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1.
Future Microbiol ; 14: 1235-1242, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31475868

RESUMEN

Sarecycline is a novel, narrow-spectrum, once-daily tetracycline-derived oral antibiotic that is FDA-approved in the US to be taken with or without food for moderate-to-severe acne vulgaris for ages 9 years of age and older. Sarecycline possesses anti-inflammatory properties and potent activity against Gram-positive bacteria, including activity against multiple strains of Cutibacterium acnes, while exhibiting minimal activity against enteric aerobic Gram-negative bacteria. Unlike many acne studies, sarecycline was investigated for chest and back acne. Significant reduction in inflammatory lesions was seen at week 12 at 1.5 mg/kg/day of sarecycline, with statistically significant improvement seen as early as week 3. No reports of phototoxicity, dizziness, pseudotumor cerebri or lupus but 1.2% nausea and 1.2% vaginal candidiasis was reported in the pivotal Phase III studies.


Asunto(s)
Acné Vulgar/tratamiento farmacológico , Antibacterianos/uso terapéutico , Bacterias/efectos de los fármacos , Tetraciclinas/uso terapéutico , Acné Vulgar/microbiología , Antiinflamatorios/uso terapéutico , Ensayos Clínicos Fase III como Asunto , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Propionibacteriaceae/efectos de los fármacos
2.
Rev. chil. infectol ; 35(5): 465-475, 2018. tab
Artículo en Español | LILACS | ID: biblio-978059

RESUMEN

Resumen La resistencia bacteriana se ha incrementado en América Latina y el mundo, por lo que se requiere investigación y creación de nuevos antimicrobianos capaces de erradicar a los microorganismos resistentes. Se realizó una revisión acerca de nuevas cefalosporinas y sus combinaciones con un inhibidor de β-lactamasas, recopilando información de espectro, farmacocinética, farmacodinamia y estudios clínicos de las indicaciones actuales para ceftarolina, ceftazidima/avibactam y ceftolozano/tazobactam. La primera, con actividad frente a Staphylococcus aureus y Staphylococcus coagulasa negativa sensibles y resistentes a meticilina, y contra Streptococcus pneumoniae resistente a penicilina; por lo tanto, aprobada para uso en neumonía bacteriana adquirida en comunidad e infecciones bacterianas de piel y tejidos blandos. Entre las nuevas combinaciones, ceftazidima, una cefalosporina de tercera generación con actividad anti-pseudomonas, asociada a avibactam, un inhibidor de β-lactamasas, ha demostrado efectividad en el tratamiento de infecciones abdominales e infecciones urinarias complicadas. Por último, la combinación ceftolozano y el conocido tazobactam presenta acción comparable a la combinación de ceftazidima y avibactam por su actividad contra bacilos gramnegativos y, en combinación con metronidazol no presenta inferioridad a meropenem en infecciones intra-abdominales. Se presentan los estudios clínicos y las potenciales indicaciones y escenarios de uso de estas cefalosporinas.


Bacterial resistance has increased in Latin America and the world, making research and creation of new antimicrobials capable of eradicating resistant microorganisms essential. A review of new cephalosporins and their combinations with a beta-lactamase inhibitor was conducted, collecting data on the spectrum, pharmacokinetic and pharmacodynamic profile and clinical studies of the current indications for ceftaroline, and the combinations ceftazidime with avibactam and ceftolozane with tazobactam. The first one has activity against methicillin-resistant Staphylococcus aureus and coagulase negative Staphylococcus (SCoN) and against penicillin-resistant Streptococcus pneumoniae, therefore approved for use in community-acquired pneumonia and acute bacterial skin and skin structure infections. Among the new combinations, ceftazidime, a third generation cephalosporin with antipseudomonal activity, associated with avibactam, a betalactamase inhibitor, has been shown to be effective in the treatment of abdominal infections and complicated urinary infections. Finally, the combination of ceftolozane with tazobactam has comparable action to ceftazidime with avibactam due to its activity against Gram negative rods, and in combination with metronidazole they do not present inferiority to meropenem in intra-abdominal infections. The clinical studies are presented, as well as the potential indications and clinical scenarios for their use of this cephalosporins.


Asunto(s)
Humanos , Cefalosporinas/uso terapéutico , Cefalosporinas/farmacología , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Ceftazidima/uso terapéutico , Ceftazidima/farmacología , Combinación de Medicamentos , Compuestos de Azabiciclo/uso terapéutico , Compuestos de Azabiciclo/farmacología , Tazobactam/uso terapéutico , Tazobactam/farmacología
3.
Rev. chil. infectol ; 35(5): 547-552, 2018. tab
Artículo en Español | LILACS | ID: biblio-978068

RESUMEN

Resumen Introducción: La sepsis neonatal nosocomial (SNN) es una entidad frecuente en las unidades de cuidados intensivos, donde causa una gran morbimortalidad. La ubicación más frecuente es bacteriemia, seguido de neumonía asociada a ventilador mecánico y vía urinaria. Objetivo: Conocer la etiología y localización más frecuente de la infección en el SNN. Población, Material y Métodos: Estudio retrospectivo, de prevalencias de enero a diciembre de 2015, realizado en la Unidad de Cuidados Intensivos Neonatal de un hospital de alta complejidad. Fueron incluidos todos los neonatos. Resultados: Se incluyeron 70 pacientes, se analizaron 88 episodios de SNN. La localización más frecuente fue sangre 40% de los casos, seguido de orina y aspirado traqueal en 25% respectivamente. Los microorganismos más frecuentemente aislados fueron Staphylococcus de diferentes tipos, seguido de Acinetobacter baumannii multi-resistente. La afectación del SNC fue de 32%. La mortalidad fue de 34%, elevándose a 50% ante un segundo episodio de SNN. La terapia empírica de elección fue vancomicina y carbapenem, ajustándose a antibiograma. Conclusiones: La infección más frecuente fue la bacteremia, principalmente por Staphylococcus resistentes a meticilina. La afectación del SNC fue elevada, lo mismo que la mortalidad.


