Bayesian approach to urinary ESBL-producing Escherichia coli

This is a retrospective study about the prevalence of ESBL-producing Escherichia coli (EEC) in urinary specimens from patients from the Comunitat Valenciana from January 2007 to December 2008. Data were retrieved from RedMIVA, and Bayesian generalized linear mixed models were considered to study the prevalence of EEC with regard to demographical and microbiological factors. The total number of infections considered was 164,502, the amount of urinary isolates was 70,827 belonging to 49,304 different patients, and 5,161 (7.3%) of the urinary isolates were EEC. Three out of four E. coli were isolated in women (76.8%), men showed higher rates of EEC (9.7% in men vs. 6.5% in women). EEC patients were, in average, 10.8 years older, and hospitalization was more frequent (9.9% vs. 6.9%). Resistance to non-β-lactams antimicrobials was higher in EEC. The rates of ciprofloxacin and co-trimoxazol resistance in EEC were 75.5% and 52.0%, respectively, whereas it ranged between 1.4-12.4% for the rest of antimicrobials.Prior EEC infection and hospitalization were the most relevant risk factors and increased the expected EEC probability approximately 400% and 50% respectively. Other infections played an important and positive role too, Enterobacteriaceae, P. aeruginosa and other bacteria being the most relevant elements. Female gender was a protective factor and reduced the risk by approximately 25% while age was an additive risk factor. Finally, an open-access web-based software was constructed to compute the probability that an E. coli in a urinary infection be an EEC from a specific combination of risk factors. This pharmacovigilance tool should prove useful to monitor and control antimicrobial resistance spread

Risk factors for multidrug-resistant pathogens in bronchiectasis exacerbations

Background: Non-cystic fibrosis bronchiectasis is a chronic structural lung condition that courses with recurrent infectious exacerbations that lead to frequent antibiotic treatment making this population more susceptible to acquire pathogens with antibiotic resistance. We aimed to investigate risk factors associated with isolation of multidrug-resistant pathogens in bronchiectasis exacerbations. Methods: A prospective observational study was conducted in two tertiary-care hospitals, enrolling patients when first exacerbation appeared. Multidrug-resistance was determined according to European Centre of Diseases Prevention and Control classification. Results: Two hundred thirty three exacerbations were included and microorganisms were isolated in 159 episodes. Multidrug-resistant pathogens were found in 20.1% episodes: Pseudomonas aeruginosa (48.5%), methicillin-resistant Staphylococcus aureus (18.2%) and Extended spectrum betalactamase + Enterobacteriaceae (6.1%), and they were more frequent in exacerbations requiring hospitalization (24.5% vs. 10.2%, p: 0.016). Three independent multidrugresistant risk factors were found: chronic renal disease (Odds ratio (OR), 7.60, 95% CI 1.92-30.09), hospitalization in the previous year (OR, 3.88 95% CI 1.37-11.02) and prior multidrug-resistant isolation (OR, 5.58, 95% CI 2.02-15.46). The proportion of multidrug-resistant in the 233 exacerbations was as follows: 3.9% in patients without risk factors, 12.6% in those with 1 factor and 53.6% if ≥2 risk factors. Conclusions: Hospitalization in the previous year, chronic renal disease, and prior multidrug-resistant isolation are risk factors for identification multidrug-resistant pathogens in exacerbations. This information may assist clinicians in choosing empirical antibiotics in daily clinical practice

Starkeya nomas sp. nov., a prosthecate and budding bacterium isolated from an immunocompromized patient

Strain HF14-78462T is an environmental bacterium found in clinical samples from an immunocompromized patient in 2014 at Hospital Universitari i Politècnic La Fe (Valencia, Spain). Phenotypically, strain HF14-78462T cells were Gram-stain-negative, aerobic, non-spore forming and non-motile small rods which formed mucous and whitish-translucent colonies when incubated at 20-36 °C. Phylogenetic analyses based on the 16S rRNA genes and the whole genomes of closest sequenced relatives confirmed that strain HF14-78462T is affiliated with the genus Starkeya. The strain was oxidase, catalase and urease positive; but indole, lysine decarboxylase, ornithine decarboxylase and DNase negative, did not produce H2S and was able to utilize a wide variety of carbon sources including acetamide, adonitol, amygdalin, l-arabinose, citric acid, glucose, mannitol and melibiose. Unlike Starkeya novella and Starkeya koreensis, strain HF14-78462T failed to grow in thiosulphate-oxidizing media and had a narrower temperature growth range. Its genome was characterized by a size of 4.83 Mbp and a C+G content of 67.75 mol%. Major fatty acids were C18:1 ω7c, cyclo C19 : 0 and C16 : 0, its polar acids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and an aminophospholipid; while the ubiquinones were Q9 (1.8 %) and Q10 (98.2 %). Digital DNA-DNA hybridization values were 41 and 41.4 against S. novella and S. koreensis, respectively, while average nucleotide identity values were around 84 %. Phenotypic, average nucleotide identity and phylogenomic comparative studies suggest that strain HF14-78462T is a new representative of the genus Starkeya and the name Starkeya nomas sp. nov. is proposed. The type strain is HF14-78462T (=CECT 30124T=LMG 31874T).Financial support was obtained by the IIS project 2013/0437.S

