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1.
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
2.
Proc Natl Acad Sci U S A ; 117(37): 22967-22973, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32868444

RESUMO

Hospital-acquired infections are a global health problem that threatens patients' treatment in intensive care units, causing thousands of deaths and a considerable increase in hospitalization costs. The endotracheal tube (ETT) is a medical device placed in the patient's trachea to assist breathing and delivering oxygen into the lungs. However, bacterial biofilms forming at the surface of the ETT and the development of multidrug-resistant bacteria are considered the primary causes of ventilator-associated pneumonia (VAP), a severe hospital-acquired infection for significant mortality. Under these circumstances, there has been a need to administrate antibiotics together. Although necessary, it has led to a rapid increase in bacterial resistance to antibiotics. Therefore, it becomes necessary to develop alternatives to prevent and combat these bacterial infections. One possibility is to turn the ETT itself into a bactericide. Some examples reported in the literature present drawbacks. To overcome those issues, we have designed a photosensitizer-containing ETT to be used in photodynamic inactivation (PDI) to avoid bacteria biofilm formation and prevent VAP occurrence during tracheal intubation. This work describes ETT's functionalization with curcumin photosensitizer, as well as its evaluation in PDI against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli A significant photoinactivation (up to 95%) against Gram-negative and Gram-positive bacteria was observed when curcumin-functionalized endotracheal (ETT-curc) was used. These remarkable results demonstrate this strategy's potential to combat hospital-acquired infections and contribute to fighting antimicrobial resistance.


Assuntos
Antibacterianos/farmacologia , Curcumina/farmacologia , Intubação Intratraqueal/instrumentação , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Curcumina/química , Humanos , Intubação Intratraqueal/efeitos adversos , Pneumonia Associada à Ventilação Mecânica/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia
3.
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
4.
PLoS One ; 15(8): e0237752, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817626

RESUMO

Pseudomonas aeruginosa remains a leading cause of nosocomial and serious life-threatening infections, and contributes to increased mortality in immunocompromised individuals. P. aeruginosa infection triggers host immune response and often provokes potent inflammatory mediators, which do not necessarily eradicate the causative pathogen. On the other hand, it causes severe airway damage and eventually decreased lung function. Such unfavorable outcomes of inflammatory injury have necessitated the development of novel effective agents that can combat with P. aeruginosa-mediated inflammation. Herein, we investigated the potential of quercetin in regulating P. aeruginosa-induced inflammation, with particular emphasized on the interleukin-1ß (IL-1ß). Our results showed that quercetin exerted the potent inhibitory activity against the production of IL-1ß in macrophages infected by live P. aeruginosa PAO1, without exhibiting cytotoxicity. According to our settings, such the potent inhibitory activity of quercetin was clearly demonstrated through its ability to efficiently inhibit IL-1ß during P. aeruginosa infection, pre- or even post-infection. In addition, quercetin strongly suppressed MAPK signaling pathway by inhibiting phosphorylation of the p38 MAPK and JNK2, and molecular docking study supported well with this observation. Moreover, quercetin reduced the NLRP3 expression and inhibited the P. aeruginosa-mediated cleavage of caspase-1 as well as mature IL-1ß. These results thus indicated that quercetin inhibition of P. aeruginosa-induced IL-1ß production is mediated by suppressing the initial priming step and by inhibiting the NLRP3 inflammasome activation. Taken together, our findings demonstrated the promising regulatory activity of quercetin against IL-1ß production in P. aeruginosa-infected macrophages, and indicated that quercetin has the potential to be effective as a novel therapeutic agent for treatment of P. aeruginosa-induced inflammation.


Assuntos
Interleucina-1beta/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Infecções por Pseudomonas/tratamento farmacológico , Quercetina/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/genética , Macrófagos/efeitos dos fármacos , Macrófagos/microbiologia , Infecções por Pseudomonas/genética , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Transdução de Sinais/efeitos dos fármacos
5.
PLoS One ; 15(8): e0237263, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764812

