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association between sequevar and antibiotic treatment outcome in patients with mycobacterium abscessus complex infections in japan.macrolide susceptibility differs between subspecies in the mycobacterium abscessus complex, likely due to differences in erm(41) sequevars. patients with m. abscessus complex infection generally show poor clinical outcomes in response to antibiotic treatment. here, the association between genotype and treatment outcome was investigated.201829227218
in vitro activity of tedizolid against the mycobacterium abscessus complex.infections due to mycobacterium abscessus carry a poor prognosis since this rapidly growing mycobacterium is intrinsically resistant to most antibiotics. here, we evaluate the in vitro activity of the new oxazolidinone tedizolid against a collection of 44m. abscessus clinical isolates. the mic50s and mic90s of tedizolid (2 and 8μg/ml, respectively) were 2- to 16-fold lower than those of linezolid. there was no difference between the 3m. abscessus subspecies. time-kill assays did not show any bac ...201729217419
activity of rifabutin and hemi-synthetic derivatives against mycobacterium abscessus.mycobacterium abscessus causes a wide range of clinical diseases that are difficult to treat. this microorganism is resistant not only to the classical antituberculosis agents but also to most of the antimicrobials that are currently available, resulting in limited therapeutic options and treatment failure. this scenario stresses the need to search for new drugs with activity against m. abscessus.201729205119
curcumin, an antibiotic resistance breaker against a multiresistant clinical isolate of mycobacterium abscessus.curcumin, a phenolic compound extracted from curcuma longa, exerts multiple pharmacological effects, including an antimicrobial action. mycobacterium abscessus, an environmental, nontuberculous, rapidly growing mycobacterium, is an emerging human pathogen causing serious lung infections and one of the most difficult to treat, due to its multidrug resistance and biofilm-forming ability. we wanted to evaluate the antimicrobial and antivirulence activity of curcumin and its ability to synergize wit ...201729193368
risk factors for the development of chronic pulmonary aspergillosis in patients with nontuberculous mycobacterial lung disease.nontuberculous mycobacterial lung disease (ntm-ld) is increasingly recognized as an important predisposing condition for the development of chronic pulmonary aspergillosis (cpa), but there are limited data on the risk factors for cpa development in ntm-ld patients. we reviewed the medical records of 566 patients who, at the time of diagnosis of ntm-ld, did not have cpa and who received ≥12 months of treatment for ntm-ld between january 2010 and june 2015. of these patients, 41 (7.2%) developed c ...201729190796
reporter-based assays for high-throughput drug screening against mycobacterium abscessus.mycobacterium abscessus is a non-tuberculous mycobacterium that causes pulmonary and non-pulmonary infections. m. abscessus is resistant to many chemotherapeutic agents and the current treatment options show poor clinical outcomes. thus, there is a dire need to find new antimicrobials effective at killing m. abscessus. screening drug libraries to identify potential antimicrobials has been impeded by the lack of validated hts assays for m. abscessus. in this study, we developed two 384-well high- ...201729176967
antibiotic resistance in mycobacterium abscessus and mycobacterium fortuitum isolates from malaysian patients.rapidly growing mycobacterial species (rgm) are increasingly being recognized as the cause of various superficial and deep infections in humans. two of the species most frequently isolated from clinical specimens are mycobacterium abscessus and mycobacterium fortuitum. both species are associated with antibiotic resistances that may complicate therapy. this paper describes the pattern of resistance to five antibiotics commonly prescribed for rgm infections, in m. abscessus and m. fortuitum isola ...201729171453
nucleotide-binding oligomerization domain 2 contributes to limiting growth of mycobacterium abscessus in the lung of mice by regulating cytokines and nitric oxide production.mycobacterium abscessus is a prominent cause of pulmonary infection in immunosuppressed patients and those with cystic fibrosis. nucleotide-binding oligomerization domain (nod) 2 is a cytosolic receptor which senses a bacterial peptidoglycan component, muramyl dipeptide (mdp). although nucleotide-binding oligomerization domain 2 (nod2) contributes to protect host against various microbial infections, it is still unclear whether nod2 is essential to regulate host immune responses against m. absce ...201729163541
lipoprotein glycosylation by protein-o-mannosyltransferase (mab_1122c) contributes to low cell envelope permeability and antibiotic resistance of mycobacterium abscessus.lipoproteins are important components of the mycobacterial cell envelope due to their function in cell wall homeostasis and bacterial virulence. they are post-translationally modified with lipid- and glycosyl-residues in various species and interference with acylation or glycosylation leads to reduced growth and attenuated virulence in mycobacterium tuberculosis. lipoproteins are also expressed in the emerging and highly drug resistant pathogen mycobacterium abscessus which frequently affects th ...201729163413
