Database : MEDLINE
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[PMID]: 29458544
[Au] Autor:Aguilar-Ayala DA; Cnockaert M; Vandamme P; Palomino JC; Martin A; Gonzalez-Y-Merchand J
[Ad] Address:2​Laboratory of Microbiology, Department of Biochemistry and Microbiology, Ghent University, Ghent 9000, Belgium.
[Ti] Title:Antimicrobial activity against Mycobacterium tuberculosis under in vitro lipid-rich dormancy conditions.
[So] Source:J Med Microbiol;67(3):282-285, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Although tuberculosis treatment is dependent on drug-susceptibility testing (DST) and molecular drug-resistance detection, treatment failure and relapse remain a challenge. This could be partially due to the emergence of antibiotic-tolerant dormant mycobacteria, where host lipids have been shown to play an important role. This study evaluated the susceptibility of Mycobacterium tuberculosis to two antibiotic combinations - rifampicin, moxifloxacin, amikacin and metronidazole (RIF-MXF-AMK-MTZ), and rifampicin, moxifloxacin, amikacin and pretomanid (RIF-MXF-AMK-PA) - in a lipid-rich dormancy model. Although their effectiveness in in vitro cultures with dextrose as a carbon source has been proved, we observed that none of the antibiotic mixtures were bactericidal in the presence of lipids. The presence of lipids may confer tolerance to M. tuberculosis against the mixture of antibiotics tested and such tolerance could be even higher during the dormant stages. The implementation of lipids in DST on clinical isolates could potentially lead to a better treatment strategy.
[Mh] MeSH terms primary: Anti-Bacterial Agents/pharmacology
Lipids/pharmacology
Mycobacterium tuberculosis/drug effects
Mycobacterium tuberculosis/physiology
[Mh] MeSH terms secundary: Amikacin/pharmacology
Antitubercular Agents/pharmacology
Drug Tolerance
Fluoroquinolones/pharmacology
Genetic Fitness
Genotype
Humans
Lipid Metabolism
Microbial Sensitivity Tests
Models, Biological
Mycobacterium Infections, Nontuberculous/microbiology
Mycobacterium tuberculosis/genetics
Mycobacterium tuberculosis/growth & development
Nitroimidazoles/pharmacology
Rifampin/pharmacology
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (2-nitro-6-(4-(trifluoromethoxy)benzyloxy)-6,7-dihydro-5H-imidazo(2,1-b)(1,3)oxazine); 0 (Anti-Bacterial Agents); 0 (Antitubercular Agents); 0 (Fluoroquinolones); 0 (Lipids); 0 (Nitroimidazoles); 84319SGC3C (Amikacin); U188XYD42P (moxifloxacin); VJT6J7R4TR (Rifampin)
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[Js] Journal subset:IM
[Da] Date of entry for processing:180221
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000681

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[PMID]: 29516887
[Au] Autor:Tortone CA; Zumárraga MJ; Gioffr AK; Oriani DS
[Ad] Address:Laboratory of Mycobacteria, Faculty of Veterinary Sciences, National University of La Pampa, General Pico, La Pampa, Argentina.
[Ti] Title:Utilization of molecular and conventional methods for the identification of nontuberculous mycobacteria isolated from different water sources.
[So] Source:Int J Mycobacteriol;7(1):53-60, 2018 Jan-Mar.
