To read the full review go to: Non-corticosteroid adjuvant therapies for acute bacterial meningitis

Plain language summary

Review question

We wanted to find out if adjuvant therapies (therapies used in addition to standard treatment methods) other than corticosteroids (a type of anti-inflammatory drug) are better or worse than standard treatment (antibiotics, used with or without corticosteroids) alone or with a placebo (dummy treatment) in treating people with acute bacterial meningitis (a bacterial infection of the membranes that surround and protect the brain). To answer this question, we reviewed the available evidence on the effect of adjuvant therapies other than corticosteroids on death, hearing loss, and other neurological sequelae (aftereffects of a disease) in people with acute bacterial meningitis.

Background

Acute bacterial meningitis is an infection of the protective membranes that surround the brain, known as the meninges. Meningitis causes inflammation and damage to the brain tissue, leading to death in 7% to 50% of cases. Survivors often have neurological sequelae (neurological symptoms that persist after the infection is cured, such as hearing loss, physical disability (impairment), localised problems (focal neurological deficits, or loss of normal function of brain, spinal cord, or nerves that is localised to a specific area of the body), seizures, and cognitive impairment, which often lead to learning difficulties in children and trouble returning to work for adults) that can last for weeks to years. Bacterial meningitis is treated with antibiotics as the primary therapy, with corticosteroids the only recommended adjuvant therapy that has been shown to improve outcomes. We wanted to find out whether the use of adjuvant therapies other than corticosteroids is better or worse than standard treatment alone or with a placebo in people with acute bacterial meningitis.

Search date

The evidence is current to September 2021.

Study characteristics

We assessed all adjuvant pharmacological (drug) therapies (except corticosteroids) for which we found randomised controlled trials (a type of study where participants are randomly assigned to one of two or more treatment groups) conducted in people with acute bacterial meningitis. We found eight studies examining five different interventions.

Three studies (1274 participants) evaluated paracetamol in children (excluding newborns) with bacterial meningitis. The studies were funded by government funding organisations and research foundations. One study additionally reported funding support from a daily newspaper, and one study reported funding support from a pharmaceutical company.

Two studies (49 participants) evaluated immunoglobulins in bacterial meningitis. One study included children (excluding newborns), whilst the other study included adults of unspecified age. Funding sources were not specified. One study received the study medication from a pharmaceutical company.

One study (15 participants) evaluated heparin (blood thinner) in adults with bacterial meningitis. The study was funded by a research foundation.

One study (57 participants) evaluated pentoxifylline in children (excluding newborns) with bacterial meningitis. Funding sources for the study were not specified.

One study (30 participants) evaluated a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide in children (excluding newborns). Funding sources for the study were not specified.

Key results

We found that paracetamol may make little or no difference for the number of deaths (paracetamol 35.2% (potentially causing between 7.1% fewer deaths up to 3.4% more deaths) versus placebo 37.4%, low certainty evidence). Paracetamol may make little to no difference in hearing loss (paracetamol 19.6% versus placebo 18.8%, low certainty evidence); neurological sequelae other than hearing loss (paracetamol 32.1% versus placebo 20.6%, low certainty evidence); or severe hearing loss (paracetamol 11.7% versus placebo 12.2%, low certainty evidence). Paracetamol may lead to slightly more short-term neurological sequelae other than hearing loss (paracetamol 15.7% versus placebo 7.9%, low certainty evidence) and slightly more long-term neurological sequelae other than hearing loss (paracetamol 8.8% versus placebo 3.8%, low certainty evidence). No side effects were reported.

The effect of immunoglobulins, heparin, pentoxifylline, and a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide on number of deaths is uncertain due to the very low certainty of the evidence. No side effects were reported for immunoglobulins (very low certainty evidence), and a 3.3% rate of allergic reactions was reported in patients receiving a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide (intervention group) (very low certainty evidence). None of our other outcomes (hearing loss, neurological sequelae other than hearing loss, severe hearing loss, and short-term or long-term neurological sequelae other than hearing loss) were reported in these studies.

Certainty of the evidence

The certainty of evidence for paracetamol was low for all outcomes due to issues with study design, inconsistency of results and too few participants in the studies and sparse reporting of the outcomes of interest for this review. The certainty of evidence was very low for all other treatments due to issues with study design and not enough data. No conclusions could be drawn about the effectiveness of any of the evaluated treatments at this time because of the limited and low certainty of the evidence. This may change if results from larger studies with improved design become available.