Prosthetic Joint Infection: Diagnosis Update


IDSA criteria

One or more of the following are present:

1. Indistinguishable microorganism isolated from two or more periprosthetic fluid or tissue samples

AND/OR

2. Sinus tract communicating with the affected joint

AND/OR

3. Intraoperative purulence

AND/OR

4. Acute inflammation on histologic examination

Original MSIS criteria

One or more of the following are present:

1. Indistinguishable microorganism isolated from two or more periprosthetic fluid or tissue samples

AND/OR

2. Sinus tract communicating with affected joint or

AND/OR

3. Four of the following are present:

(a) Elevated serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)

(b) Elevated synovial fluid leucocyte count

(c) Elevated synovial fluid polymorphonuclear leucocyte percentage

(d) Intraoperative purulence

(e) Greater than five neutrophils per high-power field in 5 high-power fields observed from histologic analysis of periprosthetic tissue at 400× magnification

(f) Isolation of a microorganism from a single periprosthetic fluid or tissue specimen

Revised MSIS criteria

One or more of the following are present:

1. Indistinguishable microorganism isolated on two or more periprosthetic fluid or tissue samples

AND/OR

2. Sinus tract communicating with affected joint

AND/OR

Three of the following are present:

1. Elevated serum CRP and ESR

2. Elevated synovial fluid leucocyte count or ++ change on leucocyte esterase test strip

3. Elevated synovial fluid polymorphonuclear leucocyte percentage

4. Greater than five neutrophils per high-power field in 5 high-power fields observed from histologic analysis of periprosthetic tissue at 400× magnification

5. Single positive culture



The revised MSIS criteria also attempted to provide clarity for the cut-offs for different biochemical markers, according to the acuity of the infection, as outlined in Table 3.2 [3]. The thresholds described in the revised MSIS criteria will be discussed in more detail in this chapter. Finally, authors of all three criteria clearly state that, in patients not meeting diagnostic criteria, PJI may still be present and therefore clinical judgement is advocated [14].


Table 3.2
Diagnostic thresholds for minor criteria according to the revised musculoskeletal infection society definition (Adapted from Parvizi and Gehrke [3])




























Criterion

Acute prosthetic joint infection (<90 days)

Chronic prosthetic joint infection (>90 days)

Erythrocyte sedimentation rate (ESR) (mm/h)

No threshold determined

30

C-reactive protein (CRP) (mg/L)

100

10

Synovial leucocyte count (cells/μL)

10,000

3000

Synovial polymorphonuclear leucocyte percent

90

80

Another challenge with diagnosis of PJI is the crossover between pathogen and contaminant. Coagulase-negative staphylococci , such as Staphylococcus epidermidis, are the most common causes of PJI. Conversely coagulase-negative staphylococci are the major cause of contamination of microbiological specimens. For example, in a large cohort study with 369 subjects undertaken at Mayo Clinic, Rochester, MN, USA, 25% of infections were due to coagulase-negative Staphylococcus species, isolated in 29 of the 117 subjects meeting the IDSA criteria for infection. However, coagulase-negative Staphylococcus species were the most common contaminants, isolated in 33 of the 252 subjects (13%) of patients not meeting the IDSA criteria for PJI [6]. Diagnostic tests that clearly differentiate whether an isolated microorganism is a true pathogen or a contaminant do not exist in clinical practice; therefore, it frequently falls to clinical judgement to assess the significance of isolated organisms.

Further compounding PJI diagnosis is the overlap in symptomatology between septic failure (i.e. PJI) and aseptic failure; in particular, pain is the most common symptom of PJI and, however, is also the predominant symptom of aseptic failure [7, 8]. The challenge in differentiating between aseptic and septic failure based on clinical history and examination alone results in a need for diagnostic testing [7].

Finally, the diagnosis of shoulder arthroplasty infections is particularly challenging. C. acnes is the predominant organism associated with shoulder PJI [9]. This organism behaves differently compared to other organisms, such as Staphylococcus aureus . It causes more indolent infections and does not incite the same inflammatory reaction as other organisms, and isolation of some strains may require extended incubation of microbiological cultures, a situation that is, in part, method dependent [1012].

