Premature Therapeutic Antimicrobial Treatments Can Compromise the Diagnosis of Late Periprosthetic Joint Infection

Clinical Orthopaedics and Related Research® Clin Orthop Relat Res (2015) 473:2244–2249 DOI 10.1007/s11999-015-4142-z A Publication of The Association of Bone and Joint Surgeons® SYMPOSIUM: 2014 MUSCULOSKELETAL INFECTION SOCIETY Premature Therapeutic Antimicrobial Treatments Can Compromise the Diagnosis of Late Periprosthetic Joint Infection Alisina Shahi MD, Carl Deirmengian MD, Carlos Higuera MD, Antonia Chen MD, MBA, Camilo Restrepo MD, Benjamin Zmistowski MD, Javad Parvizi MD Published online: 21 January 2015 Ó The Association of Bone and Joint Surgeons1 2015 Abstract Background In the absence of positive cultures and draining sinuses, the diagnosis of periprosthetic joint infection (PJI) relies on laboratory values. It is unknown if administration of antibiotics within 2 weeks before diagnostic evaluations can affect these tests in patients with PJI. Questions/purposes The purpose of this study was to investigate the correlation of antibiotic administration with (1) fluctuations in the synovial fluid and serology laboratory values; and (2) sensitivity of the diagnostic tests in patients with late PJI (per Musculoskeletal Infection Society [MSIS] criteria). Methods Synovial white blood cell (WBC) count, polymorphonuclear neutrophil (PMN) percentage, and serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as well as culture results were investigated in 161 patients undergoing total knee arthroplasty with late PJI diagnosed with the MSIS criteria. Depending on whether presampling antibiotics were used, patients were divided in two groups (53 [33%] patients were on antibiotics). The median laboratory values and the false-negative rates were compared between the two groups. Results The median of all variables were lower in the antibiotic group compared with the other group: ESR (mm/hr): 70 versus 85, difference of medians (DOM) = 15 mm/hr, p = 0.018; CRP (mg/L): 72 versus 130, DOM = 58 mg/L, p = 0.038; synovial WBC (cells/lL): 29,170 versus 46,900, DOM = 17,730, p = 0.022; and synovial PMN%: 88.5% versus 92.5%, DOM = 4%, p = 0.012. Furthermore, using the MSIS cutoffs, the false-negative rates of several parameters were higher in the antibiotic group; ESR: 19.2% (nine of 47) versus 6.1% (six of 99) (relative risk, 3.1; 95% confidence interval [CI], 1.2–8.3; p = 0.020); CRP: 14.9% (seven of 47) versus 2.00% (two of 100) (relative risk, 7.4; 95% CI, 1.6–34.4); PMN%: 23.1% (12 of 52) versus 9.4% (10 of 106) (relative risk, 2.4; 95% CI, 1.1–5.2; p = 0.027). One author certifies that he (JP) has or may receive payments or benefits, during the study period, in an amount of USD 10,000 to USD 100,000, from Zimmer (Warsaw, IN, USA). One author certifies that he (JP) has or may receive payments or benefits, during the study period, in an amount of USD 10,000 to USD 100,000 from Smith & Nephew (Andover, MA, USA). One author certifies that he (JP) has or may receive payments or benefits, during the study period, in an amount of less than USD 10,000 from ConvaTec (Skillman, NJ, USA). One author certifies that he (JP) has or may receive payments or benefits, during the study period, in an amount of USD 10,000 from TissueGene (Rockville, MD, USA). One author certifies that he (JP) has or may receive payments or benefits, during the study period, in an amount of less than USD 10,000 from CeramTec (Plochingen, Germany). One author certifies that he (JP) has or may receive payments or benefits, during the study period, in an amount of USD 10,000 from Medtronic (Minneapolis, MN, USA). One author (JP) has stock options with CD Diagnostics (Wynnewood, PA, USA), Hip Innovation Technology (Plantation, FL, USA), and PRN (Plymouth Meeting, PA, USA). All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research1 editors and board members are on file with the publication and can be viewed on request. Each author certifies that his or her institution approved the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research. 123 A. Shahi, C. Deirmengian, A. Chen, C. Restrepo, B. Zmistowski, J. Parvizi (&) The Rothman Institute at Thomas Jefferson University, 125 S 9th Street, Suite 1000, Philadelphia, PA 19107, USA e-mail: ; C. Higuera Department of Orthopaedic Surgery, The Cleveland Clinic, Cleveland, OH, USA Volume 473, Number 7, July 2015 Patients in the antibiotic group also had higher rates of negative cultures: 26.4% (14 of 53) versus 12.9% (14 of 108) (relative risk, 2.0; 95% CI, 1.05–3.9; p = 0.046). Conclusions It appears that premature antibiotic treatments are associated with lower medians of diagnostic laboratory values. Thus, and in line with the guideline recommendations of the American Academy of Orthopaedic Surgeons, patients with suspected late-PJI should not receive antibiotics until the diagnosis is reached or refuted. Level of Evidence Level III, diagnostic study. Introduction The diagnosis of periprosthetic joint infection (PJI) remains a challenge with no definitive standards. To address this issue, the Musculoskeletal Infection Society (MSIS) has recommended criteria to better define and diagnose PJI, criteria that underwent a modification during the 2013 International Consensus Meeting (ICM) on PJI [18, 21]. Proper diagnosis of PJI relies on a detailed patient history, physical examinations, serologic tests, and radiologic assessments [1, 20, 22]. Additionally, isolation of the microorganism is imperative for proper diagnosis and successful treatment of the patient with PJI [18, 22]. However, the available tests for diagnosis of PJI are far from perfect. Cultures, for example, are negative in 7% to 12% of patients with PJI [5, 10, 16, 19]. Culture-negative PJI can potentially complicate case classification and management and is an additional source of stress for both the patient and surgeon. Antimicrobial treatments have been reported to be a cause of culture-negative PJI [5, 17]. According to the definition of PJI, in the absence of major criteria, ie, communicating sinus tract or two positive cultures, serologic results are the bedrock of diagnosis [18]. Although the adverse effects of antibiotic administration on culture results has been well studied [5, 15, 26] and the clinical practice guideline of the American Academy of Orthopaedic Surgeons (AAOS) recommends withholding antibiotics for at least 2 weeks before aspiration to increase the culture yield [8], it is still unknown whether preaspiration antibiotic administration can affect synovial fluid cell counts and serology results. The purpose of our comparative study was to evaluate the association of preaspiration antibiotic administration with (1) fluctuations in synovial fluid white blood cell (WBC) count, polymorphonuclear neutrophil (PMN) percentage, serum erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP); and (2) sensitivity of the diagnostic tests in patient (...truncated)