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1.
BMC Infect Dis ; 20(1): 507, 2020 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-32660436

RESUMEN

BACKGROUND: Group A streptococcus (GAS) is an important human pathogen responsible for a broad range of infections. Epidemiological surveillance has been crucial to detect changes in the geographical and temporal variation of the disease pattern. The objective of this study was to investigate the molecular epidemiological characteristics and antimicrobial resistance of GAS isolates from patients in Children's Hospital in Beijing. METHODS: From 2016 to 2017, pharyngeal swab samples were collected from the outpatients in Children's Hospital, Capital Institute of Pediatrics, who were diagnosed with scarlet fever. Antimicrobial susceptibility test was performed according to the distribution of conventional antibiotics and Clinical and Laboratory Standards Institute (CLSI) recommendations. The distribution of the macrolide-resistance genes (ermB, ermA, mefA), emm (M protein-coding gene) typing, and superantigens (SAg) gene profiling were examined by polymerase chain reaction (PCR). RESULTS: A total of 297 GAS isolates were collected. The susceptibility of the isolates to penicillin, ceftriaxone, and levofloxacin was 100%. The resistance rate to erythromycin and clindamycin was 98.3 and 96.6%, respectively. The dominant emm types were emm12 (65.32%), emm1 (27.61%), emm75 (2.69%), and emm89 (1.35%). Of the 297 isolates, 290 (97.64%) carried the ermB gene, and 5 (1.68%) carried the mefA gene, while none carried the ermA gene. The most common superantigen genes identified from GAS isolates were smeZ (96.97%), speC (92.59%), speG (91.58%), ssa (85.52%), speI (54.55%), speH (52.19%), and speA (34.34%). Isolates with the genotype emm1 possessed speA, speC, speG, speJ, speM, ssa, and smeZ, while emm12 possessed speC, speG, speH, speI, speM, ssa, and smeZ superantigens. CONCLUSIONS: The prevalent strain of GAS isolates in Beijing has a high resistance rate to macrolides; however, penicillin can still be the preferred antibiotic for treatment. Erythromycin resistance was predominantly mediated by ermB. The common emm types were emm12 and emm1. There was a correlation between emm and the superantigen gene. Thus, long-term monitoring and investigation of the emm types and superantigen genes of GAS prevalence are imperative.


Asunto(s)
Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana/genética , Penicilinas/uso terapéutico , Escarlatina/tratamiento farmacológico , Escarlatina/epidemiología , Streptococcus pyogenes/inmunología , Adolescente , Antígenos Bacterianos/genética , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas Bacterianas/genética , Beijing/epidemiología , Reanimación Cardiopulmonar , Proteínas Portadoras/genética , Niño , Preescolar , Eritromicina/uso terapéutico , Femenino , Hospitales Pediátricos , Humanos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Escarlatina/microbiología , Streptococcus pyogenes/aislamiento & purificación , Superantígenos/genética
2.
Cochrane Database Syst Rev ; 5: CD011368, 2020 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-32356369

