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1.
BMC Infect Dis ; 20(1): 667, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912204

RESUMO

BACKGROUND: Frequencies of polymicrobial infection and pathogens evidenced in course of infected nonunion treatment are largely unknown. Therefore, this study aims at investigating microbial patterns in infected nonunions. METHODS: Surgically treated patients with long bone infected nonunion admitted between January 2010 and March 2018 were included in the study. Microbiological culture and polymerase-chain-reaction results of tissue samples of initial and follow-up revision surgeries were assessed and compared with patient and treatment characteristics. RESULTS: Forty two patients with a mean age of 53.9 ± 17.7 years were included. In six patients (14.3%) polymicrobial infection was evident. A change of pathogens evidenced in course of the treatment occurred in 21 patients (50%). In 16 patients (38.1%) previously detected bacteria could be determined by microbial testing after further revision surgery. Staphylococcus aureus was most often detected (n = 34, 30.6%), followed by Enterococcus spp. (n = 25, 22.5%) and Staphylococcus epidermidis (n = 18, 16.2%). Five Staphylococcus aureus were resistant to methicillin (MRSA). In patients without polymicrobial infection or further germ detection in course of the treatment, 86.4% of the infections were due to Staphylococcus spp.. Infections due to Streptococcus spp. and gram-negative bacteria were only present in patients with polymicrobial infection and germ-change in course of the treatment. CONCLUSION: A low rate of polymicrobial infections was evidenced in the present study. Germ-change often occurs in course of revision surgeries. Prospective studies with more sensitive diagnostic tools are necessary to elucidate the therapeutical relevance of microbiological testing results for surgical as well as medical treatment in infected nonunions.


Assuntos
Coinfecção/diagnóstico , Enterococcus/genética , Consolidação da Fratura , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Enterococcus/isolamento & purificação , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Reoperação , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Resultado do Tratamento , Adulto Jovem
2.
Antimicrob Resist Infect Control ; 9(1): 153, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962731

RESUMO

BACKGROUND: A considerable proportion of patients hospitalized with coronavirus disease 2019 (COVID-19) acquired secondary bacterial infections (SBIs). The etiology and antimicrobial resistance of bacteria were reported and used to provide a theoretical basis for appropriate infection therapy. METHODS: This retrospective study reviewed electronic medical records of all the patients hospitalized with COVID-19 in the Wuhan Union Hospital between January 27 and March 17, 2020. According to the inclusion and exclusion criteria, patients who acquired SBIs were enrolled. Demographic, clinical course, etiology, and antimicrobial resistance data of the SBIs were collected. Outcomes were also compared between patients who were classified as severe and critical on admission. RESULTS: Among 1495 patients hospitalized with COVID-19, 102 (6.8%) patients had acquired SBIs, and almost half of them (49.0%, 50/102) died during hospitalization. Compared with severe patients, critical patients had a higher chance of SBIs. Among the 159 strains of bacteria isolated from the SBIs, 136 strains (85.5%) were Gram-negative bacteria. The top three bacteria of SBIs were A. baumannii (35.8%, 57/159), K. pneumoniae (30.8%, 49/159), and S. maltophilia (6.3%, 10/159). The isolation rates of carbapenem-resistant A. baumannii and K. pneumoniae were 91.2 and 75.5%, respectively. Meticillin resistance was present in 100% of Staphylococcus aureus and Coagulase negative staphylococci, and vancomycin resistance was not found. CONCLUSIONS: SBIs may occur in patients hospitalized with COVID-19 and lead to high mortality. The incidence of SBIs was associated with the severity of illness on admission. Gram-negative bacteria, especially A. baumannii and K. pneumoniae, were the main bacteria, and the resistance rates of the major isolated bacteria were generally high. This was a single-center study; thus, our results should be externally examined when applied in other institutions.


