Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.597
Filtrar
1.
Arch Microbiol ; 204(7): 391, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35699800

RESUMO

Antimicrobial resistance is an alarming problem, especially due to emergence of methicillin-resistance Staphylococcus aureus (MRSA). World Health Organization (WHO) has already listed MRSA as a top priority pathogen for the development of novel antibacterial agents. Presently, different therapeutic approaches against bacterial infections are in practice which includes targeting bacterial virulence factors, bacteriophage therapy, and manipulation of the microbiome. Natural products have been efficiently used for centuries to combat bacterial infections. Morchella is a natural fungal product which has been reported to possess broad-spectrum biological activities against bacterial infections. Hence, this study was aimed to evaluate the antibacterial efficacy of two macro-fungi against S. aureus, MRSA, and Streptococcus pyogenes (S. pyogenes). The antibacterial potential of both fungal extracts (Morchella esculenta and Morchella conica) was evaluated using disk diffusion and standard broth microdilution methods. The chemical compounds of both fungi were investigated using ultra-performance liquid chromatography mass spectroscopy (UPLC-MS) analysis. All fungal extracts inhibited growth of tested bacteria with inhibitory zone ranging from 10.66 ± 0.3 to 21.00 ± 1.5 mm. The minimum inhibitory concentration (MIC) of tested bacterial growth ranged from 03.33 to 16.0 mg/ml. It was noteworthy that Morchella extracts prevented S. aureus growth in a bactericidal manner with minimal bactericidal concentration (MBC) of 8-16 mg/ml. The extracts were also more effective against MRSA than currently available antibiotics. In conclusion, the growth inhibition of tested bacteria by fungal extracts revealed their potential as antibacterial agents and their compounds may be used as drug candidates.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Ascomicetos , Cromatografia Líquida , Meticilina/farmacologia , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , Staphylococcus aureus , Streptococcus pyogenes , Espectrometria de Massas em Tandem
2.
Biocontrol Sci ; 27(2): 87-97, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35753797

RESUMO

This study determined the prevalence of Staphylococcus aureus in food of animal origin, investigated its antimicrobial susceptibility profiles and antimicrobial-resistant genes encoding resistance to methicillin (mecA), penicillin (blaZ), and vancomycin (vanA). Two hundred and sixty food samples, including raw retail milk, meat, and meat products, were obtained from local retail shops in Mansoura city, Egypt. The overall prevalence of S. aureus in the total examined food samples was 32.69% (85/260). Methicillin-resistant S. aureus (MRSA) was identified in 11.15% (29/260) of the tested food samples. S. aureus indicated a high resistance to nalidixic acid, penicillin, ampicillin, cefuroxime, trimethoprim/sulfamethoxazole, and azithromycin. The multiple antibiotic resistance (MAR) rate was 89.4% of the total S. aureus isolates, and MARindex ranges from 0.05-0.64. Genotypically, mecA and blaZ genes were identified in a percentage of 34.11% and 82.35%, respectively, while no isolates harbored the vanA gene. The presence of MAR S. aureus particularly, MRSA in food samples, is of great concern and represents a possible threat to the community. Therefore, the study's findings highlight the importance of establishing vigilant food safety practices for food handlers to inhibit the transmission of S. aureus through the food chain to reduce public health risks.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Microbiologia de Alimentos , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus
3.
J Antibiot (Tokyo) ; 75(6): 354-359, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35459856

RESUMO

Epsilon-poly-L-lysine (EPL) is an antimicrobial peptide with low mammalian toxicity; thus, it is commonly used as food preservative. Here, the capacity of EPL to improve the efficacy of the antibiotics ampicillin (AMP), gentamycin (GEN), tetracycline (TCN), and methicillin (MET) against four bacterial pathogens, namely Pseudomonas aeruginosa PAO1, Klebsiella pneumoniae CG43, MET-sensitive Staphylococcus aureus ATCC 25923 (MSSA), and MET-resistant S. aureus ATCC 33591 (MRSA), was investigated. Some antibiotic-EPL combinations, i.e., AMP-EPL, GEN-EPL, and TCN-EPL, were particularly active against the pathogens through synergy, partial synergy, or additive effects. Additionally, MET-EPL displayed a partial synergistic effect against MRSA. GEN-EPL had the most powerful antimicrobial effect against MSSA: it eradicated the bacterium within an hour. Conversely, AMP-EPL and MET-EPL were the least potent combinations against MRSA, and TCN-EPL was least potent against K. pneumoniae; for these combinations, bactericidal activities occurred >10 h after initial treatments. All antibiotic-EPL treatments showed inhibitory activities against P. aeruginosa biofilm formation and enhanced preformed biofilm disruption in vitro. Similarly, the inhibition of biofilm formation on a porcine skin model was observed. Moreover, no significant cytotoxicity was detected for any antibiotic-EPL treatment in tests using Balb/3t3 fibroblasts. Given the rise in antibiotic-resistant bacteria, combining antibiotics with EPL may enhance antibiotic effectiveness, as shown in this study, while helping to avoid antimicrobial resistance.


Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Monofosfato de Adenosina , Ampicilina/farmacologia , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Gentamicinas/farmacologia , Mamíferos , Meticilina/farmacologia , Testes de Sensibilidade Microbiana , Polilisina/farmacologia , Pseudomonas aeruginosa , Suínos
4.
Sci Rep ; 12(1): 6668, 2022 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-35461321

RESUMO

Biofilm-associated infections are of great concern because they are associated with antibiotic resistance and immune evasion. Co-colonization by Staphylococcus aureus and Streptococcus pneumoniae is possible and a threat in clinical practice. We investigated the interaction between S. aureus and S. pneumoniae in mixed biofilms and tested new antibiofilm therapies with antioxidants N-acetyl-L-cysteine (NAC) and cysteamine (Cys). We developed two in vitro S. aureus-S. pneumoniae mixed biofilms in 96-well polystyrene microtiter plates and we treated in vitro biofilms with Cys and NAC analyzing their effect by CV staining and viable plate counting. S. pneumoniae needed a higher proportion of cells in the inoculum and planktonic culture to reach a similar population rate in the mixed biofilm. We demonstrated the effect of Cys in preventing S. aureus biofilms and S. aureus-S. pneumoniae mixed biofilms. Moreover, administration of 5 mg/ml of NAC nearly eradicated the S. pneumoniae population and killed nearly 94% of MSSA cells and 99% of MRSA cells in the mixed biofilms. The methicillin resistance background did not change the antioxidants effect in S. aureus. These results identify NAC and Cys as promising repurposed drug candidates for the prevention and treatment of mixed biofilms by S. pneumoniae and S. aureus.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Acetilcisteína/farmacologia , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Biofilmes , Cisteamina/farmacologia , Meticilina/farmacologia , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Streptococcus pneumoniae
5.
Microbiol Spectr ; 10(3): e0153021, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35438533

RESUMO

Our objective was to examine whether empirical antimicrobial therapy (EAT) against methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) with piperacillin-tazobactam (TZP), cefuroxime or combination therapy with one of these was differentially associated with 7-, 30-, and 90- day all-cause mortality or MS-SAB relapse. A multicenter retrospective cohort study of adults with MS-SAB from 2009 through 2018 was used, and 7-, 30-, 90-day mortality and relapse within 90 days were assessed and expressed as hazard ratio (HR) with a 95% confidence interval (95% CI) using Cox proportional hazard regression analysis. Matching of the two monotherapy groups was performed using propensity score matching. In total, 1158 MS-SAB cases were included and received one of three EAT regimens: TZP (n = 429), cefuroxime (n = 337), or TZP or cefuroxime with one or more additional effective antimicrobial (n = 392). The overall 30-day mortality was 28.0% (25.5 to 30.3%). After adjustment and matching, there was no significant difference in 7-, 30-, or 90-day mortality between the therapy groups. The matched HR of death was 0.81 (95% CI, 0.38 to 1.76) at 7 days, 0.82 (95% CI, 0.47 to 1.46) at 30 days, and 0.81 (95% CI, 0.50 to 1.32) at 90 days for TZP compared with cefuroxime. Adjusted HR of 90-day relapse was insignificant between the three therapy groups: TZP: 1.55 (95% CI, 0.54 to 4.43); combination therapy: 1.73 (95% CI, 0.62 to 4.80) compared to cefuroxime. There was no significant difference in 7-, 30-, or 90-day mortality or relapse between MS-SAB patients treated with empirical TZP or cefuroxime after adjustment and matching of covariables. IMPORTANCE This multicenter retrospective matched cohort study evaluated the effect of empirical antimicrobial therapy on the clinical outcome of methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) in >1100 adult patients. To the best of our knowledge, this is the largest study to date evaluating the effect of empirical treatment on the MS-SAB outcome. Importantly, the study found no significant difference in either short- or long-term mortality nor relapse between patients with MS-SAB receiving empirical treatment with cefuroxime or piperacillin-tazobactam. As such, this study provides crucial contemporary data supporting the widespread clinical practice of initiating empirical antimicrobial therapy of sepsis with ß-lactam-ß-lactamase-inhibitor.


