scholarly journals Cardiac gene expression and function in a mouse model of community-acquired methicillin-resistant Staphylococcus aureus sepsis: Role of inflammatory caspases 1 and 11

2019 ◽  
Vol 17 ◽  
pp. 205873921983838
Author(s):  
Janet R Hume ◽  
Yuan Zhang ◽  
Lei Zhang ◽  
Marnie Peterson ◽  
Deborah L Carlson
Keyword(s):  
Staphylococcus Aureus ◽  
Inflammatory Mediators ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Myocardial Dysfunction ◽  
Methicillin Resistant ◽  
Tnf Α ◽  
Significant Difference ◽  
Invasive Infections ◽  
Cardiac Gene ◽  
And Function

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an important cause of invasive infections, including sepsis associated with myocardial dysfunction. Caspases 1 and 11, involved in activation of the inflammasome, have been shown to be critical in response to sepsis as well as myocardial dysfunction of numerous etiologies. We examined the survival, myocardial function, and production of inflammatory mediators in mice lacking caspases 1 and 11. Cas 1/11 KO mice demonstrated no significant difference in mortality or in cardiac shortening fraction relative to control mice. Cas 1/11 KO mice had significantly reduced upregulation of expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the heart relative to control mice after CA-MRSA infection, as well as reduced serum production of IL-1β, TNF-α, and IL-6, with no difference in IL-10 production. Other inflammatory mediators beyond IL-1β, TNF-α, and IL-6 may be involved in myocardial dysfunction in CA-MRSA sepsis.

scholarly journals Daptomycin versus Vancomycin for the Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infection with or without Endocarditis: A Systematic Review and Meta-Analysis

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1014
Author(s):  
Alberto Enrico Maraolo ◽  
Agnese Giaccone ◽  
Ivan Gentile ◽  
Annalisa Saracino ◽  
Davide Fiore Bavaro
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Meta Analysis ◽  
Bloodstream Infections ◽  
Clinical Failure ◽  
Methicillin Resistant ◽  
Significant Difference ◽  
All Cause Mortality ◽  
Invasive Infections ◽  
Secondary Outcomes

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of invasive infections, mainly bloodstream infections (BSI) with or without endocarditis. The purpose of this meta-analysis was to compare vancomycin, the mainstay treatment, with daptomycin as therapeutic options in this context. Materials: PubMed, Embase and the Cochrane Database were searched from their inception to 15 February 2020. The primary outcome was all-cause mortality. Secondary outcomes included clinical failure, infection recurrence, persistence of infection, length-of-stay, antibiotic discontinuation due to adverse events (AEs) and 30-day re-admission. This study was registered with PROSPERO, CRD42020169413. Results: Eight studies (1226 patients, 554 vs. 672 in daptomycin vs. vancomycin, respectively) were included. No significant difference in terms of overall mortality was observed [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.40–1.33, I2 = 67%]. Daptomycin was associated with a significantly reduced risk of clinical failure (OR 0.58, 95% CI 0.38–0.89, I2 = 60%), as confirmed by pooling adjusted effect sizes (adjusted OR against the use of vancomycin 1.94, 95%CI 1.33–1.82, I2 = 41%), and was linked with fewer treatment-limiting AEs (OR 0.15, 95%CI 0.06–0.36, I2 = 19%). No difference emerged between the two treatments as secondary outcomes. Results were not robust to unmeasured confounding (E-value lower than 95% CI 1.00 for all-cause mortality). Conclusions: Against MRSA BSI, with or without endocarditis, daptomycin seems to be associated with a lower risk of clinical failure and treatment-limiting AEs compared with vancomycin. Further studies are needed to better characterize the differences between the two drugs.

scholarly journals The basis of α-hemolysis Negative Methicillin-resistant Staphylococcus Aureus Isolates from Beijing Children’s Hospital

2021 ◽  
Author(s):  
Lijuan Wang ◽  
Chen Sun ◽  
Suyun Qian ◽  
Yingchao Liu ◽  
Kaihu Yao ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Amino Acid ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Clonal Complex ◽  
Common Mutation ◽  
Rna Expression ◽  
Single Mutation ◽  
Methicillin Resistant ◽  
Significant Difference ◽  
Important Virulence Factor

