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1.
J Indian Soc Pedod Prev Dent ; 38(3): 289-292, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33004728

RESUMO

Objective: In this coronavirus disease 2019 pandemic, pediatric children who are admitted in the intensive care unit (ICU) are more susceptible to ventilator-associated pneumonia. Ventilator-associated pneumonia is the second-most common hospital-acquired infection in pediatric ICU. Oral hygiene maintenance is a challenge here. To maintain oral hygiene and to prevent colonization of microorganisms such as Pseudomonas aeruginosa and Staphylococcus aureus which cause ventilator-associated pneumonia, a study was conducted, which aimed at finding the efficacy of chlorhexidine (CHX) wipes (as an oral hygiene aid) on colonization of these organisms in pediatric ICU. Methods and Methodology: The study was conducted among twenty children (8 in ventilation and 12 without ventilation) in the age range of 6-14 years admitted in the pediatric ICU. Swab sample was taken on the 1st day from both groups. Culturing of swab sample was done for colonization of microorganisms. CHX gluconate with a concentration of 0.2% was used as wipes. Swab sample was collected at the end of the 2nd day. Culturing of swab sample was done for colonization of microorganisms. Statistical analysis was done. Results: A statistically significant difference (P ≤ 0.04) was seen in the ventilator group with a mean of 0.75 ± 13.241 in the reduction of S. aureus count. P. aeruginosa growth was not seen in either of the groups before or after the use of CHX wipe. Conclusions: Standard oral hygiene practice has the potential to contribute to improved oral and general health of children in pediatric ICU. CHX wipes significantly reduced S. aureus count in ventilator patients. Hence, it could be used as an effective antimicrobial agent in pediatric ICU.


Assuntos
Clorexidina , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Staphylococcus aureus , Adolescente , Betacoronavirus , Criança , Humanos , Unidades de Terapia Intensiva Pediátrica , Pseudomonas aeruginosa
2.
Vestn Oftalmol ; 136(6): 42-49, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33084278

RESUMO

PURPOSE: To perform a comparative assessment of the bactericidal and fungicidal effects of various parts of the radiation spectrum (Ultraviolet A, red, green and blue). MATERIAL AND METHODS: The study included strains of the most clinically significant microorganisms, which are the most common causes of purulent keratitis - S. aureus, P. aeruginosa and fungi C. albicans. After populating the surface of Petri dishes uniformly with microorganisms of each culture, on four out of the five specimens the central zone of the surface with a diameter of 1 cm was irradiated with light of different spectrum - from ultraviolet to red, with a total radiation energy density of 5.4 J/cm2. One specimen remained as the control subject. After irradiation, scanning electron microscopy with lanthanides contrasting (SEMLC) was used to evaluate the total metabolic activity, the activity of the efflux systems and the morphological characteristics of the microorganisms. RESULTS: The damaging effect of visible spectrum light and UVA radiation on S. aureus, P. aeruginosa and C. albicans cultures was proved by SEMLC. Green spectrum emission with a wavelength of 500 nm had the highest antimicrobial activity. It was manifested by a decrease in the overall level of metabolic activity (from 40-63 c.u. to 26-37 c.u. (S. aureus (p<0.01), P. aeruginosa (p<0.01) and C. albicans (p<0.05)), as well as a 2-fold increase in the proportion of S. aureus cells with active efflux systems. CONCLUSION: SEMLC allows evaluation of parameters of the microorganisms` state: morphological (form and size) and functional (general metabolic activity, activation of efflux systems). Investigation of S. aureus, P. aeruginosa and C. albicans cultures using SEMLC demonstrated the antimicrobial activity of green spectrum radiation of 500 nm wavelength. This will serve as a basis for further research and development of a method of treating infectious keratitis using green light.


Assuntos
Pseudomonas aeruginosa , Staphylococcus aureus , Antibacterianos , Luz , Raios Ultravioleta
3.
Lancet Respir Med ; 8(10): 975-986, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33007285

