Principles of antimicrobial therapy

We have discussed important factors involved in choosing appropriate antimicrobial regimens for the treatment of bacterial meningitis and brain abscess to illustrate common themes relevant to the treatment of these diseases. We have limited this review to these conditions for two main reasons: (1) the principles involved in optimal antimicrobial therapy for these diseases likely apply to other CNS infections, such as viral and fungal diseases; and (2) little pharmacological information is currently available for other types of CNS infections. Many of the studies addressing the relevant pharmacological and microbiological aspects of antimicrobial therapy for CNS infections have been performed in experimental animal models and, as a result, the information derived from these studies may be different when examined in appropriate human studies. Our current understanding of appropriate antimicrobial therapy for CNS infections may be summarized as follows: 1. Choose bactericidal antimicrobials that effectively cross the BBB to achieve CSF concentrations well above the MBC (≥ 10-fold) for the suspected bacterial pathogen(s). 2. Take into consideration the relevant PD parameters underlying the bactericidal activity of the antimicrobials used to treat bacterial meningitis, such as t > MBC or AUC/MBC. 3. Tailor the antimicrobial regimen based on microbiological information, once available. However, with respect to brain abscess therapy, keep in mind that anaerobes are commonly involved, but difficult to culture, and consider including antianaerobic therapy even if the bacterial cultures do not grow anaerobes. 4. Treat bacterial meningitis caused by nonmeningococcal pathogens for 7-10 days, but monitor clinical progress to determine whether the patient should continue on a more prolonged antimicrobial course. Meningococcal meningitis may be treated with 3-4 days of effective antimicrobial therapy, again with the caveat that the patient's clinical course should dictate duration of therapy. 5. Treat brain abscess, preferably after aspiration/ drainage, for at least 6 weeks with intravenous antimicrobials. Base decisions regarding duration of antimicrobials for brain abscess on the clinical response (e.g., improved symptoms, lack of new neurological findings) and radiographic changes (e.g., reduction in cavity size).