Intraventricular antibiotics for bacterial meningitis in neonates

Abstract

In one trial that enrolled infants with gram-negative meningitis and ventriculitis, the use of intraventricular antibiotics in addition to intravenous antibiotics resulted in a three-fold increased RR for mortality compared to standard treatment with intravenous antibiotics alone. Based on this result, intraventricular antibiotics as tested in this trial should be avoided. Further trials comparing these interventions are not justified in this population.

Early Inhaled Budesonide for the Prevention of Bronchopulmonary Dysplasia

“…for death at 36 weeks (postmenstrual age) of 0.73 (95% CI, 0.44 to 1.21). 12 In two of the trials, as in our trial, glucocorticoids were administered within 24 hours after birth 21,22 ; in both of these trials, the risk ratio for death was below 1.…”

“…dysplasia. 12 We speculate that aside from our trial including a large enough sample size to enable us to detect a clinically meaningful treatment effect, our positive finding with respect to the reduced incidence of bronchopulmonary dysplasia may be attributable to the early initiation of therapy and the choice of dose, since it has been shown repeatedly that only a fraction of the administered inhaled dose is deposited in the lungs. 11,26,27 Budesonide was associated with a significantly lower risk than the risk with placebo of two additional prespecified secondary outcomesa patent ductus arteriosus considered by clinical staff to require surgical ligation and the requirement for reintubation after the last administration of the study drug.…”

“…12 However, we consider it unlikely that increased systemic absorption of the study drug could explain any differences in mortality. A meta-analysis of randomized trials of the early use of systemic postnatal glucocorticoids, as compared with placebo, in preterm infants did not show an increased risk of mortality up to the time of hospital discharge (risk ratio, 1.00; 95% CI, 0.89 to 1.13).…”

Early Inhaled Budesonide for the Prevention of Bronchopulmonary Dysplasia

“…for death at 36 weeks (postmenstrual age) of 0.73 (95% CI, 0.44 to 1.21). 12 In two of the trials, as in our trial, glucocorticoids were administered within 24 hours after birth 21,22 ; in both of these trials, the risk ratio for death was below 1.…”

“…dysplasia. 12 We speculate that aside from our trial including a large enough sample size to enable us to detect a clinically meaningful treatment effect, our positive finding with respect to the reduced incidence of bronchopulmonary dysplasia may be attributable to the early initiation of therapy and the choice of dose, since it has been shown repeatedly that only a fraction of the administered inhaled dose is deposited in the lungs. 11,26,27 Budesonide was associated with a significantly lower risk than the risk with placebo of two additional prespecified secondary outcomesa patent ductus arteriosus considered by clinical staff to require surgical ligation and the requirement for reintubation after the last administration of the study drug.…”

“…12 However, we consider it unlikely that increased systemic absorption of the study drug could explain any differences in mortality. A meta-analysis of randomized trials of the early use of systemic postnatal glucocorticoids, as compared with placebo, in preterm infants did not show an increased risk of mortality up to the time of hospital discharge (risk ratio, 1.00; 95% CI, 0.89 to 1.13).…”

Challenges in Diagnosis and Treatment of Neonatal Ventriculitis: A Case Report and Systematic Review of Difficult-to-Treat Central Nervous System Infection Resistant to Conventional Therapy

“…31,32,35,38 GNB pathogens, in particular E. coli, Klebsiella, and Pseudomonas species, are detected in 20 to 25% of early-onset bacteremia and 14% of infant meningitis worldwide. 61 Acinetobacter 8), left against advice (6), survivors (22), and neurologic sequelae (8) Bentlin et al 45 Epidemiological study…”

“…Drugs weakly penetrate the blood-brain barrier, and CSF flow may be obstructed by cellular debris and proteins. 8 Persistently poor clinical and laboratory findings suggest an unsatisfactory response and that a second delivery method is required to increase drug concentrations in the ventricles. IVT therapy refers to direct instillation of the drug into the ventricular system via an EVD or a reservoir.…”

Early Inhaled Budesonide for the Prevention of Bronchopulmonary Dysplasia

“…for death at 36 weeks (postmenstrual age) of 0.73 (95% CI, 0.44 to 1.21). 12 In two of the trials, as in our trial, glucocorticoids were administered within 24 hours after birth 21,22 ; in both of these trials, the risk ratio for death was below 1.…”