Introduction: Nosocomial neonatal sepsis (NNS) is a frequent entity in intensive care units, causing great morbidity and mortality. The most frequent site is blood, followed by lungs and urine. Objective: To know the etiology and most frequent localization of infection in the NNS. Population, Material and Methods: Cross sectional study, from January to December 2015, performed in a teaching hospital. All newborns infants were included. Results: 70 patients were included, 88 episodes of NNS were analyzed. The most frequent localization was bacteremia in 40% of cases, followed by urinary tract infection and VAP in 25% respectively. The bacteria most frequently isolated were staphylococci of different types, followed by multiresistant Acinetobacter. The CNS involvement was 32%. Mortality was 34%, rising up to 50% with a second episode of NNS. The empirical therapy of choice was vancomycin and carbapenem, adjusting to antibiogram. Conclusions: The most frequent infection was bacteremia, mainly by staphylococci resistant to methicillin. CNS involvement was elevated, as well as mortality.


Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Infección Hospitalaria/microbiología , Sepsis Neonatal/microbiología , Bacterias Aerobias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Unidades de Cuidado Intensivo Neonatal , Pruebas de Sensibilidad Microbiana , Estudios Retrospectivos , Edad Gestacional , Bacteriemia/microbiología , Neumonía Asociada al Ventilador/microbiología , Bacterias Aerobias Gramnegativas/clasificación , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/clasificación , Bacterias Grampositivas/efectos de los fármacos , Antibacterianos/farmacología
4.
Artículo en Inglés | MEDLINE | ID: mdl-28348155

RESUMEN

The correlation of the clinical efficacy of ceftazidime-avibactam (plus metronidazole) with that of meropenem was evaluated in subjects infected with Gram-negative isolates having characterized ß-lactam resistance mechanisms from the complicated intra-abdominal infection (cIAI) phase 3 clinical trials. Enterobacteriaceae isolates displaying ceftriaxone and/or ceftazidime MIC values of ≥2 µg/ml and Pseudomonas aeruginosa isolates with ceftazidime MIC values of ≥16 µg/ml were characterized for extended-spectrum-ß-lactamase (ESBL) content. Enterobacteriaceae and P. aeruginosa isolates with imipenem and meropenem MIC values of ≥2 and ≥8 µg/ml, respectively, were tested for carbapenemase genes. The primary efficacy endpoint was clinical cure at test of cure (TOC) among the members of the microbiologically modified intention-to-treat (mMITT) population. A total of 14.5% (56/387) and 18.8% (74/394) of patients in the ceftazidime-avibactam and meropenem arms had isolates that met the MIC screening criteria at the baseline visit, respectively. CTX-M variants alone (29.7%; 41/138) or in combination with OXA-1/30 (35.5%; 49/138), most commonly, blaCTX-M group 1 variants (79/90; 87.8%), represented the ß-lactamases most frequently observed among Enterobacteriaceae isolates. Among the patients infected with pathogens that did not meet the screening criteria, 82.2% showed clinical cure in the ceftazidime-avibactam group versus 85.9% in the meropenem group. Among patients infected with any pathogens that met the MIC screening criteria, clinical cure rates at TOC were 87.5% and 86.5% for the ceftazidime-avibactam and meropenem groups, respectively. Ceftazidime-avibactam had clinical cure rates of 92.5% to 90.5% among patients infected with ESBL- and/or carbapenemase-producing Enterobacteriaceae strains at the baseline visit, while meropenem showed rates of 84.9% to 85.4%. The ceftazidime-avibactam and meropenem groups had cure rates of 75.0% and 86.7%, respectively, among patients having any pathogens producing AmpC enzymes. The efficacy of ceftazidime-avibactam was similar to that of meropenem for treatment of cIAI caused by ESBL-producing organisms. (This study has been registered at ClinicalTrials.gov under registration no. NCT01499290 and NCT01500239.).


Asunto(s)
Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Bacterias Aerobias Gramnegativas/patogenicidad , Infecciones Intraabdominales/tratamiento farmacológico , beta-Lactamasas/farmacología , beta-Lactamasas/uso terapéutico , Compuestos de Azabiciclo , Ceftazidima , Combinación de Medicamentos , Escherichia coli/efectos de los fármacos , Escherichia coli/patogenicidad , Humanos , Infecciones Intraabdominales/microbiología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/patogenicidad , Pruebas de Sensibilidad Microbiana
5.
Future Microbiol ; 11: 1421-1434, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27539442

RESUMEN

Omadacycline is a first-in-class aminomethylcycline antibiotic that circumvents common tetracycline resistance mechanisms. In vitro omadacycline has potent activity against Gram-positive aerobic bacteria including methicillin-resistant Staphylococcus aureus, penicillin-resistant and multidrug-resistant Streptococcus pneumoniae, and vancomycin-resistant Enterococcus spp. It is also active against common Gram-negative aerobes, some anaerobes and atypical bacteria including Legionella spp. and Chlamydia spp. Ongoing Phase III clinical trials with omadacycline are investigating once daily doses of 100 mg intravenously followed by once-daily doses of 300 mg orally for the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. This paper provides an overview of the microbiology, nonclinical evaluations, clinical pharmacology and initial clinical experience with omadacycline.