Assuntos
Bacteriemia , Infecções Estafilocócicas , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Cefuroxima/farmacologia , Cefuroxima/uso terapêutico , Estudos de Coortes , Humanos , Meticilina/farmacologia , Meticilina/uso terapêutico , Piperacilina/farmacologia , Piperacilina/uso terapêutico , Recidiva , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Tazobactam/farmacologia , Tazobactam/uso terapêutico , Resultado do Tratamento
6.
Exp Eye Res ; 218: 109016, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35257714

RESUMO

The ever-increasing incidence of methicillin-resistant strains of Staphylococcus aureus (MRSA) endophthalmitis is of particular concern as they are associated with poor outcomes. To compare the histology and whole transcriptome of Methicillin resistant (MRSA) and Methicillin-susceptible (MSSA) Staphylococcus aureus endophthalmitis in an experimental murine model. MRSA and MSSA endophthalmitis was induced in C57BL/6 mice and disease progression was scored clinically and histologically at 24 h p.i. Retinal changes were monitored by H&E, CD45, MPO and GFAP staining followed by retinal cell death evaluation. Whole Transcriptome was analysed using the SuperPrint G3 Mouse Gene Expression v2 chip. Differential gene expression analysis (Limma package, R) was done followed by enrichment of pathways (KEGG database). Increased corneal haze, diminished vitreous clarity and red reflex was observed in MRSA infected mice eye compared to MSSA (p = 0.04). Histological assessment also corroborated with increased disease severity in MRSA (p = 0.02). Although MRSA infected eye displayed higher CD45+ cells and greater GFAP intensity, the difference was not statistically significant. However, higher retinal cell death was found to be associated with the MRSA infection (p = 0.007). Our study also revealed that MRSA infection induces changes in host transcriptome (FC = 1.5, p = 0.05), revealing the involvement of several interleukins (IL-11,15,10,1ra), chemokines (CCL-11, CXCL-1), Interferon receptors, GM-CSF, M-CSF, MMPs, Neruopilin2 (NRP-2), Ubiquitin associated peptidase and apoptotic ligands. ErbB signalling, JAK-STAT, adipocytokine and Ras signalling were the top divergently enriched pathways. Our study confirms the differential host immune response triggered by MRSA infection in the eye. Our study may help to elucidate the mechanisms of pathogenesis and to identify additional candidate drug targets for the treatment of MRSA endophthalmitis.


Assuntos
Endoftalmite , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Modelos Animais de Doenças , Endoftalmite/tratamento farmacológico , Meticilina/farmacologia , Meticilina/uso terapêutico , Resistência a Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/genética , Camundongos , Camundongos Endogâmicos C57BL , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Transcriptoma
7.
Eur J Med Chem ; 234: 114204, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35279608

RESUMO

A set of structurally related diphenylurea derivatives bearing aminoguanidine moiety were synthesized, and their antibacterial activity was assessed against a panel of multi-drug resistant Gram-positive clinical isolates. Two compounds 6 and 24 were identified with better bacteriological profile than the lead compound I. The multi-step resistance development studies indicated that MRSA are less likely to develop resistance toward diphenylurea compounds. Moreover, these compounds demonstrated a prolonged post-antibiotic effect than that of vancomycin. Furthermore, compounds 6 and 24 were able to re-sensitize VRSA to vancomycin, resulting in 8- to more than 32-fold improvement in vancomycin MIC values against clinical VRSA isolates. Finally, when assessed in an in vivo skin infection mouse model, the efficacy of compound 24 was very comparable to that of the commercially available fusidic acid ointment. Additionally, the diphenylurea 24 did not have a pronounced effect on the animal weights along the experiment indicating its safety and tolerability to mice. Taken together, these results indicate that the diphenylurea scaffold merits further investigation as a promising anti-staphylococcal treatment option.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Meticilina/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus , Relação Estrutura-Atividade , Vancomicina/farmacologia , Staphylococcus aureus Resistente à Vancomicina
8.
J Arthroplasty ; 37(7S): S674-S677, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35283230

