• Title/Summary/Keyword: Linezolid

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Evaluation of the Efficacy and Safety of Linezolid by Meta-analysis for Multidrug-resistant Tuberculosis Patients (다제내성결핵 환자에서 메타분석을 통한 Linezolid의 효능 및 안전성 평가)

  • Woojin Jung;Taewook Sung;Ae Jin Kim;Jung-woo Chae;Hwi-yeol Yun
    • Korean Journal of Clinical Pharmacy
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    • v.33 no.4
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    • pp.278-289
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    • 2023
  • Background: Linezolid has been widely used in the treatment for multidrug-resistant tuberculosis. However, there are limitations to use it such as long treatment, because of related side effects, even adequate treatment period has been needed for remission of multidrug-resistant tuberculosis (MDR-TB). Method: The meta-analysis was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. To choose literatures, systematic literature reviews were conducted with databases of PubMed, Web of Science, and EMBASE. Results: Efficacy and safety of Linezolid were determined by 85% (95% CI=79~89%, p<0.05) in the sputum culture conversion and 55% (95% CI=45~64%, p<0.01) in side effects related to linezolid, respectively. In addition, I2 was estimated by 72%. In the subgroup analysis, efficacy and safety by dose and region were analyzed. In the subgroup analysis, compared with the linezolid dose in groups greater than 600 mg/day and less than 600 mg/day, this study showed 85% (95% CI 79~90%, p>0.05) in 206 patients and 82% (95% CI 73~89%, p<0.05) in 297 patients, respectively. Also, in the subgroup analysis, adverse effects caused by linezolid occurred more than 50% of treated patients. Conclusion: Therapeutic efficacy of linezolid for MDR-TB patients was confirmed regardless of the initial dose of linezolid, especially for sputum culture conversion and it was recommended that the dose of linezolid has been more effective below 600 mg/day. However, it should be necessary to closely monitored for safety issues since serious side effects possibly occurred by administration of long period treatment.

Concise Clinical Review of Hematologic Toxicity of Linezolid in Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: Role of Mitochondria

  • Oehadian, Amaylia;Santoso, Prayudi;Menzies, Dick;Ruslami, Rovina
    • Tuberculosis and Respiratory Diseases
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    • v.85 no.2
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    • pp.111-121
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    • 2022
  • Multidrug-resistant tuberculosis (MDR-TB) is caused by an organism that is resistant to both rifampicin and isoniazid. Extensively drug-resistant TB, a rare type of MDR-TB, is caused by an organism that is resistant to quinolone and one of group A TB drugs (i.e., linezolid and bedaquiline). In 2018, the World Health Organization revised the groupings of TB medicines and reclassified linezolid as a group A drug for the treatment of MDR-TB. Linezolid is a synthetic antimicrobial agent in the oxazolidinone class. Although linezolid has a good efficacy, it can cause substantial adverse events, especially hematologic toxicity. In both TB infection and linezolid mechanism of action, mitochondrial dysfunction plays an important role. In this concise review, characteristics of linezolid as an anti-TB drug are summarized, including its efficacy, pathogenesis of hematologic toxicity highlighting mitochondrial dysfunction, and the monitoring and management of hematologic toxicity.

Linezolid Treatment for Osteomyelitis due to Staphylococcus Epidermidis with Reduced Vancomycin Susceptibility

  • Nam, Joon-Rok;Kim, Myoung-Soo;Lee, Chae-Heuck;Whang, Dong-Hee
    • Journal of Korean Neurosurgical Society
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    • v.43 no.6
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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.

Drastic Growth of ALT/AST Level after First Doses of Intravenous Injection of Linezolid, Moxifloxacin and Aztreonam for a Patient with Community Acquired Pneumonia & Severe Sepsis: A Case Report (지역사회 획득성 폐렴 및 중증 패혈증이 있는 한 환자에게 Linezolid, Moxifloxacin과 Aztreonam을 초회 정맥 주사 후 ALT/AST 수치의 큰 폭 증가 증례 보고)

