RESUMEN
OBJECTIVE: To review the effectiveness and safety of rifaximin in the treatment of hepatic encephalopathy (HE). DATA SOURCES: MEDLINE (1990-October 2008) was searched using the terms rifaximin, rifamycins, hepatic encephalopathy, liver cirrhosis, and acute liver failure. Other sources included the bibliographies of pertinent articles as well as programs and abstracts from infectious diseases and gastrointestinal diseases meetings. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the search were evaluated. All primary literature that addressed the efficacy and safety of rifaximin in the treatment of HE was included in this review. DATA SYNTHESIS: HE is a complex neuropsychiatric syndrome seen in patients with liver failure. It is characterized by disturbances in consciousness and behavior, personality changes, fluctuating neurologic signs, asterixis, and electroencephalographic changes. Although the etiology of HE is unknown, the accumulation of several gut-derived toxins such as mercaptans, ammonia, and benzodiazepine has been implicated. Current treatment options for HE include agents that reduce the concentration of these toxins, such as nonabsorbable disaccharides and antibiotics. Several studies have evaluated the use of rifaximin in the treatment of HE. They include a dose-finding study, 9 open-label studies, and 4 double-blind studies comparing rifaximin with either nonabsorbable disaccharides or antibiotics. Commonly used outcomes in most of these studies were changes in portal systemic encephalopathy index and the improvement in HE grade. Despite various limitations of the studies, rifaximin showed superior efficacy compared with lactulose for the treatment of HE, similar efficacy to paromomycin, and similar or greater efficacy than neomycin. Rifaximin was found to be associated with fewer hospitalizations, fewer days of hospitalization, and lower hospitalization charges than were seen with lactulose. Rifaximin also had a better tolerance profile than the comparative agents. CONCLUSIONS: Rifaximin appears to be an effective and safe treatment option for HE. Better-designed studies are needed to characterize its efficacy in the treatment of HE.
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Fármacos Gastrointestinales/uso terapéutico , Encefalopatía Hepática/tratamiento farmacológico , Rifamicinas/uso terapéutico , Animales , Ensayos Clínicos como Asunto/métodos , Fármacos Gastrointestinales/farmacocinética , Encefalopatía Hepática/metabolismo , Humanos , Rifamicinas/farmacocinética , Rifaximina , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
PURPOSE: Significant publications on infectious diseases (ID) pharmacotherapy in 2007 were compiled and summarized. SUMMARY: On January 2, 2008, the 21 members of the Houston Infectious Disease Network (HIDN) were asked to select an article that was published in a peer-reviewed journal between January 1 and December 31, 2007, and write a summary highlighting why the article was significant to the diagnosis or treatment of ID. Articles were selected based on prior "top 10" presentations at major ID and pharmacy meetings or were listed as major articles in prominent ID journals. Priority was given to peer-reviewed publications and nationally recognized clinical treatment guidelines. Nineteen articles and summaries were submitted by HIDN members. The publication listing was distributed to Society of Infectious Diseases Pharmacists members via an Internet survey in early February 2008. Members were asked to select the 10 most significant articles relating to ID pharmacotherapy from the list of 19 and were allowed to add an additional article that was not already listed. A total of 102 individuals participated in the survey. A listing of the top 10 articles published in 2007 and one honorable mention was compiled, and the significance of each article was summarized. CONCLUSION: The increased number of articles in the peer-reviewed medical literature related to the diagnosis and treatment of ID has made it challenging to maintain a contemporary knowledge base of key publications. This summary of significant ID articles published in 2007 can help to alleviate the burden of knowledge management.