Abstract Background. Methicillin-resistant Staphylococcus aureus (MRSA) Clonal Complex 59 (CC59) clone has spread among Chinese children, resulting in many Staphylococcus aureus infections. α-hemolysin (Hlα) is an important virulence factor of Staphylococcus aureus, but little research has been done on CC59 isolates with negative α-hemolysis. Results. During the 4 periods (2009-2011, 2012-2013, 2016, 2017), 291 MRSA isolates were collected. Isolates with β and δ hemolysis accounted for 60.47% among the MRSA isolates in 2009-2011; 56.41% in 2012-2013; 77.14% in 2016; and 56.25% in 2017. most ST59 isolates (94.38%), 9 ST338 isolates (100%) showed β and δ hemolysis, both ST59 and ST338 clone belong to CC59 clone. Twenty-two ST239 isolates (73.33%), 8 ST88 isolates (80%), 4 ST5 isolates (100%), 13 ST22 isolates (92.86%) and 6 ST398 isolates (85.71%) showed α and δ hemolysis. α hemolysin in most clinical isolates is highly conservative, each showed one amino acid locus variation, the most common mutation was threonine at position 275 instead of isoleucine, then glutamic acid replaced aspartic acid at 208. Seventeen ST59 and 2 ST338 isolates had no mutation, 3 ST59 isolates showed single mutation (C448G), and only one ST59 isolate showed multilocus mutation. Other ST typing, such as ST1, ST5, ST88, ST20, ST239 and ST398, all had multilocus mutations, sites were from 3 to 8, no conservative sequence was found among isolates with the same ST typing. The carrying rates of RNA III, Rot, agrA, SarR, SarU and SigB were all over 93%, the carrying rates of SarZ and SarA genes were 41.86% and 34.88% respectively. Trancriptional levels of hlα in isolates showed α and δ hemolysis and β and δ hemolysis were equal. USA300 and R23 produced Hlα, R23 didn’t showed α hemolysis phenotype.Conclusions. Most clinical CC59 isolates from children in China were α hemolysis negative. There was no statistically significant difference in hlα gene and RNA expression, they produced the protein. The reason for the phenotypic deletion probably related to β hemolysin (Hlβ).

scholarly journals PREPARATION OF COLD CREAM AGAINST CLINICAL PATHOGEN USING CARALLUMA ADSCENDENS VAR. ATTENUATA

2020 ◽  
pp. 120-123
Author(s):  
SUNDAR MADASAMY ◽  
SURESH SUNDAN ◽  
LINGAKUMAR KRISHNASAMY
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Positive Control ◽  
Diffusion Method ◽  
Methicillin Resistant ◽  
Cold Cream ◽  
Significant Difference ◽  
Vancomycin Resistant

Objective: A simple formulation of cold cream from methanolic extract Caralluma adscendens var. attenuata (MECA) and their antimicrobial activity was tested against various clinical pathogens, namely, Escherichia coli, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and Candida albicans. Methods: Methanol extract of these plant extract was prepared by the Soxhlet method. We analyzed phytochemical nature of theses plant, and subsequently, a cream was formulated cold-cream C. adscendens var. attenuata (FCA) different concentration such as FCA 50 mg, FCA 100 mg, and FCA 200 mg. In the present study, aimed to the antimicrobial activity of cold cream was measured by agar well diffusion method, and standard antibiotic Neosporin (market available) cream was used as positive control and dummy cold cream (without-MECA) were used as the negative control. Results: Phytochemical screening showed that the plant extracts were found a rich source of secondary metabolites. For more, the efficacy of cold cream from MECA extracts to against the clinical pathogen. Positive control Neosporin and 200 mg FCA cream was a highly significant difference in the zone of inhibition when compared to dummy cream. The 200 mg FCA was activity against Escherichia coli, methicillin-resistant Staphylococcus aureus, vancomycin-resistant E. faecium, and C. albicans highly significantly difference (p<0.05) compared FCA 50 mg and FAC 100 mg creams. Conclusion: The results from this study suggested that the cold cream form base of MECA crude had antimicrobial activity in the different clinical pathogen. They could be used as an alternative source to conventional antimicrobial agents for the treatment of pathological infection.

