RESUMO
The parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide. This infection often remains asymptomatic and is related to several health complications. The traditional treatment for trichomoniasis is the use of drugs of the 5-nitroimidazole family, such as metronidazole; however, scientific reports indicate an increasing number of drug-resistant strains. Benzimidazole derivatives could offer an alternative in the search for new anti-trichomonas drugs. In this sense, two attractive candidates are the compounds O2N-BZM7 and O2N-BZM9 (1H-benzimidazole derivatives), since, through in vitro tests, they have shown a higher trichomonacide activity. In this study, we determined the effect on the expression level of metabolic genes in T. vaginalis. The results show that genes involved in redox balance (NADHOX, G6PD::6PGL) are overexpressed, as well as the gene that participates in the first reaction of glycolysis (CK); on the other hand, structural genes such as ACT and TUB are decreased in expression in trophozoites treated with the compound O2N-BZM9, which would probably affect its morphology, motility and virulence. These results align with the trichomonacidal activity of the compounds, with benzimidazole O2N-BZM9 being the most potent, with an IC50 value of 4.8 µM. These results are promising for potential future therapeutic applications.
Assuntos
Benzimidazóis , Trichomonas vaginalis , Trichomonas vaginalis/efeitos dos fármacos , Trichomonas vaginalis/genética , Trichomonas vaginalis/metabolismo , Benzimidazóis/farmacologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Antiprotozoários/farmacologia , Antitricômonas/farmacologiaRESUMO
Metronidazole (MTZ) is the most common drug used against Trichomonas vaginalis (T. vaginalis) infections; however, treatment failures and high rates of recurrence of trichomoniasis have been reported, suggesting the presence of resistance in T. vaginalis to MTZ. Therefore, research into new therapeutic options against T. vaginalis infections has become increasingly urgent. This study investigated the trichomonacidal activity of a series of five imidazole carbamate compounds (AGR-1, AGR-2, AGR-3, AGR-4, and AGR-5) through in vitro susceptibility assays to determine the IC50 value of each compound. All five compounds demonstrated potent trichomonacidal activity, with IC50 values in the nanomolar range and AGR-2 being the most potent (IC50 400 nM). To gain insight into molecular events related to AGR-induced cell death in T. vaginalis, we analyzed the expression profiles of some metabolic genes in the trophozoites exposed to AGR compounds and MTZ. It was found that both AGR and MTZ compounds reduced the expression of the glycolytic genes (CK, PFK, TPI, and ENOL) and genes involved in metabolism (G6PD, TKT, TALDO, NADHOX, ACT, and TUB), suggesting that disturbing these key metabolic genes alters the survival of the T. vaginalis parasite and that they probably share a similar mechanism of action. Additionally, the compounds showed low cytotoxicity in the Caco-2 and HT29 cell lines, and the results of the ADMET analysis indicated that these compounds have pharmacokinetic properties similar to those of MTZ. The findings offer significant insights that can serve as a basis for future in vivo studies of the compounds as a potential new treatment against T. vaginalis.
Assuntos
Carbamatos , Imidazóis , Trichomonas vaginalis , Trichomonas vaginalis/efeitos dos fármacos , Trichomonas vaginalis/genética , Trichomonas vaginalis/crescimento & desenvolvimento , Imidazóis/farmacologia , Imidazóis/química , Humanos , Carbamatos/farmacologia , Carbamatos/química , Metronidazol/farmacologia , Metronidazol/química , Regulação da Expressão Gênica/efeitos dos fármacos , Trofozoítos/efeitos dos fármacosRESUMO
Giardiasis, which is caused by Giardia lamblia infection, is a relevant cause of morbidity and mortality worldwide. Because no vaccines are currently available to treat giardiasis, chemotherapeutic drugs are the main options for controlling infection. Evidence has shown that the nitro drug nitazoxanide (NTZ) is a commonly prescribed treatment for giardiasis; however, the mechanisms underlying NTZ's antigiardial activity are not well-understood. Herein, we identified the glucose-6-phosphate::6-phosphogluconate dehydrogenase (GlG6PD::6PGL) fused enzyme as a nitazoxanide target, as NTZ behaves as a GlG6PD::6PGL catalytic inhibitor. Furthermore, fluorescence assays suggest alterations in the stability of GlG6PD::6PGL protein, whereas the results indicate a loss of catalytic activity due to conformational and folding changes. Molecular docking and dynamic simulation studies suggest a model of NTZ binding on the active site of the G6PD domain and near the structural NADP+ binding site. The findings of this study provide a novel mechanistic basis and strategy for the antigiardial activity of the NTZ drug.