Assuntos
Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , Farmacorresistência Bacteriana/fisiologia , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções Estafilocócicas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Betacoronavirus , China/epidemiologia , Coinfecção/mortalidade , Infecções por Coronavirus/patologia , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico
3.
Nat Commun ; 11(1): 4446, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895387

RESUMO

Owing to the poor penetration depth of light, phototherapy, including photothermal and photodynamic therapies, remains severely ineffective in treating deep tissue infections such as methicillin-resistant Staphylococcus aureus (MRSA)-infected osteomyelitis. Here, we report a microwave-excited antibacterial nanocapturer system for treating deep tissue infections that consists of microwave-responsive Fe3O4/CNT and the chemotherapy agent gentamicin (Gent). This system, Fe3O4/CNT/Gent, is proven to efficiently target and eradicate MRSA-infected rabbit tibia osteomyelitis. Its robust antibacterial effectiveness is attributed to the precise bacteria-capturing ability and magnetic targeting of the nanocapturer, as well as the subsequent synergistic effects of precise microwaveocaloric therapy from Fe3O4/CNT and chemotherapy from the effective release of antibiotics in infection sites. The advanced target-nanocapturer of microwave-excited microwaveocaloric-chemotherapy with effective targeting developed in this study makes a major step forward in microwave therapy for deep tissue infections.


Assuntos
Nanopartículas de Magnetita/uso terapêutico , Micro-Ondas/uso terapêutico , Osteomielite/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Animais , Antibacterianos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Tratamento Farmacológico/métodos , Óxido Ferroso-Férrico/uso terapêutico , Gentamicinas/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Nanotubos de Carbono , Osteomielite/microbiologia , Coelhos
4.
PLoS Biol ; 18(9): e3000856, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32941420

RESUMO

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


Assuntos
Antibacterianos/administração & dosagem , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana/métodos , Algoritmos , Andinocilina/administração & dosagem , Andinocilina/farmacologia , Antibacterianos/farmacologia , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Humanos , Testes de Sensibilidade Microbiana/instrumentação , Nitrofurantoína/administração & dosagem , Nitrofurantoína/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Reprodutibilidade dos Testes , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Trimetoprima/administração & dosagem , Trimetoprima/farmacologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
5.
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
6.
J Assoc Physicians India ; 68(8): 30-36, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32738837

RESUMO

Background: Levonadifloxacin is a novel broad-spectrum anti-MRSA agents belonging to the benzoquinolizine subclass of quinolone. It is developed for oral or intravenous administration for the treatment of infections caused by Gram-positive organisms including methicillin-resistant Staphylococcus aureus (MRSA). Objectives: To establish the non-inferiority of levonadifloxacin compared with linezolid for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and to compare the safety of the two antimicrobials. Subjects and methods: This was a Phase 3, multicentre, randomized, open-label, active- comparator study with 500 subjects. Oral levonadifloxacin 1000 mg was compared with oral linezolid 600 mg whereas IV levonadifloxacin 800mg was compared with IV linezolid 600 mg, each treatment was administered twice daily for 7-10 days. Non-inferiority was evaluated by comparing oral levonadifloxacin to oral linezolid and IV levonadifloxacin to IV linezolid for overall clinical response at TOC (Test of Cure) Visit. Results: The clinical cure rates observed at the TOC in the mITT (modified Intent to treat) populations for levonadifloxacin was numerically higher compared to linezolid in the IV sub-group [(91.0% verses 87.8%); treatment difference of 3.2% (95%CI, -4.5 to 10.9)] and in the oral sub-group (95.2% versus 93.6%); treatment difference of 1.6 % [95%CI, -4.2 to 7.3]). As the lowerbound of the 95% CI around the treatment difference was greater than -15% for both subgroups, the primary objective of the study was met. Therefore, both IV levonadifloxacin and oral levonadifloxacin were non-inferior to IV linezolid and oral linezolid, respectively. The majority of subjects in the micro-ITT population had a baseline infection caused by S. aureus with approximately 30% of subjects having MRSA. Levonadifloxacin (IV and oral) had a higher clinical cure rate at TOC for MRSA patients compared with linezolid (IV and oral), (95.0% vs. 89.3% respectively). Levonadifloxacin showed evidence of favourable clinical and microbiological efficacy in subjects with concurrent bacteraemia as well as in subjects with diabetes including diabetic foot infections caused by Gram-positive pathogens including MRSA. Pharmacokinetic analysis showed that bioavailability of oral levonadifloxacin was 90% and similar pharmacokinetic profile of levonadifloxacin by both routes provide an option for IV to oral switch for the treatment of subjects. Incidences of treatment-emergent adverse events (TEAEs) were similar between treatment groups and between IV (20.8% vs. 22.4%, for levonadifloxacin and linezolid, respectively) and oral therapy (16.0% vs. 13.5%, respectively), There were no SAEs or deaths related to study drug and the majority of the AEs observed were mild in nature. Overall, the administration of both IV and oral levonadifloxacin was well-tolerated in subjects with ABSSSI. Conclusions: The results demonstrate that IV and oral levonadifloxacin therapy has excellent clinical activity against MRSA and offers advantage compared to other quinolones which generally lack MRSA coverage. Levonadifloxacin is safe and well tolerated in the treatment of ABSSSI caused by Gram -positive pathogens including MRSA as well as non-inferior to IV and oral linezolid, respectively. Similar pharmacokinetic profile of IV and oral levonadifloxacin provides an option for IV to oral switch for the treatment of subjects. Both oral and IV levonadifloxacin have recently been granted approval in India for the treatment of ABSSSI including diabetic foot infections and concurrent bacteraemia in adults (18 years of age or older). ClinicalTrials.gov Registration: NCT03405064. CTRI No.: CTRI/2017/06/008843.


