Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 702
Filtrar
1.
Cochrane Database Syst Rev ; 1: CD013198, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33448349

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterised by persistent respiratory symptoms and airflow limitation. Acute exacerbations punctuate the natural history of COPD and are associated with increased morbidity and mortality and disease progression. Chronic airflow limitation is caused by a combination of small airways (bronchitis) and parenchymal destruction (emphysema), which can impact day-to-day activities and overall quality of life. In carefully selected patients with COPD, long-term, prophylactic use of antibiotics may reduce bacterial load, inflammation of the airways, and the frequency of exacerbations. OBJECTIVES: To assess effects of different prophylactic antibiotics on exacerbations, quality of life, and serious adverse events in people with COPD in three separate network meta-analyses (NMAs), and to provide rankings of identified antibiotics. SEARCH METHODS: To identify eligible randomised controlled trials (RCTs), we searched the Cochrane Airways Group Specialised Register of trials and clinical trials registries. We conducted the most recent search on 22 January 2020. SELECTION CRITERIA: We included RCTs with a parallel design of at least 12 weeks' duration evaluating long-term administration of antibiotics prophylactically compared with other antibiotics, or placebo, for patients with COPD. DATA COLLECTION AND ANALYSIS: This Cochrane Review collected and updated pair-wise data from two previous Cochrane Reviews. Searches were updated and additional studies included. We conducted three separate network meta-analyses (NMAs) within a Bayesian framework to assess three outcomes: exacerbations, quality of life, and serious adverse events. For quality of life, we collected data from St George's Respiratory Questionnaire (SGRQ). Using previously validated methods, we selected the simplest model that could adequately fit the data for every analysis. We used threshold analysis to indicate which results were robust to potential biases, taking into account each study's contributions to the overall results and network structure. Probability ranking was performed for each antibiotic class for exacerbations, quality of life, and serious adverse events. MAIN RESULTS: Characteristics of studies and participants Eight trials were conducted at multiple sites that included hospital clinics or academic health centres. Seven were single-centre trials conducted in hospital clinics. Two trials did not report settings. Trials durations ranged from 12 to 52 weeks. Most participants had moderate to severe disease. Mean age ranged from 64 years to 73 years, and more males were recruited (51% to 100%). Forced expiratory volume in one second (FEV1) ranged from 0.935 to 1.36 L. Most participants had previous exacerbations. Data from 12 studies were included in the NMAs (3405 participants; 16 treatment arms including placebo). Prophylactic antibiotics evaluated were macrolides (azithromycin and erythromycin), tetracyclines (doxycyclines), quinolones (moxifloxacin) and macrolides plus tetracyclines (roxithromycin plus doxycycline). Risk of bias and threshold analysis Most studies were at low risk across domains, except detection bias, for which only seven studies were judged at low risk. In the threshold analysis for exacerbations, all comparisons in which one antibiotic was compared with another were robust to sampling variation, especially macrolide comparisons. Comparisons of classes with placebo were sensitive to potential bias, especially macrolide versus placebo, therefore, any bias in the comparison was likely to favour the active class, so any adjustment would bring the estimated relative effect closer to the null value, thus quinolone may become the best class to prevent exacerbations. Exacerbations Nine studies were included (2732 participants) in this NMA (exacerbations analysed as time to first exacerbation or people with one or more exacerbations). Macrolides and quinolones reduced exacerbations. Macrolides had a greater effect in reducing exacerbations compared with placebo (macrolides: hazard ratio (HR) 0.67, 95% credible interval (CrI) 0.60 to 0.75; quinolones: HR 0.89, 95% CrI 0.75 to 1.04), resulting in 127 fewer people per 1000 experiencing exacerbations on macrolides. The difference in exacerbations between tetracyclines and placebo was uncertain (HR 1.29, 95% CrI 0.66 to 2.41). Macrolides ranked first (95% CrI first to second), with quinolones ranked second (95% CrI second to third). Tetracyclines ranked fourth, which was lower than placebo (ranked third). Contributing studies were considered as low risk of bias in a threshold analysis. Quality of life (SGRQ) Seven studies were included (2237 participants) in this NMA. SGRQ scores improved with macrolide treatment compared with placebo (fixed effect-fixed class effect: mean difference (MD) -2.30, 95% CrI -3.61 to -0.99), but the mean difference did not reach the minimally clinical important difference (MCID) of 4 points. Tetracyclines and quinolones did not improve quality of life any more than placebo, and we did not detect a difference between antibiotic classes. Serious adverse events Nine studies were included (3180 participants) in the NMA. Macrolides reduced the odds of a serious adverse event compared with placebo (fixed effect-fixed class effect: odds ratio (OR) 0.76, 95% CrI 0.62 to 0.93). There was probably little to no difference in the effect of quinolone compared with placebo or tetracycline plus macrolide compared with placebo. There was probably little to no difference in serious adverse events between quinolones or tetracycline plus macrolide. With macrolide treatment 49 fewer people per 1000 experienced a serious adverse event compared with those given placebo. Macrolides ranked first, followed by quinolones. Tetracycline did not rank better than placebo. Drug resistance Ten studies reported drug resistance. Results were not combined due to variation in outcome measures. All studies concluded that prophylactic antibiotic administration was associated with the development of antimicrobial resistance. AUTHORS' CONCLUSIONS: This NMA evaluated the safety and efficacy of different antibiotics used prophylactically for COPD patients. Compared to placebo, prolonged administration of macrolides (ranked first) appeared beneficial in prolonging the time to next exacerbation, improving quality of life, and reducing serious adverse events. No clear benefits were associated with use of quinolones or tetracyclines. In addition, antibiotic resistance was a concern and could not be thoroughly assessed in this review. Given the trade-off between effectiveness, safety, and risk of antibiotic resistance, prophylactic administration of antibiotics may be best reserved for selected patients, such as those experiencing frequent exacerbations. However, none of the eligible studies excluded patients with previously isolated non-tuberculous mycobacteria, which would contraindicate prophylactic administration of antibiotics, due to the risk of developing resistant non-tuberculous mycobacteria.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Carga Bacteriana/efeitos dos fármacos , Progressão da Doença , Metanálise em Rede , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Adulto , Idoso , Antibacterianos/efeitos adversos , Antibioticoprofilaxia/efeitos adversos , Teorema de Bayes , Viés , Feminino , Volume Expiratório Forçado , Humanos , Macrolídeos/efeitos adversos , Macrolídeos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/microbiologia , Qualidade de Vida , Quinolonas/efeitos adversos , Quinolonas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Tetraciclinas/efeitos adversos , Tetraciclinas/uso terapêutico , Resultado do Tratamento
2.
PLoS Negl Trop Dis ; 14(9): e0008583, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32936818

