Pre-admission antibiotics for suspected cases of meningococcal disease

Meningococcal disease is a contagious, bacterial disease caused by Neisseria meningitidis (N. meningitidis) that, if not treated early, can rapidly lead to death or disabling consequences such as visual, hearing and intellectual impairments.

Administering antibiotics as soon as the condition is suspected and before the diagnosis is confirmed, has been advocated to prevent death and disabling consequences. However, this might result in treating people without the disease with unnecessary antibiotics.

This review update evaluated the effectiveness and safety of pre-admission antibiotics versus no pre-admission antibiotics or placebo and different pre-admission antibiotic regimens in preventing death, lack of clinical improvement and disabling consequences in those suspected to have meningococcal disease.

We found no randomised controlled trials comparing pre-admission antibiotics with placebo or no intervention (up to date 3 May 2013). We identified one well conducted trial in Niger, Africa during an epidemic of meningococcal disease in 2005 including 510 adults and children older than two months, suspected to have meningococcal disease but who were not severely ill. They were randomised to receive a single injection of either ceftriaxone (a newer antibiotic) (251 participants) or a long-acting form of chloramphenicol (an older antibiotic) (259 participants) before confirming the diagnosis. Médecins Sans Frontières sponsored this study.

Both antibiotics were effective in preventing death over the first 72 hours in 477 (95%) of the 503 evaluable participants. In the 308 participants with confirmed meningococcal disease, 154/160 (96%) given the newer antibiotic and 143/148 (95.5%) given the older antibiotic survived. Similar proportions with confirmed disease given the newer antibiotic (3/160; 2%) and the older antibiotic (2/148; 2%) did not show a clinical improvement. Those developing disabling consequences with the newer antibiotic (14/154;9%) and with the older antibiotic (9/143; 6%) were similar. However, larger trials from other parts of the world are needed to be fully confident that the two treatments are equally effective. No serious adverse events were reported with either antibiotic.

Due to the serious complications of meningococcal disease, it would be difficult, for ethical reasons, to undertake randomised controlled trials comparing the use of antibiotics as soon as the diagnosis is suspected versus no antibiotics. Further trials comparing different antibiotics in suspected meningococcal disease, especially in more severe forms, will provide insights that could help prevent death and the serious consequences of this disease.

Authors' conclusions: 

We found no reliable evidence to support or refute the use of pre-admission antibiotics for suspected cases of non-severe meningococcal disease. Evidence of moderate quality from one RCT indicated that single intramuscular injections of ceftriaxone and long-acting chloramphenicol were equally effective, safe and economical in reducing serious outcomes. The choice between these antibiotics would be based on affordability, availability and patterns of antibiotic resistance.

Further RCTs comparing different pre-admission antibiotics, accompanied by intensive supportive measures, are ethically justifiable in participants with severe illness, and are needed to provide reliable evidence in different clinical settings.

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Background: 

Meningococcal disease can lead to death or disability within hours after onset. Pre-admission antibiotics aim to reduce the risk of serious disease and death by preventing delays in starting therapy before confirmation of the diagnosis.

Objectives: 

To study the effectiveness and safety of pre-admission antibiotics versus no pre-admission antibiotics or placebo, and different pre-admission antibiotic regimens in decreasing mortality, clinical failure and morbidity in people suspected of meningococcal disease.

Search strategy: 

We updated searches of CENTRAL (2013, Issue 4), MEDLINE (1966 to April week 4, 2013), EMBASE (1980 to May 2013), Web of Science (1985 to May 2013), CAB Abstracts (1985 to May 2013), LILACS (1982 to May 2013) and prospective trials registries to May 2013.

Selection criteria: 

Randomised controlled trials (RCTs) or quasi-RCTs comparing antibiotics versus placebo or no intervention, in people with suspected meningococcal infection, or different antibiotics administered before admission to hospital or confirmation of the diagnosis.

Data collection and analysis: 

Two review authors independently assessed trial quality and extracted data from the search results. We calculated the risk ratio (RR) and 95% confidence interval (CI) for dichotomous data. We included only one trial so data synthesis was not performed. We assessed the overall quality of the evidence using the GRADE approach.

Main results: 

We found no RCTs that compared pre-admission antibiotics versus no pre-admission antibiotics or placebo. One open-label, non-inferiority RCT, conducted during an epidemic in Niger, evaluated a single dose of intramuscular ceftriaxone versus a single dose of intramuscular long-acting (oily) chloramphenicol. Ceftriaxone was not inferior to chloramphenicol in reducing mortality (RR 1.2, 95% CI 0.6 to 2.6; N = 503; 308 confirmed meningococcal meningitis; 26 deaths; moderate-quality evidence), clinical failures (RR 0.8, 95% CI 0.3 to 2.2; N = 477, 18 clinical failures; moderate-quality evidence) or neurological sequelae (RR 1.3, 95% CI 0.6 to 2.6; N = 477; 29 with sequelae; low-quality evidence). No adverse effects of treatment were reported. Estimated treatment costs were similar. No data were available on disease burden due to sequelae.