[Is] ISSN:2212-554X
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Background: The environment is the nontuberculous mycobacteria (NTM) reservoir, opportunistic pathogens of great diversity and ubiquity, which is observed in the constant description of new species capable of causing infection. Since its introduction, molecular methods are essential for species identification. Most comparative studies between molecular and conventional methods, have used isolated strains from clinical samples. Methods: The aim of this study was to evaluate the usefulness of molecular methods, especially the hsp65-PRA (PCR-Restriction Enzyme Analysis), and biochemical tests in the identification of NTM recovered from water of different origins, using the sequencing of 16S rRNA and hsp 65 genes as assessment methods of the previous ones. Species identification was performed for all 56 NTM isolates what were recovered from 32 (42.1%) positive water samples, using conventional phenotypic methods, hsp65-PRA, partial sequencing of 16S rRNA and sequencing of hsp 65 genes. Results: Phenotypic evaluation and hsp65-PRA were concordant with 23 (41.1%) isolates. Also, the PRA was concordant with 16 (28.6%) and 27 (48.2%) isolates, with the partial sequencing of 16S rRNA and sequencing of hsp 65 genes, respectively. It is considered that the 19.6% (n = 11) could not be identified. Conclusion: Identification of NTM environmental isolates to the species level, especially when they are pigmented and fast-growing, both the analysis of the restriction patterns obtained by PRA and the sequencing of the 16S rRNA and hsp 65 genes are insufficient by themselves. Although they are demanding and time-consuming, biochemical tests are very useful to support data obtained by molecular methods.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:In-Data-Review
[do] DOI:10.4103/ijmy.ijmy_192_17

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[PMID]: 29516885
[Au] Autor:Caskey S; Moore JE; Rendall JC
[Ad] Address:Regional Adult Cystic Fibrosis Centre, Belfast City Hospital, Northern Ireland, UK.
[Ti] Title: activity of seven hospital biocides against : Implications for patients with cystic fibrosis.
[So] Source:Int J Mycobacteriol;7(1):45-47, 2018 Jan-Mar.
[Is] ISSN:2212-554X
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Background: Mycobacterium abscessus pulmonary infection has recently emerged as a significant pathogen in patients with cystic fibrosis (CF) and is associated with significant morbidity and accelerated pulmonary decline. There is a paucity of data describing the activity of hospital biocides against this organism. Methods: M. abscessus isolates (n = 13) were recovered from CF and non-CF respiratory specimens. Seven commonly employed hospital biocides with generic ingredients as follows: acetone, propan-2-ol, diethylene glycol, 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one, chlorine dioxide, 4% chlorhexidine, alcohol, and disodium carbonate, compound with hydrogen peroxide, 10% sodium hypochlorite were assayed for their biocidal activity against M. abscessus. Fresh cultures of M. abscessus were exposed to biocide in liquid medium as per manufacturers' instruction and were immediately plated following the completion of the contact period. The mean concentration of M. abscessus plated was 9.82 × 10 colony-forming units (range: 1.63 × 10 -1.12 × 10 ). In addition, the remaining bacteria/biocide solution was enriched nonselectively in Mueller Hinton broth (37°C/1 week) and then plated. Results: All M. abscessus isolates survived in alkyl dimethyl benzyl ammonium chloride, 5-chloro-2-methyl-2H-isothiazol-3-one (EC No. 247-500-7) and 2-methyl-2H-isothiazol-3-one, 4% Chlorhexidine™, O-phenylphenol and Sodium Lauryl Sulfate™ and disodium carbonate, compound with hydrogen peroxide. One out of 13 M. abscessus cultures was killed by Chlorine Dioxide™ and one by Sodium Dichloroisocyanurate™, representing a 5-log kill. Two isolates were killed by Alcohol™ again representing a 5 log kill. Following enrichment, O-phenylphenol and Sodium Lauryl Sulfate™ showed the greatest biocidal activity with 11/13 isolates, whereas 2/13 cultures were killed by sodium dichloroisocyanurate™. All other biocide/culture combinations yielded growth. Conclusion: These data indicate that M. abscessus may persist after exposure to several common hospital biocides. Further work is urgently needed to define unequivocal biocide contact treatments to prevent cross-infection with this mycobacterial species in this patient population and thus ensure effective infection control and prevention.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:In-Data-Review
[do] DOI:10.4103/ijmy.ijmy_197_17

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[PMID]: 29214755
[Au] Autor:Kim CK; Cho EA; Shin DM; Choi SW; Shin SY
[Ad] Address:Department of Laboratory Medicine, Hanyang University Guri Hospital, Guri, Korea. psoas95@gmail.com.
[Ti] Title:Comparative Evaluation of the Loop-Mediated Isothermal Amplification Assay for Detecting Pulmonary Tuberculosis.
[So] Source:Ann Lab Med;38(2):119-124, 2018 Mar.
