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2.
Folia Med (Plovdiv) ; 66(2): 282-286, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38690826

RESUMO

The diagnosis of intrathoracic non-tuberculous mycobacteriosis (NTM) is challenging. We report a case of a pediatric pulmonary NTM with endobronchial lesion and lymphadenitis in a child with HIV infection diagnosed by bronchoscopic biopsy, EBUS-TBNA and probe-based confocal laser endomicroscopy (pCLE). The pCLE showed a large number of highly fluorescent cells and zones of density and disorganized elastin fibers at alveolar areas. A combination of diagnostic endoscopic procedures is required to establish the diagnosis of NTM.


Assuntos
Broncoscopia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Infecções por HIV , Microscopia Confocal , Infecções por Mycobacterium não Tuberculosas , Humanos , Broncoscopia/métodos , Criança , Microscopia Confocal/métodos , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/patologia , Masculino , Infecções por HIV/complicações , Infecções por HIV/patologia , Biópsia/métodos
3.
MMWR Morb Mortal Wkly Rep ; 73(18): 420-422, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722805

RESUMO

Mycobacterium abscessus is an intrinsically drug-resistant, rapidly growing, nontuberculous mycobacterium; extrapulmonary infections have been reported in association with medical tourism (1). During November-December 2022, two Colorado hospitals (hospitals A and B) treated patient A, a Colorado woman aged 30-39 years, for M. abscessus meningitis. In October 2022, she had received intrathecal donor embryonic stem cell injections in Baja California, Mexico to treat multiple sclerosis and subsequently experienced headaches and fevers, consistent with meningitis. Her cerebrospinal fluid revealed neutrophilic pleocytosis and grew M. abscessus in culture at hospital A. Hospital A's physicians consulted hospital B's infectious diseases (ID) physicians to co-manage this patient (2).


Assuntos
Surtos de Doenças , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Humanos , Colorado/epidemiologia , Adulto , Feminino , México/epidemiologia , Mycobacterium abscessus/isolamento & purificação , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Arizona/epidemiologia , Transplante de Células-Tronco
4.
Sci Rep ; 14(1): 11187, 2024 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755267

RESUMO

Mycobacteroides (Mycobacterium) abscessus, which causes a variety of infectious diseases in humans, is becoming detected more frequently in clinical specimens as cases are spreading worldwide. Taxonomically, M. abscessus is composed of three subspecies of M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp. massiliense, with different susceptibilities to macrolides. In order to identify rapidly these three subspecies, we determined useful biomarker proteins, including ribosomal protein L29, L30, and hemophore-related protein, for distinguishing the subspecies of M. abscessus using the matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) profiles. Thirty-three clinical strains of M. abscessus were correctly identified at the subspecies-level by the three biomarker protein peaks. This study ultimately demonstrates the potential of routine MALDI-MS-based laboratory methods for early identification and treatment for M. abscessus infections.


Assuntos
Proteínas de Bactérias , Mycobacterium abscessus , Proteínas Ribossômicas , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Proteínas Ribossômicas/metabolismo , Proteínas Ribossômicas/análise , Mycobacterium abscessus/metabolismo , Proteínas de Bactérias/metabolismo , Humanos , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Biomarcadores/análise , Biomarcadores/metabolismo
5.
Life Sci Alliance ; 7(7)2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38744470

RESUMO

Developing effective tuberculosis drugs is hindered by mycobacteria's intrinsic antibiotic resistance because of their impermeable cell envelope. Using benzothiazole compounds, we aimed to increase mycobacterial cell envelope permeability and weaken the defenses of Mycobacterium marinum, serving as a model for Mycobacterium tuberculosis Initial hit, BT-08, significantly boosted ethidium bromide uptake, indicating enhanced membrane permeability. It also demonstrated efficacy in the M. marinum-zebrafish embryo infection model and M. tuberculosis-infected macrophages. Notably, BT-08 synergized with established antibiotics, including vancomycin and rifampicin. Subsequent medicinal chemistry optimization led to BT-37, a non-toxic and more potent derivative, also enhancing ethidium bromide uptake and maintaining synergy with rifampicin in infected zebrafish embryos. Mutants of M. marinum resistant to BT-37 revealed that MMAR_0407 (Rv0164) is the molecular target and that this target plays a role in the observed synergy and permeability. This study introduces novel compounds targeting a new mycobacterial vulnerability and highlights their cooperative and synergistic interactions with existing antibiotics.


