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1.
Drugs Today (Barc) ; 56(9): 583-598, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33025952

RESUMO

Acute bacterial skin and skin structure infections (ABSSSIs) are one of the most common types of infections due to methicillin-resistant Staphylococcus aureus (MRSA). The standard of care for ABSSSI includes glycopeptides such as vancomycin, teicoplanin, oxazolidinones and fluoroquinolones, which are potent broad-spectrum antibacterial agents. Unfortunately, due to indiscriminate utilization, resistance to these agents is rising and identification of novel agents is an urgent unmet medical need. In this context, levonadifloxacin (WCK-771) is a novel, hydrate arginine salt of nadifloxacin with improved bactericidal activity against MRSA as well as fluoroquinolone-resistant S. aureus by targeting bacterial DNA supercoiling enzymes DNA gyrase and topoisomerase IV. Levonadifloxacin displays a broad-spectrum bactericidal activity against Gram-positive and Gram-negative bacteria, atypical bacteria, anaerobic bacteria and bioterror pathogens with a very low frequency of mutation. Levonadifloxacin also displays improved activity under low pH biofilm environments. The drug has successfully completed phase I, phase II and phase III clinical trials in India. The U.S. Food and Drug Administration (FDA) granted a Qualified Infectious Disease Product (QIDP) designation to levonadifloxacin for the treatment of MRSA infections in August 2014.


Assuntos
Antibacterianos/uso terapêutico , Quinolizinas/uso terapêutico , Quinolonas/uso terapêutico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Ensaios Clínicos como Assunto , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
2.
AAPS PharmSciTech ; 21(7): 286, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33063151

RESUMO

The CoViD-19 pandemic has caused a sudden spike in demand and production of hand sanitisers. Concerns are rising regarding the quality of such products, as the safeguard of consumers is a priority worldwide. We analyse here the ethanolic content of seven off-the-shelf hand sanitiser gels (two biocides and five cosmetics) from the Italian market, using gas chromatography. The WHO recommends that products containing ethanol should have 60-95% (v/v) alcohol. Four of the tested hand gels have ethanolic contents within the recommended range, while three products (all cosmetics) contain < 60% (v/v), i.e. 52.1% (w/w), ethanol. The product with the lowest alcoholic content has 37.1% w/w ethanol. Toxic methanol is not found in any of the hand sanitisers. We show, in addition, that products with the highest ethanolic content have generally greater antibacterial activity. In conclusion, all tested products are complying with the EU regulations, as the three "substandard" products are classified as cosmetics, whose purpose is cleaning and not disinfecting. Nevertheless, if such hand cleaners were inappropriately used as hand disinfectants, they might be ineffective. Thus, consumer safety relays on awareness and ability to distinguish between biocidal and cosmetics hand gels. The obtained results might sensitise the scientific community, health agencies and ultimately consumers towards the risks of using hand sanitisers of substandard alcoholic concentration. If the wrong product is chosen by consumers, public health can be compromised by the inappropriate use of "low-dosed" cosmetic gels as disinfectants, particularly during the period of the CoViD-19 pandemic.


Assuntos
Infecções por Coronavirus , Higienizadores de Mão/análise , Pandemias , Pneumonia Viral , Antibacterianos/análise , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Cromatografia Gasosa , Cosméticos , Escherichia coli/efeitos dos fármacos , Etanol/análise , Europa (Continente) , Géis , Desinfecção das Mãos , Higienizadores de Mão/farmacologia , Higienizadores de Mão/normas , Metanol/análise , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos
3.
BMC Infect Dis ; 20(1): 646, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873235