scholarly journals 554. The Changing Epidemiology of Methicillin-Resistant Staphylococcus aureus Causing Bacteremia in Hiroshima, Japan During 2008–2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S263-S263
Author(s):  
Hiroki Kitagawa ◽  
Junzo Hisatsune ◽  
Hiroki Ohge ◽  
Motoyuki Sugai
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Sccmec Type ◽  
University Hospital ◽  
Methicillin Resistant ◽  
Type Iv ◽  
Time Period ◽  
Invasive Infections ◽  
Toxic Shock Syndrome Toxin ◽  
Mrsa Strains

Abstract Background Recently, the Japanese intrinsic community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) clone (CA-MRSA/J), classified as sequence type (ST) 8 carrying staphylococcal cassette chromosome mec (SCCmec) type IVl (ST8-IVl), has been identified that causes invasive infections similar to those of USA300 clone. However, epidemiological information regarding epidemic CA-MRSA clones is limited in Japan. This study was performed to investigate the changing epidemiology of MRSA causing bacteremia in Japan. Methods We performed whole-genome sequencing of MRSA isolates causing bacteremia at Hiroshima University Hospital between January 2008 and December 2017. MRSA isolates were subjected to multilocus sequence typing, SCCmec typing and were analyzed for virulence factors. Clinical data of patients with MRSA bacteremia were analyzed. Results A total of 193 MRSA strains causing bacteremia were identified during the study period. Among these, most belonged to ST764-IIa (30%; 59 of 193) and ST5-IIa (26.9%; 52 of 193). The proportion of ST5-IIa MRSA decreased from 39.6% (42 of 106) in 2008–2012 to 11.5% (10 of 87) in 2013–2017, and that of ST764-IIa MRSA increased from 23.6% (25 of 106) to 39.1% (34 of 87) in the same time period. The proportion of CA-MRSA (MRSA carrying SCCmec type IV or V) increased from 28.3% (30 of 106) in 2008–2012 to 42.5% (37 of 87) in 2013–2017. In CA-MRSA strains, clonal complex (CC) 8-IV MRSA was predominant (76.1%; 51 of 67). Those belonging to CC8-IV MRSA isolates were ST380-IVc (18 of 51), ST8-IVl (CA-MRSA/J; 15 of 51), ST8-IVj (15 of 51), ST8-IVa (2 of 51), and ST4803-IVl (1 of 51). The rate of hospital-onset infections of ST380-IVc, ST8-IVl, and ST8-IVj were 83.3%, 46.7%, and 60%, respectively. In CA-MRSA/J strains, including their variants (e.g., ST4803-IVl), 14 of 16 strains (87.5%) carried genes for toxic shock syndrome toxin (tst-1), enterotoxin C (sec), and enterotoxin L (sel), while none of the ST380-IVc and ST8-IVj MRSA strains carried these genes. Conclusion During the study period of 10 years, predominant ST5-IIa MRSA causing hospital-onset infections was replaced by ST764-IIa MRSA. In CA-MRSA clone, ST380-IVc, ST8-IVl (CA-MRSA/J), and ST8-IVj were dominant and have already spread to the healthcare environment. Disclosures All authors: No reported disclosures.

scholarly journals 204. Clinical Outcomes with Ceftaroline Monotherapy versus Daptomycin-Ceftaroline Combination Therapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S209-S210
Author(s):  
Gabriela Andonie ◽  
Elizabeth O Hand ◽  
Kelly R Reveles ◽  
Kristi A Traugott
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Clinical Outcomes ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Controlled Trial ◽  
Primary Source ◽  
Retrospective Chart Review ◽  
Combination Group ◽  
Methicillin Resistant ◽  
Significant Difference

