RESUMEN
BACKGROUND: Candida auris infections have been reported worldwide since the pathogen was isolated in 2009. AIM: To analyse the incidence of cutaneous and intestinal colonization, and connection with infections by the organism, in a hospital setting of a C. auris epidemic. METHODS: This was a retrospective study in intensive care units (ICUs) at a 1200-bed Italian hospital. The incidence of cutaneous positive swabs, and cutaneous carriers, for C. auris was compared to that of rectal positive swabs, and intestinal carriers, and both were correlated with C. auris infections. FINDINGS: A total of 399 patients were included. Seventy-seven patients were infected by C. auris. The ratio of C. auris positive skin swabs from screening in ICUs was 24%. The ratio obtained from infected patients and intestinal C. auris carriers was 49.1%, likewise rectal swabs from a similar cohort of patients (P = 0.373). Of this cohort, 39.7% and 5.5% were colonized only in skin and in rectum, respectively, while 54.8% was colonized in both sites. Of skin swabs, 12.3% and 83.6%, respectively, were always positive and variable over time in single subjects, while 31.5% and 41.1% of rectal swabs were always positive and variable (P = 0.000). Intestinal colonization was associated with increased risk for C. auris urinary infections (P = 0.006). CONCLUSION: C. auris intestinal carriers were fewer than cutaneous carriers, but more continuously colonized. Rectal and skin swabs can be good tools for surveillance, respectively, of colonization and of hygiene measures effectiveness. Urinary tract infections by C. auris appeared to increase along with gastrointestinal presence of the yeast.
Asunto(s)
Candida auris , Enfermedad Crítica , Antifúngicos/uso terapéutico , Candida , Brotes de Enfermedades , Humanos , Recto , Estudios RetrospectivosRESUMEN
BACKGROUND: Surveillance of carbapenem-resistant Enterobacterales (CRE) carriers is the first measure of hospital infection control. Screening of CRE carriage can be assessed through culture and molecular techniques, each with specific properties of turnaround-times, sensitivity and specificity. METHODS: This was a prospective study in a 1200-bed university hospital in Genoa, Italy, where CRE screening is performed analysing cultures from rectal swabs. Our 18-months intervention was to extend the incubation time of the corresponding plates from 48 to 288 h, after reporting negative tests, to evaluate the possible impact on the cultures. FINDINGS: A total of 362 patients giving 19,278 swabs and corresponding plates were included. After baseline incubation, plate positivity was 3%, while after the overall lengthened times it was 3.7%. Extended incubation was associated with change in the relative frequency of the most represented species. In particular, we observed reduced presence of total and resistant Klebsiella pneumoniae strains (P<0.001) and increased presence of Enterobacter cloacae complex, total and sensitive (P<0.001). By extending incubation time, a reduced frequency of overall Enterobacterales strains with high resistance to ertapenem (MIC ≥4 mg/L) was also found (P=0.005), particularly that of K. pneumoniae (P<0.001), while the presence of E. cloacae complex increased among organisms with low resistance levels to ertapenem (P<0.001). CONCLUSIONS: Extending the incubation time of the cultures increased the number of CREs grown, and expanded the bacterial scenario of rectal colonization through the recovery of poorly resistant strains and otherwise undetected species.
Asunto(s)
Carbapenémicos , Klebsiella pneumoniae , Humanos , Carbapenémicos/farmacología , Ertapenem , Estudios Prospectivos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Pruebas de Sensibilidad Microbiana , beta-LactamasasRESUMEN
Minimum inhibitory concentrations (MICs) and mutant prevention concentrations (MPCs) of prulifloxacin against 30 strains of Escherichia coli isolated from urinary tract infections as well as the 'biological cost' related to acquisition of resistance to the same drug in 10 uropathogenic E. coli were assessed. In terms of MIC(90), prulifloxacin was more potent than ciprofloxacin and levofloxacin. Prulifloxacin produced lower or equal MPC values than the other two fluoroquinolones (93.3% and 73.3% compared with levofloxacin and ciprofloxacin, respectively). Compared with susceptible strains, prulifloxacin-resistant mutants showed a reduced rate of growth (ranging from 20.0% to 98.0% in different culture media and incubation conditions) and a decreased fitness index (ranging from 0.959 to 0.999). They were also impaired in their ability to adhere to uroepithelial cells and urinary catheters (11.7-66.4% and 16.3-78.3% reduction, respectively) and showed a lower surface hydrophobicity (51.2-76.0%). They were more susceptible to ultraviolet irradiation (30.6-93.8% excess mortality), showed increased resistance to colicins and diminished transfer of plasmids (<1-8.5x10(-8) vs. 3.3x10(-7)-2.4x10(-4)). Synthesis of haemolysin and type I fimbriae and production of flagella were also adversely affected. This study demonstrates a strict relationship between acquisition of prulifloxacin resistance and loss of important virulence traits. In this transition, E. coli pays a severe biological cost that entails a general reduction of fitness, thus compromising competition with susceptible wild-type strains in the absence of the drug.