Assuntos
Giardia lamblia , Giardíase , Humanos , Giardíase/tratamento farmacológico , Simulação de Acoplamento Molecular , Tiazóis/farmacologia , Tiazóis/uso terapêuticoRESUMO
Protozoan parasites, such as Giardia lamblia and Trichomonas vaginalis, cause the most prevalent infections in humans in developing countries and provoke significant morbidity and mortality in endemic countries. Despite its side-effects, metronidazole is still the drug of choice as a giardiacidal and trichomonacidal tissue-active agent. However, the emergence of metronidazole resistance and its evolved strategies of parasites to evade innate host defenses have hindered the identification and development of new therapeutic strategies against these parasites. Here, we tested five synthesized benzimidazole derivatives as possible drugs for treating giardiasis and trichomoniasis, probing the bifunctional enzyme glucose 6-phosphate dehydrogenase::6-phosphogluconolactone from G. lamblia (GlG6PD::6PGL) and T. vaginalis (TvG6PD::6PGL) as a drug target. The investigated benzimidazole derivatives were H-B2M1, H-B2M2, H2N-BZM6, O2N-BZM7, and O2N-BZM9. The recombinant enzymes were used in inhibition assays, and in silico computational predictions and spectroscopic studies were applied to follow the structural alteration of the enzymes and identify the possible mechanism of inhibition. We identified two potent benzimidazole compounds (O2N-BZM7 and O2N-BZM9), which are capable of inhibiting both protozoan G6PD::6PGL enzymes and in vitro assays with these parasites, showing that these compounds also affect their viability. These results demonstrate that other therapeutic targets of the compounds are the enzymes GlG6PD::6PGL and TvG6PD::6PGL, which contribute to their antiparasitic effect and their possible use in antigiardial and trichomonacidal therapies.
Assuntos
Antiprotozoários , Giardia lamblia , Parasitos , Trichomonas vaginalis , Animais , Humanos , Metronidazol/farmacologia , Antiparasitários/farmacologia , Benzimidazóis/farmacologia , Antiprotozoários/farmacologiaRESUMO
A possible inhibitor of proteases, which contains an indole core and an aromatic polar acetylene, was designed and synthesized. This indole derivative has a molecular architecture kindred to biologically relevant species and was obtained through five synthetic steps with an overall yield of 37% from the 2,2'-(phenylazanediyl)di(ethan-1-ol). The indole derivative was evaluated through docking assays using the main protease (SARS-CoV-2-Mpro) as a molecular target, which plays a key role in the replication process of this virus. Additionally, the indole derivative was evaluated as an inhibitor of the enzyme kallikrein 5 (KLK5), which is a serine protease that can be considered as an anticancer drug target.
Assuntos
Acetileno/química , Antivirais/química , Antivirais/síntese química , Indóis/química , Inibidores de Proteases/química , Inibidores de Proteases/síntese química , SARS-CoV-2/enzimologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antivirais/farmacologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Descoberta de Drogas , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Calicreínas/antagonistas & inibidores , Modelos Moleculares , Simulação de Acoplamento Molecular , Inibidores de Proteases/farmacologia , SARS-CoV-2/efeitos dos fármacos , Tratamento Farmacológico da COVID-19RESUMO
Giardiasis is a diarrheal disease that is highly prevalent in developing countries. Several drugs are available for the treatment of this parasitosis; however, failures in drug therapy are common, and have adverse effects and increased resistance of the parasite to the drug, generating the need to find new alternative treatments. In this study, we synthesized a series of 2-mercaptobenzimidazoles that are derivatives of omeprazole, and the chemical structures were confirmed through mass, 1H NMR, and 13C NMR techniques. The in vitro efficacy compounds against Giardia, as well as its effect on the inhibition of triosephosphate isomerase (TPI) recombinant, were investigated, the inactivation assays were performed with 0.2 mg/mL of the enzyme incubating for 2 h at 37 °C in TE buffer, pH 7.4 with increasing concentrations of the compounds. Among the target compounds, H-BZM2, O2N-BZM7, and O2N-BZM9 had greater antigiardial activity (IC50: 36, 14, and 17 µM on trophozoites), and inhibited the TPI enzyme (K2: 2.3, 3.2, and 2.8 M-1 s-1) respectively, loading alterations on the secondary structure, global stability, and tertiary structure of the TPI protein. Finally, we demonstrated that it had low toxicity on Caco-2 and HT29 cells. This finding makes it an attractive potential starting point for new antigiardial drugs.
Assuntos
Antiprotozoários/farmacologia , Benzimidazóis/farmacologia , Giardia lamblia/efeitos dos fármacos , Omeprazol/farmacologia , Antiprotozoários/síntese química , Antiprotozoários/química , Benzimidazóis/síntese química , Benzimidazóis/química , Células CACO-2 , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Ativação Enzimática/efeitos dos fármacos , Giardia lamblia/enzimologia , Células HT29 , Humanos , Cinética , Lansoprazol/farmacologia , Simulação de Acoplamento Molecular , Omeprazol/síntese química , Omeprazol/química , Espectrometria de Fluorescência , Triose-Fosfato Isomerase/antagonistas & inibidores , Triose-Fosfato Isomerase/química , Trofozoítos/efeitos dos fármacosRESUMO
Gliomas are heterogeneous, solid, and intracranial tumors that originate from glial cells. Malignant cells from the tumor undergo metabolic alterations to obtain the energy required for proliferation and the invasion of the cerebral parenchyma. The alterations in the expression of the genes related to the metabolic pathways can be detected in biopsies of gliomas of different CNS WHO grades. In this study, we evaluated the expression of 16 candidate reference genes in the HMC3 microglia cell line. Then, statistical algorithms such as BestKeeper, the comparative ΔCT method, geNorm, NormFinder, and RefFinder were applied to obtain the genes most suitable to be considered as references for measuring the levels of expression in glioma samples. The results show that PKM and TPI1 are two novel genes suitable for genic expression studies on gliomas. Finally, we analyzed the expression of genes involved in metabolic pathways in clinical samples of brain gliomas of different CNS WHO grades. RT-qPCR analysis showed that in CNS WHO grade 3 and 4 gliomas, the expression levels of HK1, PFKM, GAPDH, G6PD, PGD1, IDH1, FASN, ACACA, and ELOVL2 were higher than those of CNS WHO grade 1 and 2 glioma biopsies. Hence, our results suggest that reference genes from metabolic pathways have different expression profiles depending on the stratification of gliomas and constitute a potential model for studying the development of this type of tumor and the search for molecular targets to treat gliomas.
Assuntos
Reação em Cadeia da Polimerase em Tempo Real , Padrões de ReferênciaRESUMO
BACKGROUND: Active peptides produced by monocytes, in response to endotoxin, initiate and maintain the acute phase of inflammatory response. Some antibiotics have been reported to have immunomodulatory effects in addition to their antimicrobial activity. We examined the effect of linezolid on cytokine synthesis. METHODS: The modulatory effects of erythromycin and linezolid were evaluated in LPS-stimulated human peripheral blood mononuclear cells (PBMCs). Blood was obtained by venipuncture from healthy donor volunteers. PBMCs were separated by Ficoll-Paque. More than 90% of the cells were monocytes as determined by esterase staining. Cells were incubated in the presence of LPS, with or without various concentrations of erythromycin and linezolid. The concentration of each cytokine was determined by ELISA with commercially available reagents. RESULTS: The two drugs suppressed significantly the synthesis of the cytokines tested in a concentration-dependent manner. CONCLUSIONS: These data indicate that antibacterial agents may modify acute phase inflammatory response through their effects on cytokines synthesis by monocytes.