RESUMO

BACKGROUND: COVID-19 is known as a new viral infection. Viral-bacterial co-infections are one of the biggest medical concerns, resulting in increased mortality rates. To date, few studies have investigated bacterial superinfections in COVID-19 patients. Hence, we designed the current study on COVID-19 patients admitted to ICUs. METHODS: Nineteen patients admitted to our ICUs were enrolled in this study. To detect COVID-19, reverse transcription real-time polymerase chain reaction was performed. Endotracheal aspirate samples were also collected and cultured on different media to support the growth of the bacteria. After incubation, formed colonies on the media were identified using Gram staining and other biochemical tests. Antimicrobial susceptibility testing was carried out based on the CLSI recommendations. RESULTS: Of nineteen COVID-19 patients, 11 (58%) patients were male and 8 (42%) were female, with a mean age of ~ 67 years old. The average ICU length of stay was ~ 15 days and at the end of the study, 18 cases (95%) expired and only was 1 case (5%) discharged. In total, all patients were found positive for bacterial infections, including seventeen Acinetobacter baumannii (90%) and two Staphylococcus aureus (10%) strains. There was no difference in the bacteria species detected in any of the sampling points. Seventeen of 17 strains of Acinetobacter baumannii were resistant to the evaluated antibiotics. No metallo-beta-lactamases -producing Acinetobacter baumannii strain was found. One of the Staphylococcus aureus isolates was detected as methicillin-resistant Staphylococcus aureus and isolated from the patient who died, while another Staphylococcus aureus strain was susceptible to tested drugs and identified as methicillin-sensitive Staphylococcus aureus. CONCLUSIONS: Our findings emphasize the concern of superinfection in COVID-19 patients due to Acinetobacter baumannii and Staphylococcus aureus. Consequently, it is important to pay attention to bacterial co-infections in critical patients positive for COVID-19.


Assuntos
Infecções por Acinetobacter/complicações , Acinetobacter baumannii/isolamento & purificação , Betacoronavirus/fisiologia , Coinfecção/epidemiologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Infecções Estafilocócicas/complicações , Staphylococcus aureus/isolamento & purificação , Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Complicações do Diabetes/epidemiologia , Feminino , Cardiopatias/complicações , Humanos , Hipertensão/complicações , Unidades de Terapia Intensiva , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Sistema Respiratório/microbiologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos
4.
Int J Nanomedicine ; 15: 6433-6449, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922010

RESUMO

Background: Electrospun nanofibers based on Colocasia esculenta tuber (CET) protein are considered as a promising material for wound dressing applications. However, the use of these nanofibers in aqueous conditions has poor stability. The present study was performed to obtain insights into the crosslinked electrospun CET's protein-chitosan (CS)-poly(ethylene oxide) (PEO) nanofibers and to evaluate their potential for wound dressing applications. Methods: The electrospun nanofibers were crosslinked with glutaraldehyde (GA) vapor and heat treatment (HT) to enhance their physicochemical stability. The crosslinked nanofibers were characterized by protein profiles, morphology structures, thermal behavior, mechanical properties, and degradation behavior. Furthermore, the antibacterial properties and cytocompatibility were analyzed by antibacterial assessment and cell proliferation. Results: The protein profiles of the electrospun CET's protein-CS-PEO nanofibers before and after HT crosslinking contained one major bioactive protein with a molecular weight of 14.4 kDa. Scanning electron microscopy images of the crosslinked nanofibers indicated preservation of the structure after immersion in phosphate buffered saline. The crosslinked nanofibers resulted in higher ultimate tensile strength and lower ultimate strain compared to the non-crosslinked nanofibers. GA vapor crosslinking showed higher water stability compared to HT crosslinking. The in vitro antibacterial activity of the crosslinked nanofibers showed a stronger bacteriostatic effect on Staphylococcus aureus than on Escherichia coli. Human skin fibroblast cell proliferation on crosslinked GA vapor and HT nanofibers with 1% (w/v) CS and 2% (w/v) CET's protein demonstrated the highest among all the other crosslinked nanofibers after seven days of cell culture. Cell proliferation and cell morphology results revealed that introducing higher CET's protein concentration on crosslinked nanofibers could increase cell proliferation of the crosslinked nanofibers. Conclusion: These results are promising for the potential use of the crosslinked electrospun CET's protein-CS-PEO nanofibers as bioactive wound dressing materials.


Assuntos
Antibacterianos/farmacologia , Quitosana/química , Colocasia/química , Reagentes para Ligações Cruzadas/química , Nanofibras/química , Proteínas de Plantas/química , Tubérculos/química , Polietilenoglicóis/química , Animais , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Células NIH 3T3 , Nanofibras/ultraestrutura , Proteínas de Plantas/ultraestrutura , Staphylococcus aureus/efeitos dos fármacos , Estresse Mecânico , Temperatura
5.
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
6.
BMC Infect Dis ; 20(1): 621, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32831057