[Is] ISSN:2234-3814
[Cp] Country of publication:Korea (South)
[La] Language:eng
[Ab] Abstract:BACKGROUND: Early detection of tuberculosis (TB) is challenging in resource-poor settings because of limited accessibility to molecular diagnostics. The aim of this study was to evaluate the performance of the loop-mediated isothermal amplification kit (TB-LAMP) for TB diagnosis compared with conventional and molecular tests. METHODS: A total of 290 consecutive sputum samples were collected from May till September, 2015. All samples were processed using the N-Acetyl-L-cysteine (NALC) NaOH method and tested by smear microscopy, solid and liquid culture, real-time PCR, and TB-LAMP. RESULTS: The sensitivity of TB-LAMP for smear-positive and smear-negative samples with culture positivity was 92.0% and 58.8%, respectively. TB-LAMP was positive in 14.9% of TB culture-negative samples; however, all those samples were also positive by real-time PCR. In addition, none of the samples positive for nontuberculous mycobacteria by culture were positive by TB-LAMP. The overall agreement between TB-LAMP and real-time PCR was good; however, the concordance rate was significantly lower for real-time PCR positive samples with Ct values of 30-35. CONCLUSIONS: TB-LAMP could replace smear microscopy and increase TB diagnostic capacity when Xpert MTB/RIF is not feasible because of poor infrastructure.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:In-Process
[do] DOI:10.3343/alm.2018.38.2.119

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[PMID]: 29506377
[Au] Autor:Giordani B; Amato A; Majo F; Ferrari G; Quattrucci S; Minicucci L; Padoan R; Floridia G; Puppo Fornaro G; Taruscio D; Salvatore M; Gruppo di lavoro RIFC
[Ad] Address:Lega italiana fibrosi cistica ONLUS, Roma.
[Ti] Title:Registro italiano Fibrosi Cistica. Rapporto 2011-2014. [Italian Cystic Fibrosis Registry. Report 2011-2014].
[So] Source:Epidemiol Prev;42(1S1):1-32, 2018 Jan-Feb.
[Is] ISSN:1120-9763
[Cp] Country of publication:Italy
[La] Language:ita
[Ab] Abstract:INTRODUCTION: The Italian Cystic Fibrosis Registry (ICFR) is based on a new agreement about the data flow towards the Registry signed on October, 4th 2016 by the Centre for Rare Diseases of the Italian National Institute of Health (NIH), the clinicians of the Italian National Referral and Support Centres for Cystic Fibrosis, the Paediatric Hospital "Bambino Gesù" (Rome), the Italian Cystic Fibrosis Society, and the Italian League for Cystic Fibrosis. OBJECTIVES: The aim of the present Report is to improve the knowledge on cystic fibrosis (CF) through the epidemiological description of Italian patients. The members of the Scientific and Technical Committee have to write a report on data collected by ICFR, in order to contribute to achieve the aims of ICFR itself, i.e., to improve the care of CF patients. In particular, the Report should contribute to the following objectives: - to analyze the medium and long-term clinical and epidemiological trends of the disease; - to identify the main healthcare needs at regional and national level in order to contribute to the healthcare programmes and to the distribution of resources; - to compare Italian data with the international ones. DESIGN: Analyses and results described in the present Report are referred to patients in charge to the Italian National Referral and Support Centres for Cystic Fibrosis in the period 2011-2014. Data were sent by Centres by means of a specific software (Camilla, Ibis Informatica) and has undergone a double quality control (QC): the first by NIH and the second at a European level (before the inclusion of the Italian data within the European Cystic Fibrosis Registry). These QCs assure the completeness and accuracy of data as well as their consistency with European core data. SETTING AND PARTICIPANTS: A total of 29 different CF centres (referral, support, and Paediatric Hospital "Bambino Gesù") sent their data to ICFR; data referred to the period 2011-2014. Data regarding Sardinia Region (Southern Italy) are missing; data from Molise (Southern Italy) CF centre refer only to 2014. RESULTS: The present Report has been organized into 10 sections. 