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patients who experienced treatment failure (ratio¼1.02/month,95% CI 0.97–1.07, P ¼0.038 for the interaction between timeand treatment failure) (Figure 1d). However, CRP was not auseful test to predict failure within 1 year (AUROC¼0.55).

We also examined the absolute neutrophil counts. The neutro-phil count fell over time after DAIR (22.6×109 cells/L/week,P ,0.0005) and after two-stage revision (21.2×109 cells/L/week,P ,0.0005), but was not associated with treatment failure afterDAIR (0.23×109 cells/L higher, 95% CI 21.3 to 1.8, P ¼0.8) orafter two-stage revision (0.38×109 cells/L higher, 95% CI 20.4 to

0.8, P ¼

0.6), and so was not analysed further.

Discussion

Treatment failure after DAIR was associated with a CRP that wasslow to normalize post-operatively, or a high CRPduring long-termfollow-up. Treatment failure after two-stage revision was associ-ated with a high CRP during long-term follow-up, but not withthe rate of post-operative normalization. However, CRP could notbe recommended as a diagnostic test based on the sensitivityand specificity values indicated by ROCs. This does not reflectlimited power of the study, but the wide scatter of individual

readings in both outcome groups, as found in previousstudies.5–7 We did not detect statistically significant trends overtime in the white cell count, neutrophil count or platelet count(data not shown), and did not measure procalcitonin orinterleukin-6.

Measuring a single CRP may cost 15 US dollars (i.e. $56000 forthe 3732 tests analysed here or $215/patient), but inappropriatemanagement decisions (for instance, invasive sampling ordelayed re-implantation) may be much more costly.

Observational data are prone to bias. For instance, high CRP

during two-stage revision was associated with delayedre-implantation. Since CRP was not, in fact, associated with treat-ment failure or additional surgical debridement, this indicatesthat implantation was delayed simply by the clinician’s responseto the high CRP. However, irrespective of potential biases, thevery wide scatter of CRP readings irrespective of outcome indi-cates the limitation of the test.

Serial CRP measurements are cheap, biologicall y plausible,predict the response to treatment for endocarditis10 and so arereadily included in the care bundles for infectious diseases.During treatment for PJI, we found that CRP monitoring was apoor test of cure. In order to avoid triggering needless

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Figure 1. Profile of plasma CRP concentrations over time in patients treated with DAIR according to eventual success or failure of treatment. Best-fitlines are fit by fractional polynomials with 95% CIs shown by the shaded area for (a) CRP concentrations by days since DAIR, (b) CRP concentrations by

days before failure, excluding 180 days post-DAIR, (c) CRP concentrations by days since first-stage revision, excluding concentrations after secondstage and (d) CRP concentrations by days before failure, excluding 28 days post-re-implantation.

Bejon et al.

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interventions on the one hand, or delaying clinically indicatedinterventions on the other, we recommend against routinelymonitoring CRP during treatment of PJI.

FundingThe study was carried out as part of a routine service audit. P. B. is sup-ported by the NIHR Biomedical Research Centre in Oxford.

Transparency declarationsI. B. has received honoraria for serving on advisory boards (Pfizer) andlecture fees (Pfizer and Nordic Pharma). P. M.-S. is advisor to WrightMedical Technologies and receives royalties from the Corin Group. A. R. B.has received honoraria for serving on advisory boards (Pfizer andMacrochem), for serving on speakers bureaus (Merck) and for producingsponsored non-promotional educational materials (Merck). All otherauthors: none to declare.

Supplementary dataFigure S1 and S2 are available as Supplementary data at JAC Online(http://jac.oxfordjournals.org/).

References1 HPA. Fourth Report of the Mandatory Surveillance of Surgical SiteInfection in Orthopaedic Surgery. April 2004 to March 2008. http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1227774003450 (12 April2011, date last accessed).

2 Zimmerli W, Ochsner PE. Management of infection associated withprosthetic joints. Infection 2003; 31: 99–108.

3 Atkins BL, Athanasou N, Deeks JJ et al. Prospective evaluation of criteria for microbiological diagnosis of prosthetic-joint infection atrevision arthroplasty. The OSIRIS Collaborative Study Group. J ClinMicrobiol 1998; 36: 2932–9.

4 Berbari E, Mabry T, Tsaras G et al. Inflammatory blood laboratory levelsas markers of prosthetic joint infection: a systematic review andmeta-analysis. J Bone Joint Surg Am 2010; 92: 2102–9.

5 Ghanem E, Azzam K, Seeley M et al. Staged revision forknee arthroplasty infection: what is the role of serologic testsbefore reimplantation? Clin Orthop Relat Res 2009; 467:1699–705.

6 Kusuma SK, Ward J, Jacofsky M et al. What is the role of serologicaltesting between stages of two-stage reconstruction of the infectedprosthetic knee? Clin Orthop Relat Res 2010; 469: 1002–8.

7 Shukla SK, Ward JP, Jacofsky MC et al. Perioperative testing forpersistent sepsis following resection arthroplasty of the hip forperiprosthetic infection. J Arthroplasty 2010; 25: 87–91.

8 Bejon P, Berendt A, Atkins BL et al. Two-stage revision for

prosthetic joint infection: predictors of outcome and the role of reimplantation microbiology. J Antimicrob Chemother 2010; 65:569–75.

9 Byren I, Bejon P, Atkins BL et al. One hundred and twelve infectedarthroplasties treated with ‘DAIR’ (debridement, antibiotics and implantretention): antibiotic duration and outcome. J Antimicrob Chemother 2009; 63: 1264–71.

10 Verhagen DW, Hermanides J, Korevaar JC et al. Prognostic value of serial C-reactive protein measurements in left-sided native valveendocarditis. Arch Intern Med 2008; 168: 302–7.

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