 6 months (Asunto(s)
Antiinfecciosos/uso terapéutico
, Pefloxacina/uso terapéutico
, Síndrome de Schnitzler/tratamiento farmacológico
, Adulto
, Anciano
, Anciano de 80 o más Años
, Antiinfecciosos/administración & dosificación
, Estudios de Cohortes
, Quimioterapia Combinada
, Glucocorticoides/administración & dosificación
, Humanos
, Persona de Mediana Edad
, Pefloxacina/administración & dosificación
, Estudios Retrospectivos
, Resultado del Tratamiento
RESUMEN
BACKGROUND: Acute pancreatitis is a potentially serious condition. It carries an overall mortality rate of 10-15%. Infectious complications account for approximately 80% of deaths from acute pancreatitis, and the question arises whether or not prophylactic antibiotics are useful in the prevention of these complications. Therefore, we performed an evidence-based analysis to assess the effect of available prophylactic antimicrobial treatment on the development of infected necrosis and sepsis, need for surgery, and mortality. METHODS: A comprehensive PubMed search was performed evaluating the value of prophylactic administration of parenteral antibiotics in patients with acute necrotizing pancreatitis. Only articles published in English language between January 1990 and May 2006 were included. The search strategy initially generated 692 articles related to antibiotics in the treatment of acute pancreatitis. This number was reduced to 97 publications related to clinical trials on the same topic. Finally, 10 randomized clinical trials concerning prophylactic parenteral antibiotics in patients with acute necrotizing pancreatitis were identified. We have performed a meta-analysis using the random-effects model to assess the impact of prophylactic antibiotics on development of infected pancreatic necrosis and sepsis, need for surgery, and overall mortality. RESULTS: Patients with necrotizing acute pancreatitis should receive effective antibiotic prophylaxis (i.e., carbapenems intravenously) to decrease the risk of infected necrosis and sepsis and need of surgery. CONCLUSIONS: While providing new insights into key aspects of antibiotic prophylaxis, this evidence-based analysis highlights the need for further clinical trials regarding the indications for antibiotic prophylaxis.
Asunto(s)
Profilaxis Antibiótica , Carbapenémicos/uso terapéutico , Medicina Basada en la Evidencia , Pancreatitis Aguda Necrotizante/complicaciones , Pancreatitis Aguda Necrotizante/tratamiento farmacológico , Sepsis/prevención & control , Carbapenémicos/administración & dosificación , Interpretación Estadística de Datos , Humanos , Imipenem/administración & dosificación , Imipenem/uso terapéutico , Incidencia , Inyecciones Intravenosas , Necrosis/prevención & control , Oportunidad Relativa , Páncreas/patología , Pancreatitis Aguda Necrotizante/diagnóstico por imagen , Pancreatitis Aguda Necrotizante/mortalidad , Pancreatitis Aguda Necrotizante/patología , Pancreatitis Aguda Necrotizante/cirugía , Pefloxacina/administración & dosificación , Pefloxacina/uso terapéutico , Prevalencia , Ensayos Clínicos Controlados Aleatorios como Asunto , Riesgo , Factores de Riesgo , Sepsis/epidemiología , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
The purpose of our work was to develop an ophthalmic delivery system of a flouroquinolone antibiotic, pefloxacin mesylate, based on the concept of ion-activated in situ gelation. Gelrite gellan gum, a novel ophthalmic vehicle, that gels in the presence of mono- or divalent-cations present in the lacrimal fluid, was used as the gelling agent. The developed formulation was compared with marketed eye drops in efficacy of treatment of bacterial conjunctivitis that was induced artificially in rabbits. The formulations were evaluated for rheological characteristics, in vitro release behavior, antimicrobial efficacy, and efficacy against bacterial conjunctivitis. We found that in situ gelling formulations passed the test for sterility. The formulations exhibited a first-order release pattern over 12 hr in in vitro release studies. The developed formulation was effective against selected micro-organisms in antimicrobial efficacy studies. The shelf lives of formulation was >2 years. The formulation demonstrated better therapeutic efficacy compared with standard eye drops because it improved the clinical parameters monitored for prolonged periods. The developed formulations can be considered as a viable alternative to conventional eye drops.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Pefloxacina/administración & dosificación , Polisacáridos Bacterianos/química , Animales , Antiinfecciosos/administración & dosificación , Antiinfecciosos/química , Antiinfecciosos/farmacocinética , Humor Acuoso/química , Disponibilidad Biológica , Conjuntivitis Bacteriana/tratamiento farmacológico , Estabilidad de Medicamentos , Geles/química , Cinética , Masculino , Soluciones Oftálmicas/administración & dosificación , Soluciones Oftálmicas/química , Soluciones Oftálmicas/farmacocinética , Pefloxacina/química , Pefloxacina/farmacocinética , Transición de Fase , Pseudomonas aeruginosa/efectos de los fármacos , Conejos , Reología , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , Lágrimas/químicaRESUMEN