Assuntos
Benzotiazóis , Sinergismo Farmacológico , Mycobacterium marinum , Peixe-Zebra , Animais , Benzotiazóis/farmacologia , Mycobacterium marinum/efeitos dos fármacos , Antituberculosos/farmacologia , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Humanos , Antibacterianos/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/microbiologia , Macrófagos/metabolismo , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Rifampina/farmacologia
6.
PLoS One ; 19(5): e0303516, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38728330

RESUMO

Increasingly prevalent, nontuberculous mycobacteria (NTM) infections affect approximately 20% of people with cystic fibrosis (CF). Previous studies of CF sputum identified lower levels of the host metabolite itaconate in those infected with NTM. Itaconate can inhibit the growth of M. tuberculosis (MTB) in vitro via the inhibition of the glyoxylate cycle enzyme (ICL), but its impact on NTM is unclear. To test itaconic acid's (IA) effect on NTM growth, laboratory and CF clinical strains of Mycobacterium abscessus and Mycobacterium avium were cultured in 7H9 minimal media supplemented with 1-10 mM of IA and short-chain fatty acids (SCFA). M. avium and M. abscessus grew when supplemented with SCFAs, whereas the addition of IA (≥ 10 mM) completely inhibited NTM growth. NTM supplemented with acetate or propionate and 5 mM IA displayed slower growth than NTM cultured with SCFA and ≤ 1 mM of IA. However, IA's inhibition of NTM was pH dependent; as similar and higher quantities (100 mM) of pH adjusted IA (pH 7) did not inhibit growth in vitro, while in an acidic minimal media (pH 6.1), 1 to 5 mM of non-pH adjusted IA inhibited growth. None of the examined isolates displayed the ability to utilize IA as a carbon source, and IA added to M. abscessus isocitrate lyase (ICL) decreased enzymatic activity. Lastly, the addition of cell-permeable 4-octyl itaconate (4-OI) to THP-1 cells enhanced NTM clearance, demonstrating a potential role for IA/itaconate in host defense against NTM infections.


Assuntos
Succinatos , Succinatos/farmacologia , Succinatos/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Micobactérias não Tuberculosas/efeitos dos fármacos , Micobactérias não Tuberculosas/crescimento & desenvolvimento , Células THP-1 , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium avium/efeitos dos fármacos , Mycobacterium avium/crescimento & desenvolvimento , Mycobacterium abscessus/efeitos dos fármacos , Mycobacterium abscessus/crescimento & desenvolvimento , Mycobacterium abscessus/metabolismo
7.
J Investig Med High Impact Case Rep ; 12: 23247096241253343, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38767131

RESUMO

The association between Hairy Cell Leukemia (HCL) and non-tuberculous mycobacterial infections (NTMs) is well described, most notably Mycobacterium kansasii. The exact pathophysiology is not known. We report a case of a 31-year-old male with concomitantly diagnosed HCL and disseminated M kansasii infection who presented with rash, pancytopenia, and bulky axillary lymphadenopathy. The M kansasii was initially diagnosed through use of cell-free DNA detection and confirmed by bone marrow and lymph node cultures. Hairy Cell Leukemia was diagnosed with peripheral flow cytometry and confirmed via the same bone marrow sample. His HCL was put into remission with a single course of cladribine and rituximab chemotherapy; however, his M kansasii infection persisted for 6 months despite aggressive antimicrobial and surgical therapy. It was finally controlled using high-dose rifampin in combination with azithromycin and ethambutol. This case highlights the known link between HCL and M kansasii. Furthermore, it hints at potential causes beyond chemotherapy-induced immunocompromise. Notable possibilities include HCL cells acting as sanctuary sites for M kansasii to evade the immune system, and subclinical M kansasii infections causing NLRP3 inflammasome overactivation to trigger the oncogenic transformation to HCL. More research into the pathophysiologic link between HCL and M kansasii infections would allow for more effective prevention, diagnosis, and treatment of these severe atypical infections which are the major cause of morbidity in the cladribine era of HCL treatment.