mycobacterium abscessus, a taxonomic puzzle. 201829139343
a temperature sensitive mycobacterium paragordonae induces enhanced protective immune responses against mycobacterial infections in the mouse model.recently, we introduced a temperature sensitive mycobacterium spp., mycobacterium paragordonae (mpg). here, we checked its potential as a candidate for live vaccination against mycobacterium tuberculosis and mycobacterium abscessus. intravenous infections of mice with mpg led to lower colony forming units (cfus) compared to infection with bcg, suggesting its usefulness as a live vaccine. the analyses of immune responses indicated that the highly protective immunity elicited by mpg was dependent ...201729123166
antibiofilm activity of nanoemulsions of cymbopogon flexuosus against rapidly growing mycobacteria.rapidly growing mycobacteria (rgm) are opportunistic microorganisms that can cause both local and disseminated infections. when in biofilm, these pathogens become highly resistant to antimicrobials used in clinical practice. composed abundantly of polymeric substances, biofilms delay the diffusion of antimicrobials, preventing the drug from penetrating the deeper layers and having an effective action. therefore, the search for new and alternative therapeutic options has become of fundamental imp ...201729122674
genomic comparisons reveal microevolutionary differences in mycobacterium abscessus subspecies.mycobacterium abscessus, a rapid-growing non-tuberculous mycobacterium, has been the cause of sporadic and outbreak infections world-wide. the subspecies in m. abscessus complex (m. abscessus, m. massiliense, and m. bolletii) are associated with different biologic and pathogenic characteristics and are known to be among the most frequently isolated opportunistic pathogens from clinical material. to date, the evolutionary forces that could have contributed to these biological and clinical differe ...201729109707
antimicrobial resistance in mycobacterium abscessus complex isolated from patients with skin and soft tissue infections at a tertiary teaching hospital in taiwan.mycobacterium abscessus complex (mabc) is the most common non-tuberculous mycobacterium that causes complicated skin and soft tissue infections (csstis). the selection of antimycobacterial agents for successful treatment of such infections is a critical issue.201729091186
lack of association between rrl and erm(41) mutations and clarithromycin resistance in mycobacterium abscessus complex.mycobacterium abscessus complex (mabc) includes species with high resistance rates among mycobacterial pathogens. in fact, mabc infections may not respond to clarithromycin treatment, which has historically been very effective against mabc infection. molecular markers have been proposed to detect both acquired (rrl polymorphisms) and inducible (erm(41) polymorphisms) clarithromycin resistance in mabc isolates.201729091138
in vitro activity between linezolid and other antimicrobial agents against mycobacterium abscessus complex.linezolid (lzd) serves as an effective option in the treatment of mycobacterium abscessus complex (mabc) infection. unfortunately, the combined activities of lzd with other antimicrobial agents against mabc have not been evaluated systemically. in this study, we randomly selected 32 mycobacterium abscessus and 32 mycobacterium massiliense isolates for the determination of in vitro synergistic effect between lzd and other antimicrobial agents, including amikacin (amk), moxifloxacin (mox), cefoxit ...201829089153
rapid detection of mutations in erm(41) and rrl associated with clarithromycin resistance in mycobacterium abscessus complex by denaturing gradient gel electrophoresis.clarithromycin resistance is increasing dramatically among mycobacterium abscessus complex. the main resistance mechanisms are mutations in the erm(41) and rrl genes. here we report pcr-based denaturing gradient gel electrophoresis (dgge) as an alternative method for rapidly detection of mutations in erm(41) and rrl among m. abscessus isolates. four primer sets targeting the full-length erm(41) gene and a 354bp fragment of the rrl gene were designed. a combination of 16 different dgge patterns w ...201729079298
in vitro evaluation of povidone-iodine and chlorhexidine against outbreak and nonoutbreak strains of mycobacterium abscessus using standard quantitative suspension and carrier testing.povidone-iodine (pi) and chlorhexidine (chx) are widely used antiseptics active against conventional staphylococcus aureus, enterobacteriaceae, candida species, and viruses, but their efficacy against mycobacterium abscessus remains unproven. we determined the in vitro potency of alcoholic pi and chx against m. abscessus subsp. abscessus (atcc 19977), m. abscessus subsp. bolletii (bcrc 16915), and our outbreak strain of m. abscessus subsp. massiliense (tpe 101) in reference to staphylococcus aur ...201829061748