Asunto(s)
Infecciones Bacterianas/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Tetraciclinas/farmacocinética , Tetraciclinas/uso terapéutico , Bacterias/efectos de los fármacos , Chlamydia/efectos de los fármacos , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Esquema de Medicación , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Legionella/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Piel/microbiología , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Streptococcus pneumoniae/efectos de los fármacos , Tetraciclinas/administración & dosificación , Tetraciclinas/química , Enterococos Resistentes a la Vancomicina/efectos de los fármacos
6.
Surg Infect (Larchmt) ; 17(4): 473-8, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27104633

RESUMEN

BACKGROUND: Ceftazidime-avibactam is ceftazidime combined with the novel non-ß-lactam ß-lactamase inhibitor avibactam, which inhibits Ambler class A (e.g., extended-spectrum ß-lactamase [ESBL] and KPC), class C, and some class D enzymes. We evaluated the activity of ceftazidime-avibactam against aerobic gram negative bacteria causing intra-abdominal infections (IAI). METHODS: A total of 1,540 isolates were collected, one each from patient, with IAI in 57 United States hospitals in 2012-2014. Susceptibility testing was performed by reference broth microdilution methods, and Enterobacteriaceae isolates with an ESBL phenotype were evaluated by a microarray-based assay for the presence of genes encoding the CTX-M, TEM, SHV, KPC, NDM, and transferable AmpC enzymes. RESULTS: All Escherichia coli isolates were susceptible to ceftazidime-avibactam, whereas the susceptibility rates for meropenem, piperacillin-tazobactam, and gentamicin were 99.8%, 93.6%, and 85.5%, respectively. Among Klebsiella pneumoniae isolates, the highest ceftazidime-avibactam minimum inhibitory concentration (MIC) value was only 2 mcg/mL (MIC50/90 0.12/0.25 mcg/mL; 100% susceptible), whereas susceptibility rates to meropenem and gentamicin were 94.5% and 91.9%, respectively. The ESBL-phenotype rates among E. coli and K. pneumoniae were 15.8% and 13.3%, respectively. Overall, only one Enterobacteriaceae isolate (Enterobacter cloacae) was not susceptible to ceftazidime-avibactam and had negative results for all ß-lactamases tested. Against Pseudomonas aeruginosa, ceftazidime-avibactam (MIC50/90 2/4 mcg/mL; 97.1% susceptible) and amikacin (MIC50/90 2/8 mcg/mL; 99.0% susceptible) were the most active compounds, and ceftazidime-avibactam retained activity against many meropenem-non-susceptible (88.6% susceptible) and piperacillin-tazobactam-non-susceptible (82.9% susceptible) strains. CONCLUSION: Ceftazidime-avibactam coverage (98.7% inhibited at ≤8 mcg/mL) of intra-abdominal infection pathogens was greater than that observed for meropenem (95.7% susceptible) and piperacillin-tazobactam (88.4% susceptible).


Asunto(s)
Antibacterianos/uso terapéutico , Compuestos de Azabiciclo/uso terapéutico , Ceftazidima/uso terapéutico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones Intraabdominales/tratamiento farmacológico , Combinación de Medicamentos , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Bacterias Aerobias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/epidemiología , Humanos , Infecciones Intraabdominales/epidemiología , Pruebas de Sensibilidad Microbiana , Estados Unidos/epidemiología
7.
Pharm Biol ; 53(9): 1386-90, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25874387

RESUMEN

CONTEXT: Amanita ovoidea (Bull.) Link (Amanitaceae) is a well-known species due to its pleasant aroma and flavor since ancient times in the worldwide. This species is also known in Turkey and people consume it extensively. OBJECTIVE: To evaluate medicinal importance of A. ovoidea for human health, to explain the effect of mushroom extracts on bacterial DNA, and to find preventive role on bacterial disease. MATERIALS AND METHODS: Chloroform, acetone, and methanol extracts of A. ovoidea were tested for the antimicrobial activities against four Gram-positive bacteria, five Gram-negative bacteria, and yeast using a micro-dilution method. In addition, DNA binding, DNA cleavage activity, and restriction enzyme digestion of the methanol extract of A. ovoidea were examined at different concentrations (40.000-78.125 µg/mL). RESULTS: The highest minimum inhibitory concentration (MIC) value observed against the test micro-organisms was with the chloroform extract (MIC 19.5 µg/mL concentration) against Candida albicans. Other highest antimicrobial effects observed against the test micro-organisms were with the methanol extracts against Bacillus subtilis, Staphylococcus aureus, Listeria monocytogenes, Streptococcus pyogenes, Candida albicans, Klebsiella pneumoniae, Proteus vulgaris, and Salmonella enteritidis (MICs, 78 µg/mL concentrations). All concentrations reduced the mobility of plasmid DNA. BamHI and HindIII targeted specially to supercoils and cut them. Amanita ovoidea extract prevented cutting with HindIII by binding especially to the AA region in open circular DNA. DISCUSSION AND CONCLUSION: Present results demonstrated that A. ovoidea has excellent antimicrobial and antifungal activities by its DNA interaction activity on pBR322.


