Abscessus Infection Research Articles

Outcome according to subspecies following lung transplantation in cystic fibrosis pediatric patients infected with Mycobacterium abscessus.

Mycobacterium abscessus infection has been associated with variable outcomes following lung transplantation. Mabscessus comprises three subspecies (Mabscessus subsp abscessus, Mabscessus subsp massiliense, and Mabscessus subsp bolletii). We investigated whether lung transplantation outcome in cystic fibrosis (CF) patients in a single center was related to the Mabscessus subspecies and genetic cluster. CF patients with chronic Mabscessus infection transplanted at Great Ormond Street Hospital between 2004 and 2017 were retrospectively examined. All Mabscessus isolates were identified to subspecies level by polymerase chain reaction and sequencing. Genetic cluster was determined by variable number tandem repeat profiling and whole-genome sequencing (WGS), and sequence type inferred from WGS. Thirteen patients with chronic Mabscessus infection underwent heart/lung or lung transplantation. Subspecies identification showed n=1 with Mabscessus bolletii, n=5 with Mabscessus massiliense, and n=7 with Mabscessus abscessus infection. Eight (62%) patients (one with Mabscessus massiliense and seven with Mabscessus abscessus) died post-lung transplant. The patient with Mabscessus bolletii and three patients with Mabscessus massiliense did well post-transplant. One patient with Mabscessus massiliense is receiving ongoing treatment. Dramatically worse outcomes are observed in patients infected with Mabscessus subspecies abscessus, the majority of whom were infected with ST-1 and ST-26 strains. Patients infected with other Mabcsessus strains can have acceptable outcomes.

A mouse model of pulmonary Mycobacteroides abscessus infection

There is no preclinical mouse model to investigate pulmonary Mycobacteroides abscessus (formerly Mycobacterium abscessus) infection in an immunocompetent mouse strain, especially in the context of antibiotic testing and regimen development. We developed a mouse model of pulmonary M. abscessus infection using the aerosolized route of infection that leads to an increase in bacterial burden post- implantation and develops pathology as a result. In this mouse model, treatment with corticosteroid allows for initial proliferation and sustained M. abscessus pulmonary infection and permits evaluation of efficacies of antibiotics. Administration of corticosteroids that permitted higher levels of bacterial burden in the lungs were more likely to have pathology. Treatment of mice with antibiotics administered intranasally or subcutaneously significantly reduced lung M. abscessus burden. In addition to the reference strain, independent clinical isolates of M. abscessus also readily establish infection and proliferate in the lungs of mice in this model.

Mycobacterium abscessus infection of a new tattoo in an Australian traveller returning from Bali, Indonesia.

Skin infection with atypical mycobacteria can occur following inoculation by tattooing. It may be seen in clinical practice with increasing frequency due to the popularity of tattooing among travellers. Diagnosis requires fresh tissue biopsy requested for mycobacterial culture, and treatment involves prolonged combination antimicrobial therapy guided by sensitivities.

Efflux Pumps Contribute to Intrinsic Clarithromycin Resistance in Clinical, Mycobacterium abscessus Isolates.

PurposeThe emergence of clarithromycin resistance is a challenge in treating Mycobacterium abscessus infections. Known mechanisms that contribute to intrinsic clarithromycin resistance focus on rrl gene-related mutations, but resistant clinical isolates often exhibit an inconsistent rrl genotype.Patients and MethodsIn this study, 194 clinical Mycobacterium abscessus isolates were collected from patients with lung infections and the whole genome of each isolate was sequenced. A comprehensive examination of the molecular mechanisms underlying intrinsic clarithromycin resistance was performed, combining MIC determination, comparative genome sequence analysis and qRT-PCR.ResultsOf the 194 isolates, 13 (6.7%) were clarithromycin resistant; only seven of these harbored a rrl 2270/2271 mutation. The remaining six resistant isolates did not exhibit a specific resistance-associated mutation in the clarithromycin target-site genes, rrl, rplC, rplD and rplV, or in the rrl modification gene erm(41). qRT-PCR analysis showed that the increased expression of the efflux pump genes, MAB_2355c, MAB_1409c and MAB_1846, as well as their positive regulatory gene whiB7, consistently correlated with increased clarithromycin resistance. The presence of efflux pump inhibitors significantly decreased the MIC of clarithromycin for nonsusceptible isolates, especially the intrinsic resistant isolates that exhibited no rrl 2270/2271 mutation.ConclusionThese findings indicate that efflux pumps play a prominent role in the intrinsic resistance of M. abscessus to clarithromycin, complementing other known resistance mechanisms.

