OBJECTIVE: The incidence of lung infections is increasing worldwide in individuals suffering from cystic fibrosis and chronic obstructive pulmonary diseases. Mycobacterium abscessus is associated to chronic lung deterioration in these populations. The intrinsic resistance of M. abscessus to most conventional antibiotics jeopardizes treatment success rates. To date no single drug has been developed targeting specifically M. abscessus. Our objective was to characterize the pyrithione-core drug-like small molecule named VOMG as a new compound active against M. abscessus and other pathogens.
METHODS: We used a multidisciplinary approach including microbiological, chemical, biochemical and transcriptomics procedures to validate VOMG as a promising anti-M. abscessus drug candidate.
RESULTS: We report for the first time the in vitro and in vivo bactericidal activity of VOMG against M. abscessus and other pathogens. Besides being active against M. abscessus biofilm, the compound showed a favourable pharmacology (ADME-Tox) profile. Frequency of resistance studies were unable to isolate resistant mutants. VOMG inhibits cell division, particularly the FtsZ enzyme.
CONCLUSIONS: VOMG is a new drug-like molecule discovered against M. abscessus inhibiting cell division with broad spectrum activity against other microbial pathogens.

暂无摘要。

暂无摘要。

BACKGROUND: Although nontuberculous mycobacterial (NTM) infection is a common cause of pulmonary disease worldwide, few studies have focused on epidemiological and therapeutic factors related to NTM cases in Anhui Province, China. This retrospective study aimed to identify aetiological and clinical factors, and treatment outcomes of patients with NTM pulmonary disease (NTMPD) in Anhui.
METHODS: Retrospective clinical data obtained from medical records of NTMPD patients seeking care at Anhui Chest Hospital from July 2019 to June 2022 were analyzed. Treatment outcomes were compared between two patient groups: one receiving a standardised NTM treatment regimen and the other receiving precision treatment regimens.
RESULTS: Genotypic analysis of 672 clinical NTMPD-associated isolates revealed that most were Mycobacterium intracellulare, while drug-susceptibility test results demonstrated diverse antibiotic resistance profiles for these isolates. Cough was the most common symptom for 101 NTMPD patients. After patients of both groups received treatment, symptoms improved, sputum culture conversion was observed for some patients, imaging findings stabilised; however, no statistically significant intergroup differences in treatment outcomes were found.
CONCLUSIONS: In this study, M. intracellulare was the predominant NTM species identified in isolates obtained from NTMPD patients. Drug resistance profiles of our patient isolates were complex, highlighting the need for administration of timely, more effective, standardised treatments for patients with NTMPD in Anhui Province, China.

UNASSIGNED: It is essential to consider non-tuberculosis mycobacterium in HIV-positive patients with fever, abdominal pain, weight loss, and splenomegaly.
UNASSIGNED: Mycobacterium genavense is an opportunistic slow-growing nontuberculous mycobacterium in patients with immunocompromised backgrounds, especially HIV-positive patients. In this study, we present two cases of Mycobacterium genovese infection in HIV-positive patients with a good clinical response to accurate treatment.

Elexacaftor/tezacaftor/ivacaftor (ETI) is a CFTR modulator therapy that has dramatically improved the health outcomes for many people with cystic fibrosis (pwCF). There is increasing interest in the role of CFTR modulators in the prevention and treatment of respiratory infections in pwCF. A male patient with F508del homozygous cystic fibrosis developed cavitary Mycobacteroides abscessus subspecies bolletii & massiliense respiratory infection. Antimycobacterial treatment was not given as, in discussion with the patient\'s family, it was deemed unlikely that the intensive regimen would be tolerated by the patient on account of his autism spectrum disorder. Following initiation of ETI, there was a rapid clinical and radiological improvement in this patient\'s cavitary lung disease. This case adds to the evidence base that suggests CFTR modulators, particularly ETI, may restore innate immune function leading to improved outcomes for pulmonary infection in pwCF.

A 30-year-old African American male presented with pain and swelling of the right foot one month after receiving a tattoo on this foot in prison. During his admission for presumed cellulitis, he developed a rash on his contralateral (left) leg, which had been tattooed 10 months prior. A biopsy of the contralateral (left) leg showed acute, chronic, and granulomatous inflammation with a differential diagnosis including infection. His overall condition and both legs worsened, prompting biopsy and tissue culture of the right ankle and foot. Pathology of the right foot showed a granulomatous reaction. Culture grew Mycobacterium chelonae. This case highlights the importance of considering infectious etiologies for rashes appearing within tattoos and represents the importance of a full investigation to obtain the correct diagnosis.

OBJECTIVE: Predicting progression of nontuberculous mycobacterial lung disease (NTM-LD) remains challenging. This study evaluated whether sputum bacterial microbiome diversity can be the biomarker and provide novel insights into related phenotypes and treatment timing.
METHODS: We analyzed 126 sputum microbiomes of 126 patients with newly diagnosed NTM-LD due to Mycobacterium avium complex, M. abscessus complex, and M. kansasii between May 2020 and December 2021. Patients were followed for 2 years to determine their disease progression status. We identified consistently representative genera that differentiated the progressor and nonprogressor by using six methodologies. These genera were used to construct a prediction model using random forest with 5-fold cross validation.
RESULTS: Disease progression occurred in 49 (38.6%) patients. Compared with nonprogressors, α-diversity was lower in the progressors. Significant compositional differences existed in the β-diversity between groups (p=0.001). The prediction model for NTM-LD progression constructed using seven genera (Burkholderia, Pseudomonas, Sphingomonas, Candidatus Saccharibacteria, Phocaeicola, Pelomonas, and Phascolarctobacterium) with significantly differential abundance achieved an area under curve of 0.871.
CONCLUSIONS: Identification of the composition of sputum bacterial microbiome facilitates prediction of the course of NTM-LD, and maybe used to develop precision treatment involving modulating the respiratory microbiome composition to ameliorate NTM-LD.

In outpatient settings, Mycobacterium chelonae complex infection brought on by cosmetic injections are rather uncommon. We came across a case of infection brought on by a commercial stem cell injection.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are environmental organisms that are increasingly contributing to human infections. Mycobacterium immunogenum, a variant of NTM discovered in 2001, is a rapidly growing mycobacterium that exhibits multidrug resistance. Reports of infections caused by this organism, particularly tenosynovitis in the musculoskeletal system, are limited.
METHODS: A 71-year-old female with vesicular pemphigus, undergoing immunosuppressive therapy, presented with a progressively enlarging tumour on the dorsum of her right hand, along with erythematous papules that extended across her right forearm. The specimens of skin tissues and blood cultures revealed the presence of M. immunogenum. Magnetic resonance imaging evaluation led to the diagnosis of pyogenic extensor tenosynovitis. A multidrug regimen, comprising amikacin and clarithromycin, was initiated, followed by synovectomy. The patient underwent a course of 180 days of antimicrobial therapy and demonstrated no signs of disease recurrence one year after treatment completion.
CONCLUSIONS: Early diagnosis and surgical intervention are crucial to prevent the adverse prognostic implications of pyogenic extensor tenosynovitis caused by M. immunogenum. Effective management requires precise microbial identification and susceptibility testing, necessitating collaborative engagement with microbiological laboratories.