RESUMO

BACKGROUND: Chronic infected wounds are generally difficult to manage and treatment can be particularly challenging in resource-limited settings where diagnostic testing is not readily available. In this study, the epidemiology of microbial pathogens in chronically infected wounds in rural Ghana was assessed to support therapeutic choices for physicians. METHODS: Culture-based bacterial diagnostics including antimicrobial resistance testing were performed on samples collected from patients with chronic wounds at a hospital in Asante Akim North Municipality, Ghana. Fungal detection was performed by broad-range fungal PCR and sequencing of amplicons. RESULTS: In total, 105 patients were enrolled in the study, from which 207 potential bacterial pathogens were isolated. Enterobacteriaceae (n = 84, 41%) constituted the most frequently isolated group of pathogens. On species level, Pseudomonas aeruginosa (n = 50, 24%) and Staphylococcus aureus (n = 28, 14%) were predominant. High resistance rates were documented, comprising 29% methicillin resistance in S. aureus as well as resistance to 3rd generation cephalosporins and fluoroquinolones in 33% and 58% of Enterobacteriaceae, respectively. One P. aeruginosa strain with carbapenem resistance was identified. The most frequently detected fungi were Candida tropicalis. CONCLUSIONS: The pathogen distribution in chronic wounds in rural Ghana matched the internationally observed patterns with a predominance of P. aeruginosa and S. aureus. Very high resistance rates discourage antibiotic therapy but suggest an urgent need for microbiological diagnostic approaches, including antimicrobial resistance testing to guide the management of patients with chronic wounds in Ghana.


Assuntos
Antibacterianos/farmacologia , Bactérias/isolamento & purificação , Fungos/isolamento & purificação , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Adulto , Idoso , Animais , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Candida tropicalis/efeitos dos fármacos , Candida tropicalis/isolamento & purificação , Farmacorresistência Bacteriana , Farmacorresistência Fúngica , Feminino , Fungos/efeitos dos fármacos , Gana/epidemiologia , Hospitais de Distrito , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Infecção dos Ferimentos/epidemiologia , Adulto Jovem
6.
Int J Nanomedicine ; 15: 5147-5163, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764942

RESUMO

Background: In the last decades, nosocomial infections caused by drug-resistant Pseudomonas aeruginosa became a common problem in healthcare facilities. Antibiotics are becoming less effective as new resistant strains appear. Therefore, the development of novel enhanced activity antibacterial agents becomes very significant. A combination of nanomaterials with different physical and chemical properties enables us to generate novel multi-functional derivatives. In this study, graphene oxide and polyvinylpyrrolidone-stabilized silver nanoparticles hybrid nanocomposite (GO-Ag HN) were synthesized. The relation between antibiotic resistance and GO-Ag HN potential toxicity to clinical P. aeruginosa strains, their antibiotic resistance, and molecular mechanisms were assessed. Methods: Chemical state, particle size distribution, and morphology of synthesized GO-Ag NH were investigated using spectroscopy and microscopy techniques (UV-Vis, FTIR, XPS, TEM, SEM, AFM). Broad-spectrum antibiotic resistance of P. aeruginosa strains was determined using E-test. Antibiotic resistance genes were identified using polymerase chain reaction (PCR). Results: In this study, the toxicity of the GO-Ag NH to the isolated clinical P. aeruginosa strains has been investigated. A high antibiotic resistance level (92%) was found among P. aeruginosa strains. The most prevalent antibiotic resistance gene among tested strains was the AMPC beta-lactamase gene (65.6%). UV-vis, FTIR, and XPS studies confirmed the formation of the silver nanoparticles on the GO nanosheets. The functionalization process occurred through the interaction between Ag nanoparticles, GO, and polyvinylpyrrolidone used for nanoparticle stabilization. SEM analysis revealed that GO nanosheets undergo partial fragmentation during hybrid nanocomposite preparation, which remarkably increases the number of sharp edges and their mediated cutting effect. TEM analysis showed that GO-Ag HN spherical Ag nanoparticles mainly 9-12 nm in size were irregularly precipitated on the GO nanosheet surface. A higher density of Ag NPs was observed in the sheets' wrinkles, corrugations, and sharp edges. This hybrid nanocomposite poses enhanced antibacterial activity against carbapenem-resistant P. aeruginosa strains through a possible synergy between toxicity mechanisms of GO nanosheets and Ag nanoparticles. With incubation time increasing up to 10 minutes, the survival of P. aeruginosa decreased significantly. Conclusion: A graphene oxide and silver nanoparticles hybrid composite has been shown to be a promising material to control nosocomial infections caused by bacteria strains resistant to most antibiotics.