RESUMO

BACKGROUND: We aimed to describe an outbreak of cutaneous abscesses caused by Panton-Valentine leukocidin (PVL)-producing methicillin-susceptible Staphylococcus aureus (MSSA) among gold mine workers. METHODS: In February 2018, we retrospectively reviewed a random sample of 50 medical records from 243 cases and conducted face-to-face interviews using a structured questionnaire. Pus aspirates were sent to the National Institute for Communicable Diseases from prospectively-identified cases (November 2017-March 2018). Nasopharyngeal swabs were collected during a colonisation survey in February 2018. Staphylococcus aureus isolates were screened with a conventional PCR for lukS/F-PV. Pulsed-field gel electrophoresis (PFGE) was performed to determine the genetic relatedness among the isolates. A sample of isolates were selected for whole genome sequencing (WGS). We conducted an assessment on biological risks associated with mining activities. RESULTS: From January 2017 to February 2018, 10% (350/3582) of mine workers sought care for cutaneous abscesses. Forty-seven medical files were available for review, 96% were male (n = 45) with a mean age of 43 years (SD = 7). About 52% (24/46) were involved in stoping and 28% (13/47) worked on a particular level. We cultured S. aureus from 79% (30/38) of cases with a submitted specimen and 14% (12/83) from colonisation swabs. All isolates were susceptible to cloxacillin. Seventy-one percent of S. aureus isolates (30/42) were PVL-PCR-positive. Six PFGE clusters were identified, 57% (21/37) were closely related. WGS analysis found nine different sequence types. PFGE and WGS analysis showed more than one cluster of S. aureus infections involving closely related isolates. Test reports for feed and product water of the mine showed that total plate counts were above the limits of 1000 cfu/ml, coliform counts > 10 cfu/100 ml and presence of faecal coliforms. Best practices were poorly implemented as some mine workers washed protective clothing with untreated water and hung them for drying at the underground surface. CONCLUSIONS: PVL-producing MSSA caused an outbreak of cutaneous abscesses among underground workers at a gold mining company. To our knowledge, no other outbreaks of PVL-producing S. aureus involving skin and soft tissue infections have been reported in mining facilities in South Africa. We recommend that worker awareness of infection prevention and control practices be strengthened.


Assuntos
Abscesso/microbiologia , Dermatopatias/epidemiologia , Infecções dos Tecidos Moles/epidemiologia , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/patogenicidade , Adulto , Toxinas Bacterianas/metabolismo , Surtos de Doenças , Eletroforese em Gel de Campo Pulsado , Exotoxinas/metabolismo , Feminino , Ouro , Humanos , Leucocidinas/metabolismo , Masculino , Meticilina/farmacologia , Pessoa de Meia-Idade , Mineradores , Estudos Retrospectivos , Dermatopatias/microbiologia , Infecções dos Tecidos Moles/microbiologia , África do Sul/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo
7.
Zhonghua Er Ke Za Zhi ; 58(8): 628-634, 2020 Aug 02.
Artigo em Chinês | MEDLINE | ID: mdl-32842382

