The Prevalence, Genotype and Antimicrobial Susceptibility of High-and Low-Level Mupirocin Resistant Methicillin-Resistant Staphylococcus aureus

( Se Young Park ),( Shin Moo Kim ),( Seok Don Park ) 대한피부과학회 2012 Annals of Dermatology Vol.24 No.1

Background: Mupirocin has been used for the treatment of skin infections and eradication of nasal carriage of methicillin- resistant Staphylococcus aureus (MRSA). The increased use of this antibiotic has been accompanied by outbreaks of MRSA that are resistant to mupirocin. Objective: This study aims to determine the prevalence, genotype and antimicrobial susceptibility of mupirocin-resistant MRSA from 4 Korean hospitals. Methods: A total 193 MRSA clinical isolates were collected from four university hospitals. Antimicrobial susceptibility tests, including mupirocin, and pulsed-field gel electrophoresis (PFGE) pattern analysis were performed. Results: Overall, 27 of the 193 (14.1%) MRSA isolates were resistant to mupirocin. All of the (A) hospital isolates showed high-level (HL) mupirocin resistance and the low-level (LL) mupirocin resistant strains were from three other hospitals. The PFGE patterns of 16 mupirocin-resistant isolates were divided into 5 clusters (1-5), and the nine HL mupirocin- resistant isolates belonged to cluster 1. Both the HL and LL mupirocin-resistant MRSA isolates were susceptible to vancomycin and rifampin, but they were resistant to ciprofloxacin, clindamycin and tetracycline. The erythromycin and fusidic acid resistance rates were different between the HL and LL resistant isolates. Conclusion: HL mupirocin-resistant isolates that could transfer this resistance to other bacteria were detected and these isolates were clonally related. The emergence of mupirocin resistant isolates emphasizes the importance of using antibiotics judiciously and carefully monitoring the prevalence of mupirocin resistance. (Ann Dermatol 24(1) 32∼38, 2012)

Drug utilization review of mupirocin ointment in a Korean university-affiliated hospital

( Sung Hee Youn ),( Seung Soon Lee ),( Sukyeon Kim ),( Jeong A Lee ),( Bum Joon Kim ),( Jounghee Kim ),( Hye Kyung Han ),( Jae Seok Kim ) 대한내과학회 2015 The Korean Journal of Internal Medicine Vol.30 No.4

Background/Aims: Intranasal mupirocin and chlorhexidine bathing are candidate strategies to prevent healthcare-associated infections caused by methicillin- resistant Staphylococcus aureus (MRSA). In Korea, intranasal mupirocin is not available, and mupirocin ointment, an over-the-counter drug, has been used indiscriminately. Furthermore, because it is covered by health insurance, mupirocin is easy to prescribe within hospitals. Methods: We performed a mupirocin drug utilization review (DUR) within Hallym University Sacred Heart Hospital. Annual use of mupirocin was investigated between 2003 and 2013, and monthly consumption of mupirocin was assessed during the final 2-year period. The DUR focused on August 2012, the period of highest use of mupirocin. Also, we investigated trends in mupirocin resistance in MRSA between 2011 and 2013.Results: Annual consumption of mupirocin increased from 3,529 tubes in 2003 to 6,475 tubes in 2013. During August 2012, 817 tubes were prescribed to 598 patients; of these, 84.9% were prescribed to outpatients, and 77.6% at the dermatology department. The most common indication was prevention of skin infections (84.9%), and the ointment was combined with systemic antibiotics in 62.9% of cases. Theaverage duration of systemic antibiotic administration was about 7.8 days. The rate of low-level mupirocin resistance in MRSA increased from 8.0% to 22.0%, and that of high-level mupirocin resistance increased from about 4.0% to about 7.5%.Conclusions: Inappropriate use of mupirocin is prevalent. Considering the increase in resistance and the future application of intranasal mupirocin, prophylactic use of mupirocin in dermatology departments should be reconsidered.

In Vitro Antimicrobial Activities of Fusidic Acid and Retapamulin against Mupirocin- and Methicillin-Resistant Staphylococcus aureus

( Sang Hyun Park ),( Jin Kyung Kim ),( Kun Park ) 대한피부과학회 2015 Annals of Dermatology Vol.27 No.5

Background: The in vitro activities of retapamulin and fusidic acid against clinical isolates of mupirocin-resistant and methicillin- resistant Staphylococcus aureus (MRSA) from Korea are not well understood. Objective: This study aimed to determine the activities of retapamulin and fusidic acid against clinical isolates of mupirocin-resistant MRSA. Methods: Clinical isolates of mupirocin-resistant MRSA were collected from two tertiary hospitals. The minimal inhibitory concentrations of mupirocin, fusidic acid, and retapamulin were determined using agar dilution method. Polymerase chain reaction was used to confirm the identity of the species and the presence of resistance genes. Pulsed-field gel electrophoresis (PFGE) patterns of chromosomal DNA were used to determine the genetic similarity of high-level mupirocin-resistant isolates. Results: Of the 497 MRSA isolates tested, 22 (4.4%) were mupirocin-resistant. Of these, 9 (1.8%) and 13 (2.6%) had high-level and low-level mupirocin resistance, respectively. Analysis of the PFGE patterns of the high-level mupirocin-resistant MRSA isolates identified five clusters. All 13 of the low-level mupirocin-resistant isolates were resistant to fusidic acid but susceptible to retapamulin. However, among the 9 high-level mupirocin-resistant isolates, 56% were resistant to fusidic acid, and all were susceptible to retapamulin. Conclusion: Retapamulin is highly active in vitro against Korean clinical isolates of high-level mupirocinand methicillin-resistant Staphylococcus aureus with different genetic backgrounds. Fusidic acid is more active against high-level mupirocin-resistant MRSA than low-level mupirocin- resistant MRSA. (Ann Dermatol 27(5) 551∼556, 2015)

국내 한 대학병원에서 수집된 Mupirocin 내성 포도알균의 내성 유전자 및 항생물질 감수성 분석

민유홍,이종서,권애란,심미자,최응칠,Min, Yu-Hong,Lee, Jong-Seo,Kwon, Ae-Ran,Shim, Mi-Ja,Choi, Eung-Chil 한국미생물학회 2012 미생물학회지 Vol.48 No.2