Assuntos
Antibacterianos/uso terapêutico , Fluoroquinolonas/uso terapêutico , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas/tratamento farmacológico , Adolescente , Adulto , Humanos , Índia , Linezolida , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus , Resultado do Tratamento
7.
BMC Infect Dis ; 20(1): 583, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762676

RESUMO

BACKGROUND: Dengue fever is endemic and a leading health problem in Sri Lanka. Increased incidence of concurrent bacteremia in patients with dengue infection is a recognized complication. However, Staphylococcal endocarditis following dengue fever is uncommon. Quadricuspid aortic valve (QAV) is a rare congenital anomaly and few cases of infective endocarditis have been reported in QAV. CASE PRESENTATION: A 32-year-old Sri Lankan male presented to the National Hospital of Sri Lanka with recurrence of fever and acute left hemiplegia following an uncomplicated recovery of dengue fever. He was diagnosed to have Staphylococcal infective endocarditis of quadricuspid aortic valve, with septic emboli to brain and spleen. He was managed with intravenous vancomycin initially, however, due to inadequate response, intravenous linezolid was added. He developed rhabdomyolysis with very high creatine phosphokinase leading to acute kidney injury, which settled with the cessation of linezolid. The patient succumbed to his illness despite aggressive antimicrobial therapy and maximum supportive care while being assessed for aortic valve replacement. CONCLUSIONS: This case illustrates three clinical issues that a clinician should be aware of. Firstly, the possibility of a serious secondary bacterial infection as a cause for recurrence of fever following dengue infection. Secondly, this case highlights the importance of identifying QAV as a cause for complicated infective endocarditis of increased severity. The report also denotes the value of being vigilant of linezolid induced rhabdomyolysis which had a causal relationship with the commencement of the drug and its cessation.


Assuntos
Valva Aórtica/anormalidades , Dengue/complicações , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/etiologia , Doenças das Valvas Cardíacas/diagnóstico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/etiologia , Staphylococcus aureus/isolamento & purificação , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/mortalidade , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Hemocultura , Dengue/tratamento farmacológico , Dengue/virologia , Vírus da Dengue , Endocardite Bacteriana/tratamento farmacológico , Evolução Fatal , Febre/tratamento farmacológico , Humanos , Linezolida/farmacologia , Linezolida/uso terapêutico , Masculino , Rabdomiólise/induzido quimicamente , Rabdomiólise/complicações , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Acidente Vascular Cerebral/mortalidade
8.
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
9.
Circ J ; 84(10): 1887, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32779609
10.
PLoS One ; 15(8): e0237714, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804961

