RESUMEN
Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis are bacterial species which frequently co-colonise the nasopharynx, but can also transit to the middle ear to cause otitis media. Chronic otitis media is often associated with a polymicrobial infection by these bacteria. However, despite being present in polymicrobial infections, the molecular interactions between these bacterial species remain poorly understood. We have previously reported competitive interactions driven by pH and growth phase between H. influenzae and S. pneumoniae. In this study, we have revealed competitive interactions between the three otopathogens, which resulted in reduction of H. influenzae viability in co-culture with S. pneumoniae and in triple-species culture. Transcriptomic analysis by mRNA sequencing identified a central role of arginine in mediating these interactions. Arginine supplementation was able to increase H. influenzae survival in a dual-species environment with S. pneumoniae, and in a triple-species environment. Arginine was used by H. influenzae for ATP production, and levels of ATP generated in dual- and triple-species co-culture at early stages of growth were significantly higher than the combined ATP levels of single-species cultures. These results indicate a central role for arginine-mediated ATP production by H. influenzae in the polymicrobial community.
Asunto(s)
Coinfección , Otitis Media , Adenosina Trifosfato , Arginina , Coinfección/microbiología , Haemophilus influenzae/genética , Humanos , Moraxella catarrhalis/genética , Otitis Media/microbiología , Streptococcus pneumoniae/genéticaRESUMEN
OBJECTIVE: Previous investigations suggest the use of extract from the root of Pelargonium sidoides (EPs 7630) for the therapy of uncomplicated acute upper airway inflammations, due to its strong antimicrobial and immunomodulatory effect. We aimed to compare clinical efficacy, safety and bactericidal effect of EPs 7630 and amoxicillin monotherapy in treatment of patients with mild to moderate acute bacterial rhinosinusitis (ABRS). METHODS: Fifty ABRS patients were divided into two groups by randomization. Group 1 (n = 25) received EPs 7630 tablets, 3 × 20 mg/day per os for 10 days. Group 2 (n = 25) received amoxicillin tablets 3 × 500 mg/day per os, for 10 days. We assessed total symptom score (TSS), individual symptom scores for each symptom (nasal obstruction, rhinorrhea, postnasal drip, facial pain/pressure, loss of the sense of smell), endoscopic findings, including total endoscopic score (TES) and individual endoscopic signs (mucosal edema, mucopurulent secretion), before and after treatment. Samples of discharge taken from the middle meatus of all patients were cultivated for bacteria before and after therapy. RESULTS: Higher absolute improvement after treatment was found for TSS, nasal obstruction, facial pain/pressure, impaired sense of smell, TES, mucosal edema and mucopurulent secretion in EPs 7630 group compared to amoxicillin group (P < .001 for all parameters). However, there were no differences in absolute improvement of rhinorrhea score and postnasal drip score between groups (P = .248; P = .679, respectively). Fewer types of bacteria grew on culture from middle meatal samples in EPs 7630 group compared to amoxicillin group. There were no reported adverse events from patients from either group. CONCLUSION: Our results demonstrated better clinical and antimicrobial efficacy of EPs 7630 than amoxicillin. EPs 7630 was shown as a potent agent and good alternative to antibiotic treatment of uncomplicated ABRS.
Asunto(s)
Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/uso terapéutico , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Adulto , Infecciones Bacterianas/fisiopatología , Edema/fisiopatología , Dolor Facial/fisiopatología , Femenino , Infecciones por Haemophilus/tratamiento farmacológico , Haemophilus influenzae , Humanos , Masculino , Persona de Mediana Edad , Moraxella catarrhalis , Infecciones por Moraxellaceae/tratamiento farmacológico , Mucosa Nasal , Obstrucción Nasal/fisiopatología , Trastornos del Olfato/fisiopatología , Infecciones Neumocócicas/tratamiento farmacológico , Rinitis/fisiopatología , Sinusitis/fisiopatología , Streptococcus pneumoniae , Adulto JovenRESUMEN
OBJECTIVE: For the majority of people with acute sore throat, over-the-counter treatments represent the primary option for symptomatic relief. This study evaluated the in vitro bactericidal activity of lozenges containing the antiseptic hexylresorcinol against five bacteria associated with acute sore throat: Staphylococcus aureus, Streptococcus pyogenes, Moraxella catarrhalis, Haemophilus influenzae and Fusobacterium necrophorum. RESULTS: Hexylresorcinol 2.4 mg lozenges were dissolved into 5 mL of artificial saliva medium. Inoculum cultures were prepared in triplicate for each test organism to give an approximate population of 108 colony-forming units (cfu)/mL. Bactericidal activity was measured by log reduction in cfu. Greater than 3log10 reductions in cfu were observed at 1 min after dissolved hexylresorcinol lozenges were added to S. aureus (log10 reduction cfu/mL ± standard deviation, 3.3 ± 0.2), M. catarrhalis (4.7 ± 0.4), H. influenzae (5.8 ± 0.4) and F. necrophorum (4.5 ± 0.2) and by 5 min for S. pyogenes (4.3 ± 0.4). Hexylresorcinol lozenges achieved a > 99.9% reduction in cfu against all tested organisms within 5 min, which is consistent with the duration for a lozenge to dissolve in the mouth. In conclusion, in vitro data indicate that hexylresorcinol lozenges offer rapid bactericidal activity against organisms implicated in acute sore throat.
