Slow initial β-lactam infusion and oral paracetamol to treat childhood bacterial meningitis: a randomised, controlled trial

Pelkonen, Tuula; Roine, Irmeli; Cruzeiro, Manuel Leite; Pitkäranta, Anne; Kataja, Matti; Peltola, Heikki

doi:10.1016/s1473-3099(11)70055-x

Cited by 85 publications

(86 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition to corticosteroids, several other adjunctive approaches may be useful (Table) [60][61][62][63][64][65][66][67] ; although there is no proved clinical evidence for use of these therapies and some are only experimental. The use of bactericidal but nonbacteriolitic antibiotics to reduce endotoxin and other injurious substance release into CSF as rifampicin and daptomycin have been investigated in animal models of pneumococcal meningitis 63 .…”

Section: Neuronal Damage and Targets For Adjunctive Therapymentioning

confidence: 99%

Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches

Barichello

Generoso

Collodel

et al. 2012

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

Pneumococcal meningitis is a life-threatening disease characterized by an acute purulent infection affecting piamater, arachnoid and the subarachnoid space. The intense inflammatory host's response is potentially fatal and contributes to the neurological sequelae. Streptococcus pneumoniae colonizes the nasopharynx, followed by bacteremia, microbial invasion and blood-brain barrier traversal. S. pneumoniae is recognized by antigen-presenting cells through the binding of Toll-like receptors inducing the activation of factor nuclear kappa B or mitogen-activated protein kinase pathways and subsequent up-regulation of lymphocyte populations and expression of numerous proteins involved in inflammation and immune response. Many brain cells can produce cytokines, chemokines and others pro-inflammatory molecules in response to bacteria stimuli, as consequence, polymorphonuclear are attracted, activated and released in large amounts of superoxide anion and nitric oxide, leading to the peroxynitrite formation, generating oxidative stress. This cascade leads to lipid peroxidation, mitochondrial damage, blood-brain barrier breakdown contributing to cell injury during pneumococcal meningitis.

show abstract

Section: Neuronal Damage and Targets For Adjunctive Therapymentioning

confidence: 99%

Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches

Barichello

Generoso

Collodel

et al. 2012

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

show abstract

“…The changes in the concentrations of MMP-9 and TIMP-1 and their MR from admission to 1 week of treatment (day 7) were analyzed using paired CSF samples taken, whenever enough CSF was available, on those days from patients of a previous BM study (8) (Table 1; see also Fig. S1 in the supplemental material).…”

mentioning

confidence: 99%

“…S1 in the supplemental material). All patients were treated with intravenous cefotaxime but were randomized to receive it during the first 24 h either as a continuous infusion or as an every-6-hour bolus (8). No adjuvant dexamethasone was given, but all the patients received oral glycerol (9).…”

mentioning

confidence: 99%

Changes in MMP-9 and TIMP-1 Concentrations in Cerebrospinal Fluid after 1 Week of Treatment of Childhood Bacterial Meningitis