Assuntos
Farmacorresistência Bacteriana/genética , Grafite/química , Grafite/farmacologia , Nanopartículas Metálicas/química , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Prata/química , Antibacterianos/química , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos
7.
PLoS One ; 15(7): e0235740, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32678859

RESUMO

This study evaluated the larvicidal activity of Origanum majorana Linnaeus essential oil, identified the chemical composition, evaluated the antimicrobial, cytotoxic and antioxidant potential. The larvicidal activity was evaluated against larvae of the third stage of Aedes aegypti Linaeus, whereas the chemical composition was identified by gas chromatography coupled to mass spectrometer, the antimicrobial activity was carried out against the bacteria Pseudomonas aeruginosa, Escherichia coli and Staphylococcus auereus, the antioxidant activity was evaluated from of 2.2-diphenyl-1-picryl-hydrazila sequestration and Artemia salina Leach cytotoxicity. Regarding to the results, the larvicidal activity showed that O. majorana L. essential oil caused high mortality in A. aegypti L. larvae. In the chromatographic analysis, the main component found in O. majorana L. essential oil was pulegone (57.05%), followed by the other components verbenone (16.92%), trans-p-menthan-2-one (8.57%), iso-menthone (5.58%), piperitone (2.83%), 3-octanol (2.35%) and isopulegol (1.47%). The antimicrobial activity showed that E. coli and P. aeruginosa bacteria were more sensitive to oil than S. aureus, which was resistant at all concentrations. Essential oil did not present antioxidant activity, but it has high cytotoxic activity against A. salina L.


Assuntos
Aedes/efeitos dos fármacos , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Óleos Voláteis/farmacologia , Origanum/química , Animais , Antibacterianos/química , Antioxidantes/farmacologia , Bactérias/crescimento & desenvolvimento , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Folhas de Planta/química , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
8.
Int J Nanomedicine ; 15: 4607-4623, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636621

RESUMO

Aim: The interaction of NPs with biological systems may reveal useful details about their pharmacodynamic, anticancer and antibacterial effects. Methods: Herein, the interaction of as-synthesized Co3O4 NPs with HSA was explored by different kinds of fluorescence and CD spectroscopic methods, as well as molecular docking studies. Also, the anticancer effect of Co3O4 NPs against leukemia K562 cells was investigated by MTT, LDH, caspase, real-time PCR, ROS, cell cycle, and apoptosis assays. Afterwards, the antibacterial effects of Co3O4 NPs against three pathogenic bacteria were disclosed by antibacterial assays. Results: Different characterization methods such as TEM, DLS, zeta potential and XRD studies proved that fabricated Co3O4 NPs by sol-gel method have a diameter of around 50 nm, hydrodynamic radius of 177 nm with a charge distribution of -33.04 mV and a well-defined crystalline phase. Intrinsic, extrinsic, and synchronous fluorescence as well as CD studies, respectively, showed that the HSA undergoes some fluorescence quenching, minor conformational changes, microenvironmental changes as well as no structural changes in the secondary structure, after interaction with Co3O4 NPs. Molecular docking results also verified that the spherical clusters with a dimension of 1.5 nm exhibit the most binding energy with HSA molecules. Anticancer assays demonstrated that Co3O4 NPs can selectively lead to the reduction of K562 cell viability through the cell membrane damage, activation of caspase-9, -8 and -3, elevation of Bax/Bcl-2 mRNA ratio, ROS production, cell cycle arrest, and apoptosis. Finally, antibacterial assays disclosed that Co3O4 NPs can stimulate a promising antibacterial effect against pathogenic bacteria. Conclusion: In general, these observations can provide useful information for the early stages of nanomaterial applications in therapeutic platforms.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Cobalto/química , Cobalto/farmacologia , Nanopartículas Metálicas/química , Óxidos/química , Óxidos/farmacologia , Albumina Sérica Humana/metabolismo , Antibacterianos/química , Antibacterianos/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cobalto/metabolismo , Escherichia coli/efeitos dos fármacos , Humanos , Células K562 , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Óxidos/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Albumina Sérica Humana/química , Staphylococcus aureus/efeitos dos fármacos , Difração de Raios X
9.
PLoS One ; 15(7): e0236599, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32722685

RESUMO

The increasing prevalence of carbon nanotubes (CNTs) as components of new functional materials has the unintended consequence of causing increases in CNT concentrations in aqueous environments. Aqueous systems are reservoirs for bacteria, including human and animal pathogens, that can form biofilms. At high concentrations, CNTs have been shown to display biocidal effects; however, at low concentrations, the interaction between CNTs and bacteria is more complicated, and antimicrobial action is highly dependent upon the properties of the CNTs in suspension. Here, impact of low concentrations of multiwalled CNTs (MWCNTs) on the biofilm-forming opportunistic human pathogen Pseudomonas aeruginosa is studied. Using phase contrast and confocal microscopy, flow cytometry, and antibiotic tolerance assays, it is found that sub-lethal concentrations (2 mg/L) of MWCNTs promote aggregation of P. aeruginosa into multicellular clusters. However, the antibiotic tolerance of these "young" bacterial-CNT aggregates is similar to that of CNT-free cultures. Overall, our results indicate that the co-occurrence of MWCNTs and P. aeruginosa in aqueous systems, which promotes the increased number and size of bacterial aggregates, could increase the dose to which humans or animals are exposed.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Nanotubos de Carbono/química , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Suspensões
10.
Artigo em Inglês | MEDLINE | ID: mdl-32614255