molecular mechanisms of intrinsic streptomycin resistance in mycobacterium abscessus.streptomycin, the first drug used for the treatment of tuberculosis, shows limited activity against the highly resistant pathogen mycobacterium abscessus we recently identified two aminoglycoside-acetylating genes [aac(2') and eis2] which, however, do not affect susceptibility to streptomycin. this suggests the existence of a discrete mechanism of streptomycin resistance. m. abscessus blastp analysis identified mab_2385 as a close homologue of the 3″-o-phosphotransferase [aph(3″)] from the oppor ...201829061744
causative species of nontuberculous mycobacterial lung disease and comparative investigation on clinical features of mycobacterium abscessus complex disease: a retrospective analysis for two major hospitals in a subtropical region of japan.nontuberculous mycobacteria (ntm) lung disease is increasing globally. although the etiological epidemiology of ntm is different across regions, mycobacterium avium complex (mac) is the leading cause of ntm lung disease in most countries, including mainland japan. okinawa is located in the southernmost region of japan and is the only prefecture categorized as a subtropical region in japan, it is therefore likely the etiological epidemiology of ntm lung disease is different from mainland japan. f ...201729059250
survival of pathogenic mycobacterium abscessus subsp. massiliense in acanthamoeba castellanii.we used an amoeba model to study the intracellular growth and cytotoxicity of clinical strains of mycobacterium abscessus subsp. massiliense (mabsm) isolated from 2 patients (one with cystic fibrosis, the other one with idiopathic bronchiectasis) during the early (smooth colonies) and late stage (rough colonies) of chronic pulmonary infection. acanthamoeba castellanii were infected with mabsm (moi 100) and samples collected every 24 h for 72 h. results showed mabsm is able to survive in trophozo ...201829056478
clinical mycobacterium abscessus strain inhibits autophagy flux and promotes its growth in murine macrophages.autophagy is known to be a vital homeostatic defense process that controls mycobacterial infection. however, the relationship between autophagy response and the virulence of mycobacterium abscessus strain uc22 has not been reported. here, we demonstrate that m. abscessus induces autophagy and inhibits autophagy flux in murine macrophages. further, the rough variant of m. abscessus, uc22 that is a highly virulent clinical isolate, significantly inhibited autophagic flux than the smooth variant of ...201729044406
mycobacterium abscessus and massiliense lung infection during macrolide treatment for bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation.in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-sct), post-transplant lung infection is critical for their prognosis. mycobacterium abscessus complex is not fully recognized as a nontuberculous mycobacteria (ntm) pathogen of post-sct lung infection. here, we present three post-allogeneic sct patients who developed pulmonary infection caused by m. abscessus complex including m. abscessus and m. massiliense. in all three cases, macrolide antibiotics had been adminis ...201828988958
mycobacterium abscessus complex infections in children: a review.infections in children with mycobacterium abscessus complex represent a particular challenge for clinicians. increasing incidence of these infections worldwide has necessitated focused attention to improve both diagnostic as well as treatment modalities. published medical literature was reviewed, with emphasis on material published in the past 5 years.201728983867
non-tuberculous mycobacterium bacteraemia in a pregnant systemic lupus erythematosus (sle) patient: a case review and pooled case analysis.non-tuberculous mycobacteria (ntm) are recognized as an important cause of human diseases and infections. it is commonly known to cause infections of the skin, soft tissue infections, and pulmonary infection as well as bacteraemia. we report a challenging case of severe mycobacterium abscessus bacteraemia in a pregnant lady with active systemic lupus erythematous (sle). a comprehensive literature review of ntm infection among sle patients was also performed, and pooled analysis of the reported c ...201728971307
effect of β-lactamase production and β-lactam instability on mic testing results for mycobacterium abscessus.limited treatment options available for mycobacterium abscessus infections include the parenteral β-lactam antibiotics cefoxitin and imipenem, which show moderate in vitro activity. other β-lactam antibiotics (except meropenem) have no considerable in vitro activity, due to their rapid hydrolysis by a broad-spectrum β-lactamase (bla_mab). we here addressed the impact of β-lactamase production and β-lactam in vitro stability on m. abscessus mic results and determined the epidemiological cut-off ( ...201728961987
relationship between antibiotic susceptibility and genotype in mycobacterium abscessus clinical isolates.this study aimed to determine the antibiotic susceptibility and resistance related genotypes of mycobacterium abscessus. one hundred sixty-two clinical isolates were collected. genomic data were obtained by whole genome sequencing. single nucleotide polymorphism (snp) analysis was conducted using the ncbi genbank database and blast algorithm. the following genes were of interest: erm(41), rrl and rrs. erm(41) was further divided into 3 sequevars: erm(41)c28, erm(41)t28, and m type [erm(41) with ...201728959242
