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Clin Evid. 2004; 2004: 0907.
Published online 2004 October 1.
PMCID: PMC2907554

Meningococcal disease

Dr Jailson B B Correia, MBBS, MTropPaed# and C A A Hart, MBBS, BSc, PhD, FRCPCH, FRCPath, Professor#

Abstract

Introduction

Neisseria meningitides (the meningococcus) causes sporadic cases of conjunctivitis, septic arthritis, meningitis and septicaemia in temperate countries, but regular epidemics occur in sub-Saharan Africa. Transmission is via close contact, with young children and students most at risk of infection and of death in the UK. About 10-15% of people carry the meningococcus in the throat, but invasive disease is associated with recent acquisition of a virulent strain. In developed countries, mortality is up to 25% for people with septicaemia, but less than 1% for meningitis alone.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent meningococcal disease in contacts and carriers? What are the effects of interventions to treat suspected cases of meningococcal disease before admission to hospital? What are the effects of treatments for meningococcal meningitis on admission in children and in adults? What are the effects of treatments for meningococcal septicaemia in children and in adults? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2004 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 26 systematic reviews, RCTs or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding corticosteroids, antibiotics for throat carriage, pre-admission parenteral penicillin, prophylactic antibiotics in contacts.

Key Points

Neisseria meningitides (the meningococcus) causes sporadic cases of conjunctivitis, septic arthritis, meningitis and septicaemia in temperate countries, but regular epidemics occur in sub-Saharan Africa.

  • Transmission is via close contact, with young children and students most at risk of infection and of death in the UK.
  • About 10-15% of people carry the meningococcus in the throat, but invasive disease is associated with recent acquisition of a virulent strain.
  • In developed countries, mortality is up to 25% for people with septicaemia, but less than 1% for meningitis alone.

Antibiotics can reduce carriage of meningococci in the throat compared with placebo, but we don't know whether this leads to a reduced risk of meningococcal disease, as no studies have been found.

Prophylactic antibiotics may reduce the risks of infection in contacts, although no good quality studies have been found that confirm this.

We don't know whether pre-admission parenteral penicillin is beneficial, as we found no studies, but the potential benefits of early treatment are likely to outweigh any harm from its use.

Adding corticosteroids to treatment reduces mortality in adults with bacterial meningitis of any cause, but we don't know whether it is beneficial in the subgroup of people with meningococcal meningitis.

  • Corticosteroids may not prevent neurological sequelae in adults.
  • Adding corticosteroids to treatment reduces severe hearing loss in children, but has not been shown to reduce mortality, and we don't know whether it is beneficial in the subgroup with meningococcal disease.

We don't know whether adding corticosteroids is beneficial in children or adults with meningococcal septicaemia, as no studies have been found.

  • Corticosteroids have not been shown to reduce mortality in adults or children with severe sepsis.

About this condition

Definition

Meningococcal disease is any clinical condition caused by Neisseria meningitidis (the meningococcus) groups A, B, C, W135, or other serogroups. These conditions include purulent conjunctivitis, septic arthritis, meningitis, and septicaemia with or without meningitis. In this chapter we cover meningococcal meningitis and meningococcal septicaemia with or without meningitis.

Incidence/ Prevalence

Meningococcal disease is sporadic in temperate countries, and is most commonly caused by group B or C meningococci. The annual incidence in Europe varies from fewer than 1 case/100 000 people in France, up to 4-5 cases/100 000 people in the UK and Spain, and in the USA it is 0.6-1.5 cases/100 000 people. Occasional outbreaks occur among close family contacts, secondary school pupils, military recruits, and students living in halls of residence. Sub-Saharan Africa has regular epidemics in countries lying in the expanded "meningitis belt", reaching 500 cases/100 000 people during epidemics, which are usually due to serogroup A, although recent outbreaks of serogroup W135 cause concern. In sub-Saharan Africa, over 90% of cases present with meningitis alone.

