Genotypic and Phenotypic Characteristics of Staphylococcus aureus Prosthetic Joint Infections: Insight on the Pathogenesis and Prognosis of a Multicenter Prospective Cohort (original) (raw)
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Genomic characterization and outcome of prosthetic joint infections caused by Staphylococcus aureus
Scientific Reports
Staphylococcus aureus is a commensal colonizing the skin and mucous membranes. it can also act as a pathogen, and is the most common microorganism isolated from prosthetic joint infections (PJIs). The aim of this study was to explore the genomic relatedness between commensal and PJI S. aureus strains as well as microbial traits and host-related risk factors for treatment failure. Whole-genome sequencing (WGS) was performed on S. aureus isolates obtained from PJIs (n = 100) and control isolates from nares (n = 101). Corresponding clinical data for the PJI patients were extracted from medical records. No PJI-specific clusters were found in the WGS phylogeny, and the distribution of the various clonal complexes and prevalence of virulence genes among isolates from PJIs and nares was almost equal. Isolates from patients with treatment success and failure were genetically very similar, while the presence of an antibiotic-resistant phenotype and the use of non-biofilm-active antimicrobial treatment were both associated with failure.In conclusion, commensal and PJI isolates of S. aureus in arthroplasty patients were genetically indistinguishable, suggesting that commensal S. aureus clones are capable of causing PJIs. Furthermore, no association between genetic traits and outcome could be demonstrated, stressing the importance of patient-related factors in the treatment of S. aureus PJIs. Worldwide, millions of patients undergo arthroplasty surgery every year, with an expected increase in the coming years 1. Staphylococcus aureus is a major cause of both community-acquired and nosocomial infections, and is regularly reported to be the most common pathogen in prosthetic joint infections (PJIs) 2,3. Risk factors for developing PJIs are related to deficiencies in host defense due to age, obesity, previous surgery, smoking, and immune deficiencies (e.g. rheumatoid arthritis, diabetes mellitus), as well as exogenous factors such as timing and selection of antibiotic prophylaxis, extended operation time, and blood transfusions 4-8. Implant-sparing curative treatment of acute PJIs, whether occurring early in the postoperative period or later through hematogenous seeding, relies on a regimen of debridement, antibiotics, irrigation, and retention of the prosthesis (DAIR) 9. This is possible, provided that the infection has not persisted for more than approximately three weeks and that the isolate is susceptible to biofilm-active antibiotic treatment (i.e. rifampin for staphylococcal infections) 10. However, there are reports suggesting an even shorter time to intervention is needed for a successful treatment 11,12. The impact of risk factors on outcome of treatment has not been fully explored, but recent reports have proposed new risk scores to better guide the choice of treatment 13-15. S. aureus is a commensal of the human skin, nares, and mucous membranes, but also a human pathogen due to its invasive capacity. S. aureus infections occur among both otherwise-healthy individuals and those with co-morbidities, and nasal carriage has been associated with invasive disease 16. The pathogenesis of S. aureus infection in PJIs involves several critical steps: invasion of host tissues, evasion of the immune system, adhesion to surfaces, and biofilm formation 3,17. Cell surface components, enzymes, and exotoxins are important virulence factors for invasion, evasion, and propagation 3. By persisting in biofilm, bacteria evade neutrophil killing and
American Journal of Infection Control, 2005
Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as an important cause of staphylococcal infections, but there have been little data on whether CA-MRSA causes health care-associated infections. Methods: A case-control study was performed to identify risk factors for prosthetic joint infections (PJI). Antibiograms of isolates associated with PJI were reviewed. Molecular typing of available MRSA isolates was done using pulsed field gel electrophoresis (PFGE). Nares cultures of health care workers who provided care to those orthopedic patients were obtained. Results: Over a 13-month period (January 2003-January 2004), 9.5% of patients with prosthetic hip (THA) or knee (TKA) joint surgery developed PJI (7 TKA and 2 THA). The mean time to development of PJI was 20 days. Five infections were caused by CA-MRSA and 3 by methicillin-susceptible S aureus; one was culture negative. All CA-MRSA isolates had identical antibiograms (resistant to b-lactams and erythromycin; susceptible to clindamycin, trimethoprim-sulfamethoxazole, rifampin, gentamicin, levofloxacin, and vancomycin). Molecular typing of 2 available CA-MRSA isolates revealed that these were the USA300 clone; these isolates were PVL1 and carried SCCmec IV. CA-MRSA was not recovered from nares cultures from 31 health care workers. In multivariate analysis, TKA (OR, 8.1; 95% CI: 1.3-48.1) and surgery time .180 minutes (OR, 7.4; 95% CI: 1.4-39.6) were associated with PJI. Conclusion: We have demonstrated that the CA-MRSA USA300 clone is no longer just a cause of community-aquired infections but has also emerged as a cause of health care-associated infections, causing PJI at our institution.
