Antimicrobial therapy for pulmonary pathogenic colonisation and infection by Pseudomonas aeruginosa in cystic fibrosis patients.

Pseudomonas aeruginosa colonisation has a negative effect on pulmonary function in cystic fibrosis patients. The organism can only be eradicated in the early stage of colonisation, while reduction of bacterial density is desirable during chronic colonisation or exacerbations. Monthly, or at least 3-monthly, microbiological culture is advisable for patients without previous evidence of P. aeruginosa colonisation. Cultures should be performed at least every 2-3 months in patients with well-established colonisation, and always during exacerbations or hospitalisations. Treatment of patients following the first isolation of P. aeruginosa, but with no clinical signs of colonisation, should be with oral ciprofloxacin (15-20 mg/kg twice-daily for 3-4 weeks) plus inhaled tobramycin or colistin (intravenous treatment with or without inhaled treatment can be used as an alternative), while patients with acute infection should be treated for 14-21 days with high doses of two intravenous antimicrobial agents, with or without an inhaled treatment during or at the end of the intravenous treatment. Maintenance treatment after development of chronic P. aeruginosa infection/colonisation (pathogenic colonisation) in stable patients (aged>6 years) should be with inhaled tobramycin (300 mg twice-daily) in 28-day cycles (on-off) or, as an alternative, colistin (1-3 million units twice-daily). Colistin is also a possible choice for patients aged<6 years. Treatment can be completed with oral ciprofloxacin (3-4 weeks every 3-4 months) for patients with mild pulmonary symptoms, or intravenously (every 3-4 months) for those with severe symptoms or isolates with ciprofloxacin resistance. Moderate and serious exacerbations can be treated with intravenous ceftazidime (50-70 mg/kg three-times-daily) or cefepime (50 mg/kg three-times-daily) plus tobramycin (5-10 mg/kg every 24 h) or amikacin (20-30 mg/kg every 24 h) for 2-3 weeks. Oral ciprofloxacin is recommended for patients with mild pulmonary disease. If multiresistant P. aeruginosa is isolated, antimicrobial agents that retain activity are recommended and epidemiological control measures should be established.

Relationship between pharmacokinetics and pharmacodynamics of beta-lactams and outcome.

The in-vitro susceptibility of an organism and the pharmacokinetics of an antimicrobial agent are two basic factors on which the choice of standardised treatment regimens is based. However, the inter-individual variability of these factors, which modifies the exposure of bacteria to an antibiotic in terms of time and quantity, is not usually taken into account. In 87 patients treated with beta-lactams (ceftriaxone, cefepime or piperacillin), the probability of failure was greater when the infectious process was located in tissues with barriers to the distribution of beta-lactams. Mean MICs of piperacillin and cefepime, but not ceftriaxone, were below the breakpoints in cases of both recovery and failure, but organisms isolated from patients with a poor outcome had higher MICs. Therefore, the use of breakpoints to determine the susceptibility of microorganisms was not satisfactory in predicting the outcome for a large number of patients. If MICs are determined and plasma concentrations are monitored, dosages can be adjusted according to these parameters, thereby allowing antibiotic treatment to be individualised.

Rapid liquid chromatographic assay for the determination of acetaminophen in plasma after propacetamol administration: application to pharmacokinetic studies.

A simple method for the rapid estimation of acetaminophen in plasma is described here. p-Propionamidophenol was used as internal standard. The assay involved a single ethyl acetate extraction and liquid chromatographic analysis at a wavelength of 242 nm using a reversed-phase encapped column, with a mobile phase of acetonitrile and 0.005 M potassium dihydrogen phosphate adjusted at pH 3.00. The limit of quantitation of acetaminophen by this method was 0.05 microg ml(-1), only 0.1 ml of the plasma sample was required for the determination. The calibration graph was linear from 0.05 to 100 microg ml(-1). Intra and inter-day precision (CV) did not exceed 8.93%. Mean recoveries of 90.31% with a CV of 1.38% were obtained. Applicability of the method was demonstrated by a pharmacokinetic study in normal volunteers who received 2 mg propacetamol.

A sensitive method for the determination of gemfibrozil in human plasma samples by RP-LC.

A sensitive high-performance liquid chromatographic assay for the quantitative determination of gemfibrozil is described in this work. Ibuprofen was used as internal standard. The assay involved a single cyclohexane extraction and LC analysis with fluorescence detection. Chromatography was performed at 40 degrees C on a Hypersil ODS column. The mobile phase was a mixture of a solution of phosphoric acid 0.4% and acetonitrile (45:55). The method was validated. The detection limit of this method was 0.025 microg ml(-1); only 0.5 ml of the plasma sample was required for the determination. The calibration graph was linear from 0.05 to 0.5 microg ml(-1) and required a cubic equation from 0.5 to 30 microg ml(-1). Intra and inter-day precision (C.V.) did no exceed 15%. Mean recoveries were of 90.15+/-6.9% (C.V.'s<8%) for gemfibrozil and 93.10% for ibuprofen Applicability of the method was demonstrated by a pharmacokinetic study in normal volunteers who received gemfibrozil by oral route.

[Pharmacology of antimicrobials used in the treatment of serious Gram-positive bacteria infections]. / Farmacología de antimicrobianos utilizados en el tratamiento de las infecciones graves por bacterias grampositivas.

Antimicrobials with specific activity against Gram-positive cocci (glycopeptides, oxazolidinones and streptogramins) have pharmacokinetic differences that are important to know. Linezolid and teicoplanin can be administered extravascularly due to their good bioavailability, allowing their use as sequential therapy in patients requiring prolonged treatment. All of these antimicrobials have an adequate distribution in extracellular tissues, even teicoplanin, due to the balance between the fraction that is bound and unbound to plasma proteins and its long terminal half-life. As the elimination of glycopeptides is almost exclusively renal, it is necessary to perform a posology adjustment in patients with renal failure. Quinupristin/dalfopristin and linezolid are metabolized by the liver, but CYP450 is only involved in streptogramin elimination.

Clinical pharmacokinetics of ferric natural protein in iron-deficient females.

Although iron therapy is very common, few studies have assessed iron absorption or iron kinetics in general, particularly with Fe(3+). This was the primary objective of this study, with assessment of tolerance as a secondary objective. Eight nonsmoking iron-deficient females without other associated pathologies, with an average age of 21.62 +/- 1.69 years, were studied. The diagnosis of iron deficiency was established by determination of sideraemia (28.7 +/- 13.5 microg/dl), iron binding capacity (380.5 +/- 70.2 microg/dl) and ferritin (5 +/- 1.4 microg/L) on the prestudy visit. The women remained in the Phase I Unit during days 0, 1, 2 and 3 of the study. A serum iron concentration curve was obtained daily from blood samples drawn at 0, 1, 2, 4, 6, 8 and 12 hours postdose. Therapy with ferric natural protein (ferrimannitol ovoalbumin) 40mg twice daily was started on day 1 of the study and continued for 30 days. The following parameters were evaluated: area under the curve (AUC(0-12h)), peak iron concentration (C(max)) and time to reach peak concentration (t(max)). Serum iron concentration-time curves were practically flat on day 0, but showed an increase following ferric therapy (Friedman, p < 0.05), confirming the usefulness of the postabsorption test and good absorption of ferric iron (Fe(3+)). The increase in AUC (314.65 +/- 67.9 to 1174.44 +/- 1071.8 microg/dl.h) and C(max) (49 +/- 24.4 to 146 +/- 101.9 microg/dl) from day 1 and the correlation between both parameters (r(2) > 0.85, p

[Treatment with tacrolimus in autoimmune diseases]. / Posibles indicaciones del tratamiento de las enfermedades autoinmunes con tacrolimus.

Tacrolimus is an immunosuppressive drug used most successfully as a primary drug to suppress the rejection of transplants. Tacrolimus may also be useful as a novel therapy for autoimmune disease. There are various reports in the bibliography about the use of tacrolimus in the treatment of some autoimmune diseases: inflammatory bowel disease, autoimmune hepatitis, cutaneous, neurologic, renal, endocrine or eye disease. In this review of more than 130 papers, we discuss the rationale for the use of tacrolimus in autoimmune disease and report the clinical experience with the drug in the management of a variety of autoimmune diseases. But, although there are a lot questions that require future research (dose, duration of treatment, when to begin tacrolimus treatment, how to monitor it, etc.), there is also wide experience with tacrolimus in the treatment of this type of disease.

[Levofloxacin. Clinical experience with long-term treatment of osteoarticular infections]. / Levofloxacino. Experiencia clínica en tratamientos de larga duración de infecciones osteoarticulares.

We evaluated the efficacy and safety profile of the long-term administration of levofloxacin in osteoarticular infections. For this purpose, 50 patients were included during the years 1999 to 2001 on an initial estimation to be under treatment with this antibiotic for at least 4 weeks. Forty six percent (46%) of patients were male and received treatment during a mean-time of 122.8 days. In forty one of a total of forty nine evaluable patients (83.7%) outcome was considered satisfactory with a total recovery or improvement of disease. Clinical and analytical series of examinations were performed, with no significant abnormalities being observed. Five (5) patients presented a total of 7 adverse events: gastrointestinal intolerance (3), oral mycosis (1), petechia (1), parestesia (1) and pruriginous rash(1). Only in three cases interruption of therapy was considered necessary. In conclusion, levofloxacin presents an adequate efficacy and is a well-tolerated therapy; both characteristics make it an appropriate treatment for those infections that require long-term therapy.