Asunto(s)
Antiinfecciosos Urinarios/farmacología , Dioxolanos/farmacología , Farmacorresistencia Bacteriana/fisiología , Escherichia coli/efectos de los fármacos , Fluoroquinolonas/farmacología , Piperazinas/farmacología , Quinolonas/farmacología , Infecciones Urinarias/microbiología , Adhesión Bacteriana/fisiología , Ciprofloxacina/farmacología , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Proteínas Hemolisinas/antagonistas & inhibidores , Humanos , Técnicas In Vitro , Levofloxacino , Pruebas de Sensibilidad Microbiana , Ofloxacino/farmacología , Rayos Ultravioleta , Infecciones Urinarias/tratamiento farmacológicoRESUMEN
The aim of this study was to assess whether moxifloxacin is able to inhibit the synthesis of and to disrupt biofilms produced in vitro by bacterial pathogens involved in acute bacterial exacerbations of chronic bronchitis. Three strains each of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Staphylococcus aureus and Escherichia coli recently isolated from clinical respiratory specimens and capable of slime production were used. Biofilm formation on polystyrene plates was quantified spectrophotometrically by established methodologies. Moxifloxacin (0.5 mg/L) inhibited slime synthesis by >70% in S. aureus, H. influenzae and S. pneumoniae, 45-70% in E. coli and 35-70% in M. catarrhalis. Disruption of pre-formed structures was also promoted by moxifloxacin both for initial (5h) and mature (48 h) biofilms. Drug concentrations reached during therapy (0.5-4 mg/L) resulted in a breakdown of initial biofilm of 60-80% in H. influenzae and S. pneumoniae, 48-86% in S. aureus, 37-69% in M. catarrhalis and 51-71% in E. coli. Mature biofilms were less susceptible to degradation. Moxifloxacin at concentrations that can be achieved in the bronchial mucosa during therapy therefore promotes a significant inhibition of biofilm synthesis and induces slime disruption, a feature that may be instrumental in reducing the exacerbations so frequently observed in this condition.
Asunto(s)
Antibacterianos/farmacología , Compuestos Aza/farmacología , Biopelículas/efectos de los fármacos , Bronquitis Crónica/microbiología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Quinolinas/farmacología , Biomasa , Fluoroquinolonas , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/microbiología , Bacterias Grampositivas/aislamiento & purificación , Infecciones por Bacterias Grampositivas/microbiología , Pruebas de Sensibilidad Microbiana , Moxifloxacino , EspectrofotometríaRESUMEN
The activity of amphotericin B, fluconazole, flucytosine, itraconazole and voriconazole was tested in vitro against 618 clinical Candida spp. isolates, using the broth microdilution or the disk diffusion method (voriconazole). Amphotericin B and voriconazole were the most potent antifungal agents assayed (100% of susceptible strains). Resistance to fluconazole and itraconazole was detected in three (0.7%) and 11 (2.7%) isolates of Candida albicans and in four (3.7%) isolates of Candida glabrata. Flucytosine intermediate, resistant strains, or both, were observed in C. albicans (0.3% and 0.7%), C. glabrata (2.8% intermediate) and C. tropicalis (15.2% and 15.2%). C. krusei was the least susceptible species to azoles. No statistically significant differences in the rates of resistant isolates depending on site of infection and age of the patient were observed, with the exception of C. albicans and itraconazole (higher percentage of resistance in children). At present, acquired antifungal resistance represents an uncommon finding in most Candida spp. circulating in Northern Italy.