RESUMO

Recently, Silver nanoparticles (AgNPs) have become widely applied nanomaterial in human contacting areas such as cosmetics, food and medicine due to their antibacterial property. On the other hand, surfactants are essential ingredient of several industrial and consumer formulations. Based on these important applications, the current research was aimed to carry out the synthesis and characterization of Tween 80 capped silver nanoparticles (T80-AgNPs) using gamma radiation reduction method. Characterization of T80-AgNPs was occurred by using UV-Vis, XRD, FTIR and TEM techniques. UV-Visible spectra showed surface plasmon resonance (SPR) peak in the range of 420 nm signifying the synthesis of colloidal AgNPs. TEM confirmed the formation of spherical and uniformly distributed AgNPs with average size of 18 nm. XRD analysis illustrated the formation of pure crystalline AgNPs. The FTIR analysis provides evidence for the stabilization of AgNPs by Tween 80. The synthesized T80-AgNPs were evaluated for antibacterial activity against both Escherichia coli (E. coli) as gram negative (G -ve) bacteria and Staphylococcus aureus (S. aureus) as gram positive (G + ve) bacteria and anti-biofilm activity to P. aeruginosa. The results show that T80-AgNPs exhibits excellent antibacterial and antibiofilm activities.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Raios gama , Nanopartículas Metálicas/química , Polissorbatos/química , Prata/química , Biofilmes/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Prata/farmacologia , Nitrato de Prata/química , Staphylococcus aureus/efeitos dos fármacos
11.
Proc Natl Acad Sci U S A ; 117(32): 19455-19464, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32703812

RESUMO

A better understanding of how antibiotic exposure impacts the evolution of resistance in bacterial populations is crucial for designing more sustainable treatment strategies. The conventional approach to this question is to measure the range of concentrations over which resistant strain(s) are selectively favored over a sensitive strain. Here, we instead investigate how antibiotic concentration impacts the initial establishment of resistance from single cells, mimicking the clonal expansion of a resistant lineage following mutation or horizontal gene transfer. Using two Pseudomonas aeruginosa strains carrying resistance plasmids, we show that single resistant cells have <5% probability of detectable outgrowth at antibiotic concentrations as low as one-eighth of the resistant strain's minimum inhibitory concentration (MIC). This low probability of establishment is due to detrimental effects of antibiotics on resistant cells, coupled with the inherently stochastic nature of cell division and death on the single-cell level, which leads to loss of many nascent resistant lineages. Our findings suggest that moderate doses of antibiotics, well below the MIC of resistant strains, may effectively restrict de novo emergence of resistance even though they cannot clear already-large resistant populations.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Modelos Teóricos , Plasmídeos/genética , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/crescimento & desenvolvimento , Análise de Célula Única , Processos Estocásticos
12.
PLoS One ; 15(6): e0235059, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574199

RESUMO

BACKGROUND: To support effective antibiotic selection in empirical treatments, infection control interventions, and antimicrobial resistance containment strategies, many medical institutions collect antimicrobial susceptibility test data conducted at their facilities to prepare cumulative antibiograms. AIM: To evaluate how the setpoints of duplicate isolate removal period and data collection period affect the calculated susceptibility rates in antibiograms. METHODS: The Sakai City Medical Center is a regional core hospital for tertiary emergency medical care with 480 beds for general clinical care. In this study, all the Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae isolates collected at the Sakai City Medical Center Clinical Laboratory between July 2013 and December 2018 were subjected to antimicrobial susceptibility tests and the resulting data was analyzed. FINDINGS: The longer the duplicate isolate removal period, the fewer the isolates are available for every bacterial species. Differences in the length of the duplicate isolate removal period affected P. aeruginosa susceptibility rates to ß-lactam antibiotics by up to 10.8%. The setpoint of the data collection period affected the antimicrobial susceptibility rates by up to 7.3%. We found that a significant change in susceptibility could be missed depending on the setting of the data collection period, in preparing antibiogram of ß-lactam antibiotics for P. aeruginosa. CONCLUSIONS: When referring to antibiograms, medical professionals involved in infectious disease treatment should be aware that the parameter values, such as the duplicate isolate removal period and the data collection period, affect P. aeruginosa susceptibility rates especially to ß-lactam antibiotics. And antibiogram should be updated within the shortest time period that is practically possible, taking into account restrictions such as numbers of specimen.