1. Demography - number of Italian patients with cystic fibrosis (CF) in 2014 was 4,981 and their median age was 20.4 years; estimated 2014 CF prevalence was 8.2/100,000 residents in Italy; on average, 52.1% of the patients were male and CF distribution showed higher frequency in patients aged from 7 to 35 years. On average, 53.7% of CF patients are aged more than 18 years. 2. Diagnoses - most of the CF patients were diagnosed before two years of age (around 66%); a significant proportion of patients (on average, 12%) was diagnosed in adult age. 3. New diagnoses - new diagnoses were 187 in 2011, 200 in 2012, 160 in 2013, and 135 in 2014. Estimated incidence was 1/4,052 live births in 2011; 1/4,313 in 2012; 1/5,189 in 2013 and 1/8,243 in 2014. 4. Genetics - 99.5% of patients was studied at the molecular level, with identification of 90.1% of Cystic Fibrosis Transmembrane Regulator CFTR mutations; [delta]508F was the most frequent mutation (44.8% in 2014). 5. Lung function - FEV1 (Forced Expiratory Volume in the first second) scores progressively decreased shortly before the start of adult age, in accordance with the natural history of the disease. Most of the patients between 6 and 17 years of age reported a FEV1 % ≥ 70% of the predicted value, while the proportion of patients with severe lung disease (FEV1 % <40% of the predicted value) is <2% over the period 2011-2014. 6. Nutrition - most critical periods come out during the first 6 months of life and during adolescence. Prevalence of malnourished male aged 12-17 years decreases over the period 2011-2014; an increasing percentage of patient (both male and female) with a suboptimal body mass index value is observed among patients aged more than 18 years 7. Complications - the presence of missing data represents an obstacle in the correct evaluation of prevalence value of complications related to Italian patients within ICFR. Nevertheless, it was estimated that, in 2014, the principal complication in patients aged <18 years was hepatopathies (15%), while in patients aged more than 18 years the principal complications were due to hepatopathies (25%) and diabetes (22%). 8. Transplantation - during the period 2011-2014, 135 patients ageed between 7 and 53 years received a double lung transplant; median age at transplantation was 32.5 years. Median duration of waiting list for transplantation is estimated in 11 months. 9. Microbiology - analyses were referred to test performed in 2014. Prevalence of adult patients with Pseudomonas aeruginosa chronic infection is 49.4% compared to 14.5% of paediatric patients; Staphylococcus aureus chronic infection is present in 48% of adult patients and 45.6% of paediatric patients; Burkholderia Cepacia complex is present almost exclusively in adult patients (4.9%); Nontuberculous mycobacteria is present in 0.9% and 0.3% of adult and paediatric patients, respectively; Stenotrophomonas maltophilia infection is present in 4.6% of patients (both adults and paediatric). 10. Mortality - RIFC data show that 176 patients (median age 32 years; 81 males and 95 females) died in the period 2011-2014. CONCLUSIONS: The present Report shows that CF population is growing (median age), so paediatric mortality is decreasing. A very low percentage of paediatric population is characterized by complication of pulmonary functions; adult patients are characterized by an increase of age at death (more than 30 years of age). ICFR Report may represent an important tool to analyze clinical and epidemiological trends of the disease as well as to identify the main healthcare needs at regional and national level to contribute to the healthcare programmes and to the distribution of the resources.
[Pt] Publication type:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:In-Process
[do] DOI:10.19191/EP18.1-S1.P001.001

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[PMID]: 29440575
[Au] Autor:Haig SJ; Kotlarz N; LiPuma JJ; Raskin L
[Ad] Address:Department of Civil & Environmental Engineering, University of Michigan, Ann Arbor, Michigan, USA.
[Ti] Title:A High-Throughput Approach for Identification of Nontuberculous Mycobacteria in Drinking Water Reveals Relationship between Water Age and .
[So] Source:MBio;9(1), 2018 Feb 13.