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Enfermedades Transmisibles/tratamiento farmacológico , Revisión por Pares/métodos , Publicaciones/clasificación , Femenino , Humanos , Masculino , Publicaciones Periódicas como AsuntoRESUMEN
STUDY OBJECTIVE: To evaluate the efficacy, safety, and lipid-lowering effects after switching from a non-atazanavir-containing, protease inhibitor-based highly active antiretroviral therapy (HAART) to atazanavir-ritonavir-based HAART in patients infected with human immunodeficiency virus (HIV). DESIGN: Multicenter, noncontrolled, retrospective study. SETTING: Three tertiary teaching hospitals. PATIENTS: Thirty-six patients with HIV infection, aged 18 years or older, who were receiving non-atazanavir-containing, protease inhibitor-based HAART that was switched to atazanavir 300 mg-ritonavir 100 mg-based HAART without changes in nucleoside reverse transcriptase inhibitors and confounders known to alter serum lipid levels. MEASUREMENTS AND MAIN RESULTS: Lipid profiles measured 4 weeks-6 months before the switch, as well as follow-up lipid profiles measured 4 weeks-6 months after receiving the new HAART regimen, were evaluated. The switch resulted in the following changes in lipid levels: total cholesterol -9% (p=0.002), low-density lipoprotein cholesterol -13% (p<0.001), high-density lipoprotein cholesterol (HDL) -2% (p=0.431), triglycerides -23% (p=0.007), non-HDL -11% (p=0.002), total cholesterol:HDL ratio -10% (p=0.004), and triglyceride:HDL ratio -24% (p=0.019). A subgroup analysis was conducted on the lipid profiles of nine patients who still met the strict inclusion and exclusion criteria up to 9 months after the switch; it showed that the reductions in their lipid profiles were sustained. In addition, 33% more patients achieved their National Cholesterol Education Panel (NCEP) Adult Treatment Panel (ATP) III cholesterol goals. No significant changes were noted in median (interquartile range) CD4+ counts (372 [236-551] and 361 [217-464] cells/mm(3), p=0.118) or in number of patients with undetectable HIV viral loads ([defined as < 50 copies/ml] 32/36 and 31/36 patients, p>0.05) between baseline and after the switch, respectively. CONCLUSION: Switching to an atazanavir-ritonavir-based HAART regimen was associated with significant improvement in lipid profiles, similar to those seen in clinical trials, without compromising safety or viral and immunologic control. In addition, more patients were able to achieve their NCEP ATP III goals.
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Fármacos Anti-VIH/uso terapéutico , Dislipidemias/tratamiento farmacológico , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Oligopéptidos/uso terapéutico , Piridinas/uso terapéutico , Ritonavir/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa , Sulfato de Atazanavir , Índice de Masa Corporal , Peso Corporal , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/complicaciones , Inhibidores de la Proteasa del VIH/efectos adversos , Humanos , Lípidos/sangre , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Oligopéptidos/efectos adversos , Piridinas/efectos adversos , Estudios Retrospectivos , Ritonavir/efectos adversosRESUMEN
OBJECTIVE: To discuss current and potential treatment options for nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA). DATA SOURCES: A MEDLINE search (1966-January 2007) was conducted to identify English-language literature on pharmacotherapy of nosocomial pneumonia and the bibliographies of pertinent articles. Programs and abstracts from infectious disease meetings were also searched. Search terms included MRSA, nosocomial pneumonia, pulmonary infections, vancomycin, quinupristin/dalfopristin, linezolid, daptomycin, tigecycline, dalbavancin, oritavancin, and ceftobiprole. DATA SELECTION AND DATA EXTRACTION: All articles were critically evaluated and all pertinent information was included in this review. DATA SYNTHESIS: Vancomycin has been the drug of choice for MRSA infections for many years. Recent data suggest that linezolid may be superior to vancomycin in the treatment of MRSA nosocomial pneumonia. However, there are limitations to the available data. Therefore, prospective, randomized studies are needed before linezolid is recommended as the preferred first-line therapy. Other approved agents for nosocomial MRSA infections, such as quinupristin/dalfopristin and daptomycin, should not be used in the treatment of MRSA pneumonia, as they were inferior in clinical trials. Tigecycline has excellent activity against MRSA in vitro, but should not be routinely used for the treatment of MRSA pneumonia, as clinical data are lacking. In a Phase III clinical trial, an anti-MRSA cephalosporin, ceftobiprole, is being evaluated for effectiveness against nosocomial pneumonia. Investigational glycopeptides may eventually have a role in the treatment of nosocomial pneumonia, but data are currently lacking. CONCLUSIONS: Vancomycin is still the drug of choice for treatment of MRSA pneumonia, and linezolid should be used as an alternative agent. Linezolid should carry strong consideration for patients with vancomycin-induced nephrotoxicity or a documented lack of response to vancomycin. Tigecycline and investigational agents with activity against MRSA may be future options for nosocomial pneumonia due to MRSA.