Assuntos
Leucemia de Células Pilosas , Infecções por Mycobacterium não Tuberculosas , Mycobacterium kansasii , Humanos , Masculino , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/tratamento farmacológico , Adulto , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/complicações , Cladribina/uso terapêutico , Rifampina/uso terapêutico , Azitromicina/uso terapêutico , Rituximab/uso terapêutico
8.
BMC Microbiol ; 24(1): 172, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38760693

RESUMO

BACKGROUND: We evaluated whether the sputum bacterial microbiome differs between nontuberculous mycobacteria pulmonary disease (NTM-PD) patients with stable disease not requiring antibiotic treatment and those requiring antibiotics. METHODS: We collected sputum samples from 21 clinically stable NTM-PD patients (stable group) and 14 NTM-PD patients needing antibiotic treatment (treatment group). We also obtained 13 follow-up samples from the stable group. We analyzed the 48 samples using 16S rRNA gene sequencing (V3-V4 region) and compared the groups. RESULTS: In the linear discriminant analysis effect size (LEfSe) analysis, the species Porphyromonas pasteri, Haemophilus parahaemolyticus, Prevotella nanceiensis, and Gemella haemolysans were significantly more prevalent in the sputum of the stable group compared to the treatment group. No taxa showed significant differences in alpha-/beta-diversity or LEfSe between the 21 baseline and 13 follow-up sputum samples in the stable group. In the stable group, the genus Bergeyella and species Prevotella oris were less common in patients who achieved spontaneous culture conversion (n = 9) compared to those with persistent NTM positivity (n = 12) (effect size 3.04, p = 0.039 for Bergeyella; effect size 3.64, p = 0.033 for P. oris). In the treatment group, H. parainfluenzae was more common in patients with treatment success (n = 7) than in treatment-refractory patients (n = 7) (effect size 4.74, p = 0.013). CONCLUSIONS: Our study identified distinct bacterial taxa in the sputum of NTM-PD patients based on disease status. These results suggest the presence of a microbial environment that helps maintain disease stability.


Assuntos
Microbiota , Infecções por Mycobacterium não Tuberculosas , RNA Ribossômico 16S , Escarro , Humanos , Escarro/microbiologia , Masculino , Feminino , Microbiota/genética , Microbiota/efeitos dos fármacos , Idoso , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , RNA Ribossômico 16S/genética , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Micobactérias não Tuberculosas/isolamento & purificação , Micobactérias não Tuberculosas/genética , Micobactérias não Tuberculosas/classificação , Micobactérias não Tuberculosas/efeitos dos fármacos , DNA Bacteriano/genética , Pneumopatias/microbiologia , Pneumopatias/tratamento farmacológico
9.
J Korean Med Sci ; 39(20): e167, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38804011

RESUMO

BACKGROUND: Coinfections with multiple nontuberculous mycobacterial (NTM) species have not been widely studied. We aimed to evaluate the clinical characteristics and treatment outcomes in patients with NTM-pulmonary disease (PD) caused by coinfection with multiple NTM species. METHODS: We retrospectively reviewed patients with NTM-PD at a tertiary referral hospital in Korea between March 2012 and December 2018. Coinfection was defined as two or more species of NTM pathogens isolated from the same respiratory specimen or different specimens within three months. RESULTS: Among 1,009 patients with NTM-PD, 147 (14.6%) NTM coinfections were observed (average age 64.7 years, 69.4% women). NTM species were identified more frequently (median 6 vs. 3 times, P < 0.001) in the coinfection group than in the single species group, and follow-up duration was also longer in the coinfection group (median 44.9 vs. 27.1 months, P < 0.001). Mycobacterium avium complex (MAC) and M. abscessus and M. massiliense (MAB) were the dominant combinations (n = 71, 48.3%). For patients treated for over six months in the MAC plus MAB group (n = 31), sputum culture conversion and microbiological cure were achieved in 67.7% and 41.9% of patients, respectively. We divided the MAC plus MAB coinfection group into three subgroups according to the target mycobacteria; however, no statistical differences were found in the treatment outcomes. CONCLUSION: In NTM-PD cases, a significant number of multiple NTM species coinfections occurred. Proper identification of all cultured NTM species through follow-up is necessary to detect multispecies coinfections. Further research is needed to understand the nature of NTM-PD in such cases.