Asunto(s)
Infecciones Bacterianas/tratamiento farmacológico , Resfriado Común/tratamiento farmacológico , Hexilresorcinol/uso terapéutico , Orofaringe/efectos de los fármacos , Administración Oral , Antiinfecciosos Locales/administración & dosificación , Antiinfecciosos Locales/uso terapéutico , Infecciones Bacterianas/microbiología , Carga Bacteriana/efectos de los fármacos , Resfriado Común/microbiología , Fusobacterium necrophorum/efectos de los fármacos , Fusobacterium necrophorum/fisiología , Haemophilus influenzae/efectos de los fármacos , Haemophilus influenzae/fisiología , Hexilresorcinol/administración & dosificación , Humanos , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/efectos de los fármacos , Moraxella catarrhalis/fisiología , Orofaringe/microbiología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología , Streptococcus pyogenes/efectos de los fármacos , Streptococcus pyogenes/fisiología , Factores de TiempoRESUMEN
INTRODUCTION: Moraxella catarrhalis is an important but insufficiently studied respiratory pathogen. AIM: To determine antibiotic susceptibility and impact of recent antibiotics on M. catarrhalis from children with chronic endobronchial suppuration. METHODOLOGY: We cultured nasopharyngeal (NP) swabs and bronchoalveolar lavage (BAL) fluids collected from children who were prospectively enrolled in studies of chronic cough and had flexible bronchoscopy performed. Recent ß-lactam or macrolide antibiotic use was recorded. M. catarrhalis isolates stored at -80 °C were re-cultured and susceptibility determined to a range of antibiotics including the macrolide antibiotic erythromycin. RESULTS: Data from concurrently collected NP and BAL specimens were available from 547 children (median age 2.4 years) enrolled from 2007 to 2016. M. catarrhalis NP carriage was detected in 149 (27â %) children and lower airway infection (≥104 c.f.u. ml-1 BAL) in 67 (12â %) children. In total, 91 â% of 222 M. catarrhalis isolates were ß-lactamase producers, and non-susceptibility was high to benzylpenicillin (98 %), cefaclor (39 %) and cotrimoxazole (38 %). Overall, >97 â% isolates were susceptible to cefuroxime, chloramphenicol, erythromycin and tetracycline; three isolates were erythromycin-resistant (MIC >0.5 mg l-1). Recent macrolide antibiotics (n=152 children, 28 %) were associated with significantly reduced M. catarrhalis carriage and lower airway infection episodes compared to children who did not receive macrolides; odds ratios 0.19 (95 â% CI 0.10-0.35) and 0.15 (0.04-0.41), respectively. CONCLUSION: Despite the frequent use of macrolides, few macrolide-resistant isolates were detected. This suggests a fitness cost associated with macrolide resistance in M. catarrhalis. Macrolide antibiotics remain an effective choice for treating M. catarrhalis lower airway infection in children with chronic endobronchial suppuration.
Asunto(s)
Bronquiectasia/tratamiento farmacológico , Bronquiectasia/microbiología , Macrólidos/farmacología , Macrólidos/uso terapéutico , Moraxella catarrhalis/efectos de los fármacos , Infecciones por Moraxellaceae/tratamiento farmacológico , Infecciones por Moraxellaceae/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bronquiectasia/patología , Líquido del Lavado Bronquioalveolar/microbiología , Preescolar , Enfermedad Crónica , Farmacorresistencia Bacteriana , Femenino , Humanos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/aislamiento & purificación , Infecciones por Moraxellaceae/patología , Nasofaringe/microbiología , Supuración , beta-Lactamasas/biosíntesisRESUMEN
The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2014. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between January 2014 and April 2015 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1534 strains (335 Staphylococcus aureus, 264 Streptococcus pneumoniae, 29 Streptococcus pyogenes, 281 Haemophilus influenzae, 164 Moraxella catarrhalis, 207 Klebsiella pneumoniae, and 254 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 43.6%, and those of penicillin-susceptible S. pneumoniae was 100%. Among H. influenzae, 8.2% of them were found to be ß-lactamase-producing ampicillin-resistant strains, and 49.1% to be ß-lactamase-non-producing ampicillin-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 9.2% and 0.4%, respectively.