RESUMO

BACKGROUND: Chronic pulmonary infection with Pseudomonas aeruginosa is one of the most important causes of mortality and morbidity in cystic fibrosis. If antibiotics are commenced promptly, infection can be eradicated. The aim of the trial was to compare the effectiveness and safety of intravenous ceftazidime and tobramycin versus oral ciprofloxacin in the eradication of P aeruginosa. METHODS: We did a multicentre, parallel group, open-label, randomised controlled trial in 72 cystic fibrosis centres (70 in the UK and two in Italy). Eligible participants were older than 28 days with an isolate of P aeruginosa (either the first ever isolate or a new isolate after at least 1 year free of infection). Participants were excluded if the P aeruginosa was resistant to, or they had a contraindication to, one or more of the trial antibiotics; if they were already receiving P aeruginosa suppressive therapy; if they had received any P aeruginosa eradication therapy within the previous 9 months; or if they were pregnant or breastfeeding. We used web-based randomisation to assign patients to 14 days intravenous ceftazidime and tobramycin or 12 weeks oral ciprofloxacin. Both were combined with 12 weeks inhaled colistimethate sodium. Randomisation lists were generated by a statistician, who had no involvement in the trial, using a computer-generated list. Randomisation was stratified by centre and because of the nature of the interventions, blinding was not possible. Our primary outcome was eradication of P aeruginosa at 3 months and remaining free of infection to 15 months. Primary analysis used intention to treat (powered for superiority). Safety analysis included patients who received at least one dose of study drug. TORPEDO-CF was registered on the ISRCTN register, ISRCTN02734162, and EudraCT, 2009-012575-10. FINDINGS: Between Oct 5, 2010, and Jan 27, 2017, 286 patients were randomly assigned to treatment: 137 to intravenous antibiotics and 149 to oral antibiotics. 55 (44%) of 125 participants in the intravenous group and 68 (52%) of 130 participants in the oral group achieved the primary outcome. Participants randomly assigned to the intravenous group were less likely to achieve the primary outcome, although the difference between groups was not statistically significant (relative risk 0·84, 95% CI 0·65-1·09; p=0·18). 11 serious adverse events occurred in ten (8%) of 126 participants in the intravenous antibiotics group and 17 serious adverse events in 12 (8%) of 146 participants in the oral antibiotics group. INTERPRETATION: Compared with oral therapy, intravenous antibiotics did not achieve sustained eradication of P aeruginosa in a greater proportion of patients with cystic fibrosis and was more expensive. Although there were fewer hospitalisations in the intravenous group than the oral group during follow-up, this confers no advantage over oral treatment because intravenous eradication frequently requires hospitalisation. These results do not support the use of intravenous antibiotics to eradicate P aeruginosa in cystic fibrosis. FUNDING: National Institute for Health Research Health Technology Assessment Programme.


Assuntos
Antibacterianos/administração & dosagem , Ceftazidima/administração & dosagem , Fibrose Cística/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa , Tobramicina/administração & dosagem , Administração Intravenosa , Administração Oral , Adolescente , Adulto , Criança , Pré-Escolar , Fibrose Cística/tratamento farmacológico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Infecções por Pseudomonas/complicações , Resultado do Tratamento , Adulto Jovem
4.
Nat Commun ; 11(1): 4948, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009415

RESUMO

The tripartite multidrug efflux system MexAB-OprM is a major actor in Pseudomonas aeruginosa antibiotic resistance by exporting a large variety of antimicrobial compounds. Crystal structures of MexB and of its Escherichia coli homolog AcrB had revealed asymmetric trimers depicting a directional drug pathway by a conformational interconversion (from Loose and Tight binding pockets to Open gate (LTO) for drug exit). It remains unclear how MexB acquires its LTO form. Here by performing functional and cryo-EM structural investigations of MexB at various stages of the assembly process, we unveil that MexB inserted in lipid membrane is not set for active transport because it displays an inactive LTC form with a Closed exit gate. In the tripartite complex, OprM and MexA form a corset-like platform that converts MexB into the active form. Our findings shed new light on the resistance nodulation cell division (RND) cognate partners which act as allosteric factors eliciting the functional drug extrusion.


Assuntos
Antibacterianos/metabolismo , Proteínas da Membrana Bacteriana Externa/metabolismo , Chaperonas Moleculares/metabolismo , Pseudomonas aeruginosa/metabolismo , Regulação Alostérica , Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/ultraestrutura , Transporte Biológico , Modelos Moleculares , Domínios Proteicos
5.
BMC Infect Dis ; 20(1): 729, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028225

RESUMO

BACKGROUND: This study describes the disease burden, clinical characteristics, antibiotic management, impact of multidrug resistance and outcome of Pseudomonas aeruginosa bloodstream infection (PABSI) among children admitted to a tertiary referral hospital for children in Cape Town, South Africa. METHODS: A retrospective descriptive study was conducted at a paediatric referral hospital in Cape Town, South Africa. Demographic and clinical details, antibiotic management and patient outcome information were extracted from medical and laboratory records. Antibiotic susceptibility results of identified organisms were obtained from the National Health Laboratory Service database. RESULTS: The incidence risk of PABSI was 5.4 (95% CI: 4.34-6.54) PABSI episodes / 10,000 hospital admissions and the most common presenting feature was respiratory distress, 34/91 (37.4%). Overall, 69/91 (75.8%) of the PA isolates were susceptible to all antipseudomonal antibiotic classes evaluated. Fifty (54.9%) of the PABSI episodes were treated with appropriate empiric antibiotic therapy. The mortality rate was 24.2% and in multivariable analysis, empiric antibiotic therapy to which PA isolates were not susceptible, infections present on admission, and not being in the intensive care unit at the time that PABSI was diagnosed were significantly associated with 14-day mortality. CONCLUSIONS: PABSI caused appreciable mortality, however, appropriate empiric antibiotic therapy was associated with reduced 14-day mortality.