Pefloxacin mesylate is a flouroquinolone antibacterial drug effective in the treatment of bacterial conjunctivitis. The objective of the present work was to develop ocular inserts of pefloxacin mesylate and evaluate their potential for sustained ocular delivery. Reservoir-type ocular inserts were prepared by the film casting technique in teflon coated Petri dishes and characterized in vitro by drug release studies using a flow-through apparatus that simulated the eye conditions. Six formulations were developed, which differed in the ratio of polymers Eudragit RS 100 and Eudragit RL 100 used for the preparation of the rate controlling membrane. All formulations carried 0.72 mg pefloxacin mesylate, 2.69 mg polyvinyl pyrrolidone (PVP) K-30, plasticizers, propylene glycol (10% m/m) and dibutyl phthalate (15%, m/m). The optimized formulation was subjected to microbiological studies, in vivo studies, interaction studies, and stability studies to assess the effectiveness of the formulation. Cumulative drug released from the formulation ranged from 90-98% within 48 to 120 hours. On the basis of in vitro drug release studies, the formulation with Eudragit RS 100/Eudragit RL 100 (4:1) was found to be better than the other formulations and it was selected as an optimized formulation. On the basis of in vitro, microbiological, in vivo drug release, interaction and stability studies, it can be concluded that this ocular insert formulation provided the desired drug release in vitro for 5 days and remained stable and intact at ambient conditions.
Asunto(s)
Antibacterianos/administración & dosificación , Pefloxacina/administración & dosificación , Resinas Acrílicas/química , Administración Tópica , Animales , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Recuento de Colonia Microbiana , Preparaciones de Acción Retardada , Composición de Medicamentos , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Excipientes/química , Femenino , Cinética , Masculino , Pefloxacina/química , Pefloxacina/farmacocinética , Pefloxacina/farmacología , Conejos , Solubilidad , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrolloRESUMEN
Multiple-dose pharmacokinetics of pefloxacin were evaluated in 25 patients with hepatocellular insufficiency. The severity of liver disease was graded A, B or C according to the Child-Pugh classification. Pharmacokinetic parameters evaluated in patients on day 1 of treatment were compared with those computed in 11 healthy volunteers (the control group) after a single dose. Blood samples were taken at frequent intervals after drug administration and assayed by high performance liquid chromatography. The mean age of patients with liver impairment was slightly greater (59.5 years, range 33 to 81 years) than that of the control group (46.7 years, range 42 to 51 years). In the patients with liver disease, the mean (+/- SD) half-life of elimination, although highly variable, was significantly longer (46.3 +/- 42.5 hours) than in the control group (11.3 +/- 3.5 hours, p < 0.001). The total clearance was significantly decreased (1.76 +/- 1.31 L/h vs 6.03 +/- 2.99 L/h in the control group). In groups B and C of the Child-Pugh classification, total body clearance was about 30% of normal values. Elimination half-life increased by 200% in group B and 373% in group C compared with values in healthy volunteers. Intergroup differences (group B vs group C of the Child-Pugh classification) were not statistically significant. The minimum concentrations inhibiting 90% of Gram-negative strains (MIC90) were exceeded by plasma pefloxacin concentrations throughout treatment. For most patients, trough plasma concentrations were above 2 mg/L and peak plasma concentrations averaged 8.5 mg/L. Large inter- and intraindividual variations in the elimination half-life, total clearance and volume of distribution were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Hepatopatías/metabolismo , Pefloxacina/farmacocinética , Adulto , Anciano , Anciano de 80 o más Años , Esquema de Medicación , Tolerancia a Medicamentos , Femenino , Bacterias Gramnegativas/efectos de los fármacos , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Pefloxacina/administración & dosificación , Pefloxacina/metabolismoRESUMEN
BACKGROUND: A number of triple drug regimens using proton pump inhibitors and two antibiotics have been evaluated in the West and reported to achieve Helicobacter pylori eradication rates of over 90%. In developing countries however, these combinations have neither been well evaluated, nor the optimum treatment for H. pylori infection well defined. AIM: To compare the combination of a proton pump inhibitor with a nitroimidazole and another antibiotic in eradicating H. pylori infection and healing duodenal ulcer. METHODS: Sixty consecutive patients with active duodenal ulcer who were positive for H. pylori (by rapid urease test and 14C-urea breath test) were randomized into three treatments groups: (1) LAS (n=21): lansoprazole 30 mg o.m., amoxycillin 500 mg q.d.s. and secnidazole 2 g on alternate days for 2 weeks; (2) LCS (n=18): lansoprazole 30 mg o.m., clarithromycin 500 mg b.d. and secnidazole 2 g on alternate days for 1 week; (3) LPS (n=21): lansoprazole 30 mg o.m., pefloxacin 400 mg o.m. and secnidazole 2 g on alternate days for 2 weeks. Urease and breath tests were performed at 0, 6 and 12 weeks to check for H. pylori eradication. RESULTS: Intention-to-treat eradication rates were as follows: LAS 86%, LCS 83%, LPS 71%; the overall ulcer healing rate was 90% at 6 weeks. CONCLUSIONS: High H. pylori eradication rates were achieved using the amoxycillin- and clarithromycin-based therapies. Fewer side-effects, better compliance and low cost favoured the amoxycillin-based therapy.