Asunto(s)
Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Monitoreo Epidemiológico , Infecciones del Sistema Respiratorio/prevención & control , Programas de Optimización del Uso de los Antimicrobianos , Haemophilus influenzae/efectos de los fármacos , Humanos , Japón/epidemiología , Klebsiella pneumoniae/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Infecciones del Sistema Respiratorio/microbiología , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pyogenes/efectos de los fármacosRESUMEN
Lefamulin, the first semisynthetic pleuromutilin antibacterial for intravenous and oral treatment of community-acquired bacterial pneumonia (CABP), and comparators were evaluated for in vitro activity against a global collection of pathogens commonly causing CABP (n = 8595) from the 2015 and 2016 SENTRY Antimicrobial Surveillance Program. Lefamulin was highly active against the pathogens Streptococcus pneumoniae, including multidrug-resistant and extensively drug-resistant strains (MIC50/90 for total and resistant subsets, 0.06/0.12 µg/ml; 100% inhibited at ≤1 µg/ml), Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA; both MIC50/90, 0.06/0.12 µg/ml; 99.8% and 99.6% inhibited at ≤1 µg/ml, respectively), Haemophilus influenzae (MIC50/90, 0.5/1 µg/ml; 93.8% inhibited at ≤1 µg/ml), and Moraxella catarrhalis (MIC50/90, 0.06/0.12 µg/ml; 100% inhibited at ≤0.25 µg/ml), and its activity was unaffected by resistance to other antibacterial classes.
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Diterpenos/uso terapéutico , Neumonía Bacteriana/tratamiento farmacológico , Compuestos Policíclicos/uso terapéutico , Tioglicolatos/uso terapéutico , Infecciones Comunitarias Adquiridas/microbiología , Infecciones por Haemophilus/tratamiento farmacológico , Haemophilus influenzae/efectos de los fármacos , Humanos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/efectos de los fármacos , Infecciones por Moraxellaceae/tratamiento farmacológico , Infecciones Neumocócicas/tratamiento farmacológico , Neumonía Bacteriana/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Streptococcus pneumoniae/efectos de los fármacosRESUMEN
One-hundred and sixty-eight aqueous and organic extracts of 42 selected bryophyte species were screened in vitro for antiproliferative activity on a panel of human gynecological cancer cell lines containing HeLa (cervix epithelial adenocarcinoma), A2780 (ovarian carcinoma), and T47D (invasive ductal breast carcinoma) cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and for antibacterial activity on 11 strains using the disc-diffusion method. A total of 99 extracts derived from 41 species exerted ≥25% inhibition of proliferation of at least one of the cancer cell lines at 10 µg/mL. In the cases of Brachythecium rutabulum, Encalypta streptocarpa, Climacium dendroides, Neckera besseri, Pleurozium schreberi, and Pseudoleskeella nervosa, more than one extract was active in the antiproliferative assay, whereas the highest activity was observed in the case of Paraleucobryum longifolium. From the tested families, Brachytheciaceae and Amblystegiaceae provided the highest number of antiproliferative extracts. Only 19 samples of 15 taxa showed moderate antibacterial activity, including the most active Plagiomnium cuspidatum, being active on 8 tested strains. Methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus were the most susceptible to the assayed species. This is the first report on the bioactivities of these 14 species.
