Pulmonary Nontuberculous Mycobacterial Infection Research Articles

Efficacy of SPR720 in murine models of non-tuberculous mycobacterial pulmonary infection.

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing worldwide, with Mycobacterium avium complex (MAC) and Mycobacterium abscessus as the predominant pathogens. Current treatments are poorly tolerated and modestly effective, highlighting the need for new treatments. SPR719, the active moiety of the benzimidazole prodrug SPR720, inhibits the ATPase subunits of DNA gyrase B, a target not exploited by current antibiotics, and therefore, no cross-resistance is expected with standard-of-care (SOC) agents. To evaluate the in vitro activity of SPR719 against MAC and M. abscessus clinical isolates, including those resistant to SOC agents, and in vivo efficacy of SPR720 in murine non-tuberculous mycobacteria (NTM) pulmonary infection models. NTM isolates were tested for susceptibility to SPR719. Chronic C3HeB/FeJ and severe combined immunodeficient murine models of pulmonary infection were used to assess efficacy of SPR720 against MAC and M. abscessus, respectively. SPR719 was active against MAC (MIC90, 2 mg/L) and M. abscessus (MIC90, 4 mg/L) clinical isolates. Efficacy of SPR720 was demonstrated against MAC pulmonary infection, both as a monotherapy and in combination with SOC agents. SPR720 monotherapy exhibited dose-dependent reduction in bacterial burden, with the largest reduction observed when combined with clarithromycin and ethambutol. Efficacy of SPR720 was also demonstrated against M. abscessus pulmonary infection where monotherapy exhibited a dose-dependent reduction in bacterial burden with further reductions detected when combined with SOC agents. In vitro activity of SPR720 against common NTM pathogens and efficacy in murine infections warrant the continued clinical evaluation of SPR720 as a new oral option for the treatment of NTM-PD.

The risk of pulmonary NTM infections and water-quality constituents among persons with cystic fibrosis in the United States, 2010-2019.

The prevalence of nontuberculous mycobacterial (NTM) pulmonary disease varies geographically in the United States. Previous studies indicate that the presence of certain water-quality constituents in source water increases NTM infection risk. To identify water-quality constituents that influence the risk of NTM pulmonary infection in persons with cystic fibrosis in the United States. We conducted a population-based case-control study using NTM incidence data collected from the Cystic Fibrosis Foundation Patient Registry during 2010-2019. We linked patient zip code to the county and associated patient county of residence with surface water data extracted from the Water Quality Portal. We used logistic regression models to estimate the odds of NTM infection as a function of water-quality constituents. We modeled two outcomes: pulmonary infection due to Mycobacterium avium complex (MAC) and Mycobacterium abscessus species. We identified 484 MAC cases, 222 M. abscessus cases and 2816 NTM-negative cystic fibrosis controls resident in 11 states. In multivariable models, we found that for every 1-standardized unit increase in the log concentration of sulfate and vanadium in surface water at the county level, the odds of infection increased by 39% and 21%, respectively, among persons with cystic fibrosis with MAC compared with cystic fibrosis-NTM-negative controls. When modeling M. abscessus as the dependent variable, every 1-standardized unit increase in the log concentration of molybdenum increased the odds of infection by 36%. These findings suggest that naturally occurring and anthropogenic water-quality constituents may influence the NTM abundance in water sources that supply municipal water systems, thereby increasing MAC and M. abscessus infection risk.

Pulmonary coccidioidomycosis complicated by nontuberculous mycobacterial pulmonary diseases with a literature review.

Following endobronchial examination, a young mine supervisor was treated with antibiotics for a pulmonary nontuberculous mycobacterial infection for approximately 1 year. However, a review of the radiological findings, which had not been previously assessed, revealed a different possibility. Accordingly, pulmonary resection was performed, enabling histopathological analysis, which showed numerous yeast-like fungi. Given the history of a stay in the southwestern United States for 2 months in 2009, 8 years previously, coccidioidomycosis was strongly suspected and the diagnosis was subsequently confirmed by serology and polymerase chain reaction testing of the excised specimen. Here, we report an educational case emphasizing the importance of meticulous medical history-taking and awareness of endemic mycoses in other countries in the context of globalization.

Prevalence and risk factors of non-tuberculous mycobacterial pulmonary isolates and infection in interstitial lung disease associated with systemic autoimmune disease.