In the last decade, there has been an upsurge of studies examining optimisation of PJI diagnosis, with significant advances having been made in PJI diagnosis and interpretation of results of diagnostic testing. This chapter will review the current state of PJI diagnosis.



3.2 Clinical Diagnosis



3.2.1 Diagnostic Criteria


As noted by the authors of the PJI diagnostic criteria , clinical assessment and judgement remain of critical importance for the diagnosis of these infections. Two main classifications systems have been developed to assist in the assessment of patients. Zimmerli et al. classified PJI as “early” developing in the first 3 months after surgery, “delayed” occurring 3 to 24 months after surgery and “late” occurring greater than 24 months after joint replacement surgery [7]. A similar classification system was developed by Tsukayama et al., with PJI classified as “early postoperative” developing within 4 weeks of the index procedure, “late chronic” developing after 4 weeks of the index procedure with an insidious clinical presentation and “acute haematogenous” developing after 4 weeks of the index procedure with an acute onset of symptoms [13]. These classification systems loosely relate to symptomatology and likely pathogens associated with PJI and inform management strategies, particularly with the classification system developed by Tsukayama and colleagues (Table 3.3) [3, 13].


Table 3.3
Typical clinical features, biomarker profile and microorganisms according to prosthetic joint infection classification proposed by Tsukayama et al. [13] and the revised MSIS criteria (Parvizi and Gehrke [3])




































































Classification

Days from surgery (days)

Clinical features

Serum CRP (mg/L)

Serum ESR

Synovial leukocyte count

Synovial PMN%

Typical pathogens

Early postoperative

≤30

• Purulent discharge/ooze

>100

Nil threshold determined

>10,000 cells/μL

>90

Staphylococcus aureus

• Erythema

• Swelling of index joint

• Dehiscence

Gram-negative bacilli

• Pain

• ±Fever

Late chronic

≥30

• Insidious onset of pain (“grumblers”)

>10

>30 mm/h

>3000 cells/μL

>80

Coagulase-negative staphylococci

• ±Sinus tract

Cutibacterium acnes

Acute haematogenous

≥30

• Sudden onset of pain

>100

Nil threshold determined

>10,000 cells/μL

>90

Staphylococcus aureus

• Swelling of index joint

Streptococcus species

• ±Fever


CRP C-reactive protein, ESR erythrocyte sedimentation rate, PMN polymorphonuclear leukocytes


3.2.2 Clinical Presentation


In early infections , patients typically present with surgical wound complications, such as purulent discharge, erythema and swelling of the affected joint [7, 1416]. Early infections are typically associated with organisms such as S. aureus [7, 1416]. In acute haematogenous infections, patients often report sudden onset of pain at the site of a prosthetic joint that has been previously asymptomatic, with or without swelling or fever [7, 1416]. Organisms such as Streptococcus species and S. aureus are classic organisms associated with acute haematogenous PJIs [7, 1416]. In late chronic infections, many of the typical symptoms of infection are absent. Pain is the predominant feature, with patients reporting a history of slowly increasing pain involving the prosthetic joint [7, 1416]. A discharging sinus, when present, is typically associated with chronic, indolent presentations [2, 7, 13, 15]. These infections are classically associated with coagulase-negative staphylococci [16]. As previously discussed, C. acnes has a predilection for infecting shoulder joints and tends to cause indolent infections [1720]. Classic features of infection are frequently absent, with pain and stiffness of the shoulder joint being the predominant symptoms. Bruising along the surgical wound has been described as a pathognomonic sign of C. acnes shoulder arthroplasty infection [1720].

Regardless of which classification system is applied, classification of PJI influences management decisions; debridement and retention of the prosthesis is a potential treatment option for early and acute haematogenous infections but not for delayed or late chronic infections [1, 4, 7].

