Post on 19-Oct-2021
1-Specificity
Se
ns
itiv
ity
Erythrocyte Sedimentation Rate But Not C-Reactive Protein
Independently Predicts Osteomyelitis Recurrence
Introduction Osteomyelitis (OM) is a “difficult to treat infection” which is often chronic and prone to
recurrences
C-Reactive Protein (CRP) levels and Erythrocyte Sedimentation Rate (ESR) are
commonly used to determine the duration of antibiotic therapy
However, there are scant data on the use of ESR and CRP in predicting recurrence
This study aims to investigate the association between ESR and CRP and OM recurrence
Se
ns
itiv
ity
1-Specificity
44 re-admitted with
recurrence of OM
by July 2012
68 with no
recurrence of OM
by July 2012
P=0.019
CRP≥5mg/L
CRP<5mg/L
Re
cu
rre
nc
e-f
ree
Su
rviv
al
Follow-up Time / Months
P<0.001
ESR≥20mm/h
ESR<20mm/h
Follow-up Time / Months
Rec
urr
en
ce
-fre
e S
urv
iva
l
Fig. 5: Survival curve for nadir ESR≥20mm/h against recurrence
Fig. 4: Survival curve for nadir CRP≥5mg/L against recurrence
Ziwei LIN1, Anupama VASUDEVAN2, Paul Ananth TAMBYAH1,2
1 Yong Loo Lin School of Medicine, National University of Singapore, 2 Division of Infectious Diseases, University Medicine Cluster, National University Hospital
Methodology This is a retrospective cohort study, where records of OM patients seen at National
University Hospital, a tertiary hospital in Singapore, from Jan 2005 to Jan 2012 were
reviewed
Primary outcome was recurrence: re-admission for bone infection or overlying soft tissue
infection at the same site as the index admission
Analysis with nadir values of ESR and CRP was done with Kaplan Meier estimate and
Cox-Regression model
Results
112 patients participating in study
25 excluded due to lack
of CRP/ESR readings,
discontinuity of follow-
up, and death during
admission.
Median follow-up
time: 21.4 months
(0.4 – 73.9 months)
Table 1: Patient Demographics
Factor Hazard Ratio (95% CI) P
ESR ≥ 20mm/h 4.19 (1.74 - 10.1) 0.001
MRSA 2.55 (1.29 - 5.03) 0.007
Use of oral antibiotics only 5.42 (1.84 – 16.0) 0.002
Non-healing wound 2.23 (1.06 - 4.72) 0.036
Table 6: Multivariate analysis with Cox-Regression
Conclusion ESR but not CRP independently predicts OM recurrence, and hence may be useful in
guiding antibiotic therapy
While clinical factors must be taken into consideration, ESR values provide an objective
means of indicating recurrence risk
ESR is more sensitive, specific and independently associated with OM recurrence.
However, clinical trials using ESR to guide therapy should be done to validate current
clinical practice.
Characteristic n HR (95% CI)
P
Recurrence No recurrence Total
Antibiotic therapy
Intravenous and oral
Intravenous only
Intravenous≥4 weeks
Per Oral only
44 (39.3%)
35 (38.9%)
5 (27.8%)
24 (54.5%)
4 (100.0%)
68 (60.7%)
55 (61.1%)
13 (72.2%)
20 (45.5%)
0 (0.0%)
112
90
18
44
4
NA
0.85 (0.41-1.77)
0.64 (0.25-1.61)
1.14 (0.63-2.07)
8.94 (3.13-25.6)
NA
0.664
0.339
0.658
<0.001
Surgical intervention
Debridement
Amputation
Removal of Implant
32 (39.0%)
22 (37.9%)
7 (41.2%)
3 (18.8%)
50 (61.0%)
36 (62.1%)
10 (58.8%)
13 (81.3%)
82
58
17
16
0.97 (0.49-1.88)
0.93 (0.51-1.69)
0.94 (0.42-2.09)
0.39 (0.12-1.29)
0.919
0.810
0.872
0.124
Table 3: Treatment Modalities
137 patients with OM from
Jan 2005 – Jan 2012
Table 5: Sensitivity, Specificity, Positive Predictive Value (PPV) & Negative Predictive
Value (NPV) of nadir CRP & ESR for predicting OM recurrence
Sensitivity Specificity PPV NPV P
CRP≥5mg/L 0.636 0.588 0.500 0.714 0.019
ESR≥20mm/h 0.864 0.529 0.543 0.857 <0.001
Cut-offs for nadir CRP and ESR
were determined by ROC (Fig. 2
and 3)
ESR≥20mm/h (P<0.001) and
CRP≥5mg/L (P=0.019) were
used as they had the highest
sensitivity (Fig. 4, 5 and Table 5)
Table 2: Patient and Infection Characteristics
References 1. Michail M, Jude E, Liaskos C, Karamagiolis S, Makrilakis K, Dimitroulis D, et al. The Performance of Serum Inflammatory
Markers for the Diagnosis and Follow-up of Patients With Osteomyelitis. The international journal of lower extremity wounds.
