Efficacy and safety of fosfomycin plus imipenem as rescue therapy for complicated bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: a multicenter clinical trial.

BACKGROUND: There is an urgent need for alternative rescue therapies in invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We assessed the clinical efficacy and safety of the combination of fosfomycin and imipenem as rescue therapy for MRSA infective endocarditis and complicated bacteremia. METHODS: The trial was conducted between 2001 and 2010 in 3 Spanish hospitals. Adult patients with complicated MRSA bacteremia or endocarditis requiring rescue therapy were eligible for the study. Treatment with fosfomycin (2 g/6 hours IV) plus imipenem (1 g/6 hours IV) was started and monitored. The primary efficacy endpoints were percentage of sterile blood cultures at 72 hours and clinical success rate assessed at the test-of-cure visit (45 days after the end of therapy). RESULTS: The combination was administered in 12 patients with endocarditis, 2 with vascular graft infection, and 2 with complicated bacteremia. Therapy had previously failed with vancomycin in 9 patients, daptomycin in 2, and sequential antibiotics in 5. Blood cultures were negative 72 hours after the first dose of the combination in all cases. The success rate was 69%, and only 1 of 5 deaths was related to the MRSA infection. Although the combination was safe in most patients (94%), a patient with liver cirrhosis died of multiorgan failure secondary to sodium overload. There were no episodes of breakthrough bacteremia or relapse. CONCLUSIONS: Fosfomycin plus imipenem was an effective and safe combination when used as rescue therapy for complicated MRSA bloodstream infections and deserves further clinical evaluation as initial therapy in these infections.

A review of the factors influencing antimicrobial prescribing.

There are multiple benefits of appropriate antimicrobial prescribing: it has a direct impact on clinical outcomes, avoids adverse effects, is cost effective and, perhaps most importantly, it helps to prevent the emergence of resistance. However, any physician can prescribe antibiotics, which is not the case with other clinically relevant drugs. There is great variability in the prescribing physician's (PP) training, motivation, workload and setting, including accessibility to infectious diseases consultants and/or diagnostic techniques, and therefore there is a high risk of inappropriate prescription. Many antibiotic prescribing errors occur around the selection and duration of treatment. This includes a low threshold for the indication of antibiotics, delayed initiation of treatment when indicated, limited knowledge of local antimicrobial resistance patterns by the PPs, errors in the final choice of dose, route or drug and a lack of de-escalation. Similarly, the prescription of prophylactic antibiotics to prevent surgical site infections, despite being commonly accepted, is suboptimal. Factors that may explain suboptimal use are related to the absence of well-defined protocols, poor knowledge of prophylactic protocols, miscommunication or disagreement between physicians, logistical problems, and a lack of audits. A proper understanding of the prescribing process can guide interventions to improve the PP's practices. Some of the potential interventions included in a stewardship program are education in antimicrobial prescribing, information on the local resistance patterns and accessibility to a qualified infectious diseases consultant.

New trends in infective endocarditis.

The present article is an update of the literature on endocarditis. A multidisciplinary group of Spanish physicians with an interest in cardiac infections selected the most important papers produced lately in the field. Two of the members of the group discussed the content of each of the selected papers, with a critical review by others members of the panel. After a review of the state of the art papers from the fields of epidemiology, new causative microorganisms (bacterial and fungal), clinical findings including those in special patients, laboratory diagnosis, prognostic factors, nosocomial endocarditis, prophylaxis, new drugs and guidelines for antibiotic treatment were discussed by the group.

Update on bacterial pathogens: virulence and resistance.

The present article is an update of the literature on bacterial pathogens. Recognizing the interest and scientific and public health importance of infections produced by bacterial pathogens with new virulence mechanisms and/or new mechanisms of resistance to antimicrobial agents, a multidisciplinary group of Spanish physicians and microbiologists organized a joint session and revised the most important papers produced in the field during 2006. Each article was analyzed and discussed by one of the members of the panel. This paper focus on a variety of diseases that pose major clinical and public health challenges today; and include infections produced by community-acquired methicillin-resistant Staphylococcus aureus and S. aureus small colony variants, infections produced by multiply resistant coagulase-negative staphylococci, pneumococcal infections, human listeriosis, meningococcal disease, Haemophilus influenzae, pertussis, Escherichia coli, ESBL-producing organisms, and infections due to non-fermenters. After a review of the state of the art, papers selected in this field are discussed.

