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Staphylococcus aureus genotype variation among and within periprosthetic joint infections.

ABSTRACT: Staphylococcus aureus is a common organism in orthopedic infections, but little is known about the genetic diversity of strains during an infectious process. Using periprosthetic joint infection (PJI) as a model, a prospective study was designed to quantify genetic variation among S. aureus strains both among and within patients. Whole genome sequencing and multilocus sequence typing was performed to genotype these two populations at high resolution. In nasal cultures, 78% of strains were of clonal complexes CC5, CC8, and CC30. In PJI cultures, only 63% could be classified in these common clonal complexes. The PJI cultures had a larger proportion of atypical strains, and these atypical strains were associated with poor host status and compromised immune conditions. Mutations in genes involved in fibronectin binding (ebh, fnbA, clfA, and clfB) systematically distinguished later PJI isolates from the first PJI isolate from each patient. Repeated mutations in S. aureus genes associated with extracellular matrix binding were identified, suggesting adaptive, parallel evolution of S. aureus during the development of PJI.

SUBMITTER: Ma D

PROVIDER: S-EPMC8435540 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Staphylococcus aureus genotype variation among and within periprosthetic joint infections.

Ma Dongzhu D Brothers Kimberly M KM Maher Patrick L PL Phillips Nathan J NJ Simonetti Deborah D William Pasculle Anthony A Richardson Anthony R AR Cooper Vaughn S VS Urish Kenneth L KL

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20210402 2

Staphylococcus aureus is a common organism in orthopedic infections, but little is known about the genetic diversity of strains during an infectious process. Using periprosthetic joint infection (PJI) as a model, a prospective study was designed to quantify genetic variation among S. aureus strains both among and within patients. Whole genome sequencing and multilocus sequence typing was performed to genotype these two populations at high resolution. In nasal cultures, 78% of strains were of clo ...[more]

PMID: 33713379

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Project description:The approach of sequencing or genotyping to characterize the pathogenic potential of staphylococci from orthopedic device-related infection (ODRI) has been applied in recent studies. These studies described the genomic carriage of virulence in clinical strains and compared it with those in commensal strains. Only a few studies have directly correlated genomic profiles to patient outcome and phenotypic virulence properties in periprosthetic joint infections (PJIs). We investigated the association between genomic variations and virulence-associated phenotypes (biofilm-forming ability and antimicrobial resistance) in 111 staphylococcal strains isolated from patients with PJI and the infection outcome (resolved/unresolved). The presence of a strong biofilm phenotype in Staphylococcus aureus and an antibiotic-resistant phenotype in Staphylococcus epidermidis were both associated with treatment failure of PJI. In S. epidermidis, multidrug resistance (MDR) and resistance to rifampicin were associated with unresolved infection. Sequence type 45 (ST45) and ST2 were particularly enriched in S. aureus and S. epidermidis, respectively. S. epidermidis ST2 caused the majority of relapses and was associated with MDR and strong biofilm production, whereas ST215 correlated with MDR and non/weak biofilm production. S. aureus agr II correlated with resolved infection, while S. epidermidis agr I was associated with strong biofilm production and agr III with non/weak production. Collectively, our results highlight the importance of careful genomic and phenotypic characterization to anticipate the probability of the strain causing treatment failure in PJI. Due to the high rate of resistant S. epidermidis strains identified, this study provides evidence that the current recommended treatment of rifampicin and a fluoroquinolone should not be administered without knowledge of the resistance pattern. IMPORTANCE This study addresses the presence and frequency of particular genetic variants and virulence factors found in staphylococcal bacteria causing periprosthetic joint infection (PJI) of the hip and knee to ascertain their clinical relevance as predictors of treatment failure. We characterized the genetic virulence traits of a large collection of clinical staphylococci isolated from patients with PJI and evaluated their association with the patient's infection outcome. The results showed that S. aureus strains that produced strong biofilms and S. epidermidis strains with resistance to several antibiotics associated significantly with unresolved infection. Some particular genetic variants associated with biofilm formation and multidrug resistance. These traits should be considered important risk factors for the diagnosis and treatment guidance in PJI.

Project description:Current laboratory protocols for periprosthetic joint infections (PJIs) involve a standard 10- to 14-day incubation period. However, recent evidence indicates considerable variability in the time to diagnosis (TTD) between acute and chronic PJIs. TTD is also influenced by the employed culture media and sample types. Enriched liquid media, such as broths and blood culture bottles, along with sonication fluid culture, are commonly used, though their incremental benefit for PJI diagnosis remains debated. We retrospectively analyzed 187 confirmed hip and knee PJIs, each with at least three intraoperative samples. Comparison of TTD among early acute (n = 68), late acute (n = 52), and late chronic (n = 67) PJIs revealed a significant difference, particularly between late acute and late chronic infections (P < 0.004). Early acute and late acute PJIs were diagnosed within 5 days in 97.1% and 98.1% of cases, respectively, contrasting with 14 days required for 97.1% of late chronic PJIs. Enriched liquid media significantly improved species detection, especially in polymicrobial and anaerobic infections. Pediatric and anaerobic blood culture bottles demonstrated superior efficacy over thioglycolate broths for diagnostic confirmation. Sonication fluid culture was essential for confirming diagnoses in 17.6% of cases. Our findings highlight that clinical presentation, rather than time since primary arthroplasty, should guide incubation duration: both early acute and late acute PJIs can be diagnosed within 5 days. Medical microbiology laboratories should consider shorter incubation times for acute PJIs to optimize diagnostic efficiency. The use of blood culture bottles and sonication fluid culture proves invaluable for accurate PJI diagnosis.ImportanceWhile molecular techniques are becoming increasingly employed, culture remains the gold standard for diagnosing periprosthetic joint infections. However, guidance for laboratory protocols is limited and highly variable. This article aims to increase diagnostic efficiency by providing concrete recommendations for medical microbiology laboratories.

Dataset Information

Staphylococcus aureus genotype variation among and within periprosthetic joint infections.

Publications

Staphylococcus aureus genotype variation among and within periprosthetic joint infections.

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