Population pharmacokinetics and dosing simulations of total and unbound temocillin in the plasma and CSF of neurocritically ill patients with external ventricular drain-related cerebral ventriculitis.

BACKGROUND: Cerebral ventriculitis might be caused by Gram-negative bacteria, including ESBL producers. Temocillin may be a useful treatment option in this scenario; however, no consistent data are available regarding its penetration into the CSF. OBJECTIVES: To describe the population pharmacokinetics of temocillin in plasma and CSF and to determine the probability for different simulated dosing regimens to achieve pharmacokinetic/pharmacodynamic (PK/PD) targets in the CSF. METHODS: Ten post-neurosurgical critically ill adult patients requiring continuous drainage of CSF were included in this monocentric, prospective, open-label, non-randomized study. They received 2 g loading dose temocillin over 30 min IV infusion, followed by a 6 g continuous infusion over 24 h. Total and unbound concentrations were measured in plasma (n = 88 and 86) and CSF (n = 88 and 88) samples and used to build a population PK model. Monte Carlo simulations were performed to estimate the PTA at 100% Css>MIC (steady state concentration above the MIC) in CSF. RESULTS: All patients were infected with Enterobacterales with temocillin MICs ≤8 mg/L. The median (min-max) temocillin penetration in CSF was 12.1% (4.3-25.5) at steady state. Temocillin unbound plasma pharmacokinetics were best described by a one-compartment model. PTA for the applied dosing regimen was >90% for bacteria with MIC ≤ 4 mg/L. CONCLUSIONS: The currently approved dose of 6 g by continuous infusion may be adequate for the treatment of ventriculitis by Enterobacterales with MIC ≤ 4 mg/L if considering 100% Css>MIC as the PK/PD target to reach. Higher maintenance doses could help covering higher MICs, but their safety would need to be assessed.

Streptococcus intermedius causing primary bacterial ventriculitis in a patient with severe periodontitis - a case report.

BACKGROUND: Streptococcus intermedius is a member of the S. anginosus group and is part of the normal oral microbiota. It can cause pyogenic infections in various organs, primarily in the head and neck area, including brain abscesses and meningitis. However, ventriculitis due to periodontitis has not been reported previously. CASE PRESENTATION: A 64-year-old male was admitted to the hospital with a headache, fever and later imbalance, blurred vision, and general slowness. Neurological examination revealed nuchal rigidity and general clumsiness. Meningitis was suspected, and the patient was treated with dexamethasone, ceftriaxone and acyclovir. A brain computer tomography (CT) scan was normal, and cerebrospinal fluid (CSF) Gram staining and bacterial cultures remained negative, so the antibacterial treatment was discontinued. Nine days after admission, the patient's condition deteriorated. The antibacterial treatment was restarted, and a brain magnetic resonance imaging revealed ventriculitis. A subsequent CT scan showed hydrocephalus, so a ventriculostomy was performed. In CSF Gram staining, chains of gram-positive cocci were observed. Bacterial cultures remained negative, but a bacterial PCR detected Streptococcus intermedius. An orthopantomography revealed advanced periodontal destruction in several teeth and periapical abscesses, which were subsequently operated on. The patient was discharged in good condition after one month. CONCLUSIONS: Poor dental health can lead to life-threatening infections in the central nervous system, even in a completely healthy individual. Primary bacterial ventriculitis is a diagnostic challenge, which may result in delayed treatment and increased mortality.

Systematic review and meta-analysis of intraventricular antibiotics for neonatal meningitis and ventriculitis.

PURPOSE: We aimed to determine the safety and effectiveness of intraventricular antibiotics in neonates with meningitis and/or ventriculitis and analyze the quality of available evidence. METHODS: DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, EMBASE, LILACS, and SCOPUS up to 17 February 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomized experimental and observational studies were included. The Cochrane methodology was used for systematic reviews. RESULTS: Twenty-six observational studies and one randomized clinical trial involving 272 patients were included. The risk of bias in both pediatric and neurosurgical studies was high, and the quality of evidence was low (evidence level C). In the pediatric studies, no significant differences in mortality were found between intraventricular antibiotics and only systemic antibiotic [25.4% vs 16.1%, OR = 0.96 (0.42-2.24), P = 0.93]. However, when analyzing the minimum administered doses, we found a lower mortality when a minimum duration of 3 days for intraventricular antibiotics was used compared to only systemic antibiotic [4.3% vs 17%, OR = 0.22 (0.07-0.72), P = 0.01]. In the neurosurgical studies, the use of intraventricular antibiotics in ventriculitis generally results in a mortality of 5% and a morbidity of 25%, which is lower than that in cases where intraventricular antibiotics were not used, with an average mortality of 37.3% and a morbidity of 50%. CONCLUSION: Considering the low quality of evidence in pediatric and neurosurgical studies, we can conclude with a low level of certainty that intraventricular antibiotics may not significantly impact mortality in neonatal meningitis and ventriculitis. However, reduced mortality was observed in cases treated with a minimum duration of 3 days of intraventricular antibiotic, particularly the multidrug-resistant or treatment-refractory infections. Higher-quality studies are needed to improve the quality of evidence and certainty regarding the use of intraventricular antibiotics for treating neonatal meningitis and ventriculitis.