Assuntos
Acetamidas/farmacologia , Citocinas/biossíntese , Monócitos/metabolismo , Oxazolidinonas/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , Inibidores da Síntese de Proteínas/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Eritromicina/farmacologia , Humanos , Inflamação/metabolismo , Linezolida , Lipopolissacarídeos/farmacologia , Monócitos/citologiaRESUMO
BACKGROUND: Urinary tract infection in children is well recognized as a cause of acute morbidity and chronic medical conditions. As a result, appropriate use of antimicrobial agents, however, increases antibiotic resistance and complicates its treatment due to increased patient morbidity, costs, rates of hospitalization, and use of broader-spectrum antibiotics. The goal of this study was to determine antibiotic susceptibility to commonly used agents for urinary tract infection against recent urinary isolates. METHODS: A total of 457 consecutive children attending the emergency room at the Hospital Infantil de México Federico Gómez with symptoms of uncomplicated lower urinary tract infection were eligible for inclusion. Patients who had had symptoms for≥7 days and those who had had previous episodes of urinary tract infection, received antibiotics or other complicated factors were excluded. Midstream and catheter urine specimens were collected. All isolates were identified and the in vitro activities of antimicrobials were determined. RESULTS: The most frequently isolated urinary pathogens were as follows: Escherichia coli (E. coli) (312, 68.3%), Enterococcus spp. (42, 11%), Klebsiella pneumoniae (K. pneumoniae) (40, 8.7%), Pseudomonas aeruginosa (P. aeruginosa) (34, 7.5%), Proteus mirabilis (P. mirabilis) (21, 4.5%), Enterobacter cloacae (8, 1.7%). The resistance to trimetoprim/sulfametoxazol (%) was 73.7, 62.2, 100, 52, and 50, respectively, for E. coli, K. pneumoniae, P. aeruginosa, P. mirabilis and Enterobacter spp., 92.5 for Enterococcus faecalis (E. faecalis) and 49.9 for Enterococcus faecium (E. faecium). Ampicillin was 86.3, 45, 100, 47.9, and 66.6% for the same strains, ciprofloxacin 33.8, 9, 18.8, 0, 0%, nitrofurantoin 4.4, 13, 97.7, 70, 0%; to E. faecalis 0% and 16.7% to E. faecium. CONCLUSIONS: Frequently prescribed empirical agents for uncomplicated urinary tract infection demonstrate lowered in vitro susceptibilities when tested against recent clinical isolates.
RESUMO
Introducción: La infección del tracto urinario en los niños es reconocida como una causa de morbilidad y de condiciones médicas crónicas, por lo que resulta indispensable conocer con claridad la patogénesis de esta enfermedad. Sin embargo, la resistencia creciente complica su tratamiento ya que aumenta la morbilidad, los costos, la estancia hospitalaria y el uso de fármacos de mayor espectro antimicrobiano. El propósito de este estudio fue determinar la susceptibilidad antimicrobiana de los uropatógenos aislados en niños. Métodos: Se incluyeron en el estudio 457 niños que asistieron a la consulta externa y a urgencias del Hospital Infantil de México Federico Gómez, con síntomas de infección del tracto urinario baja no complicada. La orina fue tomada a la mitad del chorro o por cateterismo, y se realizó la identificación y la susceptibilidad antimicrobiana. Resultados: Los patógenos aislados con mayor frecuencia fueron: Escherichia coli (E. coli) (312, 68.3%), Enterococcus spp. (42, 11%), Klebsiella pneumoniae (K. pneumoniae) (40, 8.7%), Pseudomonas aeruginosa (P. aeruginosa) (34, 7.5%), Proteus mirabilis (P. mirabilis) (21, 4.5%), Enterobacter cloacae (8, 1.7%). La resistencia para trimetoprima/sulfametoxazol fue del 73.7, 62.2, 100, 52, 50%,respectivamente, para E. coli, K. pneumoniae, P. aeruginosa, P. mirabilis y Enterobacter spp., del 92.5% para Enterococcus faecalis (E. faecalis) y del 49.9% para Enterococcus faecium (E. faecium). Para ampicilina fue del 86.3, 45, 100, 47.9 y 66.6% para las mismas bacterias, respectivamente. Para ciprofloxacina del 33.8, 9, 18.8, 0 y 0%; para nitrofurantoína del 4.4, 13, 97.7, 70, 0% para enterobacterias, del 0% para E. faecalis y del 16.7% para E. faecium. Conclusiones: Los antimicrobianos frecuentemente prescritos para el tratamiento empírico de la infección del tracto urinario no complicada demuestran resistencia importante o baja susceptibilidad cuando se les probó frente a las cepas aisladas.