Asunto(s)
Amanita , Antibacterianos/farmacología , Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Plásmidos/efectos de los fármacos , Acetona/química , Amanita/química , Antibacterianos/aislamiento & purificación , Antifúngicos/aislamiento & purificación , Candida albicans/crecimiento & desarrollo , Cloroformo/química , Bacterias Aerobias Gramnegativas/crecimiento & desarrollo , Bacterias Grampositivas/crecimiento & desarrollo , Metanol/química , Pruebas de Sensibilidad Microbiana , Fitoterapia , Solventes/química
8.
Pharm Biol ; 53(9): 1339-43, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25864864

RESUMEN

CONTEXT: Brazilin is a major active principle of Caesalpinia sappan L. (Leguminosae or Fabaceae). For industry aspects, brazilin-rich extract (BRE) has been prepared and standardized to contain 39% w/w brazilin. BRE may have more advantages than brazilin in term of a lower-cost production process. OBJECTIVES: To investigate the antioxidant, antibacterial, and anti-inflammatory activities of BRE. MATERIAL AND METHODS: BRE was prepared by a simple one-step purification of the crude ethanol extract of C. sappan heartwood (CSE) using a Diaion® HP-20 column. The antioxidant activities were determined using three methods, including DPPH radical scavenging, reducing power, and ß-carotene bleaching assays, at concentration ranges of 1-10, 10-100, and 10-100 µg/mL, respectively. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of BRE (15.6-1000 µg/mL) against Gram-positive and Gram-negative bacteria were determined by the broth microdilution method. Anti-inflammatory activity of BRE (0.1-5 µg/mL) was evaluated as anti-denaturation activity using bovine serum albumin as a substrate. RESULTS AND DISCUSSION: On the basis of ß-carotene bleaching assay, BRE showed antioxidant activity with an EC50 value of 60.5 µg/mL, which was almost equal to that of pure brazilin (52.1 µg/mL). Gram-positive bacteria were more sensitive to all tested samples than Gram-negative bacteria. BRE possessed higher antibacterial activities than CSE, but lower than brazilin. MIC/MBC values of 62.5-125/125 and 250-500/250-500 µg/mL were obtained for BRE against Gram-positive and Gram-negative bacteria, respectively. A low concentration (0.1 µg/mL) of brazilin, BRE, and CSE showed anti-inflammatory activity by inhibiting protein denaturation up to 46.8, 54.1, and 61.9%, respectively.


Asunto(s)
Antibacterianos/farmacología , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Benzopiranos/farmacología , Caesalpinia , Extractos Vegetales/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/normas , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/normas , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antioxidantes/normas , Benzopiranos/química , Benzopiranos/aislamiento & purificación , Benzopiranos/normas , Compuestos de Bifenilo/química , Caesalpinia/química , Relación Dosis-Respuesta a Droga , Etanol/química , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Bacterias Aerobias Gramnegativas/crecimiento & desarrollo , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Oxidación-Reducción , Fitoterapia , Picratos/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/normas , Plantas Medicinales , Desnaturalización Proteica , Albúmina Sérica Bovina/química , Solventes/química , beta Caroteno/química
9.
J Chemother ; 27(2): 67-73, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24548089

RESUMEN

The study for monitoring antimicrobial resistance trends (SMART) surveillance program monitors the epidemiology and trends in antibiotic resistance of intra-abdominal pathogens to currently used therapies. The current report describes such trends during 2010-2011. A total of 25,746 Gram-negative clinical isolates from intra-abdominal infections were collected and classified as hospital-associated (HA) if the hospital length of stay (LOS) at the time of specimen collection was ≥48 hours, community-associated (CA) if LOS at the time of specimen collection was <48 hours, or unknown (no designation given by participating centre). A total of 92 different species were collected of which the most common was Escherichia coli: 39% of all isolates in North America to 55% in Africa. Klebsiella pneumoniae was the second most common pathogen: 11% of all isolates from Europe to 19% of all isolates from Asia. Isolates were from multiple intra-abdominal sources of which 32% were peritoneal fluid, 20% were intra-abdominal abscesses, and 16.5% were gall bladder infections. Isolates were further classified as HA (55% of all isolates), CA (39% of all isolates), or unknown (6% of all isolates). The most active antibiotics tested were imipenem, ertapenem, amikacin, and piperacillin-tazobactam. Resistance rates to all other antibiotics tested were high. Considering the current data set and high-level resistance of intra-abdominal pathogens to various antibiotics, further monitoring of the epidemiology of intra-abdominal infections and their susceptibility to antibiotics through SMART is warranted.


Asunto(s)
Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Salud Global , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones Intraabdominales/tratamiento farmacológico , Absceso Abdominal/tratamiento farmacológico , Absceso Abdominal/epidemiología , Absceso Abdominal/microbiología , Antibacterianos/farmacología , Líquido Ascítico/microbiología , Colecistitis/tratamiento farmacológico , Colecistitis/epidemiología , Colecistitis/microbiología , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Farmacorresistencia Bacteriana Múltiple , Monitoreo Epidemiológico , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Bacterias Aerobias Gramnegativas/crecimiento & desarrollo , Bacterias Aerobias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Incidencia , Infecciones Intraabdominales/epidemiología , Infecciones Intraabdominales/microbiología , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/epidemiología , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/crecimiento & desarrollo , Klebsiella pneumoniae/aislamiento & purificación , Tiempo de Internación , Pruebas de Sensibilidad Microbiana
10.
Acta Pharm ; 64(3): 379-85, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25296683

RESUMEN

This study evaluated the effectiveness of the essential oil of Pimenta pseudocaryophyllus in inhibiting the growth of the main bacteria responsible for bad perspiration odor (Staphylococcus epidermidis, Proteus hauseri, Micrococcus yunnanensis and Corynebacterium xerosis). The chemical profile of the essential oil was evaluated by high-resolution gas chromatography (HR-GC) and four constituents were identified, eugenol being the major component (88.6%). The antimicrobial activity was evaluated by means of the turbidimetric method, using the microdilution assay. The minimum inhibitory concentration (MIC) values of the essential oil ranged from 500 to 1,000 µg mL⁻¹. Scanning electron microscope (SEM) observations confirmed the physical damage and morphological alteration of the test bacteria treated with the essential oil, reference drugs and eugenol. The findings of the study demonstrated that this essential oil can be used in the formulation of personal care products.