The timing of prosthesis failure also aids clinical acumen. In a prospective cohort study by Portillo and colleagues, the underlying indication for prosthesis revision was examined, comparing the median time for revision due to PJI, mechanical failure (such as dislocation) and aseptic failure. Overall, the need for revision within 2 years of the index procedure was highly predictive of PJI with a calculated risk ratio of 2.9 (95% confidence interval 1.8–4.8). The authors also noted that infections occurring after 2 years were more likely to be acute haematogenous infections and were easily clinically distinguishable from aseptic failure [21].


3.3 Blood Inflammatory Markers



3.3.1 Blood White Cell Count


A number of studies have assessed the utility of blood markers in the diagnosis of PJI. Elevated blood white cell count is a poor predictor of infection; in most series, fewer than 10% of patients with PJI have an elevated peripheral blood white cell count [7, 8, 22]. In a systematic review and meta-analysis performed by Berbari and colleagues, the pooled sensitivity of an elevated peripheral blood white cell count was 45% (95% confidence interval 41–49%) [22]. Two studies published subsequent to the meta-analysis by Berbari et al. have demonstrated diverse results (Table 3.4) [1, 2, 12, 2230]. Glehr and colleagues examined blood markers in patients undergoing hip or knee revision surgery [23]. The study included 124 revision arthroplasties, of which 78 met the original MSIS diagnostic criteria for PJI. Applying a cut-off of 7355 white cells/μL, the sensitivity was 73%, higher than the sensitivity reported in the meta-analysis. In contrast, in a second study by Randau and colleagues, applying a threshold of 10,300 cell/μL, the sensitivity of peripheral blood white cell count was only 21.3% (95% confidence interval 10.7–35.7%) [24]. Despite the low sensitivity, measurement of blood white cell count is commonly performed as part of standard preoperative workup.


Table 3.4
Selected literature review of test performance for serum white cell count, C-reactive protein and erythrocyte sedimentation rate






















































































































































































































































































































































Biomarker

Reference

Joint(s)

Chronicitya

Numberb

Thresholdc

Prosthetic joint infection criteria

Sensitivity (%)

Specificity (%)

White cell count (WCC)
 
Berbari et al. [22]d

Knee and hip

Not specified

3909

Not specified

Not specified

45

87
 
Glehr et al. [23]

Knee and hip

Not specified

124

WCC > 7355cells/μL

Original MSIS criteria [2]

73

72
 
Randau et al. [24]

Knee and hip

Not specified

120

WCC > 10,300cells/μL

IDSA criteria [1]

21

94

C-reactive protein (CRP)
 
Berbari et al. [22]d

Knee and hip

Not specified

3909

Not specified

Not specified

88

74
 
Glehr et al. [23]

Knee and hip

Not specified

124

Not specified

Original MSIS criteria [2]

84

79
 
Randau et al. [24]

Knee and hip

Not specified

120

CRP >9.1 mg/L

Osmon et al. [1] IDSA criteria

62

83
 
Ettinger et al. [25]

Knee, hip and shoulder

Chronic (>4 weeks)

98

CRP >0.3 mg/dL

Original MSIS criteria [2]

80

64
 
Alijanipour et al. [26]

Knee and hip

Acute (<4 weeks)

1773

CRP >23.5 mg/L

Original MSIS criteria [2]

87

94
 
Bedair et al. [27]

Knee

Acute (<6 weeks)

146

CRP ≥166 mg/dL

One or more of the following:

1. Intraoperative purulence

2. Positive culture on solid media

53

86
 
Alijanipour et al. [26]

Knee

Chronic (>4 weeks)

759

CRP >23.5 mg/L

Original MSIS criteria [2]

92

94
 
Piper et al. [12]

Knee

Not specified

297

CRP >14.5 mg/L

One or more of the following:

1. Intraoperative purulence

2. Histology consistent with infection

3. Sinus tract

4. Positive tissue and sonicate culture

79

88
 
Yi et al. [28]

Hip

Acute (<6 weeks)

73

CRP > 93 mg/L

One or more of the following:

