From the Guidelines
The intensive phase of Levofloxacin treatment in tuberculous meningitis typically involves a dose of 750-1000 mg daily, administered for 2 months in combination with other first-line antitubercular medications, although the exact details of levofloxacin use are being evaluated in ongoing studies 1.
Key Considerations
- The use of levofloxacin in tuberculous meningitis is being investigated in a large randomized controlled trial to evaluate its impact on reducing mortality when combined with higher-dose rifampicin during the intensive phase of treatment 1.
- The continuation phase of treatment involves a prolonged course of antitubercular therapy, with a total duration of approximately 9-12 months, although the optimal duration is not well defined 1.
Treatment Phases
- Intensive Phase: 2 months of combination therapy with levofloxacin and other first-line medications, such as isoniazid, rifampicin, and pyrazinamide 1.
- Continuation Phase: 7-10 months of therapy with isoniazid and rifampicin, with the possibility of adding levofloxacin or other medications based on ongoing research and clinical guidelines 1. It is essential to note that the current guidelines for tuberculous meningitis treatment are based on expert opinion and ongoing research, and the role of levofloxacin in the treatment regimen is still being evaluated 1.
From the Research
Intensive Phase of Levofloxacin Treatment
- The intensive phase of levofloxacin treatment in tuberculous meningitis typically involves a combination of four drugs: isoniazid, rifampicin, ethambutol, and pyrazinamid, given for 2 months 2.
- Some studies have suggested that the intensive phase may be inadequate and should be revisited in terms of duration of treatment, choice of drugs during continuation-phase therapy, or both 3.
- The use of high-dose rifampicin (15 mg/kg/day) and levofloxacin has been investigated as an intensified regimen, but it did not improve survival or other outcomes in a randomized controlled trial 4, 5.
Continuation Phase of Levofloxacin Treatment
- The continuation phase typically involves a longer period of bitherapy with isoniazid and rifampicin, lasting at least 4 months but usually extended to 7 or 10 months as a precaution 2.
- The choice of drugs during the continuation phase may need to be revisited, with some studies suggesting that higher doses of isoniazid may be necessary, especially in fast metabolizers 4.
- The use of levofloxacin in the continuation phase has not been well established, but it may be considered as an option in certain cases, such as in patients with isoniazid-resistant M. tuberculosis 5.
Pharmacokinetics and Pharmacodynamics
- The pharmacokinetics and pharmacodynamics of levofloxacin in the treatment of tuberculous meningitis have been studied, with results showing that rifampicin 15 mg/kg increased plasma and cerebrospinal fluid exposures compared with 10 mg/kg 4.
- However, there was no relationship between rifampin exposure and survival, and isoniazid exposure was associated with survival, with low exposure predictive of death 4.