mycobacterium abscessus lymphadenitis in bone marrow transplant patient.non-tuberculous mycobacteria (ntm) are acid-fast bacteria categorized into rapidly growing and slow growing mycobacteria. ntm are more common in transplant patients who are immunocompromised. here we report the case of a post- bone marrow transplant adolescent male presenting with submandibular swelling and fever. the gland was excised and the histopathology showed chronic granulomatous inflammation. culture grew mycobacterium abscessus which was sensitive to amikacin, linezolid and clarithromyc ...201728955087
anti-interferon-γ autoantibody-associated disseminated mycobacterium abscessus infection mimicking parotid cancer with multiple metastases: a case report.among the nontuberculous mycobacteria, mycobacterium abscessus is a common cause of skin, soft tissue, and bone infections. however, disseminated m. abscessus infection that mimics cancer metastasis with an underlying relatively immunocompetent condition has rarely been reported.201728953638
effectiveness of an ultraviolet-c disinfection system for reduction of healthcare-associated pathogens.healthcare-associated infections caused by multidrug-resistant (mdr) pathogens are significantly associated with increased mortality and morbidity. environmental cleaning can reduce transmission of these pathogens but is often inadequate. adjunctive methods are warranted to enhance the effectiveness of disinfection particularly in hospital settings where healthcare-associated infections are of major concern.201728951015
mycobacterium abscessus glossitis. 201728948933
osteomyelitis due to multiple rare infections in a patient with idiopathic cd4 lymphocytopenia.a 26-year-old male patient presented with features suggestive of osteomyelitis involving the entire left femur, hip joint and knee joint. culture from the debrided tissue grew acinetobacter spp. and he was treated with sensitivity based antibiotics but the symptoms did not resolve. the synovial biopsy showed multinucleated giant cells and acid fast bacilli on ziehl neelsen stain. cartridge based nucleic acid amplification test (genexpert) was negative. the mycobacteria growth indicator tube cult ...201728944144
mandibular osteomyelitis and cervical lymphadenitis due to mycobacterium abscessus: surgical management of a pediatric cohort with a shared epidemiologic exposure.mycobacterium abscessus has been implicated as the cause of various infections in the setting of healthcare-related "outbreaks." mandibular osteomyelitis caused by m abscessus is exceedingly rare, with only 1 patient reported in the literature. the authors describe the surgical management of 12 pediatric patients with m abscessus-related mandibular osteomyelitis and cervical lymphadenitis caused by exposure to contaminated water at a regional dental clinic.201728938329
multi-drug resistant surgical site infection due to mycobacterium abscessus complex.m. abscessus complex is notoriously resistant to most antimicrobial agents. the complex is differentiated into 3 subspecies: m. abscessus subsp. abscessus, m. abscessus subsp. massiliense, and m. abscessus subsp. bolletii. skin and soft tissue infections due to this organism can be acquired by direct contact with contaminated material through traumatic injury, surgical wound and environmental exposure or by secondary involvement of skin/soft tissue during disseminated disease. we report a case o ...201728934511
galk-based suicide vector mediated allelic exchange in mycobacterium abscessus.mycobacterium abscessus is a fast-growing environmental organism and an important emerging pathogen. it is highly resistant to many antibiotics and undergoes a smooth to rough colony morphology change that appears to be important for pathogenesis. smooth environmental strains have a glycopeptidolipid (gpl) on the surface, while certain types of clinical strains are often rough and lack this gpl, due to mutations in biosynthetic genes or the mmpl4b transporter gene. we report here the development ...201728933689
detection of bacterial pathogens from broncho-alveolar lavage by next-generation sequencing.the applications of whole-metagenome shotgun sequencing (wmgs) in routine clinical analysis are still limited. a combination of a dna extraction procedure, sequencing, and bioinformatics tools is essential for the removal of human dna and for improving bacterial species identification in a timely manner. we tackled these issues with a broncho-alveolar lavage (bal) sample from an immunocompromised patient who had developed severe chronic pneumonia. we extracted dna from the bal sample with protoc ...201728930150
vancomycin and clarithromycin show synergy against mycobacterium abscessus in vitro.lung disease caused by mycobacterium abscessus is increasing, and current clarithromycin-based treatment regimens are only moderately effective. here, we determined the effect of clarithromycin-vancomycin combination against m. abscessus complex isolates in vitro synergy was found with a fractional inhibitory concentration index (fici) score of ≤0.5 and a 4- to 10-fold decrease in mic.201728923867
respiratory infections due to nontuberculous mycobacterias.the most common infections caused by nontuberculous mycobacteria (ntm) are lung infections. the microorganisms causing these infections most frequently are mycobacterium avium complex, mycobacterium kansasii and mycobacterium abscessus complex. their incidence has increased in the last three decades. after identifying an ntm in the respiratory tract, clinical and radiological aspects must be considered to determine if isolations are clinically relevant. predisposing conditions that could contrib ...201728923675