RESUMEN

BACKGROUND: Acne is an inflammatory disorder with a high global burden. It is common in adolescents and primarily affects sebaceous gland-rich areas. The clinical benefit of the topical acne treatments azelaic acid, salicylic acid, nicotinamide, sulphur, zinc, and alpha-hydroxy acid is unclear. OBJECTIVES: To assess the effects of topical treatments (azelaic acid, salicylic acid, nicotinamide, zinc, alpha-hydroxy acid, and sulphur) for acne. SEARCH METHODS: We searched the following databases up to May 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers. SELECTION CRITERIA: Clinical randomised controlled trials of the six topical treatments compared with other topical treatments, placebo, or no treatment in people with acne. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Key outcomes included participants' global self-assessment of acne improvement (PGA), withdrawal for any reason, minor adverse events (assessed as total number of participants who experienced at least one minor adverse event), and quality of life. MAIN RESULTS: We included 49 trials (3880 reported participants) set in clinics, hospitals, research centres, and university settings in Europe, Asia, and the USA. The vast majority of participants had mild to moderate acne, were aged between 12 to 30 years (range: 10 to 45 years), and were female. Treatment lasted over eight weeks in 59% of the studies. Study duration ranged from three months to three years. We assessed 26 studies as being at high risk of bias in at least one domain, but most domains were at low or unclear risk of bias. We grouped outcome assessment into short-term (less than or equal to 4 weeks), medium-term (from 5 to 8 weeks), and long-term treatment (more than 8 weeks). The following results were measured at the end of treatment, which was mainly long-term for the PGA outcome and mixed length (medium-term mainly) for minor adverse events. Azelaic acid In terms of treatment response (PGA), azelaic acid is probably less effective than benzoyl peroxide (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.72 to 0.95; 1 study, 351 participants), but there is probably little or no difference when comparing azelaic acid to tretinoin (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 289 participants) (both moderate-quality evidence). There may be little or no difference in PGA when comparing azelaic acid to clindamycin (RR 1.13, 95% CI 0.92 to 1.38; 1 study, 229 participants; low-quality evidence), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). Low-quality evidence indicates there may be no differences in rates of withdrawal for any reason when comparing azelaic acid with benzoyl peroxide (RR 0.88, 95% CI 0.60 to 1.29; 1 study, 351 participants), clindamycin (RR 1.30, 95% CI 0.48 to 3.56; 2 studies, 329 participants), or tretinoin (RR 0.66, 95% CI 0.29 to 1.47; 2 studies, 309 participants), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). In terms of total minor adverse events, we are uncertain if there is a difference between azelaic acid compared to adapalene (1 study; 55 participants) or benzoyl peroxide (1 study, 30 participants) (both very low-quality evidence). There may be no difference when comparing azelaic acid to clindamycin (RR 1.50, 95% CI 0.67 to 3.35; 1 study, 100 participants; low-quality evidence). Total minor adverse events were not reported in the comparison of azelaic acid versus tretinoin, but individual application site reactions were reported, such as scaling. Salicylic acid For PGA, there may be little or no difference between salicylic acid and tretinoin (RR 1.00, 95% CI 0.92 to 1.09; 1 study, 46 participants; low-quality evidence); we are not certain whether there is a difference between salicylic acid and pyruvic acid (1 study, 86 participants; very low-quality evidence); and PGA was not measured in the comparison of salicylic acid versus benzoyl peroxide. There may be no difference between groups in withdrawals when comparing salicylic acid and pyruvic acid (RR 0.89, 95% CI 0.53 to 1.50; 1 study, 86 participants); when salicylic acid was compared to tretinoin, neither group had withdrawals (both based on low-quality evidence (2 studies, 74 participants)). We are uncertain whether there is a difference in withdrawals between salicylic acid and benzoyl peroxide (1 study, 41 participants; very low-quality evidence). For total minor adverse events, we are uncertain if there is any difference between salicylic acid and benzoyl peroxide (1 study, 41 participants) or tretinoin (2 studies, 74 participants) (both very low-quality evidence). This outcome was not reported for salicylic acid versus pyruvic acid, but individual application site reactions were reported, such as scaling and redness. Nicotinamide Four studies evaluated nicotinamide against clindamycin or erythromycin, but none measured PGA. Low-quality evidence showed there may be no difference in withdrawals between nicotinamide and clindamycin (RR 1.12, 95% CI 0.49 to 2.60; 3 studies, 216 participants) or erythromycin (RR 1.40, 95% CI 0.46 to 4.22; 1 study, 158 participants), or in total minor adverse events between nicotinamide and clindamycin (RR 1.20, 95% CI 0.73 to 1.99; 3 studies, 216 participants; low-quality evidence). Total minor adverse events were not reported in the nicotinamide versus erythromycin comparison. Alpha-hydroxy (fruit) acid There may be no difference in PGA when comparing glycolic acid peel to salicylic-mandelic acid peel (RR 1.06, 95% CI 0.88 to 1.26; 1 study, 40 participants; low-quality evidence), and we are uncertain if there is a difference in total minor adverse events due to very low-quality evidence (1 study, 44 participants). Neither group had withdrawals (2 studies, 84 participants; low-quality evidence). AUTHORS' CONCLUSIONS: Compared to benzoyl peroxide, azelaic acid probably leads to a worse treatment response, measured using PGA. When compared to tretinoin, azelaic acid probably makes little or no difference to treatment response. For other comparisons and outcomes the quality of evidence was low or very low. Risk of bias and imprecision limit our confidence in the evidence. We encourage the comparison of more methodologically robust head-to-head trials against commonly used active drugs.