RESUMO

Objective: To investigate the clinical characteristics of pediatric methicillin-resistant Staphylococcus aureus (MRSA) infection and the antibiotic sensitivity of the isolates. Methods: The clinical data of children with MRSA infection and antibiotic sensitivity of the isolates from 11 children's hospitals in Infectious Diseases Surveillance of Paediatrics (ISPED) group of China between January 1, 2018 and December 31, 2018 were collected retrospectively. The children's general condition, high-risk factors, antimicrobial therapy and prognosis, differences in clinical disease and laboratory test results between different age groups, and differences of antibiotic sensitivity between community-acquired (CA)-MRSA and hospital-acquired (HA)-MRSA were analyzed. The t test and Wilcoxon rank sum test were used for statistical analysis of the quantitative data and Chi-square test were used for comparison of rates. Results: Among the 452 patients, 264 were males and 188 were females, aged from 2 days to 17 years. There were 233 cases (51.5%) in the ≤1 year old group, 79 cases (17.5%) in the>1-3 years old group, 29 cases (6.4%) in the >3-5 years old group, 65 cases (14.4%) in the >5-10 years old group, and 46 cases (10.2%) in the>10 years old group. The main distributions of onset seasons were 55 cases (12.2%) in December, 47 cases (10.4%) in February, 46 cases (10.2%) in November, 45 cases (10.0%) in January, 40 cases (8.8%) in March. There were 335 cases (74.1%) CA-MRSA and 117 (25.9%) cases HA-MRSA. Among all cases, 174 cases (38.5%) had basic diseases or long-term use of hormone and immunosuppressive drugs. During the period of hospitalization, 209 cases (46.2%) received medical interventions. There were 182 patients (40.3%) had used antibiotics (ß-lactams, glycopeptides, macrolides, carbapenems, oxazolones, sulfonamides etc) 3 months before admission. The most common clinical disease was pneumonia (203 cases), followed by skin soft-tissue infection (133 cases), sepsis (92 cases), deep tissue abscess (42 cases), osteomyelitis (40 cases), and septic arthritis (26 cases), suppurative meningitis (10 cases). The proportion of pneumonia in the ≤1 year old group was higher than the >1-3 years old group,>3-5 years old group,>5-10 years old group,>10 years old group (57.5% (134/233) vs. 30.4% (24/79), 31.0% (9/29), 38.5% (25/65), 23.9% (11/46), χ(2)=17.374, 7.293, 7.410, 17.373, all P<0.01) The proportion of skin and soft tissue infections caused by CA-MRSA infection was higher than HA-MRSA (33.4% (112/335) vs. 17.9% (21/117), χ(2)=10.010, P=0.002), and the proportion of pneumonia caused by HA-MRSA infection was higher than CA-MRSA (53.0% (62/117) vs. 42.1% (141/335), χ(2)=4.166, P=0.041). The first white blood cell count of the ≤1 year old group was higher than that children > 1 year old ((15±8)×10(9)/L vs. (13±7)×10(9)/L, t=2.697, P=0.007), while the C-reactive protein of the ≤1 year old group was lower than the 1-3 years old group,>5-10 years old group,>10 years old group (8.00 (0.04-194.00) vs.17.00 (0.50-316.00), 15.20 (0.23-312.00), 21.79(0.13-219.00) mg/L, Z=3.207, 2.044, 2.513, all P<0.05), there were no significant differences in procalcitonin (PCT) between different age groups (all P>0.05). After the treatment, 131 cases were cured, 278 cases were improved, 21 cases were not cured, 12 cases died, and 10 cases were abandoned. The 452 MRSA isolates were all sensitive to vancomycin (100.0%), linezolid (100.0%), 100.0% resistant to penicillin, highly resistant to erythromycin (85.0%, 375/441), clindamycin (67.7%, 294/434), less resistant to sulfonamides (5.9%, 23/391), levofloxacin (4.5%, 19/423), gentamicin (3.2%, 14/438), rifampicin (1.8%, 8/440), minocycline (1.1%, 1/91). The antimicrobial resistance rates were not significantly different between the CA-MRSA and HA-MRSA groups (all P>0.05). Conclusions: The infection of MRSA is mainly found in infants under 3 years old. The prevalent seasons are winter and spring, and MRSA is mainly acquired in the community. The main clinical diseases are pneumonia, skin soft-tissue infection and sepsis. No MRSA isolate is resistant to vancomycin, linezolid. MRSA isolates are generally sensitive to sulfonamides, levofloxacin, gentamicin, rifampicin, minocycline, and were highly resistant to erythromycin and clindamycin. To achieve better prognosis. clinicians should initiate anti-infective treatment for children with MRSA infection according to the clinical characteristics of patients and drug sensitivity of the isolates timely and effectively.


Assuntos
Antibacterianos/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Meticilina/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Adolescente , Antibacterianos/farmacologia , Criança , Pré-Escolar , China , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Humanos , Lactente , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus/isolamento & purificação , Resultado do Tratamento
8.
Nat Commun ; 11(1): 3970, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769975

RESUMO

The rise of antibiotic resistance in many bacterial pathogens has been driven by the spread of a few successful strains, suggesting that some bacteria are genetically pre-disposed to evolving resistance. Here, we test this hypothesis by challenging a diverse set of 222 isolates of Staphylococcus aureus with the antibiotic ciprofloxacin in a large-scale evolution experiment. We find that a single efflux pump, norA, causes widespread variation in evolvability across isolates. Elevated norA expression potentiates evolution by increasing the fitness benefit provided by DNA topoisomerase mutations under ciprofloxacin treatment. Amplification of norA provides a further mechanism of rapid evolution in isolates from the CC398 lineage. Crucially, chemical inhibition of NorA effectively prevents the evolution of resistance in all isolates. Our study shows that pre-existing genetic diversity plays a key role in shaping resistance evolution, and it may be possible to predict which strains are likely to evolve resistance and to optimize inhibitor use to prevent this outcome.