RESUMO

BACKGROUND: Two-stage reimplantation is an effective treatment for periprosthetic joint infection (PJI). Many factors are involved in the variable success of this procedure. The purpose of this study is to examine the relationship between patient risk factors, comorbidities, and the pathogen on reinfection rates following two-stage reimplantation. METHODS: We evaluated 158 patients treated for PJI from 2008-2019. Only patients who had completed a two-stage exchange were included. Patient demographics, comorbidities, laboratory values, time-to-reimplantation, pathogen, antibiotic sensitivities, host status, and reinfection rates were assessed. Multivariate analysis was performed to identify correlation between risk factors and reinfection. A P-value < .05 was considered statistically significant. RESULTS: 31 patients experienced a reinfection (19.6%). There was a statistically significant association between infection with Methicillin Sensitive Staphylococcus Aureus (MSSA) and reinfection (P = .046). Patients with a reinfection also had a significantly greater median serum C-reactive protein (CRP) level (12.65 g/dL) at the time of diagnosis compared to patients without a reinfection (5.0 g/dL) (P = .010). Median Erythrocyte Sedimentation Rate (ESR) (56 in no re-infection and 69 in re-infection) and time-to-reimplantation (101 days in no reinfection and 141 days in reinfection) demonstrated a trend toward an association with re-infection but were not statistically significant (P = .055 and P = .054 respectively). CONCLUSION: As the number of arthroplasties continue to rise, PJIs are increasing proportionately and represent a significant revision burden. Elevated C-reactive protein (CRP) levels and Methicillin Sensitive Staphylococcus aureus (MSSA) infection were strongly associated with failure of a two-stage reimplantation. While not statistically significant with our numbers, there were strong trends toward an association between elevated Erythrocyte Sedimentation Rate (ESR), longer time-to-reimplantation, and reinfection.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Artroplastia do Joelho , Infecções Relacionadas à Prótese , Reinfecção , Reimplante , Infecções Estafilocócicas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Artrite Infecciosa/etiologia , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Proteína C-Reativa/análise , Humanos , Meticilina/farmacologia , Meticilina/uso terapêutico , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/etiologia , Reoperação , Estudos Retrospectivos , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/etiologia
9.
Colloids Surf B Biointerfaces ; 214: 112447, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35334310

RESUMO

The membrane of methicillin-resistant Staphylococcus aureus (MRSA) contains penicillin-binding proteins (PBPs) in the phospholipidic bilayer, with the protein PBP2a being linked with the resistance mechanism. In this work we confirm the role of PBP2a with molecular-level information obtained with Langmuir monolayers as cell membrane models. The MRSA cell membrane was mimicked with a mixed monolayer of dipalmitoyl phosphatidyl glycerol (DPPG) and cardiolipin (CL), also incorporating PBP2a. The surface pressure-area isotherms and the Brewster angle microscopy (BAM) images for these mixed monolayers were significantly affected by the antibiotic meropenem, which is PBP2a inhibitor. The meropenem effects were associated with the presence of PBP2a, as they were absent in the Langmuir monolayers without PBP2a. The relevance of PBP2a was confirmed with results where the antibiotic methicillin, known to be unsuitable to kill MRSA, had the same effects on mixed DPPG/CL and DPPG/CL-PBP2a monolayers since it prevented PBP2a from incorporating in the monolayer. The biological implication of the findings presented here is that a successful antibiotic against MRSA should be able to interact with PBP2a, but in the membrane.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Meropeném/metabolismo , Meropeném/farmacologia , Meticilina/farmacologia , Testes de Sensibilidade Microbiana , Proteínas de Ligação às Penicilinas/metabolismo , Proteínas de Ligação às Penicilinas/farmacologia
10.
Microbiol Spectr ; 10(1): e0232021, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35196789

RESUMO

Elasnin is a recently reported antibiofilm agent that is effective against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Remarkably, we observed that elasnin has a superior activity in eradicating daptomycin-resistant MRSA strain biofilm, with a lower minimum biofilm eradication concentration (MBEC) value of 0.625 µg/mL, compared to 2.5 µg/mL for the wild type. Confocal microscopy further confirmed the higher biofilm eradication on the daptomycin-resistant strain, displaying ∼53% decrease in cell density upon elasnin treatment, while the wild-type strain was only decreased by ∼15%. Quantitative proteomics revealed that the daptomycin-resistant strain has a lower expression of the membrane, cell wall, and extracellular proteins, and also proteins involved in the arginine biosynthesis, pathogenesis, and cell adhesion compared to the wild type, which may result in weaker biofilm development. This study highlights the potential clinical application of elasnin through its superior biofilm eradication activity against a daptomycin-resistant MRSA strain, and revealed the associated processes governing this superior activity through proteomics analysis. IMPORTANCE Due to the increased use of daptomycin for the treatment of MRSA infections, the emergence of daptomycin-resistant strains has become prevalent in recent years. In this study, we discovered that elasnin, a newly reported antibiofilm compound, has a superior activity in eradicating daptomycin-resistant MRSA strain biofilms compared to the wild type. Follow-up analysis revealed the reason behind this superior activity, which is the lower expression of key proteins that play a role in pathogenesis and cell adhesion in the daptomycin-resistant strain, leading to weaker biofilm development. This showcases the potential use of elasnin in clinical settings where daptomycin-resistant strains and biofilm formation are prevalent. Altogether, our study provides new insights into the mechanism of elasnin in MRSA biofilm cells and identified its superior biofilm eradicating activity in the daptomycin-resistant strain.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Daptomicina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/fisiologia , Pironas/farmacologia , Infecções Estafilocócicas/microbiologia , Farmacorresistência Bacteriana , Humanos , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico
11.
Vet Microbiol ; 267: 109374, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35220159