Non-tuberculous mycobacterial (NTM) lung disease (NTM-LD) prevalence is increasing worldwide. In this study, we aimed to evaluate the clinical significance of NTM pulmonary isolates (NTM-PI) and NTM-LD in patients with systemic autoimmune disease (SAD) who had a concurrent interstitial lung disease (ILD) diagnosis. We retrospectively identified patients with SAD who had a concurrent ILD diagnosis (SAD-ILD) and from whom clinically indicated sputum specimens were collected for NTM culture between 2003 and 2018 at a tertiary referral hospital. We analysed the prevalence and risk factors of NTM pulmonary isolates (NTM-PI; ≥1 positive culture) and NTM-LD (≥2 positive cultures). This study included 258 patients. Rheumatoid arthritis and Sjögren's syndrome were the most common SADs (32.2% and 26.7%, respectively). The NTM-negative subgroup had 204 patients (79.1%) and the NTM-PI subgroup had 54 patients (20.9%). In the NTM-PI subgroup, 33 patients had one NTM positive set of specimens (NTM 1+, 12.8% of the entire sample) and 21 had NTM-LD (8.1% of the entire sample). In a multivariable analysis, chronic kidney disease (CKD; adjusted odds ratio [aOR]: 3.10 [1.53, 6.29]) and chronic obstructive pulmonary disease (COPD; aOR: 2.59 [1.16, 5.78]) were significantly associated with NTM-PI. For NTM-LD, CKD (aOR: 2.79 [1.00, 7.76]) and COPD (aOR: 3.70 [1.23, 10.72]) remained significant risk factors. In patients with SAD-ILD, the NTM-PI and NTM-LD prevalence rates were 20.9% and 8.1%, respectively. COPD and CKD were independent risk factors of both NTM-PI and NTM-LD. Previous use of biological agents was associated with NTM-PI.

The problem of Mycobacterium abscessus complex: multi-drug resistance, bacteriophage susceptibility and potential healthcare transmission

ObjectivesMycobacterium abscessus complex is responsible for 2.6–13.0% of all non-tuberculous mycobacterial pulmonary infections and these are notoriously difficult to treat due to the complex regimens required, drug resistance and adverse effects. Hence, bacteriophages have been considered in clinical practice as an additional treatment option. Here, we evaluated antibiotic and phage susceptibility profiles of M. abscessus clinical isolates. Whole-genome sequencing (WGS) revealed the phylogenetic relationships, dominant circulating clones (DCCs), the likelihood of patient-to-patient transmission and the presence of prophages. MethodsAntibiotic susceptibility testing was performed using CLSI breakpoints (n = 95), and plaque assays were used for phage susceptibility testing (subset of n = 88, 35 rough and 53 smooth morphology). WGS was completed using the Illumina platform and analysed using Snippy/snp-dists and Discovery and Extraction of Phages Tool (DEPhT). ResultsAmikacin and Tigecycline were the most active drugs (with 2 strains resistant to amikacin, and one strain with Tigecycline MIC of 4 μg/mL). Most strains were resistant to all other drugs tested, with Linezolid and Imipenem showing the least resistance, at 38% (36/95) and 55% (52/95), respectively. Rough colony morphotype strains were more phage-susceptible than smooth strains (77%—27/35 versus 48%—25/53 in the plaque assays, but smooth strains are not killed efficiently by those phages in liquid infection assay). We have also identified 100 resident prophages, some of which were propagated lytically. DCC1 (20%—18/90) and DCC4 (22%—20/90) were observed to be the major clones and WGS identified 6 events of possible patient-to-patient transmission. DiscussionMany strains of M. abscessus complex are intrinsically resistant to available antibiotics and bacteriophages represent an alternative therapeutic option, but only for strains with rough morphology. Further studies are needed to elucidate the role of hospital-borne M. abscessus transmission.