1. Organism isolated from ≥2 cultures

2. Sinus tract

3. Two of the following:

(a) Intraoperative purulence

(b) Histology consistent with infection

(c) Single culture positive

88

100
 
Alijanipour et al. [26]

Hip

Chronic (>4 weeks)

1203

CRP >13.5 mg/L

Original MSIS criteria [2]

90

88
 
Piper et al. [12]

Hip

Not specified

221

CRP >10.3 mg/L

One or more of the following:

1. Intraoperative purulence

2. Histology consistent with infection

3. Sinus tract

4. Positive tissue and sonicate culture

74

79
 
Piper et al. [12]

Shoulder

Not specified

64

CRP >7 mg/L

One or more of the following:

1. Intraoperative purulence

2. Histology consistent with infection

3. Sinus tract

4. Positive tissue and sonicate culture

63

73

Erythrocyte sedimentation rate (ESR)
 
Berbari et al. [22]d

Knee and hip

Not specified

3909

Not specified

Not specified

75

70
 
Alijanipour et al. [26]

Knee and hip

Acute (<4 weeks)

1773

ESR >54.5 mm/h

Original MSIS criteria [2]

80

93
 
Bedair et al. [27]

Knee

Acute (<6 weeks)

146

ESR ≥120 mm/h

One or more of the following:

1. Intraoperative purulence

2. Positive culture on solid media

16

94
 
Alijanipour et al. [26]

Knee

Chronic (>4 weeks)

759

ESR >46.5 mm/h

Original MSIS criteria [2]

87

87
 
Piper et al. [12]

Knee

Not specified

297

ESR >19 mm/h

One or more of the following:

1. Intraoperative purulence

2. Histology consistent with infection

3. Sinus tract

4. Positive tissue and sonicate culture

89

74
 
Yi et al. [28]

Hip

Acute (< 6 weeks)

73

ESR > 44 mm/h

One or more of the following:

1. Organism isolated from ≥2 cultures

2. Sinus tract

3. Two of the following:

(a) Intraoperative purulence

(b) Histology consistent with infection

(c) Single culture positive

92

53
 
Alijanipour et al. [26]

Hip

Chronic (>4 weeks)

1203

ESR >48.5 mm/h

Original MSIS criteria [2]

78

90
 
Piper et al. [12]

Hip

Not specified

221

ESR >13 mm/h

One or more of the following:

1. Intraoperative purulence

2. Histology consistent with infection

3. Sinus tract

4. Positive tissue and sonicate culture

82

60
 
Piper et al. [12]

Shoulder

Not specified

64

ESR >26 mm/h

One or more of the following:

1. Intraoperative purulence

2. Histology consistent with infection

3. Sinus tract

4. Positive tissue and sonicate culture

32

93

Combined CRP and ESR
 
Austin et al. [29]

Knee

Not specified

296

CRP >10 mg/L and ESR >30 mm/h

One or more of the following:

1. Positive intraoperative cultures

2. Synovial white cell count >1760 cells/μL and PMN% >73%

3. Sinus tract

96

56
 
Piper et al. [12]

Knee

Not specified

297

CRP >14.5 mg/L or ESR > 19 mm/h

One or more of the following:

1. Intraoperative purulence

2. Histology consistent with infection

3. Sinus tract

4. Positive tissue and sonicate culture

94

69
 
Alijanipour et al. [26]

Knee

Acute and chronic

759

CRP >23.5 mg/L and ESR >46.5 mm/h

Original MSIS criteria [2]

89

85
 
Alijanipour et al. [26]

Hip

Acute and chronic

1203

CRP >13.5 mg/L and ESR >48.5 mm/h

Original MSIS criteria [2]

75

84
 
Schinsky et al. [30]

Hip

Acute and chronic

235

ESR >30 mm/h and CRP >10 mg/dL

Two of the following three:

1. Positive intraoperative culture

2. Gross purulence

3. Histology consistent with infection

90

91
 
Piper et al. [12]

Hip

Not specified

221

CRP > 10.3 mg/L or ESR > 13 mm/h

One or more of the following:

1. Intraoperative purulence

2. Histology consistent with infection

3. Sinus tract

4. Positive tissue and sonicate culture

88

55
 
Piper et al. [12]

Shoulder

Not specified

64

CRP > 7 mg/L or ESR > 26 mm/h

One or more of the following:

1. Intraoperative purulence

2. Histology consistent with infection

3. Sinus tract

4. Positive tissue and sonicate culture

63

73


aUnless otherwise specified, chronicity refers to the time from index prosthetic joint surgery until prosthetic joint revision surgery

bNumber of revision arthroplasties

cThreshold based on ROC analysis when provided

dMeta-analysis

MSIS Musculoskeletal Infection Society, IDSA Infectious Diseases Society of America


3.3.2 C-Reactive Protein and Erythrocyte Sedimentation Rate


Other biochemical tests, such as erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) , are more useful diagnostic investigations for PJI [14, 22]. These tests are inexpensive, widely available and commonly performed in this clinical setting; furthermore, clinicians are familiar with their interpretation [31]. In the study by Berbari et al., the pooled sensitivity of ESR was 75% (95% confidence interval 72–77%), and serum CRP was 88% (95% confidence interval 86–90%) for the detection of lower limb PJI [22]. In addition, studies have examined the sensitivity of combining ESR and serum CRP. In a study by Schinsky et al. examining 235 revision total hip arthroplasties, the combination of elevated ESR and serum CRP had a sensitivity of 90% and specificity of 91% [30]. Similarly, Austin et al. examined blood markers in 296 patients undergoing revision total knee arthroplasty; combining ESR and serum CRP had a sensitivity of 96%; however, the specificity was much lower at 56% [29]. As noted by Berbari et al., the cut-off values for these inflammatory markers differed in studies [22]. In addition, the thresholds for these markers differ between early and late chronic infections and by prosthesis location [26].

In attempt to provide clarity, the recent International Consensus Meeting specified cut-offs, distinguishing between acute PJI (defined as less than 90 days) and chronic PJI (defined as greater than 90 days). For CRP, the threshold for acute infections was 100 mg/L and 10 mg/L for chronic infections. For ESR, the threshold for chronic infections was 30 mm/h: no threshold was stipulated for acute infections, due to poor specificity of ESR in the early postoperative period [3, 4]. There is a paucity of data to support the thresholds suggested, and the data that does exist is conflicting. In the study by Alijanipour et al. examining 1962 patients undergoing total hip or knee revision arthroplasties, 273 of whom underwent revision for PJI, the inflammatory markers differed between early and late chronic infections with higher values noted in early infections [26]. In addition, the median CRP was higher in knee PJI (133, interquartile range [IQR] 40–207) compared to hip PJI (84, IQR 55–101; P < 0.0001). For late chronic knee infections, the optimal cut-off values based on receiver operating characteristic (ROC) analysis for CRP was 23.5 mg/L with a sensitivity of 92% and specificity of 94% and for ESR 46.5 mm/h (sensitivity 87% and specificity 87%) [26]. In late chronic hip infections, Alijanipour and colleagues suggested a cut-off of 13.5 mg/L for CRP (sensitivity 90% and specificity 88%); however, the threshold suggested for ESR (48.5 mm/h) was associated with reduced sensitivity—78% [26]. For early infections, Alijanipour et al. suggested a threshold of 54.5 mm/h for ESR (sensitivity 80% and specificity of 93%) and 23.5 mg/L for CRP (sensitivity 87% and specificity 94%) for both hips and knee joints [26].

In contrast, studies by Bedair et al. suggested an optimal CRP threshold of 166 mg/L for early postoperative knee infections (sensitivity of 53%, 95% confidence interval 43–62%, and specificity 86%, 95% confidence interval 79–92%). The ESR threshold of 120 mm/h was associated with a sensitivity of 16% (95% confidence interval 9–23%) and specificity of 94%, (95% confidence interval 90–99%) [27].

In patients undergoing hip revision surgery for early postoperative infections, Yi et al. suggested optimal cut-offs for CRP of 93 mg/L for hips (sensitivity 88%, 95% confidence interval 77–98%) [28]. Similar to the observations of Bedair et al., the optimal cut-off for ESR was 44 mm/h with excellent sensitivity (92%, 95% confidence interval 83–100%) but low specificity (53%, 95% confidence interval 38–69%) [28]. The observed poor specificity with ESR in acute infections may relate to the fact that ESR is elevated in the postoperative period in uncomplicated joint surgery. Indeed, in an early study by Shih et al., ESR remained elevated out to a year in a small subset of patients [32]. In contrast, CRP peaks on day 2 and returns to normal within 3 weeks [3134]. In addition, there may be potential overlap with other conditions that elevate inflammatory markers, such as rheumatoid arthritis [22]. Yi and colleagues also observed that combining ESR and CRP did not improve test performance in the acute setting [28]. Of further interest, in a study by Bracken et al., which compared CRP and ESR in 44 patients with fungal PJI compared to 59 patients with bacterial PJI, it was noted that these inflammatory markers did not differ between fungal and bacterial PJI [35].

These measures are of limited clinical benefit in predicting shoulder arthroplasty infections ; in a study by Piper et al., applying a cut-off of 26 mm/h for ESR and 7 mg/L for CRP, these markers had a sensitivity of 32% for ESR and 63% for CRP and a specificity of 93% for ESR and 73% for CRP [12]. In 23% of shoulder infections, the ESR and CRP were not elevated [12]. Similarly, in a study by Topolski et al., ESR (applying a cut-off of 22 mm/h) and CRP (applying a cut-off of 1 dL/L) were only elevated in 14% and 25% of patients, respectively [36].

The spectrum of reported test performance of these serum biomarkers is outlined in Table 3.4. In addition, Table 3.4 also highlights the range of definitions applied for PJI, thereby hampering the direct comparison of results between studies. Notwithstanding, ESR and CRP are relatively useful tests, given their broad availability and reasonable sensitivity; however, the optimal cut-offs according to chronicity of infection and location of the index prosthetic joint still require further study. In addition, the specificity of ESR is poor, particularly in early postoperative infections. As previously discussed, elevated ESR and CRP are minor criteria for the MSIS and revised MSIS diagnostic criteria [2, 3]. Of interest, in the diagnostic algorithm proposed by the American Academy of Orthopaedic Surgeons (Fig. 3.1), CRP and ESR are suggested as initial tests to exclude the diagnosis of PJI; however, given the variation in reported sensitivity, specificity and predictive value of these tests, the validity of this is unclear [37].

A420073_1_En_3_Fig1_HTML.gif


Figure 3.1
American Academy of Orthopaedic Surgeons algorithm for patients with higher probability of hip or knee periprosthetic joint infection (From AAOS [37], with permission)


3.3.3 Interleukin-6, Procalcitonin C and Tumour Necrosis Factor-α


Other studied serum biochemical markers of infection include interleukin-6 , tumour necrosis factor-α (TNF-α) and procalcitonin C (Table 3.5) [1, 2, 2225, 38, 39]. Interleukin-6 and TNF-α are cytokines released by monocytes and macrophages in the setting of infection [38]. Procalcitonin C is a precursor of calcitonin that has been shown to be a specific marker for a number of bacterial infections, including pneumonia and sepsis [40]. Bottner et al. compared the diagnostic utility of interleukin-6, TNF-α and procalcitonin C in 78 patients undergoing revision arthroplasties [38]. According to this study, patients were diagnosed with infection based on their having positive cultures or histological evidence of infection; however, details as to the exact aspects of these criteria were not further specified [38]. The authors noted that these serum biomarkers were all significantly elevated in patients meeting the above definition of infection, compared to patients with “aseptic loosening”. The observed sensitivity and specificity of interleukin-6 were 95% and 87%, respectively [38]. Bottner et al. also noted that in six of the seven patients with false-positive interleukin-6 results, there was associated polyethylene wear and osteolysis, which may limit its utility [38].


Table 3.5
Selected literature review of test performance for serum interleukin-6, procalcitonin and tumour necrosis factor-α












































































































































Biomarker

Reference

Joint(s)

Chronicitya

Numberb

Thresholdc

Prosthetic joint infection criteria

Sensitivity (%)

Specificity (%)

Interleukin-6 (IL-6)
 
Berbari et al. [22]d

Knee and hip

Not specified

3909

Not specified

Not specified

97

91
 
Glehr et al. [23]

Knee and hip

Not specified

124

IL-6 > 4.7 pg/mL

Original MSIS criteria [2]

81

68
 
Ettinger et al. [25]

Knee, hip and shoulder

Chronic (>4 weeks)

98

IL-6 > 5.12 pg/mL

Original MSIS criteria [2]

80

88
 
Randau et al. [24]

Knee and hip

Not specified

120

IL-6 > 2.6 pg/mL

Osmon et al. [1] IDSA criteria

79

58

Procalcitonin C (PCT)
 
Glehr et al. [23]

Knee and hip

Not specified

124

PCT >0.75 ng/mL

Original MSIS criteria [2]

48

100
 
Bottner et al. [38]

Knee and hip

Acute and chronic

78

PCT >0.3 ng/mL

1. Positive intraoperative culture

2. Histology consistent with infection

33

98
 
Yuan et al. [39]

Hip

Not specified

74

PCT >0.5 ng/mL

Two of the following three:

1. Positive intraoperative culture

2. Intraoperative purulence

3. Histology consistent with infection

80

74
 
Ettinger et al. [25]

Knee, hip and shoulder

Chronic (>4 weeks)

98

PCT >0.025 ng/mL

Original MSIS criteria [2]

90

28
 
Randau et al. [24]

Knee and hip

Not specified

120

PCT > 46 ng/mL

Osmon et al. [1] IDSA criteria

13

100

Tumour necrosis factor-alpha (TNF-α)
 
Bottner et al. [38]

Knee and hip

Acute and chronic

78

TNF-α >40.0 ng/mL

1. Positive intraoperative culture and

2. Histology consistent with infection

43

94
 
Ettinger et al. [25]

Knee, hip, and shoulder

Chronic (>4 weeks)

98

TNF-α >11.9 pg/mL

Original MSIS criteria [2]

35

86


aUnless otherwise specified, chronicity refers to the time from index prosthetic joint surgery until prosthetic joint revision surgery

bNumber of revision arthroplasties

cThreshold based on ROC analysis when provided

dMeta-analysis

MSIS Musculoskeletal Infection Society

Interleukin-6 is elevated in the postoperative period for primary arthroplasty ; however, it returns to normal levels within 2 days of the operation [38]. Therefore, there is potential diagnostic utility of interleukin-6 over CRP and ESR in the early postoperative period if infection is suspected [41, 42]. In the meta-analysis by Berbari and colleagues, the pooled sensitivity and specificity for interleukin-6 was 97% (95% confidence interval 93–99%) with a pooled specificity of 91% (95% confidence interval 87–94%) [22]. In addition to the study by Bottner et al., the meta-analysis included two other small studies [22]. In a more recent study by Glehr et al. which was not included in the meta-analysis, preoperative performance of interleukin-6 did not predict infection [23]. Applying an optimal cut-off of 4.7 pg/mL, interleukin-6 had a sensitivity of 81% and specificity of 68%. Similar sensitivities have been reported in other studies [24, 25]. Interleukin-6 is not routinely available in most commercial laboratories, and the applicability and value of this marker remain unclear [31].

