Nontuberculous mycobacteria (NTM), which include the Mycobacterium avium complex, are classified as difficult-to-treat pathogens due to their ability to quickly develop drug resistance against the most common antibiotics used to treat NTM infections. The overexpression of efflux pumps (EPs) was demonstrated to be a key mechanism of clarithromycin (CLA) resistance in NTM. Therefore, in this work, 24 compounds from an in-house library, characterized by chemical diversity, were tested as potential NTM EP inhibitors (EPIs) against Mycobacterium smegmatis mc2 155 and M. avium clinical isolates. Based on the acquired results, 12 novel analogs of the best derivatives 1b and 7b were designed and synthesized to improve the NTM EP inhibition activity. Among the second set of compounds, 13b emerged as the most potent NTM EPI. At a concentration of 4 µg/mL, it reduced the CLA minimum inhibitory concentration by 16-fold against the clinical isolate M. avium 2373 overexpressing EPs as primary mechanism of CLA resistance.

Mycobacterium gordonae (M. gordonae) is a species of nontuberculous mycobacteria (NTM) that rarely causes infection. It has previously been labeled the most common NTM contaminant. Bronchiectasis is a disease characterized by abnormal airway dilation leading to chronic cough, sputum production and pulmonary infections. Patients with bronchiectasis are at higher risk of NTM-lung disease with more pathogenic NTM species including Mycobacterium avium complex (MAC) and Mycobacterium abscessus (M. abscessus). The relationship between bronchiectasis and less-pathogenic NTM species such as M. gordonae is less well understood. We performed a retrospective study on patients who had M. gordonae isolated from respiratory specimens at UConn Health between May 2nd, 2010 and October 18th, 2022. M. gordonae was isolated 74 times from 56 patients. It was isolated 35 (47.3%) times from 31 patients with bronchiectasis and 39 (52.7%) times from 26 patients without bronchiectasis. Data was available on all mycobacterial cultures sent from May 2nd 2018 to October 18th 2022. Mycobacterial cultures sent from patients with bronchiectasis were significantly more likely to grow M. gordonae than patients without bronchiectasis (4.3% vs. 1.6%, P=0.007). Furthermore, when considered at the patient level, there remained a significant increased rate of M. gordonae isolation among patients with bronchiectasis (7.1% vs. 2.2%, P<0.001). We then looked at past and future isolation of more pathogenic NTM species and found a non-statistically increased rate of isolation of more pathogenic NTM species including MAC and M. abscessus in patients with bronchiectasis (45.2% vs. 29%, P=0.09). Based on our results, isolation of M. gordonae should raise suspicion of chronic airway disease and defects in host immune response, such as those seen in bronchiectasis. Furthermore, isolation of M. gordonae may suggest increased risk of infection with more pathogenic NTM species such as MAC and M. abscessus.

Mycobacterium avium complex (MAC) is often observed in immunocompromised individuals. However, when pulmonary MAC infection occurs in immunocompetent individuals, particularly elderly females, characteristically involving the middle lobe and lingula lobe of the lung, it is known as Lady Windermere syndrome (LWS). A 64-year-old female patient with no significant comorbidities presented with a history of low-grade intermittent fever and dry cough for one-month duration complicated with hemoptysis for two days. Her initial investigations and imaging were negative, except for the high-resolution CT (HRCT) finding of bronchiectasis involving the middle lobe and lingula lobe suggestive of MAC infection, which was further confirmed by positive sputum culture for MAC. LWS is a condition that is rarely encountered in clinical settings and seldom described in the literature. Especially in resource-limited settings, arriving at a diagnosis is further hindered by the scarce availability of advanced imaging such as HRCT. In clinical settings where pulmonary tuberculosis is endemic, the differentiation of the two conditions is of paramount importance as the treatment regimens for the two conditions are quite different.