Spray dried tigecycline dry powder aerosols for the treatment of Nontuberculous mycobacterial pulmonary infections

Nontuberculous mycobacterial (NTM) pulmonary infections are a global health concern and a significant contributor to lung disease. Systemic therapies of a cocktail of antibiotics administered over a long period often lead to adverse reactions and/or treatment failure. NTM pathogens, such as Mycobacterium abscessus (Mabs), are notoriously difficult to treat due to resistance to many traditional antibiotics. However, the antibiotic tigecycline has demonstrated efficacy in vitro and in vivo against Mabs strains varying in drug susceptibility. Tigecycline exhibits instability in aqueous medium, posing delivery challenges, and has caused severe adverse gastrointestinal effects following intravenous administration, requiring treatment discontinuation. To mitigate both of these concerns, inhalation therapies using dry powder aerosols are proposed as an alternative administration route and means of delivery. Tigecycline dry powder formulations were prepared, characterized, and optimized to develop a therapeutic aerosol with low moisture, high dispersibility, and a large fraction of particles in the respirable size range (1–5 μm). The addition of lactose, leucine, and phosphate buffer salts was investigated to achieve additional stability, dispersibility, and tolerability. Preliminary delivery of the dry powders to Mabs-infected mice for 30 min per day over 7 d demonstrated a 0.91-log (87.7%) decrease in lung bacterial burden.

Inhaled nitric oxide for adults with pulmonary non-tuberculous mycobacterial infection

QuestionThere is an increasing prevalence of nontuberculous mycobacteria pulmonary disease (NTM-PD) in the US. Treatment of NTM-PD typically requires multiple medications, which can be associated with unpleasant morbidity and eradication of infection is difficult. Therefore, there is a critical need for novel effective and well-tolerated therapies. Recent in vitro data and case reports have suggested that nitric oxide, inhaled as a gas (gNO), has antimicrobial activity against NTM. We sought to investigate the effect of gNO in patients with NTM-PD in an open-label proof of concept trial. MethodsEligible participants had NTM-PD with persistently positive respiratory cultures for NTM even if on antibiotic treatment. Participants were treated with gNO for 50 min three times daily, five days per week, for three weeks (total of 15 treatment days). ResultsTen participants, of whom nine were on long-term NTM antibiotic therapy, were enrolled. All participants completed the regimen without interruption or discontinuation. Small increases in methemoglobin were noted during treatment, and all resolved to baseline within 2 h. Four participants (40%) met the primary outcome measure of negative sputum cultures after three weeks of therapy. Following treatment discontinuation, three of these participants were again culture positive during the 3-month post-treatment monitoring period, although with measures suggesting low bacterial burden. AnswerPatients tolerated a 3-week regimen of gNO without safety concerns, and despite highly refractory disease four individuals completed the study with negative cultures, although three were again positive in subsequent months. These data support further investigation of gNO as a potential therapy for NTM-PD.

Clinical efficacy and safety of endobronchial one-way valves for the treatment of bronchopleural fistula

Objective: To investigate the efficacy and safety of interventional endobronchial one-way valves (EBV) for the treatment of peripheral bronchopleural fistula (BPF). Methods: A total of 33 patients with peripheral BPF who underwent EBV implantation in Endoscopy Center of Shanghai Pulmonary Hospital from August 2017 to December 2021 were selected as the research objects. All the patients were diagnosed with peripheral BPF before the implantation surgery. The detailed medical records of the patients were collected, and the etiology, lesion location, treatment method and operation process, treatment efficacy and postoperative complications were analyzed to evaluate the efficacy and safety of EBV implantation. Results: Of the 33 patients in our study, 26 were male and 7 were female. The median age was 54.7 (28-86) years. There were 18 cases of BPF after thoracic surgery (54.5%), 6 cases of chronic obstructive pulmonary disease complicated with spontaneous pneumothorax (18.2%), and 12 cases of pulmonary tuberculosis and non-tuberculous mycobacterial infection with spontaneous pneumothorax (36.4%). A total of 63 valves were inserted in the 33 cases, and a maximum of valves and at least one were inserted in a single case. The lesions were located in the right lower lobe in 16 cases (48.5%) and the left upper lobe in 12 cases (36.4%). Of the 33 patients undergoing EBV placement, 22 (66.7%) were successful, with chest drainage tube indwelling duration of (88.5±36.6) days and (29.6±11.4) days, respectively, before and after EBV treatment. The time from EBV placement to successful withdrawal of EBV was (102.2±31.3) days. During a postoperative follow-up of 6 months after EBV treatment, the main complications were 29 cases with attachment of secretions to the EBV (90.6%) and 13 cases (40.6%) with mild granulation proliferation. In addition, there were five patients with moderate to severe granulation proliferation (15.6%), one with valve displacement or shedding (3.1%), and one with bleeding (3.1%). Conclusions: In this study, the success rate of EBV placement and occlusion was 66.7%. Transbronchoscopic EBV placement in the treatment of peripheral BPF is a effective treatment with relatively minor complications.

