Cerebrospinal Fluid Penetration of Vancomycin During Continuous Infusion Therapy in Patients With Nosocomial Ventriculitis.

BACKGROUND: This study aimed to evaluate the utility of a commercial kit used to measure serum vancomycin concentrations to determine vancomycin concentrations in cerebrospinal fluid (CSF) samples and evaluate CSF penetration when administered as a continuous high-dose infusion in patients with nosocomial ventriculitis. METHODS: This study included patients with external ventricular drain infection who were admitted to the intensive care unit between January 2018 and September 2020. After validation, CSF samples from 33 patients were collected. All patients received 30 mg/kg of vancomycin as a loading dose followed by 60 mg/kg as a maintenance dose in continuous infusion; all CSF samples were collected at least 48 hours after the first dose. RESULTS: Thirty-three patients were enrolled in this study. The median serum creatinine level was 0.66 mg/dL (0.5-0.92; n = 30), and median creatinine clearance was 119.2 mL/min (64.6-138.4; n = 13). The median serum vancomycin 24-hour area under the curve (AUC24h) was 838 mg*h/L (515-1010). The median CSF vancomycin concentration was 5.20 mg/L (1.95-12.4). Median serum vancomycin concentration was 34.9 mg/L (21.47-42.1), and median CSF/serum ratio was 18.6% (8.4-41.5). Acute renal injury occurred in 21% (n = 7) of the patients by the end of the therapy. In addition, the vancomycin CSF/serum ratio was positively correlated with the median serum creatinine level (r = 0.670; P = 0.004). CONCLUSIONS: Commercial vancomycin kits used to measure serum samples may be used to evaluate vancomycin concentrations in the CSF. Vancomycin penetration into CSF was 18.6%.

Complement system activation contributes to the ependymal damage induced by microbial neuraminidase.

BACKGROUND: In the rat brain, a single intracerebroventricular injection of neuraminidase from Clostridium perfringens induces ependymal detachment and death. This injury occurs before the infiltration of inflammatory blood cells; some reports implicate the complement system as a cause of these injuries. Here, we set out to test the role of complement. METHODS: The assembly of the complement membrane attack complex on the ependymal epithelium of rats injected with neuraminidase was analyzed by immunohistochemistry. Complement activation, triggered by neuraminidase, and the participation of different activation pathways were analyzed by Western blot. In vitro studies used primary cultures of ependymal cells and explants of the septal ventricular wall. In these models, ependymal cells were exposed to neuraminidase in the presence or absence of complement, and their viability was assessed by observing beating of cilia or by trypan blue staining. The role of complement in ependymal damage induced by neuraminidase was analyzed in vivo in two rat models of complement blockade: systemic inhibition of C5 by using a function blocking antibody and testing in C6-deficient rats. RESULTS: The complement membrane attack complex immunolocalized on the ependymal surface in rats injected intracerebroventricularly with neuraminidase. C3 activation fragments were found in serum and cerebrospinal fluid of rats treated with neuraminidase, suggesting that neuraminidase itself activates complement. In ventricular wall explants and isolated ependymal cells, treatment with neuraminidase alone induced ependymal cell death; however, the addition of complement caused increased cell death and disorganization of the ependymal epithelium. In rats treated with anti-C5 and in C6-deficient rats, intracerebroventricular injection of neuraminidase provoked reduced ependymal alterations compared to non-treated or control rats. Immunohistochemistry confirmed the absence of membrane attack complex on the ependymal surfaces of neuraminidase-exposed rats treated with anti-C5 or deficient in C6. CONCLUSIONS: These results demonstrate that the complement system contributes to ependymal damage and death caused by neuraminidase. However, neuraminidase alone can induce moderate ependymal damage without the aid of complement.

Riesgo de ventriculitis asociado a cuidados del drenaje ventricular externo en pacientes neurocríticos / Risk of ventriculitis associated to the care of the ventricular drain in neurocritical patients

Objetivo. Analizar el riesgo de ventriculitis asociada a los cuidados del drenaje ventricular externo. Sujetos y métodos. Estudio de casos y controles en una muestra de pacientes neurocríticos del Hospital Universitario Central de Asturias (España) portadores de drenaje ventricular externo (n = 127; 49 casos y 78 controles). Se consideraron casos (variable dependiente) los pacientes con diagnóstico médico de ventriculitis siguiendo criterios establecidos. Las variables independientes fueron los cuidados del drenaje ventricular, como curas de la zona de inserción, administración de medicación intratecal, lavados, movilización y recambio del drenaje. Se controló el efecto de variables confusoras: edad, sexo, escala APACHE y diagnóstico en el momento del ingreso, comorbilidad, antibioterapia, tiempo hasta la colocación del drenaje ventricular externo y tiempo de permanencia. Resultados. Las curas del drenaje (odds ratio: 3,8; intervalo de confianza al 95%, IC 95%: 1,1-13,9) y la administración de medicación intratecal (odds ratio: 7,1; IC 95%: 2,1-23,6) se asociaron significativamente con la ventriculitis. Cuando se ajusta adicionalmente por el tiempo de permanencia del catéter, el efecto de las curas (odds ratio: 1,4; IC 95%: 0,3-6,6) pierde importancia porque ambas variables están muy relacionadas. Conclusiones. La medicación intratecal y las curas parecen asociarse con ventriculitis. La administración de medicación por el drenaje realmente refleja que el médico sospecha la ventriculitis antes de su diagnóstico y, por esta razón, la prescribe. Sin embargo, como la duración del drenaje aumenta la frecuencia de curas, parece prudente recomendar no alargar el tiempo de drenaje y mejorar la capacitación de los profesionales de enfermería para realizar curas (AU)

Aim. To analyze the risk of ventriculitis associated to the care of the external ventricular drain. Subjects and methods. Case-control study among a sample of neurocritical patients of the University Hospital of Asturias (Spain) who carried a ventricular catheter (n = 127; 49 cases and 78 controls). Main outcome was the diagnosis of ventriculitus, according to established criteria. Independent variables were related to the catheter management, including nursing cares of the insertion point, administration of intrathecal medication, flushes, changes and mobilization of the catheter. Other variables (age, sex, APACHE score, admission diagnosis, comorbidity, antibiotics, time to insertion and permanence time of the drain) were studied as covariates. Results. Nursing catheter cares (OR 3.8; 95% CI: 1.1-13.9) and administration of intrathecal medication (OR: 7.1; 95% CI: 2.1-23.6) were significantly associated with ventriculitis. After adjustment by the number of days at risk, the effect of nursing cares disappeared (OR 1.4; 95% CI: 0.3-6.6). Conclusions. Intrathecal medication and nursing cares seem to be associated with ventriculitis. The administration of medication by the ventricular drain really reflects that the physicians suspect ventriculitis before the diagnosis is confirmed and, therefore, they prescribe this medication. However, as the duration of drain increases the frequency of nursing cares, it seems prudent to recommend not lengthen the permanence of the ventricular drain and to improve the training of nurses (AU)