Asunto(s)
Antiinfecciosos/farmacología , Antineoplásicos Fitogénicos/farmacología , Briófitas/química , Extractos Vegetales/farmacología , Antiinfecciosos/química , Antineoplásicos Fitogénicos/química , Bacillus subtilis/efectos de los fármacos , Bacillus subtilis/crecimiento & desarrollo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Femenino , Humanos , Concentración 50 Inhibidora , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/efectos de los fármacos , Moraxella catarrhalis/crecimiento & desarrollo , Extractos Vegetales/químicaAsunto(s)
Antibacterianos/farmacología , Lavandula/química , Mentha spicata/química , Aceites Volátiles/farmacología , Aceites de Plantas/farmacología , Antibacterianos/química , Cromatografía de Gases y Espectrometría de Masas , Haemophilus influenzae/efectos de los fármacos , Humanos , Medicina Tradicional , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/efectos de los fármacos , Aceites Volátiles/química , Aceites de Plantas/química , Pseudomonas aeruginosa/efectos de los fármacos , Sinusitis/tratamiento farmacológico , Sinusitis/microbiología , Staphylococcus aureus/efectos de los fármacos , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pyogenes/efectos de los fármacos , TurquíaRESUMEN
Ten representative Central European phellinoid Hymenochaetaceae species (Phellinus sensu lato) were selected to examine their potential pharmacological activity. In this study 40 organic (n-hexane, chloroform, 50% methanol) and aqueous extracts with different polarities were analyzed for their antimicrobial, antioxidant, and xanthine oxidase (XO)--inhibitory properties. Fomitiporia robusta, Fuscoporia torulosa, Phellopilus nigrolimitatus, and Porodaedalea chrysoloma showed moderate antibacterial activity; Bacillus subtilis ATCC 6633, methicillin-resistant Staphylococcus aureus ATCC 43300, and Moraxella catarrhalis ATCC 43617 were the strains most susceptible to the examined fungal species. The in vitro antioxidant and XO assays demonstrated that most of the selected species possess remarkable antioxidant and XO-inhibitory activities. The water extracts in general proved to be more active antioxidants than organic extracts. In the case of F. torulosa, Ph. Nigrolimitatus, and P. chrysoloma, the results of DPPH tests correlate well with those obtained by oxygen radical absorbance capacity tests; these mushrooms presented high antioxidant activities in both assays. Future studies involving phellinoid Hymenochaetaceae species are planned, which may furnish novel results in terms of the species' pharmacological activity and the specific compounds responsible for the observed activity.
Asunto(s)
Agaricales/química , Antiinfecciosos/farmacología , Antioxidantes/farmacología , Basidiomycota/química , Xantina Oxidasa/antagonistas & inhibidores , Bacillus subtilis/efectos de los fármacos , Europa (Continente) , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Moraxella catarrhalis/efectos de los fármacosRESUMEN
Bacterial infections contribute to the disease progression of chronic obstructive pulmonary disease by stimulating mucus production in the airways. This increased mucus production and other symptoms are often alleviated when patients are treated with mucolytics such as N-acetyl-L-cysteine (NAC). Moreover, NAC has been suggested to inhibit bacterial growth. Bacteria can release membrane vesicles (MVs) in response to stress, and recent studies report a role for these proinflammatory MVs in the pathogenesis of airways disease. Yet, until now it is not clear whether NAC also affects the release of these MVs. This study set out to determine whether NAC, at concentrations reached during high-dose nebulization, affects bacterial growth and MV release of the respiratory pathogens non-typeable Haemophilus influenzae (NTHi), Moraxella catarrhalis (Mrc), Streptococcus pneumoniae (Spn) and Pseudomonas aeruginosa (Psa). We observed that NAC exerted a strong bacteriostatic effect, but also induced the release of proinflammatory MVs by NTHi, Mrc and Psa, but not by Spn. Interestingly, NAC also markedly blunted the release of TNF-α by naive macrophages in response to MVs. This suggests that the application of NAC by nebulization at a high dosage may be beneficial for patients with airway conditions associated with bacterial infections.
Asunto(s)
Acetilcisteína/farmacología , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Bacterias/crecimiento & desarrollo , Vesículas Citoplasmáticas/efectos de los fármacos , Bacterias/patogenicidad , Expectorantes/farmacología , Haemophilus influenzae/efectos de los fármacos , Haemophilus influenzae/crecimiento & desarrollo , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/microbiología , Moraxella catarrhalis/efectos de los fármacos , Moraxella catarrhalis/crecimiento & desarrollo , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/microbiología , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/crecimiento & desarrolloRESUMEN
Lipopolysaccharide (LPS) is an important surface component and a potential virulence factor in the pathogenesis of Gram-negative bacteria. UDP-N-acetylglucosamine acyltransferase (LpxA) enzyme catalyzes the first reaction of LPS biosynthesis, reversible transfer of R-3-hydroxy-acyl moiety from donor R-3-hydroxy-acyl-acyl carrier protein to the 3' hydroxyl position of UDP-N-acetyl-glucosamine. LpxA enzyme's essentiality in bacterial survival and absence of any homologous protein in humans makes it a promising target for anti-bacterial drug development. Herein, we present the crystal structure of Moraxella catarrhalis LpxA (McLpxA). We propose that L171 is responsible for limiting the acyl chain length in McLpxA to 10C or 12C. The study reveals the plausible interactions between the highly conserved clusters of basic residues at the C-terminal end of McLpxA and acidic residues of acyl carrier protein (ACP). Furthermore, the crystal structure of McLpxA was used to screen potential inhibitors from NCI open database using various computational approaches viz. pharmacophore mapping, virtual screening and molecular docking. Molecules Mol212032, Mol609399 and Mol152546 showed best binding affinity with McLpxA among all screened molecules. These molecules mimic the substrate-LpxA binding interactions.
