Early after injury, local tissue damage induces a local and systemic inflammatory response that activates the immune system and leads to the development of systemic inflammatory response syndrome (SIRS). This post-traumatic response often results in uncontrolled release of inflammatory mediators and over-activation of the immune system, which occasionally results in multiple organ dysfunction syndrome (MODS). In parallel, a state of immunosuppression develops. This counter-regulating suppression of different cellular and humoral immune functions has been termed “compensatory anti-inflammatory response syndrome (CARS).” Both SIRS and CARS occur simultaneously even in the initial phase after injury. Pro- and anti-inflammatory cytokines have been suggested to play a major role in development of SIRS, although the degree of involvement of the different cytokines is quite disparate. While TNF-α and IL-1β are quite irrelevant for predicting organ dysfunction, IL-6 is the parameter that best predicts mortality. The hyperinflammatory state seems to be the cause of post-traumatic immunosuppression and heat shock proteins (HSPs), which have been proposed as one of the endogenous stimuli for the deterioration of the immune system acting as danger-associated molecular patterns (DAMPs). Extracellular HSPA1A released from injured tissues increase up to ten times immediately after trauma and even more in patients with MODS. It has powerful immune properties that could contribute to post-traumatic immunosuppression through several mechanisms that have been previously described, so HSPs could represent trauma-associated immunomodulatory mediators. For this reason, HSPA1A has been suggested to be a helpful early prognostic biomarker of trauma after severe injury: serial quantification of serum HSPA1A and anti-Hsp70 concentrations in the first hours after trauma is proposed to be used as a predictive biomarker of MODS and immunosuppression development in polytraumatized patients.

Irrigation and debridement using an irrigation solution is a fundamental step during the surgical treatment of both acute and chronic periprosthetic joint infection (PJI). However, there is no consensus on the optimal solution, nor is there sufficient evidence on the optimal irrigation time and combination of solutions. Therefore, it is necessary to determine which solution or combination of solutions is most efficacious against biofilm, as well as the optimal irrigation time. We conducted an experimental in vitro model by inoculating stainless steel discs with ATCC strains of methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, Pseudomonas aeruginosa, and a clinical strain of Staphylococcus epidermidis. The discs were all irrigated with commonly used antiseptic solutions (10% and 3% povidone iodine, hydrogen peroxide, 3% acetic acid, and Bactisure™) for 1 min, 3 min, and 5 min and their combinations for 9 min (3 min each) vs. sterile saline as a positive control. We evaluated the reduction in biofilm based on colony-forming unit (cfu) counts and in combination assays, also based on cell viability and scanning electron microscopy. All antiseptics alone reduced more than 90% of cfu counts after 1 min of irrigation; the worst results were for hydrogen peroxide and 3% acetic acid. When solutions were sequentially combined, the best results were observed for all those starting with acetic acid, in terms of both reduction of log cfu/mL counts and viable cells. We consider that a combination of antiseptic solutions, particularly that comprising the sequence acetic acid + povidone iodine + hydrogen peroxide, would be the best option for chemical debridement during PJI surgery.

Antibiotic-loaded bone cement is the most widely used approach for the treatment of biofilm-induced septic sequelae in orthopedic surgery. Dalbavancin is a lipoglycopeptide that acts against Gram-positive bacteria and has a long half-life, so we aimed to assess whether it could be a new alternative drug in antibiotic-loaded bone cement for the treatment of periprosthetic joint infections. We assessed the elution capacity of dalbavancin and compared it with that of vancomycin in bone cement. Palacos^®R (Heraeus Medical GmbH, Wehrheim, Germany) bone cement was manually mixed with each of the antibiotics studied at 2.5% and 5%. Three cylinders were obtained from each of the mixtures; these were weighed and incubated in 5 mL phosphate-buffered saline at 37°C under shaking for 1 h, 2 h, 4 h, 8 h, 24 h, 48 h, 168 h, and 336 h. PBS was replenished at each time point. The samples were analyzed using high-performance liquid chromatography (vancomycin) and mass cytometry (dalbavancin). Elution was higher than the minimum inhibitory concentration (MIC)90 for both antibiotics after 14 days of study. The release of vancomycin at 14 days was higher than of dalbavancin at each concentration tested (p = 0.05, both). However, the cumulative release of 5% dalbavancin was similar to that of 2.5% vancomycin (p = 0.513). The elution capacity of dalbavancin reached a cumulative concentration similar to that of vancomycin. Moreover, considering that the MIC90 of dalbavancin is one third that of vancomycin (0.06 mg/L and 2 mg/L, respectively) and given the long half-life of dalbavancin, it may be a new alternative for the treatment of biofilm-related periprosthetic infections when loaded in bone cement.