Assuntos
Coinfecção , Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Micobactérias não Tuberculosas , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Idoso , Coinfecção/microbiologia , Micobactérias não Tuberculosas/isolamento & purificação , Resultado do Tratamento , Pneumopatias/microbiologia , Pneumopatias/complicações , Complexo Mycobacterium avium/isolamento & purificação , Antibacterianos/uso terapêutico , República da Coreia
10.
J Infect Dev Ctries ; 18(4): 651-654, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38728638

RESUMO

INTRODUCTION: Mycobacterium marinum infection rarely occurs and has atypical symptoms. It is challenging to distinguish disseminated M. marinum infection from multifocal dermatosis caused by other factors clinically. CASE PRESENTATION: Herein, we reported a 68-year-old male patient with Human Immunodeficiency Virus (HIV) who presented redness and swelling in his left hand after being stabbed by marine fish for over 2 months. Mycobacterium tuberculosis infection was considered according to biochemical and pathological examinations, while empirical anti-infection treatment was ineffective. RESULTS: The metagenomic next-generation sequencing (mNGS) detected a large amount of M. marinum sequences, and the patient was finally diagnosed with M. marinum infection. After one month of combination therapy with ethambutol, rifabutin, moxifloxacin, and linezolid, the swelling disappeared significantly. In this case, the successful application of mNGS in diagnosing and treating M. marinum infection has improved the understanding of the microbe both in the laboratory and clinically, especially in patients with HIV. CONCLUSIONS: For diseases with atypical symptoms or difficulty in determining the pathogens, mNGS is suggested in clinical procedures for rapid and accurate diagnosis and treatment.


Assuntos
Infecções por HIV , Infecções por Mycobacterium não Tuberculosas , Mycobacterium marinum , Humanos , Masculino , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Idoso , Mycobacterium marinum/isolamento & purificação , Mycobacterium marinum/genética , Infecções por HIV/complicações , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Etambutol/uso terapêutico , Antibacterianos/uso terapêutico
11.
Int J Mycobacteriol ; 13(1): 34-39, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38771277

RESUMO

BACKGROUND: In patients with cystic fibrosis (CF), representatives of the fast-growing Mycobacterium abscessus complex (MABSc) are often distinguished, but the culture of the material taken from such patients increases the growth time. We analyzed the terms of cultivation of MABSc representatives on dense nutrient media and also evaluated the productivity of a modified nutrient medium based on agar for the isolation of Burkholderia cepacia complex (BCC). METHODS: Sixty-four strains of MABSc isolated from patients with CF and suspected tuberculosis were analyzed. The material from the patients was cultured on a universal chromogenic medium, 5% blood agar, yolk-salt agar, selective medium for isolation of BCC, and Löwenstein-Jensen medium. The cultures were incubated for 5 days (37°C, aerobic conditions), after for 23 days (28°C, aerobic conditions). The productivity of the developed nutrient medium was evaluated by the number of cells that gave visible growth after culturing 0.1 mL of a bacterial suspension of 103 CFU/mL. RESULTS: 76.8% of the strains grew in a 2-week period, and 23.2% of the strains were obtained at a later date from 18 to 28 days (average: 21.23 days). The modified medium with a concentration of 240 mg of iron (III) polymaltose hydroxide proved to be the most optimal for the isolation of MABSc. CONCLUSION: When using a chromogenic medium for culture material from patients with CF, it is necessary to extend incubation up to 28 days to increase the probability of MABSc isolation. The modified BCC medium showed a good selectivity result but required further investigation.