Assuntos
Infecções por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Hospitais Pediátricos , Humanos , Lactente , Unidades de Terapia Intensiva , Masculino , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/mortalidade , Pseudomonas aeruginosa/efeitos dos fármacos , Estudos Retrospectivos , África do Sul/epidemiologia , Taxa de Sobrevida , Centros de Atenção Terciária
6.
Cell Host Microbe ; 28(4): 502-504, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33031766

RESUMO

Bacterial competition within host-associated polymicrobial communities shapes their composition, often with far-reaching consequences for human health. In this issue of Cell Host & Microbe, Perault et al. reveal how competition between two opportunistic pathogens could account for the epidemiology of chronic lung infections in people with cystic fibrosis.


Assuntos
Complexo Burkholderia cepacia , Fibrose Cística , Sistemas de Secreção Tipo VI , Bactérias , Humanos , Pseudomonas aeruginosa
7.
Cell Host Microbe ; 28(4): 504-506, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33031767

RESUMO

Whole-organism vaccination is a promising approach to prevent malaria. In this issue of Cell Host & Microbe, McNamara and colleagues identify epitope masking as a hindrance to antibody boosting after repeated administration of attenuated Plasmodium falciparum sporozoite vaccine.


Assuntos
Complexo Burkholderia cepacia , Vacinas Antimaláricas , Malária , Sistemas de Secreção Tipo VI , Animais , Pseudomonas aeruginosa
8.
PLoS Pathog ; 16(9): e1008867, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32925969

RESUMO

Surface attachment, an early step in the colonization of multiple host environments, activates the virulence of the human pathogen P. aeruginosa. However, the downstream toxins that mediate surface-dependent P. aeruginosa virulence remain unclear, as do the signaling pathways that lead to their activation. Here, we demonstrate that alkyl-quinolone (AQ) secondary metabolites are rapidly induced upon surface association and act directly on host cells to cause cytotoxicity. Surface-induced AQ cytotoxicity is independent of other AQ functions like quorum sensing or PQS-specific activities like iron sequestration. We further show that packaging of AQs in outer-membrane vesicles (OMVs) increases their cytotoxicity to host cells but not their ability to stimulate downstream quorum sensing pathways in bacteria. OMVs lacking AQs are significantly less cytotoxic, suggesting these molecules play a role in OMV cytotoxicity, in addition to their previously characterized role in OMV biogenesis. AQ reporters also enabled us to dissect the signal transduction pathways downstream of the two known regulators of surface-dependent virulence, the quorum sensing receptor, LasR, and the putative mechanosensor, PilY1. Specifically, we show that PilY1 regulates surface-induced AQ production by repressing the AlgR-AlgZ two-component system. AlgR then induces RhlR, which can induce the AQ biosynthesis operon under specific conditions. These findings collectively suggest that the induction of AQs upon surface association is both necessary and sufficient to explain surface-induced P. aeruginosa virulence.


Assuntos
Proteínas de Bactérias/metabolismo , Infecções por Pseudomonas/metabolismo , Pseudomonas aeruginosa , Quinolonas/farmacologia , Percepção de Quorum/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fatores de Virulência/metabolismo , Células A549 , Animais , Humanos , Camundongos , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/patogenicidade
9.
BMC Infect Dis ; 20(1): 665, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907533

RESUMO

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is a major Gram-negative pathogen, which has been reported to result in high mortality. We aim to investigate the prognostic value and optimum cut-off point of time-to-positivity (TTP) of blood culture in children with P. aeruginosa bacteremia. METHODS: From August 2014 to November 2018, we enrolled the inpatients with P. aeruginosa bacteremia in a 1500-bed tertiary teaching hospital in Chongqing, China retrospectively. Receiver operating characteristic (ROC) analysis was used to determine the optimum cut-off point of TTP, and logistic regression were employed to explore the risk factors for in-hospital mortality and septic shock. RESULTS: Totally, 52 children with P. aeruginosa bacteremia were enrolled. The standard cut-off point of TTP was18 h. Early TTP (≤18 h) group patients had remarkably higher in-hospital mortality (42.9% vs 9.7%, P = 0.014), higher incidence of septic shock (52.4% vs12.9%, P = 0.06), higher Pitt bacteremia scores [3.00 (1.00-5.00) vs 1.00 (1.00-4.00), P = 0.046] and more intensive care unit admission (61.9% vs 22.6%, P = 0.008) when compared with late TTP (> 18 h) groups. Multivariate analysis indicated TTP ≤18 h, Pitt bacteremia scores ≥4 were the independent risk factors for in-hospital mortality (OR 5.88, 95%CI 1.21-21.96, P = 0.035; OR 4.95, 95%CI 1.26-27.50, P = 0.024; respectively). The independent risk factors for septic shock were as follows: TTP ≤18 h, Pitt bacteremia scores ≥4 and hypoalbuminemia (OR 6.30, 95%CI 1.18-33.77, P = 0.032; OR 8.15, 95%CI 1.15-42.43, P = 0.014; OR 6.46, 95% CI 1.19-33.19 P = 0.031; respectively). CONCLUSIONS: Early TTP (≤18 hours) appeared to be associated with worse outcomes for P. aeruginosa bacteremia children.