Assuntos
Proteínas de Bactérias/metabolismo , Resistência Microbiana a Medicamentos , Evolução Molecular , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Ciprofloxacino/farmacologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Genoma Bacteriano , Mutação/genética , Filogenia , Staphylococcus aureus/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética
9.
BMC Infect Dis ; 20(1): 602, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32799799

RESUMO

BACKGROUND: The objectives of this study were to determine for the first time, in Morocco, the nasal carriage rate, antimicrobial susceptibility profiles and virulence genes of Staphylococcus. aureus isolated from animals and breeders in close contact. METHODS: From 2015 to 2016, 421 nasal swab samples were collected from 26 different livestock areas in Tangier. Antimicrobial susceptibility phenotypes were determined by disk diffusion according to EUCAST 2015. The presence of nuc, mecA, mecC, lukS/F-PV, and tst genes were determined by Polymerase Chain Reaction (PCR) for all isolates. RESULTS: The overall S. aureus nasal carriage rate was low in animals (9.97%) and high in breeders (60%) with a statistically significant difference, (OR = 13.536; 95% CI = 7.070-25.912; p < 0.001). In general, S. aureus strains were susceptible to the majority of antibiotics and the highest resistance rates were found against tetracycline (16.7% in animals and 10% in breeders). No Methicillin-Resistant S. aureus (MRSA) was detected in animals and breeders. A high rate of tst and lukS/F-PV genes has been recovered only from animals (11.9 and 16.7%, respectively). CONCLUSION: Despite the lower rate of nasal carriage of S. aureus and the absence of MRSA strains in our study, S. aureus strains harbored a higher frequency of tst and lukS/F-PV virulence genes, which is associated to an increased risk of infection dissemination in humans. This highlights the need for further larger and multi-center studies to better define the transmission of the pathogenic S. aureus between livestock, environment, and humans.


Assuntos
Nariz/microbiologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/veterinária , Staphylococcus aureus/efeitos dos fármacos , Animais , Animais Domésticos/microbiologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Portador Sadio , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Humanos , Leucocidinas/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Nuclease do Micrococo/genética , Marrocos/epidemiologia , Proteínas de Ligação às Penicilinas/genética , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/patogenicidade , Tetraciclina/farmacologia , Virulência/genética
10.
J Med Microbiol ; 69(9): 1132-1144, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32812863

RESUMO

Introduction. While colonization by Staphylococcus aureus in haemodialysis patients has been assessed, knowledge about colonization by beta-lactam-resistant Gram-negative bacilli is still limited.Aim. To describe clinical and molecular characteristics in haemodialysis patients colonized by S. aureus (MSSA-MRSA) and beta-lactam-resistant Gram-negative bacilli in an ambulatory renal unit.Methodology. The study included patients with central venous catheters in an outpatient haemodialysis facility in Medellín, Colombia (October 2017-October 2018). Swab specimens were collected from the nostrils and skin around vascular access to assess colonization by S. aureus (MSSA-MRSA). Stool samples were collected from each patient to evaluate beta-lactam-resistant Gram-negative bacilli colonization. Molecular typing included PFGE, multilocus sequence typing (MLST), spa typing and enterobacterial repetitive intergenic consensus-PCR (ERIC). Clinical information was obtained from medical records and personal interview.Results. A total of 210 patients were included in the study. S. aureus colonization was observed in 33.8 % (n=71) of the patients, 4.8 % (n=10) of which were colonized by methicillin-resistant S. aureus. Stool samples were collected from 165 patients and of these 41.2 % (n=68) and 11.5 % (n=19) were colonized by extended-spectrum-beta-lactamase-producing (ESBL) and carbapenem-resistant bacilli, respectively. Typing methods revealed high genetic diversity among S. aureus and ESBL-producing Gram-negative bacilli (ESBL-GNB). Antibiotic use and hospitalization in the previous 6 months were observed in more than half of the studied population.Conclusion. The high colonization by ESBL-GNB in haemodialysis patients shows evidence for the need for stronger surveillance, not only for S. aureus but also for multidrug-resistant bacilli in order to avoid their spread. Additionally, the high genetic diversity suggests other sources of transmission outside the renal unit instead of horizontal transmission between patients.