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious public health problem. There is limited information regarding the genetics of MRSA strains among the native Iraqi and incoming Syrian refugee communities. We aimed to characterize the genotypes and different virulence factors of MRSA in strains isolated from these two communities. Frozen MRSA strains (125) isolated from the native Iraqi and Syrian refugee communities were used in this study. PCR (singleplex and multiplex) and agr typing was used for the genotypic analysis of different virulence genes. We tested for the presence of virulence genes including pvl, arcA, tst, lukE/lukD, hla, hlb, eta, etb and agr. Prevalence of arcA MRSA in the Iraqi community (56.58%) was significantly higher (p = 0.008) than that in the Syrian refugee community (32.66%). Prevalence of lukE-lukD was also significantly higher (p = 0.001) in the Iraqi (82.89%) compared to that in the Syrian refugee community (57.14%). Further, prevalence of hla MRSA in the Iraqi community was (93.4%) and in the Syrian refugee community was (71.4%); (p = 0.0008). No significant differences were observed in the prevalence of pvl, tst, eta, etb and hlb. The most dominant agr types in both Iraqi (76.1% and 10.5%) and Syrian refugee (44.9% and 18.37%) communities were I and III. To sum up, no significant differences were observed between the groups for a majority of virulence factors. This is the first investigation of MRSA genotypes and virulence in both these communities. These results could be useful for further studies that assess the genetic relatedness of strains in the region for epidemiological and monitoring purposes, which would be crucial to limiting the spread of MRSA.


Assuntos
Resistência a Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Refugiados , Infecções Estafilocócicas/microbiologia , Fatores de Virulência/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/isolamento & purificação , Cidades/epidemiologia , Exotoxinas/genética , Exotoxinas/isolamento & purificação , Genes Bacterianos/genética , Técnicas de Genotipagem , Humanos , Iraque/epidemiologia , Meticilina/farmacologia , Meticilina/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Prevalência , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Síria , Transativadores/genética , Transativadores/isolamento & purificação , Fatores de Virulência/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.
Pediatrics ; 146(3)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32759380

RESUMO

Staphylococcus aureus is a common cause of community and health care-associated bacteremia, with authors of recent studies estimating the incidence of S aureus bacteremia (SAB) in high-income countries between 8 and 26 per 100 000 children per year. Despite this, <300 children worldwide have ever been randomly assigned into clinical trials to assess the efficacy of treatment of SAB. A panel of infectious diseases physicians with clinical and research interests in pediatric SAB identified 7 key clinical questions. The available literature is systematically appraised, summarizing SAB management in children in relation to these priority clinical questions. The management of neonates, children, and adolescents with SAB is predominantly based on clinical experience and trial data extrapolated from adult studies, with limited high-quality evidence available to guide management. The optimal, comprehensive management strategies for SAB in children will remain unknown until the questions outlined are answered through prospective observational cohorts and inclusion of children with SAB in clinical trials.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Adolescente , Fatores Etários , Algoritmos , Bacteriemia/diagnóstico , Bacteriemia/epidemiologia , Estudos de Casos e Controles , Infecções Relacionadas a Cateter/etiologia , Cefalosporinas/uso terapêutico , Criança , Pré-Escolar , Técnica Delfos , Esquema de Medicação , Ecocardiografia , Endocardite Bacteriana/diagnóstico por imagem , Endocardite Bacteriana/tratamento farmacológico , Glicopeptídeos/uso terapêutico , Humanos , Incidência , Lactente , Recém-Nascido , Injeções Intravenosas , Staphylococcus aureus Resistente à Meticilina , Estudos Observacionais como Assunto , Penicilinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Encaminhamento e Consulta , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/isolamento & purificação , Vancomicina/uso terapêutico , beta-Lactamas/uso terapêutico
13.
Niger J Clin Pract ; 23(7): 912-918, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620719