RESUMO

The purpose of this study was to describe the clonal diversity of Staphylococcus aureus strains derived from healthy dairy cattle and buffaloes as well as their close contact caretakers from the Nile Delta region, Egypt during 2019 and 2020, and to determine their antimicrobial resistance genotypes and virulence determinants. The study included 360 samples (120 from each, dairy cattle, buffaloes and their contact caretakers) collected from eight smallholding dairy herds.The samples included udder skin swabs, composite milk samples and rectal swabs (40 samples each of bovines) and nasal swabs, hand swabs and stool specimens (40 samples each of caretakers). S. aureus were isolated by classical techniques and characterised using the DNA microarray technology. A total of 62 methicillin-resistant (MRSA) and 130 methicillin-sensitive (MSSA) S. aureus isolates were identified. MRSA carriage rate ranged between 2.5% - 15% (Mean: 10%) in dairy cattle, 5% - 15% (9.2%) in dairy buffaloes and 27.5% - 37.5% (30.8%) among the caretakers. Nine different clonal lineages of MRSA (including CC22, CC152, CC5, CC30, CC88, CC45, CC121, CC97, and CC15), and six clonal lineages of MSSA (CC97, CC50, CC188, CC361, CC15 and CC1278) were inferred. The study demonstrated, for the first time, a high clonal diversity of multi-drug resistant S. aureus clones (particularly CC152-MRSA-V, CC30-MRSA-IV, CC121-MRSA-V, CC15-MRSA-V, CC97-MRSA-PseudoSCCmec, CC361-MSSA and CC1278-MSSA) which colonise dairy cattle and buffaloes as well as their caretakers particularly in Damietta villages that located at the northern Mediterranean coast of Egypt. The findings highlight the potential dynamics of humans and animals' S. aureus strains which may represent a health threat for both populations. The complete absence of the lukM/lukF-P83 genes in the recovered isolates indicated that all recovered cattle isolates (except for CC97) were descendants of human lineages and that these replaced the original cow lineages. Hence, a recommendation was given to farm owners to review their hygiene regimen to help minimize the microbiological risks for both populations.


Assuntos
Doenças dos Bovinos , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Búfalos/microbiologia , Bovinos , Doenças dos Bovinos/microbiologia , Células Clonais , Egito/epidemiologia , Feminino , Meticilina/farmacologia , Resistência a Meticilina/genética , Testes de Sensibilidade Microbiana/veterinária , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/veterinária , Staphylococcus aureus
12.
Antimicrob Resist Infect Control ; 11(1): 5, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35012641

RESUMO

BACKGROUND: Periprosthetic joint infection (PJI) causes significant morbidity. Methicillin sensitive Staphylococcus aureus (MSSA) is the most frequent organism, and the majority are endogenous. Decolonisation reduces PJIs but there is a paucity of evidence comparing treatments. Aims; compare 3 nasal decolonisation treatments at (1) achieving MSSA decolonisation, (2) preventing PJI. METHODS: Our hospital prospectively collected data on our MSSA decolonisation programme since 2013, including; all MSSA carriers, treatment received, MSSA status at time of surgery and all PJIs. Prior to 2017 MSSA carriers received nasal mupirocin or neomycin, from August 2017 until August 2019 nasal octenidine was used. RESULTS: During the study period 15,958 primary hip and knee replacements were performed. 3200 (20.1%) were MSSA positive at preoperative screening and received decolonisation treatment, 698 mupirocin, 1210 neomycin and 1221 octenidine. Mupirocin (89.1%) and neomycin (90.9%) were more effective at decolonisation than octenidine (50.0%, P < 0.0001). There was no difference in PJI rates (P = 0.452). CONCLUSIONS: Mupirocin and neomycin are more effective than octenidine at MSSA decolonisation. There was poor correlation between the MSSA status after treatment (on day of surgery) and PJI rates. Further research is needed to compare alternative MSSA decolonisation treatments.