Assuntos
Bacteriemia/diagnóstico , Hemocultura , Infecções por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/isolamento & purificação , Bacteriemia/mortalidade , Criança , Pré-Escolar , China , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Lactente , Unidades de Terapia Intensiva , Modelos Logísticos , Masculino , Prognóstico , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/mortalidade , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Choque Séptico/mortalidade , Centros de Atenção Terciária , Fatores de Tempo
10.
Medicine (Baltimore) ; 99(39): e22475, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991486

RESUMO

RATIONALE: Although bronchiectasis is conventionally considered a chronic pulmonary disease of adulthood, knowledge of pediatric bronchiectasis not related to cystic fibrosis started to emerge. Limited information in this field is available and the management is based on expert opinion. PATIENT CONCERNS: An 8-year-old girl admitted for 7 days history of wet cough, purulent fetid sputum, shortness of breath and low-grade fever. The wet cough has presented for the past 4 years, during which she had frequent hospitalization for recurrent lower respiratory tract infections. DIAGNOSIS: Chest high-resolution computerized tomography revealed diffuse bronchial dilations accompanied by inflammation in the bilateral lung fields. Microbiologic investigation for bronchoalveolar lavage fluid was positive for Pseudomonas aeruginosa. INTERVENTIONS: With a working diagnosis of bronchiectasis with secondary pulmonary infection, sensitive cefoperazone-sulbactam was administrated for 14 days with gradual improvement of clinical symptoms. Bronchoscopy washing substantially soothed the symptoms, reducing the cough and sputum volumes. OUTCOMES: The child was discharged after 14 days, and treated on long-term prophylactic antibiotic use (amoxicillin-clavulanic acid, 20 mg/kg/d, ≥ 4 weeks). LESSONS: Although bronchiectasisis are condition in childhood, the diagnosis is suspected in children with persistent wet or productive cough, and should be confirmed by a chest high-resolution computerized tomography scan. Antibiotics and airway clearance techniques represent the milestones of bronchiectasis management although there are only a few guidelines in children.


Assuntos
Bronquiectasia/complicações , Infecções por Pseudomonas/complicações , Pseudomonas aeruginosa/isolamento & purificação , Antibacterianos/administração & dosagem , Bronquiectasia/microbiologia , Criança , Feminino , Humanos , Infecções por Pseudomonas/tratamento farmacológico
11.
Cochrane Database Syst Rev ; 9: CD001912, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32997797

