Evaluation of combined use of the MALDI-TOF and GenomEra MRSA/SA assay for the direct detection of methicillin resistance in Staphylococcus aureus from positive blood culture bottles / Evaluación del uso combinado de ensayo de MALDI-TOF y Genomera MRSA/SA para la detección directa de la resistencia a la meticilina en Staphylococcus aureus de botellas de hemocultivo positivo

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Beyond numbers: the informative patterns of immuno-staphylococcal dynamics.

To evaluate new drugs, the immune system should be considered. Here we evaluated a proof-of-concept that uncovers bacterial-leukocyte interactions. Analyzing longitudinal leukocyte data from bovines infected with either methicillin-resistant (MRSA) or methicillin-susceptible (MSSA) Staphylococcus aureus, two methods were investigated: (i) an approach that assesses lymphocytes, monocytes, or neutrophils, separately, and (ii) a method that, using dimensionless indicators (products, ratios, or combinations derived from leukocyte data), explores the dynamics of leukocyte relationships in three-dimensional (3D) space and identifies data subsets of informative value. The classic approach not always distinguished infected from non-infected cows. In contrast, the alternative approach differentiated noninfected from infected animals and distinguished early MRSA from early MSSA and late MRSA infections. Discrimination was associated with the use of dimensionless indicators. When measured in 3D space, such indicators generated a very large number of combinations, which helped detect data subsets usually unobserved, such as non-overlapping infection-negative and -positive subsets, and several disease stages. The validity of such data subsets was determined with biologically interpretable data. This graphic, pattern recognition-based information system included but did not depend on any one number or variable. Because it can detect functions (relationships that involve two or more elements), in real time, if shown reproducible, the analysis of complex host-microbial dynamics could be used to evaluate antimicrobials.

Septic arthritis and atopic dermatitis: 2 cases and a review of the recent literature

No disponible

Caracterización de cepas de Staphylococcus epidermidis y S. haemolyticus resistentes a meticilina y linezolid en un hospital español / Characterization of methicillin- and linezolid-resistant Staphylococcus epidermidis and S. haemolyticus strains in a Spanish hospital

La resistencia a linezolid se produce generalmente por mutaciones en el ARNr 23S. El objetivo de este estudio fue caracterizar cepas de Staphylococcus epidermidis (SE) y S. haemolyticus (SH) resistentes a linezolid y meticilina (SE-LMR y SH-LMR, respectivamente) detectadas en un hospital español. Métodos Se estudiaron todas las cepas SE-LMR y SH-LMR aisladas en el periodo de junio 2009 a agosto 2011, en un hospital de segundo nivel, así como las características epidemiológicas de los pacientes. Se tiparon las cepas (25 SE-LMR y 2 SH-LMR, procedentes de 20 pacientes) y se determinó su fenotipo y genotipo de resistencia y la presencia de genes de virulencia. Resultados En todas las cepas analizadas se detectó la mutación G2603T en el ARNr 23S y también cambios aminoacídicos en las proteínas ribosomales L3 y L4. Las 25 cepas SE-LMR pertenecieron a la secuencia tipo ST2, su SCCmec fue el tipo III y presentaron 2 patrones diferentes de PFGE. El SCCmec de las 2 cepas SH-LMR fue no tipable. Las cepas SE-LMR contenían los genes de resistencia aac(6’)-aph(2”) y dfrS1, y las cepas SH-LMR poseían además el gen erm(C). No se detectaron genes de resistencia a lincomicina en las cepas SE-LMR a pesar de mostrar sensibilidad disminuida a clindamicina y resistencia a lincomicina. Conclusiones La resistencia a linezolid en el ámbito hospitalario es preocupante y requiere una continua vigilancia. Esta resistencia se asoció a la mutación G2603T en el ARNr 23S y a la presencia de cambios aminoacídicos en L3 y/o L4 (AU)

