Alcohol binge disrupts the rat intestinal barrier: the partial protective role of oleoylethanolamide.

BACKGROUND AND PURPOSE: Chronic alcohol consumption alters the gut-brain axis, but little is known about alcohol binge episodes on the functioning of the intestinal barrier. We investigated the influence of ethanol binges on bacterial translocation, gut inflammation and immunity, and tight junction (TJ) structure and the ability of the biolipid oleoylethanolamide (OEA) to prevent ethanol binge-induced intestinal barrier dysfunction. EXPERIMENTAL APPROACH: OEA was injected i.p. before repeated ethanol administration by oral gavage. Plasma, spleen, liver and mesenteric lymph nodes (MLN) were collected in sterile conditions for determination of bacterial load. Immune/inflammatory parameters, TJ proteins and apoptotic markers were determined in colonic tissue by RT-PCR and Western blotting. TJ ultrastructure was examined by transmission electron microscopy. KEY RESULTS: Ethanol binges induced bacterial translocation to the MLN (mainly) and spleen. Colonic tissues showed signs of inflammation, and activation of innate (Toll-like receptor-4) and adaptive (IgA) immune systems and TJ proteins (occludin and claudin-3) were decreased after ethanol binges. Pretreatment with OEA reduced intestinal inflammation and immune activation and partially preserved the TJ structure affected by alcohol binges but had no effect on alcohol-induced apoptosis. Ultrastructural analyses of colonic TJs revealed dilated TJs in all ethanol groups, with less electron-dense material in non-pretreated rats. The protective effects of i.p. OEA did not reduce bacterial translocation to the MLN. However, intragastric OEA administration significantly reduced plasma LPS levels and bacterial translocation to the MLN. CONCLUSION AND IMPLICATIONS: OEA-based pharmacotherapies could potentially be useful to treat disorders characterized by intestinal barrier dysfunction, including alcohol abuse.

[Is it necessary to prescribe antibiotics in impacted third molar surgical removal?: comparative study between prescribing patterns]. / ¿Está indicada la prescripción de antibióticos en la extracción del tercer molar retenido?: Estudio comparativo entre patrones de prescripción.

OBJECTIVE: To assess whether there is a significant difference in infection rate after surgery tooth extraction in two different hospitals from Norway and Spain where different surgical antimicrobial prophylaxis protocols are applied. METHODS: An analytical observational study was conducted, retrospective cohorts type, analyzing healthy patients with no risk factors, who were third molar tooth operated in maxillofacial services of two different hospitals: St. Olav in Trondheim (Norway) and Clínico San Carlos in Madrid (Spain). The collected variables were: age, number of tooth removed, anesthesia type, and observations about the course of the operation registered in the clinical history. To assess the development of postoperative infection, patient's data of those who chose the hospital as the place to remove the suture thread were collected in Norway, whereas in Spain a telephone survey was conducted to determine the course of the operation months later. RESULTS: In St. Olav Hospital 11.1% of patients operated received antibiotic regimen after surgery, while in Hospital San Carlos were 100%. The infection rate was 15% in St.Olav Hospital and 7.5% in Hospital San Carlos. These differences were no statistically significant. CONCLUSIONS: The routine administration of antibiotics to healthy patients with no risk factors undergoing impacted third molar surgical removal is a common clinical practice which it does not seem to be justified.

Genotypic and phenotypic diversity in Enterococcus faecalis: is agar invasion a pathogenicity score?

OBJECTIVES: The main objective of the present study is to analyze different genotypic and phenotypic traits related to virulence in Enterococcus faecalis, as well as evaluated the agar invasion phenotype in a collection of isolates with different clinical origins. MATERIAL AND METHODS: Seventy-nine E. faecalis isolates, with invasive and non-invasive clinical origins, have been used in this work. Presence of cytolysin activator (cylA), gelatinase (gelE), surface protein (esp), aggregation substance (asa1), endocarditis antigen (efaA), and collagen-binding protein (ace) have been analyzed by PCR. Phenotypic characterization included gelatinase activity, haemolysin production, biofilm formation and agar invasion. RESULTS: All the isolates tested harboured at least one of the virulence determinants. The 95.5% of isolates from haematologic samples were positive for agar invasion test, significantly higher than isolates from non-invasive diseases. A significant reduction in relative invasion area was observed in three selected agar-invasive strains after 15 serial passages. CONCLUSIONS: It has been observed a significant high prevalence of agar-invasion positive isolates among strains belonged to haematological samples. Agar invasiveness is reduced after adaptation of clinical isolates to laboratory conditions, showing that agar invasion phenotype can be modulate by culture conditions as other virulence factors observed in different bacterial species.