Effect of Amoxicillin in combination with Imipenem-Relebactam against Mycobacterium abscessus

Infections caused by Mycobacterium abscessus are increasing in prevalence in cystic fibrosis patients. This opportunistic pathogen′s intrinsic resistance to most antibiotics has perpetuated an urgent demand for new, more effective therapeutic interventions. Here we report a prospective advance in the treatment of M. abscessus infection; increasing the susceptibility of the organism to amoxicillin, by repurposing the β-lactamase inhibitor, relebactam, in combination with the front line M. abscessus drug imipenem. We establish by multiple in vitro methods that this combination works synergistically to inhibit M. abscessus. We also show the direct competitive inhibition of the M. abscessus β-lactamase, BlaMab, using a novel assay, which is validated kinetically using the nitrocefin reporter assay and in silico binding studies. Furthermore, we reverse the susceptibility by overexpressing BlaMab in M. abscessus, demonstrating relebactam-BlaMab target engagement. Finally, we highlight the in vitro efficacy of this combination against a panel of M. abscessus clinical isolates, revealing the therapeutic potential of the amoxicillin-imipenem-relebactam combination.

Surgical management of atypical mycobacterial cervical lymphadenitis in an outbreak of odontological infection

IntroductionWe report on our experience with surgical management of nosocomial Mycobacterium abscessus cervical lymphadenitis in the setting of an epidemic linked to a dental practice in the community. MethodsThis is an observational case series of children who required surgical treatment of cervical lymphadenitis as part of multidisciplinary management of nosocomial M. abscessus infections. We describe the criteria for surgical management of cervical lymphadenitis as well as patient characteristics and outcomes. ResultsOver 1000 children undergoing pulpectomies and pulpotomies at a local dental practice with a contaminated water source were identified as potentially susceptible to atypical mycobacteria infection, identified as M. abscessus. Between August 2016 and May 2017 108 children underwent inpatient evaluation at our institution by general pediatricians and pediatric infectious disease specialists. 90 children required at least 1 surgical intervention by pediatric otolaryngology and/or oral and maxillofacial surgery (OMFS). Children were evaluated by the Pediatric Otolaryngology service if computer tomography (CT) scan of the neck demonstrated lymph nodes of at least 1.5 cm in shortest dimension or lymph nodes with central hypolucencies suspicious for infection with central necrosis. Pediatric Otolaryngology intervened on 11 patients all of whom required selective cervical lymphadenectomy with or without curettage. These patients ranged in age from 3 to 8 years; 8 were male, 6 had concurrent pulmonary nodules. Two patients underwent curettage in addition to lymphadenectomy. Five patients required at least 2 surgical interventions by Pediatric Otolaryngology. ConclusionWe found M. abscessus to be an aggressive infection requiring early cervical lymphadenectomy in select patients.

Treatment for Mycobacterium abscessus Infection Associated with Fat Grafting.

Background: Fat grafting is a standard method for soft augmentation. However, occasionally Mycobacterium abscessus infection can be seen secondary to fat grafting. The aim of this study was to report experience with and propose standard treatment. Patients and Methods: From 2006 to 2018, 12 women who had received fat grafting for facial soft augmentation in different Chinese private clinics were reviewed. Results: The patients presented with local swelling and skin ulceration. They patients received primary infusion of antibiotic agents; however, the results were poor. After being admitted to our hospital, cultures were taