Serum immune markers can be useful in the diagnosis of periprosthetic joint infection (PJI) by detecting long-lasting abnormal immunological conditions. The purpose of this study was to examine whether serum immune markers can improve the diagnostic accuracy of PJI.We enrolled 51 PJI, 45 aseptic loosening, and 334 osteoarthritis patients for assessment of the discriminatory accuracy of serum markers including white blood cell count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and D-dimer, total protein, albumin (Alb), globulin (Glb), neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, albumin-globulin ratio (AGR), CRP-albumin ratio (CAR), and CRP-AGR ratio (CAGR). These diagnostic accuracies for low-grade PJI were also calculated in patients who had serum CRP levels < 10 mg/L.Among serum markers, Alb, Glb, AGR, CRP, ESR, CAR, and CAGR had highly accurate diagnostic accuracy for PJI, with area under the curve of 0.92, 0.90, 0.96, 0.97, 0.92, 0.97, and 0.98, respectively. In low-grade PJI patients, area under the curve of CRP, ESR, CAR, and CAGR (0.69, 0.80, 0.65, and 0.82, respectively) was decreased but that of Alb, Glb, and AGR (0.90, 0.88, and 0.95, respectively) remained high, indicating the diagnostic utility of these immune markers. The sensitivity and specificity of AGR with cutoff value of 1.1 were demonstrated as 0.92 and 0.89, respectively, and with cutoff value of 1.2, 1.00, and 0.79, respectively, in the diagnosis of low-grade infection.Our results demonstrate the potential value of Alb, Glb, AGR, and combination indices of these immune makers with CRP in improving preoperative serum diagnosis for PJI, especially in low-grade PJI.Diagnostic- Level II. 

Evaluation of Serum Albumin and Globulin in Combination with C-Reactive Protein Improves Serum Diagnostic Accuracy for Low-Grade Periprosthetic Joint Infection.

Antibacterial activity of silver doped hydroxyapatite toward multidrug-resistant clinical isolates of Acinetobacter baumannii.

Background Biofilms protect bacteria from the host immune system and many antibiotics, making the treatment of orthopaedic infections difficult. Halicin, a recently discovered antibiotic, has potent activity against nonorthopaedic infections in mice and the planktonic, free-living forms of many bacterial species, including Staphylococcus aureus, a common cause of orthopaedic infections. Importantly, halicin did not induce resistance in vitro and was effective against drug-resistant bacteria and proliferating and quiescent bacteria. Quiescence is an important cause of antibiotic tolerance in biofilms. However, whether halicin acts on biofilms has not been tested. Questions/purposes (1) Does halicin reduce the viability of S. aureus in less mature and more mature biofilms as it does in planktonic cultures? (2) How do the relative effects of halicin on S. aureus biofilms and planktonic cultures compare with those of conventional antibiotics (tobramycin, cefazolin, vancomycin, or rifampicin) that are commonly used in clinical orthopaedic infections? Methods To measure minimal biofilm eradication concentrations (MBECs) with less mature 3-day and more mature 7-day biofilms, we used 96-well peg plates that provided high throughput and excellent reproducibility. After S. aureus-Xen36 biofilm formation, planktonic bacteria were removed from the cultures, and the biofilms were exposed to various concentrations of halicin, tobramycin, cefazolin, vancomycin, or rifampicin for 20 hours. Biofilm viability was determined by measuring resazurin reduction or by counting colony-forming units after sonication. To determine effects of halicin and the conventional antibiotics on biofilm viability, we defined MBEC75 as the lowest concentration that decreased viability by 75% or more. To determine effects on bacterial viability in planktonic cultures, minimum inhibitory concentrations (MICs) were determined with the broth dilution method. Each result was measured in four to 10 independent experiments. Results We found no differences between halicin’s effectiveness against planktonic S. aureus and 3-day biofilms (MIC and MBEC75 for 3-day biofilms was 25 μM [interquartile range 25 to 25 and 25 to 25, respectively]; p > 0.99). Halicin was eightfold less effective against more mature 7-day biofilms (MBEC75 = 200 μM [100 to 200]; p < 0.001). Similarly, tobramycin was equally effective against planktonic culture and 3-day biofilms (MIC and MBEC75 for 3-day biofilms was 20 μM [20 to 20 and 10 to 20, respectively]; p > 0.99). Tobramycin’s MBEC75 against more mature 7-day biofilms was 320 μM (320 to 480), which is 16-fold greater than its planktonic MIC (p = 0.03). In contrast, the MBEC75 for cefazolin, vancomycin, and rifampicin against more mature 7-day biofilms were more than 1000-fold (> 1000; p < 0.001), 500-fold (500 to 875; p < 0.001), and 3125-fold (3125 to 5469; p = 0.004) greater than their planktonic MICs, respectively, consistent with those antibiotics’ relative inactivity against biofilms. Conclusion Halicin was as effective against S. aureus in less mature 3-day biofilms as those in planktonic cultures, but eightfold higher concentrations were needed for more mature 7-day biofilms. Tobramycin, an antibiotic whose effectiveness depends on biofilm maturity, was also as effective against S. aureus in less mature 3-day biofilms as those in planktonic cultures, but 16-fold higher concentrations were needed for more mature 7-day biofilms. In contrast, cefazolin, vancomycin, and rifampicin were substantially less active against both less and more mature biofilms than against planktonic cultures. Clinical Relevance Halicin is a promising antibiotic that may be effective against S. aureus osteomyelitis and infections on orthopaedic implants. Future studies should assess the translational value of halicin by testing its effects in animal models of orthopaedic infections; on the biofilms of other bacterial species, including multidrug-resistant bacteria; and in combination therapy with conventional antibiotics. 