서울의 한 종합병원에서 포도알균 임상균주들을 2003, 2005, 2006 및 2009년에 각각 100, 195, 151 및 112주를 수집하여 mupirocin 내성율 변화 추이를 분석하였다. Staphylococcus aureus의 mupirocin에 대한 고도내성(최소억제농도 ${\geq}512{\mu}g/ml$) 빈도는 감소 추세로 2005년 이후에는 나타나지 않았다. 반면 S. aureus의 저도내성(최소억제농도 $8-256{\mu}g/ml$)은 2005년까지 나타나지 않았으나 2006년부터 나타나기 시작하여 2009년에는 6.9%에 이르렀다. Coagulase-negative staphylococci (CNS)의 전체적인 내성율은 S. aureus와 달리 상당히 높은 수준이었다. 2003년 CNS의 고도내성율은 16.0%이었으나 지속적으로 상승하여 2009년에는 31.5%에 이르렀다. CNS의 저도내성율은 2003년 8.0%이었고 이후 11% 정도의 일정 수준을 나타내었다. 모든 고도내성 균주들에서 ileS-2의 존재가 확인되었으며, 모든 저도내성 균주들에 대하여 ileS 유전자의 염기서열을 분석한 결과, 저도내성의 원인으로 알려진 V588F 변이가 공통적으로 발견되었다. 이외에도 S. aureus에서 V458G, 그리고 CNS에서 D172A, Y490H, I750V 변이들이 새로 발견되었다. Mupirocin 내성 균주들의 oxacillin 및 피부감염 치료에 사용되는 주요 외용 항생물질들에 대한 내성율을 측정한 결과, 고도내성인 S. aureus 1주는 이들 모든 항생물질에 내성이었고 저도내성인 S. aureus 10주는 fusidic acid를 제외한 모든 항생물질에 내성이었다. Mupirocin에 고도내성(61주) 및 저도내성(27주)인 CNS 균주들은 감수성인 CNS 균주들(167주)보다 이들 항생물질에 대하여 상당히 높은 내성율을 보였다. 따라서 포도알균에 의한 피부감염의 효과적인 치료를 위해선 mupirocin 내성 균주의 출현을 방지해야 한다. We analyzed mupirocin resistance rates among staphylococcal isolates collected from a Korean hospital in 2003 (100 isolates), 2005 (195 isolates), 2006 (151 isolates), and 2009 (112 isolates). In Staphylococcus aureus, rates of high-level mupirocin resistance (MIC, minimal inhibitory concentration ${\geq}512{\mu}g/ml$) decreased and did not appear since 2005. In contrast, low-level mupirocin resistance (MIC $8-256{\mu}g/ml$) was not detected in 2003 and 2005 but its rates later increased to 6.9% in 2009. Total resistance rates of coagulase-negative staphylococci (CNS) were significantly higher than those of S. aureus. The rates of high-level resistance of CNS increased from 16.0% in 2003 to 31.5% in 2009. The rate of low-level resistance of CNS was 8.0% in 2003 and around 11% later. In all high-level resistant isolates, the ileS-2 gene was detected. All low-level resistant isolates contained the known V588F mutation in ileS gene. Previously unknown mutations such as V458G in S. aureus and D172A, Y490H and I750V in CNS were identified additionally. One S. aureus isolate with high-level resistance was resistant to oxacillin and several topical antibiotics commonly used for the treatment of skin infection. Ten S. aureus isolates with low-level resistance were also resistant to all of these antibiotics except fusidic acid. CNS isolates with high-level (61 isolates) and low-level resistance (27 isolates) exhibited significantly higher resistance rates to these antibiotics than mupirocin-susceptible CNS isolates (167 isolates). In conclusion, prevention of the emergence of mupirocin resistance is necessary for the effective treatment of skin infection by staphylococci.

뮤피로신 내성 황색포도알균의 빈도 및 임상적 특성

이아진,서헌석,전창호,김상경 대한임상미생물학회 2011 Annals of clinical microbiology Vol.14 No.1

Background: Nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) is a known risk factor for nosocomialtransmission and infection. In an effort to mitigate this problem, topical mupirocin has been widely used for clearing nasal carriage of MRSA. However, mupirocin resistance has become a worldwide concern due to increased use of the antibiotic. The aims of this study were to evaluate the clinical characteristics and prevalence of mupirocin resistance among clinical isolates of staphylococci and to investigate antimicrobial susceptibility. Methods: A total of 175 S. aureus specimens recovered over a 4-month period from various body sites were tested for resistance to mupirocin and other antibiotics using the Vitek2 automated system. The presence of the mupA gene was assessed in isolates exhibiting resistance to mupirocin and in other selected organisms. The clinical characteristics of the isolates were also reviewed. Results: Of the 175 S. aureus isolates, 9.1% (16/175) were resistant to mupirocin, with 1.7% (3/175) having high-level resistance (HR) and 7.4% (13/175) having low-level resistance (LR). Patients with HR-mupirocinresistant S. aureus had a longer duration of hospitalization (P=0.026). Of the 13 LR-mupirocin-resistant S. aureus strains, 11 had identical antibiogram patterns. The mupA gene was detected only among HR isolates. Conclusion: The rate of mupirocin resistance in the S. aureus isolates was high. The spread of mupirocinresistant S. aureus may be due to nosocomial infection.

