Long-Term Impact of Suppressive Antibiotic Therapy on Intestinal Microbiota.

The aim was to describe the safety of indefinite administration of antibiotics, the so-called suppressive antibiotic therapy (SAT) and to provide insight into their impact on gut microbiota. 17 patients with SAT were recruited, providing a fecal sample. Bacterial composition was determined by 16S rDNA massive sequencing, and their viability was explored by PCR-DGGE with and without propidium monoazide. Presence of antibiotic multirresistant bacteria was explored through the culture of feces in selective media. High intra-individual variability in the genera distribution regardless of the antibiotic or antibiotic administration ingestion period, with few statistically significant differences detected by Bray-Curtis distance-based principle component analysis, permutational multivariate analysis of variance and linear discriminant analysis effect size analysis. However, the microbiota composition of patients treated with both beta-lactams and sulfonamides clustered by a heat map. Curiously, the detection of antibiotic resistant bacteria was almost anecdotic and CTX-M-15-producing E. coli were detected in two subjects. Our work demonstrates the overall clinical safety of SAT and the low rate of the selection of multidrug-resistant bacteria triggered by this therapy. We also describe the composition of intestinal microbiota under the indefinite use of antibiotics for the first time.

Extended-pulsed fidaxomicin versus vancomycin in patients 60 years and older with Clostridium difficile infection: cost-effectiveness analysis in Spain.

The cost of treating Clostridium difficile infection (CDI) in Spain is substantial. Findings from the randomised, controlled, open-label, phase 3b/4 EXTEND study showed that an extended-pulsed fidaxomicin (EPFX) regimen was associated with improved sustained clinical cure and reduced recurrence of CDI versus vancomycin in patients aged 60 years and older. We assessed the cost-effectiveness of EPFX versus vancomycin for the treatment of CDI in patients aged 60 years and older from the perspective of the National Health System (NHS) in Spain. We used a Markov model with six health states and 1-year time horizon. Health resources, their unit costs and utilities were based on published sources. Key efficacy data and transition probabilities were obtained from the EXTEND study and published sources. A panel of Spanish clinical experts validated all model assumptions. In the analysis, 0.638 and 0.594 quality-adjusted life years (QALYs) per patient were obtained with EPFX and vancomycin, respectively, with a gain of 0.044 QALYs with EPFX. The cost per patient treated with EPFX and vancomycin was estimated to be €10,046 and €10,693, respectively, with a saving of €647 per patient treated with EPFX. For willingness-to-pay thresholds of €20,000, €25,000 and €30,000 per QALY gained, the probability that EPFX was the most cost-effective treatment was 99.3%, 99.5% and 99.9%, respectively. According to our economic model and the assumptions based on the Spanish NHS, EPFX is cost-effective compared with vancomycin for the first-line treatment of CDI in patients aged 60 years and older.

Conocimiento y percepciones de los médicos residentes españoles sobre el uso de antibióticos y sus resistencias: resultados de una encuesta multicéntrica / Knowledge and perceptions of junior and senior Spanish resident doctors about antibiotic use and resistance: Results of a multicenter survey

Antecedentes La resistencia a los antibióticos ha sido reconocida como un problema a nivel mundial. Nuestro objetivo fue conocer las percepciones de los médicos residentes españoles, respecto al uso de antibióticos y la resistencia a los mismos. Métodos Estudio descriptivo transversal mediante encuesta on-line, a todos los médicos residentes de 5 hospitales terciarios, realizada entre septiembre y noviembre de 2010. Se envió un enlace a la encuesta a través de correo electrónico a 844 médicos residentes. El cuestionario evalúa las características demográficas, el conocimiento de los residentes sobre algunos microorganismos de relevancia clínica conocida, sus hábitos en el proceso de prescripción de antibióticos y sus percepciones sobre las actividades encaminadas a mejorar el uso de antimicrobianos. Resultados Se recibieron 279 respuestas que corresponden al 33,05% de todos los residentes encuestados. La tasa de respuesta fue mayor entre los residentes de los primeros años que entre los residentes de los últimos años (39,95% vs 26,12%, p<0,05). Los residentes de todos los hospitales, especialidades y grado de experiencia, en su mayoría consideran que la resistencia antimicrobiana es un problema importante a nivel nacional (94,3%), en su institución (91,3%) y para su práctica diaria (83,8%). Los residentes consideran su formación respecto a los antibióticos insuficiente, aunque, hasta el 86,5% había recetado antibióticos en el último mes. Preferían la disponibilidad de guías locales de uso de antibióticos (65%), sesiones de enseñanza específicas, equipos de gestión de antimicrobianos o mayor facilidad de acceso a la asesoría de s (..) (AU)

