What predicts the failure of a two-stage revision for periprosthetic infection?

A revision for an infected arthroplasty (PJI) is a big deal for the patient as described in Periprosthetic infection: what does my patient care about?  The mental and physical toll is even greater when a two-stage revision is performed: two big procedures with an interposed period of living with a polymethylmethacrylate spacer between the two sides of the joint. The patient can be expected to ask how likely the two-stage procedure is to be successful if they go through all of that. We are not very good at making such predictions as I pointed out in Objective ignorance - a problem in predicting outcomes in climbing and in orthopaedic surgery

The authors of Isolation of Multiple Positive Cultures at Resection Arthroplasty is a Predictor of Failure Following Reimplantation studied 437 patients with chronic knee PJI of which almost one third had "culture negative infections," according to the 2013 Musculoskeletal Infection Society (MSIS) criteria. The minimum number of cultures obtained for all patients was 3 the average number of positive cultures was 2.9. The most commonly isolated organism at resection arthroplasty was coagulase-negative staphylococci, followed by coagulase-positive staphylococci, gram-negative organisms, and Streptococcus species. Of the positive cultures over 90% were soft issue samples (far outstripping the percent of positive cultures from cultures of synovial fluid and implant sonication). 

Among those with postive cultures, more than one of six patients experienced treatment failure defined as either any reoperation for infection or PJI-related mortality.

Almost 96% of the patients who experienced failure following reimplantation had ≥2 positive cultures isolated at the time of resection arthroplasty in comparison to those who had successful treatment (75%) Furthermore, the presence of ≥2 positive cultures at resection was associated with an 8-fold increase in the odds of failure following the completion of a 2-stage protocol when compared with the presence of a single positive intraoperative culture (20% versus 3%).

Interestingly, of the patients with positive cultures at the time of failure over half had discordant culture results, meaning that the cultures from the second revision grew different organisms than those from the first revision. In these cases perhaps the first treatment got rid of the initially infecting bugs only to leave the door open for a second species of invader into unhealthy tissue. Thus, it seems important to take multiple intraoperative tissue samples at the second stage. 

A few questions arise that I'd love some help answering:

Taken together do these data suggest that treatment failure of a two-stage revision is due to poor host resistance or to inadequate surgical and antibiotic treatment or both? 

In that the average number of cultures obtained per patient was a minimum of 3,  how senstive is threshold of  ≥2 positive cultures to the number of samples taken?  

What is the clinical importance of the observation that 75% of the patients with "successful" treatment had  ≥2 positive cultures ; i.e. is  ≥2 positive cultures at the time of the second procedure a clinically useful predictor of subsequent failure? 

What is the best postoperative antibiotic treatment to implement after revision before the results of intraoperative cultures are finalized?

How should "culture negative infections be treated"?

Is the term "unexpectedly positive cultures" helpful, or do we treat all revisions as if they are potentially infected with intraoperative cultures, debridement and postoperative antibiotics?

Infections Are Intimidating

 Black Vulture

Austin, Texas

April, 2025

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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 a shoulder infection?

While the diagnosis of obvious shoulder infection is easy: the patient has local and systemic signs of inflammation, abnormal joint fluid and serum lab tests, and positive cultures for indisputable pathogens. 

On the other hand, the diagnosis of a stealth shoulder infection is complicated: the most frequently implicated bacteria (Cutibacterium) is a commensal organism commonly isolated from normal skin, normal deep tissues and healthy shoulder joints. In a stealth infection the usual clinical evidence of infection is absent.

A pragmatic definition of bacterial infection is "bacteria doing harm". That is, the presence of bacteria in and of itself is not sufficient to prove infection. Bacteria in the large intestine; bacteria in sebaceous glands; bacteria recovered from normal joints would not meet the definition whereas E. coli colitis, acne, and joint sepsis would. 

A recent paper,The incidence of subclinical infection in patients undergoing revision shoulder stabilization surgery: a retrospective chart review, exemplifies the challenge. The authors sought to identify the incidence of subclinical infection in 107 patients undergoing revision shoulder stabilization surgery by an experienced shoulder surgeon. Notably the average time from the instability repair to revision was 8 years. The reasons for revision were not provided. Surgical findings (synovitis, purulence, gram stain results) were not given. 

Twenty-nine patients (27.1%) had positive cultures. Patients had multiple specimens sent for culture; the average and range for the number of cultures submitted is not provided. Thirteen patients had only1 positive culture (11 for Cutibacterium). 9 patients had two positive cultures Eight had 3 or more positive cultures (all for Cutibacterium). 

 The paper does not state whether the patients were given antibiotic coverage for the several weeks while the culture results were pending rather than waiting until the results were finalized. The treatment for those patients with positive cultures is not provided.

Twenty-six of these patients (90%) had positive Cutibacterium cultures. The average time to culture positivity was 11 days.

The paper does not state whether any patients developed clinical manifestations of infection.

Comment: It is difficult to know whether these positive cultures obtained on average 8 years after surgery in the absence of other supporting evidence actually represent an infection, i.e. did the bacteria cause harm?

If the surgeon is suspicious of an infection, a reasonable strategy would be to perform a thorough debridement and irrigation at the time of revision, take cultures for Cutibacterium, consider topical antibiotics, and postoperative antibiotics to be continued until the culture results are finalized.     Bases covered.

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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).

Should surgeons doubt the value of cultures in shoulder surgery?

It is well recognized that bacterial infections are important causes of failed shoulder arthroplasy, failed cuff repairs and failed fracture fixation. The organisms most commonly responsible for these infections (Cutibacterium and coagulase negative staphylococcus (CNS)) are also found on and in healthy skin of healthy individuals as well as in the environment.

Of note, these organisms can be isolated from sterile swabs and sponges that are exposed to the air in the operating room, suggesting that specimens can be contaminated by air-borne organisms, specimen handling or microbiology laboratory processing. Knowing the results of control environmental non-clinical cultures for a surgeon's operating room is important to the interpretation of the results of clinical cultures isolated from deep tissue specimens and explants obtained at the time of revision surgery.

Between-hospital variability in the results of sterile cultures is demonstrated by the reported rates of control samples that are positive for Cutibacterium which range from 4% to 9% to 15% to 20%:

In Efficacy of topical benzoyl peroxide on the reduction of Propionibacterium acnes during shoulder surgery  4% (2 of 50) of sterile control specimens were positive for P. acnes (Cutibacterium)

In The Incidence of Propionibacterium acnes in Open Shoulder Surgery: A Controlled Diagnostic Study seven (13.0%) of fifty-four sterile control specimens returned positive for culture growth. Five of these (9%) grew P. acnes (Cutibacterium), while two (4%) grew coagulase-negative S. aureus.

In Cutibacterium acnes is Isolated from Air Swabs: Time to Doubt the Value of Traditional Cultures in Shoulder Surgery? Cutibacterium was identified by culture of sterile control swabs in 6 of 40 cases (15%) swabs and coagulase negative staphylococcus (CNS) was identified in 3 of 40 (7.5%). 

In Preoperative doxycycline does not decolonize Propionibacterium acnes from the skin of the shoulder: a randomized controlled trial 20 sterile control specimens were submitted for culture, four of which (20%) grew P. acnes (Cutibacterium).

This five fold difference among hospitals in the rate of positive cultures for sterile control specimens suggests different risks of specimen contamination in the operating room, during specimen handling and/or in the microbiological laboratory.

The magnitude of contamination from these environmental sources would be expected to be small in comparison to the load of bacteria in an infected shoulder. The authors of Characterizing the Propionibacterium Load in Revision Shoulder Arthroplasty pointed to the value of assessing the amount of bacteria in a sample using a semi-quantitative report rather than simply referring to a culture result as "positive" or "negative". In 137 Cutibacterium culture-positive revision shoulder arthroplasties the culture results were characterized by a specimen Cutibacterium value (SpCV): 0 = no growth, 0.1 = broth only or one colony only, 1 = growth on one plate quadrant, 2 = growth on two plate quadrants, 3 = growth on three plate quadrants and 4 = growth on all 4 of the plate quadrants after standard microbiological plate streaking.

The authors of Preoperative Skin-Surface Cultures Can Help to Predict the Presence of Propionibacterium in Shoulder Arthroplasty Wounds used this semi-quantitative approach to report the results of cultures for sterile control swabs submitted from the operating room in 50 cases. While 2 of the control samples had positive cultures for Cutibacterium (4%), neither (0%) of the positive control samples had a SpCV of 1 or more, indicating a very low level of contamination.

Some authors have proposed that Next Generation Squencing (NGS) may be superior to cultures in detecting bacteria doing harm in shoulders. See for example, Revision shoulder arthroplasty - what is the role of next-generation sequencing?. NGS is very sensitive to the presence of bacterial RNA and DNA. In the referenced study, NGS found evidence of no fewer than 71 different organisms in specimens from cases of revision arthroplasty. including A calcoaceticus, A excentricus, A ferrireducens, A junii, A radioresistens, A rhizogenes, A tetradius, B aggregatus, B casei, B cepacia, B dorei, B fragilis, B fungorum, B mycoides, B nordii, B thermosphacta, B thetaiotaomicron, B virosa, C tuberculostearicum, C circulans, C acidisoli, C aurimucosum, C chromoreductans, C diptheriae, C hominis, C hveragerdense, C kroppenstedtii, C paradoxus, C quinii, C striatum, C testosteroni, C tuberculostearicum, C vibrioides, C xerosis, C. acnes, E coli, E hormaechei, G ruanii, K rosea, K oxytoca, K palustris, K pneumoniae L agilis, L albida L crispatus, L manihotivorans, M catarrhalis, M granosa, M luteus, P aeruginosa P agglomerans, P saccharophilia, R gnavus, R insidiosa, R picettii, S agalactiae, S aureus (MRSA) S aureus, S cohnii S condimenti, S epidermidis S hominis, S maltophilia, S melonis, S mitis, S parasanguinis, S pettenkoferi, S piscifermentans, and S sanguinis. It is not known if these results actually reflect living bacteria in the shoulder and what implications these NGS results have for treatment.

The authors of Cutibacterium acnes is Isolated from Air Swabs: Time to Doubt the Value of Traditional Cultures in Shoulder Surgery? suggest that NGS is capable of identifying pathogens and the relative percent abundance in which they appear within a sample. They state, "due to budgetary limitations and the cost of NGS, our sample size was admittedly small and only included one sample for culture and NGS from each case".

For 40 consecutive cases they opened and exposed sterile swabs to the air in the operating room for 5 seconds.  One swab was sent to their microbiology laboratory for aerobic and anaerobic culture and held for 13 days. The other sample was sent for NGS, where samples were amplified for pyrosequencing using a forward and reverse fusion primer and matched against a DNA library for species identification.

Cutibacterium was identified by culture in 6/40 (15%) swabs and coagulase negative staphylococcus (CNS) was identified in 3/40 (7.5%). When considering the semi-quantitative assessment of bacterial growth, all six samples with isolated Cutibacterium were rated as very light growth, a finding consistent with the very low SpCVs in the two positive control cultures in Preoperative Skin-Surface Cultures Can Help to Predict the Presence of Propionibacterium in Shoulder Arthroplasty Wounds . 

2/40 cases (5%) had positive NGS sequencing with polymicrobial results in the distributions shown below.

Case #6: 

P. aeruginosa (26%), P. melaninogenica (19%),  C. tuscaniense (12%),  S. mitis (9%), B. japonicum (8%), A. wolffii (7%), C. appendicis (4%), B. antiquum (4%), A. schindleri (2%)

Case #20: S. hominis (31%), S. epidermidis (24%), M. subterranean (11%), C. kroppenstedtii (8%), E. biforme (8%), P. submarinus (4%), N. oleivorans (3%), Cutibacterium (3%)

Comment: From the foregoing, it can be concluded that

(1) contamination of sterile swabs can occur between the time of opening of the swab and the final analysis of bacterial cultures by the microbiology lab. The resulting positive cultures are not "false positives" but rather positive cultures resulting from contamination

(2) the rate of contamination from the operating room environment, specimen transport and laboratory procedures varies widely among medical centers

(3) the bacterial load - as reflected by the specimen Cutibacterium value  (SpCV) -  in contaminated sterile swabs is small in comparison to the SpCV typically seen in cultures of deep tissues and explants retrieved from shoulders with periprosthetic infections; thus reporting the culture results using a  semiquantitative system to reflect bacterial load helps identify clinically important positive cultures.

(4) Next Generation Sequencing is an expensive test that reveals RNA and DNA associated with a wide range of bacterial species, the preponderance of which have not been demonstrated to be pathogenetic. Thus the value of NGS in guiding therapy in shoulders with suspected infection remains to be demonstrated.

(5) In the absence of a better alternative, surgeons should continue to use bacterial cultures (assessed for bacterial load) to help guide the management of failed shoulder surgeries potentially caused by infection.

See also: What we think we know today about Cutibacterium 

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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).

Do preoperative cultures of aspirated joint fluid agree with cultures of intraoperative tissue biopsies in cases of shoulder periprosthetic infection.

Surgeons often use cultures of aspirated joint fluid as a means of determining the presence and type of bacteria in cases of suspected periprosthetic joint infection of the shoulder (PJI).


The authors of What is the concordance rate of preoperative synovial fluid aspiration and intraoperative biopsy in detecting periprosthetic joint infection of the shoulder ? sought to evaluate the degree of agreement between preoperative synovial fluid culture results and intraoperative tissue culture results in 50 patients meeting the 2014 Musculoskeletal Infection Society criteria for shoulder PJI.

Concordance between preoperative aspiration and intraoperative tissue culture was identified in only 28 patients out of 50 (56%).

Preoperative cultures positive for Cutibacterium acnes demonstrated sensitivity, specificity, positive predictive value (PPV) and NPV lower than 0.8. More favorable concordance was observed for monomicrobial preoperative cultures, particularly for Gram-negative organisms and methicillin sensitive Staphylococcus aureus. Gram-negative pathogens demonstrated the highest sensitivity and specificity, while polymicrobial infections exhibited the lowest sensitivity and positive predictive value (PPV).




Comment: In this study there was frequent disagreement between the results of cultures of a preoperative shoulder joint fluid aspirate and the results of cultures of 5-8 intraoperative tissue samples in shoulders meeting the 2014 Musculoskeletal Infection Society criteria for shoulder PJI. The accuracy of preoperative joint fluid cultures was greater for virulent organisms; the accuracy was less for the most common organisms causing shoulder PJI: Cutibacterium and coagulase negative Staph. The reason for the discordance, especially for Cutibacterium, is due to the facts that (1) this bacterium is most commonly found in biofilms adherent to soft tissue and implants rather than freely floating in the joint fluid and (2) a single sample of joint fluid is statistically less likely to detect bacteria than multiple samples of tissue.

In our practice, joint aspiration is most helpful in the presence of an obvious periprosthetic infection where the diagnosis of PJI is not in doubt but where identifying the causative bacterium before surgery would help inform the choice of surgery and immediate postoperative antibiotic therapy (see Periprosthetic shoulder infections, single stage and two-stage revision).

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Follow on twitter: https://twitter.com/shoulderarth
Follow on facebook: click on this link
Follow on facebook: https://www.facebook.com/frederick.matsen
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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).

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?)

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

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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).

Periprosthetic infections - why is joint aspiration insensitive, how much better is tissue biopsy?

Better diagnostic value of mini-open and arthroscopically obtained tissue cultures compared to sterile punctures to identify periprosthetic shoulder infections: a retrospective cohort study

These authors sought to compare the sensitivity and specificity of sterile shoulder needle aspiration in comparison to arthroscopic and mini-open obtained cultures for detecting periprosthetic shoulder infections, using tissue cultures of revision surgery as the reference standard.

Between 2012 and 2018 joint aspiration was used to evaluate possibly infected shoulders (i.e. those with unexplained pain and stiffness after arthroplasty).   Sterile punctures were performed under fluoroscopic control. Only patients in which fluid could be aspirated were included in the study (i.e. dry taps were excluded). 

In 2018 arthroscopic and mini-open culture acquisition were used when a periprosthetic joint infection was suspected because of unexplained shoulder pain and/or stiffness. The choice of mini-open or arthroscopic tissue cultures depended on the type of the prosthesis in situ: arthroscopic tissue cultures were commonly obtained in case of a hemi or total shoulder prosthesis, whereas most mini-open biopsies were obtained in case of a reverse total shoulder prosthesis. Six separate sterile instruments were used to obtain the six samples for arthroscopic and mini open biopsies. 

During revision surgery, prophylactic antibiotics were withheld until cultures were obtained. Six tissue cultures were taken from different locations at the interface with the humerus and glenoid component using six separate sterile rongeurs were used.

Cultures were observed for 14 days. A low-grade infection was diagnosed when at least two cultures with the same low virulence organism were positive. 

The most commonly recovered organism was Cutibacterium followed by coagulase-negative staphylococcus.

As can be seen from the table below, while the aspirate cultures were specific (91%), they were insensitive (20%). By contrast arthroscopic and mini-open cultures were just as specific (86%) specific, but three times as sensitive (60%).

Comment: The bottom line of this important study is that a substantially positive culture on joint aspiration is a helpful indication of a periprosthetic infection, but a negative aspirate culture does not prove the absence of infection ("absence of evidence is not evidence of absence"). One might ask, why are tissue samples more likely to be culture positive in cases of periprosthetic infections than a fluid sample? There are at least two possible explanations. First, the aspirate is only one sample, whereas these surgeons thoughtfully obtained 6 separate tissue samples at arthroscopic, mini-open and revision surgery - thus the odds of a positive culture are greater with a higher number of samples. Secondly, a positive fluid aspirate depends on the bacteria being in planktonic form (i.e. suspended in the joint fluid); however, Cutibacterium in particular has a tendency to become embedded in tissue and in biofilms on implants rather than being freely swimming around in joint fluid. 

As in considering all tests for infection, the surgeon needs to decide how each of the possible outcomes will influence treatment. So in the case of a fluid aspirate, a negative culture result would have no effect on treatment, whereas a negative result from six tissue biopsies suggest that a periprosthetic infection is less likely. However, as shown clearly in this study, neither a negative arthroscopic or mini open set of samples can exclude the possibility of infection - in fact one third of the shoulders with negative preoperative tissue biopsies were found to have a periprosthetic infection at revision surgery.

Follow on twitter: https://twitter.com/shoulderarth

Follow on facebook: https://www.facebook.com/frederick.matsen

Follow on LinkedIn: https://www.linkedin.com/in/rick-matsen-88b1a8133/

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)

Shoulder arthritis - x-ray appearance (see this link)

The smooth and move for irreparable cuff tears (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).

This is a non-commercial site, the purpose of which is education, consistent with "Fair Use" as defined in Title 17 of the U.S. Code.          

Note that author has no financial relationships with any orthopaedic companies.

Revision shoulder arthroplasty - what type of cultures should we obtain?

 The Utility and Cost of Atypical Cultures in Revision Shoulder Arthroplasty

These authors conducted a review of 237 revision shoulder arthroplasties performed on 189 patients.

Cultures were sent on 158/237 (66.7%) of the surgeries with an average of 2.2 specimens per surgery.

Positive cultures were found in 52/341 (15.2%) aerobic cultures and 36/331 (10.9%) anaerobic

cultures. 

The most commonly isolated organism was Cutibacterium (42.2%), followed by MRSA (15.6%), coagulase-negative staphylococcus species (13.3%), and MSSA (12.2%). 

None of the fungal or acid-fast cultures were positive. 

The total billing charges for aerobic, anaerobic, fungal, and acid-fast cultures over the study period were $77,748, $23,832, $8,789, and $106,662, respectively, with fungal, and acid-fast cultures accounting for 53.2% of the total charges for all cultures. 

For a single sample sent for all four culture types, atypical cultures account for 69% of the total amount charged.

Comment: This study again demonstrates that a substantial percentage of specimens obtained at the time of revision arthroplasty are culture positive for Cutibacterium or Staph species and that male sex is a risk factor for Cutibacterium culture positivity. Finally, it points out that cultures for fungal and acid fast organisms are not of value for routine revisions, perhaps being reserved only for perplexing cases of "culture negative" infections.

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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 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).

Revision shoulder arthroplasty - what is the role of next-generation sequencing?

Comparative study of cultures and next-generation sequencing in the diagnosis of shoulder prosthetic joint infections

These authors point out that serum and synovial markers used to diagnose lower extremity prosthetic joint infection (PJI) have performed poorly for shoulder PJI. As a result, diagnosis is commonly reliant on the accuracy of positive or negative cultures.

They sought to determine the correlation between next-generation sequencing (NGS) and routine cultures in revision shoulder arthroplasty.

In 44 total revision arthroplasties tissue samples were transferred immediately into sterile specimen containers and transported for culture and NGS.

There were no cases of polymicrobial culture results; cutibacterium (formerly Propionibacterium) acnes was the most common bacterial species cultured (8 of 13 [61.5%]) and identified by NGS (12 of 17 [70.1%]) in cases of definite and probable infection. 

The concordance (κ) between the 2 diagnostic criteria for defining infection that included culture or NGS was 0.333 (fair). 

Culture data from revision shoulder arthroplasty cases commonly reveals the presence of a single organism; whereas, NGS results suggests the presence of multiple organisms (see below)

The authors conclude with the statement, "Finally, and perhaps most importantly, given our limited understanding of the normal shoulder joint microbiota, it is difficult to interpret both the NGS and culture data and to define PJI."

Comment: This paper opens an interesting discussion regarding NGS. For example, does a NGS finding of DNA similar to that from an organism, such as staph aureus, indicate that there were viable staph aureus bacteria in the sample? By contrast the growth of staph aureus in a culture would seem to provide strong evidence for the presence of viable bacteria. Secondly, would an NGS finding of K pneumonia, K oytoca, or K palustris in a sample indicate the need for anti-Klebsiella antibiotics? In other words, is there evidence suggesting that NGS finds might help guide treatment?

A related article is discussed below:
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 DNA resembling that from additional organisms.

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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Thoughts about "two positive cultures"

Many surgeons diagnose a periprosthetic infection when two specimens from a revision arthroplasty grow out the same organism. 

In considering the application of this criterion, four factors should be kept in mind. 

(1) the importance of the denominator: the chances of obtaining two positive cultures rises with the number of specimens sent for culture. If three specimens are sent and one is culture positive, the joint does not meet the criterion. However, the odds of each subsequent culture being positive in this example is one out of three. Thus if two more specimens are submitted from the same shoulder, it is very likely that one of the two would be positive, bringing the total of positive cultures to two. In that case the shoulder diagnosis would change from being uninfected to being infected just by changing the number of specimens submitted.

(2) the source of the specimen affects its likelihood of being culture positive: joint fluid specimens are less likely to be culture positive than tissue or explant cultures from the same shoulder (see this link).

(3) the media used in the culture of a specimen affects its likelihood of being culture positive: broth, aerobic and anaerobic cultures used together are most sensitive (see this link).

(4) cultures are not simply positive or negative: as shown in this article, "Characterizing the Propionibacterium Load in Revision Shoulder Arthroplasty: A Study of 137 Culture-Positive Cases" (see this link). While some positive cultures grow out only one colony or are only positive in the broth, others have 2+ growth on agar plates, indicating a much greater bacterial load.

So, while commonly used, the criterion of 'two or more positive cultures' needs to be applied being mindful of these four factors.

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