Cerebrospinal Fluid Vancomycin Research Articles

The CSF Vancomycin Concentration in Patients With Post-operative Intracranial Infection Can Be Predicted by the WBCs to Total Cells Ratio and the Serum Trough Concentration.

BackgroundThe pharmacokinetics of vancomycin in cerebrospinal fluid (CSF) is an important basis for evaluating the bactericidal effect. The accuracy of using serum vancomycin concentrations only to estimate the CSF concentrations remains controversial, may lead to underdosing.ObjectivesThe aims of this study were to evaluate the vancomycin exposure in CSF, investigate the factors affecting the vancomycin blood–brain barrier (BBB) penetration, and to establish the prediction model of vancomycin concentration in CSF.MethodsEligible patients were included and given a standard dose of vancomycin. At the fifth dose, the blood and CSF samples were collected 0.5 h before the start of infusion of vancomycin, and 1, 2, 3, and 8 h from the start of infusion, and were measured by the enzyme-multiplied immunoassay technique using the Siemens Viva-E Drug Testing System.ResultsThe AUCCSF/serum of patients with intracranial infection was higher than that of patients without (p = 0.001). The CSF concentration was relatively stable between dosing periods (p = 0.095). The area under the concentration–time curve (AUC) ratio of CSF to serum (AUCCSF/serum) in patients with intracranial infection ranged from 15.1 to 80.1% (33.23 ± 19.31%; median, 26.25%). The CSF vancomycin AUC levels were affected by the serum trough concentration (B: 5.23 ± 2.36, t = 2.22, p = 0.039), and were mainly affected by the CSF white blood cells (WBCs)/total cells (B: 113.96 ± 35.10, t = 3.25, p = 0.004) (Y = −17.86 + 5.23 × serum trough concentration + 113.96 × CSF [WBCs/total cells]; R2 = 0.473, F = 8.542, p = 0.002).ConclusionsAfter intravenous administration of vancomycin, the CSF concentration curve was fluctuated gently. The CSF vancomycin concentration in patients with postoperative intracranial infection can be predicted by the WBCs to total cells ratio and the serum trough concentration, and help to adjust the administration of vancomycin.

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

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. 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. 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). 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%.

Exploration of Vancomycin Concentrations in Cerebrospinal Fluid and Plasma after Craniocerebral Surgery

Patients who underwent cranial hematoma removal, extra-ventricular drainage, intracranial arteriovenous malformation resection, and other craniotomy procedures and were administered vancomycin were selected. Cerebrospinal fluid (CSF) and plasma specimens were collected simultaneously from patients at different time points using the random number method, and vancomycin concentrations in CSF and plasma were determined by enzyme amplification immunoassay. The ratio of vancomycin in CSF to plasma concentration was calculated, and the medical records were analyzed to initially investigate the relevant factors that can affect the drug concentration or blood-brain barrier. The mean plasma concentration of vancomycin was 11.87±8.5μg/mL, the CSF concentration was 2.42±1.34μg/mL, and the cerebral blood ratio was 0.28±0.21. This study suggests that the transmission rate of vancomycin did not increase significantly after craniocerebral surgery; due to individual differences, CSF and plasma concentrations vary greatly, and drug concentration monitoring is recommended.

Population Pharmacokinetics of Intraventricular Vancomycin in Neonatal Ventriculitis, A Preterm Pilot Study

AimIntraventricular vancomycin is an effective treatment for neonatal ventriculitis, as the cerebrospinal fluid (CSF) vancomycin levels reach adequate concentrations to achieve microbiological cure. There is no robust data on intraventricular vancomycin pharmacokinetics in the preterm population. This pilot population pharmacokinetic modelling study examines the pharmacokinetic behaviour of intraventricular vancomycin in the preterm population of < 28 weeks gestation, to inform the feasibility of future prospective studies. MethodsThe study comprised 8 preterm infants with neonatal ventriculitis (median gestation age 25.3 weeks; range 23.9 - 27.7). Population pharmacokinetics (non-linear mixed effects modelling) were described with one- and two-compartment models to fit plasma concentrations of vancomycin. A CSF compartment was added to the plasma modelling and mass transfer examined. Three covariates (serum creatinine, ventricular index (VI) and CSF protein) were tested on the final model. Area under the curve (AUC) and average CSF concentration (C average) predictions were generated from the final model and compared with time to microbiological cure. ResultsA one-compartment model provided the best fit to the data. There was no appreciable transfer between plasma and CSF. None of the covariates provided a significant reduction in the objective function value (OFV). Generally, time to sterilisation with higher CSF AUC (0-24) and C average tends to be shorter, however this should be interpreted with caution as data is erratic. ConclusionThis pilot population pharmacokinetic analysis provides important information to warrant changes in the management of intraventricular vancomycin treatment in the preterm population, such as the current use of VI as a dosing parameter. Further study with a larger data pool is necessary to investigate the influence of VI on CSF vancomycin and ascertain dosing strategies.