RESUMO

BACKGROUND: Subclinical infection with Mycobacterium leprae is one potential source of leprosy transmission, and post-exposure prophylaxis (PEP) regimens have been proposed to control this source. Because PEP trials require considerable investment, we applied a sensitive variation of the kinetic mouse footpad (MFP) screening assay to aid in the choice of drugs and regimens for clinical trials. METHODOLOGY/PRINCIPAL FINDINGS: Athymic nude mice were inoculated in the footpad (FP) with 6 x 103 viable M. leprae and treated by gastric gavage with a single dose of Rifampin (SDR), Rifampin + Ofloxacin + Minocycline (SD-ROM), or Rifapentine + Minocycline + Moxifloxacin (SD-PMM) or with the proposed PEP++ regimen of three once-monthly doses of Rifampin + Moxifloxacin (RM), Rifampin + Clarithromycin (RC), Rifapentine + Moxifloxacin (PM), or Rifapentine + Clarithromycin (PC). At various times post-treatment, DNA was purified from the FP, and M. leprae were enumerated by RLEP quantitative PCR. A regression analysis was calculated to determine the expected RLEP value if 99.9% of the bacilli were killed after the administration of each regimen. SDR and SD-ROM induced little growth delay in this highly susceptible murine model of subclinical infection. In contrast, SD-PMM delayed measurable M. leprae growth above the inoculum by 8 months. The four multi-dose regimens delayed bacterial growth for >9months post-treatment cessation. CONCLUSIONS/SIGNIFICANCE: The delay in discernable M. leprae growth post-treatment was an excellent indicator of drug efficacy for both early (3-4 months) and late (8-9 months) drug efficacy. Our data indicates that multi-dose PEP may be required to control infection in highly susceptible individuals with subclinical leprosy to prevent disease and decrease transmission.


Assuntos
Infecções Assintomáticas/terapia , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Mycobacterium leprae/efeitos dos fármacos , Profilaxia Pós-Exposição/métodos , Animais , Carga Bacteriana/efeitos dos fármacos , Claritromicina/uso terapêutico , Combinação de Medicamentos , Hanseníase/transmissão , Camundongos , Camundongos Nus , Minociclina/uso terapêutico , Moxifloxacina/uso terapêutico , Mycobacterium leprae/crescimento & desenvolvimento , Rifampina/análogos & derivados , Rifampina/uso terapêutico
3.
BMC Infect Dis ; 20(1): 505, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32660552

RESUMO

BACKGROUND: Meningococcal meningitis (MM) is a life-threatening disease associated with approximately 10% case fatality rates and neurological sequelae in 10-20% of the cases. Recently, we have shown that the matrix metalloproteinase (MMP) inhibitor BB-94 reduced brain injury in a mouse model of MM. The present study aimed to assess whether doxycycline (DOX), a tetracycline that showed a neuroprotective effect as adjuvant therapy in experimental pneumococcal meningitis (PM), would also exert a beneficial effect when given as adjunctive therapy to ceftriaxone (CRO) in experimental MM. METHODS: BALB/c mice were infected by the intracisternal route with a group C Neisseria meningitidis strain. Eighteen h post infection (hpi), animals were randomised for treatment with CRO [100 mg/kg subcutaneously (s.c.)], CRO plus DOX (30 mg/kg s.c.) or saline (control s.c.). Antibiotic treatment was repeated 24 and 40 hpi. Mouse survival and clinical signs, bacterial counts in cerebella, brain damage, MMP-9 and cyto/chemokine levels were assessed 48 hpi. RESULTS: Analysis of bacterial load in cerebella indicated that CRO and CRO + DOX were equally effective at controlling meningococcal replication. No differences in survival were observed between mice treated with CRO (94.4%) or CRO + DOX (95.5%), (p > 0.05). Treatment with CRO + DOX significantly diminished both the number of cerebral hemorrhages (p = 0.029) and the amount of MMP-9 in the brain (p = 0.046) compared to untreated controls, but not to CRO-treated animals (p > 0.05). Levels of inflammatory markers in the brain of mice that received CRO or CRO + DOX were not significantly different (p > 0.05). Overall, there were no significant differences in the parameters assessed between the groups treated with CRO alone or CRO + DOX. CONCLUSIONS: Treatment with CRO + DOX showed similar bactericidal activity to CRO in vivo, suggesting no antagonist effect of DOX on CRO. Combined therapy significantly improved mouse survival and disease severity compared to untreated animals, but addition of DOX to CRO did not offer significant benefits over CRO monotherapy. In contrast to experimental PM, DOX has no adjunctive activity in experimental MM.