RESUMO

BACKGROUND: Staphylococcus aureus causes pulmonary infection in young children with cystic fibrosis. Prophylactic antibiotics are prescribed hoping to prevent such infection and lung damage. Antibiotics have adverse effects and long-term use might lead to infection with Pseudomonas aeruginosa. This is an update of a previously published review. OBJECTIVES: To assess continuous oral antibiotic prophylaxis to prevent the acquisition of Staphylococcus aureus versus no prophylaxis in people with cystic fibrosis, we tested the following hypotheses to investigate whether prophylaxis: 1. improves clinical status, lung function and survival; 2. leads to fewer isolates of Staphylococcus aureus; 3. causes adverse effects (e.g. diarrhoea, skin rash, candidiasis); 4. leads to fewer isolates of other common pathogens from respiratory secretions; 5. leads to the emergence of antibiotic resistance and colonisation of the respiratory tract with Pseudomonas aeruginosa. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Companies manufacturing anti-staphylococcal antibiotics were contacted. Most recent search of the Group's Register: 27 February 2020. Online trials registries were also searched. Most recent search of online trials registries: 15 September 2020. SELECTION CRITERIA: Randomised trials of continuous oral prophylactic antibiotics (given for at least one year) compared to intermittent antibiotics given 'as required', in people with cystic fibrosis of any disease severity. DATA COLLECTION AND ANALYSIS: The authors assessed studies for eligibility and methodological quality and extracted data. The quality of the evidence was assessed using the GRADE criteria. The review's primary outcomes of interest were lung function by spirometry (forced expiratory volume in one second (FEV1)) and the number of people with one or more isolates of Staphylococcus aureus (sensitive strains). MAIN RESULTS: We included four studies, with a total of 401 randomised participants aged zero to seven years on enrolment; one study is ongoing. The two older included studies generally had a higher risk of bias across all domains, but in particular due to a lack of blinding and incomplete outcome data, than the two more recent studies. We only regarded the most recent study as being generally free of bias, although even here we were not certain of the effect of the per protocol analysis on the study results. Evidence quality was judged to be low for all outcomes assessed after being downgraded based on GRADE assessments. Downgrading decisions were due to limitations in study design (all outcomes), for imprecision and for inconsistency . Prophylactic anti-staphylococcal antibiotics probably make little or no difference to lung function measured as FEV1 % predicted after six years (mean difference (MD) -2.30, 95% confidence interval (CI) -13.59 to 8.99, one study, n = 119, low-quality evidence); but may reduce the number of children having one or more isolates of Staphylococcus aureus at two years (odds ratio (OR) 0.21, 95% CI 0.13 to 0.35, three studies, n = 315, low-quality evidence). At the same time point, there may be little or no effect on nutrition as reported using weight z score (MD 0.06, 95% CI -0.33 to 0.45, two studies, n = 140, low-quality evidence), additional courses of antibiotics (OR 0.18, 95% CI 0.01 to 3.60, one study, n = 119, low-quality evidence) or adverse effects (low-quality evidence). There was no difference in the number of isolates of Pseudomonas aeruginosa between groups at two years (OR 0.74, 95% CI 0.45 to 1.23, three studies, n = 312, low-quality evidence), though there was a trend towards a lower cumulative isolation rate of Pseudomonas aeruginosa in the prophylaxis group at two and three years and towards a higher rate from four to six years. As the studies reviewed lasted six years or less, conclusions cannot be drawn about the long-term effects of prophylaxis. AUTHORS' CONCLUSIONS: Anti-staphylococcal antibiotic prophylaxis may lead to fewer children having isolates of Staphylococcus aureus, when commenced early in infancy and continued up to six years of age. The clinical importance of this finding is uncertain. Further research may establish whether the trend towards more children with CF with Pseudomonas aeruginosa, after four to six years of prophylaxis, is a chance finding and whether choice of antibiotic or duration of treatment might influence this.


Assuntos
Antibioticoprofilaxia , Fibrose Cística/microbiologia , Infecções Respiratórias/prevenção & controle , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus , Viés , Criança , Pré-Escolar , Farmacorresistência Bacteriana , Volume Expiratório Forçado , Crescimento , Humanos , Lactente , Recém-Nascido , Pseudomonas aeruginosa/isolamento & purificação , Ensaios Clínicos Controlados Aleatórios como Assunto , Staphylococcus aureus/isolamento & purificação
12.
PLoS One ; 15(9): e0237851, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877414

RESUMO

This study examined the antibacterial effect of protoporphyrin IX-ethylenediamine derivative (PPIX-ED)-mediated photodynamic antimicrobial chemotherapy (PPIX-ED-PACT) against Pseudomonas aeruginosa in vitro and in vivo. PPIX-ED potently inhibited the growth of Pseudomonas aeruginosa by inducing reactive oxygen species production via photoactivation. Atomic force microscopy revealed that PPIX-ED-PACT induced the leakage of bacterial content by degrading the bacterial membrane and wall. As revealed using acridine orange/ethidium bromide staining, PPIX-ED-PACT altered the permeability of the bacterial membrane. In addition, the antibacterial effect of PPIX-ED-PACT was demonstrated in an in vivo model of P. aeruginosa-infected wounds. PPIX-ED (100 µM) decreased the number of P. aeruginosa colony-forming units by 4.2 log10. Moreover, histological analysis illustrated that the wound healing rate was 98% on day 14 after treatment, which was 10% higher than that in the control group. According to the present findings, PPIX-ED-PACT can effectively inhibit the growth of P. aeruginosa in vitro and in vivo.


Assuntos
Antibacterianos/uso terapêutico , Fotoquimioterapia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/fisiologia , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Animais , Antibacterianos/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/efeitos da radiação , Etilenodiaminas/química , Etilenodiaminas/farmacologia , Etilenodiaminas/uso terapêutico , Feminino , Luz , Camundongos , Camundongos Endogâmicos BALB C , Viabilidade Microbiana/efeitos dos fármacos , Modelos Biológicos , Células NIH 3T3 , Fotodegradação , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Protoporfirinas/química , Protoporfirinas/farmacologia , Protoporfirinas/uso terapêutico , Pseudomonas aeruginosa/efeitos da radiação , Cicatrização/efeitos dos fármacos
13.
PLoS Biol ; 18(9): e3000856, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32941420

RESUMO

Antibiotic combination therapies are important for the efficient treatment of many types of infections, including those caused by antibiotic-resistant pathogens. Combination treatment strategies are typically used under the assumption that synergies are conserved across species and strains, even though recent results show that the combined treatment effect is determined by specific drug-strain interactions that can vary extensively and unpredictably, both between and within bacterial species. To address this problem, we present a new method in which antibiotic synergy is rapidly quantified on a case-by-case basis, allowing for improved combination therapy. The novel CombiANT methodology consists of a 3D-printed agar plate insert that produces defined diffusion landscapes of 3 antibiotics, permitting synergy quantification between all 3 antibiotic pairs with a single test. Automated image analysis yields fractional inhibitory concentration indices (FICis) with high accuracy and precision. A technical validation with 3 major pathogens, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, showed equivalent performance to checkerboard methodology, with the advantage of strongly reduced assay complexity and costs for CombiANT. A synergy screening of 10 antibiotic combinations for 12 E. coli urinary tract infection (UTI) clinical isolates illustrates the need for refined combination treatment strategies. For example, combinations of trimethoprim (TMP) + nitrofurantoin (NIT) and TMP + mecillinam (MEC) showed synergy, but only for certain individual isolates, whereas MEC + NIT combinations showed antagonistic interactions across all tested strains. These data suggest that the CombiANT methodology could allow personalized clinical synergy testing and large-scale screening. We anticipate that CombiANT will greatly facilitate clinical and basic research of antibiotic synergy.


Assuntos
Antibacterianos/administração & dosagem , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana/métodos , Algoritmos , Andinocilina/administração & dosagem , Andinocilina/farmacologia , Antibacterianos/farmacologia , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Humanos , Testes de Sensibilidade Microbiana/instrumentação , Nitrofurantoína/administração & dosagem , Nitrofurantoína/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Reprodutibilidade dos Testes , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Trimetoprima/administração & dosagem , Trimetoprima/farmacologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
14.
Sci Total Environ ; 738: 140277, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32806351

RESUMO

Although bacterial degradation of polynuclear aromatic hydrocarbons (PAH) have been studied using various pure cultures, only a few studies have explored the degradation kinetics and uptake mechanism of nitrogen heterocyclic PAHs (PANH) with three or more rings. This work explored growth kinetics of a PAH degrading bacterial strain, Pseudomonas aeruginosa RS1 on carbazole (CBZ) and concomitant degradation kinetics of CBZ over the concentration range 25 to 500 mg/L. For CBZ acclimatized strain, the specific growth rate (µ) and specific CBZ uptake rate (q) varied from 0.96 ± 0.05 to 2 ± 0.15 day-1 and from 0.002 ± 0.001 to 0.02 ± 0.01 mg CBZ mg VSS-1 day-1, respectively. The Moser and Monod model provided best fits to the µ vs CBZ concentration and q vs CBZ concentration profiles, respectively. Biosurfactant activity did not play a role in CBZ uptake. However, elevation in cell surface hydrophobicity as revealed through the water contact angle values on bacterial cell mat indicated the possible role of direct interfacial uptake in facilitating CBZ uptake over and above uptake after dissolution. Elevated catechol 1,2-dioxygenase enzyme activity was observed during CBZ degradation. Interestingly, the specific activity of this enzyme was higher in the culture supernatant than in the cell extract. However, during CBZ degradation, accumulation of some toxic metabolites in the aqueous phase was revealed through increase in TOC of the aqueous phase and Kirby-Bauer disc diffusion study performed using a E. coli strain. Both aqueous phase TOC and toxicity decreased beyond the log growth phase indicating further utilization of the degradation intermediates.


Assuntos
Pseudomonas aeruginosa , Esgotos , Biodegradação Ambiental , Carbazóis , Escherichia coli , Cinética
15.
Ecotoxicol Environ Saf ; 202: 110919, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800254

RESUMO

In this study, Pseudomonas aeruginosa was applied to degrade tetrabromobisphenol A (TBBPA) with glucose as a co-metabolic substrate. Influencing factors of co-metabolic degradation such as pH, TBBPA and glucose concentration were examined and the degradation efficiency under optimal condition reached about 50% on the 7th day. The study also proved that the extracellular action, rather than intracellular one, played a leading role in TBBPA degradation. Five metabolites including debromination and beta-scission products were identified in this study. The extracellular active substance pyocyanin was considered as the origin of H2O2 and OH·. The variation of concentrations of H2O2 and OH· shared the same trend, they increased in the early days and then declined gradually. On the 1st day, the OD600 of P.aeruginosa in the co-metabolic group was 6.0 times higher than the initial value while total organic carbon (TOC) decreased about 78%, which might lead to the occurrence of pyocyanin auto-poisoning. Flow cytometry was applied to detect the cellular state of P.aeruginosa during degradation. The increasing intracellular ROS showed that cells were suffering from oxidative stress and the change of membrane potential revealed that cellular dysfunction had occurred since the 1st day. This research indicated that the toxic effect on P.aeruginosa was probably not directly correlated with TBBPA, but was caused by pyocyanin auto-poisoning.


