Saturday, February 18, 2023

Why do routine cultures miss detecting Cutibacterium?

Cultures of specimens of joint fluid, deep tissue samples, and prosthetic explants (see link) are the gold standard for identifying the microbes responsible for periprosthetic joint infections (PJI). As a result it is important to optimize the sampling and culturing methods so that organism-specific treatment can be implemented. Samples of sufficient size and number are to be obtained from the joint using sterile technique. Control sterile samples are to be obtained to assess the level of environmental and laboratory contamination. Appropriate media are to be selected for broth, anaerobic and aerobic cultures for bacteria and, when indicated, for fungus, yeast and micobacteria as well. Finally, cultures need to be observed for an appropriately long time in view of the time to positivity (TTP) of the bacteria. This latter factor is important in that a too-short period of observation may miss detecting the bacteria.

The time to positivity has been studied for Cutibacterium in shoulder periprosthetic infections (PJI). For example the authors of Optimization of periprosthetic culture for diagnosis of Propionibacterium acnes prosthetic joint infection concluded that a minimum culture incubation period of 13 days should be applied to both aerobic and anaerobic culture media for all periprosthetic specimens. The authors of
Origin of Propionibacterium in Surgical Wounds and Evidence-Based Approach for Culturing Propionibacterium from Surgical Sites found that obtaining at least four specimens, observing them for seventeen days, and using three types of culture media optimize the recovery of Propionibacterium (Cutibacterium) from samples obtained at revision surgery.

Recently, the authors of Time to Positivity of Cultures Obtained for Periprosthetic Joint Infection sought to determine the TTP for pathogens commonly encountered in PJI in 536 patients who met the 2018 International Consensus Meeting (ICM) criteria for PJI and had a positive intraoperative culture. 

Synovial fluid samples had the lowest yield on culture, compared with samples taken from soft tissue and bone: 66.2% (1,199) of the soft-tissue samples, 58.6% (782) of the samples obtained from bone, while only 31.3% (112) of the synovial fluid samples were positive. An explanation for the lower sensitivity of fluid cultures is that the majority of microbes present in prosthetic joints with PJI are in a biofilm requiring tissue sampling rather than in a planktonic form accessible in joint fluid.  

When evaluating the median TTP according to specimen type, synovial fluid (TTP, 1.97 [1.1 to 3.1]; n = 112) exhibited the shortest TTP, followed by soft tissue (TTP, 3.17 [1.4 to 5.3]; n = 1,199) and bone (TTP, 4.16 [2.3 to 5.9]; n = 782). An explanation for the shorter TTP for fluid cultures is that planktonic bacteria are likely to have a faster growth rate than the sessile bacteria found in a biofilm.


The median TTP for all positive cultures was 3.3 days (IQR, 1.9 to 5.4). In order of TTP speed

Methicillin-resistant Staphylococcus aureus (TTP, 1.42 [1.0 to 2.8]; n = 85) was fastest, followed by

Gram-negative rods (TTP, 1.92 [1.0 to 3.9]; n = 163), 

Methicillin-sensitive Staphylococcus aureus (TTP, 1.95 [1.1 to 3.3] n = 393), 

Streptococcus species (TTP, 2.92 [1.2 to 4.3]; n = 230), 

Staphylococcus epidermidis (TTP, 4.20 [2.4 to 5.5]; n = 555), 

Candida species (TTP, 5.30 [3.1 to 10]; n = 63); the slowest was the commonest cause of shoulder PJI:

Cutibacterium acnes (TTP, 6.97 [5.9 to 8.2]; n = 197). Note in the chart below that almost all of the positive cultures for Cutibacterium would have been missed with the three day observation period that is typical of many labs.


The authors recommended holding cultures for 14 days to capture most of the pathogens encountered in PJI.

Comment: A culture "turns positive" when there are sufficient numbers of bacteria on the plates or in the broth to be noticed by the laboratory technologist. 

The time to turn positive is faster for organisms having shorter doubling times (e.g. MRSA from a joint fluid sample). 

It is also faster when the original sample submitted for culture has a greater number of bacteria in it (see chart below).




This study indicates that attempts to identify the organisms causative of periprosthetic infection can fail because of too-short periods of culture observation - especially for the organism most commonly responsible for shoulder periprosthetic infections: Cutibacterium.

It also shows that with most bacteria, but especially Cutibacterium, the results of cultures come far too late to guide the initial treatment. Thus initial surgical and antibiotic must be based on the physician's knowledge of the most likely causative organism. In the case of shoulder PJI, that is Cutibacterium.

You can support cutting edge shoulder research that is leading to better care for patients with shoulder problems, click on this link.

Follow on twitter: https://twitter.com/shoulderarth
Follow on facebook: click on this link
Follow on facebook: https://www.facebook.com/frederick.matsen
Follow on LinkedIn: https://www.linkedin.com/in/rick-matsen-88b1a8133/

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).