Culture-Negative Prosthetic Joint Infection

Abstract & Commentary

Dean L. Winslow, MD, FACP, FIDSA, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center; Clinical Professor of Medicine, Stanford University School of Medicine. Dr. Winslow serves as a consultant to Siemens Diagnostics, and is on the speaker's bureau for Boehringer-Ingelheim and GSK.

Synopsis: A retrospective cohort study of culture-negative (CN) prosthetic joint infection (PJI) was performed on patients who underwent total hip or total knee arthroplasty at Mayo Clinic from 1990-1999. Of the 897 episodes of PJI during this period, 60 episodes of CN PJI were identified. Of these, 53% of patients had received prior antimicrobial therapy. Outcomes following treatment with either 2-stage exchange or with debridement and retention were comparable to that seen in patients with culture-positive PJI.

Source: Berbari EF, et al. Culture-negative prosthetic joint infection. Clin Infect Dis. 2007;45:1113-1119.

This retrospective cohort study from the section of Orthopedic Infectious Diseases at Mayo Clinic presents their experience with CN PJI cases seen between 1990 and 1999. Only first episode CN PJI were included in the study. Berbari and colleagues employed a strict case definition which included the presence of purulence surrounding the prosthesis (as determined by the surgeon), histopathologic findings of acute inflammation of periprosthetic tissue samples consistent with infection, or a cutaneous sinus tract communicating with the prosthesis, in addition to there having been negative aerobic and anaerobic culture attempts. Standard culture techniques were employed, and either synovial fluid or homogenized tissue samples were used to inoculate both solid media and broth cultures. In addition to standard aerobic and anaerobic cultures, fungal and AFB cultures were set up in many cases.

Demographic characteristics of the patients were consistent with the larger group of 897 patients seen during the same time period with culture-positive PJI. The median duration from prosthesis implantation to diagnosis of CN PJI was quite long, 1269 days, and the median duration of symptoms prior to diagnosis was 103 days. Use of antimicrobial therapy during the 3 months prior to diagnosis of CN PJI was present in 32 (53%) of 60 episodes. Interestingly, outcome of therapy for the patients with CN PJI was similar to the larger group of all patients with PJI treated during the same time period. Five-year survival free of treatment failure was 82% across the 60 episodes. Looking at specific surgical therapy, the 5-year survival figures were 94% in the 34 patients who underwent 2-stage replacement and 71% for the 12 patients who underwent debridement and retention. The 8 patients who underwent resection arthroplasty were followed for only 3 years, and their survival free of treatment failure was 50% during this period.

Among the 10 total episodes where treatment failure occurred, 5 again "relapsed" with CN PJI, 2 relapses were due to S. aureus, one due to coagulase-negative staph, and one due to group B streptococcus.


It is clear that patients with CN PJI are heterogeneous with respect to etiology. The use of antibiotics within 3 months of diagnosis was probably the major factor in the causation of negative cultures in patients who clearly had PJI using the study's case definition. However, in other cases, it is likely that sampling error, or more likely sequestration of bacteria in biofilms, may have played a role. Supporting the hypothesis that organism sequestration in biofilm may play a role in false negative cultures seen in PJI is supported by an interesting paper recently published from this same group which showed that sonication of removed hip and knee prostheses was more sensitive for microbiologic diagnosis of PJI than standard methods of processing tissue for culture.1 However, this technique may be associated with increased risk of specimen contamination.2

As to treatment, it appeared that the outcome in patients treated with 2-stage replacement was superior to that seen in patients treated with debridement and retention of the prosthesis, although this conclusion must be tempered by the caveat of potential selection bias. It is of interest, that in this series, the outcome of patients treated with a first-generation cephalosporin was no worse than those treated with antimicrobials with activity against methicillin-resistant organisms or drug-resistant gram-negative rods.


1. Trampuz A, et al. Sonication of removed hip and knee prostheses for diagnosis of infection. N Engl J Med. 2007;357:654-663.

2. Trampuz A, et al. Sonication of explanted prosthetic components in bags for diagnosis of prosthetic joint infection is associated with risk of contamination. J Clin Microbiol. 2006;44:628-631.