Early Intraventricular Antibiotic Therapy Improved In-Hospital-Mortality in Neurocritical Patients with Multidrug-Resistant Bacterial Nosocomial Meningitis and Ventriculitis.

BACKGROUND: Hospital-acquired multidrug-resistant (MDR) bacterial meningitis and/or ventriculitis (MEN) is a severe condition associated with high mortality. The risk factors related to in-hospital mortality of patients with MDR bacterial MEN are unknown. We aimed to examine factors related to in-hospital mortality and evaluate their prognostic value in patients with MDR bacterial MEN treated in the neurointensive care unit. METHODS: This was a single-center retrospective cohort study of critically ill neurosurgical patients with MDR bacterial MEN admitted to our hospital between January 2003 and March 2021. Data on demographics, admission variables, treatment, time to start of intraventricular (IVT) therapy, and in-hospital mortality were analyzed. Both univariate and multivariable analyses were performed to identify determinants of in-hospital mortality. RESULTS: All 142 included patients received systemic antibiotic therapy, and 102 of them received concomitant IVT treatment. The median time to start of IVT treatment was 2 days (interquartile range 1-5 days). The time to start of IVT treatment had an effect on in-hospital mortality (hazard ratio 1.17; 95% confidence interval 1.02-1.34; adjusted p = 0.030). The cutoff time to initiate IVT treatment was identified at 3 days: patients treated within 3 days had a higher cerebrospinal fluid (CSF) sterilization rate (81.5%) and a shorter median time to CSF sterilization (7 days) compared with patients who received delayed IVT treatment (> 3 days) (48.6% and 11.5 days, respectively) and those who received intravenous antibiotics alone (42.5% and 10 days, respectively). CONCLUSIONS: Early IVT antibiotics were associated with superior outcomes in terms of the in-hospital mortality rate, time to CSF sterilization, and CSF sterilization rate compared with delayed IVT antibiotics and intravenous antibiotics alone.

Cerebrospinal fluid penetration of fosfomycin in patients with ventriculitis: an observational study.

BACKGROUND: For treatment of ventriculitis, vancomycin and meropenem are frequently used as empiric treatment but cerebrospinal fluid (CSF) penetration is highly variable and may result in subtherapeutic concentrations. Fosfomycin has been suggested for combination antibiotic therapy, but data are sparse, so far. Therefore, we studied CSF penetration of fosfomycin in ventriculitis. METHODS: Adult patients receiving a continuous infusion of fosfomycin (1 g/h) for the treatment of ventriculitis were included. Routine therapeutic drug monitoring (TDM) of fosfomycin in serum and CSF was performed with subsequent dose adaptions. Demographic and routine laboratory data including serum and CSF concentrations for fosfomycin were collected. Antibiotic CSF penetration ratio as well as basic pharmacokinetic parameters were investigated. RESULTS: Seventeen patients with 43 CSF/serum pairs were included. Median fosfomycin serum concentration was 200 [159-289] mg/L and the CSF concentration 99 [66-144] mg/L. Considering only the first measurements in each patient before a possible dose adaption, serum and CSF concentrations were 209 [163-438] mg/L and 104 [65-269] mg/L. Median CSF penetration was 46 [36-59]% resulting in 98% of CSF levels above the susceptibility breakpoint of 32 mg/L. CONCLUSION: Penetration of fosfomycin into the CSF is high, reliably leading to appropriate concentrations for the treatment of gram positive and negative bacteria. Moreover, continuous administration of fosfomycin appears to be a reasonable approach for antibiotic combination therapy in patients suffering from ventriculitis. Further studies are needed to evaluate the impact on outcome parameters.

Talaromyces rugulosus ventriculitis diagnosed by nanopore amplicon sequencing, 2022.