Background: Urinary tract infection in children is well recognized as a cause of acute morbidity and chronic medical conditions. As a result, appropriate use of antimicrobial agents, however, increases antibiotic resistance and complicates its treatment due to increased patient morbidity, costs, rates of hospitalization, and use of broader-spectrum antibiotics. The goal of this study was to determine antibiotic susceptibility to commonly used agents for urinary tract infection against recent urinary isolates. Methods: A total of 457 consecutive children attending the emergency room at the Hospital Infantil de México Federico Gómez with symptoms of uncomplicated lower urinary tract infection were eligible for inclusion. Patients who had had symptoms for ≥ 7 days and those who had had previous episodes of urinary tract infection, received antibiotics or other complicated factors were excluded. Midstream and catheter urine specimens were collected. All isolates were identified and the in vitro activities of antimicrobials were determined. Results: The most frequently isolated urinary pathogens were as follows: Escherichia coli (E. coli) (312, 68.3%), Enterococcus spp. (42, 11%), Klebsiella pneumoniae (K. pneumoniae) (40, 8.7%), Pseudomonas aeruginosa (P. aeruginosa) (34, 7.5%), Proteus mirabilis (P. mirabilis) (21, 4.5%), Enterobacter cloacae (8, 1.7%). The resistance to trimetoprim/sulfametoxazol (%) was 73.7, 62.2, 100, 52, and 50, respectively, for E. coli, K. pneumoniae, P. aeruginosa, P. mirabilis and Enterobacter spp., 92.5 for Enterococcus faecalis (E. faecalis) and 49.9 for Enterococcus faecium (E. faecium). Ampicillin was 86.3, 45, 100, 47.9, and 66.6% for the same strains, ciprofloxacin 33.8, 9, 18.8, 0, 0%, nitrofurantoin 4.4, 13, 97.7, 70, 0%; to E. faecalis 0% and 16.7% to E. faecium. Conclusions: Frequently prescribed empirical agents for uncomplicated urinary tract infection demonstrate lowered in vitro susceptibilities when tested against recent clinical isolates.
RESUMO
Las infecciones en vías urinarias afectan tanto a niños como a adultos. En niños son un problema de salud frecuente. En mujeres embarazadas merecen especial atención por los riesgos perinatales. La ausencia de nuevas moléculas antimicrobianas y el incremento en la resistencia bacteriana, favorecida por el uso indiscriminado de antibióticos, obliga a normar conductas para el abordaje y tratamiento inicial de las infecciones en vías urinarias. Este artículo fue desarrollado mediante un panel de médicos especialistas de instituciones de segundo y tercer nivel de atención, tanto públicas como privadas. Se realizó una revisión de la literatura. Ante la sospecha, el diagnóstico de infección en vías urinarias no complicada en niños debe confirmarse a través de medios bacteriológicos. El diagnóstico de infección en vías urinarias no complicada en adultos se realiza con base en el cuadro clínico. El tratamiento empírico inicial debe incluir la cobertura con antibióticos de amplio espectro y la adaptación del mismo de acuerdo con el resultado de los cultivos y de la sensibilidad reportada.
Urinary tract infection affects both children and adults. It is a common health problem in children. In pregnant women, treatment for urinary tract infection deserves special attention due to the perinatal risks. The absence of new antimicrobial molecules and the increase in bacterial resistance, the latter favored by the indiscriminate use of antibiotics, prompt us to standardize norms in the approach and initial treatment of urinary tract infection. The article was written by an independent panel from second- and third-level care public and private institutions. We conducted a review of the literature and the statements made within the framework of an interdisciplinary meeting. When urinary tract infection is suspected in children, diagnosis must be confirmed using bacteriological methods. Diagnosis of uncomplicated urinary tract infection in adults can be made based on the clinical examination. Empirical initial treatment must include wide-spectrum antibiotic options and should be modified according to culture results as well as reported sensitivity.
RESUMO
Introducción. El incremento en la resistencia de los microorganismos a los antibióticos ha provocado un aumento en la morbimortalidad de las infecciones, un mayor uso de antibióticos y el exceso en gastos de hospitalización. Por lo tanto, el objetivo de este trabajo fue describir la frecuencia de microorganismos patógenos y sus patrones de susceptibilidad bacteriana en cultivos de sangre, orina y de otros fluidos corporales en un hospital pediátrico de tercer nivel. Métodos. Se incluyeron en el estudio cepas de cultivos de sangre, orina, líquido cefalorraquídeo y otros, como pleural, pericárdico y peritoneal, de enero de 2010 a junio de 2011. La identificación y la susceptibilidad se obtuvieron utilizando el equipo Vitek 2XL, de acuerdo con las recomendaciones del Clinical and Laboratory Standards Institute . Resultados. Se aislaron e identificaron 7708 bacterias de 27,209 cultivos de muestras biológicas. Los microorganismos más frecuentes fueron Staphylococcus coagulasa negativa, Escherichia coli, Enterococcus spp, Staphylococcus aureus, Pseudomonas aeruginosa y Klebsiella pneumoniae . La actividad antimicrobiana en contra de los diferentes patógenos fue variable. Escherichia coli presentó la mayor resistencia a trimetoprima-sulfametoxazol (74%) y ampicilina-sulbactam (68%). Las mejores opciones resultaron nitrofurantoína e imipenen, con 84 y 100% de sensibilidad. La resistencia de Enterococcus faecium fue de 58% a vancomicina. Streptococcus pneumoniae presentó 100% de sensibilidad a vancomicina. Conclusiones. La frecuencia de patógenos provenientes de diferentes fluidos corporales no ha variado considerablemente. Sin embargo, el cambio más notable se observó en la resistencia, tanto en Gram positivos como en Gram negativos, en contra de los fármacos convencionales, así como en los considerados de amplio espectro.
