Dual Monoclonal Antibody Therapy for a Severe Asthma Patient.

INTRODUCTION: Omalizumab, the first biological treatment for severe allergic bronchial asthma, has been on the market for more than a decade. Omalizumab was initially considered to be an IgE-blocking agent, and therefore, an inhibitor of the Th2 (allergic or adaptive) cascade. More recently, other monoclonal antibodies for severe eosinophilic asthma have become available, which exert an anti-eosinophilic effect basically by blocking IL5 or its receptor. These agents exert this effect regardless of the origin of the eosinophils (i.e., the adaptive or the innate immune system). CASE STUDY: An oral corticosteroid-dependent allergic asthma patient was treated with omalizumab. After a year of treatment, the improvement remained very limited and the medical team proposed discontinuation. However, the patient felt that her asthma had improved and she refused to give up the therapy, which continued for ten years. The mean accumulated oral corticosteroid dose per month during the last year was around 200 mg; despite this, the FEV1 was low, Since the patient had a high number of eosinophils in peripheral blood, she accepted a switch to mepolizumab when this agent became available. One year later, the clinical improvement was limited and severe symptoms of allergy reappeared, and a combination of monoclonal antiobodies (omalizumab and mepolizumab) was proposed. RESULTS: After 24 months of dual therapy, a marked improvement in the FEV1 was observed, reaching the normal range, and the OC dose was reduced to 2.5 mg per day of prednisolone. No side effects were observed. CONCLUSIONS: In some severe allergic asthma patients with persistently high eosinophil counts in peripheral blood and who are considered non- or mild responders to anti-IgE and anti-IL5 administered individually, a combination of the two antibodies covering the entire T2 spectrum may be effective.

Determinants of empirical antipseudomonal antibiotic prescription for adults with pneumonia in the emergency department.

BACKGROUND: Antipseudomonal antibiotics should be restricted to patients at risk of Pseudomonas aeruginosa infection. However, the indications in different guidelines on community-acquired pneumonia (CAP) are discordant. Our objectives were to assess the prevalence of antipseudomonal antibiotic prescriptions and to identify determinants of empirical antibiotic choices in the emergency department. METHODS: Observational, retrospective, one-year cohort study in hospitalized adults with pneumonia. Antibiotic choices and clinical and demographic data were recorded on a standardized form. Antibiotics with antipseudomonal activity were classified into two groups: a) ß-lactam antipseudomonals (ß-APS), including carbapenems, piperacillin / tazobactam or cefepime (in monotherapy or combination) and b) monotherapy with antipseudomonal quinolones. RESULTS: Data were recorded from 549 adults with pneumonia, with Pseudomonas aeruginosa being isolated in only nine (1.6%). Most (85%) prescriptions were compliant with SEPAR guidelines and 207 (37%) patients received antibiotics with antipseudomonal activity (14% ß-APS and 23% levofloxacin). The use of ß-APS was independently associated with ICU admission (OR 8.16 95% CI 3.69-18.06) and prior hospitalization (OR 6.76 95% CI 3.02-15.15), while levofloxacin was associated with negative pneumococcal urine antigen tests (OR 3.41 95% CI 1.70-6.85) but negatively associated with ICU admission (OR 0.26 95% CI 0.08-0.86). None of these factors were associated with P aeruginosa episodes. In univariate analysis, prior P aeruginosa infection/colonization (2/9 vs 6/372, p = 0.013), severe COPD (3/9 vs 26/372, p = 0.024), multilobar involvement (7/9 vs 119/372, p = 0.007) and prior antibiotic (6/9 vs 109/372, p = 0.025) were significantly associated with P aeruginosa episodes. CONCLUSIONS: Antipseudomonal prescriptions were common, in spite of the very low incidence of Pseudomonas aeruginosa. The rationale for prescription was influenced by both severity-of-illness and pneumococcal urine antigen test (levofloxacin) and prior hospitalization and ICU admission (ß-APS). However, these factors were not associated with P aeruginosa episodes. Only prior P aeruginosa infection/colonization and severe COPD seem to be reliable indicators in clinical practice.

Benefits of low weekly doses of methotrexate in steroid-dependent asthmatic patients. A double-blind, randomized, placebo-controlled study.