Introduction Linezolid resistance is mainly due to mutations in the 23S rRNA target. The aim of this study was to characterize linezolid and methicillin resistant Staphylococcus epidermidis (SE-LMR) and S. haemolyticus (SH-LMR) strains detected in a Spanish hospital. Methods SE-LMR and SH-LMR strains obtained in the period June 2009-August 2011 in a second level hospital were recorded along with the epidemiological characteristics of the patients. These strains were typed, and their resistance, phenotype, genotype and the factors determining their virulence were analysed. Results Linezolid resistance was explained by the presence of G2603T mutation (23S rRNA) and aminoacid changes in L3 and L4 ribosomal proteins. The 25 SE-LMR strains belonged to sequence type ST2, presented SCCmec type III, and two different PFGE patterns. The two SH-LMR strains showed non-typeable SCCmec. SE-LMR strains harboured the resistance genes aac(6’)-aph(2”), and dfrS1. SH-LMR strains contained these genes and the gene erm(C). No lincomycin resistance mechanism was identified in SE-LMR strains regardless of showing lincomycin resistance and diminished susceptibility to clindamycin. Conclusions Linezolid resistance is of concern in hospitals, and requires continued vigilance. Several linezolid resistance mechanisms (mutation in 23S RNAr and amino acid changes in L3 and L4) were identified in this study (AU)

¿Es necesario conocer qué trabajadores son portadores de SARM en contacto con enfermos oncológicos? / Is it necessary to know which workers are carriers of MRSA in contact with cancer patients?

Nuestro objetivo fue determinar la prevalencia de Staphylococcus aureus resistente a meticilina (SARM) en los trabajadores que tuvieron contacto directo con enfermos oncológicos infectados por SARM e ingresados en la unidad de cuidados intensivos del Instituto Valenciano de Oncología. La prevalencia de colonización por SARM se estudió en 62 trabajadores. Las muestras obtenidas de las fosas nasales y faringe (n= 124) fueron incubadas durante 24 horas en medio de transporte Amies Viscosa (Eurotubo®) y después sembradas en agar chocolate, agar MRSA II y caldo Brain Heart Infusion. Las colonias que se identificaron mediante la tinción de Gram como cocos gram-positivos con disposición en racimos, catalasa positiva y coagulasa positiva, se procesaron para estudio de sensibilidad mediante el método de Kirby-Bauer y prueba de cribado de la meticilina (10 µg de Oxoid®) en Mueller-Hinton (Becton-Dickinson®, BD), suplementado con NaCl (2%). A los aislamientos de SARM confirmados, se les volvió a realizar estudio de sensibilidad mediante microdilución (MicroScan® de Siemens), para determinar las CMI (mg/L). La prevalencia de SARM fue del 1,61% (1 trabajador) y 12,90% (8 trabajadores) para Staphylococcus aureus sensible a meticilina (SASM), procedentes de fosas nasales. Las medidas adoptadas fueron: aplicación de mupirocina nasal al trabajador colonizado, control de las medidas de aislamiento en los pacientes colonizados y/o infectados y adoctrinamiento al personal relacionado(AU)

Our objective was to determine the prevalence of methicillin-resistant Staphylococcus aureus in workers who had direct contact with oncologic patients infected with MRSA and admitted to the intensive care unit of the Valencian Institute of Oncology. A study of prevalence of MRSA colonization of 62 workers was performed. Samples were taken from nose and pharynx in each of the workers. After 24 hours of incubation in Amies transport medium Viscose (Eurotubo®), 124 samples were seeded (N = 124) in chocolate agar agar, MRSA II and BHI broth (Brain Heart Infusion). Those colonies that were identified by Gram stain gram-positive cocci in clusters available, catalase positive and coagulase positive were processed for study of sensitivity by Kirby-Bauer method and screening test for methicillin (10ìg of Oxoid®) on Mueller-Hinton (Becton-Dickinson®, BD), supplemented with NaCl (2%). Those confirmed MRSA isolates, he returned to perform sensitivity study by microdilution (MicroScan®, Siemens) to determine the MIC (mg/L). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) was 1.61% (1) and 12.90% (8) for methicillin-sensitive Staphylococcus aureus (MSSA), from nostrils. The measures implemented were: nasal application of mupirocin to the worker colonized control isolation measures in infected patients and indoctrination of the personnel involved(AU)

Antimicrobial resistance of Staphylococcus spp. from small ruminant mastitis in Brazil / Resistência antimicrobiana de Staphylococcus spp. de mastite de pequenos ruminantes no Brasil

