Synopsis: Previous studies have suggested aseptic loosing of joint prostheses may be caused by infection with nonculturable bacteria. This study found that PCR testing of operative specimens for bacterial 16s RNA did not identify the presence of bacteria if adequate microbiologic processing of specimens was performed and was negative.

Source: Ince A, et al. Is aseptic loosening of the prosthetic cup after total hip replacement due to nonculturable bacterial pathogens with low-grade infection? Clin Infect Dis 2004; 39:1,599-1,603.

Ince, et al studied 24 patients with hip prostheses undergoing surgery for loosening of the prosthetic cup. All patients underwent preoperative joint aspiration. At operation, specimens were obtained from the neocapsule and synovium; they were sent for culture and for PCR to detect 16s ribosomal RNA. Nine patients undergoing primary hip arthroplasty served as controls. All cultures were processed according to a protocol, with incubation in brain-heart infusion broth and TVLS medium, as well as Columbia blood agar in 5% CO2 and Brucella agar under anaerobic conditions. All case and control patients had negative cultures, except for one case patient who grew Propionibacterium acnes in a single operative specimen.

All PCR determinations were negative. Patients had slightly, but not statistically significant elevated sedimentation rates and C-reactive protein levels, as compared to controls. Ince and colleagues concluded that good microbiologic processing of specimens is adequate to exclude bacterial infection in loosened hip prostheses, and PCR does not enhance diagnostic sensitivity for infection.

Comment by Robert Muder, MD, hospital epidemiologist, VA Pittsburgh Healthcare System.

The diagnosis of prosthetic joint infection often is difficult. There is no universally accepted definition for the diagnosis of infection in the absence of microbiological proof. Clinical symptoms such as pain and instability do not differentiate infection from mechanical joint failure. Several of the most common bacterial pathogens causing prosthesis infection, P. acnes and coagulase-negative staphylococci, are common skin contaminants. There is debate about the utility of histologic criteria, such as polymorphonuclear leukocyte count in tissue, in the diagnosis of infection.

To complicate things further, several studies using a variety of techniques have suggested that routine culture may fail to detect infection as a result of bacteria residing in biofilm. For example, Marinani, et al1 reported the culture only had an 18% sensitivity in detecting bacteria in patients undergoing hip arthroplasty, as compared with PCR.1 Tunney, et al2 subjected femoral prostheses removed from patients for loosing to sonication, followed by PCR, and found evidence of P. acnes or staphylococci in 72%. Cultures were positive in only 4% of patients. One potential reason for the discrepancy between those results may be the extent of microbiologic processing of both pre-operative aspirates and operative specimens. Ince and colleagues used multiple media and prolonged incubation times.

Thus, the preoperative aspirate may have identified a high proportion of patients with true bacterial infection, infections that might have been missed. This is of potential importance, as bacteria causing prosthetic joint infections residing in a biofilm are relatively inactive metabolically and may not be well adapted to growth in liquid or solid media. Less meticulous processing may fail to identify them.

This study does not fully resolve whether bacteria undetectable by culture are responsible for a significant number of cases of prosthetic joint failure. The data are sufficiently convincing that I would feel comfortable withholding antibiotic therapy from a patient with a loosened prosthetic joint if preoperative and intraoperative cultures were negative, and the ESR and C-reactive protein were normal or minimally elevated. However, specimens should be processed according to the above protocol; less extensive processing may give a false sense of security.


1. Marinani BD, et al. The Coventry Award: Polymerase chain reaction detection of bacterial infection in total knee arthroplasty. Clin Orthop 1996; 331:11-22.

2. Tunney MM, et al. Improved detection of infection in hip replacements: A currently underestimated problem. J Bone Joint Surg Br 1998; 80:3,281-3,320.