Asunto(s)
Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Antiulcerosos/uso terapéutico , Claritromicina/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Metronidazol/análogos & derivados , Omeprazol/análogos & derivados , Pefloxacina/uso terapéutico , Inhibidores de la Bomba de Protones , 2-Piridinilmetilsulfinilbencimidazoles , Adulto , Anciano , Amoxicilina/administración & dosificación , Amoxicilina/efectos adversos , Antibacterianos/administración & dosificación , Antiulcerosos/administración & dosificación , Claritromicina/administración & dosificación , Claritromicina/efectos adversos , Países en Desarrollo , Quimioterapia Combinada , Úlcera Duodenal/tratamiento farmacológico , Úlcera Duodenal/microbiología , Femenino , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Humanos , Lansoprazol , Masculino , Metronidazol/administración & dosificación , Metronidazol/uso terapéutico , Persona de Mediana Edad , Omeprazol/administración & dosificación , Omeprazol/uso terapéutico , Pefloxacina/administración & dosificación , Pefloxacina/efectos adversosRESUMEN
In an attempt to define whether intravenously administered pefloxacin might be appropriate for surgical prophylaxis in prostatectomy, 50 patients undergoing transvesical prostatectomy for benign prostate hyperplasia were given a single intravenous dose of 800 mg; surgery was then performed after 2, 4, 6, 8 or 10 h. Concentrations of pefloxacin were determined in serum and in both the centre and periphery of the prostate adenoma using a microbiological plate assay. Elevated concentrations of pefloxacin were found in the adenoma from 2 h onwards. The central and peripheral concentrations were similar and had a mean value of 4.39 microg/g of tissue. These concentrations were similar to those achieved in serum. Although concentrations of pefloxacin were not determined separately in the intercellular, interstitial or excreted fluid, the tissue levels found were well above the MICs of pefloxacin for the bacteria commonly causing acute and chronic prostatitis. These data suggest the intravenous administration of pefloxacin to be a satisfactory alternative for the surgical prophylaxis before prostatectomy as well as in the therapy of acute prostatitis.
Asunto(s)
Antiinfecciosos/farmacocinética , Pefloxacina/farmacocinética , Premedicación , Próstata/metabolismo , Hiperplasia Prostática/tratamiento farmacológico , Anciano , Antiinfecciosos/administración & dosificación , Antiinfecciosos/uso terapéutico , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Pefloxacina/administración & dosificación , Pefloxacina/uso terapéutico , Próstata/irrigación sanguínea , Prostatectomía , Hiperplasia Prostática/sangre , Hiperplasia Prostática/cirugía , Prostatitis/prevención & controlRESUMEN
The chequerboard technique was used to look for synergistic combinations of ceftazidime, imipenem and pefloxacin. The synergistic combinations were used in vivo in mice experimentally infected with Escherichia coli, Salmonella typhimurium and Pseudomonas aeruginosa. In vitro ceftazidime/imipenem, ceftazidime/pefloxacin and pefloxacin/imipenem combinations showed synergistic effects against Staphylococcus aureus and S. typhimurium and additive effects against P. aeruginosa. Only the ceftazidime/pefloxacin combination was synergistic against E. coli while the ceftazidime/imipenem and pefloxacin/imipenem combinations resulted in additive effects. In vivo, combination of ceftazidime/imipenem against E. coli infection and the pefloxacin/imipenem combination against S. typhimurium infection were protective.