[Which is the best empirical treatment in patients with urethritis?]. / ¿Qué tratamiento empírico es el más adecuado en pacientes con uretritis?

OBJECTIVE: To know the best empirical treatment of urethritis in patients at the City Center of Madrid. METHODS: 2.021 urethral exudates were analyzed in men between January 2003-December 2007. In addition to the traditional cultures, it was determined the presence of Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Trichomonas vaginalis and Herpes simplex. The susceptibility of N.gonorrhoeae and Haemophilus spp was performed by disk diffusion method and U. urealyticum by Mycoplasma IST. RESULTS: The percentage of positive samples was: 30.6%. The most frequently isolated microorganisms were: U. urealyticum 9.9%, N. gonorrhoeae 7.4%, C. trachomatis 5.1% and Haemophilus spp 3.8%. The resistance of N. gonorrhoeae in the first period was: penicillin 11.8%, tetracycline 5.9%, ciprofloxacin 8.8% and presence of betalactamase 11.8%. In the second period: penicillin 9.7%, amoxicillin/clavulanic acid 1.4%, tetracycline 8.3%, ciprofloxacin 23.6% and presence of betalactamase 10.5%. Resistance to ciprofloxacin in non-MSM (men having sex with men) was 20% and in MSM 56.2%. Resistance of Haemophilus spp in the first period was: 38.2% ampicillin, amoxicillin/clavulanic acid 8.8%, clarithromycin 35.3%, cotrimoxazole 64.7%, cefuroxime 5.9%, ciprofloxacin 8.8%, tetracycline 12.1% and presence of betalactamase 26.5%. In the second period:presence of betalactamase 41.9%, ampicillin 53.1%, amoxicillin/clavulanic acid 9.4%, cefuroxime 9.4%, clarithromycin 18.7%, tetracycline 34.4%, ciprofloxacin 15.6%, and cotrimoxazole 68.7%. Resistance of U. urealyticum was: ciprofloxacin 80.7%, ofloxacin 32.4%, erythromycin 17.5%, azithromycin 9.6%, tetracycline 3.5% and doxycycline 0.8%. CONCLUSIONS: N. gonorrhoeae showed a level of resistance to tetracycline and ciprofloxacin higher in the second period, being significant for ciprofloxacin. Quinolone resistance was higher in MSM. Haemophilus spp showed a level of resistance to ampicillin, ciprofloxacin and tetracycline higher in the second period, being significant for tetracycline. U.urealyticum showed high level of resistance to ciprofloxacin (80.7%)and ofloxacin (32.4%) and low level of resistance to doxycycline (0.8%) and tetracycline (3.5%).

Evolving architectural patterns in microbial colonies development.

Semithin sections of colonies of three ATCC strains (Staphylococcus aureus, Escherichia coli, and Candida albicans) showed that their internal structure had specific patterns that evolved over the time. These patterns generally were defined by the presence of different layers composed of microorganisms with variable population densities and dead cells. The observed structures in this study could be explained as a particular form of biofilm with an air-semisolid interface.

[Proton pump inhibitors and infection risk]. / Inhibidores de la bomba de protones y riesgo de infección.

Gastric antisecretory drugs, especially proton pump inhibitors, are among the most used drugs both in ambulatory and hospital settings, and prescription does not always follows approved indications. Experimental data suggest that gastric acid inhibition and the effects of proton pump inhibitors on the immune system can promote the development of infections. In recent years a number of observational studies have found an independent association between the use of proton pump inhibitors and an increased risk of gastrointestinal infections, including those caused by Clostridium difficile, and community and nosocomial pneumonia. This review discusses the current evidence, raises the potential pathogenic mechanisms involved and makes recommendations for current clinical practice and future research.

[Why not revisiting tinidazole as potential treatment of odontogenic infections?]. / Por qué no reevaluar el tinidazol como tratamiento potencial de infecciones odontogénicas?