Assuntos
Antibacterianos/uso terapêutico , Iminas/uso terapêutico , Mupirocina/uso terapêutico , Neomicina/uso terapêutico , Doenças Nasais/prevenção & controle , Piridinas/uso terapêutico , Infecções Estafilocócicas/prevenção & controle , Anti-Infecciosos Locais/uso terapêutico , Estudos de Coortes , Farmacorresistência Bacteriana , Inglaterra , Artropatias/microbiologia , Artropatias/prevenção & controle , Meticilina/farmacologia , Doenças Nasais/microbiologia , Estudos Retrospectivos , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia
13.
Antimicrob Agents Chemother ; 66(2): e0216621, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34978891

RESUMO

Cefazolin and ertapenem have been shown to be an effective salvage regimen for refractory methicillin-susceptible Staphylococcus aureus bacteremia. Our findings suggest cefazolin plus ertapenem in vitro stimulates interleukin-1ß release from peripheral blood monocytes both with and without S. aureus presence. This IL-1ß augmentation was primarily driven by ertapenem. These findings support further exploration of cefazolin plus ertapenem in MSSA bacteremia and may partially explain its marked potency in vivo despite modest synergy in vitro.


Assuntos
Bacteriemia , Infecções Estafilocócicas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Cefazolina/farmacologia , Cefazolina/uso terapêutico , Ertapenem , Humanos , Interleucina-1beta , Meticilina/farmacologia , Meticilina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus
14.
Int J Antimicrob Agents ; 59(3): 106537, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35093539

RESUMO

Ceftriaxone is a broad-spectrum cephalosporin that may be one option to treat methicillin-susceptible Staphylococcus aureus (MSSA). Although MSSA may be susceptible to ceftriaxone, the minimum inhibitory concentration (MIC) is generally two- to four-fold higher than other susceptible bacterial pathogens. This study aimed to explore the pharmacodynamics of ceftriaxone against MSSA and to determine the likely optimal dose. A hollow-fibre infection model was used with one clinical MSSA isolate (MIC = 4 mg/L) at an initial inoculum of 1 × 106 CFU/mL. Ceftriaxone dosing regimens of 1 g once and twice daily and 2 g once and twice daily were simulated. Ceftriaxone 1 g dosing regimens did not substantially impact bacterial killing within the first 12 h. Conversely, when administered as a 2 g dose either once or twice daily, an approximate 1-log10 bacterial reduction was observed where it plateaued for up to 96 h. No resistance was identified. Only a high ceftriaxone dose of 2 g twice daily achieves bacterial killing and sustained inhibition of bacterial growth. Ceftriaxone at routinely used doses is unsuitable for the treatment of MSSA infections and alternative agents should be preferentially used.


Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Humanos , Meticilina/farmacologia , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia
15.
Pediatr Infect Dis J ; 41(1): 12-19, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34889869

RESUMO

BACKGROUND: The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) has changed in recent years. The present article is intended to establish differences between clinical, laboratory and imaging findings and outcomes of MSSA and MRSA infections, as well as among subgroups of infection such as skin and soft tissue infection, osteoarticular, bacteremia or pneumonia in a pediatric population from Bogota, Colombia. METHODS: Retrospective cohort study using clinical records of patients under 18 years of age treated at the participating centers in Bogota, Colombia, between 2014 and 2018. The first positive S. aureus culture was studied. MSSA and MRSA were compared. The χ2 test, Fisher exact test, and Kruskal-Wallis test were calculated, and the statistical significance was presented using the difference and its 95% CI. RESULTS: Five hundred fifty-one patients were included; 211 (38%) corresponded to MRSA and 340 (62%) to MSSA for a total of 703 cultures. A significantly higher probability of having an MSSA infection than MRSA was found in patients with previous heart disease (3.3% vs. 0.5%), neurologic disease (5.9% vs. 2.5%), recent major surgeries (11% vs. 5%) or who has an implanted device (11% vs. 4%). In contrast, in severe MRSA infections (bacteremia, osteoarticular infections and pneumonia), a higher rate of complications was seen (admission to the pediatric intensive care unit, mechanical ventilation and vasoactive support), and in osteoarticular MRSA, more than 1 surgery per case was seen (89% vs. 61%). Laboratory results and mortality were similar. CONCLUSIONS: MRSA was associated with a more severe course in bacteremia, osteoarticular infections and pneumonia. Some classical risk factors associated with MRSA infections were found to be related to MSSA. In general, with the exception of skin and soft tissue infection, there was an increased risk of pediatric intensive care unit admission and mechanical and inotropic support with MRSA in a pediatric population.