BACKGROUND: Though several drugs have been tested, the choice of the ideal steroid-sparing agent in steroid-dependent asthmatic patients remains unclear. Our objective was to evaluate the efficacy and tolerance of methotrexate in low weekly doses in order to decrease chronic oral steroid requirements in asthmatic patients. DESIGN: double blind randomized placebo-controlled study. SETTING: The study was performed in a 760-bed teaching hospital. PATIENTS: 46 steroid-dependent asthmatic patients were randomized. INTERVENTIONS: PATIENTS received 10mg of methotrexate or placebo once weekly for a year. The 6-methylprednisolone was progressively tapered (2mg/day every two weeks) until FEV1 diminished by 5% or more; 6-methylprednisolone was then increased until the previous FEV1 was reached, and the procedure was repeated throughout follow-up. MEASUREMENTS: Blood and urine analyses and bone densitometry were performed at entry and at the end of the study. Pulmonary function was tested monthly during the first three months and then every three months until the end. RESULTS: Thirty-nine patients were evaluated at interim analysis. A 54.8% decrease (9.5+/-4.9 mg/day) in 6-methylprednisolone dose was observed in the methotrexate group and a 4.4% decrease (0.5+/-7.2 mg/day) in the placebo group (P<0.001). There was no significant decrease of FEV1 in either group. No changes in bone metabolism were observed except for a non-statistically significant increase in osteocalcin levels in the treated group compared to a decrease in the placebo group. Toxicity was mild. CONCLUSIONS: (1) Methotrexate is an effective steroid-sparing agent. (2) A dosage lower than the one recommended in the literature is effective. (3) Tolerance is good. (4) No benefit or detrimental effects in bone metabolism were observed after one year.

[Evolution of the use of antibiotics in a hospital long-term care center in Catalonia]. / Evolución del uso de antibióticos en un centro sociosanitario de ámbito hospitalario en Cataluña.

INTRODUCTION: Advanced age, together with immune system changes, malnutrition, chronic disease, and the institutional environment, all contribute to a higher risk of acquiring infection in the elderly. Antibiotics are widely used in geriatric centers, but often their use is not optimal. MATERIAL AND METHODS: Study carried out during the period 1992-1999 in Centro Sociosanitario Albada (Sabadell, Spain). Data were taken from the Pharmacy Department's unidose registry. We determined the most frequently used antibiotics, the hospital units with highest consumption, the variation in these factors over time, and related costs. RESULTS: A progressive increase in overall antibiotic consumption was observed during the first 5 years of the study with subsequent stabilization. The units showing highest consumption were the Moderate and Highly-Dependent Chronic Unit, the Palliative Care Unit and the Convalescence and Rehabilitation Unit, with significant increases in the Palliative Care Unit in the last two years of the study. Amoxicillin-clavulanate, ciprofloxacin and norfloxacin were the most extensively used antibiotics. Cost increases were seen in the last three years despite the stabilization of antibiotic use. CONCLUSION: We observed a change in the consumption and profile of the antimicrobial agents used in our setting, probably related to changes in the population, increases in parenteral treatment and changes in the criteria for treatment of terminal patients. The establishment of controls for antibiotic use in long-term care centers would lead to improvements in the quality of the care provided.

Evolución del uso de antibióticos en un centro sociosanitario de ámbito hospitalario en Cataluña / Evolution of the use of antibiotics in a hospital long-term care center in Catalonia

INTRODUCCIÓN. La edad avanzada junto con las modificaciones en el sistema immunitario, la malnutrición, la coexistencia de enfermedades crónicas y la propia institucionalización comportan un riesgo de adquisición de infecciones y el consiguiente uso de antibióticos, que no siempre es adecuado. MATERIAL Y MÉTODOS. Estudio realizado desde 1992 hasta 1999 en el Centro Sociosanitario Albada (CSSA). Se analizan los antibióticos más utilizados, las unidades de mayor consumo, su variación en el tiempo y los costes por consumo, a partir del registro de unidosis de que dispone el servicio de farmacia de nuestro hospital. RESULTADOS. Se observó un aumento progresivo en el consumo global de antibióticos durante los primeros 5 años de estudio, con una tendencia posterior a la estabilización. Las unidades de mayor consumo fueron la Unidad de Crónicos de Media y Alta Dependencia, la Unidad de Cuidados Paliativos y la Unidad de Convalecencia y Rehabilitación, con un incremento relevante en el consumo en la Unidad de Cuidados Paliativos en los últimos 2 años del estudio. Los antibióticos más utilizados fueron amoxicilina-ácido clavulánico, ciprofloxacino y norfloxacino. Se ha observado un incremento de los costes en los últimos 3 años, a pesar de la estabilización en la prescripción de antibióticos. CONCLUSIÓN. Se aprecia un cambio en el consumo y el perfil de antibióticos utilizados, probablemente relacionado con cambios en la población, aumento del tratamiento parenteral y cambio de criterio en el tratamiento de pacientes terminales. Establecer un control del uso de antibióticos en centros sociosanitarios permitiría mejorar la calidad asistencial (AU)