Assuntos
Antibacterianos/farmacologia , Infecção Hospitalar/microbiologia , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/microbiologia , Lactamas/farmacologia , Resistência beta-Lactâmica , Idoso , Fezes/microbiologia , Feminino , Bactérias Gram-Negativas/classificação , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/isolamento & purificação
11.
Nucleic Acids Res ; 48(15): 8545-8561, 2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32735661

RESUMO

A crucial bacterial strategy to avoid killing by antibiotics is to enter a growth arrested state, yet the molecular mechanisms behind this process remain elusive. The conditional overexpression of mazF, the endoribonuclease toxin of the MazEF toxin-antitoxin system in Staphylococcus aureus, is one approach to induce bacterial growth arrest, but its targets remain largely unknown. We used overexpression of mazF and high-throughput sequence analysis following the exact mapping of non-phosphorylated transcriptome ends (nEMOTE) technique to reveal in vivo toxin cleavage sites on a global scale. We obtained a catalogue of MazF cleavage sites and unearthed an extended MazF cleavage specificity that goes beyond the previously reported one. We correlated transcript cleavage and abundance in a global transcriptomic profiling during mazF overexpression. We observed that MazF affects RNA molecules involved in ribosome biogenesis, cell wall synthesis, cell division and RNA turnover and thus deliver a plausible explanation for how mazF overexpression induces stasis. We hypothesize that autoregulation of MazF occurs by directly modulating the MazEF operon, such as the rsbUVW genes that regulate the sigma factor SigB, including an observed cleavage site on the MazF mRNA that would ultimately play a role in entry and exit from bacterial stasis.


Assuntos
Proteínas de Ligação a DNA/genética , Endorribonucleases/genética , Proteínas de Escherichia coli/genética , Staphylococcus aureus/genética , Sistemas Toxina-Antitoxina/genética , Antibacterianos/farmacologia , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA/química , Escherichia coli/genética , Humanos , Óperon/genética , RNA Mensageiro/genética , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Especificidade por Substrato , Transcriptoma/genética
12.
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
13.
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
14.
Biomed Environ Sci ; 33(7): 471-483, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32807266

RESUMO

Objective: Owing to antibiotic abuse and the subsequent development of antibiotic resistance, bacterial infection has become one of the most persistent unresolved problems. New antibacterial agents, especially those that are environmental-friendly, are urgently needed. Methods: Melanin extracted by filtration centrifugation and acid and proteolytic hydrolysis was characterized using UV, FTIR, TEM, and XPS. Photothermal conversion was calculated, and the bacteriostatic effects, in vitro and in vivo, were assessed by plate counting and ratios (%) of wound areas. Results: Natural melanin hydrolyzed by trypsin had good photothermal conversion effects, which resulted in superior bacteriostatic activities. The extracted melanin along with laser NIR irradiation at 808 nm promoted the healing of wounds infected by drug-resistant bacteria in vivo and was biocompatible according to toxicity tests in vivo and in vitro. Conclusion: The present findings indicated a safe and efficient method of developing natural antibacterial agents.


Assuntos
Antibacterianos/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Melaninas/farmacologia , Mytilus edulis/química , Infecções Estafilocócicas/tratamento farmacológico , Cicatrização , Exoesqueleto/química , Animais , Escherichia coli/efeitos dos fármacos , Escherichia coli/efeitos da radiação , Processos Fotoquímicos , Ratos , Ratos Sprague-Dawley , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/efeitos da radiação
15.
Int J Nanomedicine ; 15: 5473-5489, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801701

RESUMO

Introduction: Biofilms protect bacteria from antibiotics and this can produce drug-resistant strains, especially the main pathogen of periodontitis, Porphyromonas gingivalis. Carbon quantum dots with various biomedical properties are considered to have great application potential in antibacterial and anti-biofilm treatment. Methods: Tinidazole carbon quantum dots (TCDs) and metronidazole carbon quantum dots (MCDs) were prepared by a hydrothermal method with the clinical antibacterial drugs tinidazole and metronidazole, respectively. Then, TCDs and MCDs were characterized by transmission electron microscopy, UV-visible spectroscopy, infrared spectroscopy and energy-dispersive spectrometry. The antibacterial effects were also investigated under different conditions. Results: The TCDs and MCDs had uniform sizes. The results of UV-visible and energy-dispersive spectrometry confirmed their important carbon polymerization structures and the activity of the nitro group, which had an evident inhibitory effect on P. gingivalis, but almost no effect on other bacteria, including Escherichia coli, Staphylococcus aureus and Prevotella nigrescens. Importantly, the TCDs could penetrate the biofilms to further effectively inhibit the growth of P. gingivalis under the biofilms. Furthermore, it was found that the antibacterial effect of TCDs lies in its ability to impair toxicity by inhibiting the major virulence factors and related genes involved in the biofilm formation of P. gingivalis, thus affecting the self-assembly of biofilm-related proteins. Conclusion: The findings demonstrate a promising new method for improving the efficiency of periodontitis treatment by penetrating the P. gingivalis biofilm with preparations of nano-level antibacterial drugs.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Porphyromonas gingivalis/efeitos dos fármacos , Pontos Quânticos/química , Animais , Antibacterianos/efeitos adversos , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Carbono/química , Carbono/farmacologia , Escherichia coli/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Metronidazol/química , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Periodontite/microbiologia , Porphyromonas gingivalis/genética , Porphyromonas gingivalis/fisiologia , Coelhos , Espectrofotometria Ultravioleta , Staphylococcus aureus/efeitos dos fármacos , Tinidazol/química , Tinidazol/farmacologia , Fatores de Virulência/antagonistas & inibidores
16.
Nat Commun ; 11(1): 3888, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32753666