Asunto(s)
Antifúngicos/farmacología , Candida/efectos de los fármacos , Adulto , Factores de Edad , Niño , Farmacorresistencia Fúngica , Fluconazol/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Factores de TiempoRESUMEN
The chemokine receptor 5 (CCR5) serves as a fusion cofactor for macrophage-tropic strains of HIV-1. In addition, CCR5 has been shown to mediate the entry of poxviruses into target cells. Individuals homozygous for the Delta32 deletion-mutation have no surface expression of CCR5 and are highly protected against HIV-1 infection. To gain insights into the evolution of the mutation in modern populations, the relatively high frequency of the Delta32-ccr5 allele in some European and Jewish populations is explored here by examining haplotypes of 3p21.3 constructed of five polymorphic marker loci surrounding CCR5. By sampling Ashkenazi, non-Ashkenazi and non-Jewish populations, we utilize the natural experiment that occurred as a consequence of the Jewish Diaspora, and demonstrate that a single mutation was responsible for all copies of Delta32. This mutation must have moved from Northern European populations to the Ashkenazi Jews where evidence suggests that Delta32 carriers of both groups were favored by repeated occurrence of epidemic small pox beginning in the 8th century AD.
Asunto(s)
Cromosomas Humanos Par 3 , Evolución Molecular , Eliminación de Gen , Variación Genética , Judíos/genética , Receptores CCR5/genética , Alelos , Quimiocina CXCL12 , Quimiocinas CXC/genética , Europa (Continente) , Frecuencia de los Genes , Pruebas Genéticas , Haplotipos , Humanos , Receptores CCR5/clasificaciónRESUMEN
Persisters are a small proportion of a bacterial population that exists in a physiological state permitting survival despite the lethal activity of antibiotics. To explain this phenomenon, it has been suggested that persisters are bacteria repairing spontaneous errors of DNA synthesis. To verify this assumption, Escherichia coli AB1157 and its lexA3 derivative were exposed to a dose 6x MIC of various antibiotics representative of different molecular mechanisms of action (ampicillin, ceftriaxone, meropenem, amikacin, ciprofloxacin). Bacterial cell counts, after 24 hr of exposure to the antimicrobials, revealed a reduction of about 90% of viable organisms in the lexA3 strains in comparison to the lexA+. In several cases, the number of colony-forming units decreased below the limit of assay. This behavior was noted with all antibiotics used, alone or in combination (amikacin plus ceftriaxone and amikacin plus ciprofloxacin). The same experiments were repeated using E. coli AB1157 cultured in the presence of mitomycin C (0.25x MIC), and the number of survivors exceeded by about 90% the values found in the nonexposed control. In contrast, in the sulA background, mitomycin C reacted synergically with all the antibiotics tested causing a strong reduction of the survivors in comparison with the control. The addition of chloramphenicol (0.125x MIC), on the contrary, caused a reduction of the number of survivors of about 90%. These findings indicate that, when DNA repair is active (a mechanism known to block cell division), the number of survivors is greater than that observed with lexA3. Thus, in addition to other possible explanations, persisters might be a fraction of bacteria that during antibiotic treatment are not growing because they are repairing spontaneous errors of DNA synthesis.
Asunto(s)
Antibacterianos/farmacología , Reparación del ADN/efectos de los fármacos , Resistencia a Medicamentos/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Cloranfenicol/farmacología , ADN Bacteriano/efectos de los fármacos , ADN Bacteriano/genética , Quimioterapia Combinada/farmacología , Escherichia coli/crecimiento & desarrollo , Genes Bacterianos/genética , Pruebas de Sensibilidad Microbiana , Mitomicina/farmacología , Mutación/genética , Inhibidores de la Síntesis del Ácido Nucleico/farmacologíaRESUMEN
Enterococci are widely distributed in the environment; within the human body, they are normal commensals of the oral cavity, gastrointestinal tract and vagina. In recent years, enterococci have become one of the most frequent causes of acquired nosocomial infections worldwide. The molecular mechanism of virulence of these bacteria is still not completely understood. The aims of this work were to characterize phenotypically 47 isolates of Enterococcus faecalis and Enterococcus faecium collected in Sardinia (Italy) by their abilities to adhere to different epithelial cell lines (Vero and Caco-2 cells) and to associate their phenotypes with the presence of known virulence genes detected within their genomes by PCR. The following genes were amplified: AS (aggregation substance), esp (surface protein gene), ace (accessory colonization factor), efaA (E. faecalis endocarditis antigen) and gelE (gelatinase). The virulence genes were detected in E. faecalis isolates only, with the exception of esp, which was found in both species. The phenotypic and genotypic results were also compared with the susceptibility of isolates to various antibiotics.