Assuntos
Bifenil Polibromatos/metabolismo , Pseudomonas aeruginosa/metabolismo , Biodegradação Ambiental , Peróxido de Hidrogênio
16.
PLoS Biol ; 18(8): e3000805, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32810152

RESUMO

Antibiotics are losing efficacy due to the rapid evolution and spread of resistance. Treatments targeting bacterial virulence factors have been considered as alternatives because they target virulence instead of pathogen viability, and should therefore exert weaker selection for resistance than conventional antibiotics. However, antivirulence treatments rarely clear infections, which compromises their clinical applications. Here, we explore the potential of combining antivirulence drugs with antibiotics against the opportunistic human pathogen Pseudomonas aeruginosa. We combined two antivirulence compounds (gallium, a siderophore quencher, and furanone C-30, a quorum sensing [QS] inhibitor) together with four clinically relevant antibiotics (ciprofloxacin, colistin, meropenem, tobramycin) in 9×9 drug concentration matrices. We found that drug-interaction patterns were concentration dependent, with promising levels of synergies occurring at intermediate drug concentrations for certain drug pairs. We then tested whether antivirulence compounds are potent adjuvants, especially when treating antibiotic resistant (AtbR) clones. We found that the addition of antivirulence compounds to antibiotics could restore growth inhibition for most AtbR clones, and even abrogate or reverse selection for resistance in five drug combination cases. Molecular analyses suggest that selection against resistant clones occurs when resistance mechanisms involve restoration of protein synthesis, but not when efflux pumps are up-regulated. Altogether, our work provides a first systematic analysis of antivirulence-antibiotic combinatorial treatments and suggests that such combinations have the potential to be both effective in treating infections and in limiting the spread of antibiotic resistance.


Assuntos
Antibacterianos/farmacologia , Ciprofloxacino/farmacologia , Colistina/farmacologia , Furanos/farmacologia , Gálio/farmacologia , Meropeném/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Tobramicina/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Testes de Sensibilidade Microbiana , Biossíntese de Proteínas/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/metabolismo , Percepção de Quorum/efeitos dos fármacos , Virulência
17.
PLoS Genet ; 16(8): e1008505, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32776934

RESUMO

Dynamic gene expression in neurons shapes fundamental processes in the nervous systems of animals. However, how neuronal activation by different stimuli can lead to distinct transcriptional responses is not well understood. We have been studying how microbial metabolites modulate gene expression in chemosensory neurons of Caenorhabditis elegans. Considering the diverse environmental stimuli that can activate chemosensory neurons of C. elegans, we sought to understand how specific transcriptional responses can be generated in these neurons in response to distinct cues. We have focused on the mechanism of rapid (<6 min) and selective transcriptional induction of daf-7, a gene encoding a TGF-ß ligand, in the ASJ chemosensory neurons in response to the pathogenic bacterium Pseudomonas aeruginosa. DAF-7 is required for the protective behavioral avoidance of P. aeruginosa by C. elegans. Here, we define the involvement of two distinct cyclic GMP (cGMP)-dependent pathways that are required for daf-7 expression in the ASJ neuron pair in response to P. aeruginosa. We show that a calcium-independent pathway dependent on the cGMP-dependent protein kinase G (PKG) EGL-4, and a canonical calcium-dependent signaling pathway dependent on the activity of a cyclic nucleotide-gated channel subunit CNG-2, function in parallel to activate rapid, selective transcription of daf-7 in response to P. aeruginosa metabolites. Our data suggest that fast, selective early transcription of neuronal genes require PKG in shaping responses to distinct microbial stimuli in a pair of C. elegans chemosensory neurons.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Células Quimiorreceptoras/metabolismo , GMP Cíclico/metabolismo , Pseudomonas aeruginosa/metabolismo , Fator de Crescimento Transformador beta/genética , Animais , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/metabolismo , Sinalização do Cálcio , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Ativação Transcricional , Fator de Crescimento Transformador beta/metabolismo
18.
Toxicon ; 186: 35-41, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32768440

RESUMO

Antimicrobial peptides have recently become extremely popular as a novel class of antimicrobial agents. AMP MK049518 (FLGLLGSVLGSVLPSIFK), identified from the crab-scorpion Didymocentrus krausi, only possesses significant antibacterial activity against Gram-positive bacteria. In this study, a derivative G2K-S3K was designed with an excellent antibacterial spectrum and significantly higher antibacterial activity compared to the natural peptide. G2K-S3K also demonstrated excellent serum- and thermal-stability and did not induce bacterial resistance. In the Staphylococcus aureus and Pseudomonas aeruginosa -induced skin infection in mice, G2K-S3K significantly decreased bacterial counts in the wound by topical application. Thus, G2K-S3K could be a potent topical anti-infective agent against the skin infection caused by S. aureus and P. aeruginosa.