Assuntos
Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Doxiciclina/uso terapêutico , Meningite Meningocócica/tratamento farmacológico , Neisseria meningitidis Sorogrupo C , Animais , Antibacterianos/administração & dosagem , Carga Bacteriana/efeitos dos fármacos , Ceftriaxona/administração & dosagem , Hemorragia Cerebral/tratamento farmacológico , Quimiocinas/análise , Quimiocinas/metabolismo , Modelos Animais de Doenças , Doxiciclina/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/metabolismo , Meningite Meningocócica/mortalidade , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Resultado do Tratamento
4.
PLoS Biol ; 18(6): e3000644, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32511236

RESUMO

Mucosa-associated invariant T (MAIT) cells are abundant antimicrobial T cells in humans and recognize antigens derived from the microbial riboflavin biosynthetic pathway presented by the MHC-Ib-related protein (MR1). However, the mechanisms responsible for MAIT cell antimicrobial activity are not fully understood, and the efficacy of these mechanisms against antibiotic resistant bacteria has not been explored. Here, we show that MAIT cells mediate MR1-restricted antimicrobial activity against Escherichia coli clinical strains in a manner dependent on the activity of cytolytic proteins but independent of production of pro-inflammatory cytokines or induction of apoptosis in infected cells. The combined action of the pore-forming antimicrobial protein granulysin and the serine protease granzyme B released in response to T cell receptor (TCR)-mediated recognition of MR1-presented antigen is essential to mediate control against both cell-associated and free-living, extracellular forms of E. coli. Furthermore, MAIT cell-mediated bacterial control extends to multidrug-resistant E. coli primary clinical isolates additionally resistant to carbapenems, a class of last resort antibiotics. Notably, high levels of granulysin and granzyme B in the MAIT cell secretomes directly damage bacterial cells by increasing their permeability, rendering initially resistant E. coli susceptible to the bactericidal activity of carbapenems. These findings define the role of cytolytic effector proteins in MAIT cell-mediated antimicrobial activity and indicate that granulysin and granzyme B synergize to restore carbapenem bactericidal activity and overcome carbapenem resistance in E. coli.


Assuntos
Antígenos de Diferenciação de Linfócitos T/metabolismo , Carbapenêmicos/farmacologia , Citotoxicidade Imunológica , Farmacorresistência Bacteriana/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Granzimas/metabolismo , Células T Invariáveis Associadas à Mucosa/imunologia , Anti-Infecciosos/farmacologia , Carga Bacteriana/efeitos dos fármacos , Citotoxicidade Imunológica/efeitos dos fármacos , Células HeLa , Humanos , Cinética
5.
Niger J Clin Pract ; 23(6): 783-791, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32525112

RESUMO

Background: Microorganisms in the mouth are protected from negative environmental conditions by forming biofilms; however, the use of anti-plaque agents in children is not preferred due to toxic side effects. Green tea has been reported to have anti-microbial and anti-dental caries properties. Aims: The aim of this study was to assess the ability of green tea extract to prevent the formation of biofilm on the teeth of children using space maintainers. Methods: Bacteria were isolated from samples obtained from children aged between 8 and 10 years. The micro-titer plate method and Congo red agar were used to assay biofilm formation. Green tea leaves were obtained from Rize, Turkey. Methanol, hexane and distilled water were used for preparing the extracts. The effects of green tea extract and chlorhexidine on biofilm formation were examined using scanning electron microscopy. Results: Presence of S. mutans 3,3, S. anginosus 2.1.b, S. dysgalactie 6.1.4.1, and E. faecium 10.2. was measured in the biofilm samples. The extracts showed a bacteriostatic effect on the test bacteria, and among the green tea extracts, the methanol extract was found to exhibit the highest efficacy against biofilm formation by S. mutans 3.3. Conclusion: Green tea extract showed good efficacy in controlling bacterial growth, and is recommended as a better-tasting alternative for daily oral hygiene due to a lack of known side effects.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Clorexidina/farmacologia , Cárie Dentária/microbiologia , Braquetes Ortodônticos/microbiologia , Extratos Vegetais/farmacologia , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus mutans/efeitos dos fármacos , Chá/química , Antioxidantes/farmacologia , Carga Bacteriana/efeitos dos fármacos , Criança , Cárie Dentária/tratamento farmacológico , Humanos , Metanol , Testes de Sensibilidade Microbiana , Boca , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Solventes/química , Streptococcus mutans/isolamento & purificação , Streptococcus mutans/fisiologia , Turquia
6.
Int J Food Microbiol ; 325: 108643, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32361054

RESUMO

Biofilms formed on food contact surfaces are frequently exposed to disinfectants at different concentrations. This study was designed to evaluate how S. Enteritidis in single species and dual species biofilms with P. fluorescens respond to quaternary ammonium compounds (QAC) residues on food contact surfaces. The 48 h-biofilms of S. Enteritidis and P. fluorescens in single/dual species were continuously exposed to 20 ppm QAC for 5 days, followed by QAC challenge at 200 ppm and 100 ppm for attached and detached cells, respectively. Biofilm structures were observed by confocal laser scanning microscopy (CLSM) and extracellular polymeric substances (EPS)-related gene expression was also evaluated. Results showed that QAC stress led to one log lower cell counts of S. Enteritidis and P. fluorescens single species biofilms. More cellulose observed by CLSM images and increased transcript levels of cellulose-related genes (csgD, bcsA and ardA) of S. Enteritidis were induced by QAC stress. Nevertheless, high percentage of membrane damaged cells in QAC pre-exposed biofilms might contribute to the increased sensitivity of S. Enteritidis in both attached and detached cells. Previous QAC exposure did not influence S. Enteritidis viable cell counts in dual specie biofilms, in which S. Enteritidis showed strong resistance to QAC with <2 log CFU/cm2 reductions. Decreased transcript levels of cellulose-related genes were observed of S. Enteritidis in dual species biofilms, but EPS-related gene expression of P. fluorescens was not affected by single/duals species. The dual species biofilm matrix which has big microcolonies extruding from bottom layers with great amounts of polysaccharides mainly produced by P. fluorescens could possibly protect S. Enteritidis against disinfection. Enhanced survival of S. Enteritidis in dual species biofilms was also found when they were detached from the coupons. Overall, our findings highlight that although repeated exposures to low dose of QAC sensitized S. Enteritidis, the presence of P. fluorescens in dual species biofilms could enhance QAC resistance of S. Enteritidis, probably contributing to survival of S. Enteritidis in food processing plants.