Background Antibiotic resistance has been recognized as a worldwide problem. Our aim was to assess the perceptions of Spanish residents about antibiotic use and resistance. Methods An online cross-sectional survey was conducted on all resident doctors in five teaching hospitals (September to November 2010). A link to the questionnaire was e-mailed to 844 doctors. The questionnaire collected demographical characteristics, residents’ knowledge about microorganisms of known clinical relevance, their habits in the antibiotic prescription process, and their perceptions on the activities aimed to improve antibiotic use. Results We received 279 responses corresponding to 33.05% of all targeted residents. The response rate was higher among junior than among senior residents (39.95% vs. 26.12%; p<0.05). Residents of all hospitals, specialties and seniority mostly considered that antimicrobial resistance was a significant problem at national level (94.3%), at their institution (91.3%), and for their daily practice (83.8%). Residents considered their training regarding antibiotics insufficient, although up to 86.5% had prescribed antibiotics in the last month. They preferred the availability of local antibiotic guidelines (65%), specific teaching sessions, specific antimicrobial management teams or readily accessible advice from a group or an infectious diseases specialist, to improve antibiotic prescribing, rather than other restrictive interventions. Conclusions Most residents at the hospitals surveyed believed that antibiotic resistance was a serious problem. The results of this survey provided very important information to optimize adherence to Antimicrobial Stewardship Programs (ASPs). Educational strategies and non-restrictive aids are the most valuable interventions, which ASPs should capitalize on to improve antimicrobial prescription (AU)

Linezolid in late-chronic prosthetic joint infection caused by gram-positive bacteria.

Linezolid may be an interesting alternative for prosthetic joint infection (PJI) due to its bioavailability and its antimicrobial spectrum. However, experience in this setting is scarce. The aim of the study was to assess linezolid's clinical and microbiological efficacy, and also its tolerance. This was a prospective, multicenter, open-label, non-comparative study of 25 patients with late-chronic PJI caused by Gram-positive bacteria managed with a two-step exchange procedure plus 6 weeks of linezolid. Twenty-two (88%) patients tolerated linezolid without major adverse effects, although a global decrease in the platelet count was observed. Three patients were withdrawn because of major toxicity, which reversed after linezolid stoppage. Among patients who completed treatment, 19 (86%) demonstrated clinical and microbiological cure. Two patients presented with clinical and microbiological failure, and one showed clinical cure and microbiological failure. In conclusion, linezolid showed good results in chronic PJI managed with a two-step exchange procedure. Tolerance seems acceptable, though close surveillance is required.

Use of tigecycline for the treatment of prolonged bacteremia due to a multiresistant VIM-1 and SHV-12 beta--lactamase-producing Klebsiella pneumoniae epidemic clone.

We report the use of tigecycline, firstly with colistin and finally alone, in a patient with a persistent breakthrough bacteremia due to a Klebsiella pneumoniae isolate harboring a metallo-beta-lactamase (VIM-1) and an extended-spectrum beta-lactamase (SHV-12). Time-kill studies demonstrated that the combination of both compounds was synergistic along the first 12 h, suppressing the regrowth observed after 3 to 6 h when colistin was tested alone.

Linezolid for the treatment of multidrug-resistant tuberculosis.

OBJECTIVES: In vitro studies have shown good activity of linezolid against Mycobacterium tuberculosis, including multidrug-resistant strains. However, clinical experience with linezolid in tuberculosis is scarce. METHODS: We report our clinical experience with five consecutive patients with multidrug-resistant tuberculosis infection treated with combination regimens that included linezolid. RESULTS: Two patients had multidrug-resistant Mycobacterium bovis infection, with resistance to 12 antituberculous agents (one of them with HIV co-infection and <50 CD4 cells/mm(3)). The other three patients were infected by multidrug-resistant M. tuberculosis strains, with resistance to all first-line drugs and other second-line drugs. All patients received linezolid in combination with thiacetazone, clofazimine or amoxicillin/clavulanate. Susceptibility tests showed linezolid MIC values < or =0.5 mg/L against all tuberculosis strains tested (standard proportion method, Middlebrook agar 7H10). In all cases, tuberculosis cultures from respiratory samples were sterile after 6 weeks of therapy. Three patients have clinical and microbiological cure of tuberculosis with a combination regimen with linezolid (range: 5-24 months). One patient was lost to follow-up at month 5. The remaining patient has completed 11 months of therapy and is still on treatment. Four patients developed anaemia and needed blood transfusions. In two of these patients, the linezolid daily-dose (600 mg twice a day) was successfully reduced to 50% (300 mg twice a day) to decrease toxicity while maintaining efficacy. Peripheral neuropathy (two patients) and pancreatitis (one patient) were other adverse events observed during linezolid treatment. CONCLUSIONS: In our experience, linezolid has been a valid alternative drug in the management of multidrug-resistant tuberculosis. The prolonged use of linezolid is frequently associated with toxicity, mainly anaemia and peripheral neuropathy, that requires special management.