Background. The increased resistance of microorganisms to antibiotics has led to an increase in morbidity and mortality from infections, increased use of antibiotics and excessive hospitalization costs. Therefore, the aim of this study was to describe the frequency of pathogens and bacterial susceptibility patterns in cultures of blood, urine and other body fluids in a tertiary pediatric hospital. We also aimed to determine the patterns of resistance in pathogens of clinical interest isolated in blood, urine and other sterile liquids in a pediatric teaching center and third-level hospital. Methods. The Institutional Antimicrobial Surveillance Program was established to monitor the predominant pathogens and antimicrobial susceptibility patterns of infections such as bacteremia, pneumonia and urinary infections. The species of each isolate was determined according to routine methodology and Vitek system from January 2010 to June 2011. Antimicrobial agents and susceptibility testing were determined using the Vitek 2XL according to the Clinical and Laboratory Standards Institute. Results. We recovered 7708 isolates from 27,209 cultures (28.3%). Gram negative represented 52.7%. A rank order showed Staphylococcus coagulase-negative , Escherichia coli, Enterococcus spp ., Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae and others. The antimicrobial susceptibility of the most frequently encountered pathogens was variable. E. coli showed the highest resistance to trimethopim-sulfamethoxazole and ampicillin-sulbactam (74 and 68%, respectively) finding the best option to be nitrofurantoin and imipenem with 84 and 100% sensitivity, respectively. Enterococcus faecium resistance was 58% vancomycin, and Streptococcus pneumoniae showed 100% sensitivity to vancomycin. Conclusions. This study emphasizes the problem of resistance and the needs to select an appropriate broad-spectrum empirical regimen guided by the knowledge of pathogen occurrences and local/regional/global resistance patterns. Such practices require the interrelation between clinical microbiology laboratories and hospital pharmacies.
RESUMO
OBJECTIVE: To study the activity of several antibiotics against Staphylococcus spp. MATERIAL AND METHODS: The study included 1209 strains of Staphylococcus spp. from two institutions; Instituto Nacional de Pediatría (National Institute of Pediatrics) and Hospital Infantil de México Federico Gómez (Mexico City Children's Hospital). Minimum Inhibitory Concentrations of all antibiotics were determined by the agar macrodilution technique and standard methods from the National Committee for Clinical Laboratory Standards. RESULTS: Resistance of S. aureus was 14.2% and that of coagulase-negative staphylococci was 53.4%. The activity of different antibiotics is presented in detail. CONCLUSIONS: Surveillance of strains resistant to methicillin is necessary. The English version of this paper is available too at: http://www.insp.mx/salud/index.html.