Assuntos
Biofilmes/efeitos dos fármacos , Desinfetantes/farmacologia , Pseudomonas fluorescens/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , Salmonella enteritidis/efeitos dos fármacos , Carga Bacteriana/efeitos dos fármacos , Desinfecção/métodos , Manipulação de Alimentos/métodos , Testes de Sensibilidade Microbiana , Pseudomonas fluorescens/crescimento & desenvolvimento , Salmonella enteritidis/crescimento & desenvolvimento
7.
PLoS One ; 15(5): e0232775, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32374766

RESUMO

Antibacterial photodynamic therapy (aPDT) and antibacterial blue light (aBL) are emerging treatment methods auxiliary to mechanical debridement for periodontitis. APDT provided with near-infrared (NIR) light in conjunction with an indocyanine green (ICG) photosensitizer has shown efficacy in several dental in-office-treatment protocols. In this study, we tested Streptococcus mutans biofilm sensitivity to either aPDT, aBL or their combination dual-light aPDT (simultaneous aPDT and aBL) exposure. Biofilm was cultured by pipetting diluted Streptococcus mutans suspension with growth medium on the bottom of well plates. Either aPDT (810 nm) or aBL (405 nm) or a dual-light aPDT (simultaneous 810 nm aPDT and 405 nm aBL) was applied with an ICG photosensitizer in cases of aPDT or dual-light, while keeping the total given radiant exposure constant at 100 J/cm2. Single-dose light exposures were given after one-day or four-day biofilm incubations. Also, a model of daily treatment was provided by repeating the same light dose daily on four-day and fourteen-day biofilm incubations. Finally, the antibacterial action of the dual-light aPDT with different energy ratios of 810 nm and 405 nm of light were examined on the single-day and four-day biofilm protocols. At the end of each experiment the bacterial viability was assessed by colony-forming unit method. Separate samples were prepared for confocal 3D biofilm imaging. On a one-day biofilm, the dual-light aPDT was significantly more efficient than aBL or aPDT, although all modalities were bactericidal. On a four-day biofilm, a single exposure of aPDT or dual-light aPDT was more efficient than aBL, resulting in a four logarithmic scale reduction in bacterial counts. Surprisingly, when the same amount of aPDT was repeated daily on a four-day or a fourteen-day biofilm, bacterial viability improved significantly. A similar improvement in bacterial viability was observed after repetitive aBL application. This viability improvement was eliminated when dual-light aPDT was applied. By changing the 405 nm to 810 nm radiant exposure ratio in dual-light aPDT, the increase in aBL improved the antibacterial action when the biofilm was older. In conclusion, when aPDT is administered repeatedly to S. mutans biofilm, a single wavelength-based aBL or aPDT leads to a significant biofilm adaptation and increased S. mutans viability. The combined use of aBL light in synchrony with aPDT arrests the adaptation and provides significantly improved and sustained antibacterial efficacy.


Assuntos
Adaptação Biológica/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Verde de Indocianina/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Streptococcus mutans/efeitos dos fármacos , Adaptação Biológica/efeitos da radiação , Carga Bacteriana/efeitos dos fármacos , Carga Bacteriana/efeitos da radiação , Biofilmes/efeitos da radiação , Humanos , Viabilidade Microbiana/efeitos dos fármacos , Viabilidade Microbiana/efeitos da radiação , Higiene Bucal/métodos , Periodontite/tratamento farmacológico , Streptococcus mutans/efeitos da radiação
8.
J Vis Exp ; (159)2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32449738

RESUMO

Cigarette smoking is the major etiological cause for lung emphysema and chronic obstructive pulmonary disease (COPD). Cigarette smoking also promotes susceptibility to bacterial infections in the respiratory system. However, the effects of cigarette smoking on bacterial infections in human lung epithelial cells have yet to be thoroughly studied. Described here is a detailed protocol for the preparation of cigarette smoking extracts (CSE), treatment of human lung epithelial cells with CSE, and bacterial infection and infection determination. CSE was prepared with a conventional method. Lung epithelial cells were treated with 4% CSE for 3 h. CSE-treated cells were, then, infected with Pseudomonas at a multiplicity of infection (MOI) of 10. Bacterial loads of the cells were determined by three different methods. The results showed that CSE increased Pseudomonas load in lung epithelial cells. This protocol, therefore, provides a simple and reproducible approach to study the effect of cigarette smoke on bacterial infections in lung epithelial cells.


Assuntos
Células Epiteliais/microbiologia , Células Epiteliais/patologia , Pulmão/patologia , Infecções por Pseudomonas/etiologia , Fumar/efeitos adversos , Carga Bacteriana/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Gentamicinas/farmacologia , Humanos , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia
9.
Eur J Immunol ; 50(5): 736-747, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32113187

RESUMO

Prolonged therapy, drug toxicity, noncompliance, immune suppression, and alarming emergence of drug resistance necessitate the search for therapeutic vaccine strategies for tuberculosis (TB). Such strategies ought to elicit not only IFN-γ, but polyfunctional response including TNF-α, which is essential for protective granuloma formation. Here, we investigated the impact of PD-1 inhibition in facilitating protective polyfunctional T cells (PFTs), bacillary clearance, and disease resolution. We have observed PD-1 inhibition preferentially rescued the suppressed PFTs in active tuberculosis patients. In addition, polyfunctional cytokine milieu favored apoptosis of infected MDMs over necrosis with markedly reduced bacillary growth (≪CFU) in our in vitro monocyte-derived macrophages (MDMs) infection model. Furthermore, the animal study revealed a significant decline in the bacterial burden in the lungs and spleen of infected mice after in vivo administration of α-PD-1 along with antitubercular treatment. Our findings suggest that rescuing polyfunctional immune response by PD-1 inhibition works synergistically with antituberculosis chemotherapy to confer improved control over bacillary growth and dissemination. In summary, our data strongly indicate the therapeutic potential of α-PD-1 as adjunct immunotherapy that can rejuvenate suppressed host immunity and enhance the efficacy of candidate therapeutic vaccine(s).