Assuntos
Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Testes de Sensibilidade Microbiana/normas , Pseudomonas aeruginosa/efeitos dos fármacos , Algoritmos , Serviço Hospitalar de Emergência , Escherichia coli/isolamento & purificação , Escherichia coli/fisiologia , Hospitalização/estatística & dados numéricos , Humanos , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/fisiologia , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/fisiologia , Centros de Atenção Terciária , Fatores de Tempo
13.
Life Sci ; 257: 117999, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32585244

RESUMO

AIM: This paper was mainly aimed at synthesis of Ce-containing nano-Mg-phosphate ceramic as a multifunctional material. MATERIALS AND METHODS: Two ceramics based on Mg3(PO4)2 and Ce0.2Mg2.8(PO4)2 formulas (MP and MP-C, respectively) were synthesized. The synthesized powders were characterized by XRD, TEM, Zeta potential, and FTIR. Also, their dissolution behavior was tested in Tris-HCl buffer solution. Moreover, the antimicrobial efficacy was evaluated against gram-positive bacteria (Bacillus sphaericus MTCC 511 &Staphylococcus aureus MTCC 87) and gram-negative bacteria (Enterobacter aerogenes MTCC 111 &Pseudomonas aeruginosa MTCC 1034) using dick diffusion assay and microdilution method. Furthermore, the cell viability test was performed for the ceramics on Vero cells (African green monkey kidney cells), and their antitumor activity was determined by PC3 cell line (prostatic cancer). Also, the cellular uptake was determined by the flow cytometry. KEY FINDINGS: The results showed that the substitution of Mg by Ce decreased the particle size from 40 to 90 nm for MP sample to 2-10 nm for MP-C sample and increased the degradation rate. Both samples showed excellent antimicrobial activities. Moreover, MP demonstrated more cell viability than MP-C on Vero cells at high concentrations, whereas, MP-C showed more antitumor activity on PC3 cells than MP sample. Moreover, MP-C showed a higher cell uptake than MP due to its smaller size and more negative charge. SIGNIFICANCE: Mg-phosphate ceramic can be used in this study successfully as a delivery system for cerium ions and showed a high antitumor activity, which makes it highly recommended as safe and effective cancer treatment materials.


Assuntos
Cerâmica/farmacologia , Cério/farmacologia , Compostos de Magnésio/farmacologia , Fosfatos/farmacologia , Animais , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Bacillaceae/efeitos dos fármacos , Osso e Ossos/microbiologia , Osso e Ossos/cirurgia , Sobrevivência Celular , Cério/metabolismo , Chlorocebus aethiops , Enterobacter aerogenes/efeitos dos fármacos , Humanos , Compostos de Magnésio/metabolismo , Testes de Sensibilidade Microbiana/métodos , Células PC-3 , Fosfatos/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Células Vero
14.
J Vis Exp ; (159)2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32478743

RESUMO

When developing novel antimicrobials, the success of animal trials is dependent on accurate extrapolation of antimicrobial efficacy from in vitro tests to animal infections in vivo. The existing in vitro tests typically overestimate antimicrobial efficacy as the presence of host tissue as a diffusion barrier is not accounted for. To overcome this bottleneck, we have developed an ex vivo porcine corneal model of bacterial keratitis using Pseudomonas aeruginosa as a prototypic organism. This article describes the preparation of the porcine cornea and protocol for establishment of the infection. Bespoke glass molds enable straightforward setup of the cornea for infection studies. The model mimics in vivo infection as bacterial proliferation is dependent on the ability of the bacterium to damage corneal tissue. Establishment of infection is verified as an increase in the number of colony forming units assessed via viable plate counts. The results demonstrate that infection can be established in a highly reproducible fashion in the ex vivo corneas using the method described here. The model can be extended in the future to mimic keratitis caused by microorganisms other than P. aeruginosa. The ultimate aim of the model is to investigate the effect of antimicrobial chemotherapy on the progress of bacterial infection in a scenario more representative of in vivo infections. In so doing, the model described here will reduce the use of animals for testing, improve success rates in clinical trials and ultimately enable rapid translation of novel antimicrobials to the clinic.


