그람양성균이 의심되거나 증명된 피부 및 연조직 감염증의 치료에 대한 Linezolid의 효능과 안전성

엄중식,이혁,신동현,김양리,김신우,이충기,송재훈,김준명,강문원,김우주 대한감염학회 2005 감염과 화학요법 Vol.37 No.2

Background : Linezolid, an oxazolidinone, has shown efficacy in the treatment of adults with nosocomial or community-acquired pneumonia, skin and soft tissue infections (SSTI), and infections due to methicillin-resistant Staphylococcus aureus. We have taken part in the study for evaluation of efficacy and safety of linezolid for the treatment of suspected or proven gram-positive SSTI in Asia. We sub-analyzed and reported the results of the study among Korean patients. Materials and Methods : A total of 60 patients were enrolled in the study for evaluation of efficacy and safety of linezolid for the treatment of gram-positive SSTI at eight teaching hospitals in Korea. We investigated patients' medical history, physical examination and laboratory study. Patients were regularly followed up to evaluate clinical response, laboratory changes, and adverse event up to 4 weeks after treatment. When possible, we performed microbiological study before and after treatment. Results : A total of 60 patients were enrolled. Average age of the patient was 50.9±15.3 years old with male to female ratio being 1.3 : 1. Cellulitis, open wound infection, skin abscess, and other clinical manifestations were observed in 47 (78.3%), 6 (10.0%), 2 (3.3%), and 5 (8.3%) patients, respectively. Forty two patients completed both follow-up and treatment and among them, treatment was successful in 38 patients (90.5%) and unsuccessful in 4 patients (9.5%). Microoranisms were isolated from seven patients and 14 isolates were documented; 11 S. aureus, 3 coagulase-negative staphylococcus. Among the seven patients, bacteria were eradicated in four patient and the organism proved to be colonization in three patients. The most frequent drug-related adverse events were gastrointestinal (21.7%), hematologic and biochemical (21.7%) and neurologic (3.3%), in decreasing order. Nausea (15%) was the most frequent symptom and there were no serious side effects related to linezolid. Conclusion : Linezolid was effective and safe in treatment of gram-positive SSTI. 배경 : Linezolid (Zyvox^(R))는 oxazolidmone 계열의 그람양성균 감염증에 대한 새로운 치료제로 그람양성균, 특히 메티실린 내성 포도구균과 반코마이신 내성 장구균에도 효과적인 것으로 알려져 있다. 연구자들은 아시아 지역에서 제 4상, 개방형, 공개, 다기관 연구로 진행되었던 "그람양성균이 의심되거나 증명된 피부 및 연조직 감염증에 대한 linezolid의 치료 효능 및 안전성"의 국내 연구결과를 분석하여 그람양성균에 의한 피부 및 연조직 감염증에 대한 linezolid의 치료 효과와 안전성을 평가하였다. 재료 및 방법 : 국내 8개 종합병원에서 피부 및 연조직 감염증의 원인으로 그람양성균이 의심되거나 증명된 입원 환자 중 사전동의를 하여 연구에 참가한 60명을 대상으로 하였다. 치료는 linezolid 주사제 1회 600 mg을 1일 2회 투여하였고 상태 호전시 연구자의 판단에 따라 동량을 경구로 전환할 수 있도록 하였다. 치료 시작부터 종료 후 4주까지 환자의 병력, 이학적 검사, 이상반응 증상 및 징후의 유무를 정기적으로 조사하였고 혈액학검사, 생화학검사, 소변검사 등의 결과를 평가하여 linezolid의 임상적 효과와 안전성을 판정하였다. 원인균의 분리를 위하여 가능한 경우 감염 병변으로 부터 그람염색 및 배양검사를 시행하였고 혈액배양검사를 함께 실시하여 미생물학적 근절여부를 판정하였다. 결과 : 환자군의 평균연령은 50.9±15.3세였고 남녀비는 1.3:1이었다. 진단별로 연조직염 47명(78.3%), 개방창생감염 6명(10.0%), 피하농양 2명(3.3%), 기타 5명(8.3%)이었고, linezolid의 평균 투여 횟수는 41.2±19.3회였다. 60명의 환자 중 추적 관찰을 포함한 모든 치료 일정을 마친 환자는 42명(70.0%)이었고 치료 성공은 38명(90.5%)이었고 4명(9.5%)이 치료에 실패하였다. 배양검사에서 7명의 환자로부터 원인균이 분리되어 4명이 미생물학적으로 박멸되었고 3명은 집락 형성으로 판정되었다. Linezolid와 관련된 이상반응은 소화기계 이상 13명(21.7%), 혈액 및 생화학적 이상 13명(21.7%), 감각신경계 이상 2명(3.3%)순이었고 단일 이상 반응으로는 오심(15%)이 가장 흔하였으나 linezolid와 관련이 증명된 중대한 이상반응은 없었다. 결론 : Linezolid는 그람양성균에 의해 발생되는 피부 및 연조직 감염증의 치료에 우수한 효과가 있었으며, 비교적 안전한 것으로 평가되었다.

