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