In-vitro activity of several antimicrobial agents against methicillin-resistant Staphylococcus aureus (MRSA) isolates expressing aminoglycoside-modifying enzymes: potency of plazomicin alone and in combination with other agents.

This study investigated the in-vitro activity of clinically relevant aminoglycosides and new antimicrobial agents-plazomicin, ceftobiprole and dalbavancin-against 55 methicillin-resistant Staphylococcus aureus (MRSA) isolates producing aminoglycoside-modifying enzymes (AMEs). The checkerboard method was used to assess synergism between plazomicin and four antibiotics (fosfomycin, ceftobiprole, cefoxitin and meropenem), and time-kill assays were performed for the most active combinations. Among the aminoglycosides tested, plazomicin was the most active agent against MRSA, with >90% of isolates being inhibited at a minimum inhibitory concentration (MIC) of ≤1 mg/L. MIC50 and MIC90 values for ceftobiprole and dalbavancin were 2 and 4 mg/L, and 0.125 and 0.125 mg/L, respectively. The most prevalent AME gene was aac(6')Ie-aph(2″)Ia (87.3%), followed by ant(4')Ia (52.7%) and aph(3')IIIa (52.7%). Plazomicin activity was not affected by the type or number of enzymes detected. In checkerboard and time-kill assays, indifference was the most common result achieved for the antibiotic combinations. Notably, no antagonism was observed with any combination tested. Overall, plazomicin in combination with meropenem had the highest synergistic effect, demonstrating synergy against seven isolates in the checkerboard assay and three isolates in time-kill curves. In conclusion, plazomicin showed potent activity against aminoglycoside-resistant MRSA isolates, regardless of the number and type of AMEs present. These findings indicate the potential utility of plazomicin in combination with meropenem for the treatment of MRSA infections.

Consenso sobre la vacunación anti-neumocócica en el adulto por riesgo de edad y patología de base. Actualización 2017 / Consensus document on pneumococcal vaccination in adults at risk by age and underlying clinical conditions. 2017 Update

La enfermedad neumocócica invasiva (ENI) y la neumonía neumocócica (NN) suponen un grave problema de salud entre los adultos de mayor edad y aquellos con determinadas condiciones y patologías de base, entre los que destacan los inmunodeprimidos y algunos inmunocompetentes, que les hacen más susceptibles a la infección y favorecen cuadros de mayor gravedad y peor evolución. Entre las estrategias para prevenir la ENI y la NN se encuentra la vacunación, aunque las coberturas vacunales son más bajas de lo deseable. Actualmente, existen 2 vacunas disponibles para el adulto. La vacuna polisacárida (VNP23), que se emplea en mayores de 2 años de edad desde hace décadas, es la que mayor número de serotipos (23) incluye, pero no genera memoria inmunitaria, los niveles de anticuerpos disminuyen con el tiempo, provoca un fenómeno de tolerancia inmunitaria y no actúa sobre la colonización nasofaríngea. La vacuna conjugada (VNC13) puede emplearse a cualquier edad de la vida a partir de las 6 semanas de vida y genera una respuesta inmunitaria más potente que la VNP23 frente a la mayoría de los 13 serotipos en ella incluidos. En el año 2013 las 16 Sociedades Científicas más directamente relacionadas con los grupos de riesgo para padecer ENI publicamos un documento de Consenso con una serie de recomendaciones basadas en las evidencias científicas respecto a la vacunación antineumocócica en el adulto con condiciones especiales y patología de base. Se estableció un compromiso de discusión y actualización ante la aparición de nuevas evidencias. Fruto de este trabajo de revisión, presentamos una actualización del anterior documento junto a otras nuevas Sociedades Científicas donde destaca la recomendación por edad (AU)

