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Staphylococcal prosthetic joint infections: similar, but still different
Örebro University, School of Medical Sciences.
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Staphylococci constitute a major part of our commensal flora but are also the most common bacteria causing prosthetic joint infections (PJIs), a dreaded complication of arthroplasty surgery. However, not all staphylococci are the same. The virulent Staphylococcus aureus has the ability to cause severe disease such as bacteremia and infective endocarditis in previously healthy people, while the coagulase-negative staphylococci Staphylococcus epidermidis and Staphylococcus capitis rarely act as pathogens unless the patient is immunocompromised or has an implanted medical device, such as a prosthetic joint. This thesis accordingly explores similarities and differences between these three staphylococci in PJIs.

S. capitis can cause early postinterventional and chronic PJIs, a finding that has not previously been described. Furthermore, its nosocomial NRCS-A outbreak sublineage, recently observed in neonatal intensive care units, is also present in adult PJIs. When comparing nasal and PJI isolates, the patterns differed between staphylococcal species. In S. capitis, the commensal and infecting strains were separated phylogenetically, while they clustered together for S. aureus. This may indicate diverse reservoirs and acquisition routes in PJIs caused by different staphylococcal species.

Outcomes in early postinterventional PJIs were similar in S. capitis and S. aureus infections, with 70–80% achieving clinical cure. In S. aureus infections, no virulence genes were significantly associated with outcome. Although multidrug resistance (MDR) was rare in S. aureus, inability to use biofilm-active antibiotics was a risk factor for failure. However, in S. epidermidis and in the NRCS-A sublineage of S. capitis, MDR and glycopeptide heteroresistance were widespread, highlighting the challenge of antibiotic resistance in the treatment of PJIs.

Place, publisher, year, edition, pages
Örebro: Örebro University , 2019. , p. 114
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 200
Keywords [en]
Prosthetic joint infections, staphylococcal infections, nasal carriage, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus capitis, NRCS-A, antibiotic resistance, heterogeneous glycopeptide resistance, whole-genome sequencing
National Category
General Practice Infectious Medicine
Research subject
Infectious Diseases
Identifiers
URN: urn:nbn:se:oru:diva-75928ISBN: 978-91-7529-305-9 (print)OAI: oai:DiVA.org:oru-75928DiVA, id: diva2:1346554
Public defence
2019-11-15, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 10:00 (English)
Opponent
Supervisors
Available from: 2019-08-28 Created: 2019-08-28 Last updated: 2019-10-22Bibliographically approved
List of papers
1. Heterogeneous glycopeptide intermediate Staphylococcus epidermidis isolated from prosthetic joint infections
Open this publication in new window or tab >>Heterogeneous glycopeptide intermediate Staphylococcus epidermidis isolated from prosthetic joint infections
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2014 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 33, no 6, p. 911-917Article in journal (Refereed) Published
Abstract [en]

Methicillin-resistant Staphylococcus epidermidis (MRSE) poses a major problem in prosthetic joint infections (PJIs). Vancomycin is often considered the drug of choice in the empirical treatment of staphylococcal PJIs. As recent decades have seen reports of heterogeneous glycopeptide intermediate S. aureus (hGISA), our aim was to examine the prevalence of heterogeneous glycopeptide intermediate S. epidermidis (hGISE) in PJIs. S. epidermidis isolates (n = 122) from 119 patients in three Swedish counties between 1993 and 2012 were included. All were isolated from perioperative tissue samples from revision surgery in clinically verified PJIs. Antimicrobial susceptibility testing against staphylococcal antibiotics was performed. The macromethod Etest (MME) and glycopeptide resistance detection (GRD) Etest were used to detect hGISE. Standard minimal inhibitory concentration (MIC) determination revealed no vancomycin-resistant isolates, while teicoplanin resistance was detected in 14 out of 122 isolates (11.5 %). hGISE was found in 95 out of 122 isolates (77.9 %), 64 out of 67 of isolates with teicoplanin MIC > 2 mg/L (95.5 %) and 31 out of 55 of isolates with teicoplanin MIC a parts per thousand currency sign2 mg/L (56.4 %). Thus, the presence of hGISE cannot be ruled out by teicoplanin MIC a parts per thousand currency sign2 mg/L alone. Multidrug resistance was detected in 86 out of 95 hGISE isolates (90.5 %) and in 16 out of 27 isolates (59.3 %), where hGISE could not be detected. In conclusion, hGISE detected by MME or GRD was common in this material. However, hGISE is difficult to detect with standard laboratory diagnostic routines. Glycopeptide treatment may not be sufficient in many of these PJIs, even if standard MIC classifies the isolated S. epidermidis as susceptible.