Ventriculitis has serious complications and a high mortality rate, so it is important to early identification of the pathogen for appropriate treatment. We report case of ventriculitis caused by Talaromyces rugulosus, a rare pathogen, in South Korea. Affected patient was immunocompromised. Repeated cerebrospinal fluid culture tests were negative, but the pathogen was identified by fungal internal transcribed spacer amplicon nanopore sequencing. The pathogen was detected outside the endemic area of talaromycosis.

Intraventricular colistin sulphate as a last resort therapy in a patient with multidrug-resistant Acinetobacter baumannii induced post-neurosurgical ventriculitis.

Limited therapeutic options exist for multidrug-resistant/extensively drug-resistant Acinetobacter baumannii (MDR/XDR-Ab) meningitis/ventriculitis. A combination of intravenous and intraventricular (IVT)/intrathecal (IT) polymyxins achieves good therapeutic outcomes for cases of healthcare-associated MDR/XDR-Ab meningitis/ventriculitis. Colistin is commercially available as colistin sulphate and its sulphomethylated derivative. However, the effect and safety of colistin sulphate in the treatment of MDR/XDR-Ab meningitis/ventriculitis has not been reported. We report on a 66-year-old male patient who developed post-neurosurgical ventriculitis caused by MDR-Ab. IVT concomitant intravenous colistin sulphate was used as a last-resort antimicrobial therapy, the patient's ventriculitis was dramatically improved, and the concentrations of CSF colistin were higher than the MIC breakpoint throughout the treatment. Meanwhile, no nephrotoxicity or neurotoxicity was observed during the treatment.

Population pharmacokinetics of vancomycin in patients with external ventricular drain-associated ventriculitis.

BACKGROUND: To determine the distribution of vancomycin into the cerebrospinal fluid (CSF) in patients with external ventricular drain (EVD)-associated ventriculitis, the pharmacokinetics of vancomycin were evaluated and covariate relationships explored. METHODS: For the population pharmacokinetic model patients were recruited in a neurocritical care unit at the University Hospital of Muenster in the period between January 2014 and June 2015. All patients had a clinical evidence of EVD-associated ventriculitis. Population pharmacokinetic analysis of vancomycin was performed using NONMEM. RESULTS: A total of 184 blood and 133 CSF samples were collected from 29 patients. The final population pharmacokinetic model is a three-compartment model with linear elimination. Creatinine clearance (ClCr ) and CSF-lactate were detected as significant covariates, showing that the total vancomycin plasma clearance (Cl) depends on ClCr and furthermore the clearance (Cldif ) between the central and CSF compartment correlates with CSF lactate concentration. Based on the final model, the following values were estimated by NONMEM: Cl = 5.15 L/h, Q (intercompartmental clearance) = 3.31 L/h, Cldif  = 0.0031 L/h, Vcentral  = 42.1 L, VCSF  = 0.32 L and the value of Vperipheral was fixed to 86.2 L. With the developed pharmacokinetic model, area under the curve (AUC) values as well as CSF trough levels were simulated. CONCLUSION: Based on our analysis, the dosing of vancomycin should be referred to the degree of inflammation (derived from the CSF lactate concentration) and renal function (derived from ClCr ).

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%.

Recurrent primary pyogenic ventriculitis in an adult woman: a case report.

BACKGROUND: Recurrent primary pyogenic ventriculitis has not been reported previously. We present a unique case of recurrent primary pyogenic ventriculitis in an adult. And we believe that our study makes a significant contribution to the literature. CASE PRESENTATION: An adult woman with uncontrolled diabetes experienced two episodes of pyogenic ventriculitis caused by Escherichia coli over 4 years. She had typical imaging features, and the source of infection was undetermined. After antibiotic treatment, she recovered fully. CONCLUSIONS: Early recognition and therapy will improve patient prognosis.

Infantile Aspergillus fumigatus ventriculitis successfully treated with monitoring of plasma and cerebrospinal fluid voriconazole concentration level.

Aspergillosis is a rare fungal infection in newborns, and its morbidity and mortality are high. Voriconazole (VRCZ) is the first-line antifungal agent for invasive Aspergillus infection, but little data is available about its pharmacokinetics in infants. We report a case of a premature infant who developed ventriculitis due to Aspergillus fumigatus and received combination antifungal therapy including VRCZ. ß-D glucan and Aspergillus antigen index were elevated in the cerebrospinal fluid (CSF). We titrated the dose of VRCZ by monitoring plasma and CSF concentrations. The CSF to plasma concentration ratio of VRCZ ranged from 0.47 to 1.36 (median 0.71). While VRCZ adequately penetrates the blood-brain barrier, its concentration is highly variable in infants.