Assuntos
Anticorpos/farmacologia , Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Animais , Carga Bacteriana/efeitos dos fármacos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/microbiologia , Terapia Combinada/métodos , Feminino , Humanos , Interferon gama/genética , Interferon gama/imunologia , Isoniazida/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/microbiologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/patogenicidade , Cultura Primária de Células , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Rifampina/farmacologia , Baço/efeitos dos fármacos , Baço/imunologia , Baço/microbiologia , Resultado do Tratamento , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
10.
BMC Res Notes ; 13(1): 99, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093784

RESUMO

OBJECTIVE: For the majority of people with acute sore throat, over-the-counter treatments represent the primary option for symptomatic relief. This study evaluated the in vitro bactericidal activity of lozenges containing the antiseptic hexylresorcinol against five bacteria associated with acute sore throat: Staphylococcus aureus, Streptococcus pyogenes, Moraxella catarrhalis, Haemophilus influenzae and Fusobacterium necrophorum. RESULTS: Hexylresorcinol 2.4 mg lozenges were dissolved into 5 mL of artificial saliva medium. Inoculum cultures were prepared in triplicate for each test organism to give an approximate population of 108 colony-forming units (cfu)/mL. Bactericidal activity was measured by log reduction in cfu. Greater than 3log10 reductions in cfu were observed at 1 min after dissolved hexylresorcinol lozenges were added to S. aureus (log10 reduction cfu/mL ± standard deviation, 3.3 ± 0.2), M. catarrhalis (4.7 ± 0.4), H. influenzae (5.8 ± 0.4) and F. necrophorum (4.5 ± 0.2) and by 5 min for S. pyogenes (4.3 ± 0.4). Hexylresorcinol lozenges achieved a > 99.9% reduction in cfu against all tested organisms within 5 min, which is consistent with the duration for a lozenge to dissolve in the mouth. In conclusion, in vitro data indicate that hexylresorcinol lozenges offer rapid bactericidal activity against organisms implicated in acute sore throat.


Assuntos
Infecções Bacterianas/tratamento farmacológico , Resfriado Comum/tratamento farmacológico , Hexilresorcinol/uso terapêutico , Orofaringe/efeitos dos fármacos , Administração Oral , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/uso terapêutico , Infecções Bacterianas/microbiologia , Carga Bacteriana/efeitos dos fármacos , Resfriado Comum/microbiologia , Fusobacterium necrophorum/efeitos dos fármacos , Fusobacterium necrophorum/fisiologia , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/fisiologia , Hexilresorcinol/administração & dosagem , Humanos , Testes de Sensibilidade Microbiana , Moraxella catarrhalis/efeitos dos fármacos , Moraxella catarrhalis/fisiologia , Orofaringe/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Streptococcus pyogenes/efeitos dos fármacos , Streptococcus pyogenes/fisiologia , Fatores de Tempo
11.
Biomater Sci ; 8(7): 1996-2006, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32073033

RESUMO

Recently, fluorenylmethyloxycarbonyl (Fmoc) conjugated amino acids (Fmoc-AA), especially Fmoc-phenylalanine (Fmoc-F), have been discovered to have antimicrobial properties specific to Gram-positive bacteria including MRSA. Their weak antibacterial activity against Gram-negative bacteria is due to their inability to cross the bacterial membrane. Here in order to increase the antibacterial spectrum of Fmoc-F, we prepared a formulation of Fmoc-F with the Gram-negative specific antibiotic aztreonam (AZT). This formulation displayed antibacterial activity against both Gram-positive and Gram-negative bacteria and significantly reduced the bacterial load in a mouse wound infection model. The combination produced a synergistic effect and higher efficacy against P. aeruginosa due to the increased Fmoc-F permeability by AZT through the bacterial membrane. This combinatorial approach could be an effective strategy for other Fmoc-AA having a Gram-positive specific antibacterial effect for the better management of bacterial wound infections.


Assuntos
Antibacterianos/administração & dosagem , Aztreonam/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Dipeptídeos/química , Fluorenos/química , Infecção dos Ferimentos/microbiologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Aztreonam/química , Aztreonam/farmacologia , Carga Bacteriana/efeitos dos fármacos , Modelos Animais de Doenças , Sinergismo Farmacológico , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hidrogéis , Camundongos , Testes de Sensibilidade Microbiana , Infecção dos Ferimentos/tratamento farmacológico
12.
J Sci Food Agric ; 100(5): 2288-2295, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31951282

RESUMO

BACKGROUND: In this study, we evaluated the combined effect of cinnamon essential oil (CEO) microemulsions, and a temperature buffering package using phase-change material (PCM) microcapsules on the physicochemical property, lipid oxidation, and bacterial load of traditional Chinese pork balls (shi zi tou) during temperature fluctuation storage for 9 days. RESULTS: Transmission electron microscope characterization revealed that n-tetradecane microcapsules possessed a core-shell spherical shape with a size ranging from 300 to 600 nm. The use of n-tetradecane microcapsule packaging was found to maintain cold storage temperature efficiently. After 9 days of storage, the combination of CEO microemulsions with n-tetradecane microcapsules did not lead to changes in the color parameters of pork balls. At day 9, n-tetradecane microcapsules, used alone or in combination with CEO microemulsions, showed lower thiobarbituric acid reactive substances (TBARS) values than the control group, while their combination exhibited the lowest pH and 1,1-diphenyl-2-picrylhydrazyl (DPPH) values. Furthermore, the combination treatment retarded the growth of total plate count, lactic acid bacteria, Enterobacteriaceae, and Staphylococcus spp. after 4 and 9 days. CONCLUSIONS: The combinations of CEO microemulsions and PCM microcapsules could extend the shelf-life of cooked pork products, suggesting a feasible strategy for meat preservation. © 2020 Society of Chemical Industry.


