RESUMEN
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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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.
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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
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
JNJ-Q2 is a broad-spectrum fluoroquinolone with bactericidal activity against Gram-positive and Gram-negative pathogens and is currently in clinical development for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin-structure infections. This study determined the activity of JNJ-Q2 against a worldwide year 2010 collection (89 centres in 27 countries) of three common respiratory pathogens (3757 isolates) from patients with CABP. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were tested by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method, and susceptibility rates for comparators were assessed using CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint criteria. JNJ-Q2 had activity against all three species, with 96.9% of strains inhibited at ≤0.015 mg/L. JNJ-Q2 [minimum inhibitory concentration for 50% and 90% of the organisms, respectively (MIC(50/90))=0.008/0.015 mg/L] demonstrated a 16-fold greater potency compared with moxifloxacin (MIC(50/90)=0.12/0.25 mg/L) and at least 128-fold greater activity compared with levofloxacin (MIC(50/90)=1/ 1 mg/L) and ciprofloxacin (MIC(50/90)=1/2 mg/L) against S. pneumoniae. Haemophilus influenzae isolates were 21.9-23.3% resistant to ampicillin, but JNJ-Q2 (MIC(50/90)≤0.004/0.015 mg/L) was at least two-fold more active than moxifloxacin (MIC(50/90)=0.015/0.03 mg/L) as well as being potent against M. catarrhalis (MIC(90)=0.015/0.015 mg/L). In conclusion, JNJ-Q2 demonstrated increased potency compared with other marketed fluoroquinolones that have been used to treat CABP pathogens, thus favouring further clinical development.
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Infecciones Comunitarias Adquiridas/microbiología , Fluoroquinolonas/farmacología , Haemophilus influenzae/efectos de los fármacos , Moraxella catarrhalis/efectos de los fármacos , Neumonía Bacteriana/microbiología , Streptococcus pneumoniae/efectos de los fármacos , Antibacterianos/farmacología , Compuestos Aza/farmacología , Evaluación Preclínica de Medicamentos , Farmacorresistencia Bacteriana Múltiple , Geografía , Haemophilus influenzae/aislamiento & purificación , Humanos , Concentración 50 Inhibidora , Levofloxacino , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/aislamiento & purificación , Moxifloxacino , Ofloxacino/farmacología , Quinolinas/farmacología , Streptococcus pneumoniae/aislamiento & purificaciónRESUMEN
OBJECTIVE: To determine the antimoraxella activity of Ethiopian medicinal plants extracts. METHODS: Two clinical isolates of Moraxella cattarhalis (M. cattarhalis) with different antibiotic sensitivity pattern were tested to determine their susceptibility to garlic [Allium sativum (A. sativum)], bark of cinnamon [Cinnamomum zeylanicum (C. zeylanicum)], clove [Syzygium aromaticum (S. aromaticum)], and leaves of avocado [Persea americana (P. americana)], rosemary [Rosmarinus officinalis (R. officinalis)] and prickly poppy [Argemone mexicana (A. mexicana)]. Disk diffusion assay and broth dilution method were used to measure zone of inhibition, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of plant extracts against M. cattarhalis. RESULTS: Both the strains of M. cattarhalis exhibited similar sensitivities to the extracts of medicinal plants. Antimoraxella activity was exhibited only by garlic, avocado leaves and cinnamon. Garlic was found to be more antagonistic to M. cattarhalis than cinnamon and avocado. Garlic and avocado leaves have shown similar MIC (30 mg/mL) where as their zone of inhibition (15 and 11 mm, respectively) were different. CONCLUSIONS: Garlic, cinnamon and avocado leaves extracts represents alternative source of natural antimicrobial substances for use in clinical practice for the treatment of cases of M. cattarhalis. Further research on the effects of these extracts on M. cattarhalis can be rewarding to pursue in the search for new broad spectrum antimicrobial agents.
