P2072 Bactericidal effect of Ltx peptides against Staphylococcus aureus in vitro and in murine skin infection model

2007 ◽  
Vol 29 ◽  
pp. S598
Author(s):  
R.L. Fischer ◽  
N. Frimodt-Møller ◽  
W. Stensen ◽  
J.S. Svendsen
Keyword(s):  
Staphylococcus Aureus ◽  
Skin Infection ◽  
Bactericidal Effect ◽  
Infection Model

scholarly journals Cefazolin and Ertapenem, a Synergistic Combination Used To Clear Persistent Staphylococcus aureus Bacteremia

2016 ◽  
Vol 60 (11) ◽  
pp. 6609-6618 ◽  
Author(s):  
George Sakoulas ◽  
Joshua Olson ◽  
Juwon Yim ◽  
Niedita B. Singh ◽  
Monika Kumaraswamy ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Skin Infection ◽  
Disk Diffusion ◽  
Pharmacodynamic Modeling ◽  
Infection Model ◽  
Content Type ◽  
Bloodstream Isolate ◽  
Drug Concentrations

ABSTRACTErtapenem and cefazolin were used in combination to successfully clear refractory methicillin-susceptibleStaphylococcus aureus(MSSA) bacteremia. In addition, recent work has demonstrated activity of combination therapy with beta-lactams from different classes against methicillin-resistantS. aureus(MRSA). The ertapenem-plus-cefazolin combination was evaluated for synergyin vitroandin vivoin a murine skin infection model using an index MSSA bloodstream isolate from a patient in whom persistent bacteremia was cleared with this combination and against a cadre of well-described research strains and clinical strains of MSSA and MRSA. Against the index MSSA bloodstream isolate, ertapenem and cefazolin showed synergy using both checkerboard (fractional inhibitory concentration [FIC] index = 0.375) and time-kill assays. Using a disk diffusion ertapenem potentiation assay, the MSSA isolate showed a cefazolin disk zone increased from 34 to 40 mm.In vitropharmacokinetic/pharmacodynamic modeling at clinically relevant drug concentrations demonstrated bactericidal activity (>3 log10-CFU/ml reduction) of the combination but bacteriostatic activity of ether drug alone at 48 h. A disk diffusion potentiation assay showed that ertapenem increased the cefazolin zone of inhibition by >3 mm for 34/35 (97%) MSSA and 10/15 (67%) MRSA strains. A murine skin infection model of MSSA showed enhanced activity of cefazolin plus ertapenem compared to monotherapy with these agents. After successful use in clearance of MSSA bacteremia, the combination of ertapenem and cefazolin showed synergy against MSSAin vitroandin vivo. This combination may warrant consideration for future clinical study in MSSA bacteremia.

scholarly journals The bactericidal effect of vancomycin is not altered by tranexamic acid, adrenalin, dexamethasone, or lidocaine in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christiane Schwerdt ◽  
Eric Röhner ◽  
Sabrina Böhle ◽  
Benjamin Jacob ◽  
Georg Matziolis
Keyword(s):  
Staphylococcus Aureus ◽  
Tranexamic Acid ◽  
Total Joint Arthroplasty ◽  
Staphylococcus Epidermidis ◽  
Joint Infection ◽  
Bactericidal Effect ◽  
Joint Arthroplasty ◽  
Zone Of Inhibition ◽  
Agar Diffusion Test

AbstractOne of the most challenging complications of total knee arthroplasty (TKA) is periprosthetic joint infection (PJI). There is growing evidence of a good anti-infective effect of intrawound vancomycin powder in total joint arthroplasty. At the same time, various different locally applied substances have become popular in total joint arthroplasty. The objective of this study was therefore to investigate a possible inhibition of the bactericidal effect of vancomycin by tranexamic acid, adrenalin, lidocaine, or dexamethasone. The bactericidal effect of vancomycin was quantified using the established method of the agar diffusion test. The plates were incubated with Staphylococcus aureus or Staphylococcus epidermidis and four wells were stamped out. The wells were filled with vancomycin alone, the tested substance alone or a mixture of the two. The fourth well remained empty as a control. The plates were incubated overnight at 37 °C and the zone of inhibition in each field was measured on the next day. All tests were run three times for each pathogen and mean values and standard deviations of the measurements were calculated. Differences between the substances were tested using the t-test at a level of significance of 0.05. The bacterial growth was homogeneous on all plates. The baseline value for the zone of inhibition of vancomycin was on average 6.2 ± 0.4 mm for Staphylococcus aureus and 12 ± 0.3 mm for Staphylococcus epidermidis. In all other substances, no inhibition was detected around the well. The combination of vancomycin and each other substance did not show any different result compared to vancomycin alone. The bactericidal effect of vancomycin on staphylococci is not altered by tranexamic acid, adrenalin, dexamethasone, or lidocaine in vitro.