Isolation and Antimicrobial Susceptibility of Mupirocin-Resistant and Methicillin-Resistant Staphylococcus aureus from Clinical Samples

Kim, Shin-Moo,Park, Se-Young,Park, Seok-Don 대한미생물학회 2011 Journal of Bacteriology and Virology Vol.41 No.4

Resistance to mupirocin in methicillin-resistant Staphylococcus aureus (MRSA) have increased with wide use of mupirocin in many countries, but the prevalence in Korea is not well-known. The aim of this study was to determine the prevalence, antimicrobial susceptibility, and clonality of mupirocin-resistant (MUP-R) isolates from three Korean hospitals. A total of 175 MRSA isolates were collected from three university hospitals in 2009-2010. Antimicrobial susceptibility was tested by the disk diffusion and the agar dilution methods. femA, mecA and mupA genes were detected by polymerase chain reactions. Pulsed-filed gel electrophoresis (PFGE) pattern of genomic DNA was determined after digestion with SmaI. Overall, 12 among the 175 MRSA isolates were resistant to mupirocin, with prevalence ranging from 0 to 10% depending on hospitals. Three high-level (HL) and nine low-level (LL) MUR-R isolates were obtained from two hospitals. All MUP-R isolates were susceptible to rifampin and vancomycin, but were resistant to ciprofloxacin, clindamycin, and erythromycin. Eight LL and one HL MUP-R isolates were also resistant to fusidic acid. PFGE analysis showed three HL MUP-R isolates belonged to arbitrary cluster 3, 5 and 6 with 60~90% similarity compared to LL MUP-R isolates. In conclusion, the HL resistance to mupirocin was detected in two hospitals, but HL MUP-R isolates were clonally not related.

복막 투석 환자에서 도관 관련 감염 및 복막염에 대한 Mupirocin과 도관 전환술(Catheter revision)의 효과

박준범,김정미,최준혁,조규향,정항재,김영진,도준영,윤경우 영남대학교 의과대학 1999 Yeungnam University Journal of Medicine Vol.16 No.2

Background: Exit site/tunnel infection causes considerable morbidity and technique failure in CAPD patients. We presently use a unique revision method for the treatment of refractory ESI/TI in CAPD patients and mupirocin prophylaxis for high risk patients. Materials and Methods: We reviewed 139 CAPD patients about the ESI/TI from October 1993 to February 1999 at Yeungnam University Hospital. At the beginning of the ESI, we usually started medications with rifampicin and ciprofloxacin and then changed the antibiotics according to the sensitivity test. If the ESI had persisted and there were TI symptoms (purulent discharge, abscess lesion around exit site). we performed catheter revision(external cuff shaving, disinfection around tunnel and new exit site on opposit direction) with a combination of proper antibiotics. We applied local mupirocin ointment at the exit site three times per week to the 34 patients who had the risk of ESI starting from October 1998. Results: The total follow-up was 2401 patient months(pt. mon). ESI occurred on 105 occasions in 36 out of 139 patients, and peritonitis occurred on 112 occasions in 67 out of 139 patients. The total number of incidences of ESI and peritonitis was 1 per 23.0 pt.mon and 1 per 21.6 pt.mon. The most common organism responsible for ESI was Staphylococcus aureus (26 of 54 isolated cases, 48%), followed by the Methicillin resistant S, aureus(MRSA) (13 cases, 24%). Seven patients(5: MRSA, 2: Pseudomonas) had to be treated with a revision to control infection. Three patients experienced ESI relapse after revision. One of them improved with antibiotics, while another needed a second revision and the remaining ??quired catheter removal due to persistent MRSA infection with re-insertion at the same ??me. But, there was no more ESI in these 3 patients who were received management to ??lapse (The mean duration: 14.0 months) The rates of ESI were significantly reduced after ??sing mupirocin than before(1 per 12.7 vs 34.0 pt.mon, P<0.01). Conclusions: In summary, revision technique can be regarded as an effective method for ??efractory ESI/TI before catheter removal. Also local mupirocin ointment can play a ??gnificant role in the prevention of ESI.