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Antibacterianos/farmacología , Moraxella catarrhalis/efectos de los fármacos , Extractos Vegetales/farmacología , Plantas Medicinales/química , Antibacterianos/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/aislamiento & purificación , Infecciones por Moraxellaceae/microbiología , Extractos Vegetales/aislamiento & purificaciónRESUMEN
PURPOSE: Curcumin exerts its anti-inflammatory activity via inhibition of nuclear factor κB. Oropharyngeal epithelia and residing bacteria closely interact in inflammation and infection. This in vitro model investigated the effects of curcumin on bacterial survival, adherence to, and invasion of upper respiratory tract epithelia, and studied its anti-inflammatory effect. We aimed to establish a model, which could offer insights into the host-pathogen interaction in cancer therapy induced mucositis. METHODS: Moraxella catarrhalis (Mcat) and the oropharyngeal epithelial cell line Detroit 562 were used. Time-kill curves assessed the inhibition of bacterial growth and adherence assays and gentamicin protection assays determined the effect of curcumin-preincubated cells on bacterial adherence and invasion. Curcumin-mediated inhibition of pro-inflammatory activation by Mcat was determined via interleukin-8 concentrations in the supernatants. The synergistic role of secretory IgA (sIgA) on adherence was investigated. RESULTS: Curcumin was bactericidal at concentrations >50 µM. Preincubation of Detroit cells for 60 min demonstrated that concentrations >100 µM inhibited bacterial adherence. Together with sIgA, curcumin inhibited adherence at concentrations ≥50 µM. Both 100 and 200 µM curcumin significantly inhibited Mcat cell invasion. Finally, curcumin inhibited Mcat-induced pro-inflammatory activation by strongly suppressing IL-8 release. At a concentration of 200 µM, 10 min of curcumin exposure inhibited IL-8 release significantly, and complete suppression required a pre-exposure time of ≥45 min. CONCLUSION: Curcumin, in clinically relevant concentrations for topical use, displayed strong antibacterial effect against a facultative upper respiratory tract pathogen by inhibiting bacterial growth, adherence, invasion, and pro-inflammatory activation of upper respiratory tract epithelial cells in vitro.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Curcumina/farmacología , Inmunoglobulina A Secretora/administración & dosificación , Moraxella catarrhalis/efectos de los fármacos , Administración Tópica , Antiinflamatorios no Esteroideos/administración & dosificación , Adhesión Bacteriana/efectos de los fármacos , Línea Celular , Curcumina/administración & dosificación , Relación Dosis-Respuesta a Droga , Células Epiteliales/efectos de los fármacos , Células Epiteliales/microbiología , Humanos , Interleucina-8/metabolismo , Infecciones por Moraxellaceae/tratamiento farmacológico , Infecciones por Moraxellaceae/microbiología , Orofaringe/citología , Orofaringe/microbiología , Estomatitis/tratamiento farmacológico , Estomatitis/etiología , Estomatitis/microbiología , Factores de TiempoRESUMEN
Resistance to macrolides and beta-lactams has increased sharply amongst key respiratory pathogens, leading to major concern. A novel series of acylides was designed to overcome this resistance and was evaluated for in vitro and in vivo activity. This series of acylides was designed starting from clarithromycin by changing the substitution on the desosamine nitrogen, followed by conversion to 3-O-acyl and 11,12-carbamate. Minimum inhibitory concentrations (MICs) of acylides were determined against susceptible as well as macrolide-lincosamide-streptogramin B (MLS(B))--and penicillin-resistant Streptococcus pneumoniae, Streptococcus pyogenes and Moraxella catarrhalis by the agar dilution method. Microbroth MICs for Haemophilus influenzae were determined according to Clinical and Laboratory Standards Institute guidelines. In vivo efficacy was determined by target organ load reduction against S. pneumoniae 3579 (ermB). The bactericidal potential of promising acylides was also determined. MICs of these compounds against S. pneumoniae, S. pyogenes, H. influenzae and M. catarrhalis were in the range of 0.06-2, 0.125-1, 1-16 and 0.015-0.5 microg/mL, respectively, irrespective of their resistance pattern. Mycoplasma pneumoniae and Legionella pneumophila showed MIC ranges of 0.004-0.125 microg/mL and 0.004-0.03 microg/mL, respectively. The acylides also showed better activity against telithromycin-resistant S. pneumoniae strains. Compounds with a 4-furan-2-yl-1H-imidazolyl side chain on the carbamate (RBx 10000296) showed a target organ load reduction of >3 log(10) colony-forming units/mL and concentration-dependent bactericidal potential against S. pneumoniae 994 mefA and H. influenzae strains. This novel and potent series of acylides active against antibiotic-resistant respiratory pathogens should be further investigated.
