Intraventricular Gentamicin in Meningitis

Kaiser, Allen B.; Wright, Peter F.; McGee, Zell A.; Dupont, William D.; Warren, R. E.; Roberton, N. R. C.; Corbeel, L; Boeck, K. De; Logghe, N.; Eggermont, Ephrem; Eeckels, R; Casaer, Paul; Vandepitte, J.; Verbist, Ludo; Frederiksen, Wilhelm; Schouenborg, P; McCracken, George H.; Mize, Susan G.

doi:10.1016/s0140-6736(80)90137-3

Cited by 7 publications

(8 citation statements)

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“…The results of the 1980 experimental study 15 were unexpected, especially for pediatricians who had already successfully used intraventricular antibiotics in neonates to treat meningitis and ventriculitis. 10–13,38,53 Furthermore, some experts have suggested that the higher mortality from intraventricular antibiotics in this experimental study could have been due to insufficient doses. 13,53 Recently, the guidelines of The Infectious Diseases Society of America on nosocomial meningitis and ventriculitis also questioned the results of the experimental study on the mortality of intraventricular antibiotics 15 due to insufficient doses, and the guidelines consider that intraventricular antibiotics are an option in neuroinfections that responds poorly to systemic treatment.…”

Section: Discussionmentioning

confidence: 88%

“…This is because, in the control group (receiving only systemic antibiotics), 10 of the 24 patients had their treatment changed (with the addition of intraventricular antibiotics) due to a lack of improvement in the characteristics of the cerebrospinal fluid, as confirmed by the same author in another publication months after the experimental clinical trial was published (in a response from the author of the study, to a letter to the editor sent by several researchers concerned about inconsistencies in this study). 13…”

Section: Resultsmentioning

confidence: 99%

“…(variable rarely reported, only in13.5% of patients) Presence of adverse effects 0/19 (0%) (variable rarely reported, only in 32.2% of patients) Reason for use • Refractory infection: 12/59 (20%) Mortality: 2/12 (16%) • Multidrug-resistant infection (adjuvant treatment): 30/59 (51%) Mortality: 3/30 (10%) • Did not report reason: 17/59 (29%) Administration route External ventricular drain (all cases)…”

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confidence: 99%

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

Valdivia,

Pérez,

Vega

et al. 2023

Preprint

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Background: Many pediatric and neurosurgical studies have been published regarding intraventricular antibiotics in neonatal meningitis and ventriculitis. 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: We systematically reviewed scientific literature from the PubMed, EMBASE, LILACS, and SCOPUS databases. 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 to 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 to 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.

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Section: Discussionmentioning

confidence: 88%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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

Valdivia,

Pérez,

Vega

et al. 2023

Preprint

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“…Los reportes derivados del estudio cooperativo sobre meningitis neonatal que señalaban una evolución adversa con mayor letalidad asociada a gentamicina intraventricular en comparación a gentamicina más ampicilina sistémica en el manejo de pacientes con meningitis neonatal, han sido criticados por la multiplicidad de sesgos en el diseño del trabajo en desmedro del grupo que recibió terapia intratecal. En efecto, se critica que los pacientes con gentamicina intratecal iniciaron su tratamiento en forma más tardía, presentaron una mayor frecuencia de bacilos resistentes a gentamicina, alcanzaron a recibir un escaso nú-mero de dosis por diferencias en la severidad inicial del cuadro, se incluyeron muertes no relacionadas al uso de antimicrobianos en el grupo intratecal y se efectuaron más cambios de tratamiento no especificados en el grupo sin terapia intratecal 46,47,49,63 . Por otra parte, la gentamicina era aplicada con punciones repetidas sobre los ventrículos, una forma de administración que aporta un riesgo intrínseco al procedimiento y que no es utilizada actualmente por el riesgo de porencefalia.…”

Section: Toxicidadunclassified

Antibióticos intratecales en pacientes adultos

2003

Rev. chil. infectol.

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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...

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“…9 In the 1970s and 1980s, intraventricular antibiotics were successfully used in some cases of neonatal meningitis. [10][11][12][13][14] In 1980, a randomized clinical trial of intraventricular gentamicin in neonatal meningitis 15 reported a very high mortality associated with the use of intraventricular antibiotics, which drastically reduced interest in the clinical use and research of intraventricular antibiotics in neonates, in contrast to the increased clinical use and research of intraventricular antibiotics in adults.…”

Section: Introductionmentioning

confidence: 99%

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

Valdivia,

Pérez,

Vega

et al. 2023

Childs Nerv Syst

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Background: Many pediatric and neurosurgical studies have been published regarding intraventricular antibiotics in neonatal meningitis and ventriculitis. 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:We systematically reviewed scientific literature from the PubMed, EMBASE, LILACS, and SCOPUS databases. 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 multidrugresistant 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.

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Intraventricular Gentamicin in Meningitis

Cited by 7 publications

References 6 publications

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

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

Antibióticos intratecales en pacientes adultos

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

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