High cure rate of periprosthetic hip joint infection with multidisciplinary team approach using standardized two-stage exchange

In this single-center prospectively followed cohort study, all hip PJI episodes from 2013 to 2015 were included, which were treated by a standardized comprehensive diagnostic and therapeutic algorithm with two-stage exchange. Native infected joints, joints with missing data, joints with mega prostheses, and patients with a follow-up period less than 24 months were excluded. The study protocol was reviewed and approved by the institutional ethics committee (EA4/040/14).

On admission, age, gender, comorbidities, history of the infected joint, the score of the Charlson comorbidity index (CCI) [12], laboratory values such as serum C-reactive protein (CRP) and blood leukocytes, and presumed route of infection (intraoperative versus hematogenous) were recorded. In addition, the following data were extracted: number of revision surgeries between stages, length of hospital stay, total duration of antimicrobial therapy, serum CRP value at the time of reimplantation, and microbiological and pathological results of revisions and reimplantation.

In this cohort, PJI was diagnosed according to proposed European Bone and Joint Infection Society (EBJIS) criteria [13], since these criteria were used in several outcome studies [14‐16]. The definition for successfully treated PJI was based on the Delphi-based international multidisciplinary consensus [17] and was further modified; treatment was considered as successful, if all of the following criteria were fulfilled at the latest follow-up: (i) infection eradication, characterized by a healed wound without fistula, drainage, or pain, and no recurrence of the infection caused by the same organism; (ii) no subsequent surgical intervention for persistent or perioperative infection after reimplantation surgery; (iii) no occurrence of PJI related mortality; and (iv) no long-term (> 6 months) antimicrobial suppression therapy.

Microorganisms such as rifampin-resistant staphylococci, enterococci, ciprofloxacin-resistant gram-negative bacteria, and fungi were defined as difficult-to-treat (DTT) due to the absence of available antibiofilm-active treatment [18].

Each patient underwent a standardized comprehensive diagnostic algorithm. All patients were evaluated by a thorough physical examination with respect to the clinical patient status and soft tissue conditions. Laboratory tests were performed including C-reactive protein (CRP), and plain anteroposterior and lateral radiographs were made. All patients with suspected PJI underwent a diagnostic arthrocentesis. The synovial fluid analysis included total cell count, differential leukocyte count, culture for aerobic and anaerobic organisms, and histological analysis. A synovial fluid leukocyte count of more than 2000/mm³ or a finding with more than 70% neutrophils was our cutoff value for the diagnosis of PJI [18]. A positive histopathology was defined as a mean of ≥ 23 granulocytes per ten high-power fields, corresponding to type 2 or type 3 periprosthetic membrane [19]. In case of a dry tap, patients with chronic painful prosthesis underwent a diagnostic surgery to gain at least five periprosthetic tissue samples for microbiological and histopathological analysis or a diagnostic explantation when the suspicion of infection was very high. The cultures were always incubated for 14 days. In case of fever or systemic infection signs, blood cultures for aerobic and anaerobic organisms were obtained and an intensive search for potential primary focus of infection, such as infectious endocarditis, dental (periodontitis, periapical dental abscess, or dental intervention), urogenital, and gastrointestinal source, was done. The explanted prosthesis was sent to sonication to increase the accuracy of microbiologic diagnosis [20].

The first stage consisted of removal of all implants, as well as infected and necrotic tissue, bone cement, and all other foreign material with a following irrigation and debridement of the surrounding tissues. In most episodes, a cement spacer was not routinely used, unless dead space management or the fixation of a proximal femur fracture was necessary.

Antibiotic treatment was started intravenously (IV) after taking multiple tissue samples during the explantation or in the case of patients presenting with sepsis preoperatively after synovial aspiration. Each patient underwent a standardized antimicrobial therapy, which was based on a previously published concept [18] under the surveillance of our infectious disease specialists [21]. IV treatment was continued for the first 2 weeks after surgery and followed by an oral regimen, if possible. In case of a persistent infection (discharging wound and/or increasing CRP without any other focus and/or local signs of infection), an irrigation and debridement (and spacer exchange, if applicable) of the explanted hip joint was performed. All patients received antibiotics until reimplantation surgery without an antibiotic-free period and diagnostic aspiration. A reimplantation was performed, when the wound was healed, soft tissues were ready for surgery, the general status of the patient was suitable, and there was no clinical sign of a persisting infection. If DTT microorganisms were isolated, a longer prosthesis-free interval (> 6 weeks) was preferred [22]. The reimplantation was used in every patient as another opportunity to perform one more thorough debridement of the surrounding soft tissues and bone prior to placement of the definitive components. During each explantation and reimplantation, at least five periprosthetic tissue samples were collected for microbiological analysis. After reimplantation, antibiotics were administered for 2 weeks via the intravenous route followed by an oral biofilm-active (in non-DTT PJI) or non-biofilm-active antimicrobial treatment (in DTT PJI) for a total treatment duration of at least 12 weeks with a minimum of 6 weeks’ antimicrobial course after reimplantation.

A therapy with biofilm-active antibiotics, such as rifampin or fluoroquinolones, was started only after reimplantation, when all drains were removed, the wound was dry, and the bacterial load was reduced by initial antimicrobial therapy not to cause the emergence of resistance [23, 24]. If medically stable, patients received antimicrobial therapy at home through a peripherally inserted central catheter (PICC) line, when oral antimicrobial therapy was not possible due to multiple drug resistance.

In case of a relevant positive culture during reimplantation (≥ 2 samples were positive for the same microorganism), or a polymicrobial infection (or if the isolated microorganism was the same as the initial infecting organism even if only one culture was positive), antimicrobial therapy was continued for 12 weeks after reimplantation. Otherwise, the standard therapy was given for 6 weeks after reimplantation as planned. A chronic antibiotic suppression was used for patients with increased risk of relapse, including a history of multiple joint infections, deficient immune system, and comorbidities predisposing to PJI [25], after individualized decision-making through a multidisciplinary team, including infectious disease specialists, internal medicine specialists, and orthopedic surgeons, who were involved in every stage of PJI management for each patient.

Patients were seen in the outpatient clinic after 3, 6, and 12 months and after that period annually. Clinical, laboratory, and radiological evaluation were performed by an orthopedic surgeon and an infectious disease specialist.