Asunto(s)
Antibacterianos/farmacología , Claritromicina/análogos & derivados , Infecciones Comunitarias Adquiridas/microbiología , Haemophilus influenzae/efectos de los fármacos , Moraxella catarrhalis/efectos de los fármacos , Neumonía Bacteriana/microbiología , Streptococcus pneumoniae/efectos de los fármacos , Administración Oral , Animales , Antibacterianos/síntesis química , Antibacterianos/uso terapéutico , Claritromicina/síntesis química , Claritromicina/farmacología , Claritromicina/uso terapéutico , Evaluación Preclínica de Medicamentos , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , Neumonía Neumocócica/tratamiento farmacológico , Factores de TiempoRESUMEN
As the need for novel antibiotic classes to combat bacterial drug resistance increases, the paucity of leads resulting from target-based antibacterial screening of pharmaceutical compound libraries is of major concern. One explanation for this lack of success is that antibacterial screening efforts have not leveraged the eukaryotic bias resulting from more extensive chemistry efforts targeting eukaryotic gene families such as G protein-coupled receptors and protein kinases. Consistent with a focus on antibacterial target space resembling these eukaryotic targets, we used whole-cell screening to identify a series of antibacterial pyridopyrimidines derived from a protein kinase inhibitor pharmacophore. In bacteria, the pyridopyrimidines target the ATP-binding site of biotin carboxylase (BC), which catalyzes the first enzymatic step of fatty acid biosynthesis. These inhibitors are effective in vitro and in vivo against fastidious gram-negative pathogens including Haemophilus influenzae. Although the BC active site has architectural similarity to those of eukaryotic protein kinases, inhibitor binding to the BC ATP-binding site is distinct from the protein kinase-binding mode, such that the inhibitors are selective for bacterial BC. In summary, we have discovered a promising class of potent antibacterials with a previously undescribed mechanism of action. In consideration of the eukaryotic bias of pharmaceutical libraries, our findings also suggest that pursuit of a novel inhibitor leads for antibacterial targets with active-site structural similarity to known human targets will likely be more fruitful than the traditional focus on unique bacterial target space, particularly when structure-based and computational methodologies are applied to ensure bacterial selectivity.
Asunto(s)
Antibacterianos/química , Ligasas de Carbono-Nitrógeno/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/farmacología , Antibacterianos/farmacología , Descubrimiento de Drogas , Evaluación Preclínica de Medicamentos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/enzimología , Haemophilus influenzae/efectos de los fármacos , Haemophilus influenzae/enzimología , Moraxella catarrhalis/efectos de los fármacos , Moraxella catarrhalis/enzimología , Inhibidores de Proteínas Quinasas/química , Pirimidinas/química , Bibliotecas de Moléculas PequeñasRESUMEN
BACKGROUND: Since 2001, long-term, low-dose azithromycin treatment has been used for CF patients chronically infected with Pseudomonas aeruginosa in the Copenhagen CF centre. Our study investigates changes in incidence of colonization with Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis and changes in macrolide sensitivity in these microorganisms during azithromycin treatment. METHODS: CF patients treated continuously with azithromycin for at least 3 months were included. Results of microbiological examination, including phage typing results of S. aureus, obtained during treatment were compared to results obtained 2 years before treatment. RESULTS: 70 patients (median age 29.1 years) treated for a median of 4 years (range 0.7-5.1) were included. Before treatment, 44 patients had at least one culture positive for S. aureus compared to 25 patients during treatment (p<0.01). Mean percentage of sputum samples with growth of S. aureus decreased from 12.1% (range 0-82.6%) before treatment to 6.1% (range 0-93.2) during treatment (p<0.0006). Prevalence's of H. influenzae and S. pneumoniae also decreased significantly. Fifteen of 214 isolates (7%) of S. aureus were macrolide resistant before treatment, increasing to 95 of 181 isolates (52.5%) during treatment (p<0.001). Macrolide resistant strains were found in 3 of 44 S. aureus colonized patients before treatment and in 11 of 25 patients at some time during treatment (p<0.03), all belonging to different phage types. First resistant S. aureus isolate was isolated after a median treatment duration of 1.5 years (range 0.3-2.9). No MRSA were isolated. Only 1 macrolide resistant isolate of M. catarrhalis was found during treatment. No macrolide resistance was found in H. influenzae or S. pneumoniae. CONCLUSION: Long-term, low-dose treatment with azithromycin in CF patients leads to reduced prevalence of S. aureus, S. pneumoniae, and H. influenzae, but increased macrolide resistance in S. aureus. Reduction in the prevalence of S. aureus will make increasing macrolide resistance clinically insignificant in these patients.