et al. 2015

Self Cite

View full text Add to dashboard Cite

We explored the changes of the initially highly upgraded cerebrospinal fluid matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of MMP 1 (TIMP-1) response during recovery of childhood bacterial meningitis and their association with outcome. The sizes of these changes varied substantially, but a steeper decrease in the MMP-9 and an increase of the TIMP-1 concentrations augured a better outcome. Matrix metalloproteinases (MMPs) are a group of zinc-dependent enzymes which, through their ability to degrade extracellular matrix and nonmatrix bioactive substances, can direct and modify multiple diverse biological and pathological processes, among them the inflammatory and immune responses (1). The MMP activities are inhibited by their specific endogenous inhibitors, the tissue inhibitors of MMPs (TIMPs). Under physiological conditions, MMP activity is precisely regulated, whereas in disease, MMP activity is unbalanced (1).In childhood bacterial meningitis (BM), the initial concentrations of MMP-9 and TIMP-1 in the cerebrospinal fluid (CSF), and their molar ratio (MR), are highly upgraded, and the highest values are associated with adverse outcomes (2-6). We studied how the response was shut down and whether this process influenced the outcome. A better understanding of the response kinetics may open novel opportunities for therapeutic interventions (1, 7).The changes in the concentrations of MMP-9 and TIMP-1 and their MR from admission to 1 week of treatment (day 7) were analyzed using paired CSF samples taken, whenever enough CSF was available, on those days from patients of a previous BM study (8) ( Table 1; see also Fig. S1 in the supplemental material). All patients were treated with intravenous cefotaxime but were randomized to receive it during the first 24 h either as a continuous infusion or as an every-6-hour bolus (8). No adjuvant dexamethasone was given, but all the patients received oral glycerol (9). The audiological outcome was tested on day 7 by brain stem auditory evoked potentials (Madsen Octavus). Deafness was defined as a hearing threshold Ͼ80 dB in the better ear. Severe neurological sequelae were defined as blindness, quadriplegia or paresis, hydrocephalus requiring a shunt, or severe psychomotor retardation at discharge.The MMP-9 and TIMP-1 concentrations were determined by enzyme-linked immunosorbent assay (ELISA), as described previously (4). The changes in percent were compared with other data using the Spearman correlation for quantitative variables and the Mann-Whitney U test or Kruskal-Wallis test for nominal variables. The day-7 values also were examined in the same manner (see Tables S2 and S4 in the supplemental material). A P value of Ͻ0.05 was taken as significant.Within 1 week, the MMP-9 concentration fell by 90% (interquartile range [IQR], 28%) ( Fig. 1) from 476 ng/ml (IQR, 752 ng/ml) to 38 ng/ml (IQR, 62 ng/ml) (P Ͻ 0.0001). The children who later died (n ϭ 3) (Table 1) had a smaller decrease of 26% (IQR, 10%; P ϭ 0.02), and their day-7 MMP-9 concentration (see Table S2 in th...

show abstract

“…[15] A recent study in children showed that a β-lactam infusion along with paracetamol lowered mortality in childhood bacterial meningitis in the first 3 days, but overall mortality was unchanged. [16] This improvement was thought to be related to the prolonged infusion of the antibiotic, rather than the adjuvant paracetamol, because the antibiotics exhibit time-dependent killing and infusion increases the time above the MIC. [17] All of our patients had confirmed meningitis, with evidence of inflammation, but there was a poor correlation between plasma and CSF levels as measured after the fifth dose.…”

Section: Discussionmentioning

confidence: 99%

A comparison of the pharmacokinetics of Aspen Ceftriaxone and Rocephin in community-acquired meningitis

et al. 2013

View full text Add to dashboard Cite

Background. Community-acquired bacterial meningitis (CABM) is a life-threatening condition that is common among immunocompromised individuals. Intravenous ceftriaxone, of which Rocephin (ROC) is the originator brand, is recommended as first-line therapy in South Africa. Despite concerns regarding therapeutic equivalence with generic agents, this is the first study that has been conducted comparing clinical pharmacokinetics (PK) of a generic ceftriaxone formulation with the originator. Objective. To compare the PK and safety of Aspen Ceftriaxone (AC) and ROC in the treatment of adult CABM. Methods. A total of 63 eligible patients were randomised 1:1 to receive 2 g of either medication twice daily for a duration based on the identity of the causative organism and their physician's clinical judgment. The primary endpoint of this study was the comparison of clinical PK, specifically the concentrations of each drug in the cerebrospinal fluid with corresponding paired plasma samples. While this study was underpowered to assess efficacy, safety could be evaluated on the basis of reported adverse events. Results. The two patient groups were epidemiologically similar. There were no statistically significant differences in PK between either agent, nor any difference with regard to safety. Conclusion. AC can be considered as equivalent to ROC with regard to PK and safety in patients with CABM. Med J 2013;103(12):906-909. S Afr

show abstract

Slow initial β-lactam infusion and oral paracetamol to treat childhood bacterial meningitis: a randomised, controlled trial

Abstract: The Päivikki and Sakari Sohlberg, the Sigrid Jusélius, and the Paediatric Research Foundations, and the daily newspaper Helsingin Sanomat.

Cited by 85 publications

References 34 publications

Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches

Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches

Changes in MMP-9 and TIMP-1 Concentrations in Cerebrospinal Fluid after 1 Week of Treatment of Childhood Bacterial Meningitis

A comparison of the pharmacokinetics of Aspen Ceftriaxone and Rocephin in community-acquired meningitis

Contact Info

Product

Resources

About