다제내성 그람양성균에 대한 Linezolid(Zyvox^(�))의 시험관내 항균력 비교

박대원,정희진,엄중식,황병연,김성범,이재갑,이연주,정혜원,정성주,박재형,이진수,손장욱,김우주,김민자,박승철 대한감염학회 2003 감염과 화학요법 Vol.35 No.5

배경 : MRSA, VRE, VRSA같은 다제 내성 그람 양성균의 등장에 따라 glycopeptide를 대체할 새로운 항생제의 개발이 필요하게 되었고 결과적으로 새로운 항생제인 linezolid라는 항생제가 개발되었다. Linezolid는 이전의 항생제와는 다른 새로운 계열의 oxazolidinone으로 경구 이용률이 우수하다. 원내 및 원외감염의 중요한 원인균이 되고 있는 MRSA, VRE에 대한 적절한 경구용 항균제가 없는 국내에서 폐렴 및 피부 연조직 감염에서 경구용으로 사용해 볼 수 있는 약제이다. 본 연구에서는 고대 구로 병원에서 분리된 MRSA, VRE 등을 대상으로 다른 여러 항균제와 비교한 linezolid의 시험관내 항균력을 조사하고자 하였다. 재료 및 방법 : 연구대상은 1998년 1월부터 2000년 12월까지 본원에서 입원 및 외래를 통하여 피부 연조직 감염증 및 호흡기 감염증, 요로감염증으로 진단된 환자들의 가검물로부터 분리된 MRSA 60균주, VRE 43균주, PRSP 25균주를 액체배지 또는 한천배지 희석법을 통하여 linezolid 및 기타 항균제에 대한 최소발육억제농도를 구하였다. 결과 : 실험에 사용한 S. aureus는 모두 MRSA였고 이들은 linezolid에 대해 MIC_(90) 2㎍/㎖(MIC 범위 1-2㎍/㎖), Enterococcus spp는 모두 VRE로 linezolid의 MIC_(90)은 2㎍/㎖로 MIC 범위는 1-4㎍/㎖였다. 한 개의 균주에서 MIC 4㎍/㎖로 중등도 감수성을 보였으나 MIC breakpoint가 (8㎍/㎖인 내성균주는 없고 모두 감수성을 보였다. S. pneumoniae의 경우 penicillin 내성이었고, linezolid MIC_(90) 1㎍/㎖ (MIC 범위 0.5-1㎍/㎖)로 전부 감수성을 보였다. 결론 : Linezolid는 MRSA를 위시한 VRE, PRSP 등의 다제 내성 그람 양성균에 대하여 우수한 시험관내 항균력을 보임을 알 수 있었다. Background : The emergence of multi-drug resistant Gram-positive cocci, such as MRSA, VRE, and VRSA, necessitated to develop new antibiotics, which could replace the glycopeptide. As a result, a new antibiotics named linezolid was developed. Linezolid is different line of oxazolidinones with a good oral bioavailability, compared to other antibiotics. Since appropriate oral antibiotics are not presently available for MRSA, which is a major cause of nosocomial and community acquired infections, the introduction of linezolid will have favorable effect on treatment of infections such as pneumonia or skin infections. In this study, we investigated the antibiotic effect of linezolid on MRSA and VRE isolated from patients who were treated in Korea University Guro Hospital. Material and Methods : By using broth microdilution and agar dilution method we measured minimum inhibitory concentration (MIC) with sixty S. aureus, forty three Enterococcus spp., and twenty five S. pneumoniae isolates from patients who were diagnosed as skin, soft tissue, respiratory, and urinary infections in Korea University Guro Hospital from January, 1998 to December, 2002. Results : All of S. aureus used in this study were MRSA, and MIG_(90) of linezolid was below 2 ㎍/㎖ (MIC ranged between 1-2 ㎍/㎖). All of Enterococcus spp. were VRE, and had MIG_(90) of 2 ㎍/㎖ (MIC ranged between 1 to 4 ㎍/㎖). One of the VRE showed intermediate susceptibility with MIC of 4 ㎍/㎖. However, none was resistant with MIC breakpoint above 8 ㎍/㎖. All of S. pneumoniae were resistant to penicillin, but they were susceptible to linezolid with MICao of 1 ㎍/㎖(MIC range 0.5-1㎍/㎖). Conclusion : In conclusions, linezolid has an excellent in vitro antibiotic effect on multi-drug resistant Gram-positive cocci, such as MRSA, PRSP, and VRE.

