scholarly journals Comparative Efficacies of Cloxacillin-Daptomycin and the Standard Cloxacillin-Rifampin Therapies against an Experimental Foreign-Body Infection by Methicillin-Susceptible Staphylococcus aureus

2014 ◽  
Vol 58 (9) ◽  
pp. 5576-5580 ◽  
Author(s):  
Cristina El Haj ◽  
Oscar Murillo ◽  
Alba Ribera ◽  
Mireia Vivas ◽  
Dolors Garcia-Somoza ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Foreign Body ◽  
Early Treatment ◽  
Infection Model ◽  
Content Type ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Mssa Infection

ABSTRACTWe compared the efficacies of daptomycin (doses equivalent to 8 to 10 mg/kg of body weight/day in humans) and cloxacillin alone with those of cloxacillin-rifampin and cloxacillin-daptomycin combinations, using a tissue cage methicillin-susceptibleStaphylococcus aureus(MSSA) infection model. Monotherapies were less effective than combinations (P< 0.05), and daptomycin resistance emerged. Cloxacillin-daptomycin proved as effective as cloxacillin-rifampin and prevented the appearance of resistance; this combination may be an alternative anti-MSSA therapy, which may offer greater benefits in the early treatment of prosthetic joint infections (PJI).

scholarly journals In VitroActivity of CEM-102 (Fusidic Acid) against Prevalent Clones and Resistant Phenotypes of Staphylococcus aureus

2013 ◽  
Vol 57 (9) ◽  
pp. 4535-4536 ◽  
Author(s):  
D. F. Sahm ◽  
J. Deane ◽  
C. M. Pillar ◽  
P. Fernandes
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Fusidic Acid ◽  
Oral Treatment ◽  
The United States ◽  
Content Type ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

ABSTRACTClinical development of CEM-102 (fusidic acid) has recently begun in the United States for chronic oral treatment of prosthetic joint infections. To support this development, thein vitroactivity of fusidic acid against importantStaphylococcus aureusclones and resistance phenotypes was determined. Against 51 such isolates, the modal fusidic acid MIC was 0.12 μg/ml (range, 0.06 to 0.25 μg/ml for 49 isolates). This level ofin vitrofusidic acid activity underscores the potential clinical utility of this compound in the United States.

scholarly journals Rifampin-Based Combination Therapy Is Active in Foreign-Body Osteomyelitis after Prior Rifampin Monotherapy

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Cassandra L. Brinkman ◽  
Suzannah M. Schmidt-Malan ◽  
Jayawant N. Mandrekar ◽  
Robin Patel
Keyword(s):  
Foreign Body ◽  
Combination Therapy ◽  
Biofilm Formation ◽  
Content Type ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Implant Retention ◽  
Rifampin Resistance ◽  
Selection Of

ABSTRACT Staphylococcal prosthetic joint infections (PJIs) are associated with biofilm formation, making them difficult to treat; if managed with debridement and implant retention, rifampin-based therapy is usually employed. Rifampin resistance potentially challenges PJI treatment. In investigating the effects of rifampin monotherapy on methicillin-resistant Staphylococcus aureus (MRSA) foreign-body osteomyelitis in rats, we previously demonstrated that rifampin resistance was selected but that it disappeared 14 days following rifampin monotherapy (1) and that rifampin resistance occurred less frequently following two rounds than following one round of rifampin monotherapy (2). Here, we compared rifampin monotherapy followed by rifampin-vancomycin combination therapy to rifampin-vancomycin combination therapy alone in experimental MRSA foreign-body osteomyelitis. Animals treated with rifampin monotherapy followed by rifampin-vancomycin combination therapy had decreased quantities of bacteria 14 days following treatment completion (P = 0.034) compared to those in animals treated with combination therapy alone. Additionally, some isolates recovered from animals treated with combination therapy alone, although still susceptible to rifampin, had higher MIC, minimum biofilm-inhibitory concentration (MBIC), and minimum biofilm-bactericidal concentration (MBBC) values than those of the inoculating strain. This suggests that rifampin may remain a feasible treatment option in foreign-body-associated orthopedic infections following the selection of rifampin resistance.

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 Comparative genomics of Staphylococcus epidermidis from prosthetic-joint infections and nares highlights genetic traits associated with antimicrobial resistance, not virulence

2021 ◽  
Author(s):  
Emeli Månsson ◽  
Thor Bech Johannesen ◽  
Åsa Nilsdotter-Augustinsson ◽  
Bo Söderquist ◽  
Marc Stegger
Keyword(s):  
Population Structure ◽  
Antimicrobial Resistance ◽  
Staphylococcus Epidermidis ◽  
Type Species ◽  
Genetic Traits ◽  
Content Type ◽  
Link Type ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

