Saturday, October 29, 2022

How does surgery for periprosthetic infection fail?

Revision surgery for periprosthetic infection may fail because of

(1) definite septic failure: persistence of infection after revision surgery as documented by positive cultures at the time of re-revision (see Factors associated with failure of surgical revision and IV antibiotics to resolve Cutibacterium periprosthetic infection of the shoulder).

(2) possible septic failure: poor restoration of comfort and function (i.e. pain, stiffness, weakness, instability) after revision in the absence of culture evidence of recurrent infection

Definite septic failure may be overlooked because
(1) a re-revision was not performed so that multiple deep tissue and explant cultures were not obtained
(2) cultures from re-revision surgery were negative even though viable bacteria were present because
    (a) an insufficient number (i.e. fewer than five) deep tissue specimens for culture were obtained at re-revision surgery (see Origin of propionibacterium in surgical wounds and evidence-based approach for culturing propionibacterium from surgical sites) and What do positive and negative Cutibacteriumculture results in periprosthetic shoulder infection mean? A multi-institutional control study
    (b) bacterial growth was suppressed by the preoperative administration of antibiotics
    (c) the concealment of bacteria in a biofilm on the prosthetic implants so that they were not detected by tissue cultures (see Culturing explants for Cutibacterium at revision shoulder arthroplasty: an analysis of explant and tissue samples at corresponding anatomic sites)
    (d) specimens obtained at re-revision were not cultured on aerobic, anaerobic, and broth media (see Origin of propionibacterium in surgical wounds and evidence-based approach for culturing propionibacterium from surgical sites)
    (e) cultures were not observed for 14 days to optimize detection of Cutibacterium (the most common organism causing shoulder periprosthetic infection) (see Prognostic factors for bacterial cultures positive for Propionibacterium acnes and other organisms in a large series of revision shoulder arthroplasties performed for stiffness, pain, or loosening)
    (f) the inability of certain strains of bacteria to form colonies on laboratory media (see Growing Unculturable Bacteria, Viable But Not Culturable (VBNC), Bacterial Viability
    (g) an intracellular location of the organisms so that they do not grow on media (see Cutibacterium acnes is an intracellular and intra-articular commensal of the human shoulder joint)

The authors of An Enhanced Understanding of Shoulder PJI using Next generation Sequencing: Findings at 3-year Clinical Follow-up suggest that a possible cause of septic failure is that cultures at the time of an index revision arthroplasty may not detect the presence of pathogentic bacteria so that the patients do not receive prolonged antibiotics beyond standard perioperative prophylaxis.. They further suggest that next generation sequencing (NGS) of samples obtained at the time of index revision may be able to detect organisms present but not isolated by traditional culture (see Comparative study of cultures and next-generation sequencing in the diagnosis of shoulder prosthetic joint infections).

They identified 6 re-revisions that yielded ≥2 positive cultures with the same bacteria. Four of these six had no growth on cultures at the index revision. NGS detected bacterial DNA at the index revision in all six cases. Patients with positive NGS results had a mean of seven (range: 1-13) unique bacterial species identified per procedure. The table below shows that NGS detected DNA from organisms that are ubiquitous in the environment and not thought to be pathogenetic (such as A. radiorestens). It also confirms that Cutibacterium was the organism commonly isolated in these six confirmed septic revisions (those that had positive cultures at re-revision - see right hand column).


Thus antibiotic and surgical treatment of a failed arthroplasty must be planned in recognition that organisms, especially Cutibacterium, may persist in the shoulder even if cultures at the time of the index surgical revision are negative. While it is suggested that failure of the index procedure to resolve the infection could be attributed to lack of treatment for an organism detected by NGS and not identified by culture at the index revision, this study does not provide evidence of persistent infection after the index revision by organisms other than Cutibacterium and Staph Epidermidis, so that prolonged antibiotic coverage for these organisms should be considered.

It is of importance to note that NGS can fail to detect viable organisms demonstrated by positive cultures (including the two most commonly isolated from shoulder periprosthetic infections: Cutibaterium and S. Epidermidis). In this study, NGS at the index revision did not detect S. Epidermidis in the one case where this organism was cultured at re-revision.


In the table below from Comparative study of cultures and next-generationsequencing in the diagnosis of shoulder prostheticjoint infections, the lack of sensitivity of NGS to Cutibaterium and S. Epidermidis is demonstrated even when these organisms are present in large numbers.



The lack of sensitivity of NGS for Cutibacterium is also pointed out by the authors of Cutibacterium acnes is less commonly identified by next-generation sequencing than culture in primary shoulder surgery, who concluded, "There was limited concordance between culture and next-generation sequencing for C. acnes identification. Further studies are needed to determine the potential for next-generation sequencing as a diagnostic tool."

Our understanding of NGS in the detection of Cutibacterium would be greatly enhanced by submitting samples containing different dilutions of the bacteria as well as control samples with no Cutibacterium or other bacteria for next generation sequencing. This would determine the sensitivity of NGS for Cutibacterium as well as the frequency with which DNAs from other bacteria were detected.




At this point it remains unclear whether next generation sequencing is of value in determining treatment of the failed arthroplasty (see 
Revision shoulder arthroplasty - what is the role of next-generation sequencing?)

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Here are some videos that are of shoulder interest
Shoulder arthritis - what you need to know (see this link).
How to x-ray the shoulder (see this link).
The ream and run procedure (see this link).
The total shoulder arthroplasty (see this link).
The cuff tear arthropathy arthroplasty (see this link).
The reverse total shoulder arthroplasty (see this link).
The smooth and move procedure for irreparable rotator cuff tears (see this link).
Shoulder rehabilitation exercises (see this link).