Fully oral targeted antibiotic therapy for Gram-positive cocci-related periprosthetic joint infections: a real-life before and after study.

BACKGROUND: The optimal length of the intravenous antibiotic treatment of periprosthetic joint infections (PJIs) generally ranges from one to six weeks and is a matter of debate. Most antibiotics active against Gram-positive cocci (GPC) exhibit both high oral bioavailability and bone diffusion. Thus, early oral therapy may be a reasonable option in GPC-related PJIs. METHODS: A 2 year before and after monocentric study that aimed to compare two antibiotic strategies. Empirical intravenous postoperative antibiotic treatment was followed by 7 to 10 days of intravenous targeted therapy ('before' group) or by full orally targeted antibiotic treatment ('after' group). The primary outcome was a treatment failure during follow-up. RESULTS: A total of 93 patients were analysed, 43 and 50 in the before and the after groups, respectively. Both groups were comparable in terms of surgical procedures, comorbidities, microbiological documentation and infection site. Antibiotics prescribed to our patients had high oral bioavailability and bone diffusion with rifampicin/fluoroquinolone combinations being the most frequent antibiotic regimens. Both hospital stay and intravenous antibiotic treatment mean durations were shorter in the before group than in the after group [15.0 versus 11.0 days; (P < 0.01) and 13.0 versus 7.0 days; P < 0.001, respectively]. The remission rate assessed after at least a year of follow-up was comparable in the before and the after groups (hazard ratio = 0.70; 95% CI 0.30-1.58). CONCLUSIONS: Full oral targeted antibiotic therapy using a drug regimen with high oral bioavailability and good bone diffusion is an option for the treatment of patients with GPC-related PJIs.

Outcome and predictors of treatment failure in total hip/knee prosthetic joint infections due to Staphylococcus aureus.

BACKGROUND: Variables associated with the outcome of patients treated for prosthetic joint infections (PJIs) due to Staphylococcus aureus are not well known. METHODS: The medical records of patients treated surgically for total hip or knee prosthesis infection due to S. aureus were reviewed. Remission was defined by the absence of local or systemic signs of implant-related infection assessed during the most recent contact with the patient. RESULTS: After a mean posttreatment follow-up period of 43.6 ± 32.1 months, 77 (78.6%) of 98 patients were in remission. Retention of the infected implants was not associated with a worse outcome than was their removal. Methicillin-resistant S. aureus (MRSA)-related PJIs were not associated with worse outcome, compared with methicillin-susceptible S. aureus (MSSA)-related PJIs. Pathogens identified during revision for failure exhibited no acquired resistance to antibiotics used as definitive therapy, in particular rifampin. In univariate analysis, parameters that differed between patients whose treatment did or did not fail were: American Society of Anesthesiologists (ASA) score, prescription of adequate empirical postsurgical antibiotic therapy, and use of rifampin combination therapy upon discharge from hospital. In multivariate analysis, ASA score ≤2 (odds ratio [OR], 6.87 [95% confidence interval {CI}, 1.45-32.45]; P = .04) and rifampin-fluoroquinolone combination therapy (OR, 0.40 [95% CI, 0.17-0.97]; P = .01) were 2 independent variables associated with remission. CONCLUSIONS: The results of the present study suggest that the ASA score significantly affects the outcome of patients treated for total hip and knee prosthetic infections due to MSSA or MRSA and that rifampin combination therapy is associated with a better outcome for these patients when compared with other antibiotic regimens.

Challenging Methicillin Resistance Detection in Bone and Joint Infections: Focus on the MRSA/SA SSTI® Strategy.

The genus Staphylococcus is the main causative agent of bone and joint infections (BJI) in which outcomes are impacted by both effective surgical and appropriate antimicrobial management. In this context, methicillin resistance (MR) detection is a microbiological challenge to optimize the anti-staphylococcal drug coverage and to secure the surgical procedure. During the last decade, molecular tools have been developed to rapidly detect bacterial-resistant strains in clinical samples. The GeneXpert MRSA/SA SSTI® assay (Cepheid, Sunnyvale, CA, USA) is a real-time PCR method aimed at detecting methicillin-resistant Staphylococcus aureus (MRSA) in skin and soft tissues infections. In the literature, this test has been reported to be diverted from its original purpose to be evaluated in surgical samples. Within the current review, we update the GeneXpert MRSA/SA SSTI® assay performance in staphylococcal species determination (i.e., S. aureus vs. coagulase-negative species) together with MR genotype detection, when performed in osteoarticular infections.

