scholarly journals Moxifloxacin Population Pharmacokinetics and Model-Based Comparison of Efficacy between Moxifloxacin and Ofloxacin in African Patients

2013 ◽  
Vol 58 (1) ◽  
pp. 503-510 ◽  
Author(s):  
Simbarashe P. Zvada ◽  
Paolo Denti ◽  
Frederick A. Sirgel ◽  
Emmanuel Chigutsa ◽  
Mark Hatherill ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Time Curve ◽  
Content Type ◽  
Safety Issues ◽  
Mdr Tb ◽  
Target Ratio ◽  
Plasma Pharmacokinetics ◽  
Stringent Target ◽  
African Patients

ABSTRACTPharmacokinetic exposure and the MIC of fluoroquinolones are important determinants of their efficacy againstMycobacterium tuberculosis. Population modeling was used to describe the steady-state plasma pharmacokinetics of moxifloxacin in 241 tuberculosis (TB) patients in southern Africa. Monte Carlo simulations were applied to obtain the area under the unbound concentration-time curve from 0 to 24 h (fAUC0–24) after daily doses of 400 mg or 800 mg moxifloxacin and 800 mg ofloxacin. The MIC distributions of ofloxacin and moxifloxacin were determined for 197 drug-resistant clinical isolates ofMycobacterium tuberculosis. For a specific MIC, the probability of target attainment (PTA) was determined for targetfAUC0–24/MIC ratios of ≥53 and ≥100. The PTAs were combined with the MIC distributions to calculate the cumulative fraction of response (CFR) for multidrug-resistant (MDR)Mycobacterium tuberculosisstrains. Even with the less stringent target ratio of ≥53, moxifloxacin at 400 mg and ofloxacin at 800 mg achieved CFRs of only 84% and 58% for multidrug-resistant isolates with resistance to an injectable drug, while the 800-mg moxifloxacin dose achieved a CFR of 98%. Using a target ratio of ≥100 for multidrug-resistant strains (without resistance to injectable agents or fluoroquinolones), the CFR was 88% for moxifloxacin and only 43% for ofloxacin, and the higher dose of 800 mg moxifloxacin was needed to achieve a CFR target of >90%. Our results indicate that moxifloxacin is more efficacious than ofloxacin in the treatment of MDR-TB. Further studies should determine the optimal pharmacodynamic target for moxifloxacin in a multidrug regimen and clarify safety issues when it is administered at higher doses.

scholarly journals Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Zhaojing Zong ◽  
Wei Jing ◽  
Jin Shi ◽  
Shu'an Wen ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Significant Difference ◽  
Mdr Tb

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

scholarly journals Mutations ingyrAandgyrBamong Fluoroquinolone- and Multidrug-Resistant Mycobacterium tuberculosis Isolates

2016 ◽  
Vol 60 (4) ◽  
pp. 2090-2096 ◽  
Author(s):  
Jung-Yien Chien ◽  
Wei-Yih Chiu ◽  
Shun-Tien Chien ◽  
Chia-Jung Chiang ◽  
Chong-Jen Yu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
East Asian ◽  
Multidrug Resistant ◽  
Molecular Techniques ◽  
Content Type ◽  
Low Level ◽  
High Prevalence ◽  
Mdr Tb ◽  
High Level

ABSTRACTIn order to correlate the mutations inside the entiregyrAandgyrBgenes with the level of resistance to ofloxacin (OFX) and moxifloxacin (MFX) in isolates of multidrug-resistantMycobacterium tuberculosis(MDR-TB), a total of 111 isolates were categorized into OFX-susceptible (MIC, ≤2 μg/ml) and low-level (MIC, 4 to 8 μg/ml) and high-level (MIC, ≥16 μg/ml) OFX-resistant isolates and MFX-susceptible (MIC, ≤0.5 μg/ml) and low-level (MIC, 1 to 2 μg/ml) and high-level (MIC, ≥4 μg/ml) MFX-resistant isolates. Resistance-associated mutations inside thegyrAgene were found in 30.2% of OFX-susceptible and 72.5% and 72.2% of low-level and high-level OFX-resistant isolates and in 28.6% of MFX-susceptible and 58.1% and 83.9% of low-level and high-level MFX-resistant isolates. Compared with OFX-susceptible isolates, low-level and high-level OFX-resistant isolates had a significantly higher prevalence of mutations atgyrAcodons 88 to 94 (17.0%, 65.0%, and 72.2%, respectively;P< 0.001) and a higher prevalence of thegyrBG512R mutation (0.0%, 2.5%, and 16.7%, respectively;P= 0.006). Similarly, compared with MFX-susceptible isolates, low-level and high-level MFX-resistant isolates had a significantly higher prevalence of mutations atgyrAcodons 88 to 94 (14.3%, 51.6%, and 80.6%, respectively;P< 0.001) as well as a higher prevalence of thegyrBG512R mutation (0.0%, 0.0%, and 12.9%, respectively;P= 0.011). D94G and D94N mutations ingyrAand the G512R mutation ingyrBwere correlated with high-level MFX resistance, while the D94A mutation was associated with low-level MFX resistance. The prevalence of mutations atgyrAcodons 88 to 94 and thegyrBG512R mutation were higher among fluoroquinolone (FQ)-susceptible East Asian (Beijing) and Indo-Oceanic strains than they were among Euro-American strains, implying that molecular techniques to detect FQ resistance may be less specific in areas with a high prevalence of East Asian (Beijing) and Indo-Oceanic strains.