There is increased awareness of the worldwide spread of specific epidemic multidrug-resistant (MDR) lineages of the human commensal Staphylococcus epidermidis . Here, using bioinformatic analyses accounting for population structure, we determined genomic traits (genes, SNPs and k-mers) that distinguish S. epidermidis causing prosthetic-joint infections (PJIs) from commensal isolates from nares, by analysing whole-genome sequencing data from S. epidermidis from PJIs prospectively collected over 10 years in Sweden, and contemporary S. epidermidis from the nares of patients scheduled for arthroplasty surgery. Previously suggested virulence determinants and the presence of genes and mutations linked to antimicrobial resistance (AMR) were also investigated. Publicly available S. epidermidis sequences were used for international extrapolation and validation of findings. Our data show that S. epidermidis causing PJIs differed from nasal isolates not by virulence but by traits associated with resistance to compounds used in prevention of PJIs: β-lactams, aminoglycosides and chlorhexidine. Almost a quarter of the PJI isolates did not belong to any of the previously described major nosocomial lineages, but the AMR-related traits were also over-represented in these isolates, as well as in international S. epidermidis isolates originating from PJIs. Genes previously associated with virulence in S. epidermidis were over-represented in individual lineages, but failed to reach statistical significance when adjusted for population structure. Our findings suggest that the current strategies for prevention of PJIs select for nosocomial MDR S. epidermidis lineages that have arisen from horizontal gene transfer of AMR-related traits into multiple genetic backgrounds.

scholarly journals Development of a Novel and Rapid Antibody-Based Diagnostic for Chronic Staphylococcus aureus Infections Based on Biofilm Antigens

2020 ◽  
Vol 58 (5) ◽  
Author(s):  
Janette M. Harro ◽  
Mark E. Shirtliff ◽  
William Arnold ◽  
Jennifer M. Kofonow ◽  
Chad Dammling ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Joint Infection ◽  
Cost Effective ◽  
Antibody Detection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Microbial Culture ◽  
Diagnostic Modality ◽  
Content Type ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

ABSTRACT Prosthetic joint infections are difficult to diagnose and treat due to biofilm formation by the causative pathogens. Pathogen identification relies on microbial culture that requires days to weeks, and in the case of chronic biofilm infections, lacks sensitivity. Diagnosis of infection is often delayed past the point of effective treatment such that only the removal of the implant is curative. Early diagnosis of an infection based on antibody detection might lead to less invasive, early interventions. Our study examined antibody-based assays against the Staphylococcus aureus biofilm-upregulated antigens SAOCOL0486 (a lipoprotein), glucosaminidase (a domain of SACOL1062), and SACOL0688 (the manganese transporter MntC) for detection of chronic S. aureus infection. We evaluated these antigens by enzyme-linked immunosorbent assay (ELISA) using sera from naive rabbits and rabbits with S. aureus-mediated osteomyelitis, and then we validated a proof of concept for the lateral flow assay (LFA). The SACOL0688 LFA demonstrated 100% specificity and 100% sensitivity. We demonstrated the clinical diagnostic utility of the SACOL0688 antigen using synovial fluid (SF) from humans with orthopedic implant infections. Elevated antibody levels to SACOL0688 in clinical SF specimens correlated with 91% sensitivity and 100% specificity for the diagnosis of S. aureus infection by ELISA. We found measuring antibodies levels to SACOL0688 in SF using ELISA or LFA provides a tool for the sensitive and specific diagnosis of S. aureus prosthetic joint infection. Development of the LFA diagnostic modality is a desirable, cost-effective option, potentially providing rapid readout in minutes for chronic biofilm 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.

scholarly journals Role of Phenol-Soluble Modulins in Formation of Staphylococcus aureus Biofilms in Synovial Fluid

2015 ◽  
Vol 83 (7) ◽  
pp. 2966-2975 ◽  
Author(s):  
Sana S. Dastgheyb ◽  
Amer E. Villaruz ◽  
Katherine Y. Le ◽  
Vee Y. Tan ◽  
Anthony C. Duong ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Synovial Fluid ◽  
Antibiotic Treatment ◽  
Joint Infection ◽  
Regulatory System ◽  
Surface Proteins ◽  
Host Matrix ◽  
Content Type ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

Staphylococcus aureusis a leading cause of prosthetic joint infections, which, as we recently showed, proceed with the involvement of biofilm-like clusters that cause recalcitrance to antibiotic treatment. Here we analyzed why these clusters grow extraordinarily large, reaching macroscopically visible extensions (>1 mm). We found that while specificS. aureussurface proteins are a prerequisite for agglomeration in synovial fluid, low activity of the Agr regulatory system and subsequent low production of the phenol-soluble modulin (PSM) surfactant peptides cause agglomerates to grow to exceptional dimensions. Our results indicate that PSMs function by disrupting interactions of biofilm matrix molecules, such as the polysaccharide intercellular adhesin (PIA), with the bacterial cell surface. Together, our findings support a two-step model of staphylococcal prosthetic joint infection: As we previously reported, interaction ofS. aureussurface proteins with host matrix proteins such as fibrin initiates agglomeration; our present results show that, thereafter, the bacterial agglomerates grow to extremely large sizes owing to the lack of PSM expression under the specific conditions present in joints. Our findings provide a mechanistic explanation for the reported extreme resistance of joint infection to antibiotic treatment, lend support to the notions that Agr functionality and PSM production play a major role in defining different forms ofS. aureusinfection, and have important implications for antistaphylococcal therapeutic strategies.

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