Asunto(s)
Antiinfecciosos/farmacología , Aceites Volátiles/farmacología , Pimenta , Aceites de Plantas/farmacología , Antiinfecciosos/aislamiento & purificación , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Bacterias Aerobias Gramnegativas/crecimiento & desarrollo , Bacterias Aerobias Gramnegativas/ultraestructura , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/crecimiento & desarrollo , Bacterias Grampositivas/ultraestructura , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Rastreo , Aceites Volátiles/aislamiento & purificación , Fitoterapia , Pimenta/química , Aceites de Plantas/aislamiento & purificación , Plantas Medicinales
11.
Indian J Cancer ; 51(4): 477-80, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-26842169

RESUMEN

BACKGROUND: Hospitalization for fever in cancer patients is associated with considerable morbidity, mortality, and cost. AIM: The aim of this study was to study the bacterial spectrum and susceptibility patterns of pathogens in culture positive patients from the oncology unit of our hospital. METHODS: We retrospectively reviewed the medical records of patients admitted in our cancer center (medical, radiation, and surgical oncology) from January to December 2013. Blood and respiratory secretions from the indoor patients were evaluated. RESULTS: Of the total 693 samples, 76.4% were Gram-negative and 23.6% were Gram-positive. The most common bacterial isolates among Gram-negative organisms in blood were Escherichia coli, Salmonella and among the Gram-positive organism were Staphylococcus aureus and Enterococcus. Among the blood isolates extended spectrum of beta-lactamase, multidrug-resistant (carbapenem-resistant) and pan resistant bugs were seen in 47%, 15%, and 5% of the blood isolates. Among the Gram-positive organisms, 25% respiratory isolates were vancomycin-resistant Enterococci. CONCLUSION: We observed a high incidence of Gram-negative isolates with clinically significant resistance to first-line antibiotics such as cephalosporin's, piperacillin tazobactum, and fluoroquinolones.


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/microbiología , Farmacorresistencia Bacteriana , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Neoplasias/complicaciones , Infecciones Bacterianas/tratamiento farmacológico , Instituciones Oncológicas , Bacterias Aerobias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Humanos , India , Pruebas de Sensibilidad Microbiana , Estudios Retrospectivos , Centros de Atención Terciaria
12.
Intensive Care Med ; 38(5): 886-93, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22302028

RESUMEN

PURPOSE: To measure renal adenosine triphosphate (ATP) (bioenergetics) during hypotensive sepsis with or without angiotensin II (Ang II) infusion. METHODS: In anaesthetised sheep implanted with a renal artery flow probe and a magnetic resonance coil around one kidney, we induced hypotensive sepsis with intravenous Escherichia coli injection. We measured mean arterial pressure (MAP), heart rate, renal blood flow RBF and renal ATP levels using magnetic resonance spectroscopy. After 2 h of sepsis, we randomly assigned sheep to receive an infusion of Ang II or vehicle intravenously and studied the effect of treatment on the same variables. RESULTS: After E. coli administration, the experimental animals developed hypotensive sepsis (MAP from 92 ± 9 at baseline to 58 ± 4 mmHg at 4 h). Initially, RBF increased, then, after 4 h, it decreased below control levels (from 175 ± 28 at baseline to 138 ± 27 mL/min). Despite decreased RBF and hypotension, renal ATP was unchanged (total ATP to inorganic phosphate ratio from 0.69 ± 0.02 to 0.70 ± 0.02). Ang II infusion restored MAP but caused significant renal vasoconstriction. However, it induced no changes in renal ATP (total ATP to inorganic phosphate ratio from 0.79 ± 0.03 to 0.80 ± 0.02). CONCLUSIONS: During early hypotensive experimental gram-negative sepsis, there was no evidence of renal bioenergetic failure despite decreased RBF. In this setting, the addition of a powerful renal vasoconstrictor does not lead to deterioration in renal bioenergetics.


Asunto(s)
Angiotensina II/uso terapéutico , Metabolismo Energético/fisiología , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/fisiopatología , Riñón/metabolismo , Sepsis/fisiopatología , Vasoconstrictores/uso terapéutico , Adenosina Trifosfato/orina , Angiotensina II/administración & dosificación , Angiotensina II/farmacología , Animales , Escherichia coli/patogenicidad , Sepsis/etiología , Ovinos , Vasoconstrictores/administración & dosificación , Vasoconstrictores/farmacología
13.
J Food Sci ; 76(6): M387-91, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21729071

RESUMEN

The effects of turmeric extract (T), shallot extract (Sh), and their combination (T + Sh) on the quality of vacuum-packaged rainbow trout (Oncorhynchus mykiss) were examined during refrigerated storage (4 ± 1 °C) over a period of 20 d. Fish samples were divided into 4 batches; 3 batches were treated by dipping for 30 min in aqueous solution of turmeric extract (1.5%; v/v), shallot extract (1.5%; v/v), or turmeric and shallot extract combination (1.5%+ 1.5% v/v), while the fourth batch was dipped in distilled water as a control sample. The control and the treated fish samples were analyzed periodically for microbiological (total viable count, psychrotrophic count), chemical (total volatile base nitrogen [TVB-N], peroxide value [PV], and thiobarbituric acid [TBA] value), and sensory characteristics. The results indicated that the effect of the T, Sh, and T + Sh on the fish samples were to enable the good quality characteristics to be retained longer and to extend the shelf life during the refrigerated storage.