Asunto(s)
Acné Vulgar/tratamiento farmacológico , Fármacos Dermatológicos/uso terapéutico , Adapaleno/efectos adversos , Adapaleno/uso terapéutico , Adolescente , Adulto , Antibacterianos/uso terapéutico , Peróxido de Benzoílo/uso terapéutico , Sesgo , Niño , Clindamicina/efectos adversos , Clindamicina/uso terapéutico , Fármacos Dermatológicos/efectos adversos , Ácidos Dicarboxílicos/efectos adversos , Ácidos Dicarboxílicos/uso terapéutico , Eritromicina/efectos adversos , Eritromicina/uso terapéutico , Femenino , Glicolatos/uso terapéutico , Humanos , Queratolíticos/uso terapéutico , Masculino , Ácidos Mandélicos/uso terapéutico , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Ácido Pirúvico/efectos adversos , Ácido Pirúvico/uso terapéutico , Calidad de Vida , Ácido Salicílico/uso terapéutico , Azufre/uso terapéutico , Tretinoina/uso terapéutico , Adulto Joven , Zinc/uso terapéutico
3.
Am J Trop Med Hyg ; 103(2): 652-658, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32458788

RESUMEN

The efficacy of commonly used antibiotics for treating severe cholera has been compromised over time because of the reduced antibiotic susceptibility. This study aimed to describe the rate of detection of Vibrio cholerae O1 from fecal samples and antimicrobial susceptibility profiles of V. cholerae O1 serotypes to commonly used antibiotics. During January 2000-December 2018, V. cholerae O1 was detected in fecal samples of 7,472 patients. Vibrio cholerae O1 Inaba serotype was predominant, ranging from 60% to 86% during the period 2000-2006 except for 2003 and 2005 when the Ogawa serotype was predominant. Later on, the Ogawa serotype became predominant from 2007 to 2015, fluctuating between 52% and 100%. However, in 2016 and 2017, isolation rates declined to 2% and 1%, respectively, but surged again to 75% in 2018. Nearly 100% of V. cholerae O1 strains were sensitive to tetracycline during 2000-2004. Thereafter, a declining trend of sensitivity was observed to be continued and dropped down to < 6% during 2012-2017 and again increased to 76% in 2018. Susceptibility to azithromycin and ciprofloxacin was nearly 100%, and susceptibility to cotrimoxazole and furazolidone was 01% throughout the study period. We also found the emergence of resistance to erythromycin in 2005 and sensitivity to cotrimoxazole in 2018. Thus, the rapid decline of the sensitivity of V. cholerae O1 to tetracycline and a reversed peak after 6 years need continued monitoring and reporting.


Asunto(s)
Antibacterianos/uso terapéutico , Cólera/microbiología , Farmacorresistencia Bacteriana/fisiología , Vibrio cholerae O1/fisiología , Adulto , Azitromicina/uso terapéutico , Bangladesh/epidemiología , Niño , Cólera/tratamiento farmacológico , Cólera/epidemiología , Ciprofloxacino/uso terapéutico , Eritromicina/uso terapéutico , Femenino , Furazolidona/uso terapéutico , Hospitales Especializados , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Tetraciclina/uso terapéutico , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Vibrio cholerae O1/aislamiento & purificación
5.
Am J Respir Crit Care Med ; 201(6): 661-670, 2020 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-31765597

RESUMEN

Rationale: Non-cystic fibrosis bronchiectasis is characterized by airway mucus accumulation and sputum production, but the role of mucus concentration in the pathogenesis of these abnormalities has not been characterized.Objectives: This study was designed to: 1) measure mucus concentration and biophysical properties of bronchiectasis mucus; 2) identify the secreted mucins contained in bronchiectasis mucus; 3) relate mucus properties to airway epithelial mucin RNA/protein expression; and 4) explore relationships between mucus hyperconcentration and disease severity.Methods: Sputum samples were collected from subjects with bronchiectasis, with and without chronic erythromycin administration, and healthy control subjects. Sputum percent solid concentrations, total and individual mucin concentrations, osmotic pressures, rheological properties, and inflammatory mediators were measured. Intracellular mucins were measured in endobronchial biopsies by immunohistochemistry and gene expression. MUC5B (mucin 5B) polymorphisms were identified by quantitative PCR. In a replication bronchiectasis cohort, spontaneously expectorated and hypertonic saline-induced sputa were collected, and mucus/mucin concentrations were measured.Measurements and Main Results: Bronchiectasis sputum exhibited increased percent solids, total and individual (MUC5B and MUC5AC) mucin concentrations, osmotic pressure, and elastic and viscous moduli compared with healthy sputum. Within subjects with bronchiectasis, sputum percent solids correlated inversely with FEV1 and positively with bronchiectasis extent, as measured by high-resolution computed tomography, and inflammatory mediators. No difference was detected in MUC5B rs35705950 SNP allele frequency between bronchiectasis and healthy individuals. Hypertonic saline inhalation acutely reduced non-cystic fibrosis bronchiectasis mucus concentration by 5%.Conclusions: Hyperconcentrated airway mucus is characteristic of subjects with bronchiectasis, likely contributes to disease pathophysiology, and may be a target for pharmacotherapy.