Assuntos
Embalagem de Alimentos , Conservação de Alimentos , Produtos da Carne/análise , Óleos Voláteis/análise , Carne Vermelha/análise , Animais , Carga Bacteriana/efeitos dos fármacos , Cinnamomum zeylanicum/química , Temperatura Baixa , Cor , Contaminação de Alimentos/prevenção & controle , Microbiologia de Alimentos , Armazenamento de Alimentos , Produtos da Carne/microbiologia , Carne Vermelha/microbiologia , Suínos , Substâncias Reativas com Ácido Tiobarbitúrico/análise
13.
Female Pelvic Med Reconstr Surg ; 26(2): 152-154, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31990805

RESUMO

OBJECTIVE: Intravesical antibiotic administration for the treatment of recurrent urinary tract infections (UTIs) provides targeted therapy that may be a useful alternative to oral antibiotics. The objective of the study was to assess the rate of UTIs before and after intravesical antibiotic instillations in community-dwelling postmenopausal women with recurrent UTIs. METHODS: Patients with recurrent UTI who underwent antibiotic bladder instillations were included. Instillation was performed in the office by trained nursing staff using either gentamycin or tobramycin. Every instillation was preceded by bladder irrigation with sterile water. Retrospective chart review was performed to compare rates of UTIs for 6 months before and after intervention. Descriptive and nonparametric statistics were used for data analysis. RESULTS: Twelve patients were evaluated. The average rate of UTIs decreased from a median of 2.5 to 1.5 infections (P = 0.025) after intravesical instillations. The number of pathogen types decreased from a median of 2.5 to 1.5 after therapy (P = 0.025). There was a reduction in bacterial antibiotic resistance after completion of instillations, with an estimated median difference of -5.250 (P = 0.065). There were no adverse effects reported during instillations. CONCLUSIONS: Intravesical instillations offer a promising therapy for the treatment of recurrent UTIs in postmenopausal women who failed oral antibiotic therapy. Future prospective studies are needed to further elucidate the clinical utility and long-term benefits of antibiotic instillations.


Assuntos
Administração Intravesical , Gentamicinas/administração & dosagem , Prevenção Secundária/métodos , Tobramicina/administração & dosagem , Infecções Urinárias , Antibacterianos/administração & dosagem , Carga Bacteriana/efeitos dos fármacos , Carga Bacteriana/estatística & dados numéricos , Farmacorresistência Bacteriana , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Retrospectivos , Resultado do Tratamento , Bexiga Urinária/microbiologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Infecções Urinárias/prevenção & controle
14.
Lasers Med Sci ; 35(6): 1341-1347, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31900691

RESUMO

Staphylococcus aureus is one of the main causative agent of infections acquired in both community and hospital environment. In this context, photodynamic therapy (PDT) consists in using a photosensitizer that, activated by light, evokes the formation of reactive oxygen species (ROS), which lead to the death of microorganisms due to oxidative damage; it is useful tool since this action, harmful to pathogens, does not significantly injure human cells. In view of this, this work proposes a more in-depth study on the use of resveratrol (RSV) as a possible photosensitizer. It was observed, in the intradermal infection model in animals' ear dermis, that photoactivated resveratrol promotes an increase in myeloperoxidase expression with reduced bacterial load in the draining lymph node. Besides that, the draining lymph node of the animals treated with photoactivated RSV controls inflammation through IL-10 production. These are pioneers data and this work being a pilot study; then, other works must be conducted with the objective of elucidate the photoactivated resveratrol mechanism of action.


Assuntos
Luz , Resveratrol/efeitos da radiação , Resveratrol/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Animais , Carga Bacteriana/efeitos dos fármacos , Caderinas/metabolismo , Derme/efeitos dos fármacos , Derme/enzimologia , Orelha/patologia , Humanos , Inflamação/patologia , Interleucina-10/biossíntese , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Camundongos Endogâmicos BALB C , Peroxidase/metabolismo , Projetos Piloto , Resveratrol/farmacologia , Staphylococcus aureus/efeitos dos fármacos
15.
Dev Comp Immunol ; 103: 103511, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31580833

RESUMO

ß-defensin is a cationic host defense peptide actively participating in host innate immune response against pathogens. In teleost fish, ß-defensin exhibits a diversity in genotypes and functions. Herein, a ß-defensin homolog (PaBD) was identified from ayu, Plecoglossus altivelis, showing multiple tissues' upregulation against Vibrio anguillarum challenge. In vivo experiments revealed that intraperitoneal injection of chemically synthesized mature PaBD (mPaBD) increased the survival rate of V. anguillarum-infected ayu, accompanied by reduced bacterial load and decreased tissue mRNA levels of tumor necrosis factor α (PaTNF-α) and interleukin 1ß (PaIL-1ß). However, in vitro, mPaBD showed weak bactericidal activity against V. anguillarum. Interestingly, mPaBD enhanced phagocytosis, intracellular bacterial killing, and respiratory burst of ayu monocytes/macrophages (MO/MΦ). Moreover, it inhibited mRNA levels of PaIL-1ß and PaTNF-α in MO/MФ upon V. anguillarum infection. In conclusion, PaBD protects ayu against V. anguillarum challenge not only through its direct antibacterial ability, but also through its immunomodulation in MO/MΦ.