Asunto(s)
Curcuma/química , Embalaje de Alimentos , Conservantes de Alimentos/química , Oncorhynchus mykiss , Extractos Vegetales/química , Alimentos Marinos/análisis , Chalotes/química , Animales , Antioxidantes/química , Antioxidantes/farmacología , Femenino , Conservantes de Alimentos/farmacología , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Bacterias Aerobias Gramnegativas/crecimiento & desarrollo , Bacterias Aerobias Gramnegativas/aislamiento & purificación , Humanos , Irán , Masculino , Viabilidad Microbiana/efectos de los fármacos , Oncorhynchus mykiss/microbiología , Extractos Vegetales/farmacología , Control de Calidad , Refrigeración , Alimentos Marinos/microbiología , Sensación , Especias/análisis , Vacio
14.
J Food Sci ; 76(6): M353-60, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21623784

RESUMEN

UNLABELLED: Blueberries for the frozen market are washed but this process sometimes is not effective or further contaminates the berries. This study was designed to optimize conditions for hot water treatment (temperature, time, and antimicrobial concentration) to remove biofilm and decrease microbial load on blueberries. Scanning electron microscopy (SEM) image showed a well-developed microbial biofilm on blueberries dipped in room temperature water. The biofilm consisted of yeast and bacterial cells attached to the berry surface in the form of microcolonies, which produced exopolymer substances between or upon the cells. Berry exposure to 75 and 90 °C showed little to no microorganisms on the blueberry surface; however, the sensory quality (wax/bloom) of berries at those temperatures was unacceptable. Response surface plots showed that increasing temperature was a significant factor on reduction of aerobic plate counts (APCs) and yeast/mold counts (YMCs) while adding Boxyl® did not have significant effect on APC. Overlaid contour plots showed that treatments of 65 to 70 °C for 10 to 15 s showed maximum reductions of 1.5 and 2.0 log CFU/g on APCs and YMCs, respectively; with acceptable level of bloom/wax score on fresh blueberries. This study showed that SEM, response surface, and overlaid contour plots proved successful in arriving at optima to reduce microbial counts while maintaining bloom/wax on the surface of the blueberries. PRACTICAL APPLICATION: Since chemical sanitizing treatments such as chlorine showed ineffectiveness to reduce microorganisms loaded on berry surface (Beuchat and others 2001, Sapers 2001), hot water treatment on fresh blueberries could maximize microbial reduction with acceptable quality of fresh blueberries.


Asunto(s)
Arándanos Azules (Planta)/microbiología , Conservación de Alimentos/métodos , Frutas/microbiología , Epidermis de la Planta/microbiología , Antiinfecciosos/farmacología , Biopelículas/efectos de los fármacos , Arándanos Azules (Planta)/química , Recuento de Colonia Microbiana , Frutas/química , Hongos/efectos de los fármacos , Hongos/aislamiento & purificación , Hongos/fisiología , Hongos/ultraestructura , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Bacterias Aerobias Gramnegativas/aislamiento & purificación , Bacterias Aerobias Gramnegativas/fisiología , Bacterias Aerobias Gramnegativas/ultraestructura , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/aislamiento & purificación , Bacterias Grampositivas/fisiología , Bacterias Grampositivas/ultraestructura , Calor , Humanos , Viabilidad Microbiana/efectos de los fármacos , Microscopía Electrónica de Rastreo , Modelos Biológicos , Oxidantes/farmacología , Pigmentación/efectos de los fármacos , Epidermis de la Planta/química , Epidermis de la Planta/efectos de los fármacos , Epidermis de la Planta/ultraestructura , Control de Calidad , Sensación , Agua/química
15.
J Food Sci ; 76(3): S164-9, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21535855

RESUMEN

Sodium acid sulfate (SAS) dip treatments were evaluated against a distilled water control and citric acid (CA) to compare its effectiveness in reducing enzymatic browning of raw, French-fry cut potatoes. Two separate studies were conducted with dip concentrations ranging from 0%, 1%, and 3% in experiment 1 to 0%, 2%, and 2.5% in experiment 2 to determine optimal dip concentrations. Russet Burbank potatoes were peeled, sliced, and dipped for 1 min and stored at 3 °C. Color, texture, fry surface pH, and microbiological analyses were conducted on days 0, 7, and 14. The 3% SAS- and CA-treated samples had significantly (p<0.0001) lower pH levels on fry surfaces than all other treatments. Both acidulants had significantly (p≤0.05) lower aerobic plate counts compared to controls in both studies by day 7. However, SAS appeared to be the most effective at the 3% level in maintaining a light fry color up to day 14 and had the highest L-values than all other treatments. The 3% SAS-treated fry slices appeared to have the least change in textural properties over storage time, having a significantly (p=0.0002) higher force value (kg force [kgf]) than the other treatments during experiment 1, without any signs of case-hardening that appeared in the control and CA-treated samples. SAS was just as comparable to CA in reducing surface fry pH and also lowering microbial counts over storage time. According to the results, SAS may be another viable acidulant to be utilized in the fresh-cut fruit and vegetable industry.