Place, publisher, year, edition, pages
New York: Springer, 2014
National Category
Infectious Medicine Microbiology in the medical area
Research subject
Infectious Diseases; Microbiology
Identifiers
urn:nbn:se:oru:diva-35350 (URN)10.1007/s10096-013-2025-3 (DOI)000335743500004 ()24338092 (PubMedID)2-s2.0-84903820002 (Scopus ID)
Note

Funding Agencies:

Research committee of Östergotland, County Council, Sweden

Research committee of Värmland, County Council, Sweden

Available from: 2014-06-13 Created: 2014-06-13 Last updated: 2019-10-21Bibliographically approved
2. Genomic characterization and outcome of prosthetic joint infections caused by Staphylococcus aureus
Open this publication in new window or tab >>Genomic characterization and outcome of prosthetic joint infections caused by Staphylococcus aureus
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(English)Manuscript (preprint) (Other academic)
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-77473 (URN)
Available from: 2019-10-21 Created: 2019-10-21 Last updated: 2019-10-21Bibliographically approved
3. Staphylococcus capitis isolated from prosthetic joint infections
Open this publication in new window or tab >>Staphylococcus capitis isolated from prosthetic joint infections
2017 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 36, no 1, p. 115-122Article in journal (Refereed) Published
Abstract [en]

Further knowledge about the clinical and microbiological characteristics of prosthetic joint infections (PJIs) caused by different coagulase-negative staphylococci (CoNS) may facilitate interpretation of microbiological findings and improve treatment algorithms. Staphylococcus capitis is a CoNS with documented potential for both human disease and nosocomial spread. As data on orthopaedic infections are scarce, our aim was to describe the clinical and microbiological characteristics of PJIs caused by S. capitis. This retrospective cohort study included three centres and 21 patients with significant growth of S. capitis during revision surgery for PJI between 2005 and 2014. Clinical data were extracted and further microbiological characterisation of the S. capitis isolates was performed. Multidrug-resistant (≥3 antibiotic groups) S. capitis was detected in 28.6 % of isolates, methicillin resistance in 38.1 % and fluoroquinolone resistance in 14.3 %; no isolates were rifampin-resistant. Heterogeneous glycopeptide-intermediate resistance was detected in 38.1 %. Biofilm-forming ability was common. All episodes were either early post-interventional or chronic, and there were no haematogenous infections. Ten patients experienced monomicrobial infections. Among patients available for evaluation, 86 % of chronic infections and 70 % of early post-interventional infections achieved clinical cure; 90 % of monomicrobial infections remained infection-free. Genetic fingerprinting with repetitive sequence-based polymerase chain reaction (rep-PCR; DiversiLab®) displayed clustering of isolates, suggesting that nosocomial spread might be present. Staphylococcus capitis has the potential to cause PJIs, with infection most likely being contracted during surgery or in the early postoperative period. As S. capitis might be an emerging nosocomial pathogen, surveillance of the prevalence of PJIs caused by S. capitis could be recommended.

Place, publisher, year, edition, pages
New York: Springer, 2017
National Category
Infectious Medicine Microbiology
Identifiers
urn:nbn:se:oru:diva-52726 (URN)10.1007/s10096-016-2777-7 (DOI)000391388800014 ()27680718 (PubMedID)2-s2.0-84988919555 (Scopus ID)
Note

Funding Agencies:

Research committee of Värmland County Council, Sweden LIVFOU-456821  LIVFOU-457061

Research committee of Östergötland County Council, Sweden LIO-447091

Örebro University, Sweden ORU 1.3.1-01273/2015

Available from: 2016-10-04 Created: 2016-10-03 Last updated: 2019-10-21Bibliographically approved
4. Presence of the neonatal Staphylococcus capitis outbreak clone (NRCS-A) in prosthetic joint infections
Open this publication in new window or tab >>Presence of the neonatal Staphylococcus capitis outbreak clone (NRCS-A) in prosthetic joint infections
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(English)Manuscript (preprint) (Other academic)
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-77474 (URN)
Available from: 2019-10-21 Created: 2019-10-21 Last updated: 2019-10-21Bibliographically approved
5. Same Organism, Different Phenotype: Are Phenotypic Criteria Adequate In Coagulase-Negative Staphylococcal Orthopaedic Implant-Associated Infections?
Open this publication in new window or tab >>Same Organism, Different Phenotype: Are Phenotypic Criteria Adequate In Coagulase-Negative Staphylococcal Orthopaedic Implant-Associated Infections?
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2019 (English)In: Journal of bone and joint infection, ISSN 2206-3552, Vol. 4, no 1, p. 16-19Article in journal (Refereed) Published
Abstract [en]

In current diagnostic criteria for implant-associated bone- and joint infections, phenotypically identical low-virulence bacteria in two intraoperative cultures are usually required. Using whole-genome sequencing, we have further characterized three phenotypically different Staphylococcus capitis isolated from one prosthetic joint infection, highlighting the challenges in defining microbiological criteria for low-virulence prosthetic joint infections.

Place, publisher, year, edition, pages
British Editorial Society of Bone and Joint Surger, 2019
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-77484 (URN)10.7150/jbji.30256 (DOI)30755843 (PubMedID)
Available from: 2019-10-21 Created: 2019-10-21 Last updated: 2019-10-21Bibliographically approved

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