[Is] ISSN:2150-7511
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Nontuberculous mycobacteria (NTM) frequently detected in drinking water (DW) include species associated with human infections, as well as species rarely linked to disease. Methods for improved the recovery of NTM DNA and high-throughput identification of NTM are needed for risk assessment of NTM infection through DW exposure. In this study, different methods of recovering bacterial DNA from DW were compared, revealing that a phenol-chloroform DNA extraction method yielded two to four times as much total DNA and eight times as much NTM DNA as two commercial DNA extraction kits. This method, combined with high-throughput, single-molecule real-time sequencing of NTM genes, allowed the identification of NTM to the species, subspecies, and (in some cases) strain levels. This approach was applied to DW samples collected from 15 households serviced by a chloraminated distribution system, with homes located in areas representing short (<24 h) and long (>24 h) distribution system residence times. Multivariate statistical analysis revealed that greater water age (i.e., combined distribution system residence time and home plumbing stagnation time) was associated with a greater relative abundance of subsp. , one of the most prevalent NTM causing infections in humans. DW from homes closer to the treatment plant (with a shorter water age) contained more diverse NTM species, including and Overall, our approach allows NTM identification to the species and subspecies levels and can be used in future studies to assess the risk of waterborne infection by providing insight into the similarity between environmental and infection-associated NTM. An extraction method for improved recovery of DNA from nontuberculous mycobacteria (NTM), combined with single-molecule real-time sequencing (PacBio) of NTM genes, was used for high-throughput characterization of NTM species and in some cases strains in drinking water (DW). The extraction procedure recovered, on average, eight times as much NTM DNA and three times as much total DNA from DW as two widely used commercial DNA extraction kits. The combined DNA extraction and sequencing approach allowed high-throughput screening of DW samples to identify NTM, revealing that the relative abundance of subsp. increased with water age. Furthermore, the two-step barcoding approach developed as part of the PacBio sequencing method makes this procedure highly adaptable, allowing it to be used for other target genes and species.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:In-Data-Review

  7 / 5330 MEDLINE  
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[PMID]: 29197331
[Au] Autor:Addo KK; Addo SO; Mensah GI; Mosi L; Bonsu FA
[Ad] Address:Department of Bacteriology, Noguchi Memorial Institute for Medical Research, University of Ghana, P.O. Box LG 581, Legon, Ghana. kaddo@noguchi.ug.edu.gh.
[Ti] Title:Genotyping and drug susceptibility testing of mycobacterial isolates from population-based tuberculosis prevalence survey in Ghana.
[So] Source:BMC Infect Dis;17(1):743, 2017 12 02.
[Is] ISSN:1471-2334
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Mycobacterium tuberculosis complex (MTBC) and Non-tuberculosis Mycobacterium (NTM) infections differ clinically, making rapid identification and drug susceptibility testing (DST) very critical for infection control and drug therapy. This study aims to use World Health Organization (WHO) approved line probe assay (LPA) to differentiate mycobacterial isolates obtained from tuberculosis (TB) prevalence survey in Ghana and to determine their drug resistance patterns. METHODS: A retrospective study was conducted whereby a total of 361 mycobacterial isolates were differentiated and their drug resistance patterns determined using GenoType Mycobacterium Assays: MTBC and CM/AS for differentiating MTBC and NTM as well MTBDRplus and NTM-DR for DST of MTBC and NTM respectively. RESULTS: Out of 361 isolates, 165 (45.7%) MTBC and 120 (33.2%) NTM (made up of 14 different species) were identified to the species levels whiles 76 (21.1%) could not be completely identified. The MTBC comprised 161 (97.6%) Mycobacterium tuberculosis and 4 (2.4%) Mycobacterium africanum. Isoniazid and rifampicin monoresistant MTBC isolates were 18/165 (10.9%) and 2/165(1.2%) respectively whiles 11/165 (6.7%) were resistant to both drugs. Majority 42/120 (35%) of NTM were M. fortuitum. DST of 28 M. avium complex and 8 M. abscessus complex species revealed that all were susceptible to macrolides (clarithromycin, azithromycin) and aminoglycosides (kanamycin, amikacin, and gentamicin). CONCLUSION: Our research signifies an important contribution to TB control in terms of knowledge of the types of mycobacterium species circulating and their drug resistance patterns in Ghana.
