RESUMO
The repurposing of gallium nitrate as an antibacterial, a drug used previously for the treatment of hypercalcemia, is a plausible alternative to combat infections by Pseudomonas aeruginosa, since it has antipseudomonal properties in vitro and in vivo in animal models and in human lung infections. Furthermore, gallium nitrate tolerance in clinical isolates is very rare. Nevertheless, studies on the reference strains PA14 and PAO1 show that resistance against gallium nitrate is achieved by decreasing gallium intracellular levels by increasing the production of pyocyanin. In this work, we induced resistance in a cystic fibrosis P. aeruginosa isolate and explored its resistance mechanisms. This isolated strain, INP-58M, was not a pyocyanin producer, and its pyoverdine levels remained unchanged upon gallium addition. However, it showed higher activities of NADPH-producing enzymes and the antioxidant enzyme SOD when gallium was added, which suggests a better antioxidant response. Remarkably, gallium intracellular levels in the resistant isolate were higher than those of the parental strain at 20 h but lower after 24 h of culture, suggesting that this strain is capable of gallium efflux.
Assuntos
Antibacterianos/farmacologia , Fibrose Cística/microbiologia , Gálio/farmacologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Reposicionamento de Medicamentos , Farmacorresistência Bacteriana , Humanos , Oligopeptídeos/biossíntese , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/metabolismo , Piocianina/biossínteseRESUMO
BackgroundThere is little information about the possible role of Helicobacter pylori infection on appetite-regulating peptides in children. This study evaluated the association between H. pylori infection and serum levels of ghrelin, leptin, and obestatin in schoolchildren.MethodsOne hundred seventy-eight schoolchildren, students at boarding schools in Mexico City, participated. H. pylori infection status was determined every 6 months for 1 year by a breath test using 13C-urea; schoolchildren with consistently positive or negative results were selected to participate. Age, sex, and body mass index (BMI) were recorded. Serum concentrations of total ghrelin, leptin, and obestatin via specific enzyme-linked immunosorbent assays were determined.ResultsSchoolchildren with H. pylori infection had lower concentration of leptin, -0.54 pg/ml (95% CI: -0.98 to -0.09), compared to the schoolchildren without infection, after adjustment by age, gender, and BMI. And the children with the infection had a median of obestatin lower in 0.99 ng/ml (95% CI: -1.93 to -0.06) compared with the uninfected children after adjustment by BMI.ConclusionAssociation was found between H. pylori infection and decreased serum concentrations of leptin and obestatin. These results suggest that in schoolchildren, H. pylori infection affects the levels of hormones implicated in regulating appetite and energy homeostasis.
Assuntos
Grelina/sangue , Infecções por Helicobacter/sangue , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Leptina/sangue , Adolescente , Fatores Etários , Regulação do Apetite , Biomarcadores/sangue , Testes Respiratórios , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Metabolismo Energético , Ensaio de Imunoadsorção Enzimática , Feminino , Infecções por Helicobacter/diagnóstico , Homeostase , Interações Hospedeiro-Patógeno , Humanos , Modelos Lineares , Masculino , México , Análise MultivariadaRESUMO
Pseudomonas aeruginosa colonizes the lungs of cystic fibrosis patients causing severe damage. This bacterium is intrinsically resistant to antibiotics and shows resistance against new antimicrobials and its virulence is controlled by the quorum-sensing response. Thus, attenuating its virulence by quorum quenching instead of inhibiting its growth has been proposed to minimize resistance; however, resistance against the canonical quorum quencher furanone C-30 can be achieved by mutations leading to increased efflux. In the present work, the effect of C-30 in the attenuation of the QS-controlled virulence factors elastase and pyocyanin was investigated in 50 isolates from cystic fibrosis patients. The results demonstrate that there is a high variability in the expression of both elastase and pyocyanin and that there are many naturally resistant C-30 strains. We report that the main mechanism of C-30 resistance in these strains was not due to enhanced efflux but a lack of permeability. Moreover, C-30 strongly inhibited the growth of several of the isolates studied, thus imposing high selective pressure for the generation of resistance.