Asunto(s)
Bronquiectasia/tratamiento farmacológico , Bronquiectasia/fisiopatología , Eritromicina/uso terapéutico , Moco/química , Sistema Respiratorio/fisiopatología , Esputo/química , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Moco/microbiología , Queensland , Esputo/microbiología
6.
Inflamm Res ; 69(1): 139-151, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31820024

RESUMEN

OBJECTIVE: Macrolides have been reported to reduce the exacerbation of severe asthma. The aim of this study was to clarify the effects and mechanisms of EM900, a non-antibiotic macrolide, on allergic airway inflammation. METHODS: Mice were sensitized and challenged by house dust mite (HDM), then exposed to polyinosinic-polycytidylic acid (poly(I:C)) as a model of asthma complicated with viral infection. Mice were administered with EM900. Airway inflammation was assessed from inflammatory cells in bronchoalveolar lavage fluid (BALF) and cytokines in lung tissues. Lung interstitial macrophages were counted by flow cytometry. Cytokine production, phosphorylation of NF-κB, and p38 in macrophages were examined by ELISA and western blotting. RESULTS: Counts of cells in BALF and concentrations of IL-13, IL-5, RANTES, IL-17A, and MIP-2 were significantly decreased by EM900 compared to those without EM900. Percentages of lung interstitial macrophages were significantly decreased with EM900. Concentrations of IL-6, RANTES, and MIP-2 induced by HDM and poly(I:C) were significantly suppressed by EM900 through the suppression of NF-κB and p38 phosphorylation in macrophages. CONCLUSIONS: HDM and poly(I:C)-induced airway inflammation is attenuated by EM900 with the inhibition of lung interstitial macrophages. Clinical use of EM900 is expected, because EM900 has inhibitory effects against airway inflammation without inducing bacterial drug resistance.


Asunto(s)
Antiinflamatorios/uso terapéutico , Asma/tratamiento farmacológico , Eritromicina/análogos & derivados , Macrófagos Alveolares/efectos de los fármacos , Virosis/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Asma/inmunología , Asma/patología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/inmunología , Modelos Animales de Enfermedad , Eritromicina/farmacología , Eritromicina/uso terapéutico , Femenino , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Macrófagos Alveolares/inmunología , Ratones Endogámicos BALB C , Poli I-C , Pyroglyphidae/inmunología , Virosis/inmunología , Virosis/patología
8.
Sci Rep ; 9(1): 19547, 2019 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-31862938

RESUMEN

The aim of this study was to evaluate the effectiveness of preventing mother to child syphilis transmission to improve pregnancy outcomes. We performed a retrospective analysis of municipal databases of mother-to-child syphilis transmission. Pregnant women with syphilis were included. Group specific pregnancy outcomes were analyzed according to treatment. A total of 28 pregnant women were diagnosed with syphilis in 2012; 321 were diagnosed with syphilis in 2018. A prevalence of 0.14% was observed amongst pregnant women in Suzhou city from 2012-2018. Primary treatments included benzathine penicillin, ceftriaxone sodium or erythromycin when patients were allergic to Benzathine penicillin. The treatment coverage was 81.57%, and only 52.86% of pregnant women were adequately treated. Adverse pregnant outcomes were higher amongst untreated women. Expanding early screening coverage and promoting treatment were key to improving pregnancy outcomes amongst women with syphilis.


Asunto(s)
Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Sífilis/prevención & control , Sífilis/transmisión , Adulto , Antibacterianos/uso terapéutico , Ceftriaxona/uso terapéutico , Eritromicina/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Penicilina G Benzatina/uso terapéutico , Embarazo , Complicaciones Infecciosas del Embarazo/prevención & control , Resultado del Embarazo , Atención Prenatal , Estudios Retrospectivos , Adulto Joven
9.
BMC Infect Dis ; 19(1): 1049, 2019 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-31829153