Invasive pneumococcal disease (IPD) and pneumococcal pneumonia (PP) represent an important health problem among aging adults and those with certain underlying pathologies and some diseases, especially immunosuppressed and some immunocompetent subjects, who are more susceptible to infections and present greater severity and worse evolution. Among the strategies to prevent IPD and PP, vaccination has its place, although vaccination coverage in this group is lower than desirable. Nowadays, there are 2 vaccines available for adults. Polysacharide vaccine (PPV23), used in patients aged 2 and older since decades ago, includes a greater number of serotypes (23), but it does not generate immune memory, antibody levels decrease with time, causes an immune tolerance phenomenon, and have no effect on nasopharyngeal colonization. PCV13 can be used from children 6 weeks of age to elderly and generates an immune response more powerful than PPV23 against most of the 13 serotypes included in it. In the year 2013 the 16 most directly related to groups of risk of presenting IPD publised a series of vaccine recommendations based on scientific evidence regarding antipneumococcal vaccination in adults with underlying pathologies and special conditions. A commitment was made about updating it if new scientific evidence became available. We present an exhaustive revised document focusing mainly in recommendation by age in which some more Scientific Societies have been involved (AU)

Epidemiology of Otitis Media with Spontaneous Perforation of the Tympanic Membrane in Young Children and Association with Bacterial Nasopharyngeal Carriage, Recurrences and Pneumococcal Vaccination in Catalonia, Spain - The Prospective HERMES Study.

The Epidemiology of otitis media with spontaneous perforation of the tympanic membrane and associated nasopharyngeal carriage of bacterial otopathogens was analysed in a county in Catalonia (Spain) with pneumococcal conjugate vaccines (PCVs) not included in the immunization programme at study time. A prospective, multicentre study was performed in 10 primary care centres and 2 hospitals (June 2011-June 2014), including all otherwise healthy children ≥2 months ≤8 years with otitis media presenting spontaneous tympanic perforation within 48h. Up to 521 otitis episodes in 487 children were included, showing by culture/PCR in middle ear fluid (MEF): Haemophilus influenzae [24.2%], both Streptococcus pneumoniae and H. influenzae [24.0%], S. pneumoniae [15.9%], Streptococcus pyogenes [13.6%], and Staphylococcus aureus [6.7%]. Culture-negative/PCR-positive otitis accounted for 31.3% (S. pneumoniae), 30.2% (H. influenzae) and 89.6% (mixed S. pneumoniae/H. influenzae infections). Overall, incidence decreased over the 3-year study period, with significant decreases in otitis by S. pneumoniae and by H. influenzae, but no decreases for mixed S. pneumoniae/H. influenzae infections. Concordance between species in nasopharynx and MEF was found in 58.3% of cases, with maximal rates for S. pyogenes (71.8%), and with identical pneumococcal serotype in 40.5% of cases. Most patients (66.6%) had past episodes. PCV13 serotypes were significantly more frequent in first episodes, in otitis by S. pneumoniae as single agent, and among MEF than nasopharyngeal isolates. All non-PCV13 serotypes separately accounted for <5% in MEF. Up to 73.9% children had received ≥1 dose of PCV, with lower carriage of PCV13 serotypes than among non-vaccinated children. Pooling pneumococcal isolates from MEF and nasopharynx, 30% were multidrug resistant, primarily belonging to serotypes 19A [29.8%], 24A [14.3%], 19F [8.3%] and 15A [6.0%]. Our results suggest that increasing PCV13 vaccination would further reduce transmission of PCV13 serotypes with special benefits for youngest children (with none or uncompleted vaccine schedules), preventing first otitis episodes and subsequent recurrences.

Detection of Escherichia coli ST131 clonal complex (ST705) and Klebsiella pneumoniae ST15 among faecal carriage of extended-spectrum ß-lactamase- and carbapenemase-producing Enterobacteriaceae.