The study aimed to determine the antimicrobial resistance patterns and to identify molecular resistance markers in Staphylococcus spp. (n=210) isolated from small ruminant mastitis in Brazil. The antimicrobial resistance patterns were evaluated by the disk diffusion test and by detection of the presence of mecA, blaZ, ermA, ermB, ermC and msrA genes by PCR. The efflux pump test was performed using ethidium bromide and biofilm production was determined by Congo red agar test along with PCR for detection of the icaD gene. The isolates were most resistant to amoxicillin (50.0%), streptomycin (42.8%), tetracycline (40.4%), lincomycin (39.0%) and erythromycin (33.8%). Pan-susceptibility to all tested drugs was observed in 71 (33.8%) isolates and 41 Staphylococcus isolates were positive for the efflux pump. Although phenotypic resistance to oxacillin was observed in 12.8% of the isolates, none harbored the mecA gene. However, 45.7% of the isolates harbored blaZ indicating that beta-lactamase production was the main mechanism associated with staphylococci resistance to beta-lactams in the present study. The other determinants of resistance to antimicrobial agents ermA, ermB, ermC, and msrA were observed in 1.4%, 10.4%, 16.2%, and 0.9% of the isolates, respectively. In addition, the icaD gen was detected in 32.9% of the isolates. Seventy three isolates (54 from goats and 19 from sheep) were negative for all resistance genes tested and 69 isolates presented two or more resistance genes. Association among blaZ, ermA, ermB, ermC and efflux pump were observed in 17 isolates, 14 of which originated from goats and three from sheep. The data obtained in this study show the resistance of the isolates to beta-lactamics, which may be associated with the use of antimicrobial drugs without veterinary control.

O presente trabalho teve como objetivo determinar os padrões de resistência a agentes antimicrobianos e identificar marcadores moleculares de resistência em Staphylococcus spp. (n=210) isolados de mastite de pequenos ruminantes no Brasil. Os padrões de resistência a agentes antimicrobianos foram avaliados pelo teste de difusão em disco e pela detecção da presença dos genes mecA, blaZ, ermA, ermB, ermC e msrA via PCR. O teste da bomba de efluxo foi realizado utilizando brometo de etídio e a produção de biofime foi determinada pelo teste do vermelho congo em paralelo com o PCR para detecção do gene icaD. Os isolados foram mais resistentes a amoxicilina (50,0%), estreptomicina (42,8%), tetraciclina (40,4%), lincomicina (39,0%) e eritromicina (33,8%). Setenta e um (33,8%) isolados foram sensíveis a todas as drogas testadas e 41 foram positivos para a bomba de efluxo. Embora a resistência fenotípica a oxacilina tenha sido observada observada em 12,8% dos isolados, nenhum possuiu o gene mecA. Entretanto, 45,7% dos isolados continham a gene blaZ, indicando que a produção de beta-lactamases foi o principal mecanismo associado com a resistência dos Staphylococcus aos beta-lactâmicos. Os outros determinantes de resistência a agentes antimicrobianos ermA, ermb, ermC e msrA foram observados em 1,4%, 10,4%, 16,2% e 0,9% dos isolados respectivamente. Além disso, o gene icaD foi detectado em 32,9% dos isolados. Setenta e três isolados (54 de cabras e 19 de ovelhas) foram negativos para todos os genes de resistência testados e 69 isolados apresentaram dois ou mais genes de resistência. A associação entre blaZ, ermA, ermB, ermC e bomba de efluxo foi observada em 17 isolados dos quais 14 eram oriundos de cabras e três de ovelhas. Os dados obtidos no presente estudo indicam a resistência dos isolados aos beta-lactâmicos, o que pode estar associado ao uso sem controle veterinário destas drogas nos animais.

Relapsing infective endocarditis following closure of ventricular septal defect.

An 8-year-old boy who had undergone Dacron patch closure of a ventricular septal defect 5 years earlier, was admitted with relapsing methicillin-resistant Staphylococcus aureus infective endocarditis and lung abscesses. Echocardiography indicated vegetation attached to the tricuspid valve and the Dacron patch. The infected patch was replaced with glutaraldehyde-treated autologous pericardium. He was discharged uneventfully and has been well for 4 years, without signs of infection.

Generation, characterization, and epitope mapping of neutralizing and protective monoclonal antibodies against staphylococcal enterotoxin B-induced lethal shock.