Asunto(s)
Enterococcus faecalis/patogenicidad , Enterococcus faecium/patogenicidad , Infecciones por Bacterias Grampositivas/microbiología , Antígenos Bacterianos/genética , Adhesión Bacteriana , Proteínas Bacterianas/genética , Biopelículas/crecimiento & desarrollo , Proteínas Portadoras/genética , Farmacorresistencia Bacteriana , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecalis/genética , Enterococcus faecium/efectos de los fármacos , Enterococcus faecium/genética , Femenino , Gelatinasas/genética , Humanos , Italia , Masculino , Proteínas de la Membrana/genética , Pruebas de Sensibilidad Microbiana , Fenotipo , Ribotipificación , Virulencia/genéticaRESUMEN
The activity of linezolid, a new oxazolidinone, was tested against 862 Gram-positive cocci isolated in Italy and compared with the activities of 12 antibiotics. Overall, MIC90s for linezolid (2-4 mg/L) indicated an in vitro activity comparable to that of vancomycin in methicillin-resistant Staphylococcus aureus (4 mg/L), S. epidermidis (2 mg/L) and methicillin-susceptible strains. Enterococcus faecalis strains were susceptible to linezolid (MIC90 2-4 mg/L), glycopeptides and beta-lactams. In E. faecium, only glycopeptides (MIC90 2 mg/L) and linezolid (MIC90 2 mg/L) were active. Linezolid was the only drug active against two strains of Enterococcus showing a VanA phenotype. Owing to its antibacterial profile, linezolid represents a promising drug for the treatment of Gram-positive infections.
Asunto(s)
Acetamidas/farmacología , Antibacterianos/farmacología , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecium/efectos de los fármacos , Oxazolidinonas/farmacología , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/clasificación , Enterococcus faecalis/aislamiento & purificación , Enterococcus faecium/aislamiento & purificación , Humanos , Italia/epidemiología , Linezolid , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
The expression of the N-methyl-D-aspartate (NMDA) receptor subunit NR2B/epsilon2 (GRIN2B) in the human adult brain was assayed by in situ hybridisation, by using a specific cRNA probe. The full length GRIN2B cDNA was cloned and sequenced. It showed a 90% nucleotide conservation when compared to the rodent homologue. GRIN2B gene is expressed at high levels in the fronto-parieto-temporal cortex and hippocampus pyramidal cells and, at a lower extent, in the basal ganglia (amygdala and striatum). The cerebellar granule cells does not show any mRNA expression. The non-ubiquitous anatomical distribution of the GRIN2B mRNA in the central nervous system suggests that the gene could be involved in specific functions pertaining to the expressing cell groups.
Asunto(s)
Química Encefálica/fisiología , Fragmentos de Péptidos/análisis , ARN Mensajero/análisis , Receptores de N-Metil-D-Aspartato/análisis , Adulto , Mapeo Cromosómico , Humanos , Hibridación in Situ , Reacción en Cadena de la Polimerasa/métodos , Receptores de N-Metil-D-Aspartato/química , Valores de Referencia , Transcripción GenéticaRESUMEN
The Italian Epidemiological Survey began a surveillance study with the aim of monitoring the antimicrobial resistance of respiratory pathogens. From 1997 to 1999, 2028 strains of Haemophilus influenzae and 523 strains of Haemophilus parainfluenzae were collected from 59 Clinical Microbiology Laboratories distributed throughout Italy. In 1998, the study was extended to include Moraxella catarrhalis and a total of 360 isolates were collected. There was a significant increase in the beta-lactamase production both for H. influenzae (from 5% in 1997 to 16% in 1999) and for H. parainfluenzae (from 5% in 1997 to 22% in 1999). Beta-lactamase production in M. catarrhalis was 84% in 1998 and 87% in 1999. Beta-lactamase production affected the susceptibility to unprotected penicillins (87% in H. influenzae, 85% in H. parainfluenzae and 34% in M. catarrhalis), and in part the susceptibility to cefaclor (about 98%). Amoxycillin/clavulanate, cefixime, ceftriaxone and ciprofloxacin were active against all strains of H. influenzae, H. parainfluenzae and M. catarrhalis.