Asunto(s)
Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Fibrosis Quística/microbiología , Infecciones por Pseudomonas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Adolescente , Adulto , Antibacterianos/farmacología , Azitromicina/farmacología , Niño , Preescolar , Enfermedad Crónica , Dinamarca , Farmacorresistencia Microbiana , Haemophilus influenzae/efectos de los fármacos , Haemophilus influenzae/aislamiento & purificación , Humanos , Lactante , Cuidados a Largo Plazo/métodos , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Moraxella catarrhalis/efectos de los fármacos , Moraxella catarrhalis/aislamiento & purificación , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/aislamiento & purificación , Estudios Retrospectivos , Esputo/microbiología , Staphylococcus aureus/aislamiento & purificación , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/aislamiento & purificación , Adulto JovenRESUMEN
Antibiotic therapy is of clinical benefit in certain patients with acute exacerbations of chronic bronchitis (AECB). In this randomised, investigator-blinded, multicentre trial, azithromycin (500mg once a day (qd) for 3 days) was compared with moxifloxacin (400mg qd for 5 days) for the treatment of outpatients with AECB (forced expiratory volume in 1s (FEV(1)) >35%). Of 342 patients randomised to either treatment, 169 received azithromycin and 173 received moxifloxacin. The mean age in the azithromycin and moxifloxacin groups was 56.4 years and 55.5 years, respectively. In the intent-to-treat analysis, clinical success rates for azithromycin and moxifloxacin were comparable at Days 10-12 (90% versus 90%, respectively) and Days 22-26 (81% versus 82%, respectively). Among patients who were culture-positive at baseline for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis or Haemophilus parainfluenzae, clinical efficacy for azithromycin versus moxifloxacin at Days 10-12 was 93% versus 84%, respectively, and at Days 22-26 it was 89% versus 73%, respectively. The incidence of at least one treatment-related adverse event (AE) in the azithromycin and moxifloxacin groups was 18.3% and 19.1%, respectively. The most common AEs were diarrhoea, nausea, abdominal pain and vaginitis. Most treatment-related AEs were of mild or moderate severity, with no serious treatment-related AEs. One subject in the moxifloxacin group discontinued treatment owing to a treatment-related AE (precordial pain and dry throat). Compliance with both regimens was >90%. Three-day azithromycin and 5-day moxifloxacin demonstrate comparable efficacy and safety for the treatment of AECB in outpatients.
Asunto(s)
Compuestos Aza/uso terapéutico , Azitromicina/uso terapéutico , Bronquitis Crónica/tratamiento farmacológico , Quinolinas/uso terapéutico , Dolor Abdominal/inducido químicamente , Adulto , Anciano , Antibacterianos/efectos adversos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Compuestos Aza/efectos adversos , Compuestos Aza/farmacología , Azitromicina/efectos adversos , Azitromicina/farmacología , Bronquitis Crónica/microbiología , Esquema de Medicación , Femenino , Fluoroquinolonas , Haemophilus influenzae/efectos de los fármacos , Haemophilus influenzae/aislamiento & purificación , Haemophilus parainfluenzae/efectos de los fármacos , Haemophilus parainfluenzae/aislamiento & purificación , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Moraxella catarrhalis/efectos de los fármacos , Moraxella catarrhalis/aislamiento & purificación , Moxifloxacino , Náusea/inducido químicamente , Cooperación del Paciente , Quinolinas/efectos adversos , Quinolinas/farmacología , Método Simple Ciego , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/aislamiento & purificación , Resultado del Tratamiento , Vaginitis/inducido químicamenteRESUMEN
This study assessed daily aspirate samples from an indwelling sinus catheter during high-dose, short-course levofloxacin (750 mg daily x 5 days) treatment of acute maxillary sinusitis. Pathogens were isolated from 4 of 18 recruited patients. Bacteriologic eradication occurred within 24 h for 3 patients and 72 h for the 4th.