RESUMEN

BACKGROUND: Diphtheria has been reported as an outbreak in some regions in Indonesia, most especially in East Java Province. Resistance to penicillin, erythromycin, and other antibiotics, single or multiple, has been reported in several studies. This study aims to evaluate the first-line antibiotic susceptibility pattern of toxigenic Corynebacterium diphtheriae isolates. METHODS: This descriptive observational study was performed from August to November 2018. C. diphtheriae isolates were collected from diphtheria patients and carriers in East Java from 2012 to 2017 and kept at the Balai Besar Laboratorium Kesehatan Daerah Surabaya or the Public Health Laboratory of Surabaya. Sample selection was done by random cluster sampling. The sensitivity test by E-test®of the five antibiotics (penicillin, oxacillin, erythromycin, azithromycin, and clarithromycin) was done to determine the minimum inhibitory concentration (MIC). The Clinical and Laboratory Standards Institute M45A (2015) Corynebacterium spp. for penicillin and erythromycin was used as standard. RESULTS: From 114 targeted isolates, 108 were viable and toxigenic. The E-test was performed on the viable isolates. The majority of the hosts were male (58.3%), with median (range) age of 6.5 (1-14) years. Half of the samples were from the 1 to 5-year-old age group. The isolates were acquired much more from patients (78.7%) than carriers (21.3%) and from pharyngeal swab (74.1%). Most of these isolates were from Madura Island (47.2%) and the northern and eastern parts of the province (horseshoe area). Mitis isolates were the major variant (76.9%). The susceptibility pattern of C. diphtheriae to erythromycin was better than that to penicillin. The E-test result for penicillin was 68.52% susceptible, 31.48% intermediate, and 0% resistant (MIC range, < 0.016 to 2 µg/L) and for erythromycin (MIC range, < 0.016 to > 256 µg/L) was 85.2% susceptible, 12% intermediate, and 2.8% resistant The MIC range for oxacillin was 1 to 96 µg/L, while for both azithromycin and clarithromycin were <  0.016 to > 256 µg/L. CONCLUSION: The susceptibility rate of C. diphtheriae to erythromycin is higher than that to penicillin. The regular update of antibiotic selection to the national guidelines is recommended. The MIC reference standard to azithromycin and clarithromycin is also needed.


Asunto(s)
Antibacterianos/uso terapéutico , Corynebacterium diphtheriae/efectos de los fármacos , Difteria/tratamiento farmacológico , Difteria/epidemiología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Eritromicina/uso terapéutico , Penicilinas/uso terapéutico , Adolescente , Niño , Preescolar , Corynebacterium diphtheriae/aislamiento & purificación , Femenino , Humanos , Indonesia/epidemiología , Lactante , Masculino , Pruebas de Sensibilidad Microbiana
12.
Artículo en Inglés | MEDLINE | ID: mdl-31605592

RESUMEN

BACKGROUND: Campylobacter infections are typically self-limited, but in cases with severe enteritis, immuno-compromised system and bacteremia, an appropriate antimicrobial treatment is demanding. Our study aim was to determine the isolation rate of Campylobacter among patients with acute enteritis in the capital of North Macedonia and its antimicrobial susceptibility. MATERIAL AND METHODS: A total number of 3820 patients clinically diagnosed as acute enteritis, were included in the study. Stool samples were collected and Campylobacter was isolated and identified by classical microbiological methods. Antimicrobial susceptibility of all isolates to Ceftriaxone, Amoxicillin-clavulonic acid, Erythromycin, Ciprofloxacin, Tetracycline and Gentamicin was determined by disc-diffusion technique. Additionally, minimal inhibitory concentrations of all Campylobacter isolates against erythromycin, ciprofloxacin and tetracycline were determined by Epsilon gradient tests. RESULTS: Campylobacter species was isolated in 97 patients. Although the mean isolation rate of Campylobacter spp. during the whole study period was 2.53%, a statistically significant increase was detected in 2016 and 2017, in comparison with the data from previous four years of the study. The isolation rate of Campylobacter spp. didn't reveal statistically significant difference between males and females (p > 0.05). 46.4 % of patients with Campylobacter enteritis were children at the age under 15 years. Forty-three C. jejuni isolates were susceptible to all six antibiotics, but the remaining 44 isolates revealed resistance to at least one antibiotic. C. coli isolates were resistant to 3 antibiotics simultaneously. Two C. coli isolates only, were susceptible to all 6 antibiotics. 40.90% of C. jejuni and 50% of C. coli isolates were resistant to beta-lactams, fluoroquinolones and tetracyclines, simultaneously. CONCLUSION: The increase of the isolation rate of Campylobacter from patients with acute enteritis indicates the need for permanent isolation and identification of Campylobacter from every clinically diagnosed patient, as acute enteritis. Erythromicin is the most effective antibiotic for treatment of Campylobacter enteritis in our patients. The high level of Campylobacter resistance to beta-lactams, fluoroquinolones and tetracyclines requires more rational approach in the treatment of Campylobacter enteritis.