PURPOSE: The objective of the present study was to evaluate the prevalence of intestinal colonization with extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) in non-selected hospitalized and non-hospitalized patients from the same geographic area of Madrid. METHODOLOGY: A total of 501 fecal samples were screened. Diluted samples in saline were cultured in MacConkey agar plates with ceftazidime, cefotaxime, imipenem and meropenem disks. Colonies growing within the inhibition zone of either disk were selected. Characterization of ESBLs and CPEs were performed by PCR and sequencing. The Wider system was used for the bacterial identification. In addition, clonal analysis was carried out for species predominant among the fecal carriage. KEY FINDINGS: Among the 501 patients enrolled, 43 (8.6 %) carried ESBL-E and 8 (1.6 %) patients exhibited CPE. The main intestinal colonizer among ESBL-E was CTX-M-producing Escherichia coli isolates in both settings (community and hospital). ST131 clonal complex was the most common among faecal ESBL-producing E. coli. All gut carriers of CPE were hospitalized patients, Klebsiella pneumoniae being the most prevalent species. Two OXA-48-producing K. pneumoniae isolates belonging to ST15 were detected. CONCLUSION: Present study reveals that faecal carriage of ESBL is common among inpatients and outpatients, whereas carbapenemase producers are only present in the hospital setting. Therefore, active surveillance will be useful for reducing transmission of antimicrobial-resistant bacteria and preventing infection.

Evaluation of the Alere i Influenza A&B assay for rapid identification of influenza A and influenza B viruses.

The Alere i Influenza A&B assay is a novel isothermal nucleic acid amplification assay capable of detecting and differentiating influenza A and B viruses in approximately 15 min with minimal hands-on time. This study was conducted in order to assess the performance of the Alere i Influenza A&B assay compared to molecular techniques, considered to be gold standard methods, to evaluate the results. A total of 119 nasopharyngeal swabs collected from inpatients with influenza-like illness were included in the study using both archived and prospectively collected samples from adults and children. Prospectively collected samples were also compared to the Alere BinaxNOW® Influenza A & B Card. The overall sensitivity for detection of influenza A and B viruses compared to those of molecular techniques were 65.96 % and 53.33 % respectively, while the specificity was 98.51 % and 95.96 %. Compared to the Alere BinaxNOW® Influenza A & B Card, the Alere i assay is considerably more sensitive for detection of influenza A and B viruses, although both tests demonstrated excellent specificity for diagnosis of influenza viruses.

[Update in Infectious Diseases 2015]. / Actualización en Patología Infecciosa 2015.

Infectious disease remains current worldwide. During the second half of 2014 an outbreak of ebolavirus hit West Africa with implications in the rest of the world. In fact, Spain declared the first imported case of this infection. Multiresistant enterobacteria outbreaks are emerging all around the world in a moment on which WHO draws attention to the limited resources, coining the term "post antibiotic era". On the other hand, 2014 went down in history as one in which hepatitis C is cured. Are also current HIV epidemiological control or strategies for antiviral and antifungal prophylaxis in immunocompromised hosts.

Actualización en Patología Infecciosa 2015 / Update in Infectious Diseases 2015

La patología infecciosa continúa estando de actualidad en el mundo. La segunda mitad de 2014 un brote de ebolavirus azotó África occidental con implicaciones en el resto del mudo, de hecho, en España se declaró el primer caso importado de esta infección. En los hospitales de todo el mundo emergen brotes de enterobacterias multirresistentes en un momento en el que la OMS llama la atención sobre los limitados recursos, acuñando el término de 'era postantibiotica'. Sin embargo, el ultimo año pasará a la historia de la medicina como aquel en el que se curó la hepatitis C. Continúan estando de actualidad la dificultad en el control epidemiológico de la transmisión del VIH o las estrategias para la profilaxis antivírica o antifúngica en el paciente inmunosuprimido (AU)

Infectious disease remains current worldwide. During the second half of 2014 an outbreak of ebolavirus hit West Africa with implications in the rest of the world. In fact, Spain declared the first imported case of this infection. Multiresistant enterobacteria outbreaks are emerging all around the world in a moment on which WHO draws attention to the limited resources, coining the term 'post antibiotic era'. On the other hand, 2014 went down in history as one in which hepatitis C is cured. Are also current HIV epidemiological control or strategies for antiviral and antifungal prophylaxis in immunocompromised hosts (AU)

Could ceftaroline be an alternative therapy for linezolid resistant Staphylococcus epidermidis infections in Intensive Care Medicine? / ¿Podría ceftarolina ser una alternativa terapéutica frente a las infecciones por Staphylococcus epidermidis en el paciente crítico?