Asunto(s)
Aciltransferasas/antagonistas & inhibidores , Aciltransferasas/metabolismo , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/farmacología , Simulación del Acoplamiento Molecular , Moraxella catarrhalis/enzimología , Aciltransferasas/química , Cristalografía por Rayos X , Evaluación Preclínica de Medicamentos , Nucleótidos/metabolismo , Conformación Proteica en Lámina beta , Especificidad por SustratoRESUMEN
BACKGROUND AND OBJECTIVE: From mid February to the end of March, each year â¼30% of Japanese have Japanese cedar pollinosis. Moreover, 10-50% of patients with this pollinosis exhibit nasal manifestations in the preseason. These patients have a predominance of neutrophils but not eosinophils in nasal swabs and high carriage of Staphylococcus aureus. We hypothesized that S. aureus or other bacteria and associated neutrophilia were involved in preseasonal symptoms. METHODS: Cytology and bacterial colony growth were assessed in nasal swabs in the groups of asymptomatic patients in the preseason (PreAsP) (n = 53) and symptomatic patients in the preseason (PreSyP) (n = 60), and in group of symptomatic patients in season (InSyP) (n = 72). RESULTS: In the preseason, high neutrophilia was present in only 20% of the PreAsP group but in 47% of the PreSyP group (p < 0.01). Nasal carriage of S. aureus in the PreAsP and PreSyP groups were 79%, 75%, respectively, whereas, for Moraxella catarrhalis, these were 9% versus 25% (PreAsP versus PreSyP group; p < 0.05). In patients with positive results for S. aureus and M. catarrhalis, the degrees of neutrophilia (-, ±, +, 2+, 3+) in the PreSyP group were larger than in the PreAsP groups (p < 0.01). In the PreSyP group, the magnitude of neutrophilia was greater (p < 0.05) in subgroups with more colonies of S. aureus than in subgroups with fewer colonies. CONCLUSION: Nasal symptoms in the preseason are associated with neutrophilia and nasal colonization with S. aureus and M. catarrhalis. Patients with symptoms in the preseason had improved symptom scores when given prophylactic treatment early in season but had more-severe symptom scores late in season than asymptomatic patients in the preseason. Neutrophil-associated tissue damage related to bacterial colonization may underlie these associations.
Asunto(s)
Enfermedades Asintomáticas/epidemiología , Moraxella catarrhalis/fisiología , Infecciones por Moraxellaceae/epidemiología , Mucosa Nasal/microbiología , Neutrófilos/inmunología , Rinitis Alérgica Estacional/epidemiología , Infecciones Estafilocócicas/epidemiología , Staphylococcus aureus/fisiología , Alérgenos/inmunología , Cryptomeria/inmunología , Eosinófilos/inmunología , Humanos , Japón/epidemiología , Infecciones por Moraxellaceae/inmunología , Mucosa Nasal/inmunología , Polen/inmunología , Rinitis Alérgica Estacional/inmunología , Estaciones del Año , Infecciones Estafilocócicas/inmunologíaRESUMEN
Although Moraxella catarrhalis is known to be susceptible to macrolides, highly macrolide-resistant M. catarrhalis isolates have recently been reported in Japan and China. In this study, we investigated the prevalence of macrolide-resistant M. catarrhalis isolates in Tokyo and Chiba, Japan, and studied the mechanisms underlying their resistance. Specifically, we determined the susceptibility of 593 clinical isolates (collected between December 2011 and May 2014) to erythromycin, using the disk diffusion method. For isolates with erythromycin resistance, we identified the MICs of seven antimicrobial agents, including macrolides, and used PFGE to analyse the clonal spread. We also performed sequencing analysis to investigate macrolide-resistance targets. Thirteen isolates (2.2â%) were found to be resistant to erythromycin, showing a high MIC90 to erythromycin, clarithromycin, clindamycin and azithromycin. However, those isolates, in addition to 156 randomly selected erythromycin-susceptible strains, were susceptible to amoxicillin-clavulanate, cefixime and levofloxacin. The 13 highly macrolide-resistant isolates were classified into 10 clades and harboured three or four A2058T-mutated 23S rRNA alleles. Three highly macrolide-resistant isolates also exhibited mutations in ribosomal proteins L4 (V27A and R161C) and L22 (K68T). To the best of our knowledge, we have demonstrated for the first time that, whilst the prevalence of macrolide-resistant M. catarrhalis isolates is low in clinical settings in Japan, genetically diverse isolates with high-level macrolide resistance due to the acquisition of an A2058T mutation in the 23S rRNA have already spread. Our study therefore lays the basis for epidemiological studies of macrolide-resistant M. catarrhalis clinical isolates.