T-cell stimulating activity of Staphylococcal enterotoxin B (SEB) is an important factor in the pathogenesis of certain staphylococcal diseases including SEB mediated shock. SEB is one of the most potent superantigens known and treatment of SEB induced shock remains a challenge. We generated and characterized murine monoclonal antibodies (mAbs) to SEB in mice. We tested mAbs neutralize mitogenic effects of SEB in vitro and in vivo with T-cell proliferation assays and 2 murine models for SEB induced lethal shock (SEBILS). Epitope mapping suggests that all these mAbs recognize conformational epitopes that are destroyed by deleting the C terminus of the protein. Further site-directed mutagenesis identified potential residues involved in binding to SEB that differ between Methicillin resistant and sensitive Staphylococcus aureus strains. Only mAb 20B1 was effective as a monotherapy in treating SEBILS in HLA DR3 transgenic mice, which exhibit enhanced sensitivity to SEB. It is noteworthy that mAbs, 14G8 and 6D3 were not protective when given alone in the HLA DR3 mice but their efficacy of protection could be greatly enhanced when mAbs were co-administered simultaneously. Our data suggest combinations of defined mAbs may constitute a better treatment strategy and provide a new insight for the development of passive immunotherapy.

Prevención y control de la infección relacionada con la asistencia en el ámbito sociosanitario / No disponible

La infección relacionada con la asistencia sanitaria (IRA) en los centros sociosanitarios (CSS) es uno de los principales problemas relacionados con la seguridad del paciente. En los últimos años, ha aumentado el componente agudo en los centros sociosanitarios. Los residentes de los CSS tienen un riesgo similar de desarrollar una IRA a de los pacientes de los hospitales agudos. Se ha publicadoun gran número de información y trabajos sobre programas de control de la infección en CSS. Las recomendaciones desarrolladas por los programas de control de infección en CSS están basadas en opiniones de expertos. Llama la atención la falta de meta-análisis y estudios controlados en este campo. El desarrollo de sistemas de vigilancia, con definiciones adaptadas de IRA en los CSS, permitela recogida sistemática de información, análisis de datos y uso de información orientado a mejorar los cuidados de los pacientes, reducir la incidencia prevenible de IRAS y comparar resultados concentros con características parecidas (AU)

The Health Care–Associated Infections (HCAI) in long-term care facilities (LTCFs) is one of the main problems related to patient safety. In recent years, acute health conditions have increased amongst nursing home residents. LTCF residents have a risk of developing HCAI that approaches that seen inacute care hospital patients. A great deal of information has been published concerning infections inthe LTCF, and infection control programs are nearly universal in that setting. Recommendations are developed for long-term care infection control programs based on expert opinions. The lack of metaanalyses and clinical randomised controlled trials in this field is surprising. The development of surveillance systems with appropriate definitions of HCAI to enable the systematic collection, data analysis and use of information in order to improve care to patients, reduce the incidence HCAI that can be prevented and enables to compare data from other facilities with same patient mix (AU)

Life-threatening infection due to community-acquired methicillin-resistant Staphylococcus aureus: case report and review.

We report an unusual case of serious, multifocal, invasive infection due to community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) in a 10-year-old girl with favorable outcome. The child manifested femoral osteomyelitis, pyomyositis, deep femoral vein thrombosis, pneumonia, encephalopathy, and disturbances of almost all organs. She remained in a critical condition for a week. Fever persisted for 6 weeks and acute phase reactants remained increased for 6 months, necessitating a 7-month antistaphylococcal therapy with a glycopeptide and clindamycin. This led to resolution of infection-associated problems during the subsequent 36 months of follow-up. CA-MRSA strain isolated from the patient harbored both staphylococcal chromosomal cassette type IV (SCCmec type IV) and Panton-Valentine leukocidin genes. A literature review of serious CA-MRSA infections indicated that only a small minority of published cases had favorable outcome.