In vitro and in vivo activities of linezolid alone and combined with vancomycin and imipenem against Staphylococcus aureus with reduced susceptibility to glycopeptides

The objective of this study was to evaluate the in vitro and in vivo efficacies of linezolid (35 mg/kg/5 h), vancomycin (60 mg/kg/5 h), imipenem (30 mg/kg/5 h), linezolid+imipenem, linezolid+vancomycin and vancomycin+imipenem against two clinical Staphylococcus aureus isolates with reduced susceptibility to glycopeptides using time–kill curves and the murine peritonitis model. Time–kill curves were performed over 24 h. For the murine peritonitis model, peritonitis was induced by the intraperitoneal inoculation of 108 CFU/ml of each bacterial strain. Four hours later (0 h), the mice were randomly assigned to a control group or to therapeutic groups receiving subcutaneous treatment for 25 h. Bacterial counts in peritoneal fluid, bacteraemia and mortality rates were determined. The time–kill curves showed that the addition of linezolid to imipenem yielded synergistic results after 24 h. The addition of linezolid decreased vancomycin activity. In the animal model, vancomycin and linezolid monotherapies produced comparable bacterial decreases in mice infected with each strain but linezolid achieved higher rates of blood sterilisation. Linezolid tested either in monotherapy or in combination showed similar efficacy against both strains in terms of bacterial killing, number of negative blood cultures and survival. Linezolid and vancomycin were moderately bactericidal and similar in efficacy against glycopeptide-intermediate or -resistant S. aureus. Linezolid combinations, as effective as linezolid tested alone, could be considered as alternative options for the treatment of glycopeptide-intermediate S. aureus (GISA) infections

A surface plasmon resonance based approach for measuring response to pneumococcal vaccine

Incidence of pneumococcal disease has increased worldwide in recent years. Response to pneumococcal vaccine is usually measured using the multiserotype enzyme-linked immunosorbent assay (ELISA) pneumococcal test. However, this approach presents several limitations. Therefore, the introduction of new and more robust analytical approaches able to provide information on the efficacy of the pneumococcal vaccine would be very beneficial for the clinical management of patients. Surface plasmon resonance (SPR) has been shown to offer a valuable understanding of vaccines' properties over the last years. The aim of this study is to evaluate the reliability of SPR for the anti-pneumococcal capsular polysaccharides (anti-PnPs) IgGs quantification in vaccinated. Fast protein liquid chromatography (FPLC) was used for the isolation of total IgGs from serum samples of vaccinated patients. Binding-SPR assays were performed to study the interaction between anti-PnPs IgGs and PCV13. A robust correlation was found between serum levels of anti-PnPs IgGs, measured by ELISA, and the SPR signal. Moreover, it was possible to correctly classify patients into "non-responder", "responder" and "high-responder" groups according to their specific SPR PCV13 response profiles. SPR technology provides a valuable tool for reliably characterize the interaction between anti-PnPs IgGs and PCV13 in a very short experimental time

Short-course versus long-course therapy of the same antibiotic for community-acquired pneumonia in adolescent and adult outpatients

BACKGROUND: Community-acquired pneumonia (CAP) is a lung infection that can be acquired during day-to-day activities in the community (not while receiving care in a hospital). Community-acquired pneumonia poses a significant public health burden in terms of mortality, morbidity, and costs. Shorter antibiotic courses for CAP may limit treatment costs and adverse effects, but the optimal duration of antibiotic treatment is uncertain. OBJECTIVES: To evaluate the efficacy and safety of short-course versus longer-course treatment with the same antibiotic at the same daily dosage for CAP in non-hospitalised adolescents and adults (outpatients). We planned to investigate non-inferiority of short-course versus longer-term course treatment for efficacy outcomes, and superiority of short-course treatment for safety outcomes. SEARCH METHODS: We searched CENTRAL, which contains the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE, Embase, five other databases, and three trials registers on 28 September 2017 together with conference proceedings, reference checking, and contact with experts and pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing short- and long-courses of the same antibiotic for CAP in adolescent and adult outpatients. DATA COLLECTION AND ANALYSIS: We planned to use standard Cochrane methods. MAIN RESULTS: Our searches identified 5260 records. We did not identify any RCTs that compared short- and longer-courses of the same antibiotic for the treatment of adolescents and adult outpatients with CAP.We excluded two RCTs that compared short courses (five compared to seven days) of the same antibiotic at the same daily dose because they evaluated antibiotics (gemifloxacin and telithromycin) not commonly used in practice for the treatment of CAP. In particular, gemifloxacin is no longer approved for the treatment of mild-to-moderate CAP due to its questionable risk-benefit balance, and reported adverse effects. Moreover, the safety profile of telithromycin is also cause for concern.We found one ongoing study that we will assess for inclusion in future updates of the review. AUTHORS' CONCLUSIONS: We found no eligible RCTs that studied a short-course of antibiotic compared to a longer-course (with the same antibiotic at the same daily dosage) for CAP in adolescent and adult outpatients. The effects of antibiotic therapy duration for CAP in adolescent and adult outpatients remains unclear.Publisher PDFPeer reviewe

