scholarly journals Rifampicin fails to eradicate mature biofilm formed by methicillin-resistant Staphylococcus aureus

2012 ◽  
Vol 45 (4) ◽  
pp. 471-474 ◽  
Author(s):  
Keli Cristine Reiter ◽  
Gustavo Enck Sambrano ◽  
Bárbara Villa ◽  
Thiago Galvão da Silva Paim ◽  
Caio Fernando de Oliveira ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Molecular Size ◽  
Bacterial Count ◽  
Minimal Bactericidal Concentration ◽  
Methicillin Resistant ◽  
Infection Treatment ◽  
Mrsa Infection ◽  
Count Recovery

INTRODUCTION: Antimicrobial activity on biofilms depends on their molecular size, positive charges, permeability coefficient, and bactericidal activity. Vancomycin is the primary choice for methicillin-resistant Staphylococcus aureus (MRSA) infection treatment; rifampicin has interesting antibiofilm properties, but its effectivity remains poorly defined. METHODS: Rifampicin activity alone and in combination with vancomycin against biofilm-forming MRSA was investigated, using a twofold serial broth microtiter method, biofilm challenge, and bacterial count recovery. RESULTS: Minimal inhibitory concentration (MIC) and minimal bactericidal concentration for vancomycin and rifampicin ranged from 0.5 to 1mg/l and 0.008 to 4mg/l, and from 1 to 4mg/l and 0.06 to 32mg/l, respectively. Mature biofilms were submitted to rifampicin and vancomycin exposure, and minimum biofilm eradication concentration ranged from 64 to 32,000 folds and from 32 to 512 folds higher than those for planktonic cells, respectively. Vancomycin (15mg/l) in combination with rifampicin at 6 dilutions higher each isolate MIC did not reach in vitro biofilm eradication but showed biofilm inhibitory capacity (1.43 and 0.56log10 CFU/ml reduction for weak and strong biofilm producers, respectively; p<0.05). CONCLUSIONS: In our setting, rifampicin alone failed to effectively kill biofilm-forming MRSA, demonstrating stronger inability to eradicate mature biofilm compared with vancomycin.

scholarly journals 1218. Retapamulin as a Potential Decolonizing Agent: Activity against Mupirocin-Resistant Strains From Pediatric Patients With Methicillin-Resistant Staphylococcus aureus Infection

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S369-S370
Author(s):  
Ami Patel ◽  
Jennifer Lighter-Fisher ◽  
Yi Fulmer ◽  
Richard Copin ◽  
Adam Ratner ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pediatric Patients ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Promising Alternative ◽  
Methicillin Resistant ◽  
Mrsa Infection ◽  
Mupirocin Resistance ◽  
Research Grant

Abstract Background Controlling methicillin-resistant Staphylococcus aureus (MRSA) colonization is a common strategy to prevent transmission and recurrent infection. Standard decolonization regimens include nasal application of mupirocin ointment; however, increasing rates of mupirocin-resistance (Mup-R) have been noted globally. At our institution there has been an increase in community-acquired MRSA (CA-MRSA) infections among children living in Brooklyn, New York. A genotypic geographic cluster of an outbreak clone of the CA-MRSA strain USA 300 with a high rate (&gt;85%) of mupirocin resistance, mediated by the plasmid borne mupA gene, was identified prompting investigation into an alternative decolonizing agent. We sought to investigate retapamulin, a topical pleuromutilin antibiotic, which has been shown to be effective against S. aureus with in vitro and in vivo activity against MRSA and a low propensity to develop resistance. Methods Broth microdilution was used to determine the minimum inhibitory concentrations (MIC) of retapamulin against 53 Mup-R MRSA isolates collected from pediatric patients (aged 9 months–17 years) presenting to our institution over an 18 month period with clinical MRSA infection. Susceptibility defined as ≤0.5 mg/L susceptible (EUCAST). Whole genome sequence data were analyzed for the presence of rplC and cfr gene mutations known to confer resistance to retapamulin. Results All 53 isolates were susceptible to retapamulin. 49/53 (92%) strains were inhibited at MIC 0.25 mg/L, 2/53 (4%) at MIC 0.125 mg/L, and 2/53 (4%) at MIC 0.5 mg/L. DNA sequence analysis showed that one isolate had a first-step mutation in the rplC gene, but it was not associated with reduced phenotypic susceptibility to retapamulin, as the MIC of that isolate was 0.25 mg/L. Conclusion Retapamulin demonstrated excellent in vitro activity against a genotypic cluster of Mup-R isolates from pediatric patients presenting to our institution with MRSA infection. These data suggest that retapamulin may be a promising alternative decolonization therapy for MRSA and a viable option to prevent the spread of mupirocin-resistant MRSA clones. Further research includes an ongoing randomized, placebo-controlled trial testing the in vivo efficacy of retapamulin as a nasal and perirectal decolonizing agent in children. Disclosures A. Patel, Aqua Pharmaceuticals: Investigator inititiated grant, Research grant. J. Lighter-Fisher, Aqua Pharmaceuticals: Investigator Initiated Grant, Research grant.

