Yonsei Med J.  2015 Jul;56(4):961-967. 10.3349/ymj.2015.56.4.961.

Low Serum Concentrations of Moxifloxacin, Prothionamide, and Cycloserine on Sputum Conversion in Multi-Drug Resistant TB

• Lee SH
• Seo KA
• Lee YM
• Lee HK
• Kim JH
• Shin C
• Ghim JR
• Shin JG
• Kim DH

• KMID: 2366335
• DOI: http://doi.org/10.3349/ymj.2015.56.4.961

Abstract

PURPOSE
Low serum concentrations of drugs used to treat multi-drug resistant tuberculosis (MDR-TB) have occasionally been associated with treatment failure. We determined the frequencies of low serum concentrations of anti-MDR-TB drugs, and assessed the effects of these concentrations on 2-month sputum conversion.
MATERIALS AND METHODS
The serum levels of moxifloxacin (MF), prothionamide (PTH), and cycloserine (CS) were determined for 89 serum samples by high-pressure liquid chromatography-tandem mass spectrometry.
RESULTS
Low serum concentrations of MF, PTH, and CS below the minimal levels of the normal ranges were 83.3% (20/24), 59.2% (29/49), and 71.2% (47/66), respectively. There were no significant differences between the 2-month sputum conversion group (n=25) and the 2-month sputum non-conversion group (n=4) in median drug concentrations (microg/mL) of MF (1.46 vs. 1.60), PTH (0.91 vs. 0.70), and CS (14.90 vs. 14.90). However, a poor compliance rate was significantly greater in the 2-month sputum non-conversion group (75.0%, 3/4) than in the 2-month sputum conversion group (0%, 0/25) (p=0.001).
CONCLUSION
The frequency of low serum concentrations of anti-MDR-TB drugs was substantial and might not affect the 2-month sputum conversion rate. Larger prospective studies with timely sampling are needed to investigate the role of therapeutic drug monitoring in MDR-TB.

Keyword

Tuberculosis; multidrug resistance; moxifloxacin; prothionamide; cycloserine; drug monitoring

MeSH Terms

Adult
Aged
Antitubercular Agents/blood/*pharmacokinetics/therapeutic use
Chromatography, High Pressure Liquid
Cycloserine/blood/*pharmacokinetics/therapeutic use
Fluoroquinolones/blood/*pharmacokinetics/therapeutic use
Humans
Medication Adherence
Middle Aged
Prothionamide/blood/*pharmacokinetics/therapeutic use
Retrospective Studies
Sputum/*microbiology
Tandem Mass Spectrometry
Tuberculosis, Multidrug-Resistant/blood/*drug therapy
Young Adult
Antitubercular Agents
Cycloserine
Fluoroquinolones
Prothionamide

Figure

• 

  Fig. 1 Serum concentrations of (A) moxifloxacin, (B) prothionamide, and (C) cycloserine in 29 MDR-TB patients. Hollow circles in (B and C) represent the assorted values marked in the conversion groups. The frequency of low serum concentrations of MF, PTH, and CS below the minimal normal range are described in the bottom line under each group. There were no differences between the 2-month sputum conversion group (n=25) and the 2-month sputum non-conversion group (n=4) in median drug concentration of MF, PTH, and CS. The median serum concentration in the 2-month sputum conversion group (n=25) and 2-month sputum non-conversion group (n=4) were as follows: (A) 1.46 µg/mL, IQR 0.33-2.17 vs. 1.60 µg/mL, IQR 0.93-2.54; (B) 0.93 µg/mL, IQR 0.35-2.34 vs. 0.70 µg/mL, IQR 0.24-1.28; and (C) 15.10 µg/mL, IQR 8.23-21.65 vs. 14.90 µg/mL, IQR 9.89-19.45. IQR, interquartile range; MDR-TB, multi-drug resistant tuberculosis; MF, moxifloxacin; PTH, prothionamide; CS, cycloserine.

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