RESUMO

Background: Investigating genetic relatedness between methicillin-resistant Staphylococcus aureus (MRSA) strains from humans and different animal species may clarify the epidemiological characteristic of MRSA infections together. Aim: The aim of the study was to perform genotypic characterization and type strains of MRSA isolated from different clinical sources, by molecular techniques. Materials and Methods: The molecular characterization of the strains was performed by polymerase chain reaction (PCR), using several specific oligonucleotides. These were as follows: S. aureus species-specific sau gene, mecA gene coding PBP2a responsible for methicillin resistance, femA gene coding for a protein, which influences the level of methicillin resistance of S. aureus, and is universally present in all MRSA strains; spa gene coding for protein A; coa gene coding for coagulase, and blaZ gene coding for the production of beta-lactamase. To determine the genetic diversity of these strains, random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) was performed. Results: Among the 415 S. aureus strains, 61 were phenotypically identified as MRSA, and confirmed as S. aureus by amplification of sau gene. However, 90.16% of the strains were mecA positive, while all were negative for femA gene. The presence and polymorphism of coa and spa genes were investigated and 83.60% and 18.03% strains were positive for coa and spa, respectively. While these strains were grouped into six coa-types by PCR, no polymorphism was found for spa gene among strains having only single 190 bp of the band. bla genes were found in 75.40% of strains. These strains were divided into 12 RAPD types. Conclusions: The results showed the relatively high heterogeneity and variation of coa gene among MRSA strains, while further studies on sequencing of these strains may identify which sequence type is predominant in this region.


Assuntos
Proteínas de Bactérias/genética , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Técnica de Amplificação ao Acaso de DNA Polimórfico/métodos , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/isolamento & purificação , Coagulase/genética , Genótipo , Humanos , Meticilina , Resistência a Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética
14.
BMC Infect Dis ; 20(1): 457, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600427

RESUMO

BACKGROUND: Indwelling central venous catheters (CVC) are used to provide long term hemodialysis. The commonest and the severe complication of CVC is the central line-associated bloodstream infection (CLABSI). This study was done to assess the etiology and infectious complications of CVC in children on long term hemodialysis. METHODS: Children newly undergoing hemodialysis and having indwelling CVC were included. They were followed up to a period of 2-years to assess infectious complications. Catheter bundle care approach was employed to prevent infections and other complications. Automated culture from the central catheter and peripheral vein and 2D echocardiography were done in each hemodialysis. Serial procalcitonin (PCT) was measured. Differential time of positivity (DTP) was used to detect CLABSI. During homestay in weekly telephone conversations were done to assess features of infection, and whenever having, we have asked to admit to the tertiary care unit. Logistic regression was performed, and the significant outcome variable was considered following multivariable analysis as a risk factor. RESULTS: Blood cultures were positive in 1090 (74.5%) out of 1462 children. According to DTP, 410 (28%) were having CLABSI, while 520 (35.6%) were having bacteremia without CLABSI. Out of 410 CLABSI patients, 79 (19.2%) were asymptomatic. Coagulase-negative Staphylococcus spp. (CoNS) bacteremia was significantly associated with asymptomatic CLABSI. Right-sided infective endocarditis (RS-IE) was significantly associated with asymptomatic CLABSI and asymptomatic bacteremia without CLABSI. CoNS was associated significantly in RS-IE following asymptomatic CLABSI and asymptomatic bacteremia. PCT was in asymptomatic CLABSI was 1.8 ± 0.9 ng/mL while in symptomatic CLABSI was 11.3 ± 2.5 ng/ml (P = 0.02). CoNS bloodstream infection, tunneled CVC, peripherally inserted central catheter, femoral site, the number of line days > 90, receipt of vancomycin, meropenem, or linezolid in the 5 days before CLABSI diagnosis and recurrent bacteremia were risk factors for asymptomatic CLABSI. CONCLUSIONS: Asymptomatic CLABSI could be a rare occurrence. CoNS was predominantly isolated in patients with asymptomatic CLABSI. RS- IE is a well-known complication in long term indwelling CVC. CoNS was significantly associated with RS-IE following asymptomatic CLABSI. Regular procalcitonin, microbiological, and imaging studies would be essential to detect infectious complications in both symptomatic and asymptomatic patients implanted with long term indwelling CVCs.