Aetiology/ Risk factors

The meningococcus colonises and infects healthy people, and is transmitted by close contact, probably by exchange of upper respiratory tract secretions (see table 1 ). The risk of transmission is greatest during the first week of contact. Risk factors include crowding and exposure to cigarette smoke. In the UK, children younger than 2 years have the highest incidence of meningococcal disease, with a second peak between ages 15-24 years. There is currently an increased incidence of meningococcal disease among university students, especially among those in their first term and living in catered accommodation, although we found no accurate numerical estimate of risk from close contact in, for example, halls of residence. Close contacts of an index case have a much higher risk of infection than do people in the general population. The risk of epidemic spread is higher with groups A and C meningococci than with group B meningococci. It is not known what makes a meningococcus virulent. Certain clones tend to predominate at different times and in different groups. Carriage of meningococcus in the throat has been reported in 10-15% of people; recent acquisition of a virulent meningococcus is more likely to be associated with invasive disease.

Table 1
Risk of infection among contacts (see text).

Prognosis

Mortality is highest in infants and adolescents, and is related to disease presentation and availability of therapeutic resources. In developed countries, case fatality rates have been around 19-25% for septicaemia, 10-12% for meningitis plus septicaemia, and less than 1% in meningitis alone, but an overall reduction in mortality was observed in recent years in people admitted to paediatric intensive care units.

Aims of intervention

To prevent disease in contacts; to prevent development of meningococcal disease and its complications, with minimal adverse effects.

Outcomes

Rates of infection; rates of eradication of throat carriage; adverse effects of treatment; mortality; sequelae.

Methods

Clinical Evidence search and appraisal May 2004, including a search for observational studies. In addition, the authors drew from a collection of references from the pre-electronic data era and cross-references from relevant papers. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).

Table
GRADE evaluation of interventions for meningococcal disease

Glossary

Carrier
Individual in whom Neisseria meningitidis can be retrieved from the nasopharynx by swabbing. Most carriers are asymptomatic and unaware of their carriage status
Contact
Those recently exposed to an index case of meningococcal disease and who have a higher risk of developing the disease when compared with the general population (usually close, prolonged contact in the same household or direct contact with respiratory secretions).
Meningitis (meningococcal)
A case with clinical signs of meningitis (i.e. fever, headache, vomiting, nuchal rigidity) plus laboratory evidence of meningococcal infection, such as a positive blood or cerebrospinal fluid culture or polymerase chain reaction.
Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Sepsis
The systemic response to infection, manifested by two or more of the following: hyperthermia (or hypothermia), high heart rate, high respiratory rate (or low PaCO2 ), high or low white blood cell count (or > 10% immature forms), although values are age dependent. Severe sepsis is associated with organ dysfunction, hypoperfusion, or hypotension. Septic shock is sepsis with hypotension, despite adequate fluid resuscitation, along with the presence of perfusion abnormalities.
Septicaemia (meningococcal)
A case with systemic signs and symptoms of infection (i.e. fever, malaise, patient “unwell”) plus a skin rash, which can be purpuric (petechial, ecchymotic) or, less often, maculopapular. The laboratory provides evidence of meningococcal infection in the blood.
Suspected cases
Cases with early clinical signs of meningitis, septicaemia, or both, where the healthcare worker (usually the general practitioner) suspects meningococcal aetiology.
Very low-quality evidence
Any estimate of effect is very uncertain.

Notes

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

Contributor Information

Dr Jailson B B Correia, Instituto Materno Infantil de Pernambuco, Recife, Brazil.

C A A Hart, Department of Medical Microbiology and Genitourinary Medicine, University of Liverpool, Liverpool, UK.

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2004; 2004: 0907.
Published online 2004 October 1.

Prophylactic antibiotics in contacts

Summary

We found no direct information about the effects of prophylactic antibiotics on the incidence of meningococcal disease among contacts. Some studies suggest that prophylactic sulfadiazine may reduce the risk of meningococcal disease over 8 weeks compared with no prophylaxis. We found no evidence regarding which contacts should be treated.