Asunto(s)
Infecciones por Campylobacter/tratamiento farmacológico , Campylobacter/aislamiento & purificación , Enteritis/microbiología , Pruebas de Sensibilidad Microbiana/métodos , Enfermedad Aguda , Adolescente , Adulto , Anciano , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antiinfecciosos/farmacología , Antiinfecciosos/uso terapéutico , Campylobacter/efectos de los fármacos , Campylobacter/crecimiento & desarrollo , Niño , Preescolar , Ciprofloxacino/farmacología , Ciprofloxacino/uso terapéutico , Estudios Transversales , Farmacorresistencia Bacteriana/fisiología , Enteritis/diagnóstico , Enteritis/tratamiento farmacológico , Eritromicina/farmacología , Eritromicina/uso terapéutico , Heces/microbiología , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , República de Macedonia del Norte , Tetraciclina/farmacología , Tetraciclina/uso terapéutico , Adulto Joven
13.
Cell Death Dis ; 10(9): 678, 2019 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-31515489

RESUMEN

Neutrophil extracellular traps (NETs) may play a critical role in smoking-related chronic airway inflammation. However, the mechanism by which NETs induced by cigarette smoke initiate the adaptive immunity in chronic obstructive pulmonary disease (COPD) is not fully understood. In this study, we explored the effects of NETs induced by cigarette smoke on the myeloid dendritic cells (mDCs) and Th1 and Th17 cells. Additionally, we observed the inhibitory effect of erythromycin on NETs induced by cigarette smoke. We found that elevated NET levels in the sputum of COPD patients were correlated with the circulating Th1 response, mDC activation and airflow limitation. NETs induced by cigarette smoke extract (CSE) could activate monocyte-derived mDCs and promote Th1 and Th17 differentiation in vitro. Erythromycin effectively inhibited NET formation induced by CSE. In vivo, erythromycin decreased NETs in the airway and ameliorated emphysema with Th1 and Th17 cell down-regulation and CD40+ and CD86+ mDCs suppression in mice chronically exposed to cigarette smoke. These findings provide direct evidence that NETs promote the differentiation of Th1 and Th17 and play a role in the adaptive immunity of smoking-related chronic lung inflammation. Erythromycin is a potential therapeutic strategy for NETs inhibition in COPD.


Asunto(s)
Eritromicina/farmacología , Eritromicina/uso terapéutico , Trampas Extracelulares/efectos de los fármacos , Inflamación/tratamiento farmacológico , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/etiología , Animales , Antígeno B7-2/metabolismo , Antígenos CD40/metabolismo , Fumar Cigarrillos/efectos adversos , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Técnica del Anticuerpo Fluorescente , Humanos , Inflamación/etiología , Masculino , Ratones , Ratones Endogámicos C57BL , Células TH1/efectos de los fármacos , Células TH1/metabolismo , Células Th17/efectos de los fármacos , Células Th17/metabolismo
14.
Sci Rep ; 9(1): 11460, 2019 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-31391518

RESUMEN

The clinical use of the antibiotic erythromycin (ery) is hampered owing to the spread of resistance genes that are mostly mutating rRNA around the ery binding site at the entrance to the protein exit tunnel. Additional effective resistance mechanisms include deletion or insertion mutations in ribosomal protein uL22, which lead to alterations of the exit tunnel shape, located 16 Å away from the drug's binding site. We determined the cryo-EM structures of the Staphylococcus aureus 70S ribosome, and its ery bound complex with a two amino acid deletion mutation in its ß hairpin loop, which grants the bacteria resistance to ery. The structures reveal that, although the binding of ery is stable, the movement of the flexible shorter uL22 loop towards the tunnel wall creates a wider path for nascent proteins, thus enabling bypass of the barrier formed by the drug. Moreover, upon drug binding, the tunnel widens further.


Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/ultraestructura , Farmacorresistencia Bacteriana/genética , Eritromicina/farmacología , Proteínas Ribosómicas/ultraestructura , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/uso terapéutico , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Sitios de Unión , Microscopía por Crioelectrón , Eritromicina/uso terapéutico , Humanos , Mutación , Unión Proteica/genética , ARN Ribosómico 23S/metabolismo , ARN Ribosómico 23S/ultraestructura , Proteínas Ribosómicas/genética , Proteínas Ribosómicas/metabolismo , Subunidades Ribosómicas Grandes Bacterianas/efectos de los fármacos , Subunidades Ribosómicas Grandes Bacterianas/metabolismo , Subunidades Ribosómicas Grandes Bacterianas/ultraestructura , Ribosomas/efectos de los fármacos , Ribosomas/metabolismo , Ribosomas/ultraestructura , Imagen Individual de Molécula , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/genética , Staphylococcus aureus/ultraestructura
15.
Hong Kong Med J ; 25(4): 287-294, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31402340

RESUMEN

INTRODUCTION: Many authoritative guidelines recommend prescribing erythromycin as antibiotic prophylaxis in patients with preterm prelabour rupture of membranes (PPROM). This study evaluated the spectrum of pathogens in PPROM and assessed the effectiveness of erythromycin prophylaxis. METHODS: This retrospective study enrolled pregnant patients who were diagnosed with PPROM and who delivered at ≥24 weeks of gestation in an obstetric unit from 2013 to 2017. Pathogens isolated from maternal, placental, and neonatal specimens were analysed; their sensitivity profiles to various antibiotics were recorded. Neonatal outcomes were also evaluated. RESULTS: The overall incidence of PPROM was 2.63%. Gram-positive bacteria were cultured in 18.4% of PPROM patients (most frequent: Group B Streptococcus [GBS; 14.6%]); Gram-negative bacteria were cultured in 12.8% of PPROM patients (most frequent: Escherichia coli [8.0%]). Both Gram-positive and Gram-negative bacteria were significantly associated with early-onset neonatal sepsis (P=0.036 and P=0.001). In analyses stratified by bacterial species, E coli was significantly associated with early-onset neonatal sepsis (P=0.004), whereas GBS was not (P=0.39). Gram-positive bacteria had high rates of resistance to common antibiotics: 42.2% of GBS and 50.0% of Enterococcus and other Streptococcus bacteria were resistant to erythromycin. Escherichia coli had high rates of resistance to ampicillin (70.3%) and gentamicin (33.3%); rates of resistance to co-amoxiclav (3.6%) and intravenous cefuroxime (14.0%) were low. CONCLUSION: Gram-positive and Gram-negative bacteria were found in 29.1% of PPROM patients. Administration of erythromycin alone was insufficient to control these bacteria in 67.7% of patients with positive cultures.


Asunto(s)
Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Eritromicina/uso terapéutico , Rotura Prematura de Membranas Fetales/microbiología , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Grampositivas/epidemiología , Adulto , Farmacorresistencia Bacteriana , Femenino , Rotura Prematura de Membranas Fetales/epidemiología , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/prevención & control , Bacterias Grampositivas/aislamiento & purificación , Infecciones por Bacterias Grampositivas/prevención & control , Hong Kong/epidemiología , Humanos , Recién Nacido , Sepsis Neonatal/epidemiología , Embarazo , Resultado del Embarazo , Estudios Retrospectivos
17.
BMC Pediatr ; 19(1): 181, 2019 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-31167650

RESUMEN

BACKGROUND: Invasive S. pyogenes diseases are uncommon, serious infections with high case fatality rates (CFR). There are few publications on this subject in the field of pediatrics. This study aimed at characterizing clinical and laboratory aspects of this disease in Chinese children. PATIENTS AND METHODS: A retrospective study was conducted and pediatric in-patients with S. pyogenes infection identified by cultures from normally sterile sites were included, who were diagnosed and treated in 9 tertiary hospitals during 2010-2017. RESULTS: A total of 66 cases were identified, in which 37 (56.1%) were male. The median age of these patients, including 11 neonates, was 3.0 y. Fifty-nine (89.4%) isolates were determined from blood. Fever was the major symptom (60/66, 90.9%) and sepsis was the most frequent presentation (64/66, 97.0%, including 42.4% with skin or soft tissue infections and 25.8% with pneumonia. The mean duration of the chief complaint was (3.8 ± 3.2) d. Only 18 (27.3%) patients had been given antibiotics prior to the hospitalization. Among all patients, 15 (22.7%) developed streptococcal toxin shock syndrome (STSS). No S. pyogenes strain was resistant to penicillin, ceftriaxone, or vancomycin, while 88.9% (56/63) and 81.4% (48/59) of the tested isolates were resistant to clindamycin and erythromycin respectively. Most of the patients were treated with ß-lactams antibiotics and 36.4% had been treated with meropenem or imipenem. Thirteen (19.7%) cases died from infection, in which 9 (13.6%) had complication with STSS. CONCLUSIONS: Invasive S. pyogenes infections often developed from skin or soft tissue infection and STSS was the main cause of death in Chinese children. Ongoing surveillance is required to gain a greater understanding of this disease.