Economic impact of an electronic alert system to prevent venous thromboembolism in hospitalised patients.

OBJECTIVES: The prevention of venous thromboembolism (VTE) is a priority for improved safety in hospitalised patients. Worldwide, there is growing concern over the undersuse of appropriate thromboprophylaxis. Computerised decision support improves the implementation of thromboprophylaxis and reduces inpatient VTE. However, an economic assessment of this approach has not yet been performed. OBJECTIVES: To evaluate the economic impact of an electronic alert (e-alert) system to prevent VTE in hospitalised patients over a 4year period. PATIENTS/METHODS: All hospitalised patients at a single institution during the first semesters of 2005-2009 (n=32280) were included. All cases of VTE developed during hospitalisation were followed and direct costs of diagnosis and management collected. RESULTS: E-alerts achieved a sustained reduction of the incidence of in-hospital VTE, OR 0.50 (95% CI, 0.29-0.84), the impact being especially significant in medical patients, OR 0.44 (95% CI, 0.22-0.86). No increase in prophylaxis-related bleeding was observed. In our setting, the mean direct cost (during hospitalisation and after discharge) of an in-hospital VTE episode is €7058. Direct costs per single hospitalised patient were reduced after e-alerts from €21.6 to €11.8, while the increased use of thromboprophylaxis and the development of e-alerts meant €3 and €0.35 per patient, respectively. Thus, the implementation of e-alerts led to a net cost saving of €6.5 per hospitalised patient. Should all hospitalised patients in Spain be considered, total yearly savings would approach €30million. CONCLUSIONS: E-alerts are useful and cost-effective tools for thromboprophylaxis strategy in hospitalised patients. Fewer thromboembolic complications and lower costs are achieved by its implementation.

Development and validation of a sensitive method for the determination of ganciclovir in human plasma samples by reversed-phase high-performance liquid chromatography.

A rapid, sensitive, specific liquid chromatographic method has been developed for the determination of therapeutic levels of ganciclovir in human plasma. Plasma (1 ml) and acyclovir (I.S.) were treated with 50% trichloroacetic acid. The supernatant was neutralized with 2 M NaOH and purified with chloroform. The aqueous phase (80 microl) was analyzed by a 3-microm Hypersil ODS C18 column with 0.04 M triethylamine-0.1 M sodium dihydrogen phosphate monohydrate as the mobile phase (1 ml/min) and ultraviolet detection at 254 nm. Calibration was linear from 50 to 10000 ng/ml. Intra- and inter-day C.V. did no exceed 6.65%. The detection limit was about 10 ng/ml.

Rotura bilateral del tendón Aquiles secundario a levofloxacino / Bilateral achilles’ tendon rupture secondary to levofloxacin

Introducción. Las fluoroquinolonas presentan una variedad de efectos secundarios que incluyen la fototoxicidad, las alteraciones dermatológicas y las tendinopatías. Éstas últimas son más frecuentes en tendones que han tenido gran estrés, como el Aquiles, pero su afección bilateral es muy infrecuente. Caso. Presentamos el caso de una paciente de 83 años que al segundo día de tratamiento con levofloxacino comienza con dolor en ambos tendones de Aquiles, que en la valoración clínica y radiológica al mes de iniciados los síntomas se aprecia rotura de ambos tendones, y requiere de tratamiento quirúrgico mediante tenorrafia y colgajos de fascia de gemelos con buena evolución posterior. Conclusiones. Se realiza una revisión de la bibliografía (AU)

Introduction. Fluoroquinolones possess several side effects including phototoxicity, skin alterations and tendinopathies. The latter are more frequent in tendons subjected to heavy stresses such as the Achilles’ tendon. However, bilateral involvement is rare.Clinical case. We present the case of an 83-year-old patient who, 2 days after beginning treatment with levofloxacin developed pain in both Achilles’ tendons. A clinical-radiological assessment one month after the onset of symptoms revealed rupture of both tendons, which made surgical treatment necessary. A tenorrhaphy was performed with gastrocnemius fascial flaps. The patient's evolution was satisfactory. Conclusions. A literature review was performed (AU)

Tratamiento antimicrobiano frente a la colonización pulmonar por Pseudomonas aeruginosa en el paciente con fibrosis quística / No disponible

No disponible

Perfil de seguridad de las fluoroquinolonas / Safety profile of the fluoroquinolones

No disponible