Benefits

We found no systematic review and no RCTs examining the effect of prophylactic antibiotics in people in contact with someone with meningococcal disease (see comment below).

Rifampicin:

We found no studies.

Phenoxymethylpenicillin:

We found one retrospective study, but the results of that study cannot be generalised beyond the sample tested.

Sulfadiazine:

One cohort study of soldiers in temporary troop camps in the 1940s compared the incidence of meningococcal disease in camps where sulfadiazine (sulphadiazine) was given to everyone after a meningococcal outbreak versus the incidence in camps where no prophylaxis was given. The study reported a higher incidence of meningococcal disease in soldiers not given prophylaxis (approximate figures 17/9500 [0.18%] v 2/7000 [0.03%] over 8 weeks, P value not reported).

Harms

Rifampicin:

No excess adverse effects compared with placebo were found in RCTs on eradicating throat carriage of meningococcal disease. However, rifampicin is known to cause various adverse effects, including turning urine and contact lenses orange, and inducing hepatic microsomal enzymes, potentially rendering oral contraception ineffective. Rifampicin prophylaxis may be associated with emergence of resistant strains.

Sulfadiazine:

One in 10 soldiers experienced minor adverse events, including headache, dizziness, tinnitus, and nausea.

Comment

RCTs addressing this question are unlikely to be performed because the intervention has few associated risks, whereas meningococcal disease has high associated risks. RCTs would also need to be large to find a difference in the incidence of meningococcal disease. In the sulfadiazine cohort study, the two infected people in the treatment group only became infected after leaving the camp.

Substantive changes

No new evidence

2004; 2004: 0907.
Published online 2004 October 1.

Antibiotics for throat carriage

Summary

INFECTION RATES Antibiotics compared with placebo (throat carriage): Antibiotics are more effective at achieving high rates of eradication of meningococcal throat carriage ( moderate-quality evidence ). We don’t know how antibiotics compare with each other at eradicating meningococcal throat carriage. NOTE We found no direct information about whether eradicating throat carriage of meningococcus reduces the risk of meningococcal disease.

Benefits

We found no systematic review.

Incidence of disease:

We found no RCTs or observational studies that examined whether eradicating throat carriage of meningococcus reduces the risk of meningococcal disease.

Throat carriage:

We found five placebo controlled RCTs that examined the effect of antibiotics on carriage of meningococcus in the throat (see table 2 ) . All trials found that antibiotics (rifampicin, minocycline, or ciprofloxacin) achieved high rates of eradication (ranging from 90–97%), except one trial of rifampicin in students with heavy growth on culture, in which the rate of eradication was 73%. Eradication rates on placebo ranged from 9–29%. We found seven RCTs that compared different antibiotic regimens (see table 3 ). One RCT conducted in the 1960s found that oral erythromycin was ineffective whereas intramuscular penicillin eradicated meningococcal carriage in 35% of carriers among army recruits during a group C meningococcal meningitis outbreak at a US army base. Another RCT found that sulfamidine was ineffective whereas rifampicin eradicated meningococcal throat carriage in nearly 80% of carriers among household contacts in northern Nigeria. Four RCTs found no significant difference between rifampicin and minocycline, ciprofloxacin, azithromycin, or intramuscular ceftriaxone in eradicating meningococcal throat carriage. However, one RCT randomised households to different treatments and found that intramuscular ceftriaxone significantly increased eradication rates compared with rifampicin (see comment below).

Table 2
Effects of antibiotics on throat carriage: results of comparative RCTs (see text).
Table 3
Effect of antibiotics on throat carriage: results of placebo controlled RCTs (see text).

Harms

Minocycline:

One RCT reported adverse effects (1 or more of nausea, anorexia, dizziness, and abdominal cramps) in 36% of participants.

Rifampicin:

See harms of postexposure antibiotic prophylaxis.

Ciprofloxacin:

Trials of single dose prophylactic regimens reported no more adverse effects than with comparators or placebo. Ciprofloxacin is contraindicated in pregnancy and in children because animal studies have indicated a possibility of articular cartilage damage in developing joints.

Ceftriaxone:

Two RCTs of ceftriaxone (given as a single intramuscular injection) found no significant adverse effects. In another RCT, 12% of participants complained of headache.

Azithromycin:

The RCT reported no serious or moderate adverse effects. It found no significant difference in the rate of adverse effects such as nausea, abdominal pain, and headache of short duration with azithromycin compared with rifampicin.

Comment

There is consensus that eradicating meningococcal throat carriage is appropriate for preventing meningococcal disease. Due to the large number of participants required, it is unlikely that RCTs will be conducted on the efficacy of prophylactic antibiotics in preventing secondary community acquired meningococcal disease in household contacts.

Ceftriaxone:

The fourth RCT used cluster randomisation, and therefore the results should be interpreted with caution.

Substantive changes

No new evidence

2004; 2004: 0907.
Published online 2004 October 1.

Pre-admission parenteral penicillin

Summary

MORTALITY Compared with no pre-admission antibiotics: We don’t know whether pre-admission parenteral penicillin is more effective at reducing mortality in people with suspected cases of meningococcal disease ( very low-quality evidence ).

Benefits

We found no systematic review or RCTs but seven observational studies on the effect of pre-admission parenteral penicillin in suspected cases of meningococcal disease (see table 4 ). We also found two reports of pooled data from three of the observational studies. The first report (3 English observational studies, 487 people) found that pre-admission parenteral antibiotics significantly reduced mortality compared with no pre-admission antibiotics (OR 2.61, 95% CI 1.04 to 7.18). However, the second report (664 people; the same people in the English studies plus partial data from a Danish cohort) found no significant benefit with pre-admission parenteral antibiotics (outcomes not specified; OR 0.82, 95% CI 0.43 to 1.56). Three observational studies found lower mortality rates with pre-admission parenteral antibiotics compared with no pre-admission antibiotics, although the difference between the two treatment groups in each study did not reach significance. However, one study did not support this finding (mortality rate 9/77 [11.7%] with pre-admission parenteral penicillin v 26/402 [7%] with no pre-admission antibiotics; OR 1.9, 95% CI 0.9 to 4.3).

Table 4
Effects of early (pre-admission) parenteral penicillin: results of observational studies (see text).

Harms

It is difficult to differentiate people with early features of meningococcal disease from those with self limiting illnesses. According to more or less strict criteria for suspicion, between 28% and 89% of individuals receive parenteral penicillin unnecessarily. One study of the harms of penicillin found that anaphylaxis occurred in about 0.04% of cases and that fatal anaphylaxis occurred in about 0.002% of cases.

Comment

We found no studies about the relationship between early treatment with antibiotics and development of subsequent antibiotic resistance. Retrospective observational studies usually provide limited evidence for treatment interventions. In the case of pre-admission penicillin, no study was able to adjust adequately for clinical severity, stage of disease progression, or cointerventions such as earlier suspicion and referral (following media coverage and official recommendation). However, it is unlikely that RCTs on pre-admission antibiotics will be performed because of the unpredictably rapid course of disease in some people and the likely risks involved in delaying treatment, combined with a low risk of causing harm.

Substantive changes

No new evidence

2004; 2004: 0907.
Published online 2004 October 1.

Adding corticosteroids

Summary

MORTALITY Adding corticosteroids compared with adding placebo to antibiotics: We don’t know whether adding corticosteroids to antiobiotics is more effective at reducing mortality in children with meningococcal meningitis ( very low-quality evidence ). Dexamethasone compared with placebo: Dexamethasone may be no more effective at reducing mortality in children with meningococcal meningitis (very low-quality evidence). NEUROLOGICAL SEQUELAE Dexamethasone compared with placebo: Dexamethasone may be no more effective at reducing neurological sequelae including hearing loss in children with meningococcal meningitis (very low-quality evidence).

