scholarly journals Virtual Screening for Novel SarA Inhibitors to Prevent Biofilm Formation of Staphylococcus aureus in Prosthetic Joint Infections

2020 ◽  
Vol 11 ◽  
Author(s):  
Jinlong Yu ◽  
Feng Jiang ◽  
Feiyang Zhang ◽  
Yunqi Pan ◽  
Jianqiang Wang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virtual Screening ◽  
Biofilm Formation ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

scholarly journals 620. Sub-MIC Concentrations of Levofloxacin and Delafloxacin Enhance Staphylococcus aureus Biofilm Formation: Significance of Maximizing Exposure

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S288-S288
Author(s):  
Emily C Bodo ◽  
Kathryn E Daffinee ◽  
Kerry LaPlante
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Growth Control ◽  
Joint Fluid ◽  
Percent Change ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Biofilm Quantification ◽  
Peak Increase

Abstract Background Fluoroquinolones are utilized in Staphylococcal prosthetic joint infections due to their anti-biofilm activity. When antibiotic dosing is not optimized or antibiotics do not reach the site of infection, additional virulence factors may upregulate. We aimed to determine whether exposure to sub-MIC concentrations of levofloxacin and delafloxacin affect biofilm formation in Staphylococcus aureus. Methods This study utilized 50 diverse methicillin-susceptible S. aureus (MSSA) clinical isolates collected between 2004 and 2018. Sources included blood, skin/tissue, bone, and joint fluid. Minimum inhibitory concentrations and minimum bactericidal concentrations were identified according to CLSI. Biofilm assays were conducted as previously described by our program. Biofilm quantification was categorized as strong (OD570 ≥ 2), moderate (OD570 ≥ 1 and < 2), or weak (OD570 < 1). Prevention assays were conducted with the addition of increasing concentrations of delafloxacin or levofloxacin. We evaluated the amount of isolates that demonstrated increased biofilm formation in the presence of sub-MIC concentrations and extent of biofilm enhancement. Percent change was calculated between OD570 of the isolate growth control without antibiotic exposure and peak biofilm OD570 when exposed to the antibiotic. Results Of the 50 MSSA isolates, 14 (28%) exhibited moderate/strong formation and 36 (32%) exhibited weak biofilm formation. 52% and 58% of the isolates demonstrated a ≥50% increase in formation when exposed to sub-MIC concentrations of delafloxacin and levofloxacin, respectively. None of the strong biofilm formers demonstrated a ≥50% peak increase in formation when exposed to the antibiotics. Of the isolates that demonstrated a ≥50% peak increase, the average percent change was 267% (±29) with levofloxacin and 258% (±33) with delafloxacin. Conclusion Sub-MIC concentrations of delafloxacin and levofloxacin increased biofilm formation in S. aureus isolates that normally exhibit weak or moderate biofilm formation when not in the presence of antibiotics. Maintaining appropriate fluoroquinolone concentrations at the site of action is critical in preventing enhancement of biofilm formation. Further research is needed to identify the mechanism behind this increase. Disclosures All authors: No reported disclosures.

scholarly journals Antibiotics in Bone Cements Used for Prosthesis Fixation: An Efficient Way to Prevent Staphylococcus aureus and Staphylococcus epidermidis Prosthetic Joint Infection

2021 ◽  
Vol 7 ◽  
Author(s):  
Andréa Cara ◽  
Mathilde Ballet ◽  
Claire Hemery ◽  
Tristan Ferry ◽  
Frédéric Laurent ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Joint Infection ◽  
Bone Cements ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Prosthesis Fixation

Prosthetic joint infections (PJIs) are one of the most frequent reasons for arthroplasty revision. These infections are mostly associated with the formation of biofilm, notably by staphylococci, such as Staphylococcus aureus and Staphylococcus epidermidis. To minimize the rates of PJIs following primary or revision total joint arthroplasty, antibiotic-loaded bone cements (ALBCs) can be used for prosthesis fixation. However, its use is still debated. Indeed, various studies reported opposite results. In this context, we aimed to compare the prophylactic anti-biofilm activity of ALBCs loaded with two antibiotics with ALBC loaded with only one antibiotic. We compared commercial ready-to-use cements containing gentamicin alone, gentamicin plus vancomycin, and gentamicin plus clindamycin to plain cement (no antibiotic), investigating staphylococcal biofilm formation for 10 strains of S. aureus and S. epidermidis with specific resistance to gentamicin, vancomycin, or clindamycin. Firstly, we performed disk diffusion assays with the elution solutions. We reported that only the cement containing gentamicin and clindamycin was able to inhibit bacterial growth at Day 9, whereas cements with gentamicin only or gentamicin and vancomycin lost their antibacterial activity at Day 3. Then, we observed that all the tested ALBCs can inhibit biofilm formation by methicillin-susceptible staphylococci without other antibiotic resistance ability. Similar results were observed when we tested vancomycin-resistant or clindamycin-resistant staphylococci, with some strain-dependent significant increase of efficacy for the two antibiotic ALBCs when compared with gentamicin-loaded cement. However, adding vancomycin or clindamycin to gentamicin allows a better inhibition of biofilm formation when gentamicin-resistant strains were used. Our in vitro results suggest that using commercially available bone cements loaded with gentamicin plus vancomycin or clindamycin for prosthesis fixation can help in preventing staphylococcal PJIs following primary arthroplasties, non-septic revisions or septic revisions, especially to prevent PJIs caused by gentamicin-resistant staphylococci.

scholarly journals Bactericidal Action of Daptomycin against Stationary-Phase and Nondividing Staphylococcus aureus Cells

2007 ◽  
Vol 51 (12) ◽  
pp. 4255-4260 ◽  
Author(s):  
Carmela T. M. Mascio ◽  
Jeff D. Alder ◽  
Jared A. Silverman
Keyword(s):  
Staphylococcus Aureus ◽  
Stationary Phase ◽  
Bactericidal Activity ◽  
Direct Action ◽  
Metabolic Inhibitor ◽  
Log Reduction ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Lipopeptide Antibiotic

ABSTRACT Most antibiotics with bactericidal activity require that the bacteria be actively dividing to produce rapid killing. However, in many infections, such as endocarditis, prosthetic joint infections, and infected embedded catheters, the bacteria divide slowly or not at all. Daptomycin is a lipopeptide antibiotic with a distinct mechanism of action that targets the cytoplasmic membrane of gram-positive organisms, including Staphylococcus aureus. Daptomycin is rapidly bactericidal against exponentially growing bacteria (a 3-log reduction in 60 min). The objectives of this study were to determine if daptomycin is bactericidal against nondividing S. aureus and to quantify the extent of the bactericidal activity. In high-inoculum methicillin-sensitive S. aureus cultures in stationary phase (1010 CFU/ml), daptomycin displayed concentration-dependent bactericidal activity, requiring 32 μg/ml to achieve a 3-log reduction. In a study comparing several antibiotics at 100 μg/ml, daptomycin demonstrated faster bactericidal activity than nafcillin, ciprofloxacin, gentamicin, and vancomycin. In experiments where bacterial cell growth was halted by the metabolic inhibitor carbonyl cyanide m-chlorophenylhydrazone or erythromycin, daptomycin (10 μg/ml) achieved the bactericidal end point (a 3-log reduction) within 2 h. In contrast, ciprofloxacin (10 μg/ml) did not produce bactericidal activity. Daptomycin (2 μg/ml) remained bactericidal against cold-arrested S. aureus, which was protected from the actions of ciprofloxacin and nafcillin. The data presented here suggest that, in contrast to that of other classes of antibiotics, the bactericidal activity of daptomycin does not require cell division or active metabolism, most likely as a consequence of its direct action on the bacterial membrane.

