JAC Advance Access published online on February 12, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh119
© 2004 by The British Society for Antimicrobial Chemotherapy
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Original article
1 S. Microbiology, Hospital General Universitario de Elche, Elche, 03203 Spain
* Corresponding author. E-mail: micro_elx{at}gva.es.
Received 8 October 2003
; revised 9 December 2003
; accepted 18 December 2003
Objectives: The mutant prevention
concentration (MPC) has recently been defined to characterize the capacity
for severely restricting the selection of resistant mutants during
antibiotic treatment. We determined this parameter for ciprofloxacin,
levofloxacin, gatifloxacin, moxifloxacin and linezolid in Mycobacterium tuberculosis clinical
isolates in our setting. Methods: We determined the antibiotic concentration
that prevents the selection of resistant mutants following inoculation
with a high mycobacteria inoculum on Middlebrook 7H11 plates with
serial dilutions of the antibiotics in 224 M. tuberculosis isolates. Results: Fifty percent of the strains exhibited
values of MPC (MPC50) lower than 0.8, 0.6, 0.4, 0.4 and
0.6 mg/L for ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin
and linezolid, respectively. If 90% of the strains are considered
(MPC90), the values are seen to rise to 2, 1.8, 1, 1.2
and 1.2 mg/L, respectively. Conclusions: When we compare this parameter
with the drug levels in serum and tissue, it can be seen that ciprofloxacin
is the least useful of the fluoroquinolones studied, whereas moxifloxacin
appears to be the most active. Linezolid exhibits excellent activity
against this microorganism (MPC90 1.2 mg/L and AUC
140.3 mg·h/L) and this makes us consider that its usefulness
in the treatment of this pathology should be thoroughly evaluated.
Keywords: tuberculosis, drug activity, fluoroquinolones,
oxazolidinones
Mutant prevention concentration: comparison of
fluoroquinolones and linezolid with Mycobacterium tuberculosis
2 S. Pharmacy, Hospital General Universitario de Elche, Elche, 03203 Spain
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