El presente artículo recoge una actualización bibliográfica de patógenos bacterianos. Dado el interés científico y la importancia que tienen para la salud pública las infecciones producidas por patógenos bacterianos con nuevos mecanismos de virulencia y/o nuevos mecanismos de resistencia a los antimicrobianos, un grupo multidisciplinario de microbiólogos y clínicos españoles, con experiencia en enfermedades infecciosas, organizó una reunión en la que se revisaron los artículos más importantes en este campo, publicados en 2006.El contenido de cada uno de los artículos seleccionados fue expuesto y discutido por uno de los miembros del grupo. Este artículo revisa algunas de las enfermedades infecciosas bacterianas que suponen hoy en día algunos de los principales retos para la salud pública e incluye las infecciones producidas por Staphylococcus aureus resistente a meticilina de adquisición comunitaria, las producidas por variantes de colonia pequeña de S. aureus, las relacionadas con estafilococos coagulasa negativa multirresistentes, la infección neumocócica, la listeriosis humana, la infección meningocócica, la tos ferina, las infecciones por Haemophilus influenzae, la diseminación de las bacterias productoras de BLEE, y las infecciones por bacilos gramnegativos no fermentadores. Tras la revisión de la situación actual, se discuten y comentan diferentes artículos relacionados con estos aspectos.

An insidious nosocomial outbreak due to Salmonella enteritidis.

OBJECTIVES: To investigate an increase in the number of Salmonella enteritidis isolates detected in a large hospital to ascertain whether it was due to a nosocomial source, to identify the mechanisms of transmission, and to institute effective control measures to prevent future episodes. DESIGN: Observational study, survey of all microbiological samples positive for S. enteritidis detected in the hospital, outbreak investigation, and review of the literature. SETTING: A tertiary-care teaching hospital for adults in Barcelona, Spain. RESULTS: During a 7-month period from May to November 1998, we identified 22 inpatients with S. enteritidis infection for whom nosocomial acquisition was strongly suspected. The attack rate was 0.138 per 1,000 patient-days. All affected patients were immunosuppressed and overall mortality was 41% (9 of 22). A sample of a meal cooked in the kitchen was culture positive for S. enteritidis. All isolates shared the same antibiotic susceptibility pattern and all except one shared the same pulsed-field gel electrophoresis (PFGE) pattern, but PFGE could not differentiate between outbreak-related and control strains. After compliance with kitchen hygiene procedures was emphasized and cleansing was intensified, no more cases were detected. CONCLUSIONS: Apparently, sporadic cases of S. enteritidis may be part of an outbreak with a low attack rate. A small but persistent inoculum affecting only individuals with special predisposition for Salmonella infection might account for this. Suspicion should be raised in hospitals and institutions with a highly susceptible population.

[Bacteremia due to Escherichia coli: epidemiological analysis and sensitivity to antibiotics in a county hospital]. / Bacteriemia por Escherichia coli: análisis epidemiológico y de la sensibilidad a los antibióticos en un hospital comarcal.

BACKGROUND AND OBJECTIVE: There are few studies analyzing the epidemiological characteristics of Escherichia coli bacteremia including the susceptibility to antibiotics and outcome. PATIENTS AND METHOD: E. coli bacteremia episodes were recorded from January 1989 to December 1998. Clinical variables, setting acquisition, source of bacteremia, outcome and susceptibility to antibiotics were included. The study was prospective and comparative. Descriptive and univariate analysis were performed. RESULTS: 330 episodes of E. coli bacteremia were recorded: 117 in women. The most frequent source was the urinary tract (68%), followed by an abdominal and biliary focus. E. coli bacteremia appeared mostly in groups II and III of McCabe & Jackson. In 46 cases (14%), E. coli bacteremia was nosocomial. Crude and related mortality was 6.6 and 4.2%, respectively. A significant increase in the resistance to ciprofloxacin was observed. CONCLUSIONS: The epidemiological characteristics of E. coli bacteremia have not changed, yet the mortality was lower in our series. Preventive measures in the hospital and a rational use of antibiotics, principally quinolones, are necessary.

Clinical impact of imipenem-resistant Pseudomonas aeruginosa bloodstream infections.