Assuntos
Doenças Assintomáticas , Bacteriemia/etiologia , Infecções Relacionadas a Cateter/diagnóstico , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/microbiologia , Cateteres Venosos Centrais/microbiologia , Infecção Hospitalar/diagnóstico , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus/isolamento & purificação , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Infecções Relacionadas a Cateter/sangue , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/microbiologia , Criança , Pré-Escolar , Coagulase/metabolismo , Infecção Hospitalar/sangue , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Endocardite/etiologia , Feminino , Seguimentos , Hospitais de Ensino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Fatores de Risco , Sri Lanka , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/enzimologia
15.
BMC Infect Dis ; 20(1): 539, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32703263

RESUMO

BACKGROUND: Staphylococcus saccharolyticus is a rarely encountered coagulase-negative, which grows slowly and its strictly anaerobic staphylococcus from the skin. It is usually considered a contaminant, but some rare reports have described deep-seated infections. Virulence factors remain poorly known, although, genomic analysis highlights pathogenic potential. CASE PRESENTATION: We report a case of Staphylococcus saccharolyticus spondylodiscitis that followed kyphoplasty, a procedure associated with a low rate but possible severe infectious complication (0.46%), and have reviewed the literature. This case specifically stresses the risk of healthcare-associated S. saccharolyticus infection in high-risk patients (those with a history of alcoholism and heavy smoking). CONCLUSION: S. saccharolyticus infection is difficult to diagnose due to microbiological characteristics of this bacterium; it requires timely treatment, and improved infection control procedure should be encouraged for high-risk patients.


Assuntos
Infecção Hospitalar/diagnóstico , Discite/diagnóstico por imagem , Cifoplastia/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Infecções Estafilocócicas/diagnóstico , Staphylococcus/isolamento & purificação , Vértebras Torácicas/microbiologia , Amoxicilina/administração & dosagem , Amoxicilina/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Coagulase/metabolismo , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Discite/tratamento farmacológico , Discite/microbiologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus/enzimologia , Vértebras Torácicas/diagnóstico por imagem , Resultado do Tratamento
16.
Am Heart J ; 227: 40-46, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32673830

RESUMO

BACKGROUND: The optimal antibiotic treatment length for infective endocarditis (IE) is uncertain. International guidelines recommend treatment duration of up to 6 weeks for patients with left-sided IE but are primarily based on historical data and expert opinion. Efficacies of modern therapies, fast recovery seen in many patients with IE, and complications to long hospital stays challenge the rationale for fixed treatment durations in all patients. OBJECTIVE: The objective was to conduct a noninferiority randomized controlled trial (acronym POET II) investigating the safety of accelerated (shortened) antibiotic therapy as compared to standard duration in patients with left-sided IE. METHODS: The POET II trial is a multicenter, multinational, open-label, noninferiority randomized controlled trial. Patients with definite left-sided IE due to Streptococcus spp, Staphylococcus aureus, or Enterococcus faecalis will be eligible for enrolment. Each patient will be randomized to accelerated antibiotic treatment or standard-length treatment (1:1) following clinical stabilization as defined by clinical parameters, laboratory values, and transesophageal echocardiography findings. Accelerated treatment will be between 2 and 4 weeks, whereas standard-length treatment will be between 4 and 6 weeks, depending on microbiologic etiology, complications, need for valve surgery, and prosthetic versus native valve endocarditis. The primary outcome is a composite of all-cause mortality, unplanned cardiac surgery, relapse of bacteremia, or embolization within 6 months of randomization. CONCLUSIONS: The POET II trial will investigate the safety of accelerated antibiotic therapy for patients with left-sided IE caused by Streptococcus spp, Staphylococcus aureus, or Enterococcus faecalis. The results of the POET II trial will improve the evidence base of treatment recommendations, and clinical practice may be altered.


Assuntos
Antibacterianos/administração & dosagem , Endocardite Bacteriana/tratamento farmacológico , Enterococcus faecalis , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Infecções Estreptocócicas/tratamento farmacológico , Estudos de Equivalência como Asunto , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Estudos Multicêntricos como Assunto , Fatores de Tempo
17.
PLoS Pathog ; 16(6): e1007806, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32497104