Assuntos
Meios de Cultura , Fibrose Cística , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Humanos , Fibrose Cística/microbiologia , Meios de Cultura/química , Mycobacterium abscessus/crescimento & desenvolvimento , Mycobacterium abscessus/isolamento & purificação , Infecções por Mycobacterium não Tuberculosas/microbiologia , Fatores de Tempo , Técnicas Bacteriológicas/métodos , Complexo Burkholderia cepacia/isolamento & purificação , Complexo Burkholderia cepacia/crescimento & desenvolvimento
12.
Microbiol Spectr ; 12(5): e0000624, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38619253

RESUMO

Mycobacterium abscessus is increasingly recognized as an emerging opportunistic pathogen causing severe lung diseases and cutaneous infections. However, treatment of M. abscessus infections remains particularly challenging, largely due to intrinsic resistance to a wide panel of antimicrobial agents. New therapeutic alternatives are urgently needed. Herein, we show that, upon limited irradiation with a blue-light source, newly developed porphyrin-peptide cage-type photosensitizers exert a strong bactericidal activity against smooth and rough variants of M. abscessus in planktonic cultures and in biofilms, at low concentrations. Atomic force microscopy unraveled important morphological alterations that include a wrinkled and irregular bacterial surface. The potential of these compounds for a photo-therapeutic use to treat M. abscessus skin infections requires further evaluations.IMPORTANCEMycobacterium abscessus causes persistent infections and is extremely difficult to eradicate. Despite intensive chemotherapy, treatment success rates remain very low. Thus, given the unsatisfactory performances of the current regimens, more effective therapeutic alternatives are needed. In this study, we evaluated the activity of newly described porphyrin-peptide cage-type conjugates in the context of photodynamic therapy. We show that upon light irradiation, these compounds were highly bactericidal against M. abscessus in vitro, thus qualifying these compounds for future studies dedicated to photo-therapeutic applications against M. abscessus skin infections.


Assuntos
Antibacterianos , Biofilmes , Testes de Sensibilidade Microbiana , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Fármacos Fotossensibilizantes , Porfirinas , Mycobacterium abscessus/efeitos dos fármacos , Porfirinas/farmacologia , Porfirinas/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Antibacterianos/farmacologia , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Humanos , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Peptídeos/farmacologia , Peptídeos/química , Fotoquimioterapia/métodos , Luz
13.
Microbiol Spectr ; 12(5): e0383723, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38619262

RESUMO

Mycobacterium abscessus, an emerging pathogen responsible for severe pulmonary infections in cystic fibrosis patients, displays either a smooth (S) or a rough (R) morphotype. Infections with M. abscessus R are associated with increased pathogenicity in animal models and humans. While the S-to-R transition correlating with reduced glycopeptidolipid (GPL) production is well-documented, the recent screening of a transposon library revealed additional gene candidates located outside of the GPL locus involved in this transition. These genes include MAB_1470c, encoding the putative lipoprotein peptidase LpqM. However, experimental confirmation of the implication of this gene in the morphotype switch is lacking. Herein, we re-examined the role of MAB_1470c, and its homolog MAB_1466c, in colonial morphotype changes by generating unmarked deletion mutants in M. abscessus S. Our results indicate that the morphotype of these mutants stayed smooth in different media. Unexpectedly, the intracellular growth of ΔMAB_1470c and ΔMAB_1466c in THP-1 macrophages was significantly reduced as compared to the parental S strain, and these defects were rescued upon complementation with their corresponding genes. Strikingly, the intracellular survival defect was further exacerbated in a mutant lacking both MAB_1470c and MAB_1466c genes. This implies that, despite their primary sequence relatedness, the two proteins are not functionally redundant. Collectively, this suggests that these two LpqM-related lipoproteins are unlikely to be involved in the S-to-R transition but are key players for intramacrophage survival of M. abscessus. IMPORTANCE: Mycobacterium abscessus causes persistent infections in patients with underlying pulmonary diseases, resulting in progressive lung function deterioration. The rough (R) morphotype is well-established as associated with chronic and more aggressive infections in patients. In this study, we individually and simultaneously deleted the MAB_1470c and MAB_1466c genes in M. abscessus S, without observing changes in colony morphotypes. However, these mutants exhibited a severe impairment in their ability to survive within human macrophages, highlighting the critical role of these two lipoproteins in M. abscessus virulence.


