Background: The sensitive and accurate diagnosis of nosocomial meningitis and ventriculitis is still a critical problem. This study was designed to explore the diagnostic value of cerebrospinal fluid heparin-binding protein (HBP) in nosocomial meningitis and ventriculitis in comparison with procalcitonin and lactate. Methods: In this observational study, 323 suspected patients were enrolled, of which 42 participants were excluded because they could not be accurately grouped, 131 subjects who were eventually diagnosed with nosocomial meningitis or ventriculitis and 150 patients in whom infection was ultimately ruled out were included in the final analysis. The main results are expressed as medians (interquartile ranges). The Chi-squared test was used to compare the baseline characteristics. The Mann–Whitney U-test was used for group and subgroup analyses. The area under the receiver operating characteristic curve was calculated to describe the diagnostic accuracy of the biomarkers. Spearman's partial correlation was used to analyze associations between the biomarkers. Statistical significance was set when p value < 0.05. Results: HBP achieved the largest area under the receiver operating characteristic curve, which was 0.99 (95% confidence interval 0.98—1.00) compared with 0.98 (95% confidence interval 0.96—0.99) for lactate and 0.69 (95% confidence interval 0.62—0.75) for procalcitonin. With a cutoff level at 23 ng/mL, HBP achieved a sensitivity of 97%, a specificity of 95%, a positive predictive value of 93% and a negative predictive value of 98%. The levels of HBP presented no significant discrepancy between patients who received previous empiric anti-infective therapy and those who did not (p > 0.05). Higher concentrations of HBP were present in patients with positive microbiological findings (p < 0.05). Levels of HBP positively correlated with polymorphonuclear cell count (Spearman's rho = 0.68, p < 0.01), white blood cell count (Spearman's rho = 0.57, p < 0.01) and lactate (Spearman's rho = 0.34, p < 0.01). Conclusions: Cerebrospinal fluid heparin-binding protein is a reliable auxiliary diagnostic marker that is preferable over lactate and procalcitonin in identifying nosocomial meningitis and ventriculitis, and it also contributes to solving the diagnostic difficulties caused by empiric antibiotherapy.

Carbapenem-resistant Gram-negative bacteria-related health care-associated ventriculitis and meningitis is a clinical threat because of the poor outcome and challenges in treatment. We reached several conclusions: (i) the antimicrobial resistance of pathogens is severe, and some antimicrobial agents represented by polymyxin are optional according to the antimicrobial susceptibility tests; (ii) in the background that the portion of carbapenems resistance in Gram-negative bacteria is increasing, there is no increasing trend for the antimicrobial resistance of carbapenem-resistant Gram-negative bacteria in the 9-year study; (iii) meropenem is the main antimicrobial agent in treatment, and trimethoprim-sulfamethoxazole, tigecycline, polymyxin, and meropenem/sulbactam are commonly used in the targeted treatment; (iv) the treatment effect was poor and affected by the treatment: timely active antimicrobial agents should be given.

Glucocorticoids (GCs) have been widely used in the treatment of severe traumatic brain injury (TBI) to inhibit neuroinflammation and alleviating brain edema and cannot be replaced by other drugs. However, their systemic application still faces many obstacles, such as the poor blood-brain-barrier (BBB) penetration and severe side effects. Therefore, new treatment strategy or compounds are urgently needed in clinic. Herein, an injectable nanocomposite hydrogel is developed as a biofunctionalized delivery platform for intraoperative administration of dexamethasone (DEX) after TBI. By using a mice TBI model, the safety and efficacy of the nanohydrogels in treating BBB disruption, brain edema and nerve injury were evaluated after TBI. The hydrogel is composed of polysaccharide matrix (carboxymethyl chitosan and oxidized dextran) and mesoporous polydopamine (MPDA) nanoparticles loaded with DEX (MPDA@DEX@gel) that could realize in situ injection, self-assembly, a high DEX loading rate and sustained release around the lesion. The MPDA@DEX@gel exhibits excellent antibacterial and hemostatic properties, good biocompatibility and antioxidation, and self-healing capability in vitro. These in vitro and in vivo results show that local application of MPDA@DEX@gel not only alleviates brain edema, promotes neuronal survival, and improves neurological function by restoring the integrity of BBB and inhibiting neuroinflammation after TBI, but also effectively avoids the peripheral and central side effects. Our study provides a promising treatment strategy for the rational use of GCs in patients with severe TBI.

Coagulase-negative staphylococci are the main pathogens in health care-associated ventriculitis and meningitis. There are three conclusions from the results of this study.