Tinidazole is a 5-nitroimidazole initially introduced into clinical medicine in 1969 for the treatment of unicellular parasites. Tinidazole offers selective bactericidal activity, not influenced by the inoculum size, against anaerobic bacteria, that make it of theoretical interest against periodontopathogen infections. This article reviews the required characteristics of an antibiotic directed to odontogenic anaerobic infections, as well as the pharmacodynamic pitfalls of common antibiotic treatments. In addition the in vitro, pharmacokinetic and pharmacodynamic properties of tinidazole are reviewed, assessing the degree of its adhesion to the required characteristics, as well as identifying the gaps to be fulfilled prior to its use in this medical field. Tinidazole offers interesting characteristics making worthy investigations as a candidate for the treatment of anaerobic odontogenic infections. \

Pharmacodynamics of simulated total versus free-drug serum concentrations of a low versus a high protein bound third-generation oral cephalosporin (Cefpodoxime versus cefditoren) against Streptococcus pneumoniae.

Pharmacodynamic parameters and bactericidal activity against Streptococcus pneumoniae were investigated by simulating total and free serum concentrations of cefpodoxime versus cefditoren. Total drug T>MIC against the penicillin-intermediate (PISP) and resistant (PRSP) strains were 70.6% and 42.9% for cefpodoxime, and 89.6% and 62.5% for cefditoren, respectively. Comparing activity of free versus total cefpodoxime, there were reductions of 8.5% and 19.1% in T>MIC, related to bactericidal activity reductions from approximately 4.5 to 3 log(10), and from 3 to 2.5 log(10 )against PISP and PRSP, respectively, at 10-12h. For cefditoren, reductions of 45.4% and 100% in T>MIC, were related to bactericidal activity reductions from approximately 5.5 to 2-2.5 log(10 )and from approximately 2.5 to 1.5 log(10 )against PISP and PRSP, respectively, at 10-12h. Higher differences in activity were found against the less resistant strains when comparing total versus free-drug profile.

Influencia del desplazamiento de la unión a proteínas por ibuprofeno en la actividad de una cefalosporina de tercera generación frente a Streptococcus pneumoniae / Influence of the displacement of protein binding by ibuprofen in the activity of a third-generation cephalosporin against Streptococcus pneumoniae

El significado clínico de la unión de los antibacterianos a las proteínas plasmáticas es un fenómeno aún no bien definido. El objetivo de esteestudio fue valorar, mediante curvas de muerte bacteriana, el efecto en la actividad bactericida in vitro del cefditoren, a concentracionespróximas a la Cmax, de una administración de 400 mg, frente a tres cepas de Streptococcus pneumoniae (CMI de cefditoren de 0,12, 0,25y 0,5 mg/l) en combinación con albúmina humana (4 g/dl) e ibuprofeno, a la concentración máxima detectada después de la administraciónde 400 mg (32,3 mg/l) y de 10 veces la Cmax (323 mg/l). El cefditoren fue rápidamente bactericida (reducción de 3 log10 UFC/ml del inóculoinicial) frente a todas las cepas empleadas a concentraciones de 4,2 mg/l, en medios de cultivo convencionales. En presencia de albúminahumana este efecto sólo se mantuvo sobre la cepa más sensible (CMI = 0,12 mg/l), detectando recrecimientos más o menos acusadoscon valores de CMI superiores. La presencia de ibuprofeno (32,3 mg/l) retrasó ligeramente la aparición de recrecimientos, mientras queel aumento de la concentración a 10 veces la Cmax de ibuprofeno recuperó la actividad bactericida en todas las cepas. En conclusión, la actividadde un antibacteriano de elevada unión a las proteínas plasmáticas no debería relacionarse exclusivamente con la fracción libre teóricaextrapolada desde las concentraciones plasmáticas. El papel de los antagonistas de la unión a las proteínas merece ser analizado dado sufrecuente uso en procesos respiratorios, particularmente asociados con la administración de cefalosporinas

The clinical significance of protein binding remains to be fully elucidated. The aim of this study was to evaluate the effect in the in vitrobactericidal activity of cefditoren through killing curves at Cmax concentrations against three Streptococcus pneumoniae strains (cefditorenMICs of 0.12, 0.25 and 0.5 mg/l) with or without human albumin (4 g/dl) and ibuprofen at Cmax concentrations (32.3 mg/l) and 10times the Cmax (323 mg/l). Cefditoren was rapidly bactericidal (3 log10 CFU/ml reduction) against the three strains at 4.2 mg/l concentrationin Mueller-Hinton broth plus 5% lysed horse blood. In presence of human albumin, this effect was maintained against the mostsusceptible strain (MIC = 0.12 mg/l). Regrowths were observed with higher MIC values. The presence of ibuprofen (32.3 mg/l) slightly delayedregrowth while the increase of ibuprofen concentration up to 10 x Cmax recovered the bactericidal activity against all strains. Theactivity of an antimicrobial with high protein binding should not be linked exclusively with the theoretical unbound fraction extrapolatedfrom the plasma concentration. The role of protein binding antagonists merits analysis due to their frequent use associated with cephalosporinsin respiratory tract infections