RESUMO

First proposed as antimicrobial agents, histones were later recognized for their role in condensing chromosomes. Histone antimicrobial activity has been reported in innate immune responses. However, how histones kill bacteria has remained elusive. The co-localization of histones with antimicrobial peptides (AMPs) in immune cells suggests that histones may be part of a larger antimicrobial mechanism in vivo. Here we report that histone H2A enters E. coli and S. aureus through membrane pores formed by the AMPs LL-37 and magainin-2. H2A enhances AMP-induced pores, depolarizes the bacterial membrane potential, and impairs membrane recovery. Inside the cytoplasm, H2A reorganizes bacterial chromosomal DNA and inhibits global transcription. Whereas bacteria recover from the pore-forming effects of LL-37, the concomitant effects of H2A and LL-37 are irrecoverable. Their combination constitutes a positive feedback loop that exponentially amplifies their antimicrobial activities, causing antimicrobial synergy. More generally, treatment with H2A and the pore-forming antibiotic polymyxin B completely eradicates bacterial growth.


Assuntos
Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/genética , Estruturas Cromossômicas/efeitos dos fármacos , Histonas/metabolismo , Prótons , Animais , Estruturas Cromossômicas/metabolismo , Cromossomos Bacterianos/metabolismo , DNA Bacteriano/metabolismo , Sinergismo Farmacológico , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Imunidade Inata , Mamíferos , Polimixina B/farmacologia , Análise de Sequência de RNA , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/metabolismo
17.
Am J Infect Control ; 48(9): 1037-1041, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32645473

RESUMO

INTRODUCTION: One of the serious consequences of the SARS-CoV-2 pandemic is the shortage of protective equipment for health personnel. N95 masks are considered one of the essential protective equipment in the management of patients with COVID-19. The shortage of N95 masks implies potential health risks for health personnel and significant economic losses for the health institution. The objective of this work was to investigate the disinfection of N95 masks artificially contaminated with SARS-CoV-2 and ESKAPE bacteria by using hydrogen peroxide plasma. MATERIAL AND METHODS: We examined the disinfection capacity of hydrogen peroxide plasma against the SARS-CoV-2 and 2 members of the ESKAPE bacteria (Acinetobacter baumannii and Staphylococcus aureus) through a study of artificial contamination in situ of N95 masks. Amplification of specific genes by real-time reverse transcription polymerase chain reaction of SARS-CoV-2 and microbiological culture of ESKAPE bacteria was performed before and after the disinfection process. RESULTS: SARS-CoV-2 was not detected in all assays using 5 different concentrations of the virus, and A baumannii and S aureus were not cultivable with inoculums of 102 to 106 CFU after disinfection tests of N95 masks with hydrogen peroxide plasma. CONCLUSION: Disinfection of N95 masks by using the hydrogen peroxide plasma technology can be an alternative for their reuse in a shortage situation. Implications for the use of disinfection technologies of N95 masks and the safety of health personnel are discussed.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/prevenção & controle , Desinfecção/métodos , Reutilização de Equipamento , Peróxido de Hidrogênio/administração & dosagem , Máscaras/microbiologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Acinetobacter baumannii/efeitos dos fármacos , Humanos , Dispositivos de Proteção Respiratória/microbiologia , Staphylococcus aureus/efeitos dos fármacos
18.
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
19.
PLoS One ; 15(7): e0234964, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614844