Assuntos
Antibacterianos/toxicidade , Proteínas de Insetos/toxicidade , Escorpiões , Staphylococcus aureus/efeitos dos fármacos , Animais , Camundongos , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas , Pseudomonas aeruginosa , Infecções Estafilocócicas
19.
BMC Infect Dis ; 20(1): 604, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807092

RESUMO

BACKGROUND: Infectious Diseases Society of America (IDSA) guidelines suggest 7-14 days' duration of antibiotic treatment for uncomplicated Gram-negative bacteria (GNB) catheter-related bloodstream infection (CRBSI). The objectives of this study were to review microbial epidemiology, to determine rate and risk factors for relapse, and to compare clinical outcomes in patients receiving long- versus short-duration antibiotic therapy. METHODS: A retrospective phase 1 study was conducted between January 2010 and October 2016 to review microbial epidemiology and to determine the incidence of and risk factors for relapse in patients with GNB CRBSI, according to the IDSA guidelines diagnostic criteria. In phase 2 of the study, patients without risk factors for relapse between November 2016 and October 2017 were prospectively recruited to receive antibiotic therapy for 7 days after catheter removal. Matched patients from the retrospective phase 1 study who had received antibiotic therapy for ≥14 days were selected as a phase 2 control group to compare outcomes. RESULTS: In phase 1, three most common pathogens identified among 174 cases were Pseudomonas aeruginosa (22.0%), Klebsiella pneumoniae (16.7%), and Stenotrophomonas maltophilia (13.4%). Eighty-nine episodes of infection occurred while patients were receiving antibiotic therapy. Of 140 cases, the relapse rate was 6.4%. Catheter retention was the only risk factor strongly associated with relapse (odds ratio = 145.32; 95% confidence interval 12.66-1667.37, P < 0.001). In phase 2, 11 patients with catheter removal were prospectively recruited to receive short-duration therapy. The number of patients with relapse receiving long- or short-duration therapy was 1 (3%) and 0 (0%), respectively (P = 1.000). CONCLUSIONS: For the management of patients with uncomplicated GNB CRBSI, empiric broad-spectrum antibiotic therapy with adequate coverage of P. aeruginosa should be chosen. Catheter removal should be performed to prevent relapse and shortening the duration of treatment could be considered. TRIAL REGISTRATION: Thai Clinical Trial Registry: TCTR20190914001 . Retrospectively registered on 13 September 2019.


Assuntos
Antibacterianos/uso terapêutico , Infecções Relacionadas a Cateter/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/microbiologia , Feminino , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Projetos Piloto , Estudos Prospectivos , Pseudomonas aeruginosa/isolamento & purificação , Recidiva , Fatores de Risco , Stenotrophomonas maltophilia/isolamento & purificação , Tailândia/epidemiologia , Adulto Jovem
20.
PLoS Genet ; 16(8): e1008783, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32813693

RESUMO

Pseudomonas aeruginosa and Candida albicans are opportunistic pathogens whose interactions involve the secreted products ethanol and phenazines. Here, we describe the role of ethanol in mixed-species co-cultures by dual-seq analyses. P. aeruginosa and C. albicans transcriptomes were assessed after growth in mono-culture or co-culture with either ethanol-producing C. albicans or a C. albicans mutant lacking the primary ethanol dehydrogenase, Adh1. Analysis of the RNA-Seq data using KEGG pathway enrichment and eADAGE methods revealed several P. aeruginosa responses to C. albicans-produced ethanol including the induction of a non-canonical low-phosphate response regulated by PhoB. C. albicans wild type, but not C. albicans adh1Δ/Δ, induces P. aeruginosa production of 5-methyl-phenazine-1-carboxylic acid (5-MPCA), which forms a red derivative within fungal cells and exhibits antifungal activity. Here, we show that C. albicans adh1Δ/Δ no longer activates P. aeruginosa PhoB and PhoB-regulated phosphatase activity, that exogenous ethanol complements this defect, and that ethanol is sufficient to activate PhoB in single-species P. aeruginosa cultures at permissive phosphate levels. The intersection of ethanol and phosphate in co-culture is inversely reflected in C. albicans; C. albicans adh1Δ/Δ had increased expression of genes regulated by Pho4, the C. albicans transcription factor that responds to low phosphate, and Pho4-dependent phosphatase activity. Together, these results show that C. albicans-produced ethanol stimulates P. aeruginosa PhoB activity and 5-MPCA-mediated antagonism, and that both responses are dependent on local phosphate concentrations. Further, our data suggest that phosphate scavenging by one species improves phosphate access for the other, thus highlighting the complex dynamics at play in microbial communities.


Assuntos
Antibiose , Candida albicans/fisiologia , Etanol/metabolismo , Fosfatos/metabolismo , Pseudomonas aeruginosa/fisiologia , Álcool Desidrogenase/genética , Álcool Desidrogenase/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Pseudomonas aeruginosa/metabolismo , Transdução de Sinais , Transcriptoma
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