Pulmonary Non-tuberculous Mycobacterial Infections in Category II Failures from National Tuberculosis Programme

Pulmonary infections due to non-tuberculous mycobacteria (NTM) are increasingly being reported. These can mimic drug-resitant tubercuolosis. A diagnosis of NTM infections needs a high degree of clinical suspicion and repeated isolation of the organism on culture. NTM infections occur commonly in immunocompromised individuals and in people with lung abnormalities. Currently there are no guidelines on drug combinations and the duration of treatment is not adequately defined. Two cases of pulmonary infection with NTM in immune-competent individuals are described in the present report. Although the bacteriological, radiological and clinical response to treatment was good; early discontinuation of treatment resulted in recurrence and change in drug susceptibility pattern, suggesting the need for prolonged treatment for achieving cure.

Vanadium in groundwater aquifers increases the risk of MAC pulmonary infection in O'ahu, Hawai'i.

To identify whether trace metals influence the risk of NTM infection in O'ahu, Hawai'i. A population-based ecologic cohort study was conducted using NTM infection incidence data from patients enrolled at Kaiser Permanente Hawai'i during 2005-2019. We obtained sociodemographic, microbiologic, and geocoded residential data for all Kaiser Permanente Hawai'i beneficiaries. To estimate the risk of NTM pulmonary infection from exposure to groundwater constituents, we obtained groundwater data from three data sources: (1) Water Quality Portal; (2) the Hawai'i Department of Health; and (3) Brigham Young University, Department of Geological Science faculty. Data were aggregated by an aquifer and were associated with the corresponding beneficiary aquifer of residence. We used Poisson regression models with backward elimination to generate models for NTM infection risk as a function of groundwater constituents. We modeled two outcomes: Mycobacterium avium complex (MAC) species and Mycobacterium abscessus group species. For every 1-unit increase in the log concentration of vanadium in groundwater at the aquifer level, infection risk increased by 22% among MAC patients. We did not observe significant associations between water-quality constituents and infection risk among M. abscessus patients. Concentrations of vanadium in groundwater were associated with MAC pulmonary infection in O'ahu, Hawai'i. These findings provide evidence that naturally occurring trace metals influence the presence of NTM in water sources that supply municipal water systems.

Treatment of Nontuberculous Mycobacterial (NTM) Pulmonary Infection in the US Bronchiectasis and NTM Registry: Treatment Patterns, Adverse Events, and Adherence to American Thoracic Society/Infectious Disease Society of America Treatment Guidelines.

Among 1038 participants with pulmonary Mycobacterium avium complex and 120 with Mycobacterium abscessus enrolled in the US Bronchiectasis and NTM Research Registry, less than half received antibiotic therapy in the 24 months before registry enrollment, of which less than half were guideline based. Adverse effects occurred in 21% of therapy recipients, of whom 33% discontinued therapy.

Incidence of Nontuberculous Mycobacterial Pulmonary Infection, by Ethnic Group, Hawaii, USA, 2005-2019.

To further clarify differences in the risk for nontuberculous mycobacterial pulmonary infection (NTM-PI) among ethnic populations in Hawaii, USA, we conducted a retrospective cohort study among beneficiaries of Kaiser Permanente Hawaii (KPH). We abstracted demographic, socioeconomic, clinical, and microbiological data from KPH electronic health records for 2005–2019. An NTM-PI case-patient was defined as a person from whom >1 NTM pulmonary isolate was obtained. We performed Cox proportional hazards regression to estimate incidence of NTM-PI while controlling for confounders. Across ethnic groups, risk for NTM-PI was higher among persons who were underweight (body mass index [BMI] <18.5 kg/m2). Among beneficiaries who self-identified as any Asian ethnicity, risk for incident NTM-PI was increased by 30%. Low BMI may increase susceptibility to NTM-PI, and risk may be higher for persons who self-identify as Asian, independent of BMI.

Cutaneous nontuberculous mycobacterial infections in Japan: Review of the Japanese literature.

