• Annals of Laboratory Medicine
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• 제38권6호
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• pp.563-568
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• 2018

Background: Delamanid, bedaquiline, and linezolid have recently been approved for the treatment of multidrug- and extensively drug-resistant (MDR and XDR, respectively) tuberculosis (TB). To use these drugs effectively, drug susceptibility tests, including rapid molecular techniques, are required for accurate diagnosis and treatment. Furthermore, mutation analyses are needed to assess the potential for resistance. We evaluated the minimum inhibitory concentrations (MICs) of these three anti-TB drugs for Korean MDR and XDR clinical strains and mutations in genes related to resistance to these drugs. Methods: MICs were determined for delamanid, bedaquiline, and linezolid using a microdilution method. The PCR products of drug resistance-related genes from 420 clinical Mycobacterium tuberculosis strains were sequenced and aligned to those of M. tuberculosis H37Rv. Results: The overall MICs for delamanid, bedaquiline, and linezolid ranged from ${\leq}0.025$ to >1.6 mg/L, ${\leq}0.0312$ to >4 mg/L, and ${\leq}0.125$ to 1 mg/L, respectively. Numerous mutations were found in drug-susceptible and -resistant strains. We did not detect specific mutations associated with resistance to bedaquiline and linezolid. However, the Gly81Ser and Gly81Asp mutations were associated with resistance to delamanid. Conclusions: We determined the MICs of three anti-TB drugs for Korean MDR and XDR strains and identified various mutations in resistance-related genes. Further studies are needed to determine the genetic mechanisms underlying resistance to these drugs.

• 한국미생물·생명공학회지
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• 제51권3호
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• pp.293-295
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• 2023

Linezolid, the first oxazolidinone introduced into human clinical use, has become a last resort antibiotic in treatment of serious infections caused by Gram-positive pathogens, including methicillin-resistant staphylococci and vancomycin-resistant enterococci. Although oxazolidinones are strictly prohibited for use in food-producing animals, occurrence of linezolid-resistant staphylococci has recently been reported in livestock farms in Korea. Here, we report the complete genome sequence of an optrA-positive linezolid-resistant Staphylococcus rostri strain PJFA-333 isolated from a pig farm in Korea.

• BMB Reports
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• 제40권6호
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• pp.881-887
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• 2007

It is a hot clinical issue whether newly approved antimicrobial agents such as daptomycin, linezolid, quinupristin/dalfopristin (synercid) and tigecycline are active enough to be used for infections caused by vancomycin resistant bacteria. We performed susceptibility tests for mupirocin, which is in widespread clinical use in Korea, and four new antimicrobials, daptomycin, linezolid, quinupristin/dalfopristin and tigecycline, against vancomycin-resistant Enterococcus faecalis and Enterococcus faecium isolated from Korean patients in 1998 and 2005 to evaluate and compare the in vitro activity of these antimicrobials. Among these agents, quinupristin/dalfopristin, which is rarely used in hospitals in Korea, showed relatively high resistance to several vancomycin-resistant enterococci (VRE) isolated in 2005. Likewise, daptomycin, linezolid and tigecycline have not yet been in clinical use in Korea. However, our results showed that most of the 2005 VRE isolates were already resistant to linezolid and daptomycin (highest minimum inhibitory concentration (MIC) value >$100{\mu}g$/ml). Compared with the other four antimicrobial agents tested in this study, tigecycline generally showed the greatest activity against VRE. However, four strains of 2005 isolates exhibited resistance against tigecycline (MIC >$12.5{\mu}g$/ml). Almost all VRE were resistant to mupirocin, whereas all E. faecium isolated in 1998 were inhibited at concentrations between $0.8\sim1.6{\mu}g$/ml. In conclusion, resistances to these new antimicrobial agents were exhibited in most of VRE strains even though these new antibiotics have been rarely used in Korean hospitals.