Interacciones entre enfermo y bacterias infecciosas causantes de neumonía

La vía respiratoria está expuesta continuamente a agentes ambientales y microorganismos potencialmente patógenos. El epitelio ciliado, los mucopolisacáridos y los macrófagos alveolares son capaces de destruir y expulsar del espacio aéreo a los agentes patógenos y evitar la progresión a una invasión tisular. Cuando dichas medidas son superadas aparece una infección que activa una serie de citocinas y marcadores inflamatorios, cuyo objetivo es instaurar una respuesta inmunitaria que elimine al patógeno. Esta reacción no se limita únicamente al pulmón, también existe una respuesta sistémica que tendrá repercusiones en el desarrollo del proceso, pronóstico y resultado final. Una vez superados los preceptos de Henle-Koch-Loeffler, que exigen que un patógeno sea aislado en cultivos puros del foco de infección y que estos mismos cultivos sean capaces de producir un cuadro similar al ser inoculados en animales de experimentación, la ciencia está buscando nuevas definiciones para los patógenos infecciosos encontrados en infecciones que expliquen que es un “agente infeccioso”, para los nuevos como los virus o priones, pero también para los clásicos como el neumococo. Los estudios, y también la práctica clínica diaria, nos enseñan que el paciente y sus circunstancias son vitales para la instauración de un determinado proceso infeccioso, para la sintomatología que presenta y sobre todo, para su evolución. Y lo que en principio sería una respuesta inmunitaria frente a una infección acaba abarcando un espectro de manifestaciones que varían desde el cuadro más simple hasta el más catastrófico que puede llevar incluso a la muerte. Características propias del paciente como la edad, hábitos tóxicos o enfermedades de base, pueden modificar la calidad y cantidad de esta respuesta; pero, también el propio agente infeccioso puede determinarla con factores intrínsecos como la presencia de una capsula, los lipopolisacaridos de la pared celular, los factores de virulencia propios de cada especie, sus componentes antigénicos, la velocidad infectiva o el quorum sensing. A pesar de las variaciones en la incidencia de la NAC entre diferentes regiones y estudios, su mayor prevalencia se encuentra en pacientes de 65 años o más, pero también en aquellos con enfermedades crónicas concomitantes, independientemente de la edad. Conocer la respuesta del organismo ante los diferentes patógenos es fundamental para entender la evolución de la enfermedad y poder modificar su evolución. Además, entender que enfermedades o hábitos tóxicos favorecen la aparición de determinados microorganismos es clave para instaurar medidas profilácticas adecuadas, como pueden ser las vacunas, e iniciar prontamente un tratamiento adecuado. Además, el medio ambiente juega un papel importante, muchas veces ignorado o asumido como “lo normal”, pero pocas veces estudiado en complejidad para intentar explicar en qué consiste dicha “normalidad”. ¿Por qué hay un aumento de NAC cuando llega el frío? ¿Qué efecto puede tener la contaminación ambiental en la instauración de una infección pulmonar? ¿O los rayos UVA?. Es por ello que este compendio de artículos incide en la importancia del paciente, del microorganismo causante y de su entorno, aportando una visión global de la enfermedad y mostrando como todos los factores interactúan para instaurar un proceso infeccioso. Este compendio de artículos incluye: 1- Menéndez R, Sahuquillo-Arce JM, Reyes S, Martínez R, Polverino E, Cillóniz C, Córdoba JG, Montull B, Torres A. Cytokine activation patterns and biomarkers are influenced by microorganisms in community-acquired pneumonia. Chest. 2012 Jun;141(6):1537-1545. doi: 10.1378/chest.11-1446. 2- Sahuquillo-Arce JM, Menéndez R, Méndez R, Amara-Elori I, Zalacain R, Capelastegui A, Aspa J, Borderías L, Martín-Villasclaras JJ, Bello S, Alfageme I, de Castro FR, Rello J, Molinos L, Ruiz-Manzano J, Torres A. Age-related risk factors for bacterial aetiology in community-acquired pneumonia. Respirology. 2016 Nov;21(8):1472-1479. doi: 10.1111/resp.12851. 3- Sahuquillo-Arce JM, Ibáñez-Martínez E, Hernández-Cabezas A, Ruiz-Gaitán A, Falomir-Salcedo P, Menéndez R, López-Hontangas JL. Influence of environmental conditions and pollution on the incidence of Streptococcus pneumoniae infections. ERJ Open Res. 2017 Dec 1;3(4). pii: 00014-2017. doi: 10.1183/23120541.00014-2017. eCollection 2017 Oct