Colonial architecture and growth dynamics of Staphylococcus aureus resistant to methicillin

El objetivo del estudio fue observar la estructura colonialy la dinámica del crecimiento de Staphylococcus aureusresistente a meticilina (SARM) empleando cortes semifinosvisualizados al microscopio óptico. Se estudiaron unacepa de S. aureus sensible a meticilina (SASM) y un SARM.Después de cada periodo de incubación (24 y 48 h) a 37ºClas colonias fueron incluidas en una resina epoxi. Cortessemifinos de 0.5 μm fueron teñidos con azul de toluidina yvisualizados al microscopio. Desde el punto de vista microscópico,no se observaron diferencias estructurales entrelas colonias de SASM y SARM. Si se observaron diferenciasen ambas cepas entre las colonias de 24 y 48 h de incubación.En las colonias de 24 h se observaron 2 capasclaramente diferenciadas: (A) una capa basal con alta densidadde población en contacto con el medio de cultivo y(B) una capa superficial con menor densidad de población.En las colonias de 48 h se observaron cuatro capas: (A)una capa basal con alta densidad de población; (B) una capaclara constituida por restos bacterianos muy degradadosen cuyo seno se observan muy escasos y dispersos cocosque conservan sus propiedades tintoriales; (C) una capamixta, constituida por una mezcla de bacterias vivas y restosbacterianos muy groseros y poco degradados y (D) unacapa superficial con menor densidad de población que lacapa basal. Las colonias forman estructuras altamente organizadasoriginadas por la disponibilidad de nutrientes ymecanismos de comunicación intercelular. La arquitecturacolonial es un proceso complejo y tiempo dependiente(AU)

The aim of the study was to explore the structure andgrowth dynamics of Staphylococcus aureus resistant to methicillin(MRSA) colonies using semithin sections visualizedby light microscope. One S. aureus susceptible to methicillin(MSSA) and one MRSA clinical strains were studied. Coloniesin agar plates were embedded in epoxy resin after each incubationperiod (24 h and 48 h) at 37ºC. Semithin sections of0.5 μm were stained with toluidine blue and visualized by lightmicroscope. Microscopically, no structural differences wereobserved between SASM and SARM colonies but differenceswere observed in both strains between 24 and 48 h incubationperiods. Colonies showed two layers clearly differentiated at24 h independently of the resistance to methicillin: (A) onebasal layer with high density of population in contact withculture media, and (B) one superficial layer with a lower densityof population. Colonies showed four layers at 48 h: (A) onebasal layer with high density of population; (B) one clear layerconstituted by very degraded bacterial remains in which canbe observed cocci dispersed with their dyeing properties; (C)one mixed layer constituted by viable bacteria and little degradedbacterial remains (D) one superficial layer with a lowerdensity of population than basal layer. Colonial architecture isa complex and time-dependent process(AU)

Impétigo bulloso causado por Staphylococcus aureus" resistente a meticilina / Bullous impetigo caused by methicillin-resistant Staphylococcus aureus

El impétigo es una infección cutánea superficial que ocurre sobre todo en la edad pediátrica, más frecuentemente por debajo de los 5 años de edad. SE clasifica en primario, que es el que tiene lugar sobre piel previamente sana, y secundario, que aparece en piel lesionada, principalmente tras un eccema. Existen dos tipos de impétigo: no bulloso, más frecuentemente, y bulloso. el agente causal predominante en todos los tipos de impétigo es Staphylococcus aureus. En los últimos años se ha descrito la emergencia de cepas de S. aureus resistentes a meticilina (SARM) como causantes de infecciones adquiridas en la comunidad, tanto leves como graves. Se presenta el caso de un varón de 8 años que presenta lesiones ampollosas dolorosas de una semana de evolución en la región lumbar. Se recoge cultivo de las lesiones y se identifica el crecimiento de colonias de S. aureus con resistencia a meticilina(AU)

Impetigo is a superficial skin disease that occurs in children, mainly before the age of five years. It is classified as primary if it occurs on previously healthy skin and secondary when it develops on damaged skin, usually following eczema. There are two types of impetigo: non-bullous, which is more frequent, and bullous. The predominant causative agent in both types is Staphylococcus aureus. In recent years, emergent methicillin-resistant strains (MRSA) that provoke mild to severe community-acquired lesions have been described. We report the case of an eight-year-old boy with painful, bullous skin lesions on his back that had developed one week earlier. A skin culture revealed the presence of colonies of methicillin-resistant S. aureaus(AU)

Dramatic results achieved with MRSA initiative.

Program achieves 60% reduction in MRSA in one year, 80% in bloodstream infections. All hospital patients are swabbed, infected patients are isolated. Education efforts continued even after program was launched.

Evaluation of the IDI-MRSA assay on the SmartCycler real-time PCR platform for rapid detection of MRSA from screening specimens.

