Cultures in periprosthetic joint infections, the imperfect gold standard?

Abstract

Culture-negative periprosthetic joint infections (PJI) are commonly described in the literature. By implementing a routine diagnostic workup and by optimizing tissue sampling and processing, the culture-negative rate can easily be reduced. When faced with a culture-negative PJI, several serological and molecular techniques are available that may aid in finding the causative microorganism. Clinical clues may guide the treating physician towards more atypical and rare microorganisms. A multidisciplinary team consisting of orthopaedic surgeons, microbiologists and infectious disease specialist are warranted in tailoring diagnostic testing and deciding on the surgical and antibiotic treatment approach.

Keywords: NGS; PJI; culture; culture-negative PJI; molecular techniques.

Figure 1

Diagnostic flow chart for culture-negative PJI and available serological and molecular techniques. ¹Preferred method due to a high likelihood of a polymicrobial PJI with commensal (skin) pathogens. ²Preferred method due to routine availability in most centres and a high likelihood of a monomicrobial PJI. If available, multiplex PCR and NGS can be alternative methods. ³In case of negative serology, an infection can be ruled out. In case of positive serology, the causative microorganisms should ideally be confirmed by a positive PCR at the site of infection. ⁴In case of an immunocompromised host with risk factors for rare fungal diseases, cultures should be incubated for 4–6 weeks. ⁵In the absence of diagnostic clues, 16S PCR and/or NGS can be performed if available. *In case the patient was not on antibiotic treatment that explains culture negativity, other difficult-to-cultivate bacteria need to be considered like myobacteria and those indicated in the table.