Pre-admission antibiotics for suspected cases of meningococcal disease.

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 METHODS: 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.

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.