Assuntos
Doenças dos Peixes/imunologia , Proteínas de Peixes/metabolismo , Osmeriformes/imunologia , Vibrioses/veterinária , Vibrio/fisiologia , beta-Defensinas/metabolismo , Sequência de Aminoácidos , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Carga Bacteriana/efeitos dos fármacos , Citocinas/genética , Doenças dos Peixes/microbiologia , Doenças dos Peixes/prevenção & controle , Proteínas de Peixes/administração & dosagem , Proteínas de Peixes/genética , Imunomodulação , Macrófagos/imunologia , Macrófagos/microbiologia , Monócitos/imunologia , Monócitos/microbiologia , Osmeriformes/classificação , Osmeriformes/genética , Fagocitose , Filogenia , Explosão Respiratória , Alinhamento de Sequência , Taxa de Sobrevida , Distribuição Tecidual , Vibrio/efeitos dos fármacos , Vibrioses/imunologia , Vibrioses/microbiologia , Vibrioses/prevenção & controle , beta-Defensinas/administração & dosagem , beta-Defensinas/genética
16.
Int J Food Microbiol ; 312: 108375, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31669767

RESUMO

Recently, oxo-biodegradable polymers have attracted much attention due to taking less time to break down after disposal in comparison to ordinary polymers. Polyvinyl alcohol/gelatin (PVA/G) nanocomposite films, containing ZnO, TiO2 or ZnO/TiO2 nanoparticles supported on 4A zeolite (4A z), are novel active packaging that can control the release of antimicrobial compounds. The present study assessed the efficacy of PVA/G nanocomposite films with 1.5% (w/w) ZnO/4A z (treatment 1), 1.5% (w/w) TiO2/4A z (treatment 2), or 1% (w/w) ZnO, TiO2/4A z (treatment 3) in controlling the microbial load and maintaining the sensory qualities of white shrimp during storage at 4 ±â€¯1 °C. Firstly, the optimum concentration of each material for addition to the film was determined by micro-dilution and disc diffusion. Secondly, the specimens were checked for total viable count (TVC), as well as the counts of each of Pseudomonas spp., Enterobacteriaceae, Shewanella putrefaciens, inoculated Staphylococcus aureus, Listeria monocytogenes, and Escherichia coli O157:H7. According to the results, the PVA/G nanocomposite films containing treatments 1-3 significantly decreased the number of bacteria in the treatment group in comparison to the control group (P < .05). The results of the antimicrobial activity of the three treatments by using the disc diffusion method revealed that the inhibition zone varied from 8.11 ±â€¯0.02 to 12.63 ±â€¯0.04 mm. Also it should be noted that, the finding of micro-dilution test varied from 1 ±â€¯0.01 to 3 ±â€¯0.01. The ZnO, TiO2/4A z nanocomposite had a significantly greater antimicrobial impact against Gram-negative bacteria compared to Gram-positive bacteria (P < .05). Finally, the microbiological and sensory investigation of the efficacy of the PVA/G nanocomposite films as active packaging materials revealed a considerable improvement in shrimp shelf life (12 days) in comparison to the control (6 days). Therefore, these nanocomposite films can be used as novel active packaging in the maintenance of the microbial load and sensory qualities of shrimp.


Assuntos
Antibacterianos/farmacologia , Embalagem de Alimentos/métodos , Armazenamento de Alimentos/métodos , Penaeidae/microbiologia , Titânio/farmacologia , Zeolitas/farmacologia , Óxido de Zinco/farmacologia , Animais , Carga Bacteriana/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Gelatina/farmacologia , Listeria monocytogenes/efeitos dos fármacos , Nanocompostos , Nanopartículas , Álcool de Polivinil/farmacologia , Refrigeração , Staphylococcus aureus/efeitos dos fármacos
17.
Protein Pept Lett ; 27(3): 236-242, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31746288

RESUMO

BACKGROUND: Host-directed therapies are a comparatively new and promising method for the treatment of tuberculosis. A variety of host pathways, vaccines and drugs have the potential to provide novel adjunctive therapies for the treatment of tuberculosis. In this connection, we have earlier reported the immunotherapeutic potential of N-formylated N-terminal peptide of glutamine synthetase of Mycobacterim tuberculosis H37Rv (Mir SA and Sharma S, 2014). Now in the present study, we investigated the immunotherapeutic effect of N-terminally formylated internal-peptide 'f- MLLLPD' of mycobacterial glutamine synthetase (Rv2220) in mouse model of tuberculosis. METHODS: The N-terminally formylated peptide, f-MLLLPD was tested for its potential to generate Reactive Oxygen Species (ROS) in murine neutrophils. Further, its therapeutic effect alone or in combination with anti-tubercular drugs was evaluated in mouse model of tuberculosis. RESULTS: The f-MLLLPD peptide treatment alone and in combination with ATDs reduced the bacterial load (indicated as colony forming units) in lungs of infected mice by 0.58 (p<0.01) and 2.92 (p<0.001) log10 units respectively and in their spleens by 0.46 (p<0.05) and 2.46 (p<0.001) log10 units respectively. In addition, the observed histopathological results correlated well with the CFU data. CONCLUSION: The results of the current study show that f-MLLLPD peptide confers an additional therapeutic efficacy to the anti-tuberculosis drugs.