Nontuberculous mycobacteria cause a wide range of infections, including cutaneous infections, in both immunocompromised and immunocompetent patients. Although pulmonary nontuberculous mycobacterial infections have increased significantly in Japan in recent years, there is less evidence on clinical and microbiological characteristics of cutaneous nontuberculous mycobacterial infections in Japan. We reviewed 86 Japanese cases reported between July 2016 and November 2021 and analyzed them in conjunction with the eight patients from our institution who were diagnosed with cutaneous nontuberculous mycobacterial infections by culture between 2015 and 2021. In the aggregate series, the average patient age was 60 years, and the ratio of immunocompromised hosts was 53%, both of which were higher than those in previous reports from other countries. No female predominance was observed, unlike in pulmonary nontuberculous mycobacteria infections. Rapidly growing mycobacteria accounted for 58% of the cases (n=54), whereas slowly growing mycobacteria for 43% (n=40). Mycobacterium marinum (also known as Mycobacteroides marinum) (n=20, 21%) was the most common cause, followed by Mycobacterium chelonae (n=18, 19%), Mycobacterium abscessus (also known as Mycobacteroides abscessus) (n=15, 16%), and Mycobacterium ulcerans (n=11, 12%). While clinical appearance was variable, M ulcerans infections usually presented with ulcers, while nodules were common among infections caused by M chelonae and M marinum. Disseminated infections involving multiple organs were observed in 23 patients (24%). Thirty-two cases (30%) were preceded by exposure, including raising or handling fish, trauma, and invasive medical procedures. Most patients were treated with more than two antibiotics and responded to therapy.

Pharmacokinetics and Adverse Effects of Clofazimine in the Treatment of Pulmonary Non-Tuberculous Mycobacterial Infection.

Clofazimine (CFZ) is used to treat pulmonary non-tuberculous mycobacterial (NTM) infection; however, its pharmacokinetics remain unexplored in patients with pulmonary NTM, and the relationship between CFZ serum concentration and adverse effects has not been investigated. The objectives of this study were to characterize the pharmacokinetics of CFZ in pulmonary NTM disease treatment and to investigate the relationship between the steady-state CFZ serum concentration and adverse effects. A prospective observational study was conducted on 45 patients with pulmonary NTM treated with CFZ (UMIN000041053). A maximum of five serum samples per patient were taken at the CFZ trough, and serum concentration was measured using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The pharmacokinetics of CFZ were analyzed using a nonlinear mixed effect model. The relationships among steady-state CFZ serum concentration and adverse effects, pigmentation, and heart rate-corrected QT (QTc) interval were investigated. Twenty-six patients had M. avium or M. intracellulare infection and nineteen had M. abscessus infection. The primary CFZ dosage was 50 mg/day. The estimated apparent CFZ clearance, apparent volume of distribution, and half-life were 2.4 L/h, 2,960 L, and 36 days, respectively. The combined use of rifampicin and CFZ significantly reduced CFZ exposure by 22%. Although there was no relationship between CFZ serum concentration and pigmentation intensity, the QTc interval was significantly correlated with CFZ serum concentration. The estimation of accurate pharmacokinetics for CFZ required approximately 5 months of monitoring. The relationship between the serum concentration and specific adverse effects of CFZ confirmed that CFZ serum concentration was not associated with pigmentation but did affect the QTc interval.

Strategy for Pre- and Post-Transplant Management of Pulmonary Nontuberculous Mycobacterial Infection

<h3>Purpose</h3> No standard procedures are available for waiting-list registration and pre-transplant treatment for transplant candidates with nontuberculous mycobacteria (NTM) infection. We hypothesized that appropriate pre-transplant treatment is associated with favorable outcomes after lung transplantation (LTx) and allows successful postoperative recovery in terms of decreased risk of <i>de novo</i> NTM infection after transplantation. <h3>Methods</h3> A retrospective chart review was conducted of a prospective database of 261 patients undergoing LTx since 2008 (living-donor LTx: 103, cadaveric LTx: 157, hybrid LTx: 1). According to our institutional policy, a negative sputum culture and no active infection on chest radiographs were required for candidate registration on the waiting list. Relevant data were extracted from the medical records. <h3>Results</h3> Eight patients (3.1%) were diagnosed with NTM infection before LTx and thirteen patients (5.0%), after LTx. In two of the eight patients, complete cure of preoperative NTM infection was attained at 18 and 21 years before LTx, respectively. The remaining six patients had pulmonary complications after hematopoietic stem cell transplantation (HSCT); three of the six patients had severe respiratory failure and urgent living-donor LTx was performed within six months after NTM infection. All eight patients are currently alive without clinical findings of NTM infection. Among thirteen patients with post-transplant NTM infection, 11 received cadaveric LTx. Eight of the thirteen patients had chronic lung allograft dysfunction (CLAD), though it was unclear whether NTM infection was a cause or result; four patients had received or registered for re-LTx. Subsequently, six patients died and only one is alive and free from NTM infection and CLAD. <h3>Conclusion</h3> Patients with pulmonary complications after HSCT may have higher risk of NTM infection. Pre-transplant treatment for NTM infection is associated with favorable outcomes after LTx. Postoperative NTM infection is possibly related to CLAD and difficult to manage; therefore, close follow-up is mandatory.