controlling extra- and intramacrophagic mycobacterium abscessus by targeting mycolic acid transport.mycobacterium abscessus is a rapidly growing mycobacterium (rgm) causing serious infections especially among cystic fibrosis patients. extremely limited therapeutic options against m. abscessus and a rise in infections with this mycobacterium require novel chemotherapies and a better understanding of how the bacterium causes infection. different from most rgm, m. abscessus can survive inside macrophages and persist for long durations in infected tissues. we recently delineated differences in the ...201728920054
increased survival and proliferation of the epidemic strain mycobacterium abscessus subsp. massiliense crm0019 in alveolar epithelial cells.outbreaks of infections caused by rapidly growing mycobacteria have been reported worldwide generally associated with medical procedures. mycobacterium abscessus subsp. massiliense crm0019 was obtained during an epidemic of postsurgical infections and was characterized by increased persistence in vivo. to better understand the successful survival strategies of this microorganism, we evaluated its infectivity and proliferation in macrophages (raw and bmdm) and alveolar epithelial cells (a549). fo ...201728903728
pediatric dental clinic-associated outbreak of mycobacterium abscessus infection.mycobacterium abscessus is an uncommon cause of invasive odontogenic infection.201728903524
compassionate nitric oxide adjuvant treatment of persistent mycobacterium infection in cystic fibrosis patients.mycobacterium abscessus is one of the most antibiotic-resistant pathogens in cystic fibrosis (cf) patients. nitric oxide (no) has broad-spectrum antimicrobial activity. clinical studies indicated that it is safe and tolerable when given as 160 ppm intermittent inhalations.201728885458
genomic epidemiology of a national outbreak of post-surgical mycobacterium abscessus wound infections in brazil.an epidemic of post-surgical wound infections, caused by a non-tuberculous mycobacterium, has been on-going in brazil. it has been unclear whether one or multiple lineages are responsible and whether their wide geographical distribution across brazil is due to spread from a single point source or is the result of human-mediated transmission. 188 isolates, collected from nine brazilian states, were whole genome sequenced and analysed using phylogenetic and comparative genomic approaches. the isol ...201728884021
nontuberculous mycobacteria in cystic fibrosis: updates and the path forward.nontuberculous mycobacteria (ntm) are troublesome pathogens that can cause significant pulmonary disease in patients with cystic fibrosis (cf). diagnosis can be difficult in the setting of underlying cf and treatment regimens are burdensome on both patients and providers. recent consensus guidelines for treatment of ntm in cf have provided a guide for the cf community, however research is lagging regarding accuracy of our diagnostic abilities and treatment efficacy. in this review, we provide ne ...201728881094
antagonism between front-line antibiotics clarithromycin and amikacin in the treatment of mycobacterium abscessus infections is mediated by the whib7 gene.combinations of antibiotics, each individually effective against mycobacterium abscessus, are routinely coadministered based on the concept that this minimizes the spread of antibiotic resistance. however, our in vitro data contradict this assumption and instead document antagonistic interactions between two antibiotics (clarithromycin and amikacin) used to treat m. abscessus infections. clinically relevant concentrations of clarithromycin induced increased resistance to both amikacin and itself ...201728874379
mycobacterium abscessus whib7 regulates a species-specific repertoire of genes to confer extreme antibiotic resistance.mycobacterium abscessus causes acute and chronic bronchopulmonary infection in patients with chronic lung damage, of which cystic fibrosis (cf) patients are particularly vulnerable. the major threat posed by this organism is its high intrinsic antibiotic resistance. a typical treatment regimen involves a 6- to 12-month-long combination therapy of clarithromycin and amikacin, with cure rates below 50% and multiple side effects, especially due to amikacin. in the present work, we show that m. absc ...201728874378
predominance of clarithromycin-susceptible mycobacterium massiliense subspecies: characterization of the mycobacterium abscessus complex at a tertiary acute care hospital.to characterize members of the mycobacterium abscessus complex, with an emphasis on the correlation between species identification and clarithromycin associated genetic polymorphisms that contribute to inducible and constitutive macrolide resistance. pcr and sequencing analysis was used to elucidate the subspecies, erm(41) genotypes and the presence of rrl mutations. m. abscessus subsp. massiliense was the dominant subspecies (70.2 %), followed by m. abscessus subsp. abscessus (23.8 %) and m. ab ...201728874233
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