Assuntos
Infecção Hospitalar/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus/efeitos dos fármacos , Coagulase , Infecção Hospitalar/microbiologia , Resistência Microbiana a Medicamentos , Humanos , Especificidade da Espécie , Infecções Estafilocócicas/microbiologia , Staphylococcus/enzimologia , Staphylococcus aureus/efeitos dos fármacosRESUMO
OBJECTIVE: To describe the antimicrobial activity of several antimicrobial agents against 97 clinical significant isolates of Enterococcus spp. MATERIAL AND METHODS: During a 2-year prospective study at Instituto Nacional de Pediatria (National Institute of Pediatrics) in Mexico City. Ninety seven strains of Enterococcus spp. (60 E faecalis and 37 E. faecium) were tested against 11 antibiotics. Susceptibility tests were performed with agar, according to the standards of the sNational Committee for Clinical Laboratory Standards (NCCLS). Isolates were screened for high-level resistance (HLR) to beta-lactams, aminoglycosides, glycopeptides and other antibiotics, as well as for vancomycin-phenotypes. Differences between proportions were evaluated with chi 2 of Fisher exact fest. RESULTS: Overall resistance rates to the antibiotics tested were: 17/97 (17.5%) to penicillin, ampicillin, amoxicillin-clavulanate and imipenem. There was neither HLR nor beta-lactamase production; 74/97 (48.4%) were resistant to erythromycin; 60% to ciprofloxacin; 31/97 (32%) to gentamicin, and 55/97 (56.7%) to streptomycin. Seven strains were vancomycin-resistant enterococci (VRE), all of them identified as E. faecium; 5/7 with Van A and 2/7 with Van B phenotypes. All the isolates were susceptible to linezolid. The difference in susceptibility among species was significant. CONCLUSIONS: Mutidrug-resistant enterococci is a real problem and continuous surveillance is necessary. The microbiology laboratory is the first line of defense against the spread of multiantibiotic-resistan enterococci in the hospital environment. All the strains recovered should be tested for susceptibility to ampicillin, streptomycin, gentamicin and glycopeptides. The English version of this paper is available too at: http://www.insp.mx/salud/index.html.
Assuntos
Antibacterianos/farmacologia , Enterococcus/efeitos dos fármacos , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Farmacorresistência Bacteriana , Resistência a Múltiplos Medicamentos , Enterococcus/isolamento & purificação , Humanos , Técnicas In Vitro , Estudos ProspectivosRESUMO
OBJECTIVE: To define epidemiologic relationships to determine the prevalence and potential risk factors for nasopharyngeal colonization by antibiotic-resistant pneumococci, their serotypes and their antibiotic susceptibility patterns in children attending a daycare center (DCC). MATERIAL AND METHODS: A prospective cohort study was conducted among children (n = 53) attending the DCC at Hospital Infantil de México Federico Gómez, which is staffed by 20 employees. Patients were enrolled in the study during a two-year period from September 1997 to September 1999. All the participants were followed prospectively, swabbing them every four months. The strains recovered were typed and screened for susceptibility to several antibiotics. The daycare records were reviewed also. Odds ratios and fisher's exact test: or chi square test of significance were computed from contingency tables as appropriate. Exact 95% confidence intervals were computed for odds ratios. Data analysis was performed using Epi statistics program version 6.04 a. RESULTS: Pneumococci were recovered from 45/53 of the infants at one or more visits. A total of 178 isolates were carried. The carriage rate was 47%. Only 7 adults acquired pneumococci during the study. Types 6, 14, 19 and 23 were prevalent and represented 77% of the total. Antibiotic-resistant strains were higher to penicillin and erythromycin. CONCLUSIONS: Children were frequent carriers of pneumococci, the rate of carriage was high in infancy and tended to decrease with age. The types commonly carried by children were the same as those causing invasive disease. There is a high proportion of carriers with antibiotic-resistant S. pneumoniae strains. Children who have had frequent antimicrobial courses are at particular risk.
Assuntos
Portador Sadio , Creches , Farmacorresistência Bacteriana , Infecções Pneumocócicas/epidemiologia , Adulto , Humanos , Lactente , Nasofaringe/microbiologia , Infecções Pneumocócicas/microbiologia , Prevalência , Estudos Prospectivos , Fatores de Risco , Streptococcus pneumoniae/efeitos dos fármacosRESUMO
OBJECTIVE: To assess the frequency of HSV-2 and Treponema pallidum markers and their relationship with characteristics of women during gynecological outpatient visits. MATERIAL AND METHODS: In 1994 and 1995, two populations of 388 and 448 women were studied in two hospitals; one in Cuernavaca, Morelos, México, and the other in Mexico City. Participants provided a blood specimen for detection of antibodies against HSV-2 and T pallidum using the Western blot technique and the VDRL and FTA-ABS tests. Also, participants answered a questionnaire on their sociodemographic characteristics and sexual behavior. The data were analyzed with the SPSS and EGRET statistical packages. RESULTS: The frequencies of HSV-2 antibodies were 28.3% in women from the first hospital, and 18.1% for those in the second. The frequencies of T pallidum antibodies were 2.3% and 1.1%, respectively. Age, marital status, education level, and number of sexual partners were associated with HSV-2 infection. CONCLUSIONS: Low frequencies were found for infection by the microorganisms studied in both groups. HSV-2 infection was associated to exposure periods, sexual behavior, and socioeconomic level. The English version of this paper is available at:http://www.insp.mx/salud/index.html.