scholarly journals Immunization with a Bacterial Lipoprotein Establishes an Immuno-Protective Response with Upregulation of Effector CD4+ T Cells and Neutrophils Against Methicillin-Resistant Staphylococcus aureus Infection

Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 138 ◽  
Author(s):  
Zhenzi Peng ◽  
Duo-Yao Cao ◽  
Hui-Ya Wu ◽  
Suguru Saito
Keyword(s):  
Staphylococcus Aureus ◽  
T Cell ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Neutrophil Function ◽  
Effector Memory ◽  
Protective Response ◽  
Methicillin Resistant ◽  
Mrsa Infection ◽  
Prevention And Cure

Staphylococcus aureus (S. aureus) is a commensal bacterium in the human body; however, the bacterium frequently generates serious inflammation and infectious diseases. Some strains of S. aureus, such as methicillin-resistant Staphylococcus aureus (MRSA), are still a serious problem in public health facilities. Thus, an effective protection strategy is eagerly expected for the prevention and cure of MRSA infection. Here, we report that a specific fraction of an S. aureus lipoprotein (SA-LP) established a protective response against MRSA infection. The fractionated S. aureus lipoprotein SA-LP-F2, which is contained in 30–50 kDa of crude S. aureus lipoprotein (SA-LP-C), effectively activated dendritic cells (DCs) and the SA-LP-F2-pulsed DCs generated IFN-γ+CD4+ T (Th1) and IL-17A+CD4+ T (Th17) cells by in vitro antigen presentation. The SA-LP-F2 immunization upregulated the Th1 and Th17 populations so that MRSA colonization on the skin was suppressed during the challenge phase with MRSA. By following the effector T cell upregulation, the neutrophil function, which was a substantial effector cell against MRSA, was also enhanced in the SA-LP-F2-immunized mice. Finally, we found that the protective effect of SA-LP-F2 immunization was maintained for at least 90 days because the immunized mice continued to show a protective response during the MRSA challenge period. In the MRSA challenge, reactivated Th1 and Th17 populations were maintained in the SA-LP-F2-immunized mice as compared to naive mice. In addition, the neutrophil population was also upregulated in the mice. The memory CD4+ T cell (central memory T; TCM and effector memory T; TEM) population was established by SA-LP-F2 immunization and was maintained at higher levels than usual. Taken together, our findings may provide a breakthrough in the establishment of an immunization strategy against MRSA infection.

scholarly journals The Stringent Response Contributes to Persistent Methicillin-Resistant Staphylococcus aureus Endovascular Infection Through the Purine Biosynthetic Pathway

2020 ◽  
Vol 222 (7) ◽  
pp. 1188-1198 ◽  
Author(s):  
Liang Li ◽  
Arnold S Bayer ◽  
Ambrose Cheung ◽  
Lou Lu ◽  
Wessam Abdelhady ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Biosynthetic Pathway ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Stringent Response ◽  
Response Mechanism ◽  
Methicillin Resistant ◽  
Life Threatening ◽  
Mrsa Infection ◽  
Outcome Differences

Abstract Persistent methicillin-resistant Staphylococcus aureus (MRSA) endovascular infections represent a significant clinical-therapeutic challenge. Of particular concern is antibiotic treatment failure in infections caused by MRSA that are “susceptible” to antibiotic in vitro. In the current study, we investigate specific purine biosynthetic pathways and stringent response mechanism(s) related to this life-threatening syndrome using genetic matched persistent and resolving MRSA clinical bacteremia isolates (PB and RB, respectively), and isogenic MRSA strain sets. We demonstrate that PB isolates (vs RB isolates) have significantly higher (p)ppGpp production, phenol-soluble-modulin expression, polymorphonuclear leukocyte lysis and survival, fibronectin/endothelial cell (EC) adherence, and EC damage. Importantly, an isogenic strain set, including JE2 parental, relP-mutant and relP-complemented strains, translated the above findings into significant outcome differences in an experimental endocarditis model. These observations indicate a significant regulation of purine biosynthesis on stringent response, and suggest the existence of a previously unknown adaptive genetic mechanism in persistent MRSA infection.

scholarly journals In Vitro and In Vivo Activity of 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] Mutilin against Methicillin-Resistant Staphylococcus aureus

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3277
Author(s):  
Yunxing Fu ◽  
Chunqing Leng ◽  
Yuan Fan ◽  
Xia Ma ◽  
Xianghui Li ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Agent ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Skin Wound ◽  
Methicillin Resistant ◽  
Wound Model ◽  
New Antibiotics ◽  
Mrsa Infection

Staphylococcus aureus (S. aureus) is a major human pathogen that requires new antibiotics with unique mechanism. A new pleuromutilin derivative, 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] mutilin (DPTM), has been synthesized and proved as a potent antibacterial agent using in vitro and in vivo assays. In the present study, DPTM was further in vitro evaluated against methicillin-resistant Staphylococcus aureus (MRSA) isolated from dairy farms and outperformed tiamulin fumarate, a pleuromutilin drug used for veterinary. Moreover, a murine skin wound model caused by MRSA infection was established, and the healing effect of DPTM was investigated. The results showed that DPTM could promote the healing of MRSA skin infection, reduce the bacterial burden of infected skin MRSA and decrease the secretion of IL-6 and TNF-α inflammatory cytokines in plasma. These results provided the basis for further in-depth drug targeted studies of DPTM as a novel antibacterial agent.

scholarly journals Antimicrobial in vitro Study of Cosmos caudatus H.B.K Leaves Extract Towards Methicillin-Resistant Staphylococcus aureus (MRSA)

2015 ◽  
pp. 1
Author(s):  
Zahrah Febianti
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Antimicrobial Effect ◽  
Control Group ◽  
Dilution Method ◽  
Minimal Bactericidal Concentration ◽  
Methicillin Resistant ◽  
Cosmos Caudatus ◽  
Significant Difference

Cosmos caudatus H.B.K leaves is known to have many active substances with antimicrobial effect such as saponin, flavonoid, poliphenol, volatile oil, costunolide, and 4,4’-bipyridin. This research is conducted to prove the antimicrobial effect of Cosmos caudatus leaves extract on gram positive Methicillin-Resistant Staphylococcus aureus (MRSA) in vitro. The sample of this research is served by Microbiology Laboratorium of Brawijaya University. An experimental study with tube dilution method was carried out. The treated groups are groups of bacteria treated with Cosmos caudatus leaves extract with a range concentrations of 14%; 12%; 10%; 8%; and 6%. The control group is groups treated with 0% extract. The result indicates that the MIC (Minimal Inhibitory Concentration) can not be observed due to the extract’s turbid green colour. The MBC (Minimal Bactericidal Concentration) is 14% for MRSA. Data analysis with CI=95% shows a significant difference of effects on the number of MRSA colonies growth (Anova, p = 0,000) with the change of extract concentrations. The correlation regression test shows a strong association between the extract concentration and the number of colonies growth (Correlation, r = -0,754, p=0,000). Cosmos caudatus leaves extract has antimicrobial effect on MRSA.Keywords : Cosmos caudatus leaves estract, Methicillin-Resistant Staphylococcus aureus (MRSA), antimicrobial.

scholarly journals Group V Phospholipase A2 Mediates Endothelial Dysfunction and Acute Lung Injury Caused by Methicillin-Resistant Staphylococcus aureus

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1731
Author(s):  
Yu Maw Htwe ◽  
Huashan Wang ◽  
Patrick Belvitch ◽  
Lucille Meliton ◽  
Mounica Bandela ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Acute Lung Injury ◽  
Endothelial Dysfunction ◽  
Lung Injury ◽  
Phospholipase A2 ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Group V ◽  
Methicillin Resistant

Lung endothelial dysfunction is a key feature of acute lung injury (ALI) and clinical acute respiratory distress syndrome (ARDS). Previous studies have identified the lipid-generating enzyme, group V phospholipase A2 (gVPLA2), as a mediator of lung endothelial barrier disruption and inflammation. The current study aimed to determine the role of gVPLA2 in mediating lung endothelial responses to methicillin-resistant Staphylococcus aureus (MRSA, USA300 strain), a major cause of ALI/ARDS. In vitro studies assessed the effects of gVPLA2 inhibition on lung endothelial cell (EC) permeability after exposure to heat-killed (HK) MRSA. In vivo studies assessed the effects of intratracheal live or HK-MRSA on multiple indices of ALI in wild-type (WT) and gVPLA2-deficient (KO) mice. In vitro, HK-MRSA increased gVPLA2 expression and permeability in human lung EC. Inhibition of gVPLA2 with either the PLA2 inhibitor, LY311727, or with a specific monoclonal antibody, attenuated the barrier disruption caused by HK-MRSA. LY311727 also reduced HK-MRSA-induced permeability in mouse lung EC isolated from WT but not gVPLA2-KO mice. In vivo, live MRSA caused significantly less ALI in gVPLA2 KO mice compared to WT, findings confirmed by intravital microscopy assessment in HK-MRSA-treated mice. After targeted delivery of gVPLA2 plasmid to lung endothelium using ACE antibody-conjugated liposomes, MRSA-induced ALI was significantly increased in gVPLA2-KO mice, indicating that lung endothelial expression of gVPLA2 is critical in vivo. In summary, these results demonstrate an important role for gVPLA2 in mediating MRSA-induced lung EC permeability and ALI. Thus, gVPLA2 may represent a novel therapeutic target in ALI/ARDS caused by bacterial infection.

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