Asunto(s)
Antibacterianos/farmacología , Haemophilus influenzae/efectos de los fármacos , Moraxella catarrhalis/efectos de los fármacos , Recolección de Datos , Farmacorresistencia Bacteriana , Italia , Pruebas de Sensibilidad MicrobianaRESUMEN
Antibacterial resistance was evaluated among Streptococcus pneumoniae (n=252) and Haemophilus influenzae (n=202) from two centres in Spain (Barcelona and Madrid) and two centres in Italy (Genoa and Catania) collected during 1999-2000 as part of the ongoing PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) international surveillance program. Pneumococcal nonsusceptibility to penicillin G was found to be considerably higher in Spain (53.4%) than in Italy (15.1%), whereas erythromycin A resistance was higher in Italy (42.9%) than in Spain (28.6%). Among macrolide-resistant isolates investigated for resistance genes, the prevalence of mefA was higher among isolates from Italy (20/51, 39.2%) than among Spanish isolates (2/38, 5.3%). All other macrolide-resistant isolates possessed ermB. Telithromycin possessed good anti-pneumococcal activity against isolates from both countries (MIC90 0.03 mg/L [Spain]; 0.25 mg/L [Italy]), irrespective of resistance to other antibacterials. Beta-lactamase production among H. influenzae was low: Spain, 10.9%; Italy, 1.8%. With the exception of ampicillin and co-trimoxazole, all H. influenzae isolates were highly susceptible to the antibacterials tested, and all were inhibited by telithromycin at a concentration of < or = 2 mg/L. The findings of PROTEKT 1999-2000 highlight the importance of local resistance patterns in guiding the choice of empirical antibacterials for community-acquired respiratory tract infections.
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Haemophilus influenzae/efectos de los fármacos , Streptococcus pneumoniae/efectos de los fármacos , Femenino , Haemophilus influenzae/aislamiento & purificación , Humanos , Italia , Masculino , Pruebas de Sensibilidad Microbiana , Estudios Multicéntricos como Asunto , Vigilancia de la Población , España , Streptococcus pneumoniae/aislamiento & purificaciónRESUMEN
Thiamphenicol is a derivative of chloramphenicol characterized by a spectrum comparable to that of the parent compound against multiresistant pathogens but showing satisfactory tolerability. The in vitro activity of thiamphenicol and of 11 comparative drugs against 397 recently isolated antibiotic-resistant and/or invasive pneumococci and 52 multiply-resistant MRSA including 2 VISA strains was determined. Bactericidal activity against Haemophilus influenzae and the post-antibiotic effect on Streptococcus pneumoniae, H. influenzae, Staphylococcus aureus and Escherichia coli were also assessed. Against invasive pneumococci, thiamphenicol and chloramphenicol were the most potent non-beta-lactam molecules together with vancomycin and rifampin. Against high-level penicillin-resistant strains phenicol activities were superior to those of cefotaxime, ceftriaxone and imipenem. Against MRSA thiamphenicol and chloramphenicol were second only to the glycopetides and also inhibited the VISA strains. Thiamphenicol showed a significant PAE (0.33 to 2.9h) on all pathogens studied and a powerful bactericidal effect against beta-lactamase-positive and -negative H. influenzae. These results indicate a good in vitro activity of thiamphenicol against difficult-to-treat multiply resistant pathogens.
Asunto(s)
Antibacterianos/farmacología , Haemophilus influenzae/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Streptococcus pneumoniae/efectos de los fármacos , Tianfenicol/farmacología , Farmacorresistencia Bacteriana Múltiple , Humanos , Italia , Pruebas de Sensibilidad MicrobianaRESUMEN
The aim of this study was to investigate for which conditions antibiotics are being used in community dental practice, and which clinical features represent the most common reason for an antibacterial approach to the treatment of dental conditions. The study was carried out from November 1998 to June 1999. Dentists were selected according to the different areas of southern Italy, from a list provided by the Italian Society of Dentists. Out of 87 selected dentists, 33 agreed to participate and filled in 1615 questionnaires for each therapeutic intervention ending with antibiotic treatment. Analysis of data indicated that alveolar-gingival abscesses were the most commonly treated infection, accounting for 23.6% of total treatments, followed by acute periodontitis (20.6%) and disodontiasis of the 3rd molar (18.5%). Parenteral antibiotics were chosen in 7.8% of cases. Penicillins were the most commonly used group, 40.1% of total treatments, followed by macrolides (30.2%) and cephalosporins (13.4%). Moreover, penicillins were widely used for post-surgery therapy (52.1%) and disodontiasis of the 3rd molar (50.8%), while macrolides were the most commonly used group for gingivitis (44.1%) and parodontal diseases (55.0%). The choice of parenteral antibiotics was related to severe general symptoms (odds ratios [OR], 4.4; 95% CI: 2.2-9.0), pain (OR, 2.7; 95% CI: 1.2-6.1) and lymphonodal involvement (OR, 6.4; 95% CI: 2.7-15.1). In conclusion, our study demonstrates that antibiotic treatment is often based on the eradication of as many microorganisms as possible, and on the clinical assessment of the patients, rather than on any knowledge of the pathogens involved.
