What is the significance of cultures obtained at revision arthroplasty?

During revision of shoulder arthroplasties presenting with pain, stiffness or prosthetic loosening, surgeons frequently obtain Cutibacterium-specific cultures of deep tissues and prosthetic explants because:

(1) Cutibacterium is the bacterium most commonly isolated from shoulder periprosthetic infections and (2) Cutibacterium periprosthetic infections (CPJI) typically have a stealth type presentation without the fever, chills, swelling, erythema, tenderness, and elevated serum or joint fluid inflammatory markers characteristic of the obvious periprosthetic infections from other organisms that can complicate hip and knee arthroplasties.

While some authors refer to positive cultures in the absence of obvious evidence of periprosthetic infection as unexpected, these cultures are obtained because surgeons expect some of their shoulder revisions to be sufficiently culture positive to merit treatment for CPJI. 

As an example, a young healthy man who had an initially normal post-arthroplasty course for 9 months and then develops otherwise unexplained pain and stiffness of the shoulder and who has high loads of Cutibacterium on a swab of the unprepared skin over the shoulder would be expected to be at high risk for positive Cutibacterium cultures obtained at the time of revision. In such a case multiple deep tissue and explant cultures would be submitted for aerobic and anaerobic cultures to be observed for at least 14 days. Because the cultures were expected to be positive, the revision would probably consist of a single stage prosthesis exchange after thorough debridement and lavage followed by a course of antibiotics starting immediately after surgery and continued until the results of the cultures were final. Subsequent treatment would be guided by the results of the cultures.

The authors of Evidence-Based Approach to Managing Unexpected Positive Cultures in Shoulder Arthroplasty point out that positive cultures are commonly found when surgeons send intraoperative cultures to rule out periprosthetic joint infection in failed arthroplasties that do not have obvious clinical or radiographic signs of infection. 

They conducted a review of 22 studies reporting on positive cultures from patients who did not have clinical or laboratory findings consistent with infection preoperatively. Studies that included patients with obvious periprosthetic infections were excluded. 

These authors report that the primary finding from their study was that the rate of positive deep tissue cultures was 27.5% in revision shoulder arthroplasty; Cutibacterium, accounted for 76.4% of these cases. Only 3 of the 22 studies investigated the culture rate of control cultures of inanimate specimens (sterile gauze or suture), The pooled rate of positive cultures in these three studies was 20.1%

The utilization of antibiotics and treatment regimens varied across these studies. Patient reported outcomes and re-operation rates did not differ between patients with positive and those with negative cultures. 

Based on the results of this review, the authors recommend that at least five cultures be obtained at revision arthroplasty and that two or more positive cultures are suggestive of true bacterial colonization. Cultures that have 2+ or more growth on agar plates indicate a much greater bacterial burden compared to only one colony or growth only in the broth.  The senior author’s preferred protocol is typically to put all revisions on a 14 day course of oral doxycycline while awaiting final culture data.  

The authors state that the positive culture rate in revision arthroplasty (27.5) was "only slightly greater than the control rate of culture positivity for sterile, inanimate objects (20.1%)".  However, as pointed out above, the false positive rate of 20.1% was based on only three studies, two of which cultured sterile sponges and one of which cultured sterile suture. The 20.1% figure may not accurately reflect the false positive in most medical centers. For example, in the study What do Positive and Negative Cutibacterium Culture Results in Periprosthetic Shoulder Infection Mean?, two sterile gauze samples were cultured for Cutibacterium at 11 different institutions. These samples grew Cutibacterium in only 3 of 22 samples at two of the 11 institutions, the other 9 institutions had no growth for the sterile samples. Furthermore, the strength of culture positivity was significantly lower in these negative controls compared to positive specimens (p<0.001). No negative control had >1 quadrant of Cutibacterium growth on agar plates. In sum, only 2 of the 11 institutions cultured Cutibacterium from the sterile controls and the amount of growth from these sterile controls was significantly less than that for the samples containing various concentrations of Cutibacterium. 

Similarly in Preoperative Skin-Surface Cultures Can Help to Predict the Presence of Propionibacterium in Shoulder Arthroplasty Wounds, only 2 of 50 sterile control specimens were culture positive for Cutibacterium and both of these control samples had no more than minimal growth.

Finally, in The efficacy of topical preparations in reducing the incidence of Cutibacterium acnes at the start and conclusion of total shoulder arthroplasty: a randomized controlled trial, none of the 101 control swabs that had been placed within the sterile field on the surgical trolley for the case duration were culture positive for Cutibacterium.

Thus it seems essential that each institution assess its own rate of positive cultures for sterile control specimens, rather than assuming that all institutions have the same false positive rate.

The importance of culturing multiple deep tissue and explant specimens in revision shoulder arthroplasty - even if there is no obvious evidence of infection - is demonstrated in Single-Stage Revision Is Effective for Failed Shoulder Arthroplasty with Positive Cultures for Propionibacterium: revised shoulder arthroplasties having 2 or more positive cultures for Cutibacterium and treated with single stage revision and appropriate antibiotic therapy had at least as good 4 year outcomes as for revised shoulder arthroplasties with no or minimal Cutibacterium growth. 

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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).

What is the significance of positive cultures at the time of revision? - lessons from hip arthroplasty

Prevalence and Outcomes of Unexpected Positive Intraoperative Cultures in Presumed Aseptic Revision Hip Arthroplasty

These authors reviewed all 2,288 total hip arthroplasty (THA) revisions performed at their institution from 2006 to 2019. Of these 1196 did not have preoperative evidence of infection ("presumed aseptic revision"). Three to five samples were obtained for culture at the time of revision. Positive cultures were documented for 9.2% (110) of the 1,196 presumed aseptic THA revisions.  68% of the cases had one positive culture while 32 had two or more positive cultures.  38% of the positive cultures were for Cutibacterium, 13% for Methicillin resistant Staph Epidermidis, 11% for other coagulase negative Staph, 9% for Methacilling sensitive Staph, 5% for micrococcus.

41 (38%) were treated with antibiotics (10 oral alone, 9 IV alone, 22 oral and IV).

The 2- and 5-year infection-free implant survival rates for the 1196 revisions were 93.1%  and 86.8%. 

The  2- and 5-year infection-free survival with failure due to infection with the same microorganism as identified in the initial revision as the end point were 95.8%  and 94.3%, respectively. 

Subsequent infection-related failures caused by the same microorganism as identified in the initial revision were more likely to occur after revisions with ≥2 positive culture than after those with only 1 positive culture.

They defined adverse metal reactions as any adverse local tissue reaction (ALTR), including “pseudotumors,” due to metal ions causing failure of the total joint replacement including metal-on-metal bearings, corrosion of the head-neck junction in metal-on-polyethylene bearings (“trunnionosis”), or recalled modular stems at the modular neck-stem junction. Of the variables included in multivariate Cox regression analysis, only revision for adverse metal reaction was significantly associated with an increased risk of subsequent infection-related failure; revision for adverse metal reaction was a risk factor for subsequent infection-related failure (hazard ratio [HR] = 14.4).

Patients with a single positive culture at the initial revision who were not treated with antibiotics had no subsequent periprosthetic joint infections (PJIs) caused by the same microorganism as identified in the initial revision.

Comment: Here are a few of the lessons we can learn from this study

(1) In these "apparently aseptic" cases of PJI with positive intraoperative cultures, Cutibacterium was the most common organism isolated from deep cultures. 

It is of note that most cases of shoulder PJI do not have preoperative evidence of infection and could be referred to as "apparently aseptic", i.e. "stealth" infections.  Cutibacterium is the most common organism isolated from shoulder PJI.

(2) The authors found that their increased detection of Cutibacterium compared with most

studies may be due to the extended 10-day anaerobic incubation time for their cohort. 

We hold all cultures obtained at revision shoulder arthroplasty for 14 days.

(3) An increased load of bacteria (as reflected by the number of positive cultures) found at revision arthroplasty was associated with failure of the revision to resolve the infection. 

We go one step further in determining the bacterial load by quantitating not only the number of positive cultures but also the degree of positivity of each one. See 10 points about Cutibacterium, periprosthetic infection, and revision for failed shoulder arthroplasty.

(4) Metal sensitivity may increase the likelihood of periprosthetic infection as well as the difficulty in resolving a PJI. 

The relationship of metal sensitivity to PJI surely merits further study. See Acute delayed infection: increased risk in failed metal on metal total hip arthroplasty and High rate of infection after aseptic revision of failed metal-on-metal total hip arthroplasty

How you can support research in shoulder surgery Click on this link.

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 total shoulder arthroplasty (see this link).

The ream and run technique is shown in this link.

The cuff tear arthropathy arthroplasty (see this link).

The reverse total shoulder arthroplasty (see this link).

Shoulder rehabilitation exercises (see this link).

Follow on twitter: Frederick Matsen (@shoulderarth)

Positive cultures at revision arthroplasty, expecting the unexpected

Future surgery after revision shoulder arthroplasty: the impact of unexpected positive cultures

These authors studied 117 patients having revision shoulder arthroplasty without obvious evidence of infection. The average time from the initial surgery to revision was 4.3 years. 28 of 117 (23.9%) had what they referred to as 'unexpected positive cultures ( UPCs).

The diagnoses at time of revision surgery were rotator cuff dysfunction (32/117; 27.3%), glenoid wear after shoulder hemiarthroplasty/painful shoulder hemiarthroplasty (23/117; 19.7%), glenoid loosening (17/117; 14.5%), dislocation (11/117; 9.4%), malunion/nonunion (11/117; 9.4%), instabil- ity (10/117; 8.6%), arthrofibrosis (7/117; 6.0%), and humeral loosening (6/117; 5.1%). It is not clear from the manuscript what type of revision surgeries were performed for these shoulders, specifically how many had complete single stage exchange of the prosthesis. 

Interestingly, these authors appear to routinely administer at least 2 weeks of empirical oral antibiotics after each revision surgery, so each patient received some antibiotic treatment for a possibly positive culture. The antibiotics used are not described. 18 of 28 (64.3%) patients received antibiotics for 6 weeks postoperatively without complications compared with 10 of 28 (35.7%) who received the routine 2-week empirical antibiotic regimen. The decision to continue antibiotics beyond the 2-week threshold was based on culture results, clinical presentation, and intraoperative findings. Patients with positive cultures for Propionibacterium were variably treated with no antibiotics in 8 cases, with 6 weeks of IV Vancomycin in 5 cases, and with IV Penicillin in two cases.

28 of 117 (23.9%) had what they referred to as 'unexpected positive cultures ( UPCs). 15 (57.1%) of these cultures grew Propionibacterium acnes. However, review of the data (Table II) indicate that three cases had only one specimen submitted for culture and 10 had only two cultures submitted. Over half of the cases had four or fewer cultures sent. It is recognized that the presence of Propionibacterium may be overlooked if a small number of specimens are submitted. The number of specimens submitted for culture in the 89 cases without positive cultures is not presented.

2 of 28 (7.1%) patients with UPCs required future surgery, and only 1 (3.6%) had a recurrent infection. This reinfection was in a patient who grew 1 of 6 cultures positive for P. acnes, and this reinfection was 2.2 years after the index revision. This patient did not receive a course of postoperative antibiotics (outside of the routine 2-week empirical antibiotic regimen). In addition, there were 3 patients without UPCs (3.4%; P = .959) who presented with reinfection. These 3 patients did not receive a course of postoperative antibiotics outside of the routine 2 weeks of empirical postoperative antibiotics.

18 of 89 (20.2%) patients without UPCs required 25 additional surgeries. The difference in reoperation rate between those shoulders with and without UPCs was not statistically significant.

Comment: It is critical to recognize that the need for re-revision after a shoulder arthroplasty revision may be prompted by a wide variety of mechanical factors, so that the overall re-revision rate is not a useful indicator of the importance of culture results. It is also import to recognize that the 28 cases with positive cultures presented years after the index procedure without obvious evidence of infection. This observation makes it impossible to know when a revision surgery with positive cultures has successfully eliminated bacteria from the shoulders.

In cases where these authors performed a single stage revision followed by two weeks of antibiotics, they may have adequately treated the presence of Propionibacterium as pointed out in this article,  Failed shoulder joint replacement: single stage revision when cultures are positive for Propionibacterium. The key in managing Propionibacterium appears to be the removal the implant carrying the infected biofilm.

Shoulder arthroplasty failure may or may not be associated with positive cultures. The role of bacteria in the failure remains unclear, as emphasized in this article, Glenoid loosening - is it predictive of positive cultures? and in this article,  How do revised shoulders that are culture positive for Propionibacterium differ from those that are not? In the latter article the authors reviewed records of 132 shoulders that underwent surgical revision of a shoulder arthroplasty, 66 of which became culture positive for Propionibacterium and 66 did not. The authors found that Propionibacterium-positive and Propionibacterium-negative shoulders were similar with respect to many characteristics; however, Propionibacterium-negative shoulders were revised sooner after the index procedure and were significantly more likely to be female, to have sustained a fall, to have instability, and to have rotator cuff deficiency. Intraoperatively, Propionibacterium-positive shoulders demonstrated more glenoid erosions, glenoid osteolysis, glenoid loosening, and a higher incidence of a soft tissue mem- brane between the humeral component and humeral endosteum. Shoulders culture positive for Propionibacterium were more likely to be culture positive for another bacteria. 

These authors concluded that although Propionibacterium-positive and Propionibacterium-negative shoulders have many similarities, factors such as male gender, delayed presentation, glenoid osteolysis and loosening, humeral membrane, and the absence of instability or cuff failure should arouse suspicion of Propionibacterium and suggest the need for deep cultures and consideration of aggressive surgical and medical treatment.

We conclude that this article demonstrates the need for a standardized approach to culturing and reporting quantitative culture results in cases of revision arthroplasty as emphasized in this article,  Considering the Load of Propionibacterium in Revision Shoulder Arthroplasty. Correlating the standardized quantitative culture results obtained with the management strategy and clinical outcome will inform our future understanding and management of failed shoulder arthroplasty.

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