Infectious Diseases and Therapy
Introduction: Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome. Methods: A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used Jesú s Rodríguez-Baño and Maria Dolores del Toro contributed equally as senior authors of the study. Members of The ARTHR-IS Group are listed in Acknowledgements section.
2014
Small colony variants (SCVs) are naturally occurring subpopulations of bacteria. The clinical characteristics and treatment outcomes of patients with prosthetic joint infection (PJI) caused by staphylococcal SCVs are unknown. This study was a retrospective series of 113 patients with staphylococcal PJI, with prospective testing of archived sonicate fluid samples. SCVs were defined using two-investigator review. Treatment failure was defined as (i) subsequent revision surgery for any reason, (ii) PJI after the index surgery, (iii) prosthesis nonreimplantation due to ongoing infection, or (iv) amputation of the affected limb. There were 38 subjects (34%) with SCVs and 75 (66%) with only normal-phenotype (NP) bacteria. Subjects with SCVs were more likely to have been on chronic antimicrobials prior to surgery (P ؍ 0.048), have had prior surgery for PJI (P ؍ 0.03), have had a longer duration of symptoms (P ؍ 0.0003), and have had a longer time since joint implantation (P ؍ 0.007), compared to those with only NP bacteria. Over a median follow-up of 30.6 months, 9 subjects (24%) with SCVs and 23 (32%) with only NP bacteria experienced treatment failure (P ؍ 0.51). Subjects infected with Staphylococcus aureus were more likely to fail than were those infected with Staphylococcus epidermidis (hazard ratio [HR], 4.03; 95% confidence interval [CI], 1.80 to 9.04). While frequently identified in subjects with PJI and associated with several potential predisposing factors, SCVs were not associated with excess treatment failure compared to NP infections in this study, where they were primarily managed with two-stage arthroplasty exchange. IMPORTANCE Bacteria with the small colony variant (SCV) phenotype are described in small case series as causing persistent or relapsing infection, but there are insufficient data to suggest that they should be managed differently than infection with normal-phenotype bacteria. In an effort to investigate the clinical importance of this phenotype, we determined whether SCVs were present in biofilms dislodged from the surfaces of arthroplasties of patients with staphylococcal prosthetic joint infection and assessed the clinical outcomes associated with detection of SCVs. We found that prosthetic joint infection caused by SCV staphylococci was associated with a longer duration of symptoms and more prior treatment for infection but not with an increased rate of treatment failure, compared to infection caused by normal-phenotype staphylococci.
European Journal of Clinical Microbiology & Infectious Diseases, 2012
Staphylococcus aureus is a leading cause of surgical site infections (SSIs). The association between S. aureus genotypes and the severity of illness is, however, incompletely understood. The aim of the study was to genotype S. aureus isolates from deep SSI in orthopaedic patients to identify molecular markers associated with invasive S. aureus infections. DNA microarray analysis was performed on S. aureus isolates collected from 60 patients with deep SSI following major orthopaedic surgery, while 57 isolates from nasal carriers served as controls. Genes associated with antibiotic resistance, adhesion, immune evasion, tissue invasion and toxin production were detected. The bone sialoprotein-binding protein gene (bbp) was more frequent in isolates from SSI patients compared to nasal carriers (95.0% vs. 82.5%), suggesting a role in invasive disease. No major differences in other molecular virulence markers could be distinguished among isolates from the two clinical groups, suggesting that any S. aureus strain may cause invasive infection. Our study reveals important genotypic information on isolates obtained from deep SSI following orthopaedic procedures.
The American Journal of Medicine, 2016
BACKGROUND: Staphylococcus aureus bacteremia is a life-threatening condition that may lead to metastatic infection, including prosthetic joint infection. METHODS: To assess clinical factors associated with hematogenous prosthetic joint infection, we retrospectively reviewed all patients with a joint arthroplasty in place at the time of a first episode of S. aureus bacteremia over a 5-year period at our institution. Patients with postsurgical prosthetic joint infection without hematogenous prosthetic joint infection were excluded. RESULTS: There were 85 patients (143 arthroplasties) with either no prosthetic joint infection (n ¼ 50; 58.8%) or hematogenous prosthetic joint infection in at least one arthroplasty (n ¼ 35; 41.2%). The odds of hematogenous prosthetic joint infection was significantly increased among patients with communityacquired S. aureus bacteremia (odds ratio [OR] 18.07; 95% confidence interval [CI] 2.64-infinity; P ¼ .001), as compared with nosocomial S. aureus bacteremia, in which there were no patients with hematogenous prosthetic joint infection. After adjusting for S. aureus bacteremia classification, the presence of 3 joint arthroplasties in place was associated with a nearly ninefold increased odds of hematogenous prosthetic joint infection as compared with those with 1-2 joint arthroplasties in place (OR 8.55; 95% CI 1.44-95.71; P ¼ .012). All but one joint with prosthetic joint infection demonstrated at least one clinical feature suggestive of infection. There were 4 additional S. aureus prosthetic joint infections diagnosed during a median of 3.4 years of follow-up post hospitalization for S. aureus bacteremia. CONCLUSION: Prosthetic joint infection is frequent in patients with existing arthroplasties and concomitant S. aureus bacteremia, particularly with community-acquired S. aureus bacteremia and multiple prostheses. In contrast, occult S. aureus prosthetic joint infection without clinical features suggestive of prosthetic joint infection at the time of S. aureus bacteremia is rare.
American Journal of Infection Control, 2019
Background: Prosthetic joint infections (PJI) can be devastating postoperative complications after total joint replacement (TJR). The role of decolonization of Staphylococcus aureus carriers prior to surgery still remains unclear, and the most recent guidelines do not state a formal recommendation for such strategy. Our purpose was to seek further evidence supporting preoperative screening and S aureus decolonization in patients undergoing TJR. Methods: This was a quasiexperimental quality improvement study comparing a 5-year baseline of deep and organ-space PJIs (2005-2010) to a 1-year intervention period (May 2015 to July 2016). The intervention consisted of nasal and throat screening for S aureus preoperatively and decolonization of carriers over 5 days prior to surgery. Results: Prior to the intervention, we identified 42 deep and/or organ-space PJIs in 8,505 patients undergoing TJR (0.5%). S aureus was the causal microorganism in 28 of 42 (66.6%) cases. During the intervention, 22.5% (424 of 1,883) of patients were S aureus carriers. The PJI rate was similar overall (0.4%, 7 of 1,883; odds ratio, 0.75; 95% confidence interval, 0.34-1.67; P = .58), but there was a significant reduction in S aureus PJI to only 1 case during the intervention (odds ratio, 0.15; 95% confidence interval, 0.004-0.94; P = .039). Conclusions: Active screening for S aureus and decolonization of carriers prior to TJR was associated with a reduction in PJI due to S aureus, but no changes in overall PJI rates were observed.
Open Forum Infectious Diseases
Background Treatment of staphylococcal prosthetic joint infection (PJI) usually consists of surgical debridement and prolonged rifampicin combination therapy. Tailored antimicrobial treatment alternatives are needed due to frequent side effects and drug-drug interactions with rifampicin combination therapy. We aimed to assess the effectiveness of several alternative antibiotic strategies in patients with staphylococcal PJI. Methods In this prospective, multicenter registry-based study, all consecutive patients with a staphylococcal PJI, treated with debridement, antibiotics and implant retention (DAIR) or 1-stage revision surgery between January 1, 2015 and November 3, 2020, were included. Patients were treated with a long-term rifampicin combination strategy (in 2 centers) or a short-term rifampicin combination strategy (in 3 centers). Antimicrobial treatment strategies in these centers were defined before the start of the registry. Patients were stratified in different groups, dep...