Introduction. Staphylococcus coagulasa negativo sigue generando interés en los pacientes críticos, debido a sus infecciones en los ingresos prolongados, en pacientes instrumentados y, debido a su resistencia a múltiples fármacos descrito, que incluyen la heterorresistencia a glicopéptidos y el aumento de la resistencia oxazolidinonas. Ceftarolina es una nueva cefalosporina con actividad frente a grampositivos resistentes, que, por ser un betalactámico, podría proporcionar un perfil de seguridad adecuado en el paciente crítico. El objetivo de este estudio fue determinar la actividad de ceftarolina y otros agentes antimicrobianos frente a cepas de Staphylococcus epidermidis resistente a meticilina y linezolid. Material y métodos. Estudiamos la sensibilidad de ceftarolina, tigeciclina, daptomicina y vancomicina en un total de sesenta y ocho aislamientos con significación clínica de S. epidermidis resistente a meticilina y linezolid en una Unidad de Cuidados Intensivos, usando E-test. Resultados. Todas las cepas fueron sensibles a los cuatro agentes antimicrobianos, con independencia del nivel de resistencia a linezolid. Conclusión. Ceftarolina podría ser una alternativa en el tratamiento de infecciones por S. epidermidis resistente a meticilina y linezolid en el paciente crítico (AU)

Introduction. Coagulase negative Staphylococcus continues generating interest in critically ill patients, due to their infections in extended admissions, in instrumented patients and due to their described multidrug resistance, which include glycopeptide heterorresistance and the increase in oxazolidinone resistance. Ceftaroline is a new cephalosporin with activity against resistant gram-positives, which, being betalactam, may provide adequate safety profile in the critical ill patient. The aim of this study was to determine the activity of ceftaroline and other antimicrobial agents against methicillin and linezolid-resistant Staphylococcus epidermidis. Material and methods. We studied susceptibility of ceftaroline, tigecycline, daptomycin and vancomycin in a total of sixty-eight methicillin and linezolid-resistant S. epidermidis isolates with clinical significance from an Intensive Care Unit, using E-test. Results. All strains were susceptible to the four antimicrobial agents, regardless of the level of resistance to linezolid. Conclusion. Ceftaroline could be an alternative in the treatment of methicillin and linezolid-resistant S. epidermidis infections in critically ill patients (AU)

Could ceftaroline be an alternative therapy for linezolid resistant Staphylococcus epidermidis infections in Intensive Care Medicine?

INTRODUCTION: Coagulase negative Staphylococcus continues generating interest in critically ill patients, due to their infections in extended admissions, in instrumented patients and due to their described multidrug resistance, which include glycopeptide heterorresistance and the increase in oxazolidinone resistance. Ceftaroline is a new cephalosporin with activity against resistant gram-positives, which, being betalactam, may provide adequate safety profile in the critical ill patient. The aim of this study was to determine the activity of ceftaroline and other antimicrobial agents against methicillin and linezolid-resistant Staphylococcus epidermidis. MATERIAL AND METHODS: We studied susceptibility of ceftaroline, tigecycline, daptomycin and vancomycin in a total of sixty-eight methicillin and linezolid-resistant S. epidermidis isolates with clinical significance from an Intensive Care Unit, using E-test. RESULTS: All strains were susceptible to the four antimicrobial agents, regardless of the level of resistance to linezolid. CONCLUSION: Ceftaroline could be an alternative in the treatment of methicillin and linezolid-resistant S. epidermidis infections in critically ill patients.

Characterization of Inhibitor-Resistant TEM ß-Lactamases and Mechanisms of Fluoroquinolone Resistance in Escherichia coli Isolates.