Assuntos
Staphylococcus aureus Resistente à Meticilina/patogenicidade , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/patogenicidade , Adolescente , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Colômbia/epidemiologia , Feminino , Hospitalização , Humanos , Lactente , Masculino , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Fatores de Risco , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos
16.
Artigo em Inglês | MEDLINE | ID: mdl-34861721

RESUMO

OBJECTIVE: Autogenous Staphylococcus pseudintermedius bacterins can reduce prescribing of antimicrobials in the management of canine recurrent pyoderma. However, increasing prevalence of meticillin-resistant, mecA-positive S. pseudintermedius (MRSP) raises concern over dispersal of mecA through bacterin therapy. We investigated the presence and integrity of mecA in bacterin formulations after manufacturing. MATERIAL AND METHODS: Twenty clinical isolates (12 MRSP, 7 MR-S. aureus, 1 meticillin-susceptible SP) were investigated. Pellets from overnight growth were washed 3 times with 0.5 % phenol saline, followed by addition of 0.1 ml 10 % formal-saline to 10 ml phenol-saline. Sterility was confirmed, and DNA extracted using both a standard genomic extraction kit and one recommended for formalin-fixed tissue samples (FFPE). The presence of mecA was determined after PCR and its integrity examined in 5 randomly selected samples after sequencing. RESULTS: In all bacterins from meticillin-resistant isolates, mecA was detected following FFPE extraction; products aligned fully to a reported mecA sequence. After standard DNA extraction, mecA was seen in 16/19 samples. CONCLUSION: Persistence of mecA in MRSP bacterins suggests that dispersal of this important resistance mediator through therapy may be possible. While the ability of skin bacteria to uptake naked DNA remains unclear, it seems prudent to only formulate autogenous bacterins from mecA-negative S. pseudintermedius to avoid unnecessary spread of mecA.


Assuntos
Doenças do Cão , Staphylococcus aureus Resistente à Meticilina , Pioderma , Animais , Antibacterianos/uso terapêutico , Vacinas Bacterianas , Doenças do Cão/tratamento farmacológico , Cães , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana/veterinária , Pioderma/tratamento farmacológico , Pioderma/veterinária , Staphylococcus , Staphylococcus aureus
17.
Euro Surveill ; 26(46)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34794536

RESUMO

BackgroundInvasive infections caused by Staphylococcus aureus have high clinical and epidemiological relevance. It is therefore important to monitor the S. aureus trends using suitable methods.AimThe study aimed to describe the trends of bloodstream infections (BSI) caused by meticillin-resistant S. aureus (MRSA) and meticillin-susceptible S. aureus (MSSA) in the European Union (EU) and the European Economic Area (EEA).MethodsAnnual data on S. aureus BSI from 2005 to 2018 were obtained from the European Antimicrobial Resistance Surveillance Network (EARS-Net). Trends of BSI were assessed at the EU/EEA level by adjusting for blood culture set rate (number of blood culture sets per 1,000 days of hospitalisation) and stratification by patient characteristics.ResultsConsidering a fixed cohort of laboratories consistently reporting data over the entire study period, MRSA percentages among S. aureus BSI decreased from 30.2% in 2005 to 16.3% in 2018. Concurrently, the total number of BSI caused by S. aureus increased by 57%, MSSA BSI increased by 84% and MRSA BSI decreased by 31%. All these trends were statistically significant (p < 0.001).ConclusionsThe results indicate an increasing health burden of MSSA BSI in the EU/EEA despite a significant decrease in the MRSA percentage. These findings highlight the importance of monitoring antimicrobial resistance trends by assessing not only resistance percentages but also the incidence of infections. Further research is needed on the factors associated with the observed trends and on their attributable risk.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Sepse , Infecções Estafilocócicas , União Europeia , Humanos , Meticilina/farmacologia , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus
18.
Proc Natl Acad Sci U S A ; 118(44)2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34716264

RESUMO

Bacterial cell wall peptidoglycan is essential, maintaining both cellular integrity and morphology, in the face of internal turgor pressure. Peptidoglycan synthesis is important, as it is targeted by cell wall antibiotics, including methicillin and vancomycin. Here, we have used the major human pathogen Staphylococcus aureus to elucidate both the cell wall dynamic processes essential for growth (life) and the bactericidal effects of cell wall antibiotics (death) based on the principle of coordinated peptidoglycan synthesis and hydrolysis. The death of S. aureus due to depletion of the essential, two-component and positive regulatory system for peptidoglycan hydrolase activity (WalKR) is prevented by addition of otherwise bactericidal cell wall antibiotics, resulting in stasis. In contrast, cell wall antibiotics kill via the activity of peptidoglycan hydrolases in the absence of concomitant synthesis. Both methicillin and vancomycin treatment lead to the appearance of perforating holes throughout the cell wall due to peptidoglycan hydrolases. Methicillin alone also results in plasmolysis and misshapen septa with the involvement of the major peptidoglycan hydrolase Atl, a process that is inhibited by vancomycin. The bactericidal effect of vancomycin involves the peptidoglycan hydrolase SagB. In the presence of cell wall antibiotics, the inhibition of peptidoglycan hydrolase activity using the inhibitor complestatin results in reduced killing, while, conversely, the deregulation of hydrolase activity via loss of wall teichoic acids increases the death rate. For S. aureus, the independent regulation of cell wall synthesis and hydrolysis can lead to cell growth, death, or stasis, with implications for the development of new control regimes for this important pathogen.


