Cerebrospinal fluid antibiotic levels during treatment of shunt infections

Wald, Steven L.; McLaurin, Robert L.

doi:10.3171/jns.1980.52.1.0041

Cited by 79 publications

(35 citation statements)

References 25 publications

(8 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…La concentración de estos compuestos luego de la administración intratecal debe permitir alcanzar ≥ 8-10 x [CIM] en el LCR (≥ 32-40 µg/ mL para gentamicina y ≥ 128-160 µg/mL para amikacina) 39,40 . El efecto bactericida no es tiempodependiente en los aminoglucósidos y sólo es necesario alcanzar transitoriamente estas concentraciones elevadas.…”

Section: Aspectos Farmacocinéticos Y Farmacodinámicosunclassified

“…Diferentes series de casos han demostrado la eficacia terapéutica de gentamicina o amikacina intratecal para el tratamiento de infecciones por agentes susceptibles y la seguridad y baja toxicidad de este antimicrobiano [40][41][42][43][44][45] . A pesar de que el único estudio randomizado disponible para este antimicrobiano (desarrollado con lactantes) no logró demostrar un efecto positivo para gentamicina, la literatura y evidencia respalda mayoritariamente su uso, debido a los sesgos descritos en el trabajo original (ver más adelante) [46][47][48][49] .…”

Section: Aspectos Farmacocinéticos Y Farmacodinámicosunclassified

See 1 more Smart Citation

Antibióticos intratecales en pacientes adultos

2003

Rev. chil. infectol.

View full text Add to dashboard Cite

IntroducciónLos antimicrobianos administrados por vía intratecal son necesarios en algunas infecciones del sistema nervioso central (SNC) para proveer, en un medio carente de mecanismos fagocíticos, concentraciones bactericidas de compuestos que tienen una baja penetración por la barrera hematoencefálica.La administración intratecal considera la administración intralumbar o intraventricular de medicamentos y no reemplaza la terapia sistémica para controlar la infección fuera del SNC.Los compuestos intratecales más utilizados corresponden a aminoglucósidos y vancomicina debido a la existencia y emergencia de infecciones asociadas a bacilos Gram negativos o cocáceas Gram positivas resistentes. Estos procesos incluyen meningitis o ventriculitis, en general de carácter nosocomial y asociadas a procedimientos neuroquirúrgicos y/o derivaciones ventriculares externas o internas. Las intervenciones quirúrgicas para efectuar un drenaje del LCR en pacientes con hidrocefalia hipertensiva se han expandido progresivamente en el país y las complicaciones infecciosas agregan una morbilidad o mortalidad considerable, de allí la relevancia de conocer esta forma terapéutica. Este documento trata especialmente de las ventriculitis e infecciones asociadas a drenajes ventriculares externos. Aspectos diagnósticos de las ventriculitisEl diagnóstico de ventriculitis asociada a un drenaje ventricular no ha sido estandarizado. El espectro de alternativas incluye un cultivo del Increase of ventriculitis rates associated to CNS shunts that involve multiresistant microorganisms has made relevant this route of administration due to the limited penetration of antibiotics active against multiresistant organisms through the blood brain barrier. Aminoglycosides and vancomycin are the most common antibiotics used for this purpose. In order to accomplish bactericidal activity and due to its concentration-dependent mechanism, aminoglycosides should reach concentrations 8 to 10 times above the MIC of a given Gram negative bacilli. Doses of 2 to 5 mg for gentamicin and 30 mg for amikacin every 24 h allow this purpose and has been associated to clinical cure in several reports. Vancomycin attains its bactericidal activity by a time-dependent mechanism and the best predictor of clinical efficacy is the time area under the curve (AUC) above the MIC. Doses of 20 mg every day assure an adequate temporal exposition to the drug if trough concentrations of 5 to 10 µg/ml are obtained, and have been related to clinical efficacy. Intrathecal concentrations for these antibiotics are higher and therapeutically effective when they are administered through intraventricular route than by intralumbar puncture. Intraventricular antibiotics are indicated when a patient affected by ventriculitis does not improve despite maximal-doses systemic antibiotic therapy and/or CSF remains positive for microorganisms. In order to secure efficacy, intraventricular antibiotics should be implemented with removal of the ventricular drain associated to infection. Experience with quinu...

show abstract

Section: Aspectos Farmacocinéticos Y Farmacodinámicosunclassified

Antibióticos intratecales en pacientes adultos

2003

Rev. chil. infectol.