The aim of present work was to characterize the inhibitor-resistant TEM (IRT) ß-lactamases produced by Escherichia coli in Hospital Clínico San Carlos (Madrid, Spain). Mechanisms of fluoroquinolone resistance among IRT-producing strains were also studied. Isolates with susceptibility to cephalosporins and amoxicillin-clavulanate (AMC) resistance were collected in our hospital (November 2011-July 2012) from both outpatients and hospitalized patients. Among 70 AMC-resistant E. coli strains, 28 (40%) produced IRT enzymes. Most of them were uropathogens (82.1%) and recovered from outpatients (75%). Seven different IRT enzymes were identified with TEM-30 (IRT-2) being the most prevalent, followed by TEM-40 (IRT-11). A high rate of ciprofloxacin resistance was found among IRT-producing strains (50%). Most of the ciprofloxacin-resistant isolates showed ciprofloxacin minimum inhibitory concentration >32 mg/L and contained two mutations in both gyrA and parC genes. Four IRT enzyme producers harbored the qnr gene. ST131 clone was mainly responsible for both IRT enzyme production and ciprofloxacin resistance. In conclusion, data from this study show that the frequency of IRT producers was 40% and a high rate of ciprofloxacin resistance was found among IRT-producing isolates. Current and future actions should be taken into account to avoid or reduce the development of AMC and fluoroquinolone resistance in E. coli.

The intangible benefits of vaccination - what is the true economic value of vaccination?

Previous economic evaluations of new vaccines largely focussed on a narrow set of benefit categories, including primarily health gains and disease-related medical cost-savings, which probably resulted in underestimates of the true value of these vaccines. Other economic benefits of vaccines could be considered to assess the full economic value of vaccination, such as, for example, impact of the human papillomavirus vaccine on women's fertility through the decrease in precancerous lesions and, therefore, in the number of diagnostic and treatment interventions, which can be associated with an increased risk of subsequent pregnancy complications. Vaccines' impact on resource allocation at hospital level or on antimicrobial resistance, such as pneumococcal conjugate vaccines that have substantially reduced infections due to antimicrobial non-susceptible strains, thereby rendering the residual disease easier to treat, are other examples of intangible benefits of vaccination. These benefits are generally not considered in economic evaluations because they may not be immediately visible and are difficult to quantify. However, they should be taken into consideration in health technology assessments to enable those responsible for healthcare policies to make well-informed decisions on vaccination.

Osteomielitis esternal y mediastinitis por Fusobacterium necrophorum / Sternal osteomyelitis and mediastinitis due to Fusobacterium necrophorum

No disponible

Consenso sobre la vacunación anti-neumocócica en el adulto con patología de base / No disponible

La enfermedad neumocócica invasiva (ENI) supone un grave problema de salud entre los adultos con determinadas condiciones y patologías de base, entre los que destacan los inmunodeprimidos y algunos inmunocompetentes, que les hacen más susceptibles a la infección y favorecen cuadros de mayor gravedad y peor evolución. Entre las estrategias para prevenir la ENI se encuentra la vacunación, aunque las coberturas vacunales en este grupo son más bajas de lo deseable. Actualmente, existen 2 vacunas disponibles para el adulto. La vacuna polisacárida (VNP23), que se emplea en mayores de 2 años de edad desde hace décadas, es la que mayor número de serotipos (23) incluye, pero no genera memoria inmunitaria, los niveles de anticuerpos disminuyen con el tiempo, provoca un fenómeno de tolerancia inmunitaria y no actúa sobre la colonización nasofaríngea. La vacuna conjugada (VNC13) puede emplearse desde lactantes hasta la edad adulta (la indicación en mayores de 18 años ha recibido la aprobación de la Agencia Europea del Medicamento en julio de 2013) y genera una respuesta inmunitaria más potente que la VNP23 frente a la mayoría de los 13 serotipos en ella incluidos. Las 16 Sociedades Científicas más directamente relacionadas con los grupos de riesgo para padecer ENI han trabajado en la discusión y elaboración de una serie de recomendaciones vacunales basadas en las evidencias científicas respecto a la vacunación anti-neumocócica en el adulto con condiciones y patología de base que se detallan en este documento. Se trata de un documento “vivo” que seguirá actualizándose ante nuevas evidencias científicas disponibles (AU)

Characterization and monitoring of linezolid-resistant clinical isolates of Staphylococcus epidermidis in an intensive care unit 4 years after an outbreak of infection by cfr-mediated linezolid-resistant Staphylococcus aureus.