RESUMO

In this study, a facile, ecological and economical green method is described for the fabrication of iron (Fe), copper (Cu) and silver (Ag) nanoparticles (NPs) from the extract of Syzygium cumini leaves. The obtained metal NPs were categorized using UV/Vis, SEM, TEM, FTIR and EDX-ray spectroscopy techniques. The Fe-, Cu- and Ag-NPs were crystalline, spherical and size ranged from 40-52, 28-35 and 11-19 nm, respectively. The Ag-NPs showed excellent antimicrobial activities against methicillin- and vancomycin-resistance Staphylococcus aureus bacterial strains and Aspergillus flavus and A. parasiticus fungal species. Furthermore, the aflatoxins (AFs) production was also significantly inhibited when compared with the Fe- and Cu-NPs. In contrast, the adsorption results of NPs with aflatoxin B1 (AFB1) were observed as following order Fe->Cu->Ag-NPs. The Langmuir isotherm model well described the equilibrium data by the sorption capacity of Fe-NPs (105.3 ng mg-1), Cu-NPs (88.5 ng mg-1) and Ag-NPs (81.7 ng mg-1). The adsorption was found feasible, endothermic and follow the pseudo-second order kinetic model as revealed by the thermodynamic and kinetic studies. The present findings suggests that the green synthesis of metal NPs is a simple, sustainable, non-toxic, economical and energy-effective as compared to the others conventional approaches. In addition, synthesized metal NPs might be a promising AFs adsorbent for the detoxification of AFB1 in human and animal food/feed.


Assuntos
Aflatoxina B1/isolamento & purificação , Anti-Infecciosos/metabolismo , Biotecnologia/métodos , Cobre , Química Verde/métodos , Ferro , Nanopartículas Metálicas , Extratos Vegetais/metabolismo , Folhas de Planta/metabolismo , Prata , Desintoxicação por Sorção , Syzygium/metabolismo , Adsorção , Anti-Infecciosos/farmacologia , Aspergillus/efeitos dos fármacos , Aspergillus flavus/efeitos dos fármacos , Técnicas de Química Analítica , Cobre/administração & dosagem , Cobre/farmacologia , Resistência Microbiana a Medicamentos , Ferro/administração & dosagem , Ferro/farmacologia , Cinética , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Oxirredução , Prata/administração & dosagem , Prata/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Termodinâmica , Vancomicina/farmacologia
20.
Int J Nanomedicine ; 15: 4351-4362, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606682

RESUMO

Purpose: The present study synthesized silver nanoparticles (AgNPs) using the aqueous extract of a traditional medicinal product consisting of an oleoresin (a combination of macromolecules of carbohydrates and proteins) exuded from the rhizome of the plant Ferula foetida (asafoetida gum) and evaluated its biological properties. Materials and Methods: The silver nanoparticles synthesized using asafoetida gum (As-AgNPs) were characterized using UV/Vis spectroscopy, fourier infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) with energy dispersive X-ray analysis (EDX), X-ray diffraction (XRD) and transmission electron microscopy (TEM) and EADX. The cytotoxicity and antimicrobial activity As-AgNPs were evaluated against MCF-7 cell lines and selected microbial pathogens, respectively. Results: The synthesized silver nanoparticles were crystalline in nature with a spherical shape. The average particle size was 5.6-8.6 nm. The cytotoxicity of the synthesized As-AgNPs was evaluated against MCF-7 cell lines, and the As-AgNPs were found to be effective in inhibiting the multiplication of cancer cells. The As-AgNPs exhibited significant antimicrobial activity towards E. coli, K. pneumoniae and C. albicans. The MIC of the synthesized As-AgNPs was 7.80 µg/mL for E. coli ATCC 25922, Salmonella sp. WS50- and S. typhi; 15.60 µg/mL for S. typhimurium and S. aureus WS10, and 31.20 µg/mL for K. pneumoniae and S. aureus ATCC 43300-MRSA. In addition, MIC values of 15.60 µg/mL for C. albicans ATCC8436 and 31.20 µg/mL for C. krusei ATCC6258 were obtained. Conclusion: As asafoetida is a good traditional medicine, its involvement in the synthesis of AgNPs led the silver nanoparticles to exhibit good cytotoxic and antimicrobial effects.


Assuntos
Anti-Infecciosos/farmacologia , Ferula/química , Nanopartículas Metálicas/química , Gomas Vegetais/química , Prata/farmacologia , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Células MCF-7 , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Extratos Vegetais/química , Staphylococcus aureus/efeitos dos fármacos , Difração de Raios X
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