Asunto(s)
Ácido Cítrico/química , Comida Rápida/análisis , Conservantes de Alimentos/química , Raíces de Plantas/química , Solanum tuberosum/química , Sulfatos/química , Antibacterianos/farmacología , Fenómenos Químicos , Ácido Cítrico/farmacología , Recuento de Colonia Microbiana , Color , Culinaria , Comida Rápida/microbiología , Manipulación de Alimentos , Conservantes de Alimentos/farmacología , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Bacterias Aerobias Gramnegativas/aislamiento & purificación , Concentración de Iones de Hidrógeno , Concentración Osmolar , Raíces de Plantas/microbiología , Solanum tuberosum/microbiología , Sulfatos/farmacología , Propiedades de Superficie , Factores de Tiempo
16.
Meat Sci ; 88(3): 409-14, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21345604

RESUMEN

An experiment was conducted to evaluate the effect of dipping in pomegranate fruit juice phenolics (PFJP) solution on the shelf life of chicken meat held under refrigerated storage at 4°C. Breast muscle obtained from spent hens was dipped (1:2w/v; muscle: liquid) in sterile water or in sterile water with 0.02% (v/v) PFJP, packed, stored at 4°C for 28 days and samples were analyzed on 2 days of intervals. Thiobarbituric acid reactive substance values were lower in samples treated with PFJP. Total sulfhydryl and protein bound sulfhydryl content values were higher in samples treated with PFJP. Microbial quality evaluation showed that aerobic and psychrotrophic counts were higher in samples treated without PFJP. Sensory evaluation revealed that acceptability level of samples treated without PFJP decreased on 12th day of storage. It is concluded that spent hen breast meat samples dipped in 0.02% PFJP reduced protein oxidation and inhibited microbial growth and sensorily acceptable up to 12 days of refrigerated storage at 4°C.


Asunto(s)
Flavonoides/química , Manipulación de Alimentos/métodos , Conservantes de Alimentos/química , Frutas/química , Lythraceae/química , Carne/análisis , Carne/microbiología , Fenoles/química , Animales , Carga Bacteriana/efectos de los fármacos , Bebidas/análisis , Pollos , Femenino , Flavonoides/farmacología , Microbiología de Alimentos , Conservantes de Alimentos/farmacología , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Bacterias Aerobias Gramnegativas/aislamiento & purificación , Humanos , Viabilidad Microbiana/efectos de los fármacos , Proteínas Musculares/química , Oxidación-Reducción , Fenoles/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Polifenoles , Refrigeración , Sensación , Compuestos de Sulfhidrilo/análisis , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis
17.
Infect Control Hosp Epidemiol ; 31(3): 256-61, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20055664

RESUMEN

OBJECTIVE: To determine whether the use of dual antimicrobial therapy based on the results of a combination antibiotic susceptibility report (antibiogram) increases the likelihood of selecting adequate empirical coverage in critically ill patients with infection due to potentially resistant gram-negative pathogens. DESIGN: Retrospective data analysis. SETTING: Urban academic medical center. METHODS: An analysis of culture results and susceptibility data from intensive care unit patients determined by the clinical microbiology laboratory was performed. The proportion of 5 common gram-negative pathogens susceptible to monotherapy with 1 of 3 antipseudomonal antibiotics (piperacillin-tazobactam, ceftazidime, or imipenem) was compared with the proportion susceptible to each of these 3 "backbone" agents plus 1 of 4 additional antimicrobial agents used in combination. RESULTS: More than 5,000 clinical isolates were examined. When all isolates recovered during the entire study period were included, the addition of any of the second antibiotics studied to each of the 3 backbone agents significantly increased the likelihood of covering the causative pathogen (P < .01 for each). The benefit of combination therapy was variable when results for each of the 5 organisms were examined individually. When temporal trends in susceptibility were examined, the decrease in the proportion of organisms susceptible to monotherapy was statistically significant for both imipenem and ceftazidime (P < .01). CONCLUSIONS: Reporting antibiotic susceptibility data in the form of a combination antibiogram may be useful to clinicians who are considering empirical antimicrobial therapy in the intensive care unit.


Asunto(s)
Antiinfecciosos/uso terapéutico , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Unidades de Cuidados Intensivos , Centros Médicos Académicos , Chicago , Quimioterapia Combinada , Bacterias Aerobias Gramnegativas/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana , Estudios Retrospectivos
18.
J Transl Med ; 7: 14, 2009 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-19228413