De la lisozima a la penicilina: un camino tan complejo como interesante / From lysozyme to penicillin: a complex and interesting journey

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Las claves de una época: Wright y Fleming / No disponible

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[Activity of cefpodoxime and other oral beta-lactams against Haemophilus influenzae and Streptococcus pneumoniae with different susceptibilities to penicillin]. / Actividad de cefpodoxima y otros betalactámicos orales frente a Haemophilus influenzae y Streptococcus pneumoniae con distinta sensibilidad a la penicilina.

This study explores the influence on the intrinsic activity of different oral beta-lactams of beta-lactamase production in Haemophilus influenzae and penicillin resistance in Streptococcus pneumoniae. Three substudies were performed: a) a general susceptibility study, analyzing 550 strains received by the Spanish Laboratorio de Referencia de Neumococos throughout February and March 2005; b) a study on the influence of penicillin resistance on the activity of beta-lactams, analyzing 251 penicillin-susceptible strains (MICor=2 mg/l) randomly chosen among those received by the Spanish Laboratorio de Referencia de Neumococos throughout 2005; and c) an H. influenzae susceptibility study analyzing 150 strains received by Instituto Valenciano de Microbiologia throughout 2005. A total of 71% of S. pneumoniae strains were susceptible to penicillin, 21% exhibited intermediate resistance and 8% strains presented full resistance. H. influenzae beta-lactamase production rate was 18.6%. Of the non-beta-lactamase-producing strains, 3% were not susceptible to ampicillin. Cefpodoxime and cefixime exhibited the highest intrinsic activity against H. influenzae, while amoxicillin and cefpodoxime were the most active compounds against S. pneumoniae. All H. influenzae strains were susceptible to oral cephalosporins and amoxicillin/clavulanic acid. The increase in penicillin resistance in S. pneumoniae influenced cefixime, cefaclor and cefuroxime to a higher degree than amoxicillin and cefpodoxime.

Actividad de cefpodoxima y otros betalactámicos orales frente a Haemophilus influenzae y Streptococcus pneumoniae con distinta sensibilidad a la penicilina / Activity of cefpodoxime and other oral beta-lactams against Haemophilus influenzae and Streptococcus pneumoniae with different susceptibilities to penicillin

Estudiamos la influencia de la producción de betalactamasas en Haemophilus influenzae y del grado de sensibilidad a la penicilina en Streptococcus pneumoniae sobre la actividad intrínseca de distintos betalactámicos orales. Realizamos tres subestudios: 1) un estudio general de sensibilidad, analizando 550 aislamientos consecutivos recibidos en el Laboratorio de Referencia de Neumococos durante los meses de febrero y marzo de 2005; 2) un estudio de la influencia de la sensibilidad a la penicilina sobre la actividad del resto de los betalactámicos, analizando la sensibilidad de 251 cepas sensibles a la penicilina (CMI ≤0,06 mg/l), 165 cepas con resistencia intermedia (CMI 0,12-1 mg/l) y 139 resistentes (CMI ≥2 mg/l), elegidas aleatoriamente entre todos los aislamientos recibidos durante el año 2005; y 3) un estudio de sensibilidad de H. influenzae, analizando 150 cepas recibidas por el Instituto Valenciano de Microbiología a lo largo del año 2005. El 71% de las cepas de S. pneumoniae fueron sensibles a la penicilina, el 21% presentaron baja resistencia o resistencia intermedia, y un 8% alta resistencia. La tasa de producción de betalactamasas fue del 18,6% en H. influenzae. El 3% de las cepas no productoras de betalactamasas fueron no sensibles a la ampicilina. La cefpodoxima y la cefixima presentaron la mayor actividad intrínseca frente a H. influenzae, mientras que frente a S. pneumoniae ésta correspondió a la amoxicilina y la cefpodoxima. Mientras que el 100% de las cepas de H. influenzae fueron sensibles a las cefalosporinas orales y a amoxicilina-ácido clavulánico, el aumento de la resistencia a la penicilina en S. pneumoniae afectó en mayor grado a la actividad de la cefixima, el cefaclor y la cefuroxima que a la amoxicilina y la cefpodoxima