Asunto(s)
Infecciones Estreptocócicas/diagnóstico , Streptococcus pyogenes/aislamiento & purificación , Ceftriaxona/uso terapéutico , Preescolar , China , Clindamicina/uso terapéutico , Farmacorresistencia Bacteriana , Eritromicina/uso terapéutico , Femenino , Fiebre/microbiología , Humanos , Lactante , Recién Nacido , Masculino , Penicilinas/uso terapéutico , Neumonía Neumocócica/microbiología , Estudios Retrospectivos , Sepsis/microbiología , Choque Séptico/microbiología , Enfermedades Cutáneas Bacterianas/microbiología , Infecciones de los Tejidos Blandos/microbiología , Infecciones Estreptocócicas/complicaciones , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus pyogenes/efectos de los fármacos , Centros de Atención Terciaria/estadística & datos numéricos , Vancomicina/uso terapéutico
18.
Curr Opin Crit Care ; 25(4): 349-355, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31247631

RESUMEN

PURPOSE OF REVIEW: This review provides an update of recently conducted studies and randomized controlled trials evaluating prokinetic drugs. RECENT FINDINGS: Prokinetic drugs accelerate gastric emptying and, particularly in patients with gastric dysmotility and enteral feed intolerance, their use increases the delivery of enteral nutrition. However, prokinetic drugs have not been shown to improve patient-centered outcomes in trials but benefit is assumed on the basis of observational studies, which report close associations between gastric dysmotility, enteral feed intolerance and poor outcomes, and improvement in surrogate physiological outcomes when prokinetic drugs are administered. SUMMARY: It may not be feasible to establish superiority of a prokinetic drug within a randomized controlled trial with a patient-centered event as the primary outcome. The use of metoclopramide and erythromycin as prokinetic drugs is based on observations from trials measuring surrogate physiological outcomes. Randomized controlled trials of alternative drug regimens and novel prokinetic drugs have recently been completed and results outlined.


Asunto(s)
Eritromicina/uso terapéutico , Vaciamiento Gástrico/efectos de los fármacos , Fármacos Gastrointestinales/uso terapéutico , Metoclopramida/uso terapéutico , Nutrición Enteral , Humanos , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
19.
J Trauma Acute Care Surg ; 87(4): 922-934, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31136527

RESUMEN

BACKGROUND: Ileus is a common challenge in adult surgical patients with estimated incidence to be 17% to 80%. The main mechanisms of the postoperative ileus pathophysiology are fluid overload, exogenous opioids, neurohormonal dysfunction, gastrointestinal stretch, and inflammation. Management includes addressing the underlying cause and supportive care. Multiple medical interventions have been proposed, but effectiveness is uncertain. A working group of the Eastern Association for the Surgery of Trauma aimed to evaluate the effectiveness of metoclopramide, erythromycin, and early enteral nutrition (EEN) on ileus in adult surgical patients and to develop recommendations applicable in a daily clinical practice. METHODS: Literature search identified 45 articles appropriate for inclusion. The Grading of Recommendations Assessment, Development and Evaluation methodology was applied to evaluate the effect of metoclopramide, erythromycin, and EEN on the resolution of ileus in adult surgical patients based on selected outcomes: return of normal bowel function, attainment of enteral feeding goal, and hospital length of stay. The recommendations were made based on the results of a systematic review, a meta-analysis, and evaluation of levels of evidence. RESULTS: The level of evidence for all PICOs was assessed as low. Neither metoclopramide nor erythromycin were effective in expediting the resolution of ileus. Analyses of 32 randomized controlled trials showed that EEN facilitates return of normal bowel function, achieving enteral nutrition goals, and reducing hospital length of stay. CONCLUSION: In patients who have undergone abdominal surgery, we strongly recommend EEN to expedite resolution of Ileus, but we cannot recommend for or against the use of either metoclopramide or erythromycin to hasten the resolution of ileus in these patients. LEVEL OF EVIDENCE: Type of Study Therapeutic, level II.


Asunto(s)
Nutrición Enteral/métodos , Eritromicina/uso terapéutico , Ileus , Metoclopramida/uso terapéutico , Complicaciones Posoperatorias/terapia , Adulto , Intervención Médica Temprana/métodos , Fármacos Gastrointestinales/uso terapéutico , Motilidad Gastrointestinal/efectos de los fármacos , Humanos , Ileus/etiología , Ileus/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto
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