Asunto(s)
Ceftazidima/administración & dosificación , Quimioterapia Combinada/administración & dosificación , Escherichia coli/efectos de los fármacos , Imipenem/administración & dosificación , Pefloxacina/administración & dosificación , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Animales , Sinergismo Farmacológico , Infecciones por Escherichia coli/tratamiento farmacológico , Técnicas In Vitro , Ratones , Pruebas de Sensibilidad Microbiana , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológicoRESUMEN
A 2-month clinical trial of pefloxacin and ofloxacin in previously untreated multibacillary patients was conducted at the Leonard Wood Memorial Leprosy Research Center, Cebu, the Philippines. Treatment with either pefloxacin or ofloxacin resulted in rapid clinical improvement, in this regard pefloxacin appearing somewhat superior. Reactions and side effects were minimal. Single doses of either agent did not result in significant killing of Mycobacterium leprae, but significant bactericidal activity was observed for all fluoroquinolone-treated patients by one week of daily therapy (n = 21), and either agent independently by 3 weeks of daily therapy. At the completion of therapy only two of 10 pefloxacin-treated patients and 0 of 11 ofloxacin-treated patients harboured any detectable viable M. leprae from active lesions, confirming previous work that these fluoroquinolones exhibit bactericidal activity in leprosy patients and more than that found previously for dapsone and clofazimine.
Asunto(s)
Lepra Lepromatosa/tratamiento farmacológico , Mycobacterium leprae/efectos de los fármacos , Ofloxacino/administración & dosificación , Pefloxacina/administración & dosificación , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Lepra Lepromatosa/diagnóstico , Masculino , Filipinas , Probabilidad , Estudios Prospectivos , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Reports of PM/DM associated with haematologic disorders are rare. We describe a 62-year-old man suffering from PM/DM who developed acute myeloid leukemia. The possible paraneoplastic nature of PM/DM in this patient is discussed.
Asunto(s)
Dermatomiositis/complicaciones , Leucemia Mieloide Aguda/complicaciones , Polimiositis/complicaciones , Bacteriemia/etiología , Dermatomiositis/fisiopatología , Resultado Fatal , Insuficiencia Cardíaca/etiología , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/fisiopatología , Masculino , Persona de Mediana Edad , Pefloxacina/administración & dosificación , Pefloxacina/uso terapéutico , Polimiositis/fisiopatología , Teicoplanina/administración & dosificación , Teicoplanina/uso terapéuticoRESUMEN
Ciprofloxacin, pefloxacin, norfloxacin, and ofloxacin were investigated for immunomodulatory activity on humoral and cell-mediated immune responses. Ciprofloxacin and pefloxacin altered the humoral immune responses of mice to sheep red blood cells. This effect was not exhibited by norfloxacin or ofloxacin. All four quinolones did not alter cell-mediated responses. When these antimicrobial agents were tested for their interaction with human polymorphonuclear phagocytic activity, all agents suppressed this activity. In addition, all except norfloxacin showed anti-inflammatory activity.