scholarly journals Genotypic Analysis of Genes Associated with Independent Resistance and Cross-Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis Clinical Isolates

2015 ◽  
Vol 59 (12) ◽  
pp. 7805-7810 ◽  
Author(s):  
Johana Rueda ◽  
Teresa Realpe ◽  
Gloria Isabel Mejia ◽  
Elsa Zapata ◽  
Juan Carlos Rozo ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Resistance Mutations ◽  
Content Type ◽  
Genotypic Analysis ◽  
Mdr Tb ◽  
Proportion Method ◽  
Emergence Of Resistance ◽  
Phenotypic Susceptibility

ABSTRACTEthionamide (ETH) is an antibiotic used for the treatment of multidrug-resistant (MDR) tuberculosis (TB) (MDR-TB), and its use may be limited with the emergence of resistance in theMycobacterium tuberculosispopulation. ETH resistance inM. tuberculosisis phenomenon independent or cross related when accompanied with isoniazid (INH) resistance. In most cases, resistance to INH and ETH is explained by mutations in theinhApromoter and in the following genes:katG,ethA,ethR,mshA,ndh, andinhA. We sequenced the above genes in 64M. tuberculosisisolates (n= 57 ETH-resistant MDR-TB isolates;n= 3 ETH-susceptible MDR-TB isolates; andn= 4 fully susceptible isolates). Each isolate was tested for susceptibility to first- and second-line drugs using the agar proportion method. Mutations were observed in ETH-resistant MDR-TB isolates at the following rates: 100% inkatG, 72% inethA, 45.6% inmshA, 8.7% inndh, and 33.3% ininhAor its promoter. Of the three ETH-susceptible MDR-TB isolates, all showed mutations inkatG; one had a mutation inethA, and another, inmshAandinhA. Finally, of the four fully susceptible isolates, two showed no detectable mutation in the studied genes, and two had mutations inmshAgene unrelated to the resistance. Mutations not previously reported were found in theethA,mshA,katG, andndhgenes. The concordance between the phenotypic susceptibility testing to INH and ETH and the sequencing was 1 and 0.45, respectively. Among isolates exhibiting INH resistance, the high frequency of independent resistance and cross-resistance with ETH in theM. tuberculosisisolates suggests the need to confirm the susceptibility to ETH before considering it in the treatment of patients with MDR-TB.

scholarly journals Direct Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis by Use of pncA PCR Sequencing

2019 ◽  
Vol 57 (8) ◽  
Author(s):  
Kingsley King-Gee Tam ◽  
Kenneth Siu-Sing Leung ◽  
Gilman Kit-Hang Siu ◽  
Kwok-Chiu Chang ◽  
Samson Sai-Yin Wong ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Direct Detection ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Activity Data ◽  
Content Type ◽  
Treatment Regimens ◽  
Mdr Tb ◽  
Resistant Strains ◽  
Respiratory Specimens