Halicin Is Effective Against Staphylococcus aureus Biofilms In Vitro

Hydroxyapatite (HA)-based materials are widely used in the bone defect restoration field due to their stable physical properties, good biocompatibility, and bone induction potential. To further improve their performance with extra functions such as antibacterial activity, various kinds of metal ion-doped HA-based materials have been proposed and synthesized. This paper offered a comprehensive review of metal ion-doped HA-based materials for bone defect restoration based on the introduction of the physicochemical characteristics of HA followed by the synthesis methods, properties, and applications of different kinds of metal ion (Ag+, Zn2+, Mg2+, Sr2+, Sm3+, and Ce3+)-doped HA-based materials. In addition, the underlying challenges for bone defect restoration using these materials and potential solutions were discussed.

Metal Ion-Doped Hydroxyapatite-Based Materials for Bone Defect Restoration

The superiority of immune-inflammation summary index for diagnosing periprosthetic joint infection.

Bacterial infections routinely cause inflammation and thereby impair osseointegration of orthopedic implants. Acinetobacter spp., which cause osteomyelitis following trauma, on or off the battlefield, were, however, reported to cause neither osteomyelitis nor osteolysis in rodents. We therefore compared the effects of Acinetobacter strain M2 to those of Staphylococcus aureus in a murine implant infection model. Sterile implants and implants with adherent bacteria were inserted in the femur of mice. ABSTRACT Bacterial infections routinely cause inflammation and thereby impair osseointegration of orthopedic implants. Acinetobacter spp., which cause osteomyelitis following trauma, on or off the battlefield, were, however, reported to cause neither osteomyelitis nor osteolysis in rodents. We therefore compared the effects of Acinetobacter strain M2 to those of Staphylococcus aureus in a murine implant infection model. Sterile implants and implants with adherent bacteria were inserted in the femur of mice. Bacterial burden, levels of proinflammatory cytokines, and osseointegration were measured. All infections were localized to the implant site. Infection with either S. aureus or Acinetobacter strain M2 increased the levels of proinflammatory cytokines and the chemokine CCL2 in the surrounding femurs, inhibited bone formation around the implant, and caused loss of the surrounding cortical bone, leading to decreases in both histomorphometric and biomechanical measures of osseointegration. Genetic deletion of TLR2 and TLR4 from the mice partially reduced the effects of Acinetobacter strain M2 on osseointegration but did not alter the effects of S. aureus. This is the first report that Acinetobacter spp. impair osseointegration of orthopedic implants in mice, and the murine model developed for this study will be useful for future efforts to clarify the mechanism of implant failure due to Acinetobacter spp. and to assess novel diagnostic tools or therapeutic agents.

Staphylococcus aureus and Acinetobacter baumannii Inhibit Osseointegration of Orthopedic Implants

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Staphylococcus aureus and Acinetobacter baumannii Inhibit Osseointegration of Orthopedic Implants