What information can be gathered from a synovial fluid aspirate?

Synovial fluid aspiration is often used to gather information about a possible periprosthetic infection. 

When a sufficient volume is recovered, laboratory tests may help surgeons evaluate the likelihood of a periprosthetic infection; however the aspiration attempt may not yield fluid even if it is image guided. To be clinically useful, the aspiration needs to be carried out several weeks in advance of a potential surgical revision to allow sufficient time for laboratory tests and culture results to be finalized.

The authors of Synovial Fluid Cutibacterium acnes Antigen Is Detected Among Shoulder Samples with High Inflammation and Early Culture Growth presented a three pronged analysis of 1,365 de-identified synovial fluid samples, of which 1,150 were culture-negative and 215 were culture-positive.  94 of the culture positive samples were positive for Cutibacterium and 121 for other organisms.

The samples were analyzed by (1) time to culture positivity (known to be a reflection of the load of bacteria in the sample), (2) a validated  C. acnes antigen immunoassay test, and (3) a synovial fluid inflammation score calculated from 4 tests on synovial fluid: C reactive protein,  alpha-defensin, WBC count and percent polymorphonuclear cells.  

They found that 

(1) The samples tended to cluster into high inflammation and low inflammation groups for both all specimens

and for those in specimens that were culture positive for Cutibacterium

(2) C. acnes antigen levels demonstrated moderate-strong positive correlation with inflammation, with 166-fold higher levels of C. acnes antigen in high-inflammation samples compared with low-inflammation samples. 

(3) The days to C. acnes culture positivity demonstrated weak- inverse correlation with inflammation, with 1.5-fold earlier growth among the 67 high- inflammation samples compared to the low inflammation samples. Because a positive culture depends on discernible colonies on the culture plate and because the threshold for discernability relates to the number of bacteria present, low loads of bacteria in the sample are expected to have longer time to culture positivity. 

The relationship between C acnes antigen levels (left) and days to culture positivity (right) for samples with low inflammation and high inflammation is shown below.

(4) 19.0% of high-inflammation, culture-negative fluid samples demonstrated elevated C. acnes antigen.  Elevated C. acnes antigen was observed in only 0.38% of the low-inflammation culture-negative fluid samples and in only 4.9% of the high-inflammation non-C. acnes-positive cultures. 

Here it is of note that synovial fluid cultures are not uncommonly culture negative when tissue and explant cultures are positive. This may be because there may be Cutibacterium in biofilm form in tissue but not in planktonic (free floating) form in fluid. Thus these shoulders may not have been culture negative if tissue and explant cultures had been available. Absence of evidence is not evidence of absence.

Comment: One way to put these findings together is that low loads of Cutibacterium (as indicated by longer times before cultures become positive and by low antigen levels) may be insufficient to cause a tissue damaging inflammatory response on the part of the host. If one uses the definition of infection as "bacteria doing harm", these shoulders may not meet that definition, even though there are bacteria present. On the other hand, high loads of bacteria are likely to have shorter time to culture positivity, higher antigen levels and more inflammation.

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