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Prophylactic antibiotics do not protect against meningitis in patients with basilar skull fracture

Study
Results
Comment

With a basilar skull fracture there is potential for exposure to pathogens from the respiratory tract or ear, and thus an increased risk of meningitis. There may also be leakage of the cerebrospinal fluid which could facilitate this. The logic therefore is to give antibiotics prophylactically to prevent meningitis. That this is not an effective strategy is implied by a new meta-analysis [1].

Study


The review sought out published studies on the use of prophylactic antibiotics for prevention of meningitis after basilar skull fractures, but using only MEDLINE. They found 14 studies, two of which had no extractable data. Of the other 12, nine were retrospective, one a combined retrospective and prospective study, and two were prospective and randomised. Three studies were in children. A wide variety of different antibiotics were used, were started within 72 hours of hospital admission and continued for between three days to one week after CSF leakage resolved.

Results


In the 12 studies (1,241 patients) in which there was extractable data on cases of meningitis, 5.3% (38/719) of those given antibiotics had meningitis, compared with 7.1% (37/522) of those who did not have prophylactic antibiotics (Figure). The odds ratio was 0.88 (95% CI 0.54 to 1.42). The two randomised studies had only 95 patients, and there were two cases of meningitis in the control group, and none in the treated group. Sub-group analyses showed no significant differences for patients with skull fracture and CSF leakage, or in children.


Comment


This is one of those really difficult reviews, and it is worth using it as a tutorial as to how we might evaluate evidence:

  • The review itself can be criticised, perhaps, for not trying harder to find other trials by searching other databases, including the Cochrane Library, a repository of over 200,000 controlled trials.
  • The data in the review can be criticised because only two of the 12 studies were prospective and randomised (and they were small).
  • The results of the data included showed no statistically significant benefit for antibiotics. Yet the meningitis rate was almost 2% lower with antibiotics than without. The NNT was 55, with a confidence interval from 22 to -106. In other words, although the confidence interval included antibiotics having a greater risk of meningitis, much of its range was in the area where antibiotics did actually benefit, including benefit in 1 in 22 patients.
  • There was no analysis of adverse effects from antibiotics. We had no information which might have balanced small benefits against additional harm. What we are left with is the uncertain estimate that a percent or so of meningitis cases following basilar skull fractures may be prevented by prophylactic use of antibiotics. But we don't know which antibiotic might be best, nor how long antibiotics should be given. We do know that the ultra-large clinical trial needed to resolve the uncertainty will probably never be done, so in the meantime we have to manage as best we can.

Reference:

  1. T Villalobos et al. Antibiotic prophylaxis after basilar skull fractures: a meta-analysis. Clinical Infectious Diseases 1998 27: 364-9.
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