“…dysplasia. 12 We speculate that aside from our trial including a large enough sample size to enable us to detect a clinically meaningful treatment effect, our positive finding with respect to the reduced incidence of bronchopulmonary dysplasia may be attributable to the early initiation of therapy and the choice of dose, since it has been shown repeatedly that only a fraction of the administered inhaled dose is deposited in the lungs. 11,26,27 Budesonide was associated with a significantly lower risk than the risk with placebo of two additional prespecified secondary outcomesa patent ductus arteriosus considered by clinical staff to require surgical ligation and the requirement for reintubation after the last administration of the study drug.…”

“…12 However, we consider it unlikely that increased systemic absorption of the study drug could explain any differences in mortality. A meta-analysis of randomized trials of the early use of systemic postnatal glucocorticoids, as compared with placebo, in preterm infants did not show an increased risk of mortality up to the time of hospital discharge (risk ratio, 1.00; 95% CI, 0.89 to 1.13).…”

Challenges in Diagnosis and Treatment of Neonatal Ventriculitis: A Case Report and Systematic Review of Difficult-to-Treat Central Nervous System Infection Resistant to Conventional Therapy

“…31,32,35,38 GNB pathogens, in particular E. coli, Klebsiella, and Pseudomonas species, are detected in 20 to 25% of early-onset bacteremia and 14% of infant meningitis worldwide. 61 Acinetobacter 8), left against advice (6), survivors (22), and neurologic sequelae (8) Bentlin et al 45 Epidemiological study…”

“…Drugs weakly penetrate the blood-brain barrier, and CSF flow may be obstructed by cellular debris and proteins. 8 Persistently poor clinical and laboratory findings suggest an unsatisfactory response and that a second delivery method is required to increase drug concentrations in the ventricles. IVT therapy refers to direct instillation of the drug into the ventricular system via an EVD or a reservoir.…”

Early Inhaled Budesonide for the Prevention of Bronchopulmonary Dysplasia

“…for death at 36 weeks (postmenstrual age) of 0.73 (95% CI, 0.44 to 1.21). 12 In two of the trials, as in our trial, glucocorticoids were administered within 24 hours after birth 21,22 ; in both of these trials, the risk ratio for death was below 1.…”

“…dysplasia. 12 We speculate that aside from our trial including a large enough sample size to enable us to detect a clinically meaningful treatment effect, our positive finding with respect to the reduced incidence of bronchopulmonary dysplasia may be attributable to the early initiation of therapy and the choice of dose, since it has been shown repeatedly that only a fraction of the administered inhaled dose is deposited in the lungs. 11,26,27 Budesonide was associated with a significantly lower risk than the risk with placebo of two additional prespecified secondary outcomesa patent ductus arteriosus considered by clinical staff to require surgical ligation and the requirement for reintubation after the last administration of the study drug.…”

“…12 However, we consider it unlikely that increased systemic absorption of the study drug could explain any differences in mortality. A meta-analysis of randomized trials of the early use of systemic postnatal glucocorticoids, as compared with placebo, in preterm infants did not show an increased risk of mortality up to the time of hospital discharge (risk ratio, 1.00; 95% CI, 0.89 to 1.13).…”

Challenges in Diagnosis and Treatment of Neonatal Ventriculitis: A Case Report and Systematic Review of Difficult-to-Treat Central Nervous System Infection Resistant to Conventional Therapy

“…31,32,35,38 GNB pathogens, in particular E. coli, Klebsiella, and Pseudomonas species, are detected in 20 to 25% of early-onset bacteremia and 14% of infant meningitis worldwide. 61 Acinetobacter 8), left against advice (6), survivors (22), and neurologic sequelae (8) Bentlin et al 45 Epidemiological study…”

“…Drugs weakly penetrate the blood-brain barrier, and CSF flow may be obstructed by cellular debris and proteins. 8 Persistently poor clinical and laboratory findings suggest an unsatisfactory response and that a second delivery method is required to increase drug concentrations in the ventricles. IVT therapy refers to direct instillation of the drug into the ventricular system via an EVD or a reservoir.…”