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The pharmacokinetics of trimethoprim (TMP) 811Dosing and sample collection. An intravenous preparation of TMP-SMX was supplied as 5-ml ampoules, each of which contained 80 mg of TMP (16 mg/ml) and 400 mg of SMX (80 mglml) (Bactrim, Hoffmann-LaRoche Inc., Nutley, N.J.). Each patient received a single 5-mg dose of TMP plus a 25-mg dose of SMX per kg (based on total body weight) prepared in 400 ml of 5% glucose in water. The total dose was infused intravenously over approximately 120 min within 3 h of preparation.Single CSF samples were obtained by lumbar puncture 142 to 900 min after the start of drug infusion and before the introduction of radio-opaque dye. Blood samples were collected from a peripheral intravenous catheter for the first 12 h of study and then by direct venipuncture. At least three serum samples were obtained from each patient, usually during and at the conclusion of drug infusion, and always at the time of CSF collection. In the six patients who participated in the serum pharmacokinetic study, a total of 6 to 10 blood samples were obtained from each patient up to 48 h after the start of the drug infusion. Serum and CSF samples were stored at -80°C until assay. Concn (jig/ml) in CSF/concn in serum (CSF/sestart of rum ratio) infusion (min)

Trimethoprim-sulfamethoxazole has excellent microbiologic activity against most pathogens that produce meningitis; both components of this drug have high penetration into tissues, including the cerebrospinal fluid. Clinical experience shows that trimethoprim-sulfamethoxazole may be beneficial in the treatment of gram-negative bacillary meningitis caused by organisms only moderately susceptible to third-generation cephalosporins (Enterobacter cloacae, Serratia marcescens) or resistant to these antibiotic agents (Pseudomonas cepacia, Acinetobacter). The success of trimethoprim-sulfamethoxazole in the treatment of four patients with Staphylococcus aureus and two patients with Listeria monocytogenes meningitis shows that this drug may also be useful in treating infrequent types of gram-positive meningitis.

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