Assuntos
Herpes Genital/sangue , Herpes Genital/epidemiologia , Sífilis/sangue , Sífilis/epidemiologia , Adulto , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Estudos Transversais , Feminino , Herpesvirus Humano 2/imunologia , Humanos , México/epidemiologia , Estudos Soroepidemiológicos , Treponema pallidum/imunologiaRESUMO
To examine the type distribution of pathogenic group A streptococcal (GAS) strains in Mexico, we determined the emm types of 423 GAS isolates collected from ill patients residing in Mexico (Durango or Mexico City). These included 282 throat isolates and 107 isolates from normally sterile sites. Of the other isolates, 38 were recovered from other miscellaneous infections. A total of 31 different emm types were found, revealing a broad overlap between commonly occurring emm types in Mexico and the United States. The information obtained in this study is consistent with the possibility that multivalent, M type-specific vaccines prepared for GAS strain distribution within the United States could theoretically protect against the majority of GAS strains causing disease in the two cities surveyed in Mexico.
Assuntos
Antígenos de Bactérias , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Transporte/genética , Streptococcus pyogenes/genética , Alelos , Sequência de Aminoácidos , Criança , Pré-Escolar , Humanos , México/epidemiologia , Dados de Sequência Molecular , Faringite/microbiologia , Homologia de Sequência de Aminoácidos , Choque Séptico/microbiologia , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/classificação , Streptococcus pyogenes/isolamento & purificação , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: To study the activity of several antibiotics against Staphylococcus spp. MATERIAL AND METHODS: The study included 1209 strains of Staphylococcus spp. from two institutions; Instituto Nacional de PediatrÝa (National Institute of Pediatrics) and Hospital Infantil de MÚxico Federico Gómez (Mexico City Children's Hospital). Minimum Inhibitory Concentrations of all antibiotics were determined by the agar macrodilution technique and standard methods from the National Committee for Clinical Laboratory Standards. RESULTS: Resistance of S. aureus was 14.2 and that of coagulase-negative staphylococci was 53.4. The activity of different antibiotics is presented in detail. CONCLUSIONS: Surveillance of strains resistant to methicillin is necessary. The English version of this paper is available too at: http://www.insp.mx/salud/index.html.
Assuntos
Humanos , Staphylococcus , Infecção Hospitalar/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus , Staphylococcus aureus , Coagulase , Especificidade da Espécie , Infecção Hospitalar/microbiologia , Infecções Estafilocócicas/microbiologia , Resistência Microbiana a MedicamentosRESUMO
OBJECTIVE: To describe the antimicrobial activity of several antimicrobial agents against 97 clinical significant isolates of Enterococcus spp. MATHERIAL AND METHODS: During a 2-year prospective study at Instituto Nacional de Pediatria (National Institute of Pediatrics) in Mexico City. Ninety seven strains of Enterococcus spp. (60 E. faecalis and 37 E. faecium) were tested against 11 antibiotics. Susceptibility tests were performed with agar, according to the standards of the sNational Committee for Clinical Laboratory Standards (NCCLS). Isolates were screened for high-level resistance (HLR) to beta-lactams, aminoglycosides, glycopeptides and other antibiotics, as well as for vancomycin-phenotypes. Differences between proportions were evaluated with chi2 of Fisher exact fest. RESULTS: Overall resistance rates to the antibiotics tested were: 17/97 (17.5 percent) to penicillin, ampicillin, amoxicillin-clavulanate and imipenem. There was neither HLR nor beta-lactamase production; 74/97 (48.4 percent) were resistant to erythromycin; 60 percent to ciprofloxacin; 31/97 (32 percent) to gentamicin, and 55/97 (56.7 percent) to streptomycin. Seven strains were vancomycin-resistant enterococci (VRE), all of them identified as E. faecium; 5/7 with Van A and 2/7 with Van B phenotypes. All the isolates were susceptible to linezolid. The difference in susceptibility among species was significant. CONCLUSIONS: Mutidrug-resistant enterococci is a real problem and continuous surveillance is necessary. The microbiology laboratory is the first line of defense against the spread of multiantibiotic-resistan enterococci in the hospital environment . All the strains recovered should be tested for susceptibility to ampicillin, streptomycin, gentamicin and glycopeptides