Staphylococcus aureus (S. aureus) is one of the most common causes of biofilm infections in periprosthetic joint infections (PJIs). Accumulating evidence has shown that the immunosuppressive environment established by S. aureus biofilm infection in PJIs involves the presence of myeloid-derived suppressor cells (MDSCs) and M2-macrophages. Due to the diversity of MDSCs, little is known about whether S. aureus biofilm preferentially expands specific MDSC subsets or whether MDSCs can further differentiate into M2-macrophages during S. aureus biofilm infection. Here, we show that in agreement with the results from an established rat PJI model, S. aureus biofilm cocultured with freshly isolated bone marrow cells (BMCs) in vitro significantly increases the proportions of MDSCs, total macrophages and M2-macrophages. Interestingly, we find that treatment of the BMCs in vitro with S. aureus biofilm preferentially promotes the expansion of monocytic MDSCs but not granulocytic MDSCs. Biofilm treatment also substantially enhances the overall MDSC immunosuppressive activity in addition to the MDSC expansion in vitro. Importantly, we provide evidence that S. aureus biofilm is capable of further stimulating the conversion of monocytic MDSCs into M2-macrophages in vitro and in vivo. Collectively, our studies reveal a direct link between MDSCs and M2-macrophages occurring in S. aureus-associated PJIs.

Background: Periprosthetic joint infections (PJIs) have a high incidence of recurrence after total joint replacement and are difficult to treat by debridement or antibiotic treatment. Curcumin is a natural product with anti-inflammatory and anti-bacterial properties. The low bioactivity of curcumin in water restricts its clinical application. Curcumin nanoparticles (CURN) were developed to overcome this limitation. Methods: In this study, the therapeutic effects of CURN and their anti-inflammatory functions were investigated in a Staphylococcus aureus biofilm-induced PJIs model. Results: CURN first attenuated the biofilm-induced expansion of myeloid-derived suppressor cells (MDSCs) and then regulated M1- and M2-phenotypic MDSC expression. Down-regulation of cytokines and reactive oxygen species was considered as the mechanism of CURN in reversing the suppression of T cell proliferation. The recovery of bone permeative destruction demonstrated that CURN enhanced therapeutic potency of vancomycin in vivo. Conclusion: This is the first study to demonstrate that CURN may be useful for treating PJIs.

Background: Biomarkers, such as leukocyte count, C-reactive protein (CRP), and procalcitonin (PCT), have been commonly used to predict the occurrence of life-threatening bacteremia and provide prognostic information, given the need for prompt intervention. However, such diagnosis methods require much time and money. Therefore, we propose a method with a high prediction capability using machine learning (ML) models based on complete blood count (CBC) and differential leukocyte count (DC) and compare its performance with traditional CRP or PCT biomarker methods and those of models incorporating CRP or PCT biomarkers. Methods: We collected 366,586 daily blood culture (BC) results, of which 350,775 (93.2%), 308,803 (82.1%), and 23,912 (6.4%) cases were issued CBC/DC (CBC/DC group), CRP with CBC/DC (CRP&CBC/DC group), and PCT with CBC/DC (PCT&CBC/DC group), respectively. For the ML methods, conventional logistic regression and random forest models were selected, trained, applied, and validated for each group. Fivefold validation and prediction capability were also evaluated and reported. Results: Overall, the ML methods, such as the random forest model, demonstrated promising performances. When trained with CBC/DC data, it achieved an area under the ROC curve (AUC) of 0.802, which is superior to the prediction conventionally made with CRP/PCT levels (0.699/0.731). Upon evaluating the performance enhanced by incorporating CRP or PCT biomarkers, it reported no substantial AUC increase with the addition of either CRP or PCT to CBC/DC data, which suggests the predicting power and applicability of using only CBC/DC data. Moreover, it showed competitive prognostic capability compared to the PCT test with similar all-cause in-hospital mortality (45.10% vs. 47.40%) and overall median survival time (27 vs. 25 days). Conclusions: The ML models using only CBC/DC data yielded more accurate bacteremia predictions compared to those by methods using CRP and PCT data and reached similar prognostic performance as by PCT data. Thus, such models are potentially complementary and competitive with traditional CRP and PCT biomarkers for conducting and guiding antibiotic usage.

Background: Vibrio vulnificus has been reported as the leading causative pathogen of necrotizing fasciitis (NF) and related fatality in the coastal area. Necrotizing fasciitis caused by methicillin-resistant Staphylococcus aureus (MRSA) and V. vulnificus have high mortality rates. The purpose of this prospective study was to clarify the clinical characteristics between death and survival NF patients, to investigate bacteriologic profile and mortality of NF patients, and to compare risk indicators of MRSA and V. vulnificus NF patients. Methods: This prospective study was conducted in 184 consecutive NF patients over a period of three years in a tertiary coastal hospital. Differences in mortality, laboratory findings, microbiology and clinical outcomes were compared between the death and survival groups, and the V. vulnificus and MRSA subgroups. Results: Twenty patients died, resulting in a mortality rate of 10.9%, and there were 108 patients with a monomicrobial infection (58.7%). The death group had a significantly higher incidence of shock at emergency room and bacteremia than did the survival group. Vibrio species (40 cases) and S. aureus (31 cases) were the two major pathogens. Significant differences with respect to hepatic dysfunction, shock, the event with seawater or seafood contact, bacteremia, C-reactive protein, mean platelet counts, and the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score were observes between V. vulnificus and MRSA groups. Conclusions: NF patients with both hepatic dysfunction and diabetes mellitus, bacteremia and shock have significantly higher mortality. We should be aware of the increasing incidence of monomicrobial NF and higher mortality rates of Gram-negative pathogens in the warm coastal area. LRINEC score is not a suitable diagnostic indicator for V. vulnificus NF, which is more rapidly progressive and fulminant than MRSA NF. NF needed team works by early suspicion, immediate surgical intervention and aggressive care, which can successfully decrease mortality.

Necrotizing fasciitis (NF) of the limbs caused by Aeromonas species is an extremely rare and life-threatening skin and soft tissue infection. The purpose of this study was to evaluate the specific characteristics and the independent predictors of mortality in patients with Aeromonas NF. Sixty-eight patients were retrospectively reviewed over an 18-year period. Differences in mortality, demographics data, comorbidities, symptoms and signs, laboratory findings, microbiological analysis, empiric antibiotics treatment and clinical outcomes were compared between the non-survival and the survival groups. Twenty patients died with the mortality rate of 29.4%. The non-survival group revealed significant differences in bacteremia, monomicrobial infection, cephalosporins resistance, initial ineffective empiric antibiotics usage, chronic kidney disease, chronic hepatic dysfunction, tachypnea, shock, hemorrhagic bullae, skin necrosis, leukopenia, band polymorphonuclear neutrophils >10%, anemia, and thrombocytopenia. The multivariate analysis identified four variables predicting mortality: bloodstream infection, shock, skin necrosis, and initial ineffective empirical antimicrobial usage against Aeromonas. NF caused by Aeromonas spp. revealed high mortality rates, even through aggressive surgical debridement and antibacterial therapies. Identifying those independent predictors, such as bacteremia, shock, progressive skin necrosis, monomicrobial infection, and application of the effective antimicrobial agents against Aeromonas under the supervision of infectious doctors, may improve clinical outcomes.