Rapid accurate detection is a prerequisite for the successful control of meticillin-resistant Staphylococcus aureus (MRSA). The IDI-MRSA real-time polymerase chain reaction (PCR) assay was designed to provide rapid results from nasal specimens collected in Stuart's liquid transport medium. This study has evaluated the IDI-MRSA kit for use in a clinical laboratory by investigating the following parameters: (1) limits of detection (LoD), (2) performance with Amies' gel-based transport medium, (3) ability to detect strains of MRSA in a collection representative of MRSA in Ireland since 1974 (n=113) and (4) performance in a clinical trial with swabs from nose, throat and groin/perineum sites from 202 patients. LoDs (colony-forming units per ml) of the IDI-MRSA kit, direct culture on MRSA-Select chromogenic agar (CA) and salt-enrichment culture (with subculture onto CA) were 10(3), 10(3) and 10(2), respectively. LoDs with Stuart's and Amies' transport media were comparable. All except one of the 113 MRSA isolates were detected by the kit but, when six control strains carrying staphylococcal cassette chromosome mec (SCCmec) type IV element subtypes IVa-d and SCCmec types V and V(T) were tested, the kit failed to detect MRSA carrying SCCmec V. The sensitivity and specificity for detection of MRSA from nose, throat and groin/perineum specimens were comparable with slightly lower sensitivities from throat and groin/perineum specimens compared with nasal swabs (90%, 97%; 89%, 99%; 88%, 99%, respectively). Overall sensitivity, specificity and positive and negative predictive values for specimens from all sites were 88%, 99%, 94% and 97%, respectively. Further developments to improve the sensitivity of this highly worthwhile assay are required.

Estudio comparativo de pacientes con bacteriemia por Staphylococcus aureus sensible a la meticilina frente a S. aureus resistente a la meticilina: epidemiología y factores pronósticos / A comparative study of patients with methicillin susceptible versus methicillin resistant Staphylococcus aureus bacteremia: epidemiology and prognostic factors

Fundamento y objetivo: Hay controversia sobre la influencia de la resistencia a la meticilina en el pronóstico de los pacientes con bacteriemia por Staphylococcus aureus. En este trabajo, analizamos los patrones clínicos y los factores pronósticos que se relacionan con el desarrollo de complicaciones y la mortalidad en pacientes con bacteriemia por S. aureus y valoramos la influencia de la resistencia a la meticilina (S. aureus sensible a la meticlina [SASM] frente a S. aureus resistente a la meticilina [SARM]). Pacientes y método: Estudio prospectivo y comparativo de 213 pacientes con bacteriemia por S. aureus. Resultados: Del total de pacientes con bacteriemia, 131 (61,5%) correspondían a SASM y 82 (38,5%) a SAMR. Se asociaron a SARM la adquisición nosocomial de la infección, la presencia de una enfermedad de base rápidamente fatal y ciertos factores predisponentes (diabetes mellitus, utilización de catéteres vasculares, estancia previa en unidades de cuidados intensivos y uso previo de antibióticos). Los pacientes con bacteriemia por SARM presentaron mayor gravedad clínica y desarrollaron complicaciones con más frecuencia que los pacientes con bacteriemia por SASM. La mortalidad de los casos con bacteriemia por SARM fue del 42,6%, mientras que en la de SASM fue del 16% (p < 0,05). En el análisis multivariado, del total de casos de bacteriemia por S. aureus, las variables que se asociaron a un fracaso terapéutico mayor fueron la gravedad de la enfermedad de base, una situación clínica inicial crítica-mala y el tratamiento empírico no adecuado; la resistencia a la meticilina no se asoció a más mortalidad. Conclusiones: En los pacientes con bacteriemia por S. aureus, la resistencia a la meticilina no se asocia a una mayor mortalidad cuando se hace un análisis ajustado por otros factores clínicos/pronósticos. La gravedad de la enfermedad de base, la situación clínica inicial crítica-mala y el tratamiento empírico no adecuado son los factores pronósticos relacionados con el fracaso terapéutico en los pacientes con bacteriemia por S. aureus