Resistance to linezolid is emerging among Staphylococcus epidermidis isolates. During the 4 years following an outbreak of cfr-mediated linezolid-resistant S. aureus in our intensive care unit in 2008, we analyzed the clinical context and characterized the resistance mechanisms of 100 linezolid-resistant strains of S. epidermidis. The prevalence of the cfr gene in our strains reached 50% alone or in combination with other mechanisms. The mutation G2576T in domain V was found in 22% of strains, and both the cfr gene and G2576T in 44%. We also found an association between the cfr gene and mutations in the ribosomal protein L3. All 3 mechanisms co-occurred in 1 strain. MICs in combinations rose to >256 µg/mL. 58% of colonized patients, and 90% of infected patients had previously received linezolid for at last 10 days. Vancomycin was the main antibiotic in these infections, most of which were bacteremia. We found a high prevalence of the cfr gene in our clinical S. epidermidis isolates after the 2008 outbreak, despite having implemented isolation and control measures. The potential transmissibility of this agent, even without prior exposure to linezolid, can have serious epidemiological repercussions.

Rapid diagnosis of invasive pneumococcal disease in pediatric population.

The aim of this study was to evaluate the Binax NOW immunochromatographic pneumococcal antigen test for the identification of Streptococcus pneumoniae in pleural and cerebrospinal fluids from children with suspected invasive pneumococcal disease. The results were compared with those obtained by PCR. Binax NOW was applied to these samples as recommended by the manufacturer for urine and cerebrospinal samples. Detection of pneumococcal DNA was performed by real-time PCR assay targeting the autolysin gene (lytA). Of the 199 samples analyzed, 131 were positive by both Binax NOW and lytA PCR, and 36 samples were negative by both techniques. Using the real-time PCR as a comparative method to the Binax for the detection of S. pneumoniae, the sensitivity and specificity of Binax NOW was 88% and 72.5%, respectively. Of the 145 positive samples analyzed by Binax NOW, 119 showed intense coloring of the sample line and 26 showed weak intensity. Conventional culture is the most common method in clinical settings, but Binax NOW is an easier and faster test for identifying S. pneumoniae in pleural and cerebrospinal fluids from children with suspected invasive pneumococcal disease.

In vitro activity of retapamulin against linezolid and methicillin–resistant Staphylococcus aureus isolates

Objetivos: Determinar la actividad in vitro de retapamulina y otros antibióticos tópicos (mupirocina, bacitracina y ácido fusídico) usados habitualmente para la descolonización nasal, contra Staphylococcus aureus sensible a meticilina (SASM), Staphylococcus aureus resistente a meticilina (SARM) y Staphylococcus aureus resistente a meticilina y linezolid (SARM-L). Material y métodos: Se determinaron las concentraciones mínimas inhibitorias (CMIs) en agar Mueller-Hinton de siguiendo los estándares del Clinical and Laboratory Standards Institute (CLSI) y European Committee for Antimicrobial Susceptibility Testing (EUCAST). La presencia del gen cfr en las cepas SARM-L se realizó usando la reacción en cadena de la polimerasa (PCR). Resultados: Retapamulina inhibió todas las cepas de SASM and SARM alcanzando CMIs sobre 0,125 mg/L, pero las 18 cepas SARM-L se mostraron resistentes, con CMIs en torno a 32 mg/L. La mayoria de los aislados de SASM (9/10) fueron sensibles a mupirocina con CMIs inferiores a 0,19 mg/L, aunque entre las cepas de SARM tan solo fueron sensibles la mitad. La mayoría de las cepas SARM-L (17/18) fueron resistentes a mupirocina con CMIs entre 8 mg/L y 28 mg/L. La CMI de ácido fusídico aumento sustancialmente frente a las cepas SARM-L. Frente a la bacitracina no se observaron diferencias. Conclusiones: Retapamulina demostró una excelente actividad in vitro frente a cepas SASM y SARM, pero no frente a las cepas de SARM portadoras del gen cfr. Los resultados in vitro de este estudio refrendan los puntos de corte de retapamulina de <=0,5, 1, y >=2 mg/L para sensible, intermedio y resistente, respectivamente(AU)

