Multiplex PCR of sonication fluid accurately differentiates between prosthetic joint infection and aseptic failure. 
Cultures have limited sensitivity in the diagnosis of prosthetic joint infection (PJI), especially in low-grade infections.  We assessed the value of multiplex PCR in differentiating PJI from aseptic failure (AF).  Included were patients in whom the joint prosthesis was removed and submitted for sonication.  The resulting sonication fluid was cultured and investigated by multiplex PCR, and compared with periprosthetic tissue culture.  Among 86 explanted prostheses (56 knee, 25 hip, 3 elbow and 2 shoulder prostheses), AF was diagnosed in 62 cases (72%) and PJI in 24 cases (28%).  PJI was more common detected by multiplex PCR (n=23, 96%) than by periprosthetic tissue (n=17, 71%, p=0.031) or sonication fluid culture (n=16, 67%, p=0.016).  Among 12 patients with PJI who previously received antibiotics, periprosthetic tissue cultures were positive in 8 cases (67%), sonication fluid cultures in 6 cases (50%) and multiplex PCR in 11 cases (92%).  In AF cases, periprosthetic tissue grew organisms in 11% and sonication fluid in 10%, whereas multiplex PCR detected no organisms.  Multiplex PCR of sonication fluid demonstrated high sensitivity (96%) and specificity (100%) for diagnosing PJI, providing good discriminative power towards AF, especially in patients previously receiving antibiotics.