scholarly journals Role of BrnQ1 and BrnQ2 in Branched-Chain Amino Acid Transport and Virulence in Staphylococcus aureus

2014 ◽  
Vol 83 (3) ◽  
pp. 1019-1029 ◽  
Author(s):  
Julienne C. Kaiser ◽  
Sameha Omer ◽  
Jessica R. Sheldon ◽  
Ian Welch ◽  
David E. Heinrichs
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Gene ◽  
Defined Medium ◽  
Infection Model ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Branched Chain Amino Acid ◽  
Branched Chain

The branched-chain amino acids (BCAAs; Ile, Leu, and Val) not only are important nutrients for the growth ofStaphylococcus aureusbut also are corepressors for CodY, which regulates virulence gene expression, implicating BCAAs as an important link between the metabolic state of the cell and virulence. BCAAs are either synthesized intracellularly or acquired from the environment.S. aureusencodes three putative BCAA transporters, designated BrnQ1, BrnQ2, and BrnQ3; their functions have not yet been formally tested. In this study, we mutated all threebrnQparalogs so as to characterize their substrate specificities and their roles in growthin vitroandin vivo. We demonstrated that in the community-associated, methicillin-resistantS. aureus(CA-MRSA) strain USA300, BrnQ1 is involved in uptake of all three BCAAs, BrnQ2 transports Ile, and BrnQ3 does not have a significant role in BCAA transport under the conditions tested. Of the three, only BrnQ1 is essential for USA300 to grow in a chemically defined medium that is limited for Leu or Val. Interestingly, we observed that abrnQ2mutant grew better than USA300 in media limited for Leu and Val, owing to the fact that this mutation leads to overexpression ofbrnQ1. In a murine infection model, thebrnQ1mutant was attenuated, but in contrast,brnQ2mutants had significantly increased virulence compared to that of USA300, a phenotype we suggest is at least partially linked to enhancedin vivoscavenging of Leu and Val through BrnQ1. These data uncover a hitherto-undiscovered connection between nutrient acquisition and virulence in CA-MRSA.

scholarly journals Biofilm/Persister/Stationary Phase Bacteria Cause More Severe Disease Than Log Phase Bacteria – II Infection with Persister Forms of Staphylococcus aureus Causes a Chronic Persistent Skin Infection with More Severe Lesion that Takes Longer to Heal and is not Eradicated by the Current Recommended Treatment in Mice

2018 ◽  
Author(s):  
Rebecca Yee ◽  
Yuting Yuan ◽  
Cory Brayton ◽  
Andreina Tarff Leal ◽  
Jie Feng ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Stationary Phase ◽  
Skin Infection ◽  
Bacterial Load ◽  
Mouse Skin ◽  
Infection Model ◽  
Persister Cells ◽  
Persistent Infections ◽  
Recommended Treatment ◽  
Biofilm Bacteria