Linezolid Resistance in Methicillin-Resistant Staphylococcus aureus in Korea: High Rate of False Resistance to Linezolid by the VITEK 2 System

유인영,On-Kyun Kang,Hyang Jin Shim,허희재,Nam Yong Lee 대한진단검사의학회 2020 Annals of Laboratory Medicine Vol.40 No.1

As various linezolid resistance mechanisms have been identified in methicillin-resistant Staphylococcus aureus (MRSA), we investigated the molecular characteristics of MRSA with elevated linezolid minimum inhibitory concentrations (MICs), using the VITEK 2 system (bioMérieux, Marcy-l’Étoile, France). Twenty-seven MRSA isolates from 14 patients exhibiting linezolid MICs ≥8 μg/mL were examined by broth microdilution (BMD) test as well as by sequencing for mutations in the 23S rRNA gene or ribosomal proteins (L3, L4, and L22) and the presence of the optrA, cfr, and cfr(B) genes. Of the 27 isolates, four (14.8%) from one patient were confirmed as linezolid resistant by BMD and harbored a 23S rRNA T2500A mutation. The remaining 23 were confirmed as linezolid susceptible, indicating that the linezolid-resistant results were major errors generated by VITEK 2. The most commonly detected mutation (19/27, 70.4%), L3 Gly152Asp, was detected in only linezolid-susceptible isolates. No isolates contained optrA, cfr, or cfr(B) or any L4 or L22 protein alterations. Our results show that the 23S rRNA T2500A mutation was mainly associated with linezolid resistance, while the L3 Gly152Asp mutation was not related to linezolid resistance. A confirmatory test is recommended for VITEK 2 linezolid-resistant results owing to the high probability of false resistant results.