OBJECTIVES: To describe the incidence and clinical characteristics of imipenem-resistant (IR) Pseudomonas aeruginosa bacteraemia. METHODS: We performed a retrospective study including all episodes of IR P. aeruginosa bacteraemia seen from January 2003 to December 2005 in a tertiary teaching hospital. RESULTS: There were 108 episodes of IR P. aeruginosa bacteraemia, which represented an incidence of 0.14 episodes per 1000 patient-days in 2003 and 0.11 episodes per 1000 patient-days in 2005. 83 of the episodes (77%) were nosocomially acquired. Most of patients had at least one underlying disease and had previously received antimicrobial treatment. The most frequent source was the urinary tract (31%), followed by unknown origin (22%). A total of 23 (21%) episodes were polymicrobial and 51 (47%) were caused by multidrug-resistant strains. The independent risk factors for mortality from IR P. aeruginosa bloodstream infection were a high-risk source of the bacteraemia (OR: 4.6; 95% CI 1.7-12.4; p=0.01), and presentation with severe sepsis (OR: 2.8; 95% CI 1-7.8; p=0.05). CONCLUSIONS: Our study shows that the rates of IR P. aeruginosa bacteraemia remained stable throughout the study period. The source of bacteraemia and the clinical presentation with severe sepsis were the main determinants of the prognosis.

[Impact of a prevention program for catheter-related bloodstream infection in the intensive care unit of a tertiary hospital]. / Impacto de un programa de prevención de la bacteriemia relacionada con el catéter en una unidad de cuidados intensivos de un hospital terciario.

INTRODUCTION: Catheter-related bloodstream infection (CR-BSI) is a cause of morbidity and mortality in intensive care units, and the optimal approach for preventing these infections is not well defined. Comparison of CR-BSI rates with those provided by programs such as the National Nosocomial Infection Surveillance System (NNISS) from the USA and the Spanish National Nosocomial Infection Surveillance Study (ENVIN), enable determination of the need to implement control measures. In 2000, we found that the CR-BSI rates in UCIs of our hospital were much higher than the data reported by ENVIN. OBJECTIVE: To assess the impact of implementing a protocol for proper use of intravascular catheters on CR-BSI rates in the intensive care unit (ICU) of a tertiary hospital. METHODS: Prospective study of patients admitted to the ICUs of a tertiary hospital in the months of May and June, from 2000 to 2004. In 2001, a CR-BSI prevention program including aspects related to catheter insertion and maintenance in ICU patients was implemented. We calculated infection rates per 1000 days of catheter use in all the 2-month periods studied, and compared the 2000 and 2004 results by analysis of the odds ratios and confidence intervals. RESULTS: A total of 923 patients were included. Mean age was 58.7 years (SD: 15.4), mean ICU stay was 11.6 days (SD: 11.4), mean SAPSII was 28.2 (SD: 15.9), and mortality was 20.5%. There was a significant reduction in CR-BSI rates from 13.3 episodes per 1000 days of catheter use in the first period to 3.21 in the last period (OR=3.53, 95% CI: 2.36-5.31). CONCLUSIONS: Application of a prevention program for CR-BSI and a system for monitoring BSI rates led to a significant, sustained reduction in these infections.

[Consensus document for the treatment of bacteremia and endocarditis caused by methicillin-resistent Staphylococcus aureus. Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica]. / Documento de consenso sobre el tratamiento de la bacteriemia y la endocarditis causada por Staphylococcus aureus resistente a la meticilina. Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica.

Bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and clinically important. The rise in MRSA bacteremia and endocarditis is related with the increasing use of venous catheters and other vascular procedures. Glycopeptides have been the reference drugs for treating these infections. Unfortunately their activity is not completely satisfactory, particularly against MRSA strains with MICs > 1 microg/mL. The development of new antibiotics, such as linezolid and daptomycin, and the promise of future compounds (dalvabancin, ceftobiprole and telavancin) may change the expectatives in this field.The principal aim of this consensus document was to formulate several recommendations to improve the outcome of MRSA bacteremia and endocarditis, based on the latest reported scientific evidence. This document specifically analyzes the approach for three clinical situations: venous catheter-related bacteremia, persistent bacteremia, and infective endocarditis due to MRSA.

Genotype and phenotype at baseline and at failure in human immunodeficiency virus-infected antiretroviral-naive patients in a randomized trial comparing zidovudine and lamivudine plus nelfinavir or nevirapine.

For the 127 Spanish patients enrolled in the Combine Study, a resistance substudy was performed with 100 (79%) plasma samples obtained at baseline and with 18 samples obtained from 19 patients at the time they experienced treatment failure. At baseline, primary mutations to nonnucleoside reverse-transcriptase inhibitors and protease inhibitors were not detected, whereas mutations to nucleoside reverse-transcriptase inhibitors were observed in 10% of patients. At failure, mutations were detected in 7 of 16 patients. An agreement in the results of virtual and real phenotypes was observed in the 93 samples in which both tests were performed.