• Journal of Korean Neurosurgical Society
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• 제43권6호
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• pp.307-310
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• 2008

Limited therapeutic options are available for vancomycin intermediate-resistant Staphylococcus epidermidis (VISE) infections and no optimum therapy has been established. We report a case of VISE skull osteomyelitis that was successfully treated with linezolid. The patient was a 53-year-old man who presented with headache, nausea and dysphasia. Brain computerized tomography (CT) demonstrated a subdural hematoma in the left hemisphere. Craniotomy and hematoma evacuation was performed and he showed good recovery despite a scalp wound infection caused by methicillin-resistant Staphylococcus aureus (MRSA). The organism isolated from the scalp wound was sensitive to vancomycin. The patient was treated with intravenous vancomycin for 44 days. However, he showed a high fever, persistent positive methicillin-resistant Staphylococcus epidermidis (MRSE) blood cultures, and a deteriorating clinical status. He underwent infected skull bone flap removal and linezolid treatment for 35 days. During one year of follow up, he has not had any further episodes of osteomyelitis or fever. Linezolid has shown to be effective agent to eradiate osteomyelitis caused by VISE.

• 약학회지
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• 제58권1호
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• pp.7-11
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• 2014

To study the resistance mechanism of E. faecalis to LCB01-0371, several resistant mutants to LCB01-0371 or linezolid were isolated by step-wise selection. The frequency of spontaneous mutations resistant to LCB01-0371 was lower than that of linezolid in E. faecalis. The genetic variations in resistant mutants were analyzed by DNA sequencing of domain V of 23S rRNA in each mutant. The first-step mutant to LCB01-0371 had a G2576T point mutation in V domain of 23S rRNA. However, no resistant mutant to LCB01-0371 was isolated in second-step mutant selection.

• Journal of Microbiology and Biotechnology
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• 제19권7호
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• pp.734-741
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• 2009

Recently, strains of methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin (VCM) have been clinically isolated. The antibacterial activity of a new drug, linezolid (LZD), in such a strain was evaluated by measuring bacterial metabolic activity. A total of 73 MRSA strains having various susceptibilities to VCM were subjected to a novel and highly sensitive chemiluminescence-based assay. LZD MIC in the tested strains, measured by the microbroth dilution method, was within the range 1-4 mg/l (mostly ${\leq}2$mg/l), except for one LZD-resistant strain (NRS127; MIC=7 mg/l), and showed no correlation with VCM resistance. The chemiluminescence assay demonstrated that bacterial metabolic activity was strongly suppressed with increasing LZD concentration. The chemiluminescence intensity curve had a low baseline activity without tailing in most strains. The present results suggest that LZD has strong antibacterial activity against MRSA strains, and would be effective for treatment of infections that are poorly responsive to VCM. The chemiluminescence assay facilitated sensitive and discriminative susceptibility testing within a relatively short time.

• Tuberculosis and Respiratory Diseases
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• 제74권6호
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• pp.251-255
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• 2013

Tuberculosis (TB) is one of the largest health problems in the world today. And the incidence of nontuberculous mycobacteria (NTM) lung disease appears to be increasing worldwide. Recently, an automated, nucleic acid amplification assay for the rapid detection of both Mycobacterium tuberculosis and rifampin resistance was developed (Xpert MTB/RIF). And fixed-dose combinations of anti-TB drugs and linezolid have been introduced in the treatment of TB. And new NTM species, named Mycobacterium massiliense, which is very closely related to Mycobacterium abscessus was reported. In this review, these recent advances in the diagnosis and treatment of TB and clinical characteristics of M. massiliense lung disease are discussed.

• 약학회지
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• 제53권4호
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• pp.194-200
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• 2009

Community-acquired antimicrobial resistant bacteria are an emerging problem whole world-wide. Generally, Hands are main mediator of pathogen transmission as compared with other body parts. So, the purpose of this research was to investigate the microbiological quality and antimicrobial susceptibilities of samples which were collected from the door knob and surface in public- and home-facilities, and also hand. Of total 191 samples, 71 samples (37%) were shown to be of high-level total bacterial count (>$10^8\;CFU/cm^2$). And presence of Staphylococcus and Enteric bacilli was observed in 61 samples (32%) and 76 samples (40%), respectively. Antimicrobial susceptibilities of staphylococcal isolates from the samples were tested for six different antimicrobial agents, which are in wide spread clinical use in Korea, as well as four new antimicrobials, daptomycin, linezolid, quinupristin/dalfopristin and tigecycline. Among staphylococcal isolates, antimicrobial resistance were observed in oxacillin (n=6), mupirocin (n=7), vancomycin (n=1), quinupristin/dalfopristin (n=2) and gentamicin (n=5). Fortunately, all the isolates were susceptible to new antimicrobial such as daptomycin, linezolid and tigecycline. Furthermore 4 Enterococcus faecalis were isolated from four hand samples, and all these isolates exhibited multidrug resistance to four different antimicrobial (oxacillin, quinupristin/dalfopristin, mupirocin, gentamicin). Also, 5 Escherichia coli were isolated from surface in home (n=3), door knob in public facilities (n=1) and hand (n=1). Escherichia coli isolated from hand was high-level resistant to tigecycline ($128{\mu}g$/ml) and gentamicin ($64{\mu}g$/ml).