그람양성균으로 인한 감염 척추염에서 Linezolid의 효과와 안전성

정종탁 ( Jongtak Jung ),이은영 ( Eunyoung Lee ),송경호 ( Kyoung-ho Song ),최평균 ( Pyoeng Gyun Choe ),박완범 ( Wan Beom Park ),방지환 ( Ji Hwan Bang ),김의석 ( Eu Suk Kim ),김홍빈 ( Hong Bin Kim ),박상원 ( Sang Won Park ),김남중 ( 대한내과학회 2018 대한내과학회지 Vol.93 No.5

Background/Aims: Infectious spondylitis requires long-term antibiotic treatment; however, the use of intravenous antibiotics during this period has high social and monetary costs due to hospitalization. Linezolid has high oral bioavailability and is not affected by changes in renal or hepatic function. We investigated the clinical and microbiological effects of linezolid in infectious spondylitis caused by beta-lactam resistant gram-positive bacteria. Methods: Clinical data from patients who were treated with linezolid for at least four weeks were collected retrospectively from electronic medical records at the Seoul National University Hospital, Seoul National University Bundang Hospital, and Boramae Medical Center from 2006 to 2016. Results: Twenty Korean patients were treated with linezolid for at least four weeks during the study period. Of these, 14 patients were cured, four failed, and two cases of mortality occurred due to other causes than infectious spondylitis. Ten of 13 patients who had previously been assessed as vancomycin treatment failure were cured by linezolid. Bacteremia occurred in 14 patients, and 10 of these showed persistent bacteremia at the time of linezolid administration. Eight of these cases of persistent bacteremia were cured by linezolid. Median duration of linezolid treatment was 40.5 days (28-90 days). Severe cytopenia (grade II or more of National Cancer Institute criteria) was the most common adverse event, with incidences of 11.11% for neutropenia, 12.96% for anemia, and 20.37% for thrombocytopenia. Conclusions: Linezolid can be used as an effective antibiotic agent in patients with infectious spondylitis, especially when treatment failure of the first-line treatment is expected. (Korean J Med 2018;93:464-472)

다제내성결핵 환자에서 메타분석을 통한 Linezolid의 효능 및 안전성 평가

정우진,성태욱,김애진,채정우,윤휘열 한국임상약학회 2023 한국임상약학회지 Vol.33 No.4

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.

Linezolid에 의한 유산증

이홍주 ( Hong Joo Lee ),최재호 ( Jae Ho Choi ),김선용 ( Sun Yong Kim ),정경환 ( Kyung Hwan Chung ),이태원 ( Tae Won Lee ),임천규 ( Chun Gyoo Ihm ),문주영 ( Ju Young Moon ) 대한내과학회 2012 대한내과학회지 Vol.82 No.3

Linezolid has been used for treatment of vancomycin-resistant Enterococcus faecium infection, nosocomial pneumonia caused by Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus or Streptococcus pneumoniae, and complicated and uncomplicated skin and skin structure infections. Lactic acidosis is an adverse effect associated with drugs, including metformin, the nucleoside reverse-transcriptase inhibitors and, rarely, linezolid. We report a case in which severe lactic acidosis developed as an adverse effect of linezolid in a 75-year-old woman who had been on linezolid for 30 days for treatment of a wound infection caused by methicillin-resistant coagulase-negative Staphylococcus. Discontinuation of linezolid and hemodialysis improved her lactic acidosis. (Korean J Med 2012;82:371-373)

다제내성 결핵 환자에서 장기간 Linezolid 복용에 의해 유발된 말초성 다발신경병 1예

장신혜,전하라,김성우,신정빈 대한근전도전기진단의학회 2015 대한근전도 전기진단의학회지 Vol.17 No.1

Linezolid is an antibiotic with antimycobacterial activity and used for patients with highly drug-resistant tuberculosis. Peripheral neuropathy is a rare adverse effect of linezolid therapy. However, there has not been a report of peripheral neuropathy caused by linezolid in a multidrug-resistant tuberculosis patient, domestically. We present a case of linezolidinduced peripheral neuropathy in drug-resistant tuberculosis. The patient complained of neuropathic pain and abnormal sensory symptom after treatment of linezolid and the symptoms were reduced after discontinue of linezolid.