RESUMO

Coagulase-positive staphylococci, which frequently colonize the mucosal surfaces of animals, also cause a spectrum of opportunistic infections including skin and soft tissue infections, urinary tract infections, pneumonia, and bacteremia. However, recent advances in bacterial identification have revealed that these common veterinary pathogens are in fact zoonoses that cause serious infections in human patients. The global spread of multidrug-resistant zoonotic staphylococci, in particular the emergence of methicillin-resistant organisms, is now a serious threat to both animal and human welfare. Accordingly, new therapeutic targets that can be exploited to combat staphylococcal infections are urgently needed. Enzymes of the methylerythritol phosphate pathway (MEP) of isoprenoid biosynthesis represent potential targets for treating zoonotic staphylococci. Here we demonstrate that fosmidomycin (FSM) inhibits the first step of the isoprenoid biosynthetic pathway catalyzed by deoxyxylulose phosphate reductoisomerase (DXR) in staphylococci. In addition, we have both enzymatically and structurally determined the mechanism by which FSM elicits its effect. Using a forward genetic screen, the glycerol-3-phosphate transporter GlpT that facilitates FSM uptake was identified in two zoonotic staphylococci, Staphylococcus schleiferi and Staphylococcus pseudintermedius. A series of lipophilic ester prodrugs (termed MEPicides) structurally related to FSM were synthesized, and data indicate that the presence of the prodrug moiety not only substantially increased potency of the inhibitors against staphylococci but also bypassed the need for GlpT-mediated cellular transport. Collectively, our data indicate that the prodrug MEPicides selectively and robustly inhibit DXR in zoonotic staphylococci, and further, that DXR represents a promising, druggable target for future development.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla , Pró-Fármacos , Infecções Estafilocócicas , Staphylococcus , Zoonoses , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/metabolismo , Staphylococcus/genética , Staphylococcus/crescimento & desenvolvimento , Zoonoses/tratamento farmacológico , Zoonoses/genética , Zoonoses/metabolismo , Zoonoses/microbiologia
18.
PLoS One ; 15(6): e0235006, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32559258

RESUMO

Distal limb wounds are common injuries sustained by horses and their healing is fraught with complications due to equine anatomy, prevalence of infection, and challenges associated with wound management. Gallium is a semi-metallic element that has been shown to possess antimicrobial properties and aid in wound healing in various preclinical models. The effects of Gallium have not been studied in equine wound healing. Therefore, the objective of this study was to compare healing rates between gallium-treated and untreated wounds of equine distal limbs and to demonstrate the antimicrobial effects of gallium on wounds inoculated with S. aureus. Using an established model of equine wound healing we demonstrated beneficial effects of 0.5% topical gallium maltolate on equine wound healing. Specifically we documented reduced healing times, reduced bioburden, and reduced formation of exuberant granulation tissue in wounds treated with gallium maltolate as compared with untreated wounds. Gallium appeared to exert its beneficial effects via its well-described antimicrobial actions as well as by altering the expression of specific genes known to be involved in wound healing of horses and other animals. Specifically, gallium maltolate appeared to increase expression of transforming growth factor-ß in both infected and un-infected wounds. Further work is needed to document the effects of gallium on naturally occurring equine wounds and to compare the effects of gallium with other wound treatment options. These data, however, suggest that gallium may be an attractive and novel means of improving equine distal limb wound healing.


Assuntos
Antibacterianos/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Traumatismos da Perna/tratamento farmacológico , Compostos Organometálicos/uso terapêutico , Pironas/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Administração Tópica , Animais , Antibacterianos/administração & dosagem , Carga Bacteriana , Citocinas/genética , Citocinas/metabolismo , Doenças dos Cavalos/metabolismo , Cavalos , Traumatismos da Perna/metabolismo , Traumatismos da Perna/veterinária , Compostos Organometálicos/administração & dosagem , Pironas/administração & dosagem , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/veterinária , Cicatrização
19.
PLoS One ; 15(6): e0234484, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32511271