Background and objective: The influence of methicillin resistance in Staphylococcus aureus bacteremia (SAB) continues to be controversial. The aim of this study was to evaluate risk factors and mortality predictors in patients with SAB and the influence of methicillin resistance in mortality (SAMSB vs SAMRB). Patients and method: Prospective study including 213 in-patients with SAB. Results: Of 213 episodes of SAB, 131 (61.5%) were due to SAMS and 82 (38.5%) to SAMR. Risk factors associated with SAMRB were: nosocomial infection, presence of an ultimately or rapidly fatal underlying disease, diabetes mellitus, intravenous catheters, previous ICU hospitalization and therapy with broad-spectrum antibiotics. Severity and complications were more frequent in patients with SAMRB. Mortality was 42.6% in SAMRB cases vs 16% in SAMSB cases (p < 0.05). Multivariate analysis showed as independent predictors of mortality in patients with SAB: presence of an ultimately or rapidly fatal underlying disease, acute severity of illness at onset and inappropriate empirical therapy; methicillin resistance was not an independent predictor of mortality. Conclusions: Methicillin resistence was not an independent predictor of mortality in patients with SAB. Presence of a fatal underlying disease, acute severity of illness at onset and inappropriate therapy were the main prognosis factors in patients with SAB

Occurrence of vancomycin-intermediate-resistant Staphylococcus aureus in Japan.

The Clinical and Laboratory Standards Institute (CLSI) amended the criteria for vancomycin susceptibility and resistance of Staphylococcus aureus in 2006. The earlier criteria had established that S. aureus with minimum inhibitory concentrations (MICs) of vancomycin of < or =4 microg/ml, 8 to 16 microg/ml, and > or =32 microg/ml were vancomycin-susceptible, -intermediate-resistant and -resistant, respectively. The revised recommendation states that bacteria showing vancomycin MICs of < or =2 microg/ml, 4 to 8 microg/ml, and > or =16 microg/ml are -susceptible, -intermediate-resistant, and -resistant, respectively. We examined, based on these new criteria, the vancomycin susceptibility of methicillin-resistant S. aureus (MRSA) strains isolated in Japan from 1978 through 2005 at 17 general hospitals. The results showed that, among 2446 MRSA isolates tested, 8 were classified as intermediate-vancomycin-resistant (VISA). Re-examination of vancomycin susceptibility in these 8 strains in 2006 revealed that 6 strains showed a vancomycin MIC of 4 microg/ml, as tested by the agar dilution method, broth dilution methods, and E-test; the 2 other strains had lost the vancomycin resistance. Pulsed-field gel electrophoresis (PFGE) of the chromosomal DNA of these strains exhibited five unique profiles; 2 strains isolated from the same hospital were identical. These results revealed that at least five different types of VISA strains could be identified in Japan so far according to the new CLSI criteria. All these VISA strains had type II staphylococcal cassette chromosome, mec. This study revealed, for the first time in Japan, the presence of intermediate vancomycin-resistant MRSA in this country.

The business of developing antibacterials.

Although some dazzling technical approaches have fallen short, dozens of small companies and a few major pharmas seek new products for this medically crucial, modest-growth market.

Evaluation of the humoral immune response in BALB/c mice immunized with a naked DNA vaccine anti-methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is the major pathogen involved in nosocomial infections, leading to high rates of morbidity and mortality in hospitals worldwide. The methicillin resistance occurs due to the presence of an additional penicillin-binding protein, PBP2a, which has low affinity for beta-lactam antibiotics. In the past few years, vancomycin has been the only antibiotic option for treatment of infections caused by multiresistant MRSA; however, reports of vancomycin-resistant strains have generated great concerns regarding the treatment to overcome these infections. In the present study, we report preliminary results regarding the humoral immune response generated in BALB/c mice by two different doses of naked DNA vaccine containing an internal region, comprising the serine-protease domain, of the PBP2a of MRSA. The immunization procedure consisted of four immunizations given intramuscularly within 15-day intervals. Blood was collect weekly and anti-PBP2a-specific antibodies were screened by ELISA. BALB/c mice immunized with DNA vaccine anti-PBP2a have shown higher antibody titers mainly after the fourth immunization, and intriguingly, no correlation between the humoral immune response and DNA dose was observed. Our results suggest that the DNA vaccine anti-PBP2a induced an immune response by production of specific antibodies anti-MRSA in a non-dose-dependent manner, and it could represent a new and valuable approach to produce specific antibodies for passive immunization to overcome MRSA infections.