Benefits

We found no systematic review or RCTs on adding corticosteroids specifically in children with meningococcal meningitis. We found one systematic review (search date 2002, 10 RCTs and 8 quasi-randomised studies, 4 trials including people over the age of 16 years) that compared adding corticosteroids to antibiotics versus adding placebo to antibiotics in people of all ages and bacterial meningitis of any aetiology for the outcomes of mortality, severe hearing loss, and neurological sequelae. The systematic review performed subgroup analyses for two age groups (under 16 years and over 16 years) and for the causative organisms of bacterial meningitis. It found no significant difference between adding corticosteroids and adding placebo for mortality in children with bacterial meningitis of any aetiology (14 RCTs or quasi-randomised studies, 1478 children aged under 16 years; mortality: 46/746 [6.2%] with adding corticosteroids v 48/732 [6.6%] with placebo; RR 0.95, 95% CI 0.65 to 1.37). A subgroup analysis in people with meningococcal meningitis found no significant difference between corticosteroids and placebo for the outcome of mortality in people of all ages (8 RCTs [2 RCTs included people aged over 16 years], 353 people, mortality: RR 0.61, 95% CI 0.23 to 1.64). The review found that, compared with adding placebo, adding corticosteroids significantly reduced severe hearing loss in children with bacterial meningitis of any aetiology (12 RCTs, 1013 children aged under 16 years; severe hearing loss: 15/514 [2.9%] with corticosteroids v 49/499 [9.8%] with placebo; RR 0.31, 95% CI 0.18 to 0.54). The reduction in severe hearing loss remained significant when the causative agent, Haemophilus influenzae, was excluded from the analysis (10 RCTs, 394 children aged under 16 years; severe hearing loss: 6/191 [3.1%] with adding corticosteroids v 19/203 [9.4%] with controls; RR 0.42, 95% CI 0.20 to 0.89). The review did not conduct a separate subgroup analysis for children less than 16 years of age for the outcome of neurological sequelae. It found no significant difference between adding corticosteroids and adding placebo for short term or long term neurological sequelae in people of all ages with bacterial meningitis of any aetiology (short term neurological sequelae: 8 RCTs [2 RCTs included people aged over 16 years], 482 people; RR 0.72, 95% CI 0.48 to 1.06; long term neurological sequelae: 10 RCTs [1 RCT included people aged over 16 years], 1163 people; RR 0.67, 95% CI 0.45 to 1.00). The review defined hearing loss as severe when there was bilateral hearing loss of greater than 60 dB or requiring bilateral hearing aids, and defined neurological sequelae as focal neurological deficits other than hearing loss, such as epilepsy (not present before meningitis onset), severe ataxia, and severe memory or concentration disturbance. It defined short term neurological sequelae as those assessed between discharge and 6 weeks after hospital discharge and long term neurological sequelae as those assessed between 6 and 12 months after discharge.

Harms

The systematic review recorded adverse events (clinically evident gastrointestinal bleeding, pericarditis, reactive arthritis, herpes zoster, herpes simplex or fungal infections, persistent or secondary fever) as reported in 18 trials (1183 people, including 1008 children, all aetiologies). It found no significant difference in their frequency between treatment groups (146/599 with corticosteroids v 131/584 with placebo; RR 1.06, 95% CI 0.88 to 1.27).

