Staphylococcus aureus genotype variation among and within periprosthetic joint infections

Author(s):  
Dongzhu Ma ◽  
Kimberly M. Brothers ◽  
Patrick L. Maher ◽  
Nathan J. Phillips ◽  
Deborah Simonetti ◽  
...  
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 ◽  
Vol 5 (suppl_1) ◽  
pp. S373-S374
Author(s):  
Ian Kracalik ◽  
Kelly Jackson ◽  
Joelle Nadle ◽  
Wendy Bamberg ◽  
Susan Petit ◽  
...  

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) causes >70,000 invasive infections annually in the United States, and recurrent infections pose a major clinical challenge. We examined risk factors for recurrent MRSA infections. Methods We identified patients with an initial invasive MRSA infection (isolation from a normally sterile body site) from 2006 to 2013, through active, population-based surveillance in selected counties in nine states through the Emerging Infections Program. Recurrence was defined as invasive MRSA isolation >30 days after initial isolation. We used logistic regression with backwards selection to evaluate adjusted odds ratios (aOR) associated with recurrence within 180 days, prior healthcare exposures, and initial infection type, controlling for patient demographics and comorbidities. Results Among 24,478 patients with invasive MRSA, 3,976 (16%) experienced a recurrence, including 61% (2,438) within 180 days. Risk factors for recurrence were: injection drug use (IDU) (aOR; 1.38, 95% confidence interval [CI]: 1.15–1.65), central venous catheters (aOR; 1.35, 95% CI: 1.22–1.51), dialysis (aOR; 2.00, 95% CI: 1.74–2.31), and history of MRSA colonization (aOR; 1.35, 95% CI: 1.22–1.51) (figure). Recurrence was more likely for bloodstream infections (BSI) without another infection (aOR; 2.08, 95% CI: 1.74–2.48), endocarditis (aOR; 1.46, 95% CI: 1.16–1.55), and bone/joint infections (aOR; 1.38, 95% CI: 1.20–1.59), and less likely for pneumonia (aOR: 0.75, 95% CI: 0.64–0.89), compared with other initial infection types. When assessed separately, the presence of a secondary BSI with another infection increased the odds of recurrence over that infection without a BSI (aOR: 1.96, 95% CI: 1.68–2.30). Conclusion Approximately one in six persons with invasive MRSA infection had recurrence. We identified potential opportunities to prevent recurrence through infection control (e.g., management and early removal of central catheters). Other possible areas for preventing recurrence include improving the management of patients with BSI and bone/joint infections (including both during and after antibiotic treatment) and mitigating risk of infection from IDU. Disclosures All authors: No reported disclosures.


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.


2020 ◽  
Vol 222 (9) ◽  
pp. 1498-1504
Author(s):  
Melissa J Karau ◽  
Suzannah M Schmidt-Malan ◽  
Mariana Albano ◽  
Jayawant N Mandrekar ◽  
Christina G Rivera ◽  
...  

Abstract Background Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis. Methods Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively. Results Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group. Conclusions Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.


2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Camille Kolenda ◽  
Jérôme Josse ◽  
Mathieu Medina ◽  
Cindy Fevre ◽  
Sébastien Lustig ◽  
...  

ABSTRACT Staphylococcus aureus is responsible for difficult-to-treat bone and joint infections (BJIs). This is related to its ability to form biofilm and to be internalized and persist inside osteoblasts. Recently, bacteriophage therapy has emerged as a promising option to improve treatment of such infections, but data on its activity against the specific bacterial lifestyles presented above remain scarce. We evaluated the activity of a combination of three bacteriophages, recently used for compassionate treatment in France, against S. aureus HG001 in a model of staphylococcal biofilm and a model of osteoblasts infection, alone or in association with vancomycin or rifampin. The activity of bacteriophages against biofilm-embedded S. aureus was dose dependent. In addition, synergistic effects were observed when bacteriophages were combined with antibiotics used at the lowest concentrations. Phage penetration into osteoblasts was observed only when the cells were infected, suggesting a S. aureus-dependent Trojan horse mechanism for internalization. The intracellular bacterial count of bacteria in infected osteoblasts treated with bacteriophages as well as with vancomycin was significantly higher than in cells treated with lysostaphin, used as a control condition, owing to the absence of intracellular activity and the rapid killing of bacteria released after the death of infected cells. These results suggest that bacteriophages are both inactive in the intracellular compartment after being internalized in infected osteoblasts and present a delayed killing effect on bacteria released after cell lysis into the extracellular compartment, which avoids preventing them from infecting other osteoblasts. The combination of bacteriophages tested was highly active against S. aureus embedded in biofilm but showed no activity against intracellular bacteria in the cell model used.


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