View full text Add to dashboard Cite

show abstract

“…Histopathologic changes in rabbits due to gentamicin included ependymal and brain cell damages (4,5). The highest antibiotic concentrations studied in our experiments correspond to the peak values in CSF attained by intraventricular administration in patients (6,7,23,24,42). To imitate the clinical situation of intraventricular therapy the study drugs were taken from regular injectable drug vials as sodium or sulfate salts.…”

Section: Discussionmentioning

confidence: 99%

“…The major therapeutic problems of these CNS infections are antibiotic resistance of involved, often nosocomially acquired, gram-negative and gram-positive pathogens, and limited drug penetration into CSF because of narrow therapeutic drug index or only low-grade meningeal inflammation (6,7). Therefore, to produce larger antibiotic concentrations in CSF direct drug inoculation is often recommended in addition to systemic therapy (6,7,23,24,42). Neurotoxicity represents a potential hazard for intraventricular antibiotic administration and has been clinically and experimentally repeatedly observed ( 1, 2, 4, 23-25).…”

Section: Discussionmentioning

confidence: 99%

Effects of Antimicrobial Agents Used for Therapy of CNS Infections on Dissociated Brain Cell Cultures

et al. 1988

View full text Add to dashboard Cite

ABSTRACT. The prediction, measurement, and monitoring of neurologic toxicity of antibacterial agents is an exceedingly difficult matter. In this study we investigated if in vitro exposure of cultured brain cells to antibacterial drugs could predict neurotoxicity in man. Effects of antibiotics used for therapy of bacterial CNS infections on growth and differentiation in dissociated rat brain cell cultures were studied over 24 days in culture, the drugs being added from 10 to 17 days in culture, the main differentiation phase of rat CNS cells. Our results demonstrated a reversible inhibition of cerebral sulfate transferase activity ( p < 0.001 or < 0.01) and to a lesser extent ( p < 0.001 or NS) of DNA synthesis in brain cell cultures by the highest concentrations studied of amikacin, cefuroxime, and ceftazidime which correspond to peak cerebrospinal fluid values attained by intraventricular therapy in patients. Accumulation of DNA reflects brain cell growth whereas cerebral sulfate transferase activity parallels brain cell differentiation. Our findings indicate that intraventricular therapy could be more toxic with amikacin, cefuroxime, and ceftazidime than with penicillin, chloramphenicol, or ceftriaxone. Thus, this brain cell culture model might become a supplement, complement, or even alternative technique for neurotoxicity assessment of antibiotics with proven or potential value for therapy of CNS infections. (Pediatr Res 24: 367-372,1988) Abbreviations BCC, brain cell culture CSF, cerebrospinal fluid DIC, days in culture CST, cerebral sulfate transferase reviews of case reports (1, 2). CNS toxicity is a well-described complication of intraventricular antibiotic therapy for gramnegative bacillary ventriculitis and CSF shunt infections (l,2,4-7). Animal toxicity tests bear a relatively poor predictive value for neurotoxicity in man and require the use of a high number of animals (4,5,(8)(9)(10). Therefore, back-shifting of neurotoxicity tests from the human or animal situation to a relatively simple and reproducible system in vitro was the principal aim of the present research.There are many reports presenting evidence of dose-dependent antiproliferative effects of various antibiotics on cultured eucaryotic cells. The cell types studied include human fibroblasts (1 1), bone marrow cells (12), and dissociated brain cells (1 3). As in vitro correlative of dose-related marrow suppression by chloramphenicol it was found several decades ago that this drug inhibits mitochondria1 protein synthesis not only in bacteria but also in proliferating bone marrow cells (14, 15). More recently, the inhibition of cell proliferation has most often been studied for the @-lactam antibiotics on cultured human myeloid percursor and lymphoid cells, the clinical consequences being neutropenia and impairment of cellular and humoral immune responses induced by 6-lactams (12, 16-1 8).The purpose of our investigation was to monitor the effects of antibiotics on growth and differentiation in dissociated rat BCC which might help to pred...

show abstract

“…11 Therefore, direct instillation of the drug into the CNS may be necessary to achieve CSF concentrations capable of successfully eradicating an organism. [12][13][14][15][16] The purpose of this retrospective study was to evaluate the treatment and outcomes of patients with culture proven CSF shunt infections who were treated with IV and IVT (intraventricular) vancomycin. The objectives were to determine: 1) the range and magnitude of vancomycin trough CSF concentrations following IVT vancomycin; 2) any correlation between patient demographics and CSF vancomycin concentration; and 3) eradication and complications rates following the administration of IVT vancomycin.…”

Section: Introductionmentioning

confidence: 99%

Intraventricular Vancomycin In Pediatric Patients With Cerebrospinal Fluid Shunt Infections

Al-Jeraisy¹,

Phelps

Christensen

et al. 2004

The Journal of Pediatric Pharmacology and Therapeutics

View full text Add to dashboard Cite

OBJECTIVESTo 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. METHODS 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. RESULTS 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 -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.

show abstract

Cerebrospinal fluid antibiotic levels during treatment of shunt infections

Cited by 79 publications

References 25 publications

Antibióticos intratecales en pacientes adultos

Antibióticos intratecales en pacientes adultos

Effects of Antimicrobial Agents Used for Therapy of CNS Infections on Dissociated Brain Cell Cultures

Intraventricular Vancomycin In Pediatric Patients With Cerebrospinal Fluid Shunt Infections

Contact Info

Product

Resources

About