Assuntos
Proteínas de Bactérias , Macrófagos , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Mycobacterium abscessus/genética , Mycobacterium abscessus/metabolismo , Mycobacterium abscessus/crescimento & desenvolvimento , Humanos , Macrófagos/microbiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Infecções por Mycobacterium não Tuberculosas/microbiologia , Células THP-1 , Virulência/genética
14.
BMC Pulm Med ; 24(1): 210, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684989

RESUMO

BACKGROUND: Measurement of exhaled nitric oxide (FeNO) is a potentially useful diagnostic test for asthma. However, no study has explored the relationship between FeNO and respiratory symptoms of nontuberculous mycobacterial pulmonary disease (NTM-PD) complicated with asthma. The objective of this study was to assess the utility of measuring FeNO levels in patients with NTM-PD complicated by asthma. METHODS: In this single-center retrospective cohort study, 140 NTM-PD patients with FeNO measured were enrolled. We selected NTM-PD patients who complicated with asthma as the NTM+BA group, defined using the following criteria: NTM patients with symptoms consistent with asthma, and NTM patients with symptomatic improvement after diagnostic therapy with ICS ± a long-acting beta 2-agonist (LABA). We then calculated a diagnostic cutoff point to distinguish between the NTM+BA groups and the NTM groups (all others). High-resolution computed tomography (HRCT) images were evaluated using the CT scoring system and their association with FeNO was examined. RESULTS: A total of 89 patients were included in the study. (31 in the NTM+BA group and 58 in the NTM group). Compared with the NTM group, the NTM+BA group had higher rates of allergic disease (51.6% vs. 22.4%; p=0.0085) and higher FeNO values (median, 23 [interquartile range {IQR}, 15.0-43.0] ppb vs. median, 17 [IQR, 11.8-23.0] ppb; p=0.015). With diagnostic asthma care using mainly ICS/LABA with reference to the FeNO, most patients (91.0%, 20/22) in the NTM-preceding subgroup in the NTM+BA group demonstrated a prompt improvement of their symptoms and AFB culture findings did not worsen (Culture positive rate (%): Pre-treatment: 59.1% vs. Post-treatment: 40.9%, p=0.3660) at 6 months after starting diagnostic therapy. The optimal diagnostic cutoff point of FeNO to distinguish between the two groups was calculated as 21.5 ppb by the ROC curve (sensitivity 75%, specificity 71.93%, p<0.0001; area under the curve: 0.7989). No significant correlation was observed between FeNO and the severity of CT images in the patients. CONCLUSIONS: A certain number of patients with NTM-PD showed exacerbated respiratory symptoms due to asthmatic complications. Elevated FeNO levels suggest asthma complications, even in patients with NTM.


Assuntos
Asma , Tosse , Infecções por Mycobacterium não Tuberculosas , Óxido Nítrico , Humanos , Feminino , Masculino , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/complicações , Pessoa de Meia-Idade , Estudos Retrospectivos , Asma/complicações , Asma/diagnóstico , Idoso , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Tosse/etiologia , Tomografia Computadorizada por Raios X , Teste da Fração de Óxido Nítrico Exalado , Testes Respiratórios/métodos , Curva ROC
15.
J Infect ; 88(5): 106149, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574774

RESUMO

BACKGROUND: Distinguishing between nontuberculous mycobacterial (NTM) lung infections and pulmonary tuberculosis becomes challenging due to their similar clinical manifestations and radiological images. Consequently, instances of delayed diagnosis or misdiagnosis are highly frequent. A feasible and reliable indicator of the existence of NTM in the early stages of the disease would help to solve this dilemma. METHODS: In this study, we evaluated the potential of smear-positive and Xpert assay (Cepheid, USA) negative outcomes as an early indicator of possible NTM infection in a high TB-burden setting retrospectively and prospectively. RESULTS: During the study period, 12·77% (138/1081) of the smear-positive cases yielded negative outcomes with the simultaneous Xpert assay. From the 110 patients who yielded smear-positive/Xpert-negative outcomes and cultivated strain as well, 105 (95·45%) were proved to have NTM isolated. By incorporating an additional criterion of a negative result from the Interferon-gamma release assay, the accuracy of the screening method reached 100%. Regarding the NTM presence prediction value, smear-positive/Xpert-negative has a sensitivity of 24·86% (45/181) in all NTM isolated cases but 93·75-96·55% accuracy in retrospective study or 93·75% accuracy in prospective study in smear-positive NTM isolated cases. In addition, the specificity was ∼99·47% (943/948) in smear-positive tuberculosis cases. CONCLUSION: The clue of the presence of NTM could be obtained on the first day of the hospital visit due to the point of care (POC) feature of smear testing and Xpert assay. About one-fourth of the NTM-isolated patients would benefit from this rapid, convenient, and reliable screening strategy in the given circumstance. Smear-positive/Xpert-negative outcome is an early, trustable indicator that is indicative of NTM isolation.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Micobactérias não Tuberculosas , Sensibilidade e Especificidade , Humanos , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Masculino , Feminino , Estudos Retrospectivos , Micobactérias não Tuberculosas/isolamento & purificação , Micobactérias não Tuberculosas/genética , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Adulto , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Escarro/microbiologia , Testes de Liberação de Interferon-gama/métodos , Diagnóstico Diferencial , Idoso de 80 Anos ou mais
16.
Rev Esp Quimioter ; 37(3): 266-269, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38602224