Asunto(s)
Farmacorresistencia Bacteriana Múltiple/genética , Eritromicina/uso terapéutico , Moraxella catarrhalis/efectos de los fármacos , Moraxella catarrhalis/genética , Infecciones por Moraxellaceae/tratamiento farmacológico , Antibacterianos/uso terapéutico , Azitromicina/farmacología , Claritromicina/farmacología , Clindamicina/farmacología , Japón/epidemiología , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/aislamiento & purificación , Infecciones por Moraxellaceae/epidemiología , Mutación/genética , ARN Ribosómico 23S/genéticaRESUMEN
Raspberries, derived from different cultivar varieties, are a popular ingredient of everyday diet, and their biological activity is a point of interest for researchers. The ethanol-water extracts from four varieties of red (Rubus idaeus'Ljulin', 'Veten', 'Poranna Rosa') and black (Rubus occidentalis'Litacz') raspberries were evaluated in the range of their antimicrobial properties as well as phenolic content - sanguiin H-6, free ellagic acid and anthocyanins. The antimicrobial assay was performed with the use of fifteen strains of bacteria, both Gram-negative and Gram-positive. The antimicrobial activity of the extracts varied and depended on the analysed strain of bacteria and cultivar variety, with the exception of Helicobacter pylori, towards which the extracts displayed the same growth inhibiting activity. Two human pathogens Corynebacterium diphtheriae and Moraxella catarrhalis proved to be the most sensitive to raspberry extracts. Contrary to the extracts, sanguiin H-6 and ellagic acid were only active against eight and nine bacterial strains, respectively. The determined MIC and MBC values of both compounds were several times lower than the tested extracts. The highest sensitivity of Corynebacterium diphtheriae to extracts from both black and red raspberries may be due to its sensitivity to sanguiin H-6 and ellagic acid.
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Antiinfecciosos/farmacología , Ácido Elágico/farmacología , Frutas/química , Taninos Hidrolizables/farmacología , Rubus/química , Antocianinas/análisis , Antocianinas/farmacología , Antiinfecciosos/análisis , Cromatografía Líquida de Alta Presión , Corynebacterium diphtheriae/efectos de los fármacos , Ácido Elágico/análisis , Helicobacter pylori/efectos de los fármacos , Concentración de Iones de Hidrógeno , Taninos Hidrolizables/análisis , Moraxella catarrhalis/efectos de los fármacos , Extractos Vegetales/análisis , Extractos Vegetales/farmacologíaRESUMEN
Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease. We have identified and characterized a zinc uptake ABC transporter that is present in all strains of M. catarrhalis tested. A mutant in which the znu gene cluster is knocked out shows markedly impaired growth compared to the wild type in medium that contains trace zinc; growth is restored to wild-type levels by supplementing medium with zinc but not with other divalent cations. Thermal-shift assays showed that the purified recombinant substrate binding protein ZnuA binds zinc but does not bind other divalent cations. Invasion assays with human respiratory epithelial cells demonstrated that the zinc ABC transporter of M. catarrhalis is critical for invasion of respiratory epithelial cells, an observation that is especially relevant because an intracellular reservoir of M. catarrhalis is present in the human respiratory tract and this reservoir is important for persistence. The znu knockout mutant showed marked impairment in its capacity to persist in the respiratory tract compared to the wild type in a mouse pulmonary clearance model. We conclude that the zinc uptake ABC transporter mediates uptake of zinc in environments with very low zinc concentrations and is critical for full virulence of M. catarrhalis in the respiratory tract in facilitating intracellular invasion of epithelial cells and persistence in the respiratory tract.
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Transportadoras de Casetes de Unión a ATP/metabolismo , Proteínas Portadoras/metabolismo , Moraxella catarrhalis/metabolismo , Infecciones por Moraxellaceae/metabolismo , Infecciones del Sistema Respiratorio/metabolismo , Zinc/metabolismo , Transportadoras de Casetes de Unión a ATP/genética , Animales , Proteínas Portadoras/genética , Línea Celular , Células Epiteliales/metabolismo , Células Epiteliales/microbiología , Humanos , Ratones , Ratones Endogámicos BALB C , Moraxella catarrhalis/genética , Moraxella catarrhalis/patogenicidad , Infecciones por Moraxellaceae/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Sistema Respiratorio/metabolismo , Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/genética , Infecciones del Sistema Respiratorio/microbiología , Virulencia/genéticaRESUMEN
OBJECTIVE: To prospectively identify the bacterial aetiology and antimicrobial susceptibility of problematic (recurrent and treatment failure) acute otitis media in Spanish children several years after the introduction of 7-valent pneumococcal conjugate vaccine. METHODS: Tympanocentesis or careful sampling of spontaneous otorrhoea was performed on children aged 3 to <36 months with recurrent acute otitis media, acute otitis media treatment failure or unresolved acute otitis media. RESULTS: 105 acute otitis media episodes (77 sampled by tympanocentesis, 28 otorrhoea samples) were evaluated: 46 recurrent, 35 treatment failures, 24 unresolved acute otitis media. 74 episodes (70.4%) had at least one bacterium identified on culture: Streptococcus pneumoniae was identified in 21 episodes, Haemophilus influenzae (all non-typeable) in 44, Streptococcus pyogenes in 2, Moraxella catarrhalis in 2. No statistically significant difference in bacterial aetiology by episode type was detected. Non-typeable H. influenzae was the most commonly isolated pathogen in all acute otitis media types and in all age sub-groups. Forty percent of S. pneumoniae isolates were multi-drug resistant. Pneumococcal serotype 19A was the most frequently identified serotype (7/21 episodes). Multi-drug resistance was found in 56% of 19A isolates. Of non-typeable H. influenzae isolates, 15% were ampicillin resistant and 13% were amoxicillin/clavulanate resistant. S. pneumoniae and non-typeable H. influenzae DNA were each detected in 57% of samples culture negative for these pathogens, including 12 co-infections. CONCLUSION: Combining culture and polymerase chain reaction results, H. influenzae and S. pneumoniae may be implicated in 70% and 43% of clinically problematic bacterial acute otitis media episodes, respectively. The impact of new vaccines to prevent both S. pneumoniae and non-typeable H. influenzae acute otitis media may be substantial in this population and is worth investigating.
Asunto(s)
Haemophilus influenzae/aislamiento & purificación , Moraxella catarrhalis/aislamiento & purificación , Otitis Media/microbiología , Vacunas Neumococicas , Streptococcus pneumoniae/aislamiento & purificación , Streptococcus pyogenes/aislamiento & purificación , Enfermedad Aguda , Antibacterianos/uso terapéutico , Preescolar , Farmacorresistencia Microbiana , Femenino , Vacuna Neumocócica Conjugada Heptavalente , Humanos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Otitis Media/terapia , Estudios Prospectivos , Recurrencia , España , Insuficiencia del TratamientoRESUMEN
Acute otitis media (AOM) is diagnosed based on visualization of a full or bulging tympanic membrane with middle ear effusion. The distribution of bacteria causing AOM in North America under the influence of pneumococcal conjugate vaccination and antibiotic selection pressure has resulted in a predominance of ß-lactamase-producing Haemophilus influenzae followed by penicillin-resistant Streptococcus pneumoniae. Although guidelines continue to endorse amoxicillin as the preferred treatment, amoxicillin/clavulanate in high dosage would be the preferred treatment based on the otopathogen mix currently. Antibiotic prophylaxis has fallen into disfavor as a preventative strategy for AOM recurrences.
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Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/tratamiento farmacológico , Otitis Media/diagnóstico , Otitis Media/tratamiento farmacológico , Membrana Timpánica , Factores de Edad , Amoxicilina/administración & dosificación , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Antibacterianos/administración & dosificación , Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/microbiología , Cefdinir , Ceftizoxima/análogos & derivados , Ceftizoxima/uso terapéutico , Cefuroxima/uso terapéutico , Cefalosporinas/uso terapéutico , Niño , Preescolar , Haemophilus influenzae/aislamiento & purificación , Humanos , Lactante , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/aislamiento & purificación , Otitis Media/complicaciones , Otitis Media/microbiología , Otitis Media con Derrame/diagnóstico , Otitis Media con Derrame/tratamiento farmacológico , Otoscopía , Streptococcus pneumoniae/aislamiento & purificación , Factores de Tiempo , Membrana Timpánica/patología , Membrana Timpánica/fisiopatología , Cefpodoxima ProxetiloRESUMEN
Acute rhinosinusitis is a common illness in children. Viral upper respiratory tract infection is the most common presentation of rhinosinusitis. Most children resolve the infection spontaneously and only a small proportion develops a secondary bacterial infection. The proper choice of antibiotic therapy depends on the likely infecting pathogens, bacterial antibiotic resistance, and pharmacologic profiles of antibiotics. Amoxicillin-clavulanate is currently recommended as the empiric treatment in those requiring antimicrobial therapy. Isolation of the causative agents should be considered in those who failed the initial treatment. In addition to antibiotics, adjuvant therapies and surgery may be used in the management of acute bacterial rhinosinusitis.