[Mh] MeSH terms primary: Mycobacterium tuberculosis/drug effects
Mycobacterium tuberculosis/genetics
Nontuberculous Mycobacteria/genetics
Tuberculosis/microbiology
[Mh] MeSH terms secundary: Adolescent
Adult
Aged
Clarithromycin/pharmacology
Drug Resistance, Bacterial/drug effects
Female
Genotype
Ghana
Humans
Isoniazid/pharmacology
Male
Microbial Sensitivity Tests
Middle Aged
Mycobacterium Infections, Nontuberculous/microbiology
Mycobacterium tuberculosis/isolation & purification
Nontuberculous Mycobacteria/drug effects
Nontuberculous Mycobacteria/isolation & purification
Prevalence
Retrospective Studies
Rifampin/pharmacology
Surveys and Questionnaires
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:H1250JIK0A (Clarithromycin); V83O1VOZ8L (Isoniazid); VJT6J7R4TR (Rifampin)
[Em] Entry month:1803
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[Js] Journal subset:IM
[Da] Date of entry for processing:171204
[St] Status:MEDLINE
[do] DOI:10.1186/s12879-017-2853-3

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[PMID]: 29503226
[Au] Autor:Yokoyama A; Kage H; Ohama Y; Sato T; Miyashita N; Noguchi S; Okugawa S; Yamauchi Y; Moriya K; Nagase T
[Ad] Address:Department of Respiratory Medicine, The University of Tokyo, Japan.
[Ti] Title:Mycobacterium heckeshornense lung infection diagnosed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).
[So] Source:J Infect Chemother;, 2018 Mar 01.
[Is] ISSN:1437-7780
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Identification of microorganisms by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been widely accepted. However, the significance of MALDI-TOF MS for identifying mycobacteria, particularly rare nontuberculous mycobacteria, has not been established. M. heckeshornense is one such bacteria, and distinguishing it from M. xenopi is difficult. The patient was a 40-year-old man with BehÒ«et's disease who had started treatment with prednisolone and azathioprine. A lung nodule in the right lower lobe was pointed out, and it increased in size 6 months later. Bronchoscopy was performed, and was culture positive for mycobacteria. It was identified as M. heckeshornense by MALDI-TOF MS with a score value of 1.928. Analysis of the 16S rRNA, rpoB, and hsp65 genes confirmed the result of MALDI-TOF MS. MALDI-TOF MS seems reliable for the diagnosis of M. heckeshornense infection.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:Publisher

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[PMID]: 29421865
[Au] Autor:Choi SR; Britigan BE; Switzer B; Hoke T; Moran D; Narayanasamy P
[Ad] Address:Department of Pathology and Microbiology, College of Medicine , University of Nebraska Medical Center , Omaha , Nebraska 68198 , United States.
[Ti] Title:In Vitro Efficacy of Free and Nanoparticle Formulations of Gallium(III) meso-Tetraphenylporphyrine against Mycobacterium avium and Mycobacterium abscessus and Gallium Biodistribution in Mice.
[So] Source:Mol Pharm;15(3):1215-1225, 2018 Mar 05.
[Is] ISSN:1543-8392
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The nontuberculous mycobacterial (NTM) pathogens, M. avium complex (MAC) and M. abscessus, can result in severe pulmonary infections. Current antibiotics confront significant challenges for treatment of these NTM infections due to emerging multidrug-resistance. Thus, development of new antibiotics targeted against these agents is needed. We examined the inhibitory activities of Ga(NO ) , GaCl , gallium meso-tetraphenylporphyrine (GaTP), and gallium nanoparticles (GaNP) against intra- and extracellular M. avium and M. abscessus. GaTP, an analogue of natural heme, inhibited growth of both M. avium and M. abscessus with MICs in Fe-free 7H9 media of 0.5 and 2 µg/mL, respectively. GaTP was more active than Ga(NO ) and GaCl . Ga(NO ) and GaCl were not as active in Fe-rich media compared to Fe-free media. However, GaTP was much less impacted by exogenous Fe, with MICs against M. avium and M. abscessus of 2 and 4 µg/mL, respectively, in 7H9 OADC media (Fe rich). Confocal microscopy showed that GaNP penetrates the M. avium cell wall. As assessed by determining colony forming units, GaNP inhibited the growth of NTM growing in THP-1 macrophages up to 15 days after drug-loading of the cells, confirming a prolonged growth inhibitory activity of the GaNP. Biodistribution studies of GaNP conducted in mice showed that intraperitoneal injection is more effective than intramuscular injection in delivering Ga(III) into lung tissue. GaTP exhibits potential as a lead compound for development of anti-NTM agents that target heme-bound iron uptake mechanisms by mycobacteria and inhibit growth by disrupting mycobacterial iron acquisition/utilization.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:In-Data-Review
[do] DOI:10.1021/acs.molpharmaceut.7b01036

  10 / 5330 MEDLINE  
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[PMID]: 28461147
[Au] Autor:Diel R; Ringshausen F; Richter E; Welker L; Schmitz J; Nienhaus A
[Ad] Address:Institute for Epidemiology, University Medical Hospital Schleswig-Holstein, Kiel. Member of the German Center for Lung Research (ARCN); Airway Research Center North (ARCN), German Center for Lung Research (DZL) LungClinic Grosshansdorf. Electronic address: roland.diel@epi.uni-kiel.de.