Assuntos
Parede Celular/fisiologia , Peptidoglicano/metabolismo , Staphylococcus aureus/crescimento & desenvolvimento , Antibacterianos/farmacologia , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Proteínas de Bactérias/metabolismo , Parede Celular/metabolismo , Homeostase , Meticilina/farmacologia , N-Acetil-Muramil-L-Alanina Amidase/metabolismo , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/metabolismo , Ácidos Teicoicos/metabolismo , Vancomicina/farmacologia
19.
Microbiol Res ; 252: 126864, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34521050

RESUMO

Biofilm formation by pathogenic bacteria as well as their resilience to antibiotic treatments are a major health problem. Here, we sequenced and analyzed the genome of the clinical methicillin-resistant Staphylococcus aureus S1 (MRSA-S1) strain and established its sensitivity to the combination of methicillin and the leaderless two peptides enterocin DD14 (EntDD14). Such sensitivity was assessed in vitro based on the MIC/FIC values as well as on killing curves experiments. Moreover, combination of EntDD14 and methicillin was able to reduce the biofilm formation of Staphylococcus aureus S1 of about ∼30 %. Interestingly, genes thought to be involved in the virulence of MRSA-S1, like nuc and pvl which code, respectively, for nuclease and Panton-Valentine leucocidin, were shown to be downregulated following treatment with EntDD14 and methicillin. Similar effects were registered for other genes such as cflA, cflB and icaB, coding for bacterial ligands clumping factors A, B and intercellular adhesion factor respectively. All these data, suggest that combinations of bacteriocins and antibiotics are useful as a backup for treatment of bacterial infections.


Assuntos
Farmacorresistência Bacteriana , Sinergismo Farmacológico , Staphylococcus aureus Resistente à Meticilina , Meticilina , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
20.
Int J Antimicrob Agents ; 58(5): 106429, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34469802

RESUMO

OBJECTIVES: We compared the effectiveness of cefazolin and cloxacillin as definitive antibiotic therapy for methicillin-susceptible Staphylococcus aureus (MSSA) spinal epidural abscess (SEA). METHODS: This retrospective cohort study included patients with MSSA SEA from two academic hospitals in Hamilton, Ontario, Canada, between 2014 and 2020. Patients treated with cefazolin were compared to those treated with cloxacillin. Co-primary outcomes included 90-day mortality, antibiotic failure, adverse reactions and recurrence. Inverse probability of treatment weighting using propensity scores was used to balance important prognostic factors and to estimate an adjusted risk difference. RESULTS: Of 98 patients with MSSA SEA, 50 and 48 patients were treated with cefazolin and cloxacillin, respectively. Mortality at 90 days was 8% and 13% in the cefazolin and cloxacillin groups, respectively (P = 0.52). The antibiotic failure rate was 12% and 19% in the cefazolin and cloxacillin groups, respectively (P = 0.41). The serious adverse reactions rate was 0% and 4% in the cefazolin and cloxacillin groups, respectively (P = 0.24). The recurrence rate was 2% and 8% in the cefazolin and cloxacillin groups, respectively (P = 0.20). The adjusted risk difference for mortality at 90 days was -1% [95% confidence interval (CI) -10% to 8%] favouring cefazolin. The adjusted risk differences for antibiotic failure, adverse reactions and recurrence were 1% (95% CI -12% to 14%), -5% (95% CI -11% to 2%) and -18% (-36% to -1%) respectively. CONCLUSION: Cefazolin is likely as effective as an antistaphylococcal penicillin and may be considered as a first-line treatment for MSSA SEA.


Assuntos
Antibacterianos/uso terapêutico , Cefazolina/uso terapêutico , Cloxacilina/uso terapêutico , Abscesso Epidural/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Idoso , Antibacterianos/efeitos adversos , Canadá , Cefazolina/efeitos adversos , Cloxacilina/efeitos adversos , Abscesso Epidural/microbiologia , Feminino , Humanos , Masculino , Meticilina/farmacologia , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Infecções Estafilocócicas/mortalidade , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...