RESUMEN

BACKGROUND: Nosocomial infections pose significant threats to hospitalized patients, especially the immunocompromised ones, such as cancer patients. METHODS: This study examined the microbial spectrum of gram-negative bacteria in various infection sites in patients with leukemia and solid tumors. The antimicrobial resistance patterns of the isolated bacteria were studied. RESULTS: The most frequently isolated gram-negative bacteria were Klebsiella pneumonia (31.2%) followed by Escherichia coli (22.2%). We report the isolation and identification of a number of less-frequent gram negative bacteria (Chromobacterium violacum, Burkholderia cepacia, Kluyvera ascorbata, Stenotrophomonas maltophilia, Yersinia pseudotuberculosis, and Salmonella arizona). Most of the gram-negative isolates from Respiratory Tract Infections (RTI), Gastro-intestinal Tract Infections (GITI), Urinary Tract Infections (UTI), and Bloodstream Infections (BSI) were obtained from leukemic patients. All gram-negative isolates from Skin Infections (SI) were obtained from solid-tumor patients. In both leukemic and solid-tumor patients, gram-negative bacteria causing UTI were mainly Escherichia coli and Klebsiella pneumoniae, while gram-negative bacteria causing RTI were mainly Klebsiella pneumoniae. Escherichia coli was the main gram-negative pathogen causing BSI in solid-tumor patients and GITI in leukemic patients. Isolates of Escherichia coli, Klebsiella, Enterobacter, Pseudomonas, and Acinetobacter species were resistant to most antibiotics tested. There was significant imipenem -resistance in Acinetobacter (40.9%), Pseudomonas (40%), and Enterobacter (22.2%) species, and noticeable imipinem-resistance in Klebsiella (13.9%) and Escherichia coli (8%). CONCLUSION: This is the first study to report the evolution of imipenem-resistant gram-negative strains in Egypt. Mortality rates were higher in cancer patients with nosocomial Pseudomonas infections than any other bacterial infections. Policies restricting antibiotic consumption should be implemented to avoid the evolution of newer generations of antibiotic resistant-pathogens.


Asunto(s)
Antibacterianos/uso terapéutico , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Bacterias Aerobias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/complicaciones , Hospitalización , Neoplasias/complicaciones , Neoplasias/microbiología , Bacterias Aerobias Gramnegativas/patogenicidad , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/mortalidad , Humanos , Pruebas de Sensibilidad Microbiana , Neoplasias/mortalidad
19.
Chemotherapy ; 50(5): 214-20, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15523180

RESUMEN

Owing to the predominance of gram-positive pathogens in neutropenic cancer patients, newer generation quinolones with an expanded gram-positive spectrum and enhanced potency, may have a role to play for prophylaxis and/or empiric therapy in such patients. The in vitro activity of gatifloxacin was compared with that of ciprofloxacin, levofloxacin and trovafloxacin against 848 recent clinical isolates from cancer patients. Against gram-positive organisms, gatifloxacin was the most active agent tested inhibiting all Aerococcus, Listeria monocytogens, Micrococcus, Stomatococcus mucilaginous, Bacillus, and Rhodococcus equi strains at < or =2 mg/l, its designated susceptibility breakpoint. It was also very active against methicillin-susceptible staphylococci and Streptococcus spp. (including penicillin nonsusceptible Streptococcus pneumoniae and viridans streptococci). It had moderate activity against methicillin-resistant staphylococci and Enterococcus faecalis, inhibiting 68-80% of these strains at < or =2 mg/l. Gatifloxacin also had good activity against the Enterobacteriaceae (although ciprofloxacin was more potent) inhibiting >95% of isolates at < or =1 mg/l. Nonfermentative gram-negative organisms were less susceptible to all 4 agents. Gatifloxacin was very active against Acinetobacter lwoffi (MIC100 0.12 mg/l) and had moderate activity against Acinetobacter baumanii, Chryseobacterium spp., Stenotrophomonas maltophilia, Pseudomonas aeruginosa and other Pseudomonas species. Alcaligenes xylosoxidans strains were relatively resistant to all 4 agents.


Asunto(s)
Antibacterianos/uso terapéutico , Fluoroquinolonas/uso terapéutico , Quinolonas/clasificación , Quinolonas/uso terapéutico , Antibacterianos/química , Antibacterianos/clasificación , Enterococcus/efectos de los fármacos , Fermentación , Fluoroquinolonas/farmacología , Estudios de Seguimiento , Gatifloxacina , Bacterias Aerobias Gramnegativas/clasificación , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Bacterias Aerobias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/clasificación , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana/métodos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Neoplasias/microbiología , Neutropenia/complicaciones , Neutropenia/tratamiento farmacológico , Neutropenia/microbiología , Quinolonas/química , Staphylococcus/efectos de los fármacos , Streptococcus/efectos de los fármacos
20.
Biol Pharm Bull ; 27(3): 277-81, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-14993788

RESUMEN

Catechin (epicatechin (EC), epicatechin gallate (ECg), epigallocatechin (EGC) and epigallocatechin gallate (EGCg)), which occur in green tea and black tea, possess strong bactericidal action. We observed a reactive oxygen species that was generated from the catechins as the active mechanism: and this reactive oxygen was identified. EGCg reacted with the dissolved oxygen in aqueous solution, resulting in the generation of hydrogen peroxide. Hydrogen peroxide production derived from EGCg rose with increasing pH. EGCg (0.22 mmol/l) in neutral solution (0.1 mol/l phosphate buffer pH 7.0: PBS) quantitatively generated 0.2 mmol/l hydrogen peroxide after 60 min incubation. The bactericidal effect of EGCg is dependent on hydrogen peroxide levels produced by EGCg; moreover, EGCg action was inhibited by treatment with catalase. Both bactericidal effects correlated closely when the effects of EGCg and hydrogen peroxide for the bacterium (9 of 10 kinds of bacterial strains) were examined. Therefore, hydrogen peroxide, which is generated by EGCg, appears to be involved in the bactericidal action of EGCg.


Asunto(s)
Antibacterianos/química , Catequina/análogos & derivados , Catequina/química , Peróxido de Hidrógeno/química , Oxidantes/química , Antibacterianos/farmacología , Catequina/farmacología , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Concentración de Iones de Hidrógeno , Té/química , Factores de Tiempo
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