Comment

In clinical practice, when a child is brought to hospital with bacterial meningitis, clinical signs and a cloudy cerebrospinal fluid will direct the initiation of early treatment, as timing can affect prognosis, and the decision on whether to start corticosteroids almost always precedes knowledge of the specific aetiology. Interpreting the results of available evidence on the use of corticosteroids in the context of meningococcal meningitis in children demands caution, as age- and pathogen-specific evidence is scarce. In regions where the conjugate vaccine has been introduced, the incidence of Haemophilus influenzae type b (Hib) has fallen dramatically and the applicability of evidence from trials performed prior to this change in epidemiology is questionable. It is clinically relevant to group people with non-Hib meningitis together, but this strategy is not free of caveats because the different agents in this group may have different rates of death and sequelae and respond differently to corticosteroids. We found one RCT comparing dexamethasone versus placebo in 598 Malawian children aged 2 months to 13 years with acute bacterial meningitis of all aetiologies, including 67 children with meningococcal meningitis. The RCT conducted subgroup analyses according to the causative agents of bacterial meningitis. In a subgroup analysis for the causative agent for meningococcal meningitis, Neisseria meningitidis, the RCT found no significant difference between dexamethasone and placebo for the outcomes of mortality or neurological sequelae including hearing loss (mortality: 1/32 [3%] with dexamethasone v 2/35 [6%] with placebo, P value reported as not significant; neurological sequelae including hearing loss: 5/30 [17%] with dexamethasone v 10/33 [30%] with placebo; RR 0.55, 95% CI 0.21 to 1.43, P = 0.33). The results of this Malawian RCT may not be applicable in settings other than where there is late presentation, partial and inadequate treatment, or a high prevalence of HIV, anaemia, and malnutrition, all of which may considerably alter the results.

Substantive changes

No new evidence

2004; 2004: 0907.
Published online 2004 October 1.

Adding corticosteroids

Summary

MORTALITY Adding corticosteroids compared with adding placebo to antibiotics: Adding corticosteroids to antibiotics may be no more effective at reducing mortality in people aged over 16 years with meningococcal meningitis ( very low-quality evidence ). NEUROLOGICAL SEQUELAE Adding corticosteroids compared with adding placebo to antibiotics: Adding corticosteroids to antibiotics may be no more effective at reducing neurological sequelae in people aged over 16 years with meningococcal meningitis (very low-quality evidence). NOTE We found no direct information about the effects of adding corticosteroids specifically in adults with meningococcal meningitis.

Benefits

We found no systematic review or RCTs on adding corticosteroids specifically in adults with meningococcal meningitis. We found one systematic review (search date 2003, 2 RCTs and 3 quasi-randomised studies, 623 people aged over 16 years with acute bacterial meningitis of any aetiology, including 232 people with meningococcal meningitis) comparing adding corticosteroids (dexamethasone in 4 trials; hydrocortisone in 1 RCT) versus adding placebo in people with bacterial meningitis of any aetiology for the outcomes of mortality and neurological sequelae. The review found that, compared with adding placebo, adding corticosteroids significantly reduced mortality in adults with bacterial meningitis of any aetiology (mortality: 36/308 [12%] with dexamethasone v 69/315 [22%] with placebo; RR 0.60, 95% CI 0.40 to 0.81; P = 0.02). A subgroup analysis for meningococcal meningitis found no significant difference in mortality with adding corticosteroids compared with adding placebo (RR 0.9, 95% CI 0.3 to 2.1). The review found that, compared with controls, adding corticosteroids reduced neurological sequelae in people with bacterial meningitis of any aetiology, but the difference did not quite reach significance (5 RCTs, 340 people aged over 16 years; neurological sequelae: 26/184 [14%] with dexamethasone v 35/156 [22%] with placebo; RR 0.60, 95% CI 0.40 to 1.00; P = 0.05). A subgroup analysis for meningococcal meningitis found no significant difference in neurological sequelae with adding corticosteroids compared with placebo (RR 0.5, 95% CI 0.1 to 1.7).

Harms

The systematic review recorded data on adverse events in 391 patients, with clinically evident gastrointestinal bleeding occurring in 1% of cases in the corticosteroid group and in 4% in the placebo group. It found no significant difference in the frequency of other adverse events (pericarditis, reactive arthritis, herpes zoster, herpes simplex or fungal infections, persistent or secondary fever) with corticosteroids compared with placebo (RR of any adverse event compared with placebo 1.0, 95% CI 0.5 to 2.0).