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Acetamidas/uso terapéutico , Antibacterianos/uso terapéutico , Infección Hospitalaria/tratamiento farmacológico , Resistencia a la Meticilina/efectos de los fármacos , Oxazolidinonas/uso terapéutico , Neumonía Estafilocócica/tratamiento farmacológico , Vancomicina/uso terapéutico , Acetamidas/administración & dosificación , Antibacterianos/administración & dosificación , Humanos , Linezolid , MEDLINE , Oxazolidinonas/administración & dosificación , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Vancomicina/administración & dosificaciónRESUMEN
BACKGROUND: An increased prevalence of bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) with a vancomycin hydrochloride MIC of 2 microg/mL was noted in a population of inpatients undergoing hemodialysis at Baptist Memorial Health Care, Memphis, Tennessee. OBJECTIVES: The aims of this study were to determine risk factors for infection with MRSA and to assess the differences in clinical and economic outcomes in patients undergoing hemodialysis with MRSA bacteremia with vancomycin MIC 2 microg/mL versus those with MRSA bacteremia with vancomycin MIC < or =0.5 microg/mL and uninfected controls. METHODS: This retrospective case-control study was conducted at Baptist Memorial Health Care. The study population (inpatients undergoing hemodialysis for MRSA bacteremia with vancomycin MIC 2 microg/mL [high-MIC group], MIC < or = 0.5 microg/mL [low-MIC group], and uninfected controls) was identified. Risk factors and clinical and economic outcomes (costs of hospitalization, nursing, and pharmacy) were determined and compared using univariate and multivariate statistics. RESULTS: Fifty patients with MRSA bacteremia undergoing hemodialysis were identified during the study period (high-MIC group, 17 [11 women, 6 men; mean (SD) age, 60 (17) years]; low-MIC group, 33 [23 women, 10 men; mean (SD) age, 62 (14) years]) and matched with 100 uninfected controls (57 men, 43 women; mean [SD] age, 63 [15] years). Risk factors for MRSA bacteremia found to be associated with high MIC included female sex, higher body mass index (1-point increments), recent surgery, and a history of cardiovascular disease (P < 0.05, P < 0.046, P = 0.04, and P = 0.028, respectively) (multivariate analysis). In the outcomes analysis, mortality was significantly higher in the high-MIC group compared with those in the low-MIC and control groups (35% vs 24% and 15%, respectively; P = 0.022). Total mean (SD) hospitalization costs were significantly higher in the high-MIC group compared with those in the low-MIC group and controls (US $47,624 [$80,534] vs $26,792 [$25,167] and $13,185 [$15,568], respectively; P < 0.001). Nursing costs were almost 6-fold higher in both infected groups compared with those in controls. Pharmacy costs in the low- and high-MIC groups were 3- to 6-fold higher, respectively, compared with those in controls. CONCLUSIONS: Surgery within the previous 6 months and intensive care unit admission were identified as significant risk factors for patients with MRSA bacteremia with a vancomycin MIC 2 microg/mL undergoing hemodialysis. These patients experienced a longer mean hospital length of stay and increased hospital costs compared with patients with MRSA bacteremia with a vancomycin MIC < or =0.5 microg/mL and uninfected controls.