Assuntos
Antibacterianos/metabolismo , Furanos/metabolismo , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum , Infecções Respiratórias/microbiologia , Fibrose Cística/complicações , Regulação para Baixo , Farmacorresistência Bacteriana , Humanos , Mutação , Elastase Pancreática/biossíntese , Permeabilidade , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/fisiologia , Piocianina/biossíntese , Fatores de Virulência/biossínteseRESUMO
BACKGROUND: The genes jhp0940, jhp0945, jhp0947, and jhp0949 belong to the plasticity region of the Helicobacter pylori genome. Due to their prevalence in isolates from patients with gastritis, duodenal ulcer, and gastric cancer, they have been proposed as markers of gastroduodenal diseases. These genes are associated with pro-inflammatory cytokine induction through the NF-κB activation pathway. Nevertheless, the status of these genes is unknown in H. pylori isolates from children. The aim of the present work was to determine the frequency of the jhp0940-jhp0945-jhp0947-jhp0949 genes in H. pylori isolates from children. MATERIALS AND METHODS: We identified the jhp0940, jhp0945, jhp0947, and jhp0949 genes and the relationship of each with the virulence factors cagA, cagPAI, and dupA by PCR in 49 isolates of H. pylori from children. The results were corroborated using dot blots. In addition, we compared the prevalence of these genes with the prevalence in adults. RESULTS: The prevalence of jhp0940 (53.1%), jhp0945 (44.9%), jhp0947 (77.6%), and jhp0949 (83.7%) was determined in the isolates from children, as was the prevalence of the virulence genes cagA (63.3%), cagPAI (71.4%), and dupA (37.5%). No association was found between the four genes of the plasticity region and the virulence genes. The presence of the intact locus integrated by jhp0940-jhp0945-jhp0947-jhp0949 was very common among the isolates from children. CONCLUSION: The genes jhp0940, jhp0947, and jhp0949 were present in more than 50% of the H. pylori isolates, and the joint presence of jhp0940-jhp0945-jhp0947-jhp0949 was very frequent. The frequency of these genes in isolates from children could contribute to the virulence of H. pylori and the evolution of the infection.
Assuntos
Proteínas de Bactérias/genética , Gastrite/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Adolescente , Criança , Pré-Escolar , Úlcera Duodenal/epidemiologia , Úlcera Duodenal/microbiologia , Feminino , Gastrite/epidemiologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/patogenicidade , Humanos , Masculino , México/epidemiologia , NF-kappa B/metabolismo , Úlcera Péptica/epidemiologia , Úlcera Péptica/microbiologia , Prevalência , Proteínas Serina-Treonina Quinases/genética , Neoplasias Gástricas/microbiologia , Virulência , Fatores de VirulênciaRESUMO
The novel antimicrobial gallium is a nonredox iron III analogue with bacteriostatic and bactericidal properties, effective for the treatment of Pseudomonas aeruginosa in vitro and in vivo in mouse and rabbit infection models. It interferes with iron metabolism, transport, and presumably its homeostasis. As gallium exerts its antimicrobial effects by competing with iron, we hypothesized that it ultimately will lead cells to an iron deficiency status. As iron deficiency promotes the expression of virulence factors in vitro and promotes the pathogenicity of P. aeruginosa in animal models, it is anticipated that treatment with gallium will also promote the production of virulence factors. To test this hypothesis, the reference strain PA14 and two clinical isolates from patients with cystic fibrosis were exposed to gallium, and their production of pyocyanin, rhamnolipids, elastase, alkaline protease, alginate, pyoverdine, and biofilm was determined. Gallium treatment induced the production of all the virulence factors tested in the three strains except for pyoverdine. In addition, as the Ga-induced virulence factors are quorum sensing controlled, co-administration of Ga and the quorum quencher brominated furanone C-30 was assayed, and it was found that C-30 alleviated growth inhibition from gallium. Hence, adding both C-30 and gallium may be more effective in the treatment of P. aeruginosa infections.