High-level mupirocin resistance in Gram-positive bacteria isolated from diseased companion animals

Samuth Sum,Hee-Myung PARK,오재영 대한수의학회 2020 Journal of Veterinary Science Vol.21 No.3

The purpose of this study was to investigate the high-level mupirocin resistance (HLMR) in Gram-positive bacteria isolated from companion animals. A total of 931 clinical specimens were collected from diseased pets. The detection of mupirocin-resistant bacteria and plasmid-mediated mupirocin resistance genes were evaluated by antimicrobial susceptibility tests, polymerase chain reactions, and sequencing analysis. Four-hundred and six (43.6%) bacteria were isolated and 17 (4.2%), including 14 staphylococci and 3 Corynebacterium were high-level mupirocin-resistant (MICs, ≥1,024 ug/mL) harboring mupA. Six staphylococci of HLMR strains had plasmid-mediated mupA-IS257 flanking regions. The results show that HLMR bacteria could spread in veterinary medicine in the near future.

P048 : In vitro activities of retapamulin and fusidic acid against mupirocin-resistant, methicillin-resistant staphylococcus aureus from clinical samples

( Sang Hyun Park ),( Jin Kyung Chae ),( Sun Yong Kwon ),( Ui Kyung Kim ),( Shin Moo Kim ),( Kun Park ),( Seok Don Park ) 대한피부과학회 2013 대한피부과학회 학술발표대회집 Vol.65 No.2

Background: In vitro activities of retapamulin against mupirocin- and fusidic acid- resistant, methicillin-resistant Staphylococcus aureus isolates from Korea are not well known. Objectives: The aims of the study were to determine the acitivities of retapamulin and fusidic acid against mupirocin-resistant (MUP-R) MRSA isolates from clinical specimens. Methods: MRSA isolates were collected from three university hospitals in 2009-2010. Antimicrobial susceptibility was determined by the CLSI agar dilution method. femA, mecA and mupA genes were detected by PCR. Results: 1. The MIC range of fusidic acid for the low-level MUP-R MRSA isolates were ≥128 ug/mL, but the MIC range and MIC90 for the high-level MUP-R isolates were ≤ 0.5-≥32 ug/mL, and ≥32 ug/mL, respectively. 2. The MIC ranges and MIC90s of retapamulin for both the low-level and high-level MUP-R MRSA isolates were 0.5-1 ug/mL and l ug/mL, respectively. 3. Among the 21 MUP-R MRSA isolates tested, all 13 low level-resistant isolates were resistant to fusidic acid, but susceptible to retapamulin. Among the eight high-level MUP-R isolates 63% were resistant to fusidic acid, but all were susceptible to retapamulin. Conclusion: Retapamulin is highly active against MRSA isolates resistant to mupirocin and fusidic acid.

Mupirocin으로 치료된 심상성 모창 1예

안종성,서대헌,조광현,윤재일 대한화학요법학회 1997 대한화학요법학회지 Vol.15 No.4

본 증례는 erythomycin, penicillin-G, clindamycin, gentamycin 등에 저항성을 가진 S. aureus균에 의해 발생하였고 여러 항생제의 치료에도 반응하지 않다가 국소 mupirocin의 도포로 빠른 치유를 보인 심상성 모창 1예이다. Sycosis vulgaris is a kind of infectious deep follicuhtis. In some case, there are resistance to antibiotics, causing difficulty in treatment We experienced a patient of sycosis vulgaris with multiple erythematous folhcular papules and pustules on the beard region and scalp. He had been given several medications in other hospitals, but he was not improved. We treated him with roxithromycin, an analogue of erythromycin for two weeks, but failed. After labratory investigations including antibiotics sensitivity test, topical mupirocin was tried. Skin lesions were dramatically cleared