RESUMO

OBJECTIVE: Mycobacterium avium complex (MAC) and Mycobacterium abscessus are a group of nontuberculous mycobacteria (NTM) that have been described as human pathogens. Their ability to develop biofilms in tissues and medical devices is one of the most important pathogenicity factors, with important implications in diagnosis and treatment. Macrolides are usually considered one of the bases of this treatment. METHODS: Here we have studied the biofilm prevention concentration (BPC) of 16 strains (n=16) with clarithromycin to avoid the biofilm development by these NTM. RESULTS: In this study, all M. abscessus strains have similar BPC, while MAC strains showed different values. For MAC the concentrations ranged between 1-16 mg/L, while for M. abscessus the concentration was 32 mg/L for all strains except one that was 64 mg/L. CONCLUSIONS: These results open the possibility of using macrolides for the prevention of biofilm development in patients with a risk of developing NTM disease.


Assuntos
Antibacterianos , Biofilmes , Claritromicina , Testes de Sensibilidade Microbiana , Micobactérias não Tuberculosas , Claritromicina/farmacologia , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Micobactérias não Tuberculosas/efeitos dos fármacos , Humanos , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/prevenção & controle , Complexo Mycobacterium avium/efeitos dos fármacos , Mycobacterium abscessus/efeitos dos fármacos
17.
Medicina (Kaunas) ; 60(4)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38674225

RESUMO

Background and Objectives: Tuberculosis is caused by Mycobacterium tuberculosis (MTB), while nontuberculous mycobacteria (NTM) encompass a group of mycobacterial species that are distinct from the MTB complex and leprae. Spondyloarthritis (SpA) is a group of chronic inflammatory diseases with shared clinical characteristics and is treated with biological agents; however, their use may elevate the risk of MTB and NTM infections. This study aimed to compare the incidence and risk of MTB and NTM infections in patients with SpA, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), using a population-based approach. Materials and Methods: This study included 2333 patients with SpA and 9332 age- and sex-matched controls from the Korea National Health Insurance Service-National Sample Cohort database from 2002 to 2019. The patients were identified using the International Classification of Diseases-10 codes for AS, PsA, MTB, and NTM. Results: The results showed that a negligible percentage of patients with SpA developed NTM (0.002%) and MTB (0.016%), with no significant difference in the incidence rate ratio (IRR) compared to controls. Among patients with SpA treated with biologics, the IRRs for NTM and MTB were 5.66 and 3.069, respectively; however, these were not statistically significant. No cases of NTM or MTB infection were reported in female patients with SpA treated with biologics. In both the SpA patient group and the control group, the incidence of MTB was higher in individuals over 60 years old compared to those under 60 years old. Cox proportional hazard analysis revealed a significant adjusted hazard ratio of 1.479 for MTB in patients with SpA after adjusting for age, sex, smoking history, insurance level, and comorbidities. However, this significance was not maintained when biological therapy was further adjusted. Conclusions: Our study indicated that the risks of NTM and MTB infection are not elevated in patients with SpA. Although biological use may potentially increase the risk of MTB infection, it does not lead to a significant increase in incidence rates. Proactive screening for latent tuberculosis and adequate prophylaxis using biologics can effectively manage the risk of NTM and MTB infections.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Espondilartrite , Tuberculose , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Espondilartrite/complicações , Espondilartrite/epidemiologia , Espondilartrite/tratamento farmacológico , Incidência , Tuberculose/epidemiologia , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/complicações , Idoso , Estudos de Coortes , Artrite Psoriásica/complicações , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/epidemiologia , Espondilite Anquilosante/complicações , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/epidemiologia
18.
BMJ Case Rep ; 17(4)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589234