Therapeutic monitoring of cerebrospinal fluid vancomycin concentrations and analysis of their influencing factors in neurosurgical intensive care unit patients

To evaluate cerebrospinal fluid (CSF) vancomycin concentrations and identify factors influencing CSF vancomycin concentrations in critically ill neurosurgical patients. A retrospective study was conducted. Adult patients who received vancomycin treatment and CSF vancomycin concentrations monitoring admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from January 2016 to June 2019 were enrolled. General information, vancomycin dosing regimens, CSF vancomycin concentrations, CSF drainage methods and volume of the previous day, and concurrent medications, etc. were collected for analysis. CSF vancomycin concentrations of patients with definite or indefinite central nervous system (CNS) infection, different vancomycin dosing regimens and their influencing factors were analyzed. A total of 22 patients were included. 168 CSF specimens were collected for culture, 20 specimens of which were culture positive, with a positive rate of 11.9%. Sixty cases of CSF vancomycin concentration were obtained. Among the 22 patients, 7 patients (31.8%) were diagnosed with proven CNS infection, 11 patients (50.0%) clinically diagnosed, 2 patients (9.1%) diagnosed with uncertain CNS infection, and 2 patients (9.1%) diagnosed without CNS infection. Intravenous (IV) administration of vancomycin alone was used in 15 cases (25.0%), intrathecal injection in 17 cases (28.3%), IV+intrathecal injection in 23 cases (38.3%), and IV+intraventricular administration in 5 cases (8.3%). The CSF vancomycin concentrations ranged from < 0.24 to > 100 mg/L, with an average level of 14.40 (4.79, 42.34) mg/L. (1) Administration methods of vancomycin affected CSF vancomycin concentrations. The CSF vancomycin concentration with intrathecal injection or intraventricular administration was higher than that of IV administration alone [mg/L: 25.91 (11.28, 58.17) vs. 2.71 (0.54, 5.33), U = 42.000, P < 0.01]. (2) When vancomycin was administered by IV treatment alone, CSF vancomycin concentrations were low in both groups with definite CNS infection (proven+probable) and indefinite CNS infection (possible+non-infection), the CSF vancomycin concentrations of which were 4.14 (1.40, 6.36) mg/L and 1.27 (0.24, 3.33) mg/L respectively, with no significant difference (U = 11.000, P = 0.086). (3) CSF vancomycin concentrations rose with the increased dose of vancomycin delivered by intrathecal injection or intraventricular administration. According to the dose of vancomycin administered locally on the day before therapeutic drug monitoring (TDM), cases were divided into the following groups: 0-15 mg group (n = 22), 20-35 mg group (n = 33), and 40-50 mg group (n = 5), the CSF vancomycin concentrations of which were 4.14 (1.09, 8.45), 30.52 (14.31, 59.61) and 59.43 (25.51, 92.45) mg/L respectively, with significant difference (H = 33.399, P < 0.01). Moreover, the cases of CSF vancomycin concentration of ≥ 10 mg/L accounted for 18.2%, 84.8% and 100% of these three groups, respectively. CSF vancomycin concentrations mostly reached target level when dose of vancomycin administered locally were 20 mg/L or more. It is difficult to reach target CSF vancomycin concentration for critically ill neurosurgical patients with or without CNS infection by IV treatment. Local administration is an effective treatment regimen to increase CSF vancomycin concentration.

Correlation between vancomycin penetration into cerebrospinal fluid and protein concentration in cerebrospinal fluid/serum albumin ratio.