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with poor outcomes and increased mortality. Daptomycin (DAP) and ceftaroline (CPT) in combination has been explored as a potential treatment option and showed improved outcomes compared to vancomycin/standard therapy. CPT monotherapy has been evaluated as salvage therapy for MRSA bacteremia but, to our knowledge, not as a comparator to DAP-CPT combination therapy. The purpose of this study is to compare the clinical outcomes of DAP and CPT combination therapy to CPT monotherapy in the setting of MRSA bacteremia. Methods A retrospective chart review of adult patients (≥ 18 years of age) admitted to University Health from January 2017 to December 2020 with a diagnosis of MRSA bacteremia was performed. Patients received either CPT monotherapy or DAP-CPT combination therapy for a minimum of 48 hours during their course of therapy. Results Thirty-two patients met inclusion criteria and were evaluated. Primary source of infection was pulmonary in the CPT monotherapy group (n=7/24; 29.2%) and osteomyelitis in the DAP-CPT combination group (n= 4/8; 50.0%). Median duration of bacteremia was 8 days and 9 days in the CPT monotherapy and DAP-CPT combination group, respectively. Microbiological cure was achieved in 95.8% (n=23/24) of patients in the CPT monotherapy and 100% (n=8/8) of patients in the DAP-CPT combination group. Bacteremia relapse (30 day, p=0.62; 60 day, p=0.63), readmission rates (30 day, p=0.62; 60 day, p=0.63), and mortality rates (30 day, p=0.70; 90 day, p=0.85) were similar in both groups. There was no statistically significant difference in safety parameters, including incidence of acute kidney injury (p=1.00) and creatine kinase elevations (p=1.00). Bone marrow suppression after at least 72 hours of therapy, including anemia, leukopenia, and thrombocytopenia, was also not statistically significant between groups. Conclusion This study was unable to find a statistically significant difference in clinical outcomes between patients receiving CPT monotherapy or DAP-CPT combination therapy. A large prospective, randomized controlled trial to assess CPT monotherapy and DAP-CPT combination therapy for the treatment of persistent MRSA bacteremia is warranted. Disclosures All Authors: No reported disclosures

scholarly journals PREVALENCE OF NASAL CARRIAGE OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS AMONG HEALTHCARE WORKERS IN THE DEPARTMENTS OF OTORINOLARYNGOLOGY AND DENTISTRY IN KYIV, UKRAINE

2020 ◽  
Vol 73 (12) ◽  
pp. 2563-2567
Author(s):  
Aidyn G. Salmanov ◽  
Taras P. Bondar ◽  
Yaroslav V. Shkorbotun ◽  
Evelina A. Chumak ◽  
Volodymyr O. Shkorbotun ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factor ◽  
Healthcare Workers ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Nasal Carriage ◽  
Diffusion Method ◽  
Methicillin Resistant ◽  
Significant Difference ◽  
Mrsa Strains ◽  
Encoding Genes

The aim: To obtain the first estimates of the current prevalence of nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) among healthcare workers (HCWs) in the departments of Otorinolaryngology and Dentistry and to determine of genes virulence factors (Panton Valentine Leukocidine (PVL) genes). Materials and methods: We performed a multicenter cross-sectional study. The susceptibility to antibiotics was determined by disk diffusion method according to the European Committee on Antimicrobial Susceptibility Testing. The virulence factor encoding genes, mecA, lukS-lukF, were detected by Polymerase Chain Reaction (PCR). Results: Incidence rate of S. aureus nasal carriage among HCWs was 36.2%, whereas MRSA carriage was 17%. Prevalence of MRSA carriage rate was 34.9% in Otorhinolaryngology departments and 9.7% in Dentistry. PCR testing confirmed that all MRSA strains were mecA gene-positive. The virulence factor encoding genes were detected in 82.3% of the S. aureus isolates from HCWs. Among S.aureus, the lukS-lukF genes were detected in over 59% of the strains. The lukS-lukF genes were detected in 55.5% of MRSA and in 58.9% of MSSA strains. LukS-lukF genes were most commonly co-present in MRSA strains. No significant difference was detected between the occurrences of lukS-lukF genes (P > 0.05). Conclusions: Personnell in otorhinolaryngology and dentistry departments have a high rate of nasal colonization of MRSA. This carrier state may be an important risk factor for transmission MRSA from physicians and nurses to patients and vice-versa. Screening for MRSA nasal carriage of HCWs is a key element in enabling infection control measures and early therapeutic decisions.