ABSTRACT An in-house-developed pncA sequencing assay for analysis of pyrazinamide (PZA) resistance was evaluated using 162 archived Mycobacterium tuberculosis complex (MTBC) isolates with phenotypic PZA susceptibility profiles that were well defined by analysis of Bactec MGIT 960 PZA kit and PZase activity data. Preliminary results showed 100% concordance between pncA sequencing and phenotypic PZA drug susceptibility test (DST) results among archived isolates. Also, 637 respiratory specimens were prospectively collected, and 158 were reported as MTBC positive by the Abbott Realtime MTB assay (96.3% sensitivity [95% confidence interval {CI}: 92.2% to 98.7%]; 100% specificity [95% CI: 99.2% to 100.0%]). Genotypic and phenotypic PZA resistance profiles of these 158 MTBC-positive specimens were analyzed by pncA sequencing and Bactec MGIT 960 PZA kit, respectively. For analysis of PZA resistance, pncA sequencing detected pncA mutations in 5/5 (100%) phenotypic PZA-resistant respiratory specimens within 4 working days. No pncA mutations were detected among PZA-susceptible specimens. Combining archived isolates with prospective specimens, 27 were identified as phenotypic PZA resistant with pncA mutation. Among these 27 samples, 6/27 (22.2%) phenotypic PZA-resistant strains carried novel pncA mutations without rpsA and panD mutations. These included 5 with mutations (a deletion [Del] at 383T [Del383T], Del 380 to 390, insertion of A [A Ins] at position 127, A Ins at position 407, and G Ins at position 508) in pncA structural genes and 1 with a mutation (T-12C) at the pncA promoter region. All six of these strains had no or reduced PZase activities, indicating that the novel mutations might confer PZA resistance. Additionally, 25/27 phenotypic PZA-resistant strains were confirmed multidrug-resistant tuberculosis (MDR-TB) strains. As PZA is commonly used in MDR-TB treatment regimens, direct pncA sequencing will rapidly detect PZA resistance and facilitate judicious use of PZA in treating PZA-susceptible MDR-TB.

scholarly journals Molecular Characterization of Multidrug-Resistant Mycobacterium tuberculosis Isolated in Nepal

2012 ◽  
Vol 56 (6) ◽  
pp. 2831-2836 ◽  
Author(s):  
Ajay Poudel ◽  
Chie Nakajima ◽  
Yukari Fukushima ◽  
Haruka Suzuki ◽  
Basu Dev Pandey ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Promoter Region ◽  
Multidrug Resistant ◽  
Content Type ◽  
Molecular Tests ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Substitution Mutations ◽  
Drug Resistant Strains

ABSTRACTDespite the fact that Nepal is one of the first countries globally to introduce multidrug-resistant tuberculosis (MDR-TB) case management, the number of MDR-TB cases is continuing to rise in Nepal. Rapid molecular tests applicable in this setting to identify resistant organisms would be an effective tool in reversing this trend. To develop such tools, information about the frequency and distribution of mutations that are associated with phenotypic drug resistance inMycobacterium tuberculosisis required. In the present study, we investigated the prevalence of mutations inrpoBandkatGgenes and theinhApromoter region in 158M. tuberculosisisolates (109 phenotypically MDR and 49 non-MDR isolates collected in Nepal) by DNA sequencing. Mutations affecting the 81-bp rifampin (RIF) resistance-determining region (RRDR) ofrpoBwere identified in 106 of 109 (97.3%) RIF-resistant isolates. Codons 531, 526, and 516 were the most commonly affected, at percentages of 58.7, 15.6, and 15.6%, respectively. Of 113 isoniazid (INH)-resistant isolates, 99 (87.6%) had mutations in thekatGgene, with Ser315Thr being the most prevalent (81.4%) substitution. Mutations in theinhApromoter region were detected in 14 (12.4%) INH-resistant isolates. The results from this study provide an overview of the current situation of RIF and INH resistance inM. tuberculosisin Nepal and can serve as a basis for developing or improving rapid molecular tests to monitor drug-resistant strains in this country.

scholarly journals Intra- and Extracellular Activities of Trimethoprim-Sulfamethoxazole against Susceptible and Multidrug-Resistant Mycobacterium tuberculosis

2014 ◽  
Vol 58 (12) ◽  
pp. 7557-7559 ◽  
Author(s):  
L. Davies Forsman ◽  
T. Schön ◽  
U. S. H. Simonsson ◽  
J. Bruchfeld ◽  
M. Larsson ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Treatment Option ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Potential Treatment ◽  
Time Curve ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Concentration Time ◽  
Strain H37rv