RESUMO

Inflammation plays a crucial role in the defense response of the innate immune system against pathogen infection. In this study, we selected 4 compounds for their potential or proven anti-inflammatory and/or anti-microbial properties to test on our in vitro model of bacteria-infected THP-1-derived macrophages. We first compared the capacity of sulforaphane (SFN), wogonin (WG), oltipraz (OTZ), and dimethyl fumarate (DMF) to induce the nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of the antioxidant, anti-inflammatory response pathways. Next, we performed a comparative evaluation of the antioxidant and anti-inflammatory efficacies of the 4 selected compounds. THP-1-derived macrophages and LPS-stimulated macrophages were treated with each compound and expression levels of genes coding for inflammatory cytokines IL-1ß, IL-6, and TNF-α were quantified by RT-qPCR. Moreover, expression levels of genes coding for M1 (IL-23, CCR7, IL-1ß, IL-6, and TNF-α) and M2 (PPARγ, MRC1, CCL22, and IL-10) markers were determined in classically-activated M1 macrophages treated with each compound. Finally, the effects of each compound on the intracellular bacterial survival of gram-negative E. coli and gram-positive S. aureus in THP-1-derived macrophages and PBMC-derived macrophages were examined. Our data confirmed the anti-inflammatory and antioxidant effects of SFN, WG, and DMF on LPS-stimulated THP-1-derived macrophages. In addition, SFN or WG treatment of classically-activated THP-1-derived macrophages reduced expression levels of M1 marker genes, while SFN or DMF treatment upregulated the M2 marker gene MRC1. This decrease in expression of M1 marker genes may be correlated with the decrease in intracellular S. aureus load in SFN- or DMF-treated macrophages. Interestingly, an increase in intracellular survival of E. coli in SFN-treated THP-1-derived macrophages that was not observed in PBMC-derived macrophages. Conversely, OTZ exhibited pro-oxidant and proinflammatory properties, and affected intracellular survival of E. coli in THP-1-derived macrophages. Altogether, we provide new potential therapeutic alternatives in treating inflammation and bacterial infection.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Inflamação/tratamento farmacológico , Ativação de Macrófagos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/imunologia , Estresse Oxidativo/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Fumarato de Dimetilo/farmacologia , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/imunologia , Flavanonas/farmacologia , Humanos , Inflamação/imunologia , Isotiocianatos/farmacologia , Leucócitos Mononucleares , Ativação de Macrófagos/imunologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Estresse Oxidativo/imunologia , Pirazinas/farmacologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/efeitos dos fármacos , Células THP-1
20.
PLoS One ; 15(6): e0235093, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584878

RESUMO

Bacterial biofilms are one of the major issues in the treatment of chronic infections such as chronic wounds, where biofilms are typically polymicrobial. The synergy between species can occur during most polymicrobial infections, where antimicrobial resistance enhances as a result. Furthermore, self-produced extracellular polymeric substance (EPS) in biofilms results in a high tolerance to antibiotics that complicates wound healing. Since most antibiotics fail to remove biofilms in chronic infections, new therapeutic modalities may be required. Disruption of EPS is one of the effective approaches for biofilm eradication. Therefore, degradation of EPS using enzymes may result in improved chronic wounds healing. In the current study, we investigated the efficacy of trypsin, ß-glucosidase, and DNase I enzymes on the degradation of dual-species biofilms of Pseudomonas aeruginosa and Staphylococcus aureus in a wound-like medium. These species are the two most common bacteria associated with biofilm formation in chronic wounds. Moreover, the reduction of minimum biofilm eradication concentration (MBEC) of meropenem and amikacin was evaluated when combined with enzymes. The minimum effective concentrations of trypsin, ß-glucosidase, and DNase I enzymes to degrade biofilms were 1 µg/ml, 8 U/ml, and 150 U/ml, respectively. Combination of 0.15 µg/ml trypsin and 50 U/ml DNase I had a significant effect on S. aureus-P. aeruginosa biofilms which resulted in the dispersal and dissolution of all biofilms. In the presence of the enzymatic mixture, MBECs of antibiotics showed a significant decrease (p < 0.05), at least 2.5 fold. We found that trypsin/DNase I mixture can be used as an anti-biofilm agent against dual-species biofilms of S. aureus-P. aeruginosa.


Assuntos
Antibacterianos/farmacologia , Biofilmes , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/fisiologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/fisiologia , Infecção dos Ferimentos/tratamento farmacológico , Ferimentos e Lesões/microbiologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Quimioterapia Combinada , Humanos , Infecção dos Ferimentos/microbiologia
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