Ureaplasma parvum ventriculitis related to surgery and ventricular peritoneal drainage.

Ureaplasma spp. usually causes genitourinary infections; few reports in the literature describe extragenital infections, usually in immunocompromised patients. We present a case of Ureaplasma parvum ventriculitis in an immunocompetent patient related to ventriculoperitoneal drainage and surgery. Ureaplasma parvum was detected with broad range 16S rRNA PCR and cultured on A8 agar.

High-Dosage Cefazolin Achieves Sufficient Cerebrospinal Diffusion To Treat an External Ventricular Drainage-Related Staphylococcus aureus Ventriculitis.

A patient received continuous infusion of cefazolin 10 g then 8 g daily for an external ventricular drainage-related methicillin-susceptible Staphylococcus aureus (MSSA) ventriculitis. Median free concentrations in the cerebrospinal fluid were 11.9 and 6.1 mg/liter after 10- and 8-g doses, respectively. Free concentrations in the cerebrospinal fluid were always above the MIC usually displayed by methicillin-susceptible Staphylococcus aureus (MSSA) isolates. These results support the use of high-dose cefazolin to achieve sufficient meningeal concentrations.

CSF penetration of vancomycin in critical care patients with proven or suspected ventriculitis: a prospective observational study.

BACKGROUND: Vancomycin is recommended for ventriculitis. However, penetration into the CNS is relatively poor. OBJECTIVES: To investigate the population pharmacokinetics of vancomycin in serum and CSF in critical care patients with proven or suspected CNS infections from neurosurgical procedures. PATIENTS AND METHODS: This was an observational pharmacokinetic study in critical care patients with proven or suspected CNS infections receiving intravenous vancomycin. Multiple blood and intraventricular CSF samples were collected. Population pharmacokinetic analysis and simulation were undertaken with ADAPT5 and Pmetrics. RESULTS: A total of 187 blood and CSF samples were collected from 21 patients. The median (range) Cmax and Cmin concentrations in serum were 25.67 (10.60-50.78) and 9.60 (4.46-23.56) mg/L, respectively, with a median daily dose of 2500 (500-4000) mg. The corresponding median concentrations in CSF were 0.65 (<0.24-3.83) mg/L and 0.58 (<0.24-3.95) mg/L, respectively. The median AUC0-24 in serum and CSF was 455.09 and 14.10 mg·h/L, respectively. A three-compartment linear population pharmacokinetic model best fitted the observed data. Vancomycin demonstrated poor penetration into CSF, with a median CSF/serum ratio of 3% and high intersubject pharmacokinetic variability of its penetration. CONCLUSIONS: Therapeutic drug monitoring in both serum and CSF and higher daily doses may be an option to ensure adequate trough levels and to optimize patient therapy. Novel dosing strategies designed to reduce renal toxicity, such as administration by continuous infusion, should be investigated in further clinical studies to avoid antibiotic underexposure in CSF.

Cerebrospinal fluid pharmacokinetics of ceftaroline in neurosurgical patients with an external ventricular drain.

BACKGROUND: Owing to its antibacterial properties, ceftaroline could be attractive for prevention or treatment of bacterial post-neurosurgical meningitis/ventriculitis. However, few data are available concerning its meningeal concentrations. OBJECTIVES: To investigate ceftaroline CSF pharmacokinetics in ICU patients with an external ventricular drain (EVD). METHODS: Patients received a single 600 mg dose of ceftaroline as a 1 h intravenous infusion. Blood and CSF samples were collected before and 0.5, 1, 3, 6, 12 and 24 h after the end of the infusion. Concentrations were assayed in plasma and CSF by LC-MS/MS. A two-step compartmental pharmacokinetic analysis was conducted. Ceftaroline plasma data were first analysed, and thereafter plasma parameters estimated and corrected for protein binding of 20% were fixed to fit unbound CSF concentrations. In the final model, parameters for both plasma and CSF data were simultaneously estimated. RESULTS: Nine patients with an EVD were included. The Cmax was 18.29 ± 3.33 mg/L in plasma (total concentrations) and at 0.22 ± 0.17 mg/L in CSF (unbound concentration). The model-estimated CSF input/CSF output clearance ratio was 9.4%, attesting to extensive efflux transport at the blood-CSF barrier. CONCLUSIONS: Ceftaroline CSF concentrations are too low to ensure prophylactic protection against most pathogens with MICs between 1 and 2 mg/L, owing to its limited central distribution.