Comment

In clinical practice, when a person presents with bacterial meningitis, clinical signs and a cloudy cerebrospinal fluid will direct the initiation of early treatment, as timing can affect prognosis, and the decision on whether to start corticosteroids almost always precedes knowledge of the specific aetiology. None of the RCTs included in the systematic review were powered to detect a significant effect of corticosteroid treatment in the subgroup of people with meningococcal meningitis, probably as a result of the lower rates of mortality and sequelae in this group. One RCT identified by the review, involving various European centres, took 9 years to complete, but still failed to enrol enough patients with meningococcal meningitis to achieve significant results.

Substantive changes

No new evidence

2004; 2004: 0907.
Published online 2004 October 1.

Adding corticosteroids

Summary

MORTALITY Adding corticosteroids compared with adding placebo: We don’t know whether adding corticosteroids is more effective at reducing mortality in children with meningococcal septicaemia ( moderate-quality evidence ).

Benefits

We found no systematic review or RCTs on the use of adding corticosteroids specifically in children with meningococcal septicaemia (see comment below).

Harms

We found no RCTs (see comment below).

Comment

We found one systematic review (search date 2003) in people of all ages with severe sepsis or septic shock of any bacterial aetiology. Two RCTs in children identified by the review found no significant difference in mortality between adding corticosteroids and placebo, but it is questionable whether evidence from RCTs on severe sepsis and septic shock of any aetiology can be applied to children with meningococcal septicaemia (mortality in the first RCT: 5/74 [6.8%] with adjunctive hydrocortisone v 4/61 [6.6%] with placebo, P value reported as not significant; mortality in the second RCT: 6/36 [17%] with adjunctive dexamethasone v 4/36 [11%] with placebo; P = 0.73).

Substantive changes

No new evidence

2004; 2004: 0907.
Published online 2004 October 1.

Adding corticosteroids

Summary

MORTALITY Adding corticosteroids compared with adding placebo: We don’t know whether adding corticosteroids (high dose, short courses or low dose, long courses) are more effective at reducing mortality in adults with meningococcal septicaemia ( moderate-quality evidence ).

Benefits

We found no systematic review or RCTs on the use of adding corticosteroids specifically in adults with meningococcal septicaemia (see comment below).

Harms

We found no RCTs (see comment below).

Comment

We found one systematic review (search date 2003, 13 RCTs and 3 quasi-randomised trials, 2063 people, including 1856 adults, with severe sepsis or septic shock of any bacterial aetiology) comparing adding corticosteroids (hydrocortisone, methylprednisolone, and dexamethasone) with two distinct dosing schemes — high dose, short course (>300 mg hydrocortisone or equivalent, for up to 5 days) and low dose, long course (300 mg hydrocortisone or less, for 5 days or more) — versus adding placebo. Whether the results of the review can be extrapolated to the context of meningococcal septicaemia in adults remains unclear. The review found no significant difference in all cause mortality at 28 days with adding corticosteroids compared with placebo (351/1033 [34%] with adding corticosteroids v 329/989 [33%] with placebo; RR 0.92, 95% CI 0.75 to 1.14). Similarly, it found no significant difference in all cause mortality at 28 days with adding high dose, short course corticosteroids compared with placebo. However, it found that low dose, long course corticosteroids (5 RCTs, 465 adults) significantly reduced mortality at 28 days compared with placebo (all cause mortality at 28 days: 106/236 [45%] with adding corticosteroids given at low dose for 5 days or more v 129/229 [56%] with placebo; RR 0.80, 95% CI 0.67 to 0.95). The review found no significant difference in adverse events with adding corticosteroids compared with placebo (rate of gastrointestinal bleeding: 53/684 [8%] with adding corticosteroids v 43/637 [7%] with placebo; RR 1.16, 95% CI 0.82 to 1.65; rate of superinfections: 109/882 [12%] with adding corticosteroids v 107/823 [13%] with placebo; rate of hyperglycaemia: RR 1.22, 95% CI 0.84 to 1.78).

Substantive changes

No new evidence


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