  • Yoon, Hyon-Ok;Osun, Babatunde
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.4
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    • pp.394-399
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    • 2011
  • 이 증례는 알코올 중독증을 앓은 병력을 가졌으나 간 기능에 특이한 증후가 없던 환자가, 지역 사회 획득성 폐렴으로부터 유발된 중증 패혈증 치료를 받기 위해서 linezolid, moxifloxacin 과 함께 aztreonam을 초회 정맥주사 맞은 후, 아주 높은 수치의 alanine aminotransferase (ALT), aspartate aminotransferase (AST) 혈중 농도가 검출된 경우이다. 후속 치료에서 상기 3가지 항생제 대신 vancomycin과 ceftazidime을 주사했더니, ALT/AST가 빠르게 정상화됨이 관찰되었다. 이 증례 보고는 linzolid, moxifloxacin과 aztreonam을 함께 사용할 경우, 각별한 주의 관찰이 필요하며, 알코올 중독증을 앓은 병력을 가진 환자에게 투여 시 특별한 주의와 함께 AST/ALT혈중 수치를 검사토록 권하기 위한 것이다.

Antimicrobial Activity of Mupirocin, Daptomycin, Linezolid, Quinupristin/Dalfopristin and Tigecycline against Vancomycin-Resistant Enterococci (VRE) from Clinical Isolates in Korea (1998 and 2005)

  • Lee, Do-Kyung;Kim, Yu-Na;Park, Kun-Sup;Yang, Jae-Wook;Kim, Kyung-Jae;Ha, Nam-Joo
    • BMB Reports
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    • v.40 no.6
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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.

Delamanid, Bedaquiline, and Linezolid Minimum Inhibitory Concentration Distributions and Resistance-related Gene Mutations in Multidrug-resistant and Extensively Drug-resistant Tuberculosis in Korea

  • Yang, Jeong Seong;Kim, Kyung Jong;Choi, Hongjo;Lee, Seung Heon
    • Annals of Laboratory Medicine
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    • v.38 no.6
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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.

A Case of Vancomycin-Resistant Enterococci Peritonitis in a Pediatric Patient on CAPD Successfully Treated with Linezolid (지속성 외래 복막투석 소아에서 리네졸리드로 치료한 반코마이신 내성 장구균 복막염 1례)

  • Baek, Seung-Ah;Park, Sung-Sin;Kim, Sung-Do;Cho, Byoung-Soo
    • Childhood Kidney Diseases
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    • v.12 no.2
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    • pp.245-249
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    • 2008
  • Peritonitis is one of the major complications of CAPD(continuous ambulatory peritoneal dialysis). Recently, multidrug-resistant organisms, such as vancomycin-resistant enterococcus(VRE) have been rarely reported by the pathogen as of CAPD-associated peritonitis. But, there is limited information on choices of effective therapy for VRE peritonitis in patients undergoing CAPD. We present a pediatric case of successful treatment of CAPD-associated peritonitis due to VRE with linezolid, and review of the literature.

Brain Abscess Showing a Lack of Restricted Diffusion and Successfully Treated with Linezolid

  • Kim, Joo-hyun;Park, Sang-phil;Moon, Byung-gwan;Kim, Deok-ryeong
    • Brain Tumor Research and Treatment
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    • v.6 no.2
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    • pp.92-96
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    • 2018
  • A 59-year-old patient with a history of hepatocellular carcinoma presented with decreased consciousness and left hemiparesis. A rim-enhanced mass lesion without diffusion restriction was observed in contrast-enhanced MRI including diffusion-weighted imaging. Based on these findings, metastatic brain tumor was suspected. However, brain abscess (BA) was diagnosed after multiple bacterial colonies were observed in aspiration biopsy. Initial conventional antibiotic treatment including vancomycin had failed, so linezolid was used as second-line therapy. As a result, infection signs and clinical symptoms were resolved. We report a case with atypical imaging features and antibiotic susceptibility of a BA in an immunocompromised patient undergoing chemotherapy.

Use of a Sensitive Chemiluminescence-Based Assay to Evaluate the Metabolic Suppression Activity of Linezolid on Methicillin-Resistant Staphylococcus aureus Showing Reduced Susceptibility to Vancomycin

  • Komatsu, Mitsutakal;Tajima, Yutaka;Ito, Teruyo;Yamashiro, Yuichiro;Hiramatsu, Keiichi
    • Journal of Microbiology and Biotechnology
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    • v.19 no.7
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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.