Asunto(s)
Antiinfecciosos/farmacología , Formación de Anticuerpos/efectos de los fármacos , Inmunidad Celular/efectos de los fármacos , Animales , Antiinfecciosos/administración & dosificación , Ciprofloxacina/administración & dosificación , Ciprofloxacina/farmacología , Hipersensibilidad Tardía/inmunología , Inyecciones Intramusculares , Masculino , Ratones , Norfloxacino/administración & dosificación , Norfloxacino/farmacología , Ofloxacino/administración & dosificación , Ofloxacino/farmacología , Pefloxacina/administración & dosificación , Pefloxacina/farmacología , Fagocitosis/efectos de los fármacosRESUMEN
This is the final report of a large, controlled, multicenter Italian study on immuno- and chemotherapy in adult patients with burns affecting 20 to 95% of total body surface area (mean 35%). The antibiotic treatment of burn patients consisted of topical silver sulfadiazine, short-term antimicrobial chemoprophylaxis with pefloxacin (800 mg i.v. qd) for the first 4 days and polychemotherapy with teicoplanin (800 mg i.v. qd) together with netilmicin (300 mg i.m. qd) in one or more cycles of 5-12 days. At random, half of the patients received thymostimulin, 70 mg i.m. qd for the first month and every other day thereafter. The analysis at completion of 634 valid cases showed that when the results are stratified by means of the Roi risk index, 396 of the 530 patients who contracted wound infection (84%) after chemoprophylaxis were in the first three categories and a mean of 95% survived. Of the remaining 134 patients (Roi index 4-5) only 50% survived. There was no difference in survival of the immunotherapy group in comparison with the parallel group without thymostimulin. The short-term antimicrobial prophylaxis prevented wound infection in only 104 of 634 patients (16%) and they were at low risk (84% Roi index 1). Of the bacterial pathogens involved in septic complications Staphylococcus aureus and Pseudomonas aeruginosa were prevalent (86%): eradication was achieved in 43% of patients and clinical cure or improvement were seen with combination chemotherapy in 64% of all patients, mainly with only one treatment cycle. This value increased to 79% for the 395 protocol-complying patients and went down to 20% in the 135 non-compliers. The total survival of complier and non-complier patients was 447 of the 530 valid patients (84%). The overall mortality of the 634 evaluable patients was 13.1%, ranging from less than 2% to 68%. Burn mortality was directly proportional to the percentage of burned body surface area, to increasing age and other variables of the Roi index, a 50% mortality being associated with a 72.5% total body surface area burned. Normoergic burn patients had a mortality rate of 9.1% versus 35.7% in anergic patients.
Asunto(s)
Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Quemaduras/tratamiento farmacológico , Gentamicinas/uso terapéutico , Netilmicina/uso terapéutico , Teicoplanina/uso terapéutico , Infección de Heridas/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Antiinfecciosos/administración & dosificación , Superficie Corporal , Quemaduras/mortalidad , Quemaduras/patología , Niño , Quimioterapia Combinada , Femenino , Gentamicinas/administración & dosificación , Humanos , Inmunoterapia , Inyecciones Intramusculares , Italia , Masculino , Persona de Mediana Edad , Netilmicina/administración & dosificación , Pefloxacina/administración & dosificación , Pefloxacina/uso terapéutico , Factores de Riesgo , Sulfadiazina/administración & dosificación , Sulfadiazina/uso terapéutico , Teicoplanina/administración & dosificaciónRESUMEN
Sixty patients were enrolled in a prospective, randomized study to evaluate the efficacy of two different regimens for the empirical treatment of continuous ambulatory peritoneal dialysis (CAPD) peritonitis. At presentation, Group I received intraperitoneal vancomycin (1 g) and oral pefloxacin (400 mg b.i.d.), and Group II intraperitoneal vancomycin (1 g) and gentamicin (80 mg loading dose, followed by 15 mg/2 L). Treatment duration was 14 days. Despite randomization, Group I had significantly more patients with primary Candida peritonitis. When fungal peritonitis was excluded from analysis, there were no significant differences in the treatment success rate (Group I, 73.3% vs Group II, 80.0%, p = NS), number of relapses (Group I, 0 vs Group II, 1), and Tenckhoff catheter removal rates (Group I, 26.6% vs Group II, 16.6%, p = NS) between the two groups. The patients treated with pefloxacin had an increased incidence of nausea and vomiting. In selected situations oral pefloxacin may be a suitable substitute for intraperitoneal gentamicin as out-patient therapy for CAPD peritonitis.
Asunto(s)
Quimioterapia Combinada/administración & dosificación , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Peritonitis/tratamiento farmacológico , Administración Oral , Anciano , Femenino , Gentamicinas/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Pefloxacina/administración & dosificación , Peritonitis/etiología , Peritonitis/microbiología , Insuficiencia del Tratamiento , Vancomicina/administración & dosificaciónRESUMEN
A double-blind, randomised study was conducted to compare the efficacy and safety of a combination of pefloxacin and metronidazole versus doxycycline and metronidazole in patients with pelvic inflammatory disease (PID). The clinical diagnosis had to be confirmed by laparoscopy before patients were included. Of the 74 patients who fulfilled the clinical criteria for PID, laparoscopy confirmed the diagnosis in only 40 patients (54%). The microorganism most frequently found as causative pathogen was Chlamydia trachomatis. Both treatment groups showed a good response to the study-medication. At discharge 9 patients in the pefloxacin group (45%) were cured and 10 patients (50%) had improved. In the doxycycline group 7 patients (35%) were cured and 10 patients (50%) had improved. Obviously pefloxacin/metronidazole and doxycycline/metronidazole are equally effective in the treatment of PID.