New perspectives for reassessing fosfomycin: applicability in current clinical practice / Nuevas perspectivas para la reevaluación de la fosfomicina: aplicabilidad en la práctica clínica actual

Fosfomycin is a bactericidal antibiotic that interferes with cell wall synthesis. The drug therefore has a broad spectrum of activity against a wide range of Gram-positive and Gram-negative bacteria. Both the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have started review processes of the accumulated information on the use of fosfomycin and on information from new clinical trials. The intent is to establish usage terms in Europe and to authorize the sale of fosfomycin in the US. This monograph reviews the most current aspects of the compound. From the microbiological point of view, fosfomycin's single mechanism of action can provide a synergistic effect to other classes of antibiotics, including β-lactams, aminoglycosides, lipopeptides and fluoroquinolones. The resistance mechanisms include the reduced intracellular transport of the antibiotic, the change in target and the direct inactivation of the antibiotic by metalloenzymes and kinases; however, the clinical impact of some of these mechanisms has not yet been elucidated. The lack of agreement in determining the sensitivity cutoffs between the Clinical and Laboratory Standards Institute (CLSI) (≤64 mg/L) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (≤32 mg/L), the fact that a number of microorganisms require a higher MIC (Klebsiella spp. , Enterobacter spp. , Serratia spp. , Pseudomonas aeruginosa) and the drug's different effective concentrations against Gram-positive and Gram-negative bacteria have resulted in recommended dosages for treating multiresistant microorganism infections that vary between 8 and 12 g/day for Gram-positive bacteria and 16 and 24 g/day for Gram-negative bacteria. Fosfomycin has 3 presentations (intravenous with disodium salt, oral with calcium salt and combined with tromethamine),has good distribution in tissues and abscesses and is well tolerated. The pharmacodynamic ratio of dosage production for fosfomycin is AUC/MIC. However, the pharmacokinetics/pharmacodynamic ratio could be optimized in daily practice based on the pathogen, the patient's clinical profile or the infection model. Fosfomycin is the treatment of choice for cystitis in immunocompetent patients, patients with transplants, pregnant women and in pediatric settings. The drug is especially useful due to its microbiological activity and oral posology in cystitis caused by ESBL bacteria. Administer intravenously at high doses and combined with other antimicrobial agents. Fosfomycin has been useful in treating infections by multiresistant Gram-negative bacteria, such as Enterobacteriaceae, carbapenemase carriers and P. aeruginosa, extensively resistant or panresistant in urinary infections and in skin and soft tissue. Fosfomycin has also been shown active in combination with daptomycin or imipenem in osteoarticular infections by methicillin-resistant Staphylococcus aureus. Fosfomycin is an old antibiotic that still has much to reveal

Fosfomicina es un antibiótico bactericida que interfiere en la síntesis de la pared celular. Tiene por tanto un amplio espectro de actividad contra una amplia gama de bacterias grampositivas y gramnegativas. Tanto la EMA como la FDA han iniciado trámites de revisión de la información acumulada sobre su uso y los nuevos ensayos clínicos. La intención es establecer los términos de uso en Europa y autorizar su comercialización en los EEUU. El presente monográfico trata de revisar los aspectos más actuales de la molécula. Desde el punto de vista microbiológico, su mecanismo de acción único puede proporcionar un efecto sinérgico a otras clases de antibióticos, incluidos los β-lactámicos, aminoglucósidos y fluoroquinolonas. Entre los mecanismos de resistencia se encuentran la disminución del transporte intracelular del antibiótico, la alteración en la diana y la inactivación directa del antibiótico por metaloenzimas o cinasas, sin embargo, la repercusión en la clínica de algunos de estos mecanismos no está aún contrastada. La falta de acuerdo para determinar los puntos de corte de sensibilidad entre CLSI (≤64 mg/L) y EUCAST (≤32 mg/Ll), el hecho de que algunos microorganismos exijan una CMI superior (Klebsiella spp, Enterobacter spp, Serratia spp, Pseudomonas aeruginosa) y la diferente concentración efectiva del fármaco ante grampositivos o gramnegativos hace que la recomendación posológica en el tratamiento de las infecciones por microorganismos multirresistentes pueda fluctuar entre 8 y 12 g/día frente a grampositivos y 16 y 24 g/día frente a gramnegativos. Fosfomicina tiene tres presentaciones (endovenosa en sal disódica, oral en sal cálcica o asociada a trometamina) tiene buena distribución en tejidos y abscesos y es bien tolerada. El cociente farmacodinámico de la producción posológica para fosfomicina es AUC/CMI. Sin embargo, se podría optimizar el cociente PK/PD en la práctica diaria en la función del patógeno, el perfil clínico del paciente o el modelo de infección. Fosfomicina es el tratamiento de la elección en cistitis en inmunocompetentes, en trasplantados, en gestantes y en el ámbito pediátrico. Resulta especialmente útil para su actividad microbiológica y por su posología oral en cistitis producidas por bacterias BLEE. Administrar por vía endovenosa a altas dosis y en combinación con otros antimicrobianos. Se ha encontrado útil en el tratamiento de las infecciones por gramnegativos, multirresistentes, como enterobacterias, portadoras de carbapenemasas y P. aeruginosa, extensivamente o Panrresistentes en infecciones urinarias y en piel y partes blandas. También se ha mostrado activo en combinación con daptomicina o imipenem en infección osteoarticular por Staphylococcus aureus resistente a meticilina. Estamos ante un antibiótico antiguo que queda aún por descubrir