Methicillin-Resistant Staphylococcus Aureus 감염으로 인한 병원 내 감염 폐렴치료제로서 Linezolid와 Vancomycin의 비용-효과 분석

박지현,정재홍,황성혜 한국보건의료기술평가학회 2015 보건의료기술평가 Vol.3 No.2

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is considered to be the primary cause of hospital acquired pneumonia (HAP) and MRSA-associated HAP occur a significant impact on healthcare resource use and associated economic costs. The objective of this study was to investigate the economic impact of linezolid compared with that of vancomycin in the treatment of hospitalized pa- tients with MRSA-confirmed HAP in the Korea. Methods: A 30-days decision tree model incorporat- ed published data on clinical parameters, resource use, and costs were constructed. The base case first- line treatment duration for patients with hospital-acquired pneumonia was 10 days. Treatment success, discontinuation due to adverse events, discontinuation due to lack of efficacy, and mortality were possi- ble outcomes that could impact costs. Results: The model calculated that linezolid was associated with an 1.8% higher cure rate compared with vancomycin (62.5% vs. 60.7%, respectively). Average total costs per episode for linezolid-and vancomycin-treated patients were KRW 3420971 and 3459977 respective- ly. The incremental cost-effectiveness ratio favored linezolid (versus vancomycin), with marginally low- er costs (by KRW 39006) and greater efficacy (+1.8% absolute difference in the proportion of patients successfully treated for MRSA HAP). Conclusion: The study shows that linezolid is a cost-effective al- ternative to vancomycin for HAP.

Emergence of optrA-Mediated Linezolid-Nonsusceptible Enterococcus faecalis in a Tertiary Care Hospital

Kuenyoul Park,Yun Sil Jeong,Jeonghyun Chang,Heungsup Sung,Mi-Na Kim 대한진단검사의학회 2020 Annals of Laboratory Medicine Vol.40 No.4

This study investigated resistance mechanisms and epidemiology of emerging linezolid-nonsusceptible Enterococcus faecalis (LNSEF) in a tertiary care hospital. LNSEF isolated from clinical samples were collected from November 2017 to June 2019. The isolates were investigated for linezolid resistance and the associated molecular mechanisms, including mutations of 23S rRNA domain V and acquisition of the cfr or optrA resistance gene. We used pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing for the molecular typing of the isolates. Among 4,318 E. faecalis isolates, 10 (0.23%) were linezolid-nonsusceptible. All LNSEF isolates were optrA-positive and cfr-negative. Of these isolates, five were sequence type (ST) 476, two ST585, one ST16, one ST16-like, and one ST480. Six LNSEF isolates obtained in the first year clustered to three types in the PFGE analysis: two ST476 isolates of type A, two ST585 isolates of type B, and two ST16 or ST16-like isolates of type C. Seven cases were of community-onset and three were hospital acquired, but total of eight were healthcare-associated including five community-onset. None of the patients had a history of linezolid treatment, and in one patient, we detected linezolid-susceptible E. faecalis one month before LNSEF detection. In conclusion, heterogenous clones of optrA-positive LNSEF emerged in the hospital mainly via community-onset.

장기간 Linezolid 치료 후 발생한 유산증

정승규 ( Seung Kyu Chung ),전진석 ( Jin Seok Jeon ),김태형 ( Tae Hyong Kim ),김철 ( Chul Kim ),권순효 ( Soon Hyo Kwon ),노현진 ( Hyun Jin Noh ),한동철 ( Dong Chul Han ) 대한신장학회 2009 Kidney Research and Clinical Practice Vol.28 No.1

Lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients. Although impaired tissue oxygenation is usually responsible for the rise in lactate production, lactic acidosis could be caused by drugs including metformin and the nucleoside reverse-transcriptase inhibitors. Linezolid, an oxazolidinone antibiotic, is currently indicated to treat serious infections caused by van-comycin-resistant enterococcus and other gram-positive organisms. A 74-year old woman was found to have pyogenic vertebral osteomyelitis and treated with linezolid. Thirty-one days after linezolid therapy, she developed severe lactic acidosis. We report a case of lactic acidosis associated with prolonged linezolid therapy.