[Ti] Title:Microbiological and Clinical Outcomes of Treating Non-Mycobacterium Avium Complex Nontuberculous Mycobacterial Pulmonary Disease: A Systematic Review and Meta-Analysis.
[So] Source:Chest;152(1):120-142, 2017 07.
[Is] ISSN:1931-3543
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Pulmonary disease caused by nontuberculous mycobacteria (NTM) is steadily increasing worldwide. METHODS: A systematic review of non-Mycobacterium avium complex studies published prior to October 2016 was conducted with respect to microbiological and clinical outcomes of current treatment regimens. RESULTS: We retrieved 352 citations, which yielded 24 studies eligible for evaluation. Sixteen studies were retrospective chart reviews, three studies were prospective, and only five studies were randomized. The weighted average proportion of sputum culture conversion (SCC) after subtracting posttreatment relapses for patients with M abscessus was 41.2% (95% CI, 28.6%-54.5%) but was 69.8% (95% CI, 41.0%-91.9%) with subspecies M massiliense in macrolide-containing regimens, 80.2% (95% CI, 58.4%-95.2%) in patients with M kansasii, 32.0% (95% CI, 16.5%-49.8%) for M xenopi (MX) and 54.4% (95% CI, 34.7%-73.4%) for M malmoense. SCCs in the total of 55 patients who underwent lung resection and had MX or M abscessus was high at 75.9%. The risk of bias was low in four of five randomized studies. However, heterogeneous use of outcome parameters (eight definitions of "relapse," eight of "treatment success," and four of "cure") hampered comparison of nonrandomized studies as well as producing possible bias by a posteriori exclusion (13.3%) and uncompleted treatment of participants (25.3%). CONCLUSIONS: As a sustained microbiological response without surgery is unsatisfactory in treating M abscessus, MX, and M malmoense, functional and quality of life aspects should be given more emphasis in the individual evaluation of treatment outcome. Further, properly planned studies with sufficient power are needed, as are new drugs or better-tolerated application of current antibiotics, or both.
[Mh] MeSH terms primary: Lung Diseases
Mycobacterium Infections, Nontuberculous
Mycobacterium avium Complex
Nontuberculous Mycobacteria
[Mh] MeSH terms secundary: Clinical Trials as Topic
Disease Management
Humans
Lung Diseases/diagnosis
Lung Diseases/microbiology
Lung Diseases/therapy
Microbiological Techniques/methods
Mycobacterium Infections, Nontuberculous/diagnosis
Mycobacterium Infections, Nontuberculous/microbiology
Mycobacterium Infections, Nontuberculous/therapy
Mycobacterium avium Complex/drug effects
Mycobacterium avium Complex/isolation & purification
Mycobacterium avium Complex/pathogenicity
Nontuberculous Mycobacteria/drug effects
Nontuberculous Mycobacteria/isolation & purification
Nontuberculous Mycobacteria/pathogenicity
Outcome and Process Assessment (Health Care)
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1708
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:170503
[St] Status:MEDLINE


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