Asunto(s)
Antibacterianos/uso terapéutico , Odontología Comunitaria , Utilización de Medicamentos , Adulto , Femenino , Humanos , Italia , Masculino , Persona de Mediana EdadRESUMEN
The recently discovered Human Herpesvirus 8 (HHV 8) is associated with all clinical forms of Kaposi's sarcoma. While early research suggested that the virus was transmitted sexually and that it was present only in KS patients, more recent studies seem to show that infection with the virus is more common than once thought, presenting differing distribution patterns in different geographical areas. In this study we analyze seroprevalence and transmission of HHV 8 in a sample of 86 family groups from Albania. Participants were selected among families requesting routine pre-expatriation medical examinations at the Poliambulatorio Padre "L. Monti" in Tirana. Specimens were collected from 180 healthy individuals and tested for the presence of a specific antibody. Antibody anti-HHV-8 detection was performed by immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA). The study found an overall rate of HHV 8 seroprevalence of 20.0%. In 4.5% of couples the male and female were both positive, in 30.2% at least one partner was positive; (in 17.4% only the male was positive; in 12.8% only the female). These results support the hypothesis that HHV 8 spreads via multiple transmission routes.
Asunto(s)
Infecciones por Herpesviridae/epidemiología , Herpesvirus Humano 8/aislamiento & purificación , Adolescente , Adulto , Albania/epidemiología , Anticuerpos Antivirales/sangre , Niño , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnica del Anticuerpo Fluorescente Directa , Infecciones por Herpesviridae/transmisión , Humanos , Masculino , Persona de Mediana Edad , Estudios SeroepidemiológicosRESUMEN
In this study, demethylfruticuline A (dfA) and fruticuline A (fA), two quinones representing the major diterpenoid components of the exudate produced by the aerial parts of Salvia corrugata, were assessed for their ability to modify surface characteristics, such as hydrophobicity, and to inhibit synthesis of biofilm in vitro by multiresistant Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis. Five strains of S. aureus (three meticillin-resistant and two meticillin-susceptible), five strains of S. epidermidis (four meticillin-resistant and one meticillin-susceptible) and eight vancomycin-resistant E. faecalis, all recently isolated from clinical specimens and capable of slime production, were studied. fA decrease by at least two-fold the hydrophobic properties of the S. aureus cell membrane but did not affect S. epidermidis or E. faecalis. Biofilm formation on polystyrene plates was quantified spectrophotometrically by established methodologies. Inhibition of biofilm formation was also confirmed by the Congo red agar plate assay. dfA and fA were more effective against S. aureus strains (>70% effect at subinhibitory concentrations) than against S. epidermidis in inhibiting slime synthesis. Against E. faecalis, dfA at subinhibitory concentration induced an inhibition of biofilm production of ca. 60%; fA was less active and more strain-dependent. Moreover, the two compounds were shown to possess chelating activity on divalent and trivalent metal cations. Interactions of fA and dfA with bacteria could be very complex, possibly being species-specific, and could depend not only on inhibition of exopolysaccharide synthesis but also on their chelating activity and on changes in the microorganism's surface, including cell hydrophobicity.