2013 May 9.
2. Rabjohn L, Roberts K, Troiano M, Schoenhaus H. Diagnostic and prognostic value of erythrocyte sedimentation rate in
contiguous osteomyelitis of the foot and ankle. The Journal of foot and ankle surgery : official publication of the American
College of Foot and Ankle Surgeons. 2007 Jul-Aug;46(4):230-7.
3. Unkila-Kallio L, Kallio MJ, Eskola J, Peltola H. Serum C-reactive protein, erythrocyte sedimentation rate, and white blood
cell count in acute hematogenous osteomyelitis of children.
Characteristic n HR (95% CI) P
Recurrence No Recurrence Total
Co-morbidities
Diabetes Mellitus
Hypertension
Peripheral Vascular Disease
Ischaemic Heart Disease
Previous Osteomyelitis
30 (50.0%)
23 (40.4%)
8 (53.3%)
12 (57.1%)
8 (57.1%)
30 (50.0%)
34 (59.6%)
7 (46.7%)
9 (42.9%)
6 (42.9%)
60
57
15
21
14
2.25 (1.19-4.25)
1.16 (0.64-2.09)
1.48 (0.69-3.19)
2.07 (1.07-4.03)
1.50 (0.69-3.23)
0.010
0.623
0.311
0.028
0.296
History of Trauma
Open Trauma
11 (26.2%)
5 (20.8%)
31 (73.8%)
19 (79.2%)
42
24
0.46 (0.24-0.93)
0.62 (0.18-2.13)
0.026
0.440
Prosthesis present 7 (29.2%) 17 (70.8%) 24 0.62 (0.28-1.39) 0.245
Presentation
Fever
Purulent discharge
Non-healing wound
19 (44.2%)
20 (48.8%)
35 (53.0%)
24 (55.8%)
21 (51.2%)
31 (47.0%)
43
41
66
1.43 (0.79-2.59)
1.55 (0.85-2.84)
3.26 (1.57-6.78)
0.244
0.157
0.002
Site of Infection
Upper Limb
Lower Limb
Spine
Others
1 (10.0%)
35 (48.6%)
3 (23.1%)
6 (33.3%)
9 (90.0%)
37 (51.4%)
10 (76.9%)
12 (66.7%)
10
72
13
18
0.19 (0.03-1.40)
2.76 (1.32-5.74)
0.47 (0.15-1.53)
0.74 (0.31-1.75)
0.104
0.007
0.213
0.496
0 5 10 15 20 25 30 35
Other Gram Negative bacteria
Pseudomonas Aeruginosa
Other Gram Positive bacteria
MRSA
MSSA
Recurrence No recurrence
Fig. 1: Microbiological data
HR 0.53, 95%CI 0.22-1.25, P=0.146
HR 2.37, 95%CI 1.22-4.61, P=0.009
HR 1.23, 95%CI 0.55-2.75, P=0.622
HR 0.47, 95%CI 0.18-1.19, P=0.112
HR 1.12, 95%CI 0.59-2.15, P=0.727
Characteristic n HR (95% CI) P
Recurrence No Recurrence Total
Gender
Male
Female
32 (37.6%)
12 (44.4%)
53 (62.4%)
15 (55.6%)
85
27
1.22 (0.63-2.36)
0.563
Median Age (Range):
54 (10-87)
Patients>54 years
6 (33.3%)
12 (66.7%)
18
1.17 (0.65-2.12)
0.605
Race
Chinese
Malay
Indian
Others
17 (30.4%)
12 (46.2%)
14 (51.9%)
1 (33.3%)
39 (69.6%)
14 (53.8%)
13 (48.1%)
2 (66.7%)
56
26
27
3
Reference
1.68 (0.80-3.53)
1.99 (0.98-4.03)
1.18 (0.16-8.89)
NA
0.170
0.060
0.870
Mailing address:
NUHS Tower Block, Level 11
1E Kent Ridge Road,
Singapore 119228
E-mail:
U0907274@nus.edu.sg
Telephone: +65 6772 3737
Fig. 3: ROC curve of lowest ESR value in predicting recurrence
Fig. 2: Receiver Operator Characteristic (ROC) Curve of lowest CRP in predicting recurrence