S02.KL2 PERSISTENCE OF INFECTION IN DEVICE-ASSOCIATED INFECTION

Abstract

Implant-associated infections do not spontaneously cure. The reason for persistence in device-associated infections is the biofilm, a specialized form of bacterial growth on surfaces. The biofilm represents a survival form of bacteria which is highly resistant against most antibiotics, and can persist over months or years as low-grade infection. Bacteria in biofilms enter a metabolically inactive state, embedded in an amorphous substance, called biofilm matrix. Together they form a complex three-dimensional structure with rudimentary communication and circulation systems.

As a rule, only a combined surgical and antimicrobial management can eradicate biofilms and cure implant-associated infection. In selected patients, implant infections can be cured without implant removal with early debridement and long-term antibiotic treatment acting against biofilms. In this presentation, common pitfalls and reasons for treatment failure will be outlined and discussed.

1. Adequate diagnosis. Every prosthesis with early loosening (< 2 years after implantation) or persistent/increasing pain should rise the suspicion of an implant-associated infection, which may presents without systemic signs of infection (fever), and can manifest without increased leukocyte counts or C-reactive protein). In this case, periimplant infection must be actively searched. Preoperative diagnosis includes aspiration of the synovial fluid of larger joints for Gram stain and culture; cell count and differential; and crystals (if appropriate). Swabs of the sinus tract (fistula) should not be performed, since they may not represent the causing organisms of the bone- or implant-associated infection. Intraoperative diagnosis includes multiple tissue biopsies around the prosthesis (no swabs), histopathology of the periprosthetic tissue and sonication of the removed device or its parts (if the method is available). For low-virulent organisms (such as Staphylococcus epidermidis or Propionibacterium acnes) at least two positive specimens with the same organism or an additional criterion for infection (i.e. acute inflammation in the tissue histopathology, presence of intraoperative pus or fistula) is needed. For slow-growing organisms, long incubation is needed (14 days) in order to culture these slow-growing and fastidious pathogens. Antibiotics should be discontinued at least 2 weeks prior to culture sample in order to minimize false-negative results. Novel diagnostic tests include PCR, which can also detect non-growing microorganisms and can be used for tissue specimens, joint aspirate or sonication fluid.

2. Adequate antibiotic therapy. The identification of the infecting pathogen is paramount for a successful treatment. Therefore, no empiric antibiotic therapy should be administered before diagnosis is microbiologically confirmed. Antibiotics administered for a secreting wound overlying an implant is a critical mistake, which makes the etiological diagnosis difficult. In addition, the risk of development of antimicrobial resistance is high, particularly for rifampin. Therefore, rifampin should not be administered as long as there is a contact between body surface and implant (e.g. open wound or wound dehiscence, fistula, VAC foam, drainage). In contrast, addition of rifampin is absolutely necessary for eradication of staphylococcal infections of implants in case of retention (see presentation from W. Zimmerli S02.KL1). Other common mistakes are short duration of antibiotic treatment (totally 3 months are needed for eradication of biofilm), low antibiotic dose (high dosing is needed to achieve sufficient concentration in bone) or switch from intravenous to oral antibiotics with insufficient bioavailability (such as oral betalactams) or inactivity against biofilms (such as cephalosporins, macrolides or clindamycin).

3. Adequate surgical therapy. Immediate debridement is indicated, if there is a suspicion of implant-associated infection (wound dehiscence, persisting secretion, lack of postoperative decrease of CRP). A revision is needed for diagnostic (adequate microbiological diagnosis) and therapeutic purposes (mechanical reduction of bacteria). The implant can be retained, if the symptoms of infection are lasting < 3 weeks, the prosthesis is stable and the infecting pathogen is susceptible to anti-biofilm antibiotics (i.e. staphylococci susceptible to rifampin). Importantly, a loose prosthesis can not be salvaged and always needs to be exchanged. Antimicrobial suppression therapy has a low probability of success (failure rate approximately 80% after 2 years). The drainages should be kept in place as short as possible, i.e. in general not more than 3 days. Large soft tissue defects require coverage with a flap.

In conclusion, using the proposed diagnostic and treatment algorithm (Zimmerli et al. NEJM2004; 351: 1645), the long-term success rate of periprosthetic joint infection is 80–90%. To avoid failure, it is important to select the patient for the least invasive, but still appropriate surgical and antibiotic treatment regimen and to avoid mistakes.