Assuntos
Gálio/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/metabolismo , Fatores de Virulência/metabolismo , Antibacterianos/farmacologia , Fibrose Cística/microbiologia , Humanos , Infecções por Pseudomonas/microbiologiaRESUMO
OBJECTIVES: A longitudinal, randomized, single blind study was done to evaluate the efficacy of an antibacterial hybrid molecule (beta-lactamic-fluoroquinolone) named cephalone after biliary-enteric-bypass (BEB). MATERIAL AND METHODS: Four groups of mongrel dogs were operated on three consecutive periods. Cultures of bile and liver were obtained and assessed, followed by obliteration of common bile duct and BEB to groups A, B and C. Group D served as a control. Ten days later the group A received conventional treatment based on ampicillin/gentamicin and groups B and C, cephalone in two different concentration schemes during 10 consecutive days. Further samples were processed for bacteria and additional liver biopsies were obtained for histopathological analysis. RESULTS: All three treatments reverted bacterial contamination in the liver and most of the bile samples were negative or showed a significant decrease in the number of colony forming units (p = 0.002). Histopathological analysis proved no lesions. CONCLUSIONS: Comparison of efficacy among antibacterial treatments revealed undistinguishable efficacy in this short-term assessment of bacterial contamination after BEB in dogs. The use of cephalone could be considered as a viable treatment or prophylaxis in bacterial infections occurring after BEB. Further studies are needed to assess long-term impact of the cephalone in this setting.
Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Bile/microbiologia , Cefalosporinas/uso terapêutico , Fluoroquinolonas/uso terapêutico , Fígado/microbiologia , Animais , Modelos Animais de Doenças , Cães , Combinação de Medicamentos , Feminino , MasculinoRESUMO
BACKGROUND: Mongolian gerbils that are experimentally infected with Helicobacter pylori develop a chronic inflammation that is similar to natural infections in humans. The aim of this study was to compare the antigens of H. pylori cagPAI+ and cagPAI- strains that are expressed during Meriones unguiculatus colonization. MATERIALS AND METHODS: We identified H. pylori cagPAI+ and cagPAI- strain antigens via Western blotting of samples from Mongolian gerbils that were subjected to unique, mixed, and sequential bacterial infections. RESULTS: The antigens from the J99/CG3 (cagPAI+) strain had a lower molecular weight than the antigens from the 251F/CG3 (cagPAI-) strain. There were fewer identified antigens in the single unique infections compared with the mixed and sequential infections. The number of recognized antigens that had a frequency of recognition >60% was higher for the simultaneous and sequential infection groups compared with the single infection group. A 57-kDa antigen was present in >60% of the samples and four of the five experimental groups. Antigens specific to each bacterial strain were identified; the 190- and 158-kDa antigens appear to be specific for cagPAI-, and the 70-kDa antigen appears to be specific for cagPAI+. CONCLUSIONS: In this study, we identified antigens that are common and specific to the H. pylori cagPAI+ and cagPAI- strains.
Assuntos
Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Imunoglobulina G/imunologia , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/química , Western Blotting , Modelos Animais de Doenças , Ilhas Genômicas , Gerbillinae , Infecções por Helicobacter/microbiologia , Helicobacter pylori/química , Helicobacter pylori/fisiologia , Humanos , Imunoglobulina G/sangue , Masculino , Peso Molecular , CoelhosRESUMO
Helicobacter pylori has a chromosomal pathogenicity island (cagPAI), and the presence or absence of this Island places the microorganism into two types of strains: cagPAI+ which is associated to serious infectious processes, and cagPAI- related to mild to moderate infectious events. Simultaneous colonization by cagPAI+ and cagPAI- strains is frequent and these bacteria can interact among themselves. The aim of this project was to analyze the interaction between cagPAI+ and cagPAI- strains of H. pylori in experimental infection, using the Mongolian gerbil as an experimental animal model. We employed J99 (cagPAI+) and 251F (cagPAI-) strains, and obtained 3 derivate strains in successive isolation from experimentally infected gerbils. By RAPD-PCR we found that cagPAI+ and cagPAI- underwent genetic rearrangement during the gerbil-adaptation process. We identified individual isolates from gerbils, and by in situ hybridization we established that both type of strains were able to colonize the same regions of the host's stomach, and induce a mild to moderate inflammatory process. We studied the competence between cagPAI+ and cagPAI- strains by simultaneous and sequential infections. The study shows that in both colonization experiments, the cagPAI- strains were more efficient than cagPAI+ strains in colonizing the infected host by displacing cagPAI+.