Pulmonary Nontuberculous Mycobacterial Infection in Infants: A Systematic Review.

Limited information and literature exist examining pulmonary infections caused by nontuberculous mycobacterial specifically in an infant population. The objective of our study was to summarize clinical characteristics and outcomes of infant patients with nontuberculous mycobacterial pulmonary infection via systematic literature review to identify common diagnostic and treatment regimens for this infection in infants. A search of MEDLINE and PubMed databases in October 2019 using MeSH search terms “infant,” “NTM,” “pulmonary,” and “Mycobacterium abscessus” yielded 139 articles. Inclusion criteria were i) English-language studies including cases and case series with ii) established nontuberculous mycobacterial pulmonary infection in iii) a patient population of infants no older than 24 months. Patients with cystic fibrosis and any study which did not contain relevant information such as infection and age were excluded. This yielded data on 37 patients extracted from 28 studies analyzed. The most common strain was Mycobacterium avium complex, isolated in 56.8% of patient diagnoses. Bronchoscopy/thoracoscopy with a subsequent culture were the most common diagnostic techniques, utilized in 64.9% of cases. Drug therapeutic treatment was utilized in 86% of cases, with a median of three drugs administered. Notable limitations of this study are the small sample size and its retrospective nature, which relies on information reported in previous case studies. Although there is limited formal clinician consensus on the treatment of NTM pulmonary infection and how it may differ in an infant population, our findings indicate an informal consensus typically involving diagnostic lung specimen culture and antibiotic therapy.

The Role of NRF2 in Mycobacterial Infection.

The incidence of pulmonary nontuberculous mycobacterial (NTM) infection is increasing worldwide, and its clinical outcomes with current chemotherapies are unsatisfactory. The incidence of tuberculosis (TB) is still high in Africa, and the existence of drug-resistant tuberculosis is also an important issue for treatment. To discover and develop new efficacious anti-mycobacterial treatments, it is important to understand the host-defense mechanisms against mycobacterial infection. Nuclear erythroid 2 p45-related factor-2 (NRF2) is known to be a major regulator of various antioxidant response element (ARE)-driven cytoprotective gene expressions, and its protective role has been demonstrated in infections. However, there are not many papers or reviews regarding the role of NRF2 in mycobacterial infectious disease. Therefore, this review focuses on the role of NRF2 in the pathogenesis of Mycobacterium tuberculosis and Mycobacterium avium infection.

The epidemiology, demographics, and comorbidities of pulmonary and extra-pulmonary non-tuberculous mycobacterial infections at a large central Florida Academic Hospital