ABSTRACTWe investigated the activity of trimethoprim-sulfamethoxazole (SXT) againstMycobacterium tuberculosis, the pathogen that causes tuberculosis (TB). The MIC distribution of SXT was 0.125/2.4 to 2/38 mg/liter for the 100 isolates tested, including multi- and extensively drug-resistant isolates (MDR/XDR-TB), whereas the intracellular MIC90of sulfamethoxazole (SMX) for the pansusceptible strain H37Rv was 76 mg/liter. In an exploratory analysis using a ratio of the unbound area under the concentration-time curve from 0 to 24 h over MIC (fAUC0–24/MIC) using ≥25 as a potential target, the cumulative fraction response was ≥90% at doses of ≥2,400 mg of SMX. SXT is a potential treatment option for MDR/XDR-TB.

scholarly journals Sequence Analysis of Fluoroquinolone Resistance-Associated GenesgyrAandgyrBin Clinical Mycobacterium tuberculosis Isolates from Patients Suspected of Having Multidrug-Resistant Tuberculosis in New Delhi, India

2016 ◽  
Vol 54 (9) ◽  
pp. 2298-2305 ◽  
Author(s):  
Ritu Singhal ◽  
Paul R. Reynolds ◽  
Jamie L. Marola ◽  
L. Elaine Epperson ◽  
Jyoti Arora ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Indian Subcontinent ◽  
Amino Acid Position ◽  
Multidrug Resistant ◽  
High Rate ◽  
Fluoroquinolone Resistance ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Fluoroquinolones (FQs) are broad-spectrum antibiotics recommended for the treatment of multidrug-resistant tuberculosis (MDR-TB) patients. FQ resistance, caused by mutations in thegyrAandgyrBgenes ofMycobacterium tuberculosis, is increasingly reported worldwide; however, information on mutations occurring in strains from the Indian subcontinent is scarce. Hence, in this study, we aimed to characterize mutations in thegyrAandgyrBgenes of acid-fast bacillus (AFB) smear-positive sediments or ofM. tuberculosisisolates from AFB smear-negative samples from patients in India suspected of having MDR-TB. A total of 152 samples from patients suspected of having MDR-TB were included in the study. One hundred forty-six strains detected in these samples were characterized by sequencing of thegyrAandgyrBgenes. The extracted DNA was subjected to successive amplifications using a nested PCR protocol, followed by sequencing. A total of 27 mutations were observed in thegyrAgenes of 25 strains, while no mutations were observed in thegyrBgenes. The most common mutations occurred at amino acid position 94 (13/27 [48.1%]); of these, the D94G mutation was the most prevalent. ThegyrAmutations were significantly associated with patients with rifampin (RIF)-resistant TB. Heterozygosity was seen in 4/27 (14.8%) mutations, suggesting the occurrence of mixed populations with different antimicrobial susceptibilities. A high rate of FQ-resistant mutations (17.1%) was obtained among the isolates of TB patients suspected of having MDR-TB. These observations emphasize the need for accurate and rapid molecular tests for the detection of FQ-resistant mutations at the time of MDR-TB diagnosis.

scholarly journals Amikacin Optimal Exposure Targets in the Hollow-Fiber System Model of Tuberculosis

2016 ◽  
Vol 60 (10) ◽  
pp. 5922-5927 ◽  
Author(s):  
Shashikant Srivastava ◽  
Chawanga Modongo ◽  
Chandima W. Siyambalapitiyage Dona ◽  
Jotam G. Pasipanodya ◽  
Devyani Deshpande ◽  
...  
Keyword(s):  
Hollow Fiber ◽  
Bactericidal Effect ◽  
Multidrug Resistant ◽  
System Model ◽  
Intermittent Therapy ◽  
Fiber System ◽  
Time Curve ◽  
Content Type ◽  
Concentration Time ◽  
Mdr Tb

ABSTRACTAminoglycosides such as amikacin are currently used for the treatment of multidrug-resistant tuberculosis (MDR-TB). However, formal pharmacokinetic/pharmacodynamic (PK/PD) studies to identify amikacin exposures and dosing schedules that optimizeMycobacterium tuberculosiskilling have not been performed. It is believed that aminoglycosides do not work well under acidic conditions, which, if true, would mean poor sterilizing activity against semidormant bacilli at low pH. We performed time-kill studies to compare the bactericidal effect of amikacin in log-phase-growth bacilli with the sterilizing effect in semidormant bacilli at pH 5.8 in broth. In log-phaseM. tuberculosisat normal pH versus semidormantM. tuberculosisat pH 5.8, the maximal kill (Emax) estimate and 95% confidence interval (CI) were 5.39 (95% CI, 4.91 to 5.63) versus 4.88 (CI, 4.46 to 5.22) log10CFU/ml, while the concentration mediating 50% ofEmax(EC50) was 1.0 (CI, 0. 0.86 to 1.12) versus 0.60 (CI, 0.50 to 0.66) times the MIC, respectively. Thus, the optimal exposures and kill rates identified for log-phaseM. tuberculosiswill be optimal even for semidormant bacilli. Next, we performed exposure-response and dose-scheduling studies in the hollow-fiber system model of tuberculosis using log-phaseM. tuberculosis. We recapitulated the amikacin concentration-time profiles observed in lungs of patients treated over 28 days. The PK/PD index linked toM. tuberculosiskill was the peak concentration (Cmax)-to-MIC ratio (r2> 0.99), closely followed by the area under the concentration-time curve from 0 to 24 h (AUC0–24)-to-MIC ratio (r2= 0.98). The EC90was aCmax/MIC ratio of 10.13 (95% CI, 7.73 to 12.48). The EC90is the dosing target for intermittent therapy that optimizes cure in TB programs for MDR-TB patients.

scholarly journals Pyrazinamide Susceptibility and pncA Mutation Profiles of Mycobacterium tuberculosis among Multidrug-Resistant Tuberculosis Patients in Bangladesh

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Arfatur Rahman ◽  
Sara Sabrina Ferdous ◽  
Shahriar Ahmed ◽  
S. M. Mazidur Rahman ◽  
Mohammad Khaja Mafij Uddin ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Clinical Information ◽  
Turnaround Time ◽  
Multidrug Resistant ◽  
Published Data ◽  
Genetic Lineage ◽  
Content Type ◽  
Treatment Regimens ◽  
Indicator Tube ◽  
Mdr Tb

ABSTRACT Pyrazinamide (PZA) is a frontline antituberculosis (anti-TB) drug used in both first- and second-line treatment regimens. However, due to complex laboratory requirements, the PZA susceptibility test is rarely performed, leading to a scarcity of data on susceptibility to PZA. Bangladesh is a country with a burden of high rates of both TB and multidrug-resistant TB (MDR-TB), but to our knowledge, published data on rates of PZA susceptibility (PZAs), especially among MDR-TB patients, are limited. We aimed to analyze the PZA susceptibility patterns of Mycobacterium tuberculosis isolates from MDR-TB patients and to correlate the pncA mutation with PZA resistance in Bangladesh. A total of 169 confirmed MDR M. tuberculosis isolates from a pool of specimens collected in a nationwide surveillance study were included in this analysis. All the isolates were tested for phenotypic PZA susceptibility in Bactec mycobacterial growth indicator tube (MGIT) culture medium, and the pncA gene was sequenced. We also correlated different types of clinical information and treatment outcomes with PZA susceptibility. We found that 45% of isolates were phenotypically PZA resistant. Sequencing of the pncA gene revealed a high concordance (82.2%) between the pncA gene sequence and the phenotypic assay results. A total of 64 different mutations were found, and 9 isolates harbored multiple mutations. We detected 27 new pncA mutations. We did not find any significant correlation between the different clinical categories, the genetic lineage, or treatment outcome group and PZA susceptibility. Considering the turnaround time, sequencing would be the more feasible option to determine PZA susceptibility, and further studies to investigate the MIC of PZA should be conducted to determine an effective dose of the drug.

scholarly journals Mycobacterium tuberculosis Mutations Associated with Reduced Susceptibility to Linezolid

2016 ◽  
Vol 60 (4) ◽  
pp. 2542-2544 ◽  
Author(s):  
Shuo Zhang ◽  
Jiazhen Chen ◽  
Peng Cui ◽  
Wanliang Shi ◽  
Xiaohong Shi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Rapid Detection ◽  
Multidrug Resistant ◽  
Mechanisms Of Resistance ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

ABSTRACTLinezolid (LZD) has become increasingly important for the treatment of multidrug-resistant tuberculosis (MDR-TB), but its mechanisms of resistance are not well characterized. We isolated 32 mutants ofMycobacterium tuberculosiswith reduced susceptibility to LZD, which was accounted for byrrlandrplCmutations in almost equal proportions, causing lower and higher MICs, respectively. Our findings provide useful information for the rapid detection of LZD resistance for improved treatment of MDR-TB.

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