Curcumin Nanoparticles Improved Diabetic Wounds Infected With Methicillin-Resistant Staphylococcus aureus Sensitized With HAMLET

2020 ◽  
pp. 153473462093307
Author(s):  
Saeed Taghavifar ◽  
Fatemeh Afroughi ◽  
Maryam Saadati Keyvan
Keyword(s):  
Staphylococcus Aureus ◽  
Topical Application ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Male Rats ◽  
Methicillin Resistant ◽  
Sterile Saline ◽  
Curcumin Nanoparticles ◽  
Significant Difference ◽  
Infected Wounds ◽  
Diabetic Wounds

Accurately orchestrated course of events normally observed in healing are not followed in diabetic wounds, and bacterial colonization/infection further messes up the process. Novel therapeutic options for treatment of infections caused by multidrug-resistant Staphylococcus aureus are urgently needed. HAMLET (human α-lactalbumin made lethal to tumor cells) has been reported to be able to sensitize bacterial pathogens to traditional antimicrobial agents. The aim was to assess the wound healing activity of curcumin nanoparticles in diabetic wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) sensitized with HAMLET. Fifty male rats were randomized into 5 groups of 10 animals each. In CONTROL group, 0.1-mL sterile saline 0.9% solution was added to the wounds with no infection. In MRSA group, the wounds were infected with MRSA and only treated with 0.1-mL sterile saline 0.9% solution. In MRSA/HAMLET group, infected wounds were treated with HAMLET (100 µg). In MRSA/CNP group, animals with infected wounds were treated with 0.1 mL topical application of 1 mg/mL curcumin nanoparticles. In MRSA/CNP/HAMLET group, animals with infected wounds were treated with topical application of 0.1 mL solution of curcumin nanoparticles (1 mg/mL) and HAMLET (100 µg). All test formulations were applied for 10 days, twice a day, starting from first treatment. Microbiological examination; planimetric, biochemical, histological, and quantitative morphometric studies; immunohistochemical staining for angiogenesis; determination of hydroxyproline levels; and reverse transcription polymerase chain reaction for caspase 3, Bcl-2, and p53 showed that there was significant difference between animals in MRSA/CNP/HAMLET group compared with other groups ( P < .05). Curcumin nanoparticles improved diabetic wounds infected with MRSA sensitized with HAMLET and had the potential to offer more attention to this safer agent for topical use in infected diabetic wounds.

scholarly journals Comparison of Vancomycin Treatment Failures for Methicillin-Resistant Staphylococcus aureus Bacteremia Stratified by Minimum Inhibitory Concentration

2019 ◽  
Vol 35 (5) ◽  
pp. 203-207 ◽  
Author(s):  
Mary Joyce B. Wingler ◽  
Darrell T. Childress ◽  
Ricardo A. Maldonado
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Retrospective Chart Review ◽  
High Rate ◽  
Methicillin Resistant ◽  
Staphylococcus Aureus Bacteremia ◽  
Vancomycin Mics ◽  
Significant Difference ◽  
Alternative Agent ◽  
Vancomycin Treatment

Background: Optimal treatment of methicillin-resistant Staphylococcus aureus bacteremias (MRSABs) with vancomycin minimum inhibitory concentrations (MICs) high within the susceptible range is of concern due to the high rate of mortality and increased prevalence. Objective: The purpose of this study is to evaluate vancomycin treatment failures in patients with MRSAB stratified by vancomycin MIC. Methods: In this retrospective chart review, patients ≥19 years of age with MRSAB between July 2010 and December 2016 were included if they received intravenous vancomycin for ≥72 hours. Vancomycin treatment failures were compared between patients with vancomycin MICs of ≤1 mg/L and 2 mg/L. Vancomycin treatment failure was defined as microbiological failure at 7 days. Inpatient mortality, 30-day readmission, vancomycin-associated nephrotoxicity, and early bacteremia clearance at 48 to 96 hours were assessed as secondary endpoints. Results: Fifty-eight patients were included in the vancomycin MIC ≤1 mg/L group and 22 patients in the vancomycin MIC 2 mg/L group. No significant difference was found in vancomycin treatment failures at 7 days between groups (88% vs 91%, respectively; P = .850). At 96 hours, there was no significant difference in vancomycin treatment failures between groups (72% vs 90%, respectively; P = .127). No significant difference was found in mortality ( P > .99) or 30-day readmission ( P > .99). Conclusions: In this study, vancomycin treatment failures were not more prevalent in patients with vancomycin MIC of 2 mg/L at 7 days. Regardless of MIC, antibiotics should be switched to an alternative agent at 7 days for persistent bacteremia.

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