RationaleIn the United States, non-tuberculous mycobacterium (NTM) infections are considered an important cause of morbidity and mortality, especially in people with progressive lung disease. The state of Florida has an extremely high incidence and prevalence of NTM disease which is likely a rapidly emerging infection in the state due to environmental and demographic factors. ObjectivesAdjemian et al. [1] To determine the burden of NTM disease of patients admitted to a large Central Florida academic center, Falkinham [2] to identify the most common risk factors associated with developing NTM disease in this area, and Sfeir et al. [4] to categorize antimicrobial susceptibilities and genetic resistance markers. MethodsWe conducted a retrospective case review from January 1, 2011 to December 31, 2017 in a large university-associated metropolitan hospital in west-central Florida. NTM infections were identified using TheraDoc® during the study period with the inclusion criteria of any inpatient admission, culture confirmed NTM at any site, and age ≥ 12 years. Demographic variables (including residential zip code) and comorbidity data (including solid organ transplant status, HIV status and subsequent testing results, intrinsic pulmonary disease, and cancer diagnosis of any site) were collected for each patient. Microbiologic data collected included NTM species/subspecies, anatomic location of specimen collection, antimicrobial susceptibility including minimum inhibitory concentration (MIC). All collected data were analyzed within Stata/IC14.2. Geospatial relationships between zip codes, diagnosis type, and co-morbidities were computed using Arc GIS Pro. ResultsOur results demonstrated that a substantial number of our inpatient cases with NTM were of the M. abscessus group, and with M. avium complex and M. fortuitum also representing the pathogen in numerous cases. Novel findings included compilation of the first hospital wide comprehensive NTM resistance plot to our knowledge. Our results did show a concordance with previous data with expected predominance of NTM inpatient cases in Caucasian males with pre-existing pulmonary disease, though additional work could be done with isolates within the transplant and immunosuppressed populations. ConclusionsOur data set demonstrates the most common species/subspecies of NTM infections and their associated conditions seen at our central Florida hospital, and includes an antimicrobial sensitivity analysis in toto. This could be insight into the possible prevalence of NTM in the area, and provides the foundation for future studies on both the acquisition and prevention for NTM infections in central Florida.

Nontuberculous Mycobacterial Pulmonary Infection Among Lung Transplant Recipients.

Data are limited regarding the clinical significance of nontuberculous mycobacteria pulmonary infections among lung transplant recipients. We investigated the incidence and characteristics of pulmonary nontuberculous mycobacteria infection in ourlung transplant patient population. We obtaineddata of the patients who underwent lung transplant in our center from January 1997 to March 2019. Of 690 patients, nontuberculous mycobacteria were identified in 58 patients (8.4%) over a median follow-up of 3 years. Types of species were as follows: Mycobacterium simiae (n = 24), avium complex (n = 12), abscessus (n = 9), fortuitum (n = 6), chelonae (n = 2), szulgai (n = 1), kansasii (n = 1), lentiflavum (n = 1), and undefined mycobacteria (n = 2). When we compared infections in the early versus late period posttransplant (before and after 6 months), infections with Mycobacterium simiae (16 vs 8 incidents) and Mycobacterium fortuitum (5 vs 1 incident) were more often observed within the early period, whereas most Mycobacterium abscessus (7 vs 1 incident) and Mycobacterium avium complex (9 vs 3 incidents) were observed in the later period. The median forced expiratory volume in 1 second overtime did not differ significantly between patients with and without nontuberculous mycobacteria infection (P = .29). Nontuberculous mycobacteria acquisition was significantly associated with decreased survival (relative risk of 2.41, 95% CI, 1.70-3.43; P ⟨ .001). The nontuberculous mycobacteria species isolated varied according to the time elapsed since transplant. Among lung transplant recipients, nontuberculous mycobacteria infection was associated with increased mortality but not with lung dysfunction.

Rufomycin Exhibits Dual Effects Against Mycobacterium abscessus Infection by Inducing Host Defense and Antimicrobial Activities.

Nontuberculous mycobacterial pulmonary infection is often aggravated due to antibiotic resistance issues. There is a need for development of new drugs inducing both host immune responses and antimicrobial activities. This study shows that the rufomycins 4/5/6/7 (Rufomycin 4–7), which targets ClpC1 as a subunit of caseinolytic protein complex ClpC1/ClpP1/ClpP2 of mycobacteria, exhibits a dual effect in host innate defense and in vivo antimicrobial activities against a rough morphotype of Mycobacterium abscessus (Mabs-R), a clinically severe morphotype that causes hyperinflammation. Rufomycin 4–7 treatment showed antimicrobial effects against Mabs pulmonary infection in vivo and in macrophages. In addition, Rufomycin 4–7 significantly decreased inflammation, but enhanced the autophagy/lysosomal genes through upregulation of the nuclear translocation of transcription factor EB (TFEB). Furthermore, Rufomycin 4–7 treatment effectively inhibited mitochondrial damage and oxidative stresses in macrophages during Mabs-R infection. Collectively, Rufomycin 4–7-mediated dual effects inducing both antimicrobial activities and host immune defense might confer an advantage to treatment against Mabs-R infection.