Antibiotics for preventing meningococcal infections.
BACKGROUND
Meningococcal disease is a contagious bacterial disease caused by Neisseria meningitidis (N. meningitidis). Household contacts have the highest documented risk of the disease during the first seven days of a case being detected. Prophylaxis is, therefore, 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.


OBJECTIVE
To study the effectiveness of different prophylactic treatment regimens in: (1) preventing secondary cases of meningococcal disease after contact with someone with the disease; (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 effects of prophylaxis and development of drug resistance.


METHODS
Electronic searches on the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2006), MEDLINE (January 1966 to June 2006), EMBASE (1980 to June 2006), LILACS (1982 to June 2006); and searching of references of all identified studies were performed.


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


METHODS
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.


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 (RR 0.04; 95% CI 0.01 to 0.12), rifampin (rifampicin) (RR 0.17; 95% CI 0.12 to 0.24), minocycline (RR 0.30; 95% CI 0.19 to 0.45) and ampicillin (RR 0.41; 95% CI 0.25 to 0.66) proved effective at eradicating N. meningitidis one week after treatment when compared with placebo. However, 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 at one to two weeks. Rifampin continued to be effective compared to placebo for up to four weeks after treatment but resistant isolates were seen following prophylactic treatment. No trials evaluated ceftriaxone against placebo but ceftriaxone was more effective than rifampin after one to two weeks of follow up (RR 5.93; 95% CI 1.22 to 28.68).


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. Evidence suggests that all three agents are effective with up to two weeks follow up. 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 would provide important insights.
Fraser
A
A
University of Bristol, Canynge Hall, Department of Social Medicine, Whiteladies Road, Bristol, UK. abigail.fraser@bristol.ac.uk
Gafter-Gvili
A
A
Paul
M
M
Leibovici
L
L
D000667:Ampicillin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002443:Ceftriaxone / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000627:therapeutic use; D006801:Humans; D008589:Meningococcal Infections / Q000517:prevention & control*; D008911:Minocycline / Q000627:therapeutic use; D009345:Neisseria meningitidis; D016032:Randomized Controlled Trials as Topic; D012293:Rifampin / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin; D002443:Ceftriaxone; D000667:Ampicillin; D008911:Minocycline; D012293:Rifampin