Tolerability of prolonged linezolid therapy in bone and joint infection: protective effect of rifampicin on the occurrence of anaemia?

BACKGROUND: Linezolid therapy has shown high rates of clinical success in patients with osteomyelitis and prosthetic joint infections caused by Gram-positive cocci. Recent studies have demonstrated that linezolid/rifampicin combination therapy prevents the emergence of rifampicin-resistant mutations in vitro. However, linezolid/rifampicin combination-related haematological and neurological toxicities have not been evaluated. OBJECTIVES: To assess the tolerability of prolonged linezolid/rifampicin combination therapy compared with other linezolid-containing regimens in patients with bone and joint infections. METHODS: We reviewed the medical records of 94 patients who had received linezolid for >4 weeks after bone and joint infections. Anaemia was defined as a ≥2 g/dL reduction in haemoglobin, leucopenia as a total leucocyte count <4 × 10(9)/L, and thrombocytopenia as a reduction in platelet count to <75% of baseline. RESULTS: Anaemia was less frequent among patients on linezolid/rifampicin combination therapy than among patients on linezolid alone or in combination with other drugs (9.3%, 44% and 52%, respectively; P<0.01). In multivariate analysis, age and treatment group were independently associated with anaemia. Thrombocytopenia was reported in 44% of patients on linezolid/rifampicin combination therapy, in 48% of patients on linezolid alone and in 57.7% of patients on other linezolid-containing regimens. Age was the only variable associated with thrombocytopenia (P=0.019) in univariate analysis. CONCLUSIONS: Linezolid/rifampicin combination therapy was associated with a significantly reduced incidence of anaemia among patients with bone and joint infections, but it did not have an effect on thrombocytopenia and peripheral neuropathy rates. Linezolid/rifampicin combination therapy was not associated with poor clinical outcomes.

Microbiologic profile of Staphylococci isolated from osteoarticular infections: evolution over ten years.

BACKGROUND: Staphylococci, especially coagulase-negative staphylococci (CoNS) represent the most frequent micro-organism associated with osteoarticular infections (OAIs), especially those involving orthopedic devices. The antibiotic susceptibility profile of the bacteria mostly responsible for OAIs is therefore crucial information for choosing the appropriate antibiotic regimen administered during the removal procedure until the first results of the conventional culture. METHODS: The antibiotic susceptibility profile of staphylococci isolated from OAIs in a referent center for osteoarticular infection was studied over a 10-y period to adapt antibiotic protocols to the ecology. RESULTS: From 2002 to 2011, the resistance of Staphylococcus aureus to methicillin and rifampicin decreased (27.9% versus 20.6% and 13% versus 1%, respectively); the resistance to fluoroquinolones (FQ) was stable (24% on average), and all the isolates were susceptible to glycopeptides. For CoNS, the resistance to methicillin, rifampicin, and FQ increased (30.4% versus 43.9%, 13% versus 18.5%, and 20.3% versus 34.1%, respectively) over the same period. Resistance of the CoNS to vancomycin was observed in 2011 for the first time (2.3%), and 3.8% were resistant to teicoplanin in 2002 compared with 22% in 2011, with 3.5% resistant to linezolid in 2011. CONCLUSION: The sensibility of bacteria over 10 y remained stable, except for CoNS. The increase of the resistances for CoNS led us to exclude teicoplanin from the first-line empiric antibiotic treatment, to avoid linezolid, and to prefer vancomycin or daptomycin.

Evaluation of rapid mecA gene detection versus standard culture in staphylococcal chronic prosthetic joint infections.

In case of periprosthetic joint infections, the antibiotic treatment administered intraoperatively entails consequences on bacterial ecology with potential secondary effects. This study evaluates the rapid detection of methicillin-resistant staphylococci (MRS) by Xpert® technology directly on intraoperative samples. Xpert® technology was compared to conventional culture for 104 clinical specimens performed on 30 patients. The performance of the test expressed in terms of sensitivity, specificity, positive predictive value, and negative predictive value was, respectively, 87.1%, 100%, 100%, and 94.5% for the 104 specimens, and 92.3%, 100%, 100%, and 94.4% for the 30 patients. With the rapid detection of MRS, the use of vancomycin was limited for 17 of these 30 patients. In conclusion, this technique would allow the implementation of first-line antibiotic treatment adapted to the presence of MRS or not within approximately 1 h and would strongly reduce the use of broad-spectrum antibiotics.