Current Practices of Intraventricular Antibiotic Therapy in the Treatment of Meningitis and Ventriculitis: Results from a Multicenter Retrospective Cohort Study.

BACKGROUND: Central nervous system (CNS) infections are particularly prevalent in the adult neurocritical care patient population and are associated with significant morbidity and mortality. Factors relevant to the nature of CNS infections pose significant challenges to clinicians treating afflicted patients. Intraventricular (IVT) administration of antibiotics may offer several benefits over systemic therapy; however, the outcomes and current practices of such treatments are poorly described in the literature. OBJECTIVE: To describe current practices and outcomes of patients receiving intraventricular antibiotic treatment for CNS infections in neurological intensive care units of academic medical centers nationwide. METHODS: A retrospective cohort study was conducted on patients admitted to intensive care units who received IVT antibiotic treatment at participating centers in the USA between January 01, 2003, and December 31, 2013. Clinical and laboratory parameters, microbiology, surgical and antimicrobial management, and treatment outcomes were collected and described. RESULTS: Of the 105 patients included, all received systemic antimicrobial therapy along with at least one dose of IVT antimicrobial agents. Intraventricular vancomycin was used in 52.4% of patients. The average dose was 12.2 mg/day for a median duration of 5 days. Intraventricular aminoglycosides were used in 47.5% of the patients, either alone or in combination with IVT vancomycin. The average dose of gentamicin/tobramycin was 6.7 mg/day with a median duration of 6 days. Overall mortality was 18.1%. Cerebrospinal fluid (CSF) culture sterilization occurred in 88.4% of the patients with a rate of recurrence or persistence of positive cultures of 9.5%. CONCLUSION: Intraventricular antimicrobial agents resulted in a high CSF sterilization rate. Contemporary use of this route typically results in a treatment duration of less than a week. Prospective studies are needed to establish the optimal patient population, as well as the efficacy and safety of this route of administration.

Diagnosis and treatment of severe neurosurgical patients with pyogenic ventriculitis caused by gram-negative bacteria.

The aim of the study is to explore the experiences in diagnosis and treatment of severe neurosurgical patients with pyogenic ventriculitis caused by gram-negative bacteria (G-). Nineteen patients with pyogenic ventriculitis were reviewed for their treatment. The bacterial testing results of cerebrospinal fluid (CSF), the clinical intervention, and the patients' prognosis were evaluated. The bacterial smears of ventricular drainage from all the cases were G- bacteria. Head CT and MRI scans confirmed that they were intraventricular empyema. Eighteen cases of CSF bacterial test were positive, including 12 cases of Acinetobacter baumannii positive, 2 of Klebsiella pneumonia positive, 2 of Serratia marcescens positive, 1 of Pseudomonas maltophila positive, and 1 case of Escherichia coli positive. One case of the bacterial culture was negative. All patients were treated by using intraventricular lavage in combination with intravenous and intraventricular antibiotics in accordance with the clinical conditions. After treatment for 2 to 8 weeks, 14 patients were cured (74%) and 5 were died (26%). Eight patients who were cured had received ventriculoperitoneal shunt due to hydrocephalus at 2 to 6 weeks after infection controlled, and none of them had any reinfection. Twelve of the 14 cured cases came to consciousness, but 2 were persistent in vegetative state starting before the infection; they did not show any improving consciousness after infection had been cured. Suppurative ventriculitis in severe neurosurgical patients is mainly infected by G- with a higher mortality. Early diagnosis, especially in identifying pathogen types, timely ventricular irrigation, and ventricular drainage together with intravenous and intraventricular antibiotic treatment, should improve prognosis.

The first report of human meningitis and pyogenic ventriculitis caused by Streptococcus suis: A case report.

