Antibiotics for preventing meningococcal infections

Abstract

Background: Meningococcal disease is a contagious bacterial disease caused by Neisseria meningitidis (N. meningitidis). The highest documented risk of disease is for household contacts during the first seven days of a case being detected. Prophylaxis is considered for those in close contact with people with a meningococcal infection and in populations with known high carriage rates as carriers are at increased risk of disease and may pose a risk of infection to others.

Objectives: To study the effectiveness of different prophylactic treatment regimens in: (1) preventing secondary cases of meningococcal disease after contact with a case; (2) preventing cases of meningococcal disease in populations with a high rate of N. meningitidis carriers; (3) eradicating N. meningitidis from the pharynx in healthy carriers of N. meningitidis;This review also addresses the issues of adverse affects and development of drug resistance.

Search strategy: Electronic searches on The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2004), MEDLINE (January 1966 to July 2004), EMBASE (1980 to September 2004), LILACS (1982 to July 2004), and searches of references of all identified studies.

Selection criteria: Randomised or quasi-randomised clinical trials addressing the effectiveness of different antibiotic treatments for (a) prophylaxis of/against meningococcal disease; (b) eradication of N. meningitidis.

Data collection and analysis: Two reviewers independently appraised the quality of each trial and extracted data from the included trials. Dichotomous data were analysed by calculating the relative risk (RR) and 95% confidence interval for each trial.

Main results: There were no cases of meningococcal disease during follow up in any of the trials, thus effectiveness regarding prevention of future disease cannot be directly assessed. Ciprofloxacin (relative risk (RR) 0.04; 95% CI 0.01 to 0.12), rifampin (RR 0.17; 95% CI 0.12 0.24), minocycline (RR = 0.30; 95% CI 0.19 to 0.45) and ampicillin (RR 0.41; 95% CI 0.25 0.66) proved effective at eradicating N. meningitidis one week after treatment, compared with placebo. However, after one to two weeks only rifampin (RR 0.20; 95% CI 0.14 to 0.29) and ciprofloxacin (RR 0.03; 95% CI 0.00 to 0.42) still proved effective. No trials evaluated ceftriaxone against placebo. Ceftriaxone was more effective than rifampin, after one to two weeks of follow up (RR 5.93; 95% CI 1.22 to 28.68). Rifampin continued to be effective compared to placebo until up to four weeks of post treatment follow up but resistant isolates were seen following prophylactic treatment.

Authors' conclusions: Given the fact that the use of rifampin in an outbreak setting might lead to the circulation of isolates resistant to rifampin, use of ciprofloxacin or ceftriaxone should be considered.Placebo-controlled trials do not seem ethical as prophylactic treatment has been proven to reduce the risk of disease among household contacts. More trials comparing the effectiveness of ceftriaxone, ciprofloxacin and rifampin for eradicating N. meningitidis could provide important insights.