Assuntos
Córnea/microbiologia , Córnea/patologia , Infecções Oculares Bacterianas/tratamento farmacológico , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Córnea/efeitos dos fármacos , Modelos Animais de Doenças , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/terapia , Ceratite/terapia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Esterilização , Suínos
15.
J Vis Exp ; (159)2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32478753

RESUMO

Antimicrobial resistance, a major consequence of diagnostic uncertainty and antimicrobial overprescription, is an increasingly recognized cause of severe infections, complications, and mortality worldwide with a huge impact on our society and on the health system. In particular, patients with compromised immune systems or pre-existing and chronic pathologies, such as cystic fibrosis (CF), are subjected to frequent antibiotic treatments to control the infections with the appearance and diffusion of multidrug resistant isolates. Therefore, there is an urgent need to address alternative therapies to counteract bacterial infections. Use of bacteriophages, the natural enemies of bacteria, can be a possible solution. The protocol detailed in this work describes the application of phage therapy against Pseudomonas aeruginosa infection in CF zebrafish embryos. Zebrafish embryos were infected with P. aeruginosa to demonstrate that phage therapy is effective against P. aeruginosa infections as it reduces lethality, bacterial burden and pro-inflammatory immune response in CF embryos.


Assuntos
Fibrose Cística/microbiologia , Fibrose Cística/terapia , Embrião não Mamífero/microbiologia , Terapia por Fagos , Infecções por Pseudomonas/terapia , Pseudomonas aeruginosa/fisiologia , Peixe-Zebra/embriologia , Peixe-Zebra/microbiologia , Animais , Antibacterianos/farmacologia , Bacteriófagos/fisiologia , Citocinas/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Proteínas de Fluorescência Verde/metabolismo , Mediadores da Inflamação/metabolismo , Microinjeções , Morfolinos/farmacologia , Terapia por Fagos/efeitos adversos , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Reprodutibilidade dos Testes
16.
J Vis Exp ; (159)2020 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-32510504

RESUMO

Swarming is a form of surface motility observed in many bacterial species including Pseudomonas aeruginosa and Escherichia coli. Here, dense populations of bacteria move over large distances in characteristic tendril-shaped communities over the course of hours. Swarming is sensitive to several factors including medium moisture, humidity, and nutrient content. In addition, the collective stress response, which is observed in P. aeruginosa that are stressed by antibiotics or bacteriophage (phage), repels swarms from approaching the area containing the stress. The methods described here address how to control the critical factors that affect swarming. We introduce a simple method to monitor swarming dynamics and the collective stress response with high temporal resolution using a flatbed document scanner, and describe how to compile and perform a quantitative analysis of swarms. This simple and cost-effective method provides precise and well-controlled quantification of swarming and may be extended to other types of plate-based growth assays and bacterial species.


Assuntos
Pseudomonas aeruginosa/fisiologia , Estresse Fisiológico , Imagem com Lapso de Tempo , Antibacterianos/farmacologia , Bacteriófagos/fisiologia , Análise Custo-Benefício , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/virologia , Imagem com Lapso de Tempo/economia
17.
Arch Microbiol ; 202(8): 2181-2188, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32519021

RESUMO

Bacterial quorum sensing (QS) system regulates the production of most costly but sharable extracellular products (public goods) in a growth-phase-dependent manner, and the development of this energy-intensive process is susceptible to environmental changes. However, the role of nutrient factors in dominating the QS-mediated cooperative interaction and intracellular metabolism still remains less understood. Here we studied the performance of QS system by growing Pseudomonas aeruginosa under different nutrient and culture conditions. The results of comparative-transcriptomic analyses revealed that carbon source-limitation was the main factor suppressing the activation of QS system, and a substantial number of public-good-encoding genes were induced when phosphorus is limiting in short-term culture. By contrast, although the QS regulation of P. aeruginosa in all the cultures was generally decreased along with the enrichment of QS-deficient individuals during evolution, limitation of different nutrient factors had discrepant effects in directing the formation of population structure by coordinating the production of public goods and primary metabolism, especially the starch and sucrose metabolism. These findings demonstrate the pleiotropy of QS regulation in balancing the development of cooperative behavior and metabolism, and provide a reference for further understanding the role of QS system in causing persistent infections.