Assuntos
Antígenos de Bactérias/biossíntese , Proteínas de Bactérias/biossíntese , Ilhas Genômicas , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/genética , Helicobacter pylori/patogenicidade , Fatores de Virulência/biossíntese , Animais , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Técnicas de Tipagem Bacteriana , Análise por Conglomerados , Impressões Digitais de DNA , DNA Bacteriano/genética , Gerbillinae/microbiologia , Helicobacter pylori/classificação , Helicobacter pylori/isolamento & purificação , Masculino , Técnica de Amplificação ao Acaso de DNA Polimórfico , Recombinação Genética , Índice de Gravidade de Doença , Virulência , Fatores de Virulência/genéticaRESUMO
BACKGROUND: Physicians have frequently encountered difficulties when prescribing drugs not available in doses suitable for pediatric age groups. Furthermore, children have difficulty swallowing tablets. This study aimed to determine the stability of an oral propafenone suspension made from commercial tablets with a syrup vehicle and to establish its reliable use with children. METHODS: An extemporaneous suspension of propafenone 1.5 mg/ml was prepared with commercial tablets. Its physicochemical and microbiologic stability was established by constant monitoring during 90 days at room temperature (15 +/- 5 degrees C) and at refrigeration (3-5 degrees C). Plasma levels of propafenona were measured in two children with supraventricular tachycardia at steady state. RESULTS: The suspension was stable, maintaining its original physicochemical and microbiologic properties. Moreover, no apparent changes in color or odor were observed. Plasma levels of propafenone in patients demonstrated therapeutic concentrations after they had taken the suspension, with no unwanted outcome. CONCLUSIONS: The conservation of both physicochemical and microbiologic stability of the suspension represents an option for the administration of propafenone to children.
Assuntos
Antiarrítmicos/administração & dosagem , Arritmias Cardíacas/tratamento farmacológico , Estabilidade de Medicamentos , Propafenona/administração & dosagem , Administração Oral , Análise de Variância , Antiarrítmicos/química , Química Farmacêutica , Pré-Escolar , Cromatografia Líquida , Armazenamento de Medicamentos , Humanos , Lactente , México , Propafenona/química , Suspensões , ComprimidosRESUMO
UNLABELLED: Abstract. BACKGROUND: Growing antibiotic resistance demands the constant reassessment of antimicrobial efficacy, particularly in countries with wide antibiotic abuse, where higher resistance prevalence is often found. Knowledge of resistance trends is particularly important when prescribing antibiotics empirically, as is usually the case for urinary tract infections (UTIs). Currently, in Mexico City, ampicillin, cotrimoxazole (trimethoprim/sulfamethoxazole), and ciprofloxacin are used as "first-line" antibiotic treatment for UTI. OBJECTIVE: The aim of this study was to analyze the resistance of bacterial isolates to antibiotics, with a focus on first-line antibiotics, in Mexican pediatric patients and sexually active or pregnant female outpatients. METHODS: In this multicenter susceptibility analysis, bacterial isolates from urine samples collected from pediatric patients and sexually-active or pregnant female outpatients presenting with acute, uncomplicated UTIs in Mexico City from January 2006 through June 2006, were included in the study. Samples were tested for susceptibility to 10 antibiotics by the disk-diffusion method. RESULTS: Four-hundred and seventeen bacterial isolates were derived from sexually active or pregnant female outpatients (324 Escherichia coli) and pediatric patients (93 Klebsiella pneumoniae). We found a high prevalence of resistance towards the drugs used as "first-line" when treating UTIs: ampicillin, cotrimoxazole, and ciprofloxacin (79%, 60%, and 24% resistance, respectively). Ninety-eight percent of K pneumoniae isolates were resistant to ampicillin, whereas 66% of the E coli isolates were resistant to cotrimoxazole. Resistance towards third-generation cephalosporins was also high (6%-8% of E coli and 10%-28% of K pneumoniae). This was possibly caused by chromosomal ß-lactamases, as 30% of all isolates were also resistant to amoxicillin/clavulanate. In contrast, 98% of the E coli isolates and 84% of the K pneumoniae strains (96% of all isolates) were found to be susceptible to nitrofurantoin, which has been in clinical use for much longer than most other drugs in this study. CONCLUSION: In these urine samples from laboratories in Mexico City, resistance of K pneumoniae and E coli isolates to first-line treatment (ampicillin, cotrimoxazole, or ciprofloxacin) of UTI was high, whereas most E coli and K pneumoniae isolates were susceptible to nitrofurantoin and the fourth-generation cephalosporin cefepime. (Curr Ther Res Clin Exp. 2007;68:120-126) Copyright © 2007 Excerpta Medica, Inc.