Bacterial meningitis is a life-threatening condition. Vancomycin (VCM) is one of the antibiotics used as empirical therapy for bacterial meningitis. It is essential to maintain an adequate concentration of VCM in cerebrospinal fluid (CSF) to treat bacterial meningitis effectively. VCM administered intravenously must pass the blood-brain barrier (BBB) to enter the CSF and the extent of VCM penetration into CSF varies widely among patients. Previous report indicated that CSF albumin level is useful for estimation of VCM CSF penetration. However, CSF albumin level is not measured in routine practice. We focused on CSF protein concentration that is generally examined at the beginning of diagnosis and treatment of bacterial meningitis. We examined the relationship between CSF protein concentration/serum albumin ratio and the extent of VCM penetration into CSF. This retrospective study involved 7 patients admitted to our hospital who were treated with VCM for suspected bacterial meningitis. The VCM concentrations in serum and CSF were 17.6±7.2μg/mL and 3.31±3.14μg/mL, respectively. The serum VCM concentrations showed no significant correlation with CSF VCM concentrations. On the other hand, the protein concentration in CSF/serum albumin ratio showed a strong positive correlation with the VCM CSF/serum ratio (r=0.877, p<0.005). Our study indicates that the ratio of CSF protein concentration/serum albumin is likely useful for estimating the approximate VCM CSF/serum ratio. This could contribute to an improvement in the treatment of bacterial meningitis.

Plasma and cerebrospinal fluid population pharmacokinetics of vancomycin in postoperative neurosurgical patients after combined intravenous and intraventricular administration.

Combined intravenous and intraventricular administration of vancomycin into the cerebrospinal fluid (CSF) has been increasingly utilized for neurosurgical patients, but little is known about the population pharmacokinetics of vancomycin in the plasma and CSF. The aim of our study was to identify significant factors associated with plasma and CSF vancomycin concentrations to guide clinicians with vancomycin dosing. Patients with an indwelling ventricular drainage catheter who received intravenous and intraventricular vancomycin were enrolled in this study. Blood and CSF samples were collected at scheduled times and vancomycin concentrations determined. A three-compartmental model (central, peripheral and CSF compartments) was proposed to describe the in vivo behavior of vancomycin. CSF outflow resulted in vancomycin loss, and the clearance of CSF compartment (CLCSF) was used to describe this loss. The nonlinear mixed-effects modeling method was applied to structure the population model, and the stepwise incorporation of seven covariates into the final model was attempted. Simulation was performed with the goal of CSF concentrations reaching or exceeding the minimum inhibitory concentration during therapy. Serum creatinine clearance had a significant influence on clearance of the central compartment. CLCSF had a positive correlation with drainage amount and a negative correlation with elapsed time. Model validation (bootstrap and visual predictive check) demonstrated the stability and performance of the proposed population model. A simple-to-use dosage regimen table was created based on the simulation results. The proposed final model may be used to guide clinicians with vancomycin dosing in this specific patient population.

Penetration of Vancomycin into the Cerebrospinal Fluid: A Systematic Review.

Infectious disease and pharmacokinetic textbooks indicate that vancomycin has poor penetration into the central nervous system due to its hydrophilic nature and high molecular weight. Recent literature suggests that penetration of vancomycin into cerebrospinal fluid (CSF) is higher than previously reported; therefore, we conducted a systematic review to assess the penetration of vancomycin into CSF. We searched the MEDLINE, EMBASE, and CENTRAL electronic databases for English-language human studies evaluating serum and CSF concentrations of intravenous vancomycin. In 13 identified studies, the CSF-to-serum ratio of vancomycin varied from 0.00 to 0.81. CSF penetration ranged 0.06-0.81 in patients with meningitis, 0.05-0.17 in ventriculitis, 0.00-0.36 in other infections, and 0-0.13 in patients without infection. Despite variable CSF penetration, 83% of patients with meningitis and 100% of patients with ventriculitis achieved clinical cure. No factor predicted vancomycin CSF penetration. Contrary to prior belief, studies included in our review did not show universally low penetration of vancomycin into CSF. CSF vancomycin levels were variable and did not predict clinical cure.

Population Pharmacokinetics of Vancomycin in Postoperative Neurosurgical Patients and the Application in Dosing Recommendation

Our previous study indicates that cerebrospinal fluid (CSF) albumin level is a determinant of CSF vancomycin concentration for postoperative neurosurgical patients. We aimed to develop an improved vancomycin population pharmacokinetic model with incorporation of more covariates, and to provide dosing guidance for clinicians. Vancomycin was administered intravenously to 20 patients with external ventricular drains after neurosurgical operation. Blood and CSF were collected and vancomycin concentrations were measured by HPLC. A separate CSF compartment was considered, and was linked to the central compartment by a first-order process (QCSF). The clearance of the CSF compartment (ClCSF) was used to characterize vancomycin elimination from CSF through external ventricular drain. Nonlinear mixed-effects modeling approach was used to develop the model. The CSF albumin level (mg/dL) was the covariate influencing QCSF: QCSF=0.0049+0.000021×(CSF albumin−279). The effect of body weight (BW, kg) was significant on central volume (VC): VC=27.84+0.96×(BW−69). All parameters were estimated with an acceptable precision (relative standard error: RSE% < 30.26). The performance of the final model was acceptable with our previous dataset. A simple to use dosage regimen table was created to guide clinicians with vancomycin dosing. This model incorporates variables of both CSF albumin and BW, which offers improvements to the previous pharmacokinetics model.

Therapeutic drug monitoring of cerebrospinal fluid vancomycin concentration during intraventricular administration

Limited data are available on intraventricular vancomycin dosing for meningitis. This study explored clinical characteristics that correlated with cerebrospinal fluid (CSF) concentrations. Over a nine-year period, 13 patients with 34 CSF vancomycin concentrations were evaluated. CSF output and time from dose correlated with CSF vancomycin concentration. No relationship was seen with regards to CSF protein, white blood cell count or glucose.

Population Pharmacokinetics of Vancomycin in Postoperative Neurosurgical Patients

Neurosurgical procedures may damage the blood-brain barrier to allow more vancomycin distribution into the cerebrospinal fluid (CSF) from blood after intravenous administration. However, a large intersubject variability in CSF vancomycin concentration was observed. We aimed to develop a population pharmacokinetic model to guide vancomycin dosing in patients after neurosurgical operation. Blood and CSF samples were collected and determined from postoperative neurosurgical patients after vancomycin administration. A three-compartment (central, peripheral, and CSF) model was proposed to characterize the pharmacokinetics of vancomycin. A nonlinear mixed-effects modeling approach was applied to fit the blood and CSF data simultaneously. The covariate analysis found that the CSF albumin level was strongly associated with the clearance between central and CSF compartment. Visual predictive check indicated that the proposed population pharmacokinetic model agrees well with the observed vancomycin concentrations. Individualized vancomycin dosage regimens could be developed for postoperative neurosurgical patients with different CSF albumin levels through model simulations. The CSF albumin level is a determinant of CSF vancomycin concentration.

Simultaneous determination of vancomycin and ceftazidime in cerebrospinal fluid in craniotomy patients by high-performance liquid chromatography

A simple, accurate and rapid method for simultaneous analysis of vancomycin and ceftazidime in cerebrospinal fluid (CSF), utilizing high-performance liquid chromatography (HPLC), has been developed and thoroughly validated to satisfy strict FDA guidelines for bioanalytical methods. Protein precipitation was used as the sample pretreatment method. In order to increase the accuracy, tinidazole was chosen as the internal standard. Separation was achieved on a Diamonsil C18 column (200 mm × 4.6 mm I.D., 5 μm) using a mobile phase composed of acetonitrile and acetate buffer (pH 3.5) (8:92, v/v) at room temperature (25 °C), and the detection wavelength was 240 nm. All the validation data, such as accuracy, precision, and inter-day repeatability, were within the required limits. The method was applied to determine vancomycin and ceftazidime concentrations in CSF in five craniotomy patients.

Herpes Simplex Encephalitis in a Patient With Recurrent Pituitary Adenoma Receiving Radiation Therapy