Assuntos
Glutamato-Amônia Ligase/química , Isoniazida/administração & dosagem , Mycobacterium tuberculosis/enzimologia , N-Formilmetionina Leucil-Fenilalanina/administração & dosagem , Rifampina/administração & dosagem , Tuberculose/tratamento farmacológico , Animais , Carga Bacteriana/efeitos dos fármacos , Proteínas de Bactérias/química , Proteínas de Bactérias/imunologia , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Glutamato-Amônia Ligase/imunologia , Isoniazida/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Camundongos , Mycobacterium tuberculosis/imunologia , N-Formilmetionina Leucil-Fenilalanina/imunologia , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Rifampina/farmacologia , Baço/efeitos dos fármacos , Baço/microbiologia , Tuberculose/imunologia
18.
PLoS One ; 14(12): e0226574, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31877146

RESUMO

Phage therapy offers a potential alternate strategy for the treatment of peri-prosthetic joint infection (PJI), particularly where limited effective antibiotics are available. We undertook preclinical trials to investigate the therapeutic efficacy of a phage cocktail, alone and in combination with vancomycin, to reduce bacterial numbers within the infected joint using a clinically-relevant model of Staphylococcus aureus-induced PJI. Infected animals were randomised to 4 treatment groups, with treatment commencing 21-days post-surgery: bacteriophage alone, vancomycin alone, bacteriophage and vancomycin, and sham. At day 28 post-surgery, animals were euthanised for microbiological and immunological assessment of implanted joints. Treatment with phage alone or vancomycin alone, led to 5-fold and 6.2-fold reductions, respectively in bacterial load within peri-implant tissue compared to sham-treated animals. Compared to sham-treated animals, a 22.5-fold reduction in S. aureus burden was observed within joint tissue of animals that were administered phage in combination with vancomycin, corresponding with decreased swelling in the implanted knee. Microbiological data were supported by evidence of decreased inflammation within the joints of animals administered phage in combination with vancomycin, compared to sham-treated animals. Our findings provide further support for phage therapy as a tolerable and effective adjunct treatment for PJI.


Assuntos
Bacteriófagos/fisiologia , Infecções Relacionadas à Prótese/terapia , Infecções Estafilocócicas/terapia , Staphylococcus aureus/patogenicidade , Vancomicina/administração & dosagem , Animais , Carga Bacteriana/efeitos dos fármacos , Terapia Combinada , Modelos Animais de Doenças , Masculino , Infecções Relacionadas à Prótese/microbiologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Resultado do Tratamento , Vancomicina/farmacologia
19.
Niger J Clin Pract ; 22(12): 1654-1661, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31793470

RESUMO

Background: Incomplete eradication of plaque bacteria from the plaque retentive sites and the emerging problem of antibiotic resistance led the scientific community to explore new antimicrobial strategies for improved results and shun antibiotic resistance. Objective: The purpose of this in-vitro study was to evaluate the antimicrobial effect of a novel light based therapy and to assess the susceptibility of oral plaque bacteria to light based technologies with and without photosensitizers. Materials and Methods: Four oral plaque bacterial strains were isolated from the dental plaque sample collected from the patients and exposed to various light based technologies and photodynamic therapy (PDT) with and without photosensitizers. The cultures were analysed for viable colony forming unit (CFU) counts. One-way analysis of variance was used to statistically analyse differences and the Student-Newman-Keuls method to perform multiple comparison procedures. Results: All groups showed remarkable reduction in the CFUs as compared to control group with use of light based technologies and PDT in this study. The difference of antimicrobial effect between all tested groups either with light based technologies and PDT with control group showed significant reduction in CFUs. Conclusions: From the results of this study, we concluded that light based technologies and PDT could be a valuable alternative therapy to mechanical debridement in the prevention of growth and recolonisation of oral plaque bacteria.


Assuntos
Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Placa Dentária/microbiologia , Placa Dentária/terapia , Bolsa Periodontal/microbiologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Bactérias/classificação , Bactérias/isolamento & purificação , Carga Bacteriana/efeitos dos fármacos , Placa Dentária/tratamento farmacológico , Cavidade Pulpar/efeitos dos fármacos , Cavidade Pulpar/microbiologia , Humanos , Técnicas In Vitro , Azul de Metileno/administração & dosagem , Azul de Metileno/uso terapêutico , Bolsa Periodontal/terapia , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/uso terapêutico , Titânio
20.
Sci Rep ; 9(1): 18217, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796883

RESUMO

Plasma cytokines are biomarkers of disease extent and mycobacterial burden in pulmonary tuberculosis (PTB). Whether chemokines can perform the same role in PTB is not known. We examined the plasma levels of chemokines in individuals with PTB, latent TB (LTB) or healthy controls (HC) and their association with disease severity and mycobacterial burdens in PTB. We also examined the chemokines in PTB individuals at the end of anti-tuberculous chemotherapy (ATT). PTB individuals exhibited significantly higher levels of CCL1, CCL3, CXCL1, CXCL2, CXCL9 and CXCL10 in comparison to LTB and/or HC individuals. PTB individuals with bilateral or cavitary disease displayed significantly elevated levels of CCL1, CCL3, CXCL1, CXCL10 and CXCL11 compared to those with unilateral or non-cavitary disease and also exhibited a significant positive relationship with bacterial burdens. In addition, PTB individuals with slower culture conversion displayed significantly elevated levels of CCL1, CCL3, CXCL1 and CXCL9 at the time of PTB diagnosis and prior to ATT. Finally, the chemokines were significantly reduced following successful ATT. Our data demonstrate that PTB is associated with elevated levels of chemokines, which are partially reversed followed chemotherapy. Our data demonstrate that chemokines are markers of disease severity, predicting increased bacterial burden and delayed culture conversion in PTB.


Assuntos
Antituberculosos/uso terapêutico , Quimiocinas/sangue , Tuberculose Latente/diagnóstico , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/diagnóstico , Adulto , Idoso , Antituberculosos/farmacologia , Carga Bacteriana/efeitos dos fármacos , Biomarcadores/sangue , Estudos de Casos e Controles , Quimiocinas/imunologia , Feminino , Humanos , Tuberculose Latente/sangue , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/microbiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Índice de Gravidade de Doença , Escarro/microbiologia , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA