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 ◽  
...  

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.

2007 ◽  
Vol 51 (12) ◽  
pp. 4255-4260 ◽  
Author(s):  
Carmela T. M. Mascio ◽  
Jeff D. Alder ◽  
Jared A. Silverman

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.


2018 ◽  
Author(s):  
Bernadette C Young ◽  
Sarah G Earle ◽  
Sona Soeng ◽  
Poda Sar ◽  
Varun Kumar ◽  
...  

AbstractPyomyositis is a severe bacterial infection of skeletal muscle, commonly affecting children in tropical regions and predominantly caused by Staphylococcus aureus. To understand the contribution of bacterial genomic factors to pyomyositis, we conducted a genome-wide association study of S. aureus cultured from 101 children with pyomyositis and 417 children with asymptomatic nasal carriage attending the Angkor Hospital for Children in Cambodia. We found a strong relationship between bacterial genetic variation and pyomyositis, with estimated heritability 63.8% (95% CI 49.2-78.4%). The presence of the Panton-Valentine leucocidin (PVL) locus increased the odds of pyomyositis 130-fold (p =10-17.9). The signal of association mapped both to the PVL-coding sequence and the sequence immediately upstream. Together these regions explained > 99.9% of heritability. Our results establish staphylococcal pyomyositis, like tetanus and diphtheria, as critically dependent on expression of a single toxin and demonstrate the potential for association studies to identify specific bacterial genes promoting severe human disease.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S288-S288
Author(s):  
Emily C Bodo ◽  
Kathryn E Daffinee ◽  
Kerry LaPlante

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.


2007 ◽  
Vol 34 (8) ◽  
pp. 1302-1309 ◽  
Author(s):  
Laure Sarda-Mantel ◽  
Azzam Saleh-Mghir ◽  
Mick M. Welling ◽  
Alain Meulemans ◽  
Jean-Marc Vrigneaud ◽  
...  

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