• 약학회지
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• 제52권6호
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• pp.434-440
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• 2008

The purpose of this research was to investigate the microbiological quality and antimicrobial susceptibilities of the ready-to-eat side dishes, which are were collected from the grocery stores, big markets, and department stores in Seoul throughout November, 2007. Of total 124 samples, presence of staphylococci and enteric bacilli was observed in 38 samples (31%) and 53 samples (43%), respectively. And 30 samples (24%) were shown to be of unsatisfactory quality for total bacterial count (>$10^5$). Antimicrobial susceptibilities of the staphylococci isolated from the side dishes were tested for six different antimicrobial agents, which are in widespread clinical use in Korea, as well as four new antimicrobials, daptomycin, linezolid, quinupristin/dalfopristin and tigecycline. As a result, the staphylococcal isolates were found to be resistant to oxacillin (${MIC}_{90}$, >128 ${\mu}g$/ml), teicoplanin (${MIC}_{90}$, >128 ${\mu}g$/ml), mupirocin (${MIC}_{90}$, >128 ${\mu}g$/ml), linezolid (${MIC}_{90}$, 128 ${\mu}g$/ ml) and quinupristin/dalfopristin (${MIC}_{90}$, 32 ${\mu}g$/ml). Especially, some of the staphylococcal isolates exhibited high level and multi-drug resistance. Moreover, these bacteria were also resistant to new antimicrobials, except tigecycline.

• 대한임상검사과학회지
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• 제48권4호
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• pp.335-342
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• 2016

일반적으로 지역사회 관련 경로로 감염되기 쉬운 S. aureus는 대부분이 MSSA로 알려져 있었으나 최근 CA-MRSA가 증가하고 있다. 항생제와 glycopeptides의 지속적인 남용은 VISA, VRSA가 더욱 증가할 가능성이 있다. 본 연구는 최근 10년간 일개 대학병원의 상처에서 분리한 황색 포도상 구균의 항생제 감수성 패턴과 항생제 내성의 유병률의 변화를 조사하기 위하여 실시 하였다. 본 연구에서는 남성이 여성보다 항생제 내성이 높게 나타났다. 그리고 연령에 따라 항생제 내성률이 증가하였다. 2006년 항생제 내성률은 penicillin, oxacillin, erythromycin, gentamicin, clindamycin, tetracycline, ciprofloxacin, fusidic acid, trimethoprim/sulfamethoxazole, clindamycin, rifampicin에서 각각 97.7%, 60.5%, 57.4%, 48.8%, 41.1%, 44.2%, 44.2%, 14.7%, 13.2%, 3.9% 나타났으며, 2016년 항생제 내성률은 penicillin, oxacillin, erythromycin, gentamicin, clindamycin, tetracycline, ciprofloxacin, fusidic acid, trimethoprim/sulfamethoxazole, clindamycin, rifampicin에서 각각 95.9%, 62.6%, 55.7%, 28.6%, 50.3%, 34.7%, 38.8%, 34.0%, 2.7%, 8.2%로 나타났다. Vancomycin, linezolid, quinupristin/dalfopristin, teicoplanin 는 항생제 감수성에서 100%를 나타내었다. 특히, fusidic acid는 2006년에 비하여 2016년에 내성이 19.3% 증가하였고, 감수성이 12.4% 감소하였으며, 통계적으로 유의하였다. 따라서, 미생물 및 항생제 변화의 주기적인 검토와 이해를 통해 적절한 항생제 감수성을 지속적으로 연구해야 할 것으로 사료된다.