This study explores the influence on the intrinsic activity of different oral β-lactams of β-lactamase production in Haemophilus influenzae and penicillin resistance in Streptococcus pneumoniae. Three substudies were performed: a) a general susceptibility study, analyzing 550 strains received by the Spanish Laboratorio de Referencia de Neumococos throughout February and March 2005; b) a study on the influence of penicillin resistance on the activity of β-lactams, analyzing 251 penicillin-susceptible strains (MIC ≤0.06 mg/l), 165 penicillin intermediateresistant strains (MIC 0.12–1 mg/l) and 139 penicillin-resistant strains (MIC ≥2 mg/l) randomly chosen among those received by the Spanish Laboratorio de Referencia de Neumococos throughout 2005; and c) an H. influenzae susceptibility study analyzing 150 strains received by Instituto Valenciano de Microbiología throughout 2005. A total of 71% of S. pneumoniae strains were susceptible to penicillin, 21% exhibited intermediate resistance and 8% strains presented full resistance. H. influenzae β-lactamase production rate was 18.6%. Of the non–β-lactamase-producing strains, 3% were not susceptible to ampicillin. Cefpodoxime and cefixime exhibited the highest intrinsic activity against H. influenzae, while amoxicillin and cefpodoxime were the most active compounds against S. pneumoniae. All H. influenzae strains were susceptible to oral cephalosporins and amoxicillin/clavulanic acid. The increase in penicillin resistance in S. pneumoniae influenced cefixime, cefaclor and cefuroxime to a higher degree than amoxicillin and cefpodoxime

[Influence of the displacement of protein binding by ibuprofen in the activity of a third-generation cephalosporin against Streptococcus pneumoniae]. / Influencia del desplazamiento de la unión a proteínas por ibuprofeno en la actividad de una cefalosporina de tercera generación frente a Streptococcus pneumoniae.

The clinical significance of protein binding remains to be fully elucidated. The aim of this study was to evaluate the effect in the in vitro bactericidal activity of cefditoren through killing curves at Cmax concentrations against three Streptococcus pneumoniae strains (cefditoren MICs of 0.12, 0.25 and 0.5 mg/l) with or without human albumin (4 g/dl) and ibuprofen at Cmax concentrations (32.3 mg/l) and 10 times the Cmax (323 mg/l). Cefditoren was rapidly bactericidal (3 log(10) CFU/ml reduction) against the three strains at 4.2 mg/l concentration in Mueller-Hinton broth plus 5% lysed horse blood. In presence of human albumin, this effect was maintained against the most susceptible strain (MIC = 0.12 mg/l). Regrowths were observed with higher MIC values. The presence of ibuprofen (32.3 mg/l) slightly delayed regrowth while the increase of ibuprofen concentration up to 10 x Cmax recovered the bactericidal activity against all strains. The activity of an antimicrobial with high protein binding should not be linked exclusively with the theoretical unbound fraction extrapolated from the plasma concentration. The role of protein binding antagonists merits analysis due to their frequent use associated with cephalosporins in respiratory tract infections.

Situación de la cefalosporina oral de tercera generación cefditoreno pivoxil en el tratamiento de la infección comunitaria del adulto / The role of the third-generation oral cephalosporin cefditorin pivoxil in the treatment of community-acquired infection in adults

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Actividad de los antibióticos orales frente a los microorganismos patógenos de las vías respiratorias en España / Activity of oral antibiotics against respiratory tract pathogens in Spain

El objetivo de este estudio fue realizar una encuesta de ámbito nacional para evaluar la sensibilidad de las cepas clínicas de cuatro microorganismos patógenos respiratorios a nueve antibióticos. En el estudio participaron ocho centros españoles, recogiendo un total de 977 cepas de Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae y Moraxella catarrhalis. El 37,46 por ciento de S. pneumoniae fue sensible a la penicilina, el 30,43 por ciento mostró resistencia intermedia y el 32,11 por ciento fue resistente. Las CMI90 de todos los antibióticos frente a este microorganismo fueron de 4-8 mg/l, excepto para cefaclor, cefixima y azitromicina. En el caso de S. pyogenes, todas las cepas fueron sensibles a la penicilina y las cefalosporinas, mientras que la azitromicina fue el antibiótico menos activo, con un grado de resistencia que alcanzó el 11,43 por ciento. Noventa y cinco cepas de H. influenzae fueron betalactamasa positivas (26,32 por ciento). En el caso de M. catarrhalis, sólo la penicilina y la amoxicilina tuvieron CMI90 8 mg/l (AU)