Sunday, October 1, 2017

Periprosthetic hip and knee joint infections-the role of serum D-dimer

Serum D-Dimer Test Is Promising for the Diagnosis of Periprosthetic Joint Infection and Timing of Reimplantation

These authors hypothesized that patients with PJI may have a high level of circulating serum D-dimer (a widely available test that detects fibrinolytic activities that occur during infection) and that the presence of a high level of serum D-dimer may be a sign of persistent infection in patients awaiting reimplantation.

Their cohort consisted of 245 patients: 23 undergoing primary arthroplasty, 86 having revision for aseptic failure, 57 having revision for PJI, 29 having reimplantation, and 50 withinfection in a site other than a joint. PJI was defined using the Musculoskeletal Infection Society criteria:



In all patients, serum D-dimer level, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level were measured preoperatively. In this study at least 3 intraoperative tissue culture specimens were obtained.

The culture results for patients undergoing revision for PJI are shown below
Methicillin-sensitive Staphylococcus aureus 12
Staphylococcus epidermidis 9
Methicillin-resistant Staphylococcus aureus 4
Propionibacterium acnes 3
Streptococcus agalactiae group B 2
Polymicrobial 2
Anaerobic gram-positive cocci 1
Klebsiella pneumoniae 1
Streptococcus sanguinis 1
Enterobacter cloacae 1
Streptococcus mutans 1
Serratia marcescens 1
Negative cultures 19

The median D-dimer level was significantly higher (p < 0.0001) for the patients with PJI (1,110 ng/mL [range, 243 to 8,487 ng/mL]) than for the patients with aseptic failure (299 ng/mL [range, 106 to 2,571 ng/mL). 850 ng/mL was determined as the optimal threshold value for serum D-dimer for the diagnosis of PJI.

Serum D-dimer outperformed both ESR and serum CRP, with a sensitivity of 89% and a specificity of 93%. ESR and CRP had a sensitivity of 73% and 79% and a specificity of 78% and 80%, respectively. The sensitivity and specificity of ESR and CRP combined was 84% (95% confidence interval [CI], 76% to 90%) and 47% (95% CI, 36% to 58%), respectively.

Comment: This study demonstrates that, in patients meeting the Musculoskeletal Infection Society criteria for infection, serum D-dimer has superior sensitivity to ESR, CRP or a combination of ESR and CRP.

It is of interest that in two patients with positive cultures for Propionibacterium, the ESR and CRP were in the normal range, but serum D-dimer levels were substantially above the 850 ng/mL threshold (6,381 and 1,110). It will be of great interest to investigate D-dimer in the evaluation of patients with suspected shoulder PJI with Propionibacterium.  The authors point out that ESR and CRP level may be normal in patients with PJI caused by slow-growing organisms such as Propionibacterium and that the document introducing the MSIS criteria for PJI explicitly states that the levels of some of these markers may be normal in the presence of PJI caused by slow-growing organisms that do not elicit physiological inflammation so that all minor criteria may be negative.

Another interesting finding was that D-dimer levels were not elevated in patients with infections at sites other than the hip or knee. The reason for this specificity remains to be determined.

A few comments about the application of the MSIS criteria might be made here:
(1) while one of the minor criteria relates to the number of white cells per high power field, the authors state that they do not routinely perform frozen section or histological analysis for their patients undergoing revision surgery or reimplantation because they believe such tests have serious limitations.
(2) While one of the major and one of the minor criteria relate to the number of positive cultures, it is recognized that the chances of a culture result being positive is in large part related to the number of specimens submitted, the source of these specimens (tissue, fluid, explant), the media on which these specimens are cultured and the duration of observation of the cultures. These factors are particularly important for Propionibacterium.
(3) While 38 of these patients had at least one positive culture, it is of note that 19 had negative cultures. This points to the need for a standardized approach to culturing - some of these patients may have had Propionibacterium infections that were overlooked because too few specimens were submitted, because the specimens were not cultured on triple media or because the specimens were not observed for at least 17 days. 

In considering the role of Propionibacterium in failed shoulder arthroplasty, we have found it useful to consider the load of bacteria identified when a standardized culturing protocol is followed.

Characterizing the Propionibacterium Load in Revision Shoulder Arthroplasty
A Study of 137 Culture-Positive Cases

There has been a tendency in the recent literature to report cultures obtained at revision shoulder arthroplasty as being 'positive' or 'negative' or to assign revised shoulders to arbitrarily defined categories, in some cases distinguished by a single culture result (see below).



These authors took a different approach, one that considered the semi-quantitative results of all the cultures obtained from a revised shoulder - the 'load' of bacteria recovered from the shoulder using a defined culturing protocol.

They studied 137 revision shoulder arthroplasties from which a minimum of 4 specimens had been submitted for culture and that had at least 1 was positive for Propionibacterium. Standard microbiology procedures were used to assign a semiquantitative value (0.1, 1, 2, 3, or 4), called the Specimen Propi Value, to the amount of growth in each specimen. The sum of the Specimen Propi Values for each shoulder was defined as the Shoulder Propi Score, which was then divided by the total number of specimens to calculate the Average Shoulder Propi Score.

They found that the number and percentage of positive specimen-specific cultures (of material obtained from the stem explant, head explant, glenoid explant, humeral membrane, collar membrane, other soft tissue, fluid, or other) per shoulder ranged from 1 to 6 and 14% to 100%. A high percentage of specimens (mean, 43%; median, 50%) from the culture-positive shoulders showed no growth. These observations indicate that Propionibacterium are not evenly distributed through the tissues and implants of a failed shoulder arthroplasty so that more than a few samples are necessary to detect the presence of bacteria.

Another interesting finding was that the type of specimen submitted for culture affected the likelihood of culture positivity. Only 32.6% of the fluid cultures were positive in comparison with 66.5% of the soft-tissue cultures and 55.6% of the cultures of explant specimens. The average Specimen Propi Value (and standard deviation) for fluid specimens (0.35 ± 0.89) was significantly lower than those for the soft-tissue (0.92 ± 1.50) and explant (0.66 ± 0.90) specimens (p < 0.001). This finding provides a possible explanation for the limited utility of a culture-negative joint fluid aspiration in ruling out an infection.

A third intestine finding was the inter-sex difference in Propionibacterium load recovered from revised shoulders. The Shoulder Propi Score was significantly higher in men (3.56 ± 3.74) than in women (1.22 ± 3.11) (p < 0.001). Similarly, men had a significantly higher Average Shoulder Propi Score (0.53 ± 0.51) than women (0.19 ± 0.43) (p < 0.001).

Finally. the authors found that the percent of cultures positive for Propionibacterium varied widely among the cases with no apparent 'threshold' that could be used to distinguish 'definite infection' from 'probable infection' or 'probable contaminant' (see below).





Comment: This study provides an approach for standardizing:
(1) the harvesting of specimens = five samples of explants or tissue
(2) the culturing of specimens = aerobic and anaerobic media
(3) the period of observation = at least 17 days
(4) the reporting of culture results = Specimen Propi Value, Shoulder Propi Score and Average Shoulder Propi Score.

Such standardization and objective presentation of the results may facilitate comparison among investigators with respect to the characteristics of revised shoulder arthroplasties and the effectiveness of different surgical and medical approaches to their management.

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