Assuntos
Pseudomonas aeruginosa/fisiologia , Percepção de Quorum/fisiologia , Meios de Cultura/farmacologia , Nutrientes/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos
18.
Int J Nanomedicine ; 15: 3393-3404, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32523339

RESUMO

Introduction: The efficacy of several antimicrobial agents has been hindered due to the increasing frequency of multidrug-resistant (MDR) Pseudomonas aeruginosa strains. So, the need for new antibacterial drugs or drug combinations is urgent. Recently, desirable antibacterial effects were reported for many metals nanoparticles such as TiO2 nanoparticles (TDNs). Purpose: This study aims to investigate the prevalence of MDR P. aeruginosa and assess the efficiency of TDN in the treatment of MDR P. aeruginosa-associated infections. Materials and Methods: The synthesis of TDN by the sol-gel method was carried out. Particle size measurements and morphology were done using dynamic light scattering (DLS) and high-resolution transmission electron microscopy (HR-TEM). To investigate the physical and chemical changes of drugs due to the combination, the tested drugs, both alone and in combination with TDN, were subjected to differential scanning calorimetry (DSC), infrared (IR) spectroscopy, and X-ray diffraction studies. Antimicrobial susceptibility was detected by agar disc-diffusion assay. The minimum inhibitory concentration (MIC) of TDN and the tested antibiotics were assessed by the agar dilution method. Checkerboard analysis was performed to determine the combined effect of TDN and the tested antibiotics against 25 MDR P. aeruginosa strains. Results: TDNs were prepared with an average particle size of 64.77 ± 0.14 nm with an accepted polydispersity index (PDI) value of 0.274 ± 0.004. TEM showed that the particles were shaped into irregular spheres. Twenty-five P. aeruginosa isolates that were absolutely resistant to cefepime (100%), highly resistant to ceftriaxone (96%), amikacin (80%), and ciprofloxacin (76%) were selected. Superior antibacterial activity of TDN was observed against the selected 25 MDR P. aeruginosa isolates. The combination of TDN and cefepime were found to show synergistic activity against all tested isolates followed by ceftriaxone (96%), amikacin (88%), and ciprofloxacin (80%). Conclusion: Using TDN in combination with antibiotics can help in the treatment of MDR P. aeruginosa-associated infections. So, preparation of topical pharmaceutical dosage forms containing a combination of these antibiotics and TDN can be useful against MDR P. aeruginosa.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Nanopartículas/química , Pseudomonas aeruginosa/efeitos dos fármacos , Titânio/farmacologia , Antibacterianos/uso terapêutico , Calorimetria , Ciprofloxacino/farmacologia , Ciprofloxacino/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Nanopartículas/ultraestrutura , Tamanho da Partícula , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/isolamento & purificação , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
19.
Cochrane Database Syst Rev ; 6: CD009528, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32520436

RESUMO

BACKGROUND: Clinicians typically select the antibiotics used to treat pulmonary infections in people with cystic fibrosis based on the results of antimicrobial susceptibility testing performed on bacteria traditionally grown in a planktonic mode (grown in a liquid). However, there is considerable evidence to suggest that Pseudomonas aeruginosa actually grows in a biofilm (or slime layer) in the airways of people with cystic fibrosis with chronic pulmonary infections. Therefore, choosing antibiotics based on biofilm rather than conventional antimicrobial susceptibility testing could potentially improve response to treatment of Pseudomonas aeruginosa in people with cystic fibrosis. This is an update of a previously published Cochrane Review. OBJECTIVES: To compare biofilm antimicrobial susceptibility testing-driven therapy to conventional antimicrobial susceptibility testing-driven therapy in the treatment of Pseudomonas aeruginosa infection in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Most recent search: 07 April 2020. We also searched two ongoing trials registries and the reference lists of relevant articles and reviews. Most recent searches: 07 April 2020 and 05 September 2017. SELECTION CRITERIA: Randomized controlled trials (RCTs) of antibiotic therapy based on biofilm antimicrobial susceptibility testing compared to antibiotic therapy based on conventional antimicrobial susceptibility testing in the treatment of Pseudomonas aeruginosa pulmonary infection in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two authors independently selected RCTs, assessed their risk of bias and extracted data from eligible trials. Additionally, the review authors contacted the trial investigators to obtain further information. The quality of the evidence was assessed using the GRADE criteria. MAIN RESULTS: The searches identified two multicentre, double-blind RCTs eligible for inclusion in the review with a total of 78 participants (adults and children); one RCT was undertaken in people who were clinically stable, the second was in people experiencing pulmonary exacerbations. Both RCTs prospectively assessed whether the use of biofilm antimicrobial susceptibility testing improved microbiological and clinical outcomes in participants with cystic fibrosis who were infected with Pseudomonas aeruginosa. The primary outcome was the change in sputum Pseudomonas aeruginosa density from the beginning to the end of antibiotic therapy. Although the intervention was shown to be safe, the data from these two RCTs did not provide evidence that biofilm susceptibility testing was superior to conventional susceptibility testing either in terms of microbiological or lung function outcomes. One of the trials also measured risk and time to subsequent exacerbation as well as quality of life measures and did not demonstrate any difference between groups in these outcomes. Both RCTs had an overall low risk of bias and the quality of the evidence using GRADE criteria was deemed to be moderate to high for the outcomes selected. AUTHORS' CONCLUSIONS: The current evidence is insufficient to recommend choosing antibiotics based on biofilm antimicrobial susceptibility testing rather than conventional antimicrobial susceptibility testing in the treatment of Pseudomonas aeruginosa pulmonary infections in people with cystic fibrosis. Biofilm antimicrobial susceptibility testing may be more appropriate in the development of newer, more effective formulations of drugs which can then be tested in clinical trials.