A 61-year-old male initially presented with decreased libido and right visual field loss. Evaluation revealed an elevated prolactin level and a pituitary mass consistent with a secretory pituitary adenoma. His tumor progressed on cabergoline and he subsequently underwent transphenoidal tumor debulking. Four years later, his tumor recurred, and a second resection was performed. Postoperatively his dexamethasone was tapered from 16 to 4 mg/d and stereotactic radiation therapy (180 cGy per day to a planned dose of 5040 cGy) was initiated. Two weeks into his radiation, he suddenly began to speak incoherently and had a witnessed seizure with bowel and bladder incontinence while at home. He was evaluated in the hospital where he was found to be dyspneic and febrile to 38.7°C with fluent but nonsensical speech. His baseline bitemporal hemianopsia, right-sided ptosis, and facial droop with incomplete adduction of the right eye were stable. Admission studies revealed a white cell count of 7600/mL and a CD4 count of 104/mm3. Magnetic resonance imaging of the brain demonstrated an unchanged 2.0 × 2.2 × 2.5 cm pituitary mass (Fig. 1). Diffusion-weighted magnetic resonance imaging demonstrated a new area of restricted diffusion in the left mesial temporal lobe with corresponding hyperintensity on FLAIR (Fig. 2). The cerebrospinal fluid (CSF) contained 62 white cells/µL of which 95% were neutrophils, 53 RBC/µL, a protein of 45 mg/dL, and glucose of 81 mg/dL. Phenytoin was prescribed for his witnessed seizure, dexamethasone was increased for peritumoral edema, and given his fevers and CSF findings ceftriaxone, vancomycin and acyclovir were initiated. By day 3 of admission all bacterial and fungal cultures were negative, the CSF herpes simplex virus (HSV) polymerase chain reaction was positive, and other viral polymerase chain reactions were negative. The patient completed a 14-day course of acyclovir and returned to his baseline status, which was fully oriented, conversant, and able to care for himself. He had no further fevers or seizures and continued with the planned radiation therapy.

Simultaneous determination of cefepime and vancomycin in plasma and cerebrospinal fluid by MEKC with direct sample injection and application for bacterial meningitis

A simple MEKC with UV detection at 214 nm for simultaneous analysis of cefepime and vancomycin in plasma and in cerebrospinal fluid (CSF) by direct injection without any sample pretreatment is described. The separation of cefepime and vancomycin from biological matrices was performed at 25 degrees C using a BGE consisting of a Tris buffer with SDS and methanol as the electrolyte solution. Under optimal MEKC conditions for biological samples, good separations with high efficiency and short analysis time are achieved. Several parameters affecting the separation of the drugs from biological matrices were studied, including methanol, pH, and concentrations of the Tris buffer and SDS. The linear ranges of the method for the determination of cefepime and vancomycin in plasma and in CSF using imidazole or cefazolin as an internal standard, respectively, were all over the range of 1-30 microg/mL; the detection limits of cefepime and vancomycin in biological matrices (injection 10 kV, 15 s) were 0.3 and 0.5 microg/mL, respectively. The applicability of the proposed method for the determination of cefepime and vancomycin in plasma and CSF collected after intravenous administration of the drugs in patients with meningitis was demonstrated.

Levels of Vancomycin in Cerebrospinal Fluid of Adult Patients Receiving Adjunctive Corticosteroids to Treat Pneumococcal Meningitis: A Prospective Multicenter Observational Study

Evidence from a recent randomized controlled trial suggests that dexamethasone as adjunct therapy in adult pneumococcal meningitis reduces mortality and neurological sequelae. However, adding dexamethasone has the potential to reduce penetration of vancomycin into the cerebrospinal fluid (CSF). We sought to determine concentrations of vancomycin in serum and CSF of patients with suspected or proven pneumococcal meningitis receiving dexamethasone to assess the penetration of vancomycin into the CSF during steroid therapy. In an observational open multicenter study, adult patients admitted to the intensive care unit because of suspected pneumococcal meningitis received recommended treatment for pneumococcal meningitis, comprising intravenous cefotaxime (200 mg per kg of body weight per day), vancomycin (administered as continuous infusion of 60 mg per kg of body weight per day after a loading dose of 15 mg per kg of body weight), and adjunctive therapy with dexamethasone (10 mg every 6 h). Vancomycin levels in CSF were measured on day 2 or day 3 of therapy and were correlated with protein levels in CSF and vancomycin levels in serum (determined at the same time as levels in CSF). Fourteen patients were included. Thirteen had proven pneumococcal meningitis; 1 patient, initially suspected of having pneumococcal meningitis, was finally determined to have meningitis due to Neisseria meningitidis. Mean levels of vancomycin in serum and CSF were 25.2 and 7.2 mg/L, respectively, and were positively correlated (r=0.6; P=.025). A positive correlation was also found between the ratio of vancomycin in CSF to vancomycin in serum and the level of protein in CSF (r=0.66; P=.01). Appropriate concentrations of vancomycin in CSF may be obtained even when concomitant steroids are used. Dexamethasone can, therefore, be used without fear of impeding vancomycin penetration into the CSF of patients with pneumococcal meningitis, provided that vancomycin dosage is adequate. This study is registered at http://www.ClinicalTrials.gov/ (registration number NCT00162578).