RESUMO

People who have structural or developmental lung disease are more likely to develop non-tuberculous mycobacterial infections. We present the case of a young man in his 30s who had unilateral pulmonary artery agenesis on the right side and presented with a 6-month history of productive cough and fever. His CT scan showed nodular and cavitating lesions on the right side, and sputum analysis confirmed infection with Mycobacterium chimaera He had to undergo modifications in his treatment, including a change from rifampicin to rifabutin due to drug interactions and his amikacin had to be stopped due to signs of vestibular toxicity. Using a multidisciplinary approach, we were able to formulate an appropriate drug regimen for him, and he is now under regular follow-up with infectious diseases and respiratory medicine.


Assuntos
Anormalidades Múltiplas , Pneumopatias , Pulmão , Infecções por Mycobacterium não Tuberculosas , Pneumonia , Humanos , Masculino , Pulmão/anormalidades , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Micobactérias não Tuberculosas , Artéria Pulmonar/diagnóstico por imagem , Adulto
19.
BMJ Case Rep ; 17(4)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38688568

RESUMO

Catheter-related bloodstream infection (CRBSI) is one of the common healthcare-acquired infections imposing a high burden of morbidity and mortality on the patients. Non-tuberculous mycobacterium is a rare aetiology for CRBSI and poses challenges in laboratory diagnosis and clinical management. This is a case of a woman in her early 60s with underlying end-stage renal failure, diabetes mellitus and hypertension presented with a 2-week history of high-grade fever postregular haemodialysis, vomiting, lethargy and altered mental status.Blood cultures from a permanent catheter and peripheral taken concurrently yielded Mycobacterium senegalense, identified by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry, which established the diagnosis of CRBSI atypically presented with concurrent acute intracranial bleeding and cerebrovascular infarction at initial presentation. She was started on a combination of oral azithromycin, oral amikacin and intravenous imipenem, and the permanent catheter was removed. Despite the treatments instituted, she developed septicaemia, acute myocardial infarction and macrophage activation-like syndrome, causing the patient's death.


Assuntos
Antibacterianos , Infecções Relacionadas a Cateter , Infecções por Mycobacterium não Tuberculosas , Humanos , Feminino , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/diagnóstico , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Evolução Fatal , Bacteriemia/tratamento farmacológico , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Diálise Renal , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Amicacina/uso terapêutico , Amicacina/administração & dosagem
20.
Diagn Microbiol Infect Dis ; 109(3): 116296, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38640607

RESUMO

Pulmonary infection due to Mycobacterium abscessus complex (MABC) usually occurs in children with underlying risk factors including cystic fibrosis (CF), chronic lung disease, and immunocompromised status, but rarely in immunocompetent children without underlying lung disease, especially in infants. We present a case of MABC pulmonary disease (MABC-PD) in an otherwise healthy 53-day-old male infant with one week of cough and respiratory distress. Computed tomography showed multiple masses across both lungs. Isolated mycobacteria from his bronchoalveolar lavage fluid were identified as MABC. We describe our complete evaluation, including immunodeficiency evaluation incorporating whole exome sequencing and our therapeutic process given complicated susceptibility pattern of the M. abscessus isolate, and review literature for MABC-PD in immunocompetent children. The infant was successfully treated through prolonged treatment with parenteral Amikacin, Cefoxitin, Linezolid, and Clarithromycin, combined with inhaled Amikacin.


Assuntos
Antibacterianos , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Humanos , Masculino , Mycobacterium abscessus/efeitos dos fármacos , Mycobacterium abscessus/isolamento & purificação , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Antibacterianos/uso terapêutico , Lactente , Líquido da Lavagem Broncoalveolar/microbiologia , Amicacina/uso terapêutico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/diagnóstico , Resultado do Tratamento , Tomografia Computadorizada por Raios X , Claritromicina/uso terapêutico , Linezolida/uso terapêutico
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