Influence of molecular characteristics in the prognosis of methicillin-resistant Staphylococcus aureus prosthetic joint infections: beyond the species and the antibiogram

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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390. Treatment and Outcome of Methicillin-Resistant Staphylococcus aureus Hip and Knee Prosthetic Joint Infection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.463 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S201-S201

Author(s):

Michael Henry ◽

Alberto V Carli ◽

Milan Kapadia ◽

Yu-fen Chiu ◽

Barry Brause ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Surgical Treatment ◽

Treatment Failure ◽

Methicillin Resistant Staphylococcus Aureus ◽

Infection Type ◽

Joint Infection ◽

Methicillin Resistant ◽

Prosthetic Joint ◽

Prosthetic Joint Infections ◽

Implant Retention

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) total hip and knee prosthetic joint infections (PJI) can be highly morbid and difficult to treat. Other clinical factors notwithstanding, explantation is usually recommended, although comparative treatment data are lacking. We sought to compare the success of implant retention to two-stage exchange in MRSA-infected PJI to better understand treatment options in this difficult cohort. Methods A retrospective cohort of hip and knee PJIs from 2009 to 2016 were identified by ICD code and surgical treatment. All cases met MSIS criteria for PJI, and had culture-confirmed MRSA from synovial or intra-articular tissue culture. PJIs were either treated with exchange arthroplasty or debridement with antibiotic and implant retention (DAIR). Success was defined as no further surgical treatment for infection at two years. Kaplan–Meier estimates were used to calculate the 2-year survival rate free from treatment failure. Univariate logistic regression was performed to identify risk factors associated with treatment failure. Results 65 MRSA PJIs were identified with 42 undergoing explantation and 23 undergoing DAIR. Demographics, Charlson comorbidities, infection type (early post-operative, hematogenous or late chronic), and history of prior PJI were not significantly different between treatment groups. Survivorship at two years was 75% (95% confidence interval [CI] 61–88%) for exchange compared with 29% (95% CI 10–48%) for DAIR, P = 0.0002. Within the exchange group, knee PJIs were more likely to fail than hip PJI (odds ratio [OR] 7.1, CI 1.3–38, P = 0.02), and patients with diabetes were more likely to fail (OR 17, CI 1.6–178, P = 0.02). Conclusion MRSA PJIs treated with DAIR have worse outcomes than those treated with prosthesis exchange. Further investigation is needed to identify predictors of DAIR success, to optimize surgical treatment choice, and to improve outcomes of these difficult infections. Disclosures All authors: No reported disclosures.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00824-07 ◽

2007 ◽

Vol 51 (12) ◽

pp. 4255-4260 ◽

Cited By ~ 179

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.

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Nasal carriage of methicillin-resistant Staphylococcus aureus among preclinical medical students: epidemiologic and molecular characteristics of methicillin-resistant S. aureus clones

Diagnostic Microbiology and Infectious Disease ◽

10.1016/j.diagmicrobio.2010.12.004 ◽

2011 ◽

Vol 70 (1) ◽

pp. 22-30 ◽

Cited By ~ 33

Author(s):

Xiao Xue Ma ◽

Dan Dan Sun ◽

Si Wang ◽

Mei Lian Wang ◽

Miao Li ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Medical Students ◽

Methicillin Resistant Staphylococcus Aureus ◽

Nasal Carriage ◽

Molecular Characteristics ◽

Methicillin Resistant ◽

Preclinical Medical Students

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1230. Epidemiology and Risk Factors for Recurrent Invasive Methicillin-Resistant Staphylococcus aureus Infection: nine US States, 2006–2013

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.1063 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S373-S374

Author(s):

Ian Kracalik ◽

Kelly Jackson ◽

Joelle Nadle ◽

Wendy Bamberg ◽

Susan Petit ◽

...

Keyword(s):

Risk Factors ◽

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Infection Type ◽

The United States ◽

Emerging Infections ◽

Methicillin Resistant ◽

Initial Infection ◽

Joint Infections ◽

Mrsa Infection

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.

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