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Antibacterianos/uso terapéutico , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/microbiología , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/microbiología , Rinitis , Sinusitis , Sobreinfección/diagnóstico , Sobreinfección/microbiología , Enfermedad Aguda , Infecciones Bacterianas/tratamiento farmacológico , Niño , Preescolar , Diagnóstico Diferencial , Haemophilus influenzae/aislamiento & purificación , Humanos , Imagen por Resonancia Magnética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/aislamiento & purificación , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Rinitis/complicaciones , Rinitis/diagnóstico , Rinitis/virología , Sinusitis/complicaciones , Sinusitis/diagnóstico , Sinusitis/virología , Staphylococcus aureus/aislamiento & purificación , Streptococcus pneumoniae/aislamiento & purificación , Streptococcus pyogenes/aislamiento & purificación , Sobreinfección/tratamiento farmacológico , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
This study aimed to evaluate the antimicrobial effects, the radical scavenging activity (by DPPH and ABTS tests) and the antioxidant capacity (by ß-carotene bleaching test) of Betula aetnensis leaves extract. The antimicrobial activity was tested against 14 Gram-positive clinical strains, 2 ATCC Gram-positive strains, 10 Gram-negative clinical strains and 4 Gram-negative ATCC strains. Streptococcus pyogenes Ery-S and Ery-R1 were the most sensitive. Betula aetnensis was considerably active against three bacterial strains, namely Haemophilus influenzae ATCC 49247, Amp-R1 and Moraxella catarrhalis ATCC 25238. Standard ATCC strains of Gram-positive bacteria were more sensitive than Gram-negative. Betula aetnensis showed also an interesting reducing power with TEAC values of 9.7 and a good inhibition of linoleic acid oxidation with an IC50 value of 22.0 µg mL(-1) after 30 min of incubation. The total phenol and flavonoid contents were determined with the purpose to evaluate the relationship with the observed bioactivities.
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Antibacterianos/química , Antioxidantes/química , Betula/química , Extractos Vegetales/química , Hojas de la Planta/química , Antibacterianos/farmacología , Haemophilus influenzae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/efectos de los fármacos , Extractos Vegetales/farmacologíaRESUMEN
OBJECTIVE: To perform a randomized controlled trial comparing moxifloxacin hydrochloride with polymyxin B-trimethoprim for the treatment of acute conjunctivitis. STUDY DESIGN: Patients ages 1-18 years old with acute conjunctivitis had cultures performed and were randomized to receive either moxifloxacin hydrochloride or polymyxin B-trimethoprim ophthalmic solution for 7 days. Response to treatment was determined by phone query on day 4-6 and by examination with post-treatment conjunctival culture on day 7-10. RESULTS: One hundred and twenty-four patients were enrolled. Eighty patients (65%) had recognized pathogens (55 Haemophilus influenzae, 22 Streptococcus pneumoniae, 4 Moraxella catarrhalis) isolated from their conjunctiva. One hundred fourteen (56/62 moxifloxacin and 58/62 polymyxin B-trimethoprim) completed the 4-6 day evaluation, with 43/56 (77%) of the moxifloxacin group and 42/58 (72%) of the polymyxin B-trimethoprim group clinically cured according to parents (noninferiority test P = .04). Eighty-nine (39/56 moxifloxacin and 50/58 polymyxin B-trimethoprim) patients completed the 7-10 day evaluation. Clinical cure was observed in 37/39 (95%) of the moxifloxacin and 49/51 (96%) of the polymyxin B-trimethoprim treated groups (noninferiority test P ≤ .01). Clinical cure rates for culture positive and negative conjunctivitis were not different. There was no statistically significant difference in bacteriologic cure rates between the 2 groups. CONCLUSIONS: Polymyxin B-trimethoprim continues to be an effective treatment for acute conjunctivitis with a clinical response rate that does not differ from moxifloxacin. Use of polymyxin B-trimethoprim for the treatment of conjunctivitis would result in significant cost savings compared with fluoroquinolones.