Streptococcus suis, a gram-positive facultative anaerobe commonly found in pigs, is an emerging zoonotic pathogen. Herein, we describe a case of a 45-year-old male Japanese meat wholesaler with S. suis meningitis and pyogenic ventriculitis. S. suis was isolated from his blood and cerebrospinal fluid culture, and sequence type (ST) and serotype were confirmed to be ST1 and serotype 2, respectively, by multilocus sequence typing and the Quellung reaction. Magnetic resonance imaging (MRI) revealed right labyrinthitis and pyogenic ventriculitis. The patient was treated with ceftriaxone and ampicillin for 24 days; the treatment was deemed successful based on negative blood cultures on day 4. However, the patient experienced hearing loss and a vestibular nerve disorder. S. suis is a rare pathogen in Japan but can cause severe infection and sequelae. To the best of our knowledge, this is the first report of a human case of pyogenic ventriculitis caused by S. suis. Our findings suggest that S. suis infection should be considered when hearing impairment is present in a patient with bacterial infection and that MRI can help detect ventriculitis, which can necessitate a prolonged treatment duration.

Monitoring intraventricular vancomycin for ventriculostomy access device infection in preterm infants.

PURPOSE: Ventriculitis is a known complication during external CSF drainage in preterm infants with posthaemorrhagic ventricular dilatation. Staphylococci are most frequently isolated in device-associated ventriculitis, and hence, intraventricular vancomycin is a commonly used therapy. Our aim was to study the CSF vancomycin level pattern and drug safety in ventriculostomy access device infection in preterm infants less than 28 weeks gestation. METHODS: This single-centre, retrospective case series included seven infants with a median gestational age of 25 + 4 weeks (range 23 + 6 to 27 + 5 weeks). Ventriculitis was defined as elevated CSF white cell count of > 20/mm3 or positive CSF culture. The CSF vancomycin concentrations following intraventricular vancomycin administration were studied. RESULTS: Forty treatment episodes of intraventricular vancomycin administration were studied in seven preterm infants. Maximum CSF vancomycin concentrations were 24.9 mg/L (3 mg, n = 8, observed concentration-time (OCT), hours (h) = 19), 96.3 mg/L (5 mg, n = 17, OCT(h) = 14), 94 mg/L (10 mg, n = 14, OCT(h) = 24), and 230.7 mg/L (15 mg, n = 1, OCT(h) = 24). The threshold for re-dosage is set at CSF vancomycin level of < 10 mg/L. In all patients, ventriculitis resolution (defined as sterile CSF and CSF WCC of < 20/mm3) was achieved in a median of 5.5 days (range 2-31 days). Individual microbiology data is provided in the online resource. CONCLUSION: Intraventricular vancomycin is an effective treatment for ventriculostomy access device infection in preterm infants. In doses ranging from 3 to 15 mg, sufficient CSF vancomycin level is generated to achieve microbiological cure without any reported adverse effects. Daily CSF drug monitoring is recommended to define dosage interval to maintain drug concentration above breakpoint of minimum inhibitory concentration.

Intrathecal penetration of meropenem and vancomycin administered by continuous infusion in patients suffering from ventriculitis-a retrospective analysis.

BACKGROUND: Vancomycin and meropenem are frequently used as empiric treatment for ventriculitis. Penetration into the cerebrospinal fluid (CSF) depends on various factors with a high inter-individual variability. Because attaining and maintaining adequate concentrations of meropenem and vancomycin in the CSF is crucial for their bactericidal effect, we introduced a routine therapeutic drug monitoring (TDM) from CSF and serum for both antibiotics. We studied the antibiotic penetration into the CSF. METHODS: Patient data including serum and CSF concentrations for meropenem and vancomycin were collected in a retrospective fashion. Antibiotic CSF penetration ratio was calculated for each patient. Antibiotics were administered by continuous infusion aiming for serum target concentrations of 20-30 mg/L for vancomycin and 16-32 mg/L for meropenem. RESULTS: Twenty-two patients with 36 CSF/serum pairs for meropenem and 43 pairs for vancomycin were studied. No patient suffered from renal or liver insufficiency. Mean vancomycin serum concentration was 22 ± 8 mg/L and the mean CSF concentration 4.5 ± 2.6 mg/L. CSF penetration was 20 ± 11% (coefficient of determination (R2) 0.02). For meropenem, the mean serum concentration was 30.7 ± 14.9 mg/L, mean CSF concentration 5.5 ± 5.2 mg/L, and a penetration of 18 ± 12%, R2 = 0.42. CONCLUSION: Penetration of meropenem and vancomycin into the CSF is low while showing a high interindividual variability. Various patients in our study cohort were at risk for insufficient target attainment in CSF. Continuous administration of antibiotics under routine TDM appears to be a feasible and reasonable approach for optimization of intrathecal drug levels in patients suffering from ventriculitis. TDM might guide individual dosing adaptation and efforts to predict the CSF penetration of meropenem and vancomycin in cases of ventriculitis.