scholarly journals A Biodegradable Antifungal-Loaded Sol–Gel Coating for the Prevention and Local Treatment of Yeast Prosthetic-Joint Infections

Materials ◽  
2020 ◽  
Vol 13 (14) ◽  
pp. 3144
Author(s):  
David Romera ◽  
Beatriz Toirac ◽  
John-Jairo Aguilera-Correa ◽  
Amaya García-Casas ◽  
Aránzazu Mediero ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Candida Parapsilosis ◽  
Sol Gel ◽  
Local Treatment ◽  
Mortality Rates ◽  
Clinical Use ◽  
Implant Surface ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

Fungal prosthetic-joint infections are rare but devastating complications following arthroplasty. These infections are highly recurrent and expose the patient to the development of candidemia, which has high mortality rates. Patients with this condition are often immunocompromised and present several comorbidities, and thus pose a challenge for diagnosis and treatment. The most frequently isolated organisms in these infections are Candida albicans and Candida parapsilosis, pathogens that initiate the infection by developing a biofilm on the implant surface. In this study, a novel hybrid organo–inorganic sol–gel coating was developed from a mixture of organopolysiloxanes and organophosphite, to which different concentrations of fluconazole or anidulafungin were added. Then, the capacity of these coatings to prevent biofilm formation and treat mature biofilms produced by reference and clinical strains of C. albicans and C. Parapsilosis was evaluated. Anidulafungin-loaded sol–gel coatings were more effective in preventing C. albicans biofilm formation, while fluconazole-loaded sol–gel prevented C. parapsilosis biofilm formation more effectively. Treatment with unloaded sol–gel was sufficient to reduce C. albicans biofilms, and the sol–gels loaded with fluconazole or anidulafungin slightly enhanced this effect. In contrast, unloaded coatings stimulated C. parapsilosis biofilm formation, and loading with fluconazole reduced these biofilms by up to 99%. In conclusion, these coatings represent a novel therapeutic approach with potential clinical use to prevent and treat fungal prosthetic-joint infections.

scholarly journals Molecular characteristics of Staphylococcus aureus associated prosthetic joint infections after hip fractures treated with hemiarthroplasty: a retrospective genome-wide association study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
J. Christopher Noone ◽  
Marc Stegger ◽  
Berit Lilje ◽  
Knut Stavem ◽  
Karin Helmersen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
University Hospital ◽  
Genome Wide Association ◽  
Molecular Characteristics ◽  
Joint Infections ◽  
Orthopaedic Patients ◽  
Prosthetic Joint ◽  
Genome Wide ◽  
A Genome ◽  
Prosthetic Joint Infections

Abstract A retrospective study of Staphylococcus aureus isolates from orthopaedic patients treated between 2000 and 2017 at Akershus University Hospital, Norway was performed using a genome-wide association approach. The aim was to characterize and investigate molecular characteristics unique to S. aureus isolates from HHA associated prosthetic joint infections and potentially explain the HHA patients’ elevated 1-year mortality compared to a non-HHA group. The comparison group consisted of patients with non-HHA lower-extremity implant-related S. aureus infections. S. aureus isolates from diagnostic patient samples were whole-genome sequenced. Univariate and multivariate analyses were performed to detect group-associated genetic signatures. A total of 62 HHA patients and 73 non-HHA patients were included. Median age (81 years vs. 74 years; p < 0.001) and 1-year mortality (44% vs. 15%, p < 0.001) were higher in the HHA group. A total of 20 clonal clusters (CCs) were identified; 75% of the isolates consisted of CC45, CC30, CC5, CC15, and CC1. Analyses of core and accessory genome content, including virulence, resistance genes, and k-mer analysis revealed few group-associated variants, none of which could explain the elevated 1-year mortality in HHA patients. Our findings support the premise that all S. aureus can cause invasive infections given the opportunity.

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