Since early diagnosis of sepsis may assist clinicians in initiating timely, effective, and prognosis-improving antibiotic therapy, we developed an integrated microfluidic chip (IMC) for rapid isolation of both Gram-positive and Gram-negative bacteria from blood. The device comprised a membrane-based filtration module (90 min operating time), a bacteria-capturing module using a micro-mixer containing magnetic beads coated with “flexible neck” regions of mannose-binding lectin proteins for bacteria capture (20 min), and a miniature polymerase chain reaction (PCR) module for bacteria identification (90 min via TaqMan® probe technology). The filter separated all white blood cells and 99.5% of red blood cells from bacteria, which were captured at rates approaching 85%. The PCR assay's limit of detection was 5 colony-forming units (CFU) per reaction, and the entire process was completed in only 4 h. Since this is far less than that for culture-based approaches, this IMC may serve as a promising device for detection of sepsis.

Two-stage reimplantation arthroplasty is one of the standard treatments for chronic periprosthetic joint infection (PJI). Scanty data exist regarding the risk factors for failure after two-stage reimplantation for periprosthetic hip infection. The purpose of this study was to investigate and identify the risk factors associated with failure after two-stage reimplantation hip arthroplasty. Sixty-two patients with hip PJI treated with a two-stage reimplantation protocol at our institution from 2005 to 2012 were reviewed. Patients requiring medical treatment or reoperation for recurrent infection were defined as treatment failure. A multivariate Cox proportional hazards model was used to analyze the risk factors associated with treatment failure. Of the 62 patients, 11 (17.7%) patients had developed reinfection after the two-stage reimplantation with a mean follow-up of 5.7 years. The implant survival was 82.2% (95% confidence interval [CI] 75.19−92.55) at 10 years. Multivariate analysis revealed BMI ≥30 kg/m2 (hazard ratio [HR] 9.16; 95% CI 1.51−55.3; p = 0.0158), liver cirrhosis (HR 6.39; 95% CI 1.09−37.4; p = 0.0398), gram-negative organism (HR 5.68; 95% CI 1.18−27.4; p = 0.0303), and presence of sinus tract (HR 18.2; 95% CI 2.15−153; p = 0.0077) as the independent risk factors for treatment failure. We found obesity, liver cirrhosis, gram-negative organism, and the presence of sinus tract were significantly related to the risks of failure after reimplantation arthroplasties.

Polypharmacy is routinely administered to fight severe infections, though it has led to rampant multi-drug resistance in many bacterial strains. Preferably, antimicrobial susceptibility testing (AST) would be carried out prior to antibiotic prescription, though it is generally thought to be too complex and labor-intensive. In order to assist clinicians with better antibiotic administration for the effective treatment of bacterial infections, an integrated microfluidic system (IMS) capable of automating AST for 1–2 antibiotics against clinical bacterial pathogens was developed herein. Accurate determination of the minimum and fractional inhibitory concentrations of vancomycin, gentamicin, and linezolid were determined by assaying growth of two clinical methicillin-resistant Staphylococcus aureus isolates via a colorimetric assay on-chip. By applying various antibiotic combinations against a single pathogen in multiple chambers, the IMS could identify the optimal drug combination and the minimum effective dosage by evaluating the fractional inhibitory concentration index. This IMS possessed several advantages over conventional methods, including (1) a 50% reduction in bacterial sample and reagent volume (<50 μL per well), (2) less potential for human error due to its automatic nature, (3) faster liquid manipulation time by integrating the microfluidic components rather than labor-intensive process, and (4) straightforward result interpretation via colorimetric change instead of turbidity degree. Personalized medicine for treatment of bacterial infections may therefore be realized using this IMS.

Background: The diagnosis of periprosthetic joint infection (PJI) in the early postoperative period remains a challenge. Although studies have established that serum C-reactive protein (CRP) and synovial markers may be useful, recent studies have suggested that the current thresholds used may lack sensitivity. The purpose of this study was to examine the role of serum CRP, erythrocyte sedimentation rate (ESR), synovial fluid white blood-cell (WBC) count, and polymorphonuclear neutrophil (PMN) percentage in the diagnosis of acute postoperative PJI and to identify the optimal threshold. Methods: This multicenter study included patients who were investigated for possible PJI within 90 days of an index arthroplasty. This study included 197 patients from 4 institutions who underwent total joint arthroplasty from 2000 to 2017. Of these patients, 123 were confirmed to have PJI, and 74 were ruled out as not having PJI (non-infected group). Analyses of receiver operating characteristic (ROC) curves and the area under the curve were performed to determine the value of each test and optimal cutoff values. Results: The optimal cutoff value was 6,130 cells/μL for synovial fluid WBC count (91% sensitivity and 83% specificity), 39.8 mg/L for serum CRP (91% sensitivity and 87% specificity), 39.5 mm/hr for ESR (76% sensitivity and 67% specificity), and 79.5% for PMN percentage (95% sensitivity and 59% specificity). Reducing the acute period from 90 days to 30 days or 45 days made little difference in most threshold values. However, the optimal cutoff for synovial fluid WBC count was almost twice as high (10,170 cells/μL) when using a 30-day definition instead of a 90-day definition. Conclusions: The calculated cutoffs in our study were substantially lower than the thresholds used by the Musculoskeletal Infection Society. The calculated values of this study should be used, as previous cutoffs may be too high and lack sensitivity. In addition, it appears that the threshold values, at least for some of the tests, change as the duration since the index arthroplasty lengthens. A continuum of threshold values that is dependent on the number of days since the index arthroplasty may need to be used for the diagnosis of acute PJI. Level of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.