Saturday, January 20, 2018

How should we evaluate and treat the microbiologic aspects of a patient with a failed arthroplasty?

Diagnosis of Periprosthetic Joint Infection: The Potential of Next-Generation Sequencing

These authors sought to evaluate the accuracy of next-generation sequencing in identifying the causative organism(s) in patients with periprosthetic joint infection.

Samples were collected from 65 revision arthroplasties (39 knees and 26 hips) and 17 primary arthroplasties (9 hips and 8 knees). Synovial fluid, deep tissue, and swabs were obtained at the time of the surgical procedure and were submitted for next-generation sequencing. Deep-tissue specimens were also sent to the institutional laboratory for culture.

Sensitivity and specificity were calculated for next-generation sequencing using the Musculoskeletal Infection Society (MSIS) definition of periprosthetic joint infection as the standard.

28 of the 65 revisions met the authors' criteria for infection. 17 of these were cultures positive and 25 were next-generation sequencing positive. There was concordance between next-generation sequencing and culture in 15 cases. Among the 11 cases of culture-negative periprosthetic joint infection, next-generation sequencing was able to identify an organism in 9 cases.

Next-generation sequencing identified microbes in 9 of 36 "aseptic" revisions with negative cultures and in 6 of 17 primary total joint arthroplasties. 

Next-generation sequencing detected several organisms in most positive samples. However, in the majority of patients who were infected, 1 or 2 organisms were dominant. These findings suggest that some cases of monomicrobial periprosthetic joint infection may have additional organisms that escape detection when culture is used. 

Comment: In their introduction the authors state "in up to 50% of periprosthetic joint infection cases, cultures fail to isolate the infecting organism". In the realm of revision shoulder arthroplasty, we and others have pointed out that "culture negativity", especially with regard to Propionibacterium, is often due to inadequate culture techniques: failure to obtain at least 5 deep tissue or explant samples, failure to culture on aerobic and anaerobic media and broth, and failure to observe the cultures for 17 days. Thus, unless the details of the approach to culturing are appropriate for Propionibacterium, the phrase "culture negative" must be used with caution. On the other hand, if specimen harvesting and culturing methods are appropriate and standardized, one can generate a semiquantitative picture of the culture results for the joint in question, estimating the load of bacteria in the joint rather than stating that the culture result as simply "positive" or "negative" - see this link.

Thus, it is of interest that in this study, only 60% of the lower extremity joints meeting the MSIS criteria for infection were "culture positive".

Defining and standardizing the culture practice is essential to the application of the MSIS criteria for infection, which are critically dependent on the number of specimens that are culture positive. The smaller number of specimens submitted, the fewer media used, and the shorter the period of culture observation, the less likely that bacteria will be recovered by culture and the less likely the case is to meet the criteria.

To build on this point, the authors state, "in approximately one-third of supposedly noninfected revision cases in this study, next-generation sequencing had detected bacteria. In many of these cases, Propionibacterium acnes was the predominant organism." Thus it would be important to know whether Propionibacterium-specific culturing techniques were used in the those cases; if not, it is unlikely that standard culturing techniques would have been positive for this organism. Furthermore, the detection of Propionibacterium in failed / revised hip and knee arthroplasty cases raises the concern that cases failing to meet the MSIS criteria for infection (because of the low level of inflammatory response and the difficulty of culturing Propionibacterium) may actually harbor this organism. Of note, none of the hip and knee cases in this series were culture positive for Propionibacterium. This is  in marked contrast to the results of some other studies of revised hip and knee arthroplasty in which Propionibacterium were prominent (see this link).

There is a well know saying, "absence of evidence is not evidence of absence," suggesting we be cautious in using the term 'aseptic'. We could take a number of samples of this lawn and not find any that show a poisonous mushroom, but that doesn't mean Amanita phalloides are not really there.

Finally, these authors found that next-generation sequencing was positive in approximately 35% of primary arthroplasties and 25% of revision of arthroplasties, in which the patients were presumed to be noninfected. In these cases we must wonder if these results were spurious, or (more likely in our view) that these cases actually had bacteria present, but that the presence of the bacteria (often Propionibacterium) had not manifested itself in a manner that was otherwise evident.

These authors are to be congratulated on a robust study that challenges current thinking regarding how to define a "periprosthetic infection". It prompts us to ask what may be the more important question, "what preoperative and intraoperative data do we need to select the appropriate surgical and antibiotic treatment of a patient having a revision of a failed arthroplasty?"

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