AbstractStaphylococcus aureus is an opportunistic pathogen that can cause persistent infections clinically. Treatment for chronic S. aureus infections ranges from at least one week to several months and such infections are prone to relapse likely due to the presence of persistent forms of bacteria such as persister cells. Persister cells, which are bacterial cells that become dormant under stress conditions, can be isolated in vitro but their clinical significance in in vivo infections are largely unclear. Here, we evaluated S. aureus persistent forms using stationary phase cultures and biofilm bacteria (enriched in persisters) in comparison with log phase cultures in terms of their ability to cause disease in a mouse skin infection model. Surprisingly, we found that infection of mice with stationary phase cultures and biofilm bacteria produced a more severe chronic skin infection with more pronounced lesions which took longer to heal than log phase (actively growing) cultures. After two week infection, the bacterial load and skin tissue pathology, as determined by hyperplasia, immune cell infiltration, and crust/lesion formation, of mice infected with the more persistent forms (e.g. stationary phase bacteria and biofilm bacteria) were greater than mice infected with log phase bacteria. Using our persistent infection mouse model, we showed that the clinically recommended treatment for recurrent S. aureus skin infection, doxycycline + rifampin, was not effective in eradicating the bacteria in the treatment study, despite reducing lesion sizes and pathology in infected mice. Analogous findings were also observed in a Caenorhabditis elegans model, where S.aureus stationary phase cultures caused a greater mortality than log phase culture as early as two days post-infection. Thus, we established a new model for chronic persistent infections using persister bacteria that could serve as a relevant model to evaluate therapeutic options for persistent infections in general. Our findings connect persisters with persistent infections, have implications for understanding disease pathogenesis, and are likely to be broadly valid for other pathogens.

scholarly journals Antimicrobial Activity against Intraosteoblastic Staphylococcus aureus

2015 ◽  
Vol 59 (4) ◽  
pp. 2029-2036 ◽  
Author(s):  
Florent Valour ◽  
Sophie Trouillet-Assant ◽  
Natacha Riffard ◽  
Jason Tasse ◽  
Sacha Flammier ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Ex Vivo ◽  
Joint Infection ◽  
Treatment Strategies ◽  
Bactericidal Effect ◽  
Infection Model ◽  
Content Type ◽  
Intracellular Activity ◽  
Mg63 Cells ◽  
Choice Of Treatment

ABSTRACTAlthoughStaphylococcus aureuspersistence in osteoblasts, partly as small-colony variants (SCVs), can contribute to bone and joint infection (BJI) relapses, the intracellular activity of antimicrobials is not currently considered in the choice of treatment strategies for BJI. Here, antistaphylococcal antimicrobials were evaluated for their intraosteoblastic activity and their impact on the intracellular emergence of SCVs in anex vivoosteoblast infection model. Osteoblastic MG63 cells were infected for 2 h with HG001S. aureus. After killing the remaining extracellular bacteria with lysostaphin, infected cells were incubated for 24 h with antimicrobials at the intraosseous concentrations reached with standard therapeutic doses. Intracellular bacteria and SCVs were then quantified by plating cell lysates. A bactericidal effect was observed with fosfomycin, linezolid, tigecycline, oxacillin, rifampin, ofloxacin, and clindamycin, with reductions in the intracellular inocula of −2.5, −3.1, −3.9, −4.2, −4.9, −4.9, and −5.2 log10CFU/100,000 cells, respectively (P< 10−4). Conversely, a bacteriostatic effect was observed with ceftaroline and teicoplanin, whereas vancomycin and daptomycin had no significant impact on intracellular bacterial growth. Ofloxacin, daptomycin, and vancomycin significantly limited intracellular SCV emergence. Overall, ofloxacin was the only molecule to combine an excellent intracellular activity while limiting the emergence of SCVs. These data provide a basis for refining the choice of antibiotics to prioritise in the management of BJI, justifying the combination of a fluoroquinolone for its intracellular activity with an anti-biofilm molecule, such as rifampin.

scholarly journals Activity of Telavancin against Staphylococcus aureus Isolates, Including Those with Decreased Susceptibility to Ceftaroline, from Cystic Fibrosis Patients

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Melanie Roch ◽  
Maria Celeste Varela ◽  
Agustina Taglialegna ◽  
Warren E. Rose ◽  
Adriana E. Rosato
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Galleria Mellonella ◽  
Therapeutic Option ◽  
The United States ◽  
Infection Model ◽  
Content Type ◽  
Complicated Skin ◽  
Hospital Acquired