Therapeutic vancomycin monitoring in children with hydrocephalus during treatment of shunt infections

Background The successful treatment of shunt infections in children with hydrocephalus is still an important problem. Diagnosis of shunt colonization is often very difficult. To treat serious central nervous system (CNS) infections, intraventricular therapy with antibiotics is necessary to reach adequate cerebrospinal fluid (CSF) concentrations and eradicate the infection. For optimal management of shunt infections the concentration of administered antibiotics in CSF should be measured. The antibiotic dosing could be modified in the individual patient after pharmacokinetic studies. Methods In our studies, vancomycin was applied to 10 children with hydrocephalus (including 6 with a myelomeningocele) for therapeutic purposes in shunt infections. The drug was administered IV and/or intraventricularly. During treatment the concentration of vancomycin in CSF was determined by fluorescence polarization immunoassay (FPIA) method. Results Considerable differences in vancomycin concentrations after the same intraventricular antibiotic administration were observed depending on the patient. The vancomycin levels determined at study state were often much higher than the therapeutic recommended range, and the biologic half-life period (T 1/2) of vancomycin in cerebrospinal fluid after intraventricular administration was prolonged. Conclusions The results of our studies give information about the pharmacokinetics of vancomycin in CSF in a group of children with hydrocephalus after intraventricular administration of the drug. In our investigation, the administration of doses smaller than 5 mg/24 hours is appropriate when the removed volume of CSF will be 20 to 30 mL/24 hours.

Intraventricular Vancomycin In Pediatric Patients With Cerebrospinal Fluid Shunt Infections

TO DETERMINE: 1) the range and magnitude of vancomycin trough cerebrospinal fluid (CSF) concentrations following intraventricular (IVT) vancomycin; 2) any correlation between patient demographic and CSF vancomycin concentrations; and 3) eradication and complications rates following IVT vancomycin. Medical records of pediatric patients with shunt infection who received IVT vancomycin during a 12 month period were reviewed. Demographic, microbiological data, IVT/intravenous (IV) vancomycin dosing, concomitant antibiotics, CSF and serum vancomycin concentrations, and CSF drainage output were recorded. Seventeen patients ages 4 months to 17 years were hospitalized for shunt infection. Staphylococcus epidermidis (n=12) was the predominant organism. Sixteen patients received 10 mg, and one patient received 5 mg of IVT vancomycin for 3-23 days. All but one received concurrent IV vancomycin. The mean maximum trough CSF vancomycin concentration noted for 16 patients who recieved 10 mg of IVT vancomycin was 18.4±21.8 μg/mL (range: between 0.4 to 187.3 μg/mL). All four adolescents ≥25 kg had CSF vancomycin concentrations ≤5 μg/mL, three of four infants/children between 10.1 and 24.9 kg had trough CSF vancomycin concentrations between 10-20 μg/mL, and five of nine infants <10 kg had CSF concentrations >20 μg/mL. All organisms were successfully eradicated. One patient developed chronic eosinophilia presumed related to elevated CSF vancomycin concentrations (187 μg/mL). CONCLUSIONS #ENTITYSTARTX02013;: The combination of IVT and IV vancomycin effectively eradicated CSF shunt infections. CSF vancomycin concentrations are highly variable and poorly correlated with age and CSF output. Following a 10 mg IVT vancomycin dose, CSF concentrations appear to be lower in older children and elevated in infants/young children. One infant experienced a complication related to an elevated CSF vancomycin concentration; hence, therapy must be individualized, using CSF trough vancomycin concentrations.

Sensorineural Hearing Loss Associated with Intrathecal Vancomycin

OBJECTIVETo report a case of nonreversible bilateral sensorineural hearing loss resulting from administration of intrathecal vancomycin.CASE SUMMARYA 63-year-old white man with newly diagnosed pre–B-cell acute lymphocytic leukemia developed Corynebacterium jeikeium meningitis associated with an Ommaya reservoir. The patient was treated with intravenous vancomycin for several days without symptomatic improvement, and intrathecal vancomycin was added to the treatment regimen. Difficulty in the patient's hearing was noted after the first intrathecal dose and he experienced complete hearing loss after the second intrathecal dose. An audiogram was performed and the patient was diagnosed with cranial nerve VIII bilateral sensorineural hearing loss. The Ommaya reservoir was removed and the patient was successfully treated with linezolid.DISCUSSIONOtotoxicity with intravenous vancomycin has been documented in multiple case reports, but this adverse effect has not been reported with intrathecal vancomycin. Cerebrospinal fluid vancomycin concentrations were not measured in our patient, but there was 1 documented occurrence of supratherapeutic serum vancomycin concentrations. Other drug-related causes of ototoxicity were evaluated and intrathecal vancomycin-induced ototoxicity was considered to be possible according to the Naranjo probability scale.CONCLUSIONSThe strong temporal relationship that was seen in this case suggests the possibility of an association between administration of intrathecal vancomycin and hearing loss. Healthcare providers should consider the potential for this adverse reaction with the intrathecal route of vancomycin administration.