Five conflicting studies have examined procalcitonin in the setting of PJI; in the aforementioned study by Bottner et al., the sensitivity was 33% and specificity was 98% [38]. In contrast, in a study by Yuan et al. recruiting 71 patients undergoing revision hip arthroplasty, applying a cut-off of 0.5 ng/mL, the sensitivity of procalcitonin C was 80.0% and specificity was 73.9% [39]. As in the study by Bottner et al., the study by Glehr et al. demonstrated poor sensitivity of procalcitonin (48%); however, the specificity was 100% when a cut-off of 0.75 ng/mL was applied [23]. In the study by Randau and colleagues, procalcitonin performance was very poor (12.9%; 95% confidence interval 3.6–29.8%) when a higher threshold of 46 ng/mL was applied [40]. All studies noted no superiority of procalcitonin over CRP: Bottner et al. also noted that the cost of procalcitonin was 24 times higher than CRP [23, 38, 39]. Therefore, the value of procalcitonin in this clinical setting has not been established [24]. Finally Bottner et al. also examined the test characteristics of tumour necrosis factor-α, reporting a sensitivity of 43% and specificity of 94% applying a cut-off of 40.0 ng/mL [38]. These markers, interleukin-6, tumour necrosis factor-α and procalcitonin C, have not been incorporated into any diagnostic algorithm.


3.4 Synovial Fluid Characteristics


Synovial fluid characteristics can be used to assist in diagnosis of PJI (Table 3.6) [27, 28, 30, 43, 44]. The leucocyte composition in synovial fluid differs in patients with PJI compared to inflammatory conditions such as rheumatoid arthritis. In patients with PJI, there is a predominance of CD15-positive monocytes [45]. In comparison, T lymphocytes are the predominant cell type in inflammatory conditions [45].


Table 3.6
Selected literature review of test performance for synovial leukocyte count and polymorphonuclear leucocyte percentage




















































































































Biomarker

Reference

Joint(s)

Chronicitya

Numberb

Thresholdc

Prosthetic joint infection criteria

Sensitivity (%)

Specificity (%)

Synovial leucocyte count
 
Cipriano et al. [43]

Knee and hip

Chronic

871

>3450 cells/μL

Organism isolated from ≥2 cultures or two of the following:

1. Sinus tract

2. Intraoperative purulence

3. Histology consistent with infection

91

93
 
Bedair et al. [27]

Knee

Acute (<6 weeks)

146

≥10,700 cells/μL

One or more of the following:

1. Intraoperative purulence

2. Positive culture on solid media

95

91
 
Trampuz et al. [44]

Knee

Chronic

133

>1700 cells/μL

One or more of the following:

1. Organism isolated from ≥2 cultures

2. Sinus tract

3. Purulence

4. Histology consistent with infection

94

88
 
Yi et al. [28]

Hip

Acute (<6 weeks)

73

>12,800 cells/μL

One or more of the following:

1. Organism isolated from ≥2 cultures

2. Sinus tract

3. Two of the following:

(a) Intraoperative purulence

(b) Histology consistent with infection

(c) Single culture positive

89

100
 
Schinsky et al. [30]

Hip

Acute and chronic

235

> 4200 cells/mL

Two of the following three:

1. Positive intraoperative culture

2. Gross purulence

3. Histology consistent with infection

84

93

Polymorphonuclear leucocyte percentage
 
Cipriano et al. [43]

Knee & hip

Chronic

871

>78%

1. Organism isolated from ≥2 cultures or

2. Two of the following:

(a) Sinus tract

(b) Intraoperative purulence

(c) Histology consistent with infection

95.5

87
 
Bedair et al. [27]

Knee

Acute (<6 weeks)

146

>89%

One or more of the following:

1. Intraoperative purulence

2. Positive culture on solid media

84

69
 
Trampuz et al. [44]

Knee

Chronic

133

>65%

One or more of the following:

1. Organism isolated from ≥2 cultures

2. Sinus tract

3. Purulence

4. Histology

5. Consistent with infection

97

98
 
Yi et al. [28]

Hip

Acute (<6 weeks)

73

>89%

One or more of the following:

1. Organism isolated from ≥2 cultures

2. Sinus tract

3. Two of the following:

(a) Intraoperative purulence

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Feb 8, 2018 | Posted by in ORTHOPEDIC | Comments Off on Prosthetic Joint Infection: Diagnosis Update
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