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Drug Repurposing for the Treatment of mycobacterium abscessus Infections

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感染微生物与疾病(英文) 2023年第3期5卷 101-110页

作者： Emily J.Baker Antonia Molloy Jonathan A.G.Cox School of Life and Health Sciences Aston UniversityAston TriangleBirminghamUK.

With the ever-increasing burden of antimicrobial resistance,the demand to introduce countermeasures becomes increasingly *** urgency of this need is intensified by the void in antibiotic discovery,with the identification of novel compounds declining with *** increasing concern is mycobacterium abscessus,which displays high levels of intrinsic resistance that lead to poor success rates,even after lengthy drug *** tackling these issues is now focused on the repurposing of preexisting drugs for antimycobacterial use,facilitating the discovery of antimicrobial compounds amidst a crisis where novel antibiotics are *** of this includes the use of combination treatments,whereby coadministration of synergistic compounds can reduce dose requirements and slow the progression of antimicrobial resistance in the long *** this review,we will introduce the current therapeutic options for *** and provide insight into why treatment is so *** will also compile the current updates within drug repurposing for this pathogen,including the use of unconventional agents such as antimalarial drugs,the repositioning of antitubercu-losis candidates and the repurposing of preexisting antibiotics,including the application of combination *** addition,the in vitro drug screening platforms used in their discovery will be appraised,with the view of highlighting potential future perspectives that may help increase physiological *** review provides a timely appraisal of the future of *** treatment.

关键词： drug repurposing mycobacterium abscessus antimycobacterial drug discovery antimicrobials

mycobacterium abscessus infection after facial injection of argireline:A case report

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World Journal of Clinical Cases 2021年第8期9卷 1996-2000页

作者： Chao-Feng Chen Jie Liu Shuang-Shuang Wang Yu-Fang Yao Bo Yu Xiao-Ping Hu Department of Dermatology&Venereology Peking University Shenzhen HospitalShenzhen 518036Guangdong ProvinceChina

BACKGROUND The incidence of infection with mycobacterium abscessus(***)has increased in recent *** increase is partly associated with invasive cosmetic *** SUMMARY The purpose of this case summary is to increase clinicians'awareness of *** infection and reduce mycobacterial infection caused by cosmetic *** report the case of a 45-year-old woman who received acetyl hexapeptide-8(argireline)injections in the forehead and temples,and erythema,nodules,and abscesses appeared at the injection sites after one *** pus specimens were examined by microbiological culture and confirmed to be positive for *** 500 mg twice daily and moxifloxacin 400 mg once daily were administered for 5 mo and the lesions gradually *** We report here for the first time a case of infection with *** after argireline *** condition is easily misdiagnosed as a common bacterial *** examinations are helpful for diagnosis and standardized cosmetic procedures can prevent infection with ***.

关键词： Argireline mycobacterium abscessus Nontuberculous mycobacterium Infection Injection Antibiotic therapy Case report

Clinical isolates of mycobacterium abscessus in Guangzhou area most possibly from the environmental infection showed variable susceptibility

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Chinese Medical Journal 2013年第10期126卷 1878-1883页

作者： ZHUO Feng-lin SUN Zhao-gang LI Chuan-you LIU Zhi-hui CAI Lin ZHOU Cheng ZHANG Jian-zhong Department of Dermatology Peking University People's HospitalBeijing 100044 China Beijing Key Laboratory in Tuberculosis Drug Resistance BeijingChest Hospital Capital Medical University Beijing 101149 China Department of Clinical Laboratory Guangzhou Chest HospitalGuangzhou Guangdong 510095 China

Background mycobacterium abscessus （M. abscessus） can cause a variety of human infections, involving the lung, skin and soft tissues, and is generally believed to be acquired from environmental sources. The aim of this study was to investigate the molecular diversity and antibiotic susceptibility of M. abscessus isolates as the basis for strategies to improve control and management of infection. Methods Seventy M. abscessus isolates from patients attending the Guangzhou Thoracic Hospital were identified from 2003 to 2005 by biochemical tests, gas chromatography, polymerase chain reaction （PCR）-restriction analysis （PRA） of heat shock protein gene hsp65, and sequencing of the quinolone resistance determining regions （QRDRs） of gyrA. Susceptibilities to six antibiotics were determined by micro-broth dilution. Isolates were genotyped using randomly amplified polymorphic DNA （RAPD） analysis. Results Most isolates （63/70; 90%） were susceptible to amikacin but rates of susceptibility to other antibiotics varied from moderate, clarithromycin （60%） and imipenem （43%）, to low for ciprofloxacin and ofloxacin （3%）, and 87% of isolates had intermediate susceptibility to cefoxitin. RAPD analysis showed that the 70 clinical isolates displayed 69 unique RAPD patterns. Conclusions The high genetic diversity of isolates suggests that they are not transmitted from person to person but, presumably, are acquired independently from environmental sources. M. abscessus isolates displayed variable levels of susceptibility to all antibiotics tested, other than amikacin, indicating a need for routine susceptibility testing to guide treatment.

关键词： mycobacterium abscessus prevalence genetic diversity," susceptibility

Efficacy of Moxifloxacin against mycobacterium abscessus in Zebrafish Model in vivo

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Biomedical and Environmental Sciences 2020年第5期33卷 350-358页

作者： NIE Wen Juan XIE Zhong Yao GAO Shan TENG Tian Lu ZHOU Wen Qiang SHANG Yuan Yuan JING Wei SHI Wen Hui WANG Qing Feng HUANG Xue Rui CAI Bao Yun WANG Jun WANG Jing GUO Ru GE Qi Ping NIE Li Hui HAN Xi Qin DU Ya Dong CHU Nai Hui Tuberculosis Department Beijing Chest Hospital affiliated to Capital Medical UniversityBeijing 101149China Beijing Chest Hospital affiliated to Capital Medical University Beijing 101149China

Objective Moxifloxacin(MFX)shows good in vitro activity against mycobacterium abscessus and can be a possible antibiotic therapy to treat *** infection;however,other studies have shown a lower or no *** aimed to evaluate MFX activity against *** using zebrafish(ZF)model in *** A formulation of *** labeled with CM-Dil was micro-injected into *** curves were determined by recording dead ZF every *** were lysed,and colony-forming units(CFUs)were *** dissemination and fluorescence intensity in ZF were *** rates of MFX and azithromycin(AZM,positive control)were determined and *** Significantly increased survival rate was observed with different AZM ***,increasing MFX concentration did not result in a significant decrease in ZF survival *** significant differences in bacterial burdens by CFU loads were observed between AZM and MFX groups at various *** fluorescence intensity in ZF was significantly correlated with AZM ***,with increasing MFX concentration,fluorescence intensity decreased slightly when observed under fluorescence *** rates at various concentrations were comparable between the MFX and AZM groups,with no significant *** MFX showed limited efficacy against *** in vivo using ZF *** activity in vivo needs to be confirmed.

关键词： mycobacterium abscessus Moxifloxacin Azithromycin Zebrafish

Prevalence and Antimicrobial Susceptibility of mycobacterium abscessus in a General Hospital, China

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Biomedical and Environmental Sciences 2016年第2期29卷 85-90页

作者： LI Yan Ming TONG Xun Liang XU Hong Tao JU Yang CAI Meng WANG Chen Department of Respiratory and Critical Care Medicine Beijing Hospital Department of Hospital Infection Control and Management Beijing Hospital Department of Geriatrics Beijing Hospital Department of Laboratory Medicine Beijing Hospital Department of Respiratory Medicine Chinese-Japanese Friendship Hospital

Objective To gain greater insight into the prevalence drug resistant profiles of M. abscessus from a general hospital in Beijing, China. Methods Partial gene sequencing of 16 S, hsp65, and rpo B were used to distinguish the species of NTM isolates. All strains identified as M. abscessus were further enrolled in the drug susceptibility testing by using broth microdilution method. Results We found that M. avium complex was the most frequent NTM organism, accounting for 54.1%（33/61） of all isolates. Behind MAC, the second most common organisms were M. abscessus（22 out of 61, 36.1%）. Average rates of resistance were 4.5% for AMK, 9.1% for LZD, and 13.6% for CLA, respectively. In contrast, resistance to LEV（17/22, 77.3%）, IMI（9/22, 40.9%）, and SMX（10/22, 45.5%） was noted in more than 40% of M. abscessus isolates. DNA sequencing revealed that all the CLA-resistant isolates harbored nucleotide substitutions in position 2058（1/3, 33.3%） or 2059（2/3, 66.7%） of 23 S r RNA. Conclusion In conclusion, our data demonstrated that M. intracellulare and M. abscessus were the most common NTM species in the general hospital of Beijing. CLA, AMK, LZD showed promising activity, where as LEV, IMI, and SMX exhibited poor activity against M. abscessus in vitro.

关键词： Nontuberculous mycobacteria mycobacterium abscessus China

Molecular Epidemiology of Nontuberculous Mycobacteria in a German CF Center and Clinical Course of NTM Positive Patients

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Open Journal of Medical Microbiology 2013年第1期3卷 39-47页

作者： Carolin Kroner Barbara Ganster Matthias Kappler Ann-Christin Grimmelt Bernd H.Belohradsky Michael Hogardt Gudrun Laniado Michael Meissner Soren Schubert Matthias Griese Paediatric Pneumology Dr.von Hauner Children’s HospitalLudwig-Maximilians-UniversityMunichGermany Institute for Clinical Chemistry Molecular DiagnosticsMedical Microbiology and Hygiene DepartmentLudwigshafen General HospitalLudwigshafenGermany Institute for Medical Microbiology and Infection Control University HospitalJohann-Wolfgang-Goethe-UniversityFrankfurt/MainGermany Max von Pettenkofer Institute of Hygiene and Medical Microbiology Ludwig-Maximilians-UniversityMunichGermany

Goal of this study was to analyse the clinical course of cystic fibrosis (CF) patients with nontuberculous mycobacteria (NTM) in their respiratory secretions and to investigate the molecular epidemiology of the most prevalent NTM species by multilocus sequence analysis (MLSA). The respiratory specimen and the clinical parameters forced expiratory volume in one second (FEV1), body-mass-index (BMI), erythrocyte sedimentation rate (ESR) 1 h and immunoglobulin G (IgG) of 357 CF patients, 0 - 52.4 years, mean FEV1 2009 81.5% pred were analysed between 1998 and 2010. In 13 patients NTM were detected. 12 of 13 patients carried M. abscessus, for one patient the NTM species was not characterized. 4 patients carried a second NTM species (M. avium, M. chelonae (2x), M. intracellulare). 6 patients exhibited a significant decline in FEV1, however changes in BMI, IgG and ESR were discordant. Molecular genotyping of M. abscessus isolates revealed a unique MLSA pattern in 6 patients. 2 patients harboured identical strains, and one patient a closely related strain. Whether the presence of identical strains is attributed to the acquisition of NTM clones from common environmental sources or to patient-to-patient transmission cannot be definitely clarified. Although cross-in- fection of the three patients with identical/closely related strains in the present cohort is highly unlikely, we recommend strict hygiene measures for all CF patients harbouring NTM.

关键词： Mycobacteria Nontuberculous mycobacterium abscessus Cystic Fibrosis Molecular Epidemiology Multilocus Sequence Analysis(MLSA) Interferon Gamma