Asunto(s)
Biopelículas/efectos de los fármacos , Diterpenos/farmacología , Enterococcus faecalis/efectos de los fármacos , Salvia/química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacos , Antibacterianos/farmacología , Biopelículas/crecimiento & desarrollo , Quelantes/metabolismo , Diterpenos/aislamiento & purificación , Farmacorresistencia Bacteriana Múltiple , Enterococcus faecalis/fisiología , Humanos , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/fisiología , Staphylococcus epidermidis/fisiologíaAsunto(s)
Antiinfecciosos/farmacología , Levofloxacino , Ofloxacino/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Streptococcus pneumoniae/efectos de los fármacos , Antiinfecciosos/uso terapéutico , Ciprofloxacina/farmacología , Ciprofloxacina/uso terapéutico , Farmacorresistencia Microbiana , Humanos , Italia , Pruebas de Sensibilidad Microbiana , Ofloxacino/uso terapéutico , Infecciones Neumocócicas/tratamiento farmacológico , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/aislamiento & purificación , Sensibilidad y Especificidad , Streptococcus pneumoniae/aislamiento & purificaciónRESUMEN
OBJECTIVES: The in vitro activity of ertapenem was evaluated in comparison to 21 selected agents against a large collection of recently isolated respiratory tract pathogens including: 180 Streptococcus pneumoniae, 100 Streptococcus pyogenes, 70 Haemophilus influenzae, 70 Moraxella catarrhalis, 100 methicillin-susceptible Staphylococcus aureus and 30 Klebsiella pneumoniae. Additional in vitro tests (time-kill curves with ertapenem alone and in combination with four other agents) for S. pneumoniae were carried out. METHODS: MIC determinations and time-kill curves were carried out following the procedures suggested by the NCCLS. RESULTS: According to NCCLS susceptibility breakpoints, ertapenem was comparable to the most potent compounds tested for all pathogens studied. Ertapenem was 100% active against penicillin-susceptible and -intermediate S. pneumoniae and against 60% of penicillin-resistant strains. Time-kill tests at 4x MIC confirmed a pronounced bactericidal potency of ertapenem against these organisms. Interactions of ertapenem with several other agents against pneumococci resulted in clear synergic interactions (98.4%). Indifference was extremely rare and antagonism was not observed. All S. pyogenes strains tested were inhibited by ertapenem, irrespective of their macrolide resistance phenotypes. Ertapenem was also fully active against H. influenzae (100% susceptible) and M. catarrhalis (MIC90 0.015-0.03 mg/L) even when capable of synthesizing beta-lactamases. Methicillin-susceptible S. aureus and K. pneumoniae, including extended-spectrum beta-lactamase-producing strains, were 100% susceptible to ertapenem. CONCLUSIONS: Our results indicate that ertapenem has a suitable spectrum of activity against organisms encountered in community-acquired bacterial respiratory tract infections.
Asunto(s)
Bacterias/efectos de los fármacos , Lactamas/farmacología , Infecciones del Sistema Respiratorio/microbiología , Ertapenem , Humanos , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pyogenes/efectos de los fármacos , beta-LactamasRESUMEN
The N-methyl-D-aspartate (NMDA) receptor channel is essential for synaptic transmission and synaptic plasticity underlying memory, learning, and development. Three subunits of the NMDA receptor channel, NMDAR2A, NMDAR2B, and NMDAR2C (NR2A, NR2B, and NR2C), previously identified in mouse by cDNA cloning and expression, share a high level of homology, although their patterns of expression within the brain may differ. In the present work we report the localization of the gene encoding the human NMDAR2B receptor subunit (called GRIN2B for glutamate receptor, ionotropic, N-methyl-D-aspartate 2B) to chromosome 12p12 by in situ hybridization and somatic cell hybrids.
Asunto(s)
Mapeo Cromosómico , Cromosomas Humanos Par 12 , Receptores de N-Metil-D-Aspartato/genética , Animales , Secuencia de Bases , Encéfalo/metabolismo , Cartilla de ADN/genética , Humanos , Células Híbridas , Hibridación Fluorescente in Situ , Ratones , Datos de Secuencia Molecular , Conformación Proteica , Receptores de N-Metil-D-Aspartato/químicaRESUMEN
The effects of early antiretroviral therapy on the peripheral CD8(+) T-cell population were assessed by sequentially determining the T-cell receptor (TCR) repertoire complexity in a cohort of 15 individuals recently diagnosed with human immunodeficiency virus infection. Analysis was based on quantitative TCR variable B gene (TCRBV) usage and complementary-determining region 3 length assessment. Repertories were assessed at baseline and at weeks 2, 4, 12, 24, and 72 after initiation of therapy. Early administration of highly active antiretroviral therapy has a positive effect on the preservation and homeostasis of the CD8(+) cell repertoire. Nevertheless, differences from average baseline and control TCR profiles and initial development of repertoire perturbations were observed. The findings suggest that additional therapeutic protocols will be required during primary infection to significantly prevent long-term erosion of the T-cell-mediated immune response.