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The Role of Fluoroquinolones in the Treatment of Tuberculosis in 2019
A D Pranger1,2, T S van der Werf3,4, J G W Kosterink5,6
1Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. a.d.pranger@lumc.nl.
Abstract:
The inability to use powerful antituberculosis drugs in an increasing number of patients seems to be the biggest threat towards global tuberculosis (TB) elimination. Simplified, shorter and preferably less toxic drug regimens are being investigated for pulmonary TB to counteract emergence of drug resistance. Intensified regimens with high-dose anti-TB drugs during the first weeks of treatment are being investigated for TB meningitis to increase the survival rate among these patients. Moxifloxacin, gatifloxacin and levofloxacin are seen as core agents in case of resistance or intolerance against first-line anti-TB drugs. However, based on their pharmacokinetics (PK) and pharmacodynamics (PD), these drugs are also promising for TB meningitis and might perhaps have the potential to shorten pulmonary TB treatment if dosing could be optimized. We prepared a comprehensive summary of clinical trials investigating the outcome of TB regimens based on moxifloxacin, gatifloxacin and levofloxacin in recent years. In the majority of clinical trials, treatment success was not in favour of these drugs compared to standard regimens. By discussing these results, we propose that incorporation of extended PK/PD analysis into the armamentarium of drug-development tools is needed to clarify the role of moxifloxacin, gatifloxacin and levofloxacin for TB, using the right dose. In addition, to prevent failure of treatment or emergence of drug-resistance, PK and PD variability advocates for concentration-guided dosing in patients at risk for too low a drug-exposure.
Insights
New tuberculosis (TB) drug regimens using moxifloxacin, gatifloxacin, and levofloxacin show limited success. Further pharmacokinetic and pharmacodynamic analysis is needed to optimize dosing for better TB treatment outcomes.
Area of Science:
- Infectious Diseases
- Pharmacology
- Clinical Trials
Background:
- Antituberculosis drug resistance threatens global TB elimination efforts.
- Novel, less toxic, and shorter drug regimens are crucial for pulmonary TB and TB meningitis.
- Fluoroquinolones like moxifloxacin, gatifloxacin, and levofloxacin are considered for drug-resistant TB.
Purpose of the Study:
- To summarize clinical trial outcomes of TB regimens containing moxifloxacin, gatifloxacin, and levofloxacin.
- To evaluate the potential of these fluoroquinolones in TB treatment.
- To identify needs for optimizing drug development and dosing strategies.
Main Methods:
- Comprehensive literature review of recent clinical trials involving fluoroquinolone-based TB regimens.
- Analysis of pharmacokinetics (PK) and pharmacodynamics (PD) of moxifloxacin, gatifloxacin, and levofloxacin.
- Comparison of treatment success rates between novel and standard TB regimens.
Main Results:
- Most clinical trials did not demonstrate superior treatment success for fluoroquinolone-based regimens compared to standard TB treatments.
- Pharmacokinetic and pharmacodynamic properties suggest potential for these drugs, but optimal dosing remains unclear.
- Variability in drug exposure necessitates further investigation.
Conclusions:
- Extended PK/PD analysis is essential to determine the optimal role and dosage of moxifloxacin, gatifloxacin, and levofloxacin in TB therapy.
- Concentration-guided dosing may be necessary for patients at risk of suboptimal drug exposure to prevent treatment failure and resistance.
- Further research is needed to refine fluoroquinolone-based TB treatment strategies.
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