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) acquisition in cystic fibrosis (CF) patients confers a clinical outcome worse than that in non-CF patients with an increased rate of declined lung function. Telavancin, an approved lipoglycopeptide used to treat infections due to S. aureus, has a dual mode of action causing inhibition of peptidoglycan synthesis and membrane depolarization. MRSA infections in CF patients remain an important problem with no foreseeable decline in prevalence rates. Although telavancin is currently in clinical use for the treatment of complicated skin infections and hospital-acquired pneumonia, the activity against S. aureus infections in CF patients has not been investigated. In this work, we studied the activity of telavancin against CF patient-derived S. aureus strains collected from geographically diverse CF centers in the United States. We found that the telavancin MIC90 was 0.06 μg/ml, 8-fold lower than the ceftaroline or daptomycin MIC90 and 25-fold lower than the linezolid and vancomycin MIC90. We demonstrate that telavancin at serum free concentrations has rapid bactericidal activity, with a decrease of more than 3 log10 CFU/ml being achieved during the first 4 to 6 h of treatment, performing better in this assay than vancomycin and ceftaroline, including against S. aureus strains resistant to ceftaroline. Telavancin resistance was infrequent (0.3%), although we found that it can occur in vitro in both CF- and non-CF patient-derived S. aureus strains by progressive passages with subinhibitory concentrations. Genetic analysis of telavancin-resistant in vitro mutants showed gene polymorphisms in cell wall and virulence genes and increased survival in a Galleria mellonella infection model. Thus, we conclude that telavancin represents a promising therapeutic option for infections in CF patients with potent in vitro activity and a low resistance development potential.

scholarly journals Sanguiin H-6 Fractionated from Cloudberry (Rubus chamaemorus) Seeds Can Prevent the Methicillin-Resistant Staphylococcus aureus Biofilm Development during Wound Infection

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1481
Author(s):  
John Jairo Aguilera-Correa ◽  
Sara Fernández-López ◽  
Iskra Dennisse Cuñas-Figueroa ◽  
Sandra Pérez-Rial ◽  
Hanna-Leena Alakomi ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Wound Infection ◽  
Preventive Measure ◽  
Surgical Site Infections ◽  
Infection Model ◽  
Growth Media ◽  
Methicillin Resistant ◽  
Biofilm Development

Staphylococcus aureus is the most common cause of surgical site infections and its treatment is challenging due to the emergence of multi-drug resistant strains such as methicillin-resistant S. aureus (MRSA). Natural berry-derived compounds have shown antimicrobial potential, e.g., ellagitannins such as sanguiin H-6 and lambertianin C, the main phenolic compounds in Rubus seeds, have shown antimicrobial activity. The aim of this study was to evaluate the effect of sanguiin H-6 and lambertianin C fractionated from cloudberry seeds, on the MRSA growth, and as treatment of a MRSA biofilm development in different growth media in vitro and in vivo by using a murine wound infection model where sanguiin H-6 and lambertianin C were used to prevent the MRSA infection. Sanguiin H-6 and lambertianin C inhibited the in vitro biofilm development and growth of MRSA. Furthermore, sanguiin H-6 showed significant anti-MRSA effect in the in vivo wound model. Our study shows the possible use of sanguiin H-6 as a preventive measure in surgical sites to avoid postoperative infections, whilst lambertianin C showed no anti-MRSA activity.

scholarly journals In Vitro Bactericidal Activity of Human β-Defensin 3 against Multidrug-Resistant Nosocomial Strains

2006 ◽  
Vol 50 (2) ◽  
pp. 806-809 ◽  
Author(s):  
Giuseppantonio Maisetta ◽  
Giovanna Batoni ◽  
Semih Esin ◽  
Walter Florio ◽  
Daria Bottai ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Bactericidal Activity ◽  
Stenotrophomonas Maltophilia ◽  
Bactericidal Effect ◽  
Multidrug Resistant ◽  
Bacterial Strains ◽  
Gram Negative

ABSTRACT The antimicrobial activity of human β-defensin 3 (hBD-3) against multidrug-resistant clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter baumannii was evaluated. A fast bactericidal effect (within 20 min) against all bacterial strains tested was observed. The presence of 20% human serum abolished the bactericidal activity of hBD-3 against gram-negative strains and reduced the activity of the peptide against gram-positive strains.

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