Treatment of elderly patients with uncomplicated diverticulitis, even with comorbidity, at home.

BACKGROUND: Elderly patients with uncomplicated diverticulitis are usually hospitalized. The aim of this study is to compare the outcomes of elderly patients with uncomplicated diverticulitis who were treated at home versus traditional Hospitalization. METHODS: Prospective study from March 2011 to September 2012 including patients over 70 years with uncomplicated diverticulitis admitted to Hospital at Home Unit and to Conventional Hospitalization from the Emergency Department. Patients with ß-lactam allergy or who required admission to Conventional Hospitalization for other pathology were excluded. All patients were given intravenous antibiotic. Patients transferred to Hospital at Home stayed 24h in the Observation Ward within the Emergency Department prior to discharge. Characteristics and outcomes of patients are analyzed. RESULTS: 34 patients were treated at home and 18 in hospital. Mean age was similar in both groups (77 vs 79). The oldest patient treated at home was 90 years old. 64% of patients treated in Hospital at Home had comorbidity vs 68% in Conventional Hospitalization. 11% of patients treated at home were diabetic. Thickening colonic wall was present in 100% of patients. 38% of patients treated at home had free fluid vs 42% treated in Hospital. All patients had a good clinical evolution. None of the patients treated at home was transferred to Hospital. Home treatment was associated with a cost reduction of 1368 euros per patient. CONCLUSIONS: Treatment at home of elderly patients with uncomplicated diverticulitis is as safe and effective as treatment in Hospital, even if patient has comorbidity.

Home treatment of patients with acute cholecystitis.

BACKGROUND: Patients with acute cholecystitis are treated in Hospital. The aim of the study was to analyze the security and efficacy of treating not-operated-on patients with acute cholecystitis in Hospital in the Home (HIH). METHODS: Prospective study from January 2010 to May 2011 including all patients diagnosed with acute cholecystitis, not operated on and without comorbidities admitted to HIH Unit from the Emergency Department Short Stay Unit and Observation Unit. Patients were treated with ertapenem for at least one week. Intravenous treatment was followed by oral therapy to complete 14 days of antibiotic treatment. Patient characteristics, clinical course, need for return to hospital during admission to HIH, and admission to hospital in the month after discharge from HIH are analyzed. RESULTS: 25 patients were included. Mean age was 59 years (34-82). Upon arrival to the Emergency Department, all patients suffered abdominal pain, 60% had fever, and 32% vomiting. 48% of patients had a leukocyte count over 13,000 cells/µl. All patients had cholelithiasis and a distended gallbladder. 56% showed thickening of the gallbladder wall. Fluid accumulation around the gallbladder was noted in 16% of the cases. Murphy's sign proved positive in 44%. All patients showed a favorable course. No patient required hospital readmission during stay in HIH or in the month after discharge. All patients expressed their satisfaction with treatment at home. CONCLUSIONS: Patients with acute cholecystitis and without comorbidities can be safely and effectively treated in HIH after a short monitoring period in hospital.