Abstracts of the 24th Annual Meeting of the Japan Neuroscience Society

Bacterial meningitis is a life-threatening condition. Vancomycin (VCM) is one of the antibiotics used as empirical therapy for bacterial meningitis. It is essential to maintain an adequate concentration of VCM in cerebrospinal fluid (CSF) to treat bacterial meningitis effectively. VCM administered intravenously must pass the blood-brain barrier (BBB) to enter the CSF and the extent of VCM penetration into CSF varies widely among patients. Previous report indicated that CSF albumin level is useful for estimation of VCM CSF penetration. However, CSF albumin level is not measured in routine practice. We focused on CSF protein concentration that is generally examined at the beginning of diagnosis and treatment of bacterial meningitis. We examined the relationship between CSF protein concentration/serum albumin ratio and the extent of VCM penetration into CSF.This retrospective study involved 7 patients admitted to our hospital who were treated with VCM for suspected bacterial meningitis. The VCM concentrations in serum and CSF were 17.6 ± 7.2 μg/mL and 3.31 ± 3.14 μg/mL, respectively. The serum VCM concentrations showed no significant correlation with CSF VCM concentrations. On the other hand, the protein concentration in CSF/serum albumin ratio showed a strong positive correlation with the VCM CSF/serum ratio (r = 0.877, p < 0.005). Our study indicates that the ratio of CSF protein concentration/serum albumin is likely useful for estimating the approximate VCM CSF/serum ratio. This could contribute to an improvement in the treatment of bacterial meningitis.

Serum and Cerebrospinal Fluid Vancomycin and Gentamicin Concentrations during Ventriculoperitoneal Shunt Surgery: An Observational Study

Background: Ventriculoperitoneal shunts become infected predominantly during surgery. Optimal antibiotic prophylaxis during cerebrospinal fluid (CSF) shunt surgery has not been fully determined. Objective: To quantitate the concentrations of vancomycin and gentamicin in the serum and CSF during 100 ventriculoperitoneal shunt surgeries at the time of shunt manipulation. Design: Descriptive, prospective, observational study with a 27- to 76-month postoperative follow-up period range. Setting: University hospital. Patients: Eighty-three hydrocephalic patients ranging from premature to adult ages. Interventions: Intraoperatively, children received intravenous vancomycin 15 mg/kg/dose and gentamicin 2.5 mg/kg/dose; adults received vancomycin 1 g/dose and gentamicin 1.5 mg/kg/dose. Antibiotics were continued for 24 hours postoperatively, with dosage and schedule adjusted for age. Antibiotic serum and CSF concentrations were sampled one hour after infusion, and measured via fluorescence polarization immunoassay. Meticulous surgical infection control measures were followed. Main Outcome Measures: Correlation of intraoperative serum and CSF antibiotic concentrations with postoperative infection rate. Results: Intraoperative vancomycin serum concentrations ranged from 10.8 to 53.8 μg/mL (28.0 ± 9.5 μg/mL, mean ± SD). Intraoperative gentamicin serum concentrations ranged from 3.9 to 9.4 μg/mL (4.8 ± 2.0 μg/mL). In all surgeries, intraoperative CSF vancomycin and gentamicin concentrations were low (vancomycin &lt;5 μg/mL, gentamicin &lt;2 μg/mL). The infection rate among surgeries was 2.0%, and the infection rate among patients was 2.4%. Two shunt infections occurred, one with Candida albicans and one with Citrobacter freundii. Conclusions: Serum concentrations of vancomycin and gentamicin were above the minimum inhibitory concentrations for likely pathogens in 84% and 74% of surgeries, respectively. Intraoperative bacteriostatic and bactericidal CSF antibiotic concentrations may not be necessary to achieve a low postoperative shunt infection rate. Larger confirmatory studies are needed.