Assuntos
Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Fibrose Cística/complicações , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções Respiratórias/tratamento farmacológico , Adolescente , Adulto , Biofilmes/crescimento & desenvolvimento , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Infecções por Pseudomonas/complicações , Pseudomonas aeruginosa/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Respiratórias/microbiologia , Escarro/microbiologia
20.
Cochrane Database Syst Rev ; 5: CD006961, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32412092

RESUMO

BACKGROUND: Antibiotic therapy for acute pulmonary exacerbations in people with cystic fibrosis is usually chosen based on the results of antimicrobial susceptibility testing of individual drugs. Combination antimicrobial susceptibility testing assesses the efficacy of drug combinations including two or three antibiotics in vitro and can often demonstrate antimicrobial efficacy against bacterial isolates even when individual antibiotics have little or no effect. Therefore, choosing antibiotics based on combination antimicrobial susceptibility testing could potentially improve response to treatment in people with cystic fibrosis with acute exacerbations. This is an updated version of a previously published review. OBJECTIVES: To compare antibiotic therapy based on conventional antimicrobial susceptibility testing to antibiotic therapy based on combination antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in people with cystic fibrosis and chronic infection with Pseudomonas aeruginosa. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of latest search: 19 March 2020. We also searched ongoing trials registries. Date of latest search: 07 April 2020. SELECTION CRITERIA: Randomised and quasi-randomised controlled studies of antibiotic therapy based on conventional antimicrobial susceptibility testing compared to antibiotic therapy based on combination antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in cystic fibrosis due to chronic infection with Pseudomonas aeruginosa. DATA COLLECTION AND ANALYSIS: Both authors independently selected studies, assessed their quality and extracted data from eligible studies. Additionally, the authors contacted the study investigators to obtain further information. MAIN RESULTS: The search identified one multicentre study eligible for inclusion in the review. This study prospectively assessed whether the use of multiple combination bactericidal antibiotic testing improved clinical outcomes in participants with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria. A total of 132 participants were randomised in the study. The study investigators provided data specific to the 82 participants who were only infected with Pseudomonas aeruginosa for their primary outcome of time until next pulmonary exacerbation. For participants specifically infected with only Pseudomonas aeruginosa, the hazard ratio of a subsequent exacerbation was 0.82, favouring the control group (95% confidence interval 0.44 to 1.51) (P = 0.52). No further data for any of this review's outcomes specific to participants infected with Pseudomonas aeruginosa were available. The risk of bias for the included study was deemed to be low. The quality of the evidence was moderate for the only outcome providing data solely for individuals with infection due to Pseudomonas aeruginosa. For other outcomes, we were unable to judge the quality of the evidence as no data were available for the relevant subset of participants. AUTHORS' CONCLUSIONS: The current evidence, limited to one study, shows that there is insufficient evidence to determine effect of choosing antibiotics based on combination antimicrobial susceptibility testing compared to choosing antibiotics based on conventional antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in people with cystic fibrosis with chronic Pseudomonas aeruginosa infection. A large international and multicentre study is needed to further investigate this issue. The only study included in the review was published in 2005, and we have not identified any further relevant studies up to March 2017. We therefore do not plan to update this review until new studies are published.


Assuntos
Antibacterianos/uso terapêutico , Fibrose Cística/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa , Doença Crônica , Progressão da Doença , Quimioterapia Combinada , Humanos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto
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