PCR and the Diagnosis of Occult Bacterial Infection in Hip Prostheses

Abstract & Commentary

Synopsis: Previous studies have suggested that aseptic loosing of joint prostheses may be caused by infection with non culturable 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;39:1599-1603.

Ince et al studied 24 patients with hip prostheses undergoing surgery for loosening of the prosthetic cup. All patients underwent pre-operative 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 arthoplasty 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 1 case patient who grew Proprionobacterium 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 that PCR does not enhance diagnostic sensitivity for infection.

Comment by Robert Muder, MD

The diagnosis of prosthetic joint infection is often 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, Mariani et al1 reported that the culture had only an 18% sensitivity in detecting bacteria in patients undergoing hip arthroplasty, as compared with PCR.1 Tunny 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 the results of Ince and colleagues and those of prior investigators 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 pre-operative aspirate may have identified a high proportion of patients with true bacterial infection—infections that might have been otherwise 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 the question of 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 intra-operative cultures were negative, and the ESR and C-reactive protein were normal or minimally elevated. It should be noted, however, specimens should be processed according to the above protocol; less extensive processing may give a false sense of security.

References

1. Marinani BD, et al. The Coventry Award: Polymerase Chain Reaction Detection of Bacterial Infection in Total Knee Arthoplasty. 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;80:3281-3320.

Robert Muder, MD, Hospital Epidemiologist Pittsburgh VA Medical Center Pittsburgh Section Editor, Hospital Epidemiology, is Associate Editor for Infectious Disease Alert.