The increasing prevalence of Mycobacterium avium complex (MAC) pulmonary disease poses a significant therapeutic challenge, particularly due to the limited efficacy and systemic toxicity associated with conventional guideline-based therapy. Amikacin liposome inhalation suspension (ALIS) has been developed, yet its real-world application remains underreported. This retrospective analysis, conducted from March 2021 to February 2024, examined ALIS\'s clinical use in patients aged 20 years or older with refractory MAC pulmonary disease at our institution. The primary objective of this study is to describe the patient characteristics and clinical trajectories associated with the initiation of ALIS therapy in real-world settings for individuals diagnosed with MAC pulmonary disease. Of 11 patients initiated on ALIS, one was excluded due to financial constraints impacting continuation. The analysis proceeded with the remaining 10 subjects. The mean age of participants was 70.2 years, with a predominance of female patients (n = 7, 70%) and a higher incidence of M. avium infections (n = 6, 60%). Forty percent of the cohort (n = 4) had a history of ethambutol-induced optic neuritis leading to the cessation of the drug. The average interval from the initiation of guideline-based therapy to the start of ALIS was 8.5 ± 6.9 years (mean ± standard deviation). The majority (80%) presented with positive Gaffky scores at ALIS initiation, and a significant proportion exhibited resistance to clarithromycin and ethambutol. Comorbid conditions, including diabetes and previous cancer, were noted. The study also observed elevated anti-MAC antibody levels. Treatment duration varied, with fatigue leading to discontinuation in two cases. Treatment-emergent adverse events were documented in individual patients, each presenting with grade 1 severity: hemoptysis (n = 1, 10%), elevated creatinine levels (n = 1, 10%), and dysphonia (n = 2, 20%) were observed, respectively. Correlation analysis revealed a significant inverse relationship between body mass index (BMI) and ALIS discontinuation due to fatigue, and a positive correlation between Gaffky scores and C-reactive protein (CRP) levels. These results underscore the potential benefits and limitations of ALIS, suggesting that timely intervention and comprehensive healthcare support are crucial for optimal outcomes in the treatment of advanced MAC pulmonary disease.

Mycobacterium porcinum is a nontuberculous mycobacteria (NTM) recently identified to cause human infection. Correct speciation of NTMs can be difficult and result in misdiagnosis and delayed treatment. Because of the paucity of the literature, there is a lack of awareness of the possibility of serious infections caused by M. porcinum. Although severe infections tend to occur in individuals with certain risk factors, the primary being an immunocompromised state, our case illustrates that it can also be possible in non-severely immunocompromised individuals. A 65-year-old male with a medical history of diabetes mellitus (DM), end-stage renal disease (ESRD) on hemodialysis (HD), congestive heart failure (CHF), and chronic obstructive pulmonary disease (COPD) was admitted to the emergency room due to a laceration on his right lower leg following a fall. He reported shortness of breath but denied other respiratory symptoms. On examination, he showed signs of infection and increased oxygen requirement compared to baseline. Blood culture was positive for acid-fast bacilli (AFB), initially reported as M. avium complex (MAC) and later confirmed as M. porcinum through gene sequencing and morphology analysis. Interval blood cultures taken a week later confirmed true M. porcinum bacteremia. Treatment initially involved intravenous antibiotics- imipenem and ciprofloxacin before transitioning to oral linezolid and ciprofloxacin based on sensitivities. Following 10 days of antibiotic therapy, subsequent blood cultures returned negative, and treatment with oral antibiotics was advised, with continued outpatient follow-up with infectious disease in two weeks. M. porcinum, typically considered a contaminant in healthy individuals, was identified as the causative agent of a disseminated infection in a non-severely immunocompromised patient. This case underscores the importance of accurately identifying the specific mycobacterial species, confirming true infection, and conducting antibiotic susceptibility testing due to the distinct antibiotic susceptibility profile of M. porcinum compared to other NTM like MAC.

Mycobacterium gordonae (MG) is one of the least pathogenic nontuberculous mycobacteria (NTM). We report an unusual case of MG infection in a patient with newly diagnosed lung cancer. A 61-year-old woman presented with shortness of breath and weight loss. Six months prior to admission, she was diagnosed with MG infection based on positive sputum cultures and bronchioalveolar lavage. Despite anti-mycobacterial therapy, her symptoms worsened and she lost approximately 100 pounds. A transbronchial biopsy obtained one week prior to admission revealed adenocarcinoma of the lung. At admission, vital signs were normal, and a physical exam revealed bilateral crackles. Computed tomography (CT) scan of the chest revealed infiltrates with ground-glass opacity. The patient was admitted to the oncology service for evaluation. Our findings suggest that symptomatic individuals with positive cultures of MG should proceed with extensive workup for possible underlying lung cancer especially if not responding to anti-mycobacterial therapy.

Although pulmonary artery (PA) dilation is independently associated with significant morbidity and mortality in patients with pulmonary diseases irrespective of diagnosed pulmonary hypertension, its relationship with nontuberculous mycobacteria (NTM) is unknown. The Bronchiectasis and NTM Research Registry is a multicenter registry created to foster research in non-cystic fibrosis (CF) bronchiectasis and NTM lung disease. The majority of patients with non-CF bronchiectasis at Oregon Health & Science University have NTM infections. To determine the prevalence of PA dilation in these patients and its association with supplemental oxygen use, severity of bronchiectasis, tobacco use, and NTM in the sputum culture, we evaluated the chest computed tomography (CT) scans from 321 patients in a cross-sectional analysis. We measured the severity of bronchiectasis by applying modified Reiff criteria and measured the diameters of the PA and aorta (Ao), with PA dilation defined as a PA:Ao ratio >0.9. In our cohort, the mean age was 67.3 years and 83.2% were female. The mean modified Reiff score was 7.1, indicating moderate disease severity. Forty-two patients (13.1%) were found to have PA dilation. PA dilation was positively associated with the use of supplemental oxygen (P<0.001), but there was no association between PA dilation and NTM infection.

Mycobacterium szulgai is a slow-growing nontuberculous mycobacterium (NTM). It was first described in 1972 and is responsible for less than 0.2% of all NTM infections. The most common presentation resembles pulmonary tuberculosis, but it may also present as an extrapulmonary disease. It primarily affects individuals with underlying lung disease or immunocompromising conditions. The increasing use of tumor necrosis factor-alpha inhibitors, such as adalimumab, is associated with an increased risk of serious infections. We report a case of Mycobacterium szulgai infection in a 23-year-old woman with a history of childhood pneumonia and Crohn\'s disease on adalimumab.

Cosmetic surgeries are very popular and glamorized by the mainstream media and celebrities. Many individuals perceive certain bodily features as appealing for physical attraction and will attempt to obtain these features by surgery. However, these surgeries are not without risk, and significant consequences can occur if not performed by qualified medical professionals under sterile procedures. The authors present novel cases of two healthy young female patients who underwent a Brazilian butt lift (BBL) procedure a week apart by the same plastic surgeon in Mexico and developed dark painful lesions secondary to Mycobacterium abscessus (M. abscessus), a multidrug-resistant non-tuberculous mycobacterium (NTM). The literature review shows a paucity of data concerning NTM infections via surgical procedures of this type. The first case was of a 31-year-old woman who underwent a BBL and presented with bilateral dark painful buttock lesions weeks later. The patient returned to the plastic surgeon, who drained some lesions and prescribed oral antibiotics. The patient\'s clinical status continued to deteriorate and presented to the hospital for further assessment. The patient was initially started on broad-spectrum antibiotic therapy. The patient was found to have an HIV infection with a relatively preserved CD4 lymphocyte count and was started on antiretroviral therapy (ART). Intraoperative excisional tissue sample cultures grew M. abscessus. The patient was started on empiric tigecycline, cefoxitin, and linezolid. Preliminary culture susceptibilities showed resistance to linezolid. Linezolid was discontinued, amikacin was started, and cefoxitin and tigecycline were continued. Tigecycline, cefoxitin, and amikacin were continued and final susceptibilities showed sensitivity to the current treatment. The patient received a total of four months of treatment with tigecycline, cefoxitin, and amikacin. The second case was of a 28-year-old woman who underwent a BBL a week after the first patient by the same surgeon and developed multiple gluteal and body abscesses. The patient underwent bilateral thigh and gluteal, right chest wall, and breast surgical debridements with intraoperative cultures at a different hospital facility, which grew M. abscessus. Susceptibilities were not performed there. The patient was transferred to our facility for further care. Intraoperative cultures remained negative, and the patient was treated with a six-month course of tigecycline, cefoxitin, and amikacin.

The regrowth and subsequent exposure of opportunistic pathogens (OPs) whilst reopening buildings that have been locked down due to the stay-at-home restrictions to limit the spread of COVID-19, is a public health concern. To better understand such microbiological risks due to lowered occupancy and water demand in buildings, first and post-flush water samples (n = 48) were sampled from 24 drinking water outlets from eight university buildings in two campuses (urban and rural), with various end-user occupancies. Both campuses were served with chlorinated water originating from a single drinking water distribution system in South-East Queensland, situated 14 km apart, where the rural campus had lower chlorine residuals. Culture-dependent and culture-independent methods (such as flow cytometry, qPCR and 16S rRNA gene amplicon sequencing) were used concurrently to comprehensively characterise the OPs of interest (Legionella spp., Pseudomonas aeruginosa, and nontuberculous mycobacteria (NTM)) and the premise plumbing microbiome. Results showed that buildings with extended levels of stagnation had higher and diverse levels of microbial growth, as observed in taxonomic structure and composition of the microbial communities. NTM were ubiquitous in all the outlets sampled, regardless of campus or end-user occupancy of the buildings. qPCR and culture demonstrated prevalent and higher concentrations of NTM in buildings (averaging 3.25 log10[estimated genomic copies/mL]) with extended stagnation in the urban campus. Furthermore, flushing the outlets for 30 minutes restored residual and total chlorine, and subsequently decreased the levels of Legionella by a reduction of 1 log. However, this approach was insufficient to restore total and residual chlorine levels for the outlets in the rural campus, where both Legionella and NTM levels detected by qPCR remained unchanged, regardless of building occupancy. Our findings highlight that regular monitoring of operational parameters such as residual chlorine levels, and the implementation of water risk management plans are important for non-healthcare public buildings, as the levels of OPs in these environments are typically not assessed.