Objectives: To determine the in vitro activity of retapamulin and other topical antibiotics (mupirocin, bacitracin, and fusidic acid) usually employed for nasal decolonization, against methicillin- susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and linezolid and methicillin–resistant S. aureus. Methods: The minimum inhibitory concentrations (MICs) were determined on Mueller-Hinton agar according to the guidelines of the Clinical and Laboratory Standards Institute and of the European Committee for Antimicrobial Susceptibility Testing. Presence of the cfr gene in linezolid and methicillin–resistant S. aureus isolates was detected using polymerase chain reaction. Results: Retapamulin inhibited all the isolates of MSSA and MRSA at 0.125 mg/L, but the 18 linezolid-resistant-MRSA strains proved resistant, with MICs over 32 mg/L. Most MSSA isolates (9/10) were susceptible to mupirocin with MICs under 0.19 mg/L, although this value decreased to half against MRSA, and almost all linezolid-resistant MRSA (17/18) strains were resistant to mupirocin with an MIC range of between 8 mg/L and 28 mg/L. The MIC of fusidic acid increased substantially against linezolid- resistant MRSA, whereas that of bacitracin showed no differences. Conclusions: Retapamulin demonstrated excellent in vitro activity against MSSA and MRSA strains, but not against MRSA isolates harbouring the cfr gene. The results of this in vitro study support cut-off values for retapamulin of <=0.5, 1, and >= 2 mg/L for susceptible, intermediate, and resistant strains, respectively(AU)

Structure-activity relationships of diverse oxazolidinones for linezolid-resistant Staphylococcus aureus strains possessing the cfr methyltransferase gene or ribosomal mutations.

Staphylococcal resistance to linezolid (LZD) is mediated through ribosomal mutations (23S rRNA or ribosomal proteins L3 and L4) or through methylation of 23S rRNA by the horizontally transferred Cfr methyltransferase. To investigate the structural basis for oxazolidinone activity against LZD-resistant (LZD(r)) strains, we compared structurally diverse, clinically relevant oxazolidinones, including LZD, radezolid (RX-1741), TR-700 (torezolid), and a set of TR-700 analogs (including novel CD-rings and various A-ring C-5 substituents), against a panel of laboratory-derived and clinical LZD(r) Staphylococcus aureus strains possessing a variety of resistance mechanisms. Potency against all strains was correlated with optimization of C- and D-rings, which interact with more highly conserved regions of the peptidyl transferase center binding site. Activity against cfr strains was retained with either hydroxymethyl or 1,2,3-triazole C-5 groups but was reduced by 2- to 8-fold in compounds with acetamide substituents. LZD, which possesses a C-5 acetamide group and lacks a D-ring substituent, demonstrated the lowest potency against all strains tested, particularly against cfr strains. These data reveal key features contributing to oxazolidinone activity and highlight structural tradeoffs between potency against susceptible strains and potency against strains with various resistance mechanisms.

High percentage of resistance to ciprofloxacin and qnrB19 gene identified in urinary isolates of extended-spectrum beta-lactamase-producing Escherichia coli in Madrid, Spain.

The presence of qnr genes in 191 extended-spectrum beta-lactamase-producing Escherichia coli from 2005, with 75% of resistance to ciprofloxacin, was evaluated. An SHV-12-producing E. coli carried qnrB19; both genes were transferred by conjugation. No qnrA- or qnrS-positive strains were detected. In addition, we identified 3 new parC mutations (S80W, E84R, and E84A).

Direct serogrouping of Streptococcus pneumoniae strains in clinical samples by use of a latex agglutination test.

Pneumotest-Latex (Statens Seruminstitut) was evaluated for direct serogrouping of Streptococcus pneumoniae strains in clinical samples from patients with invasive disease. The technique was accurate to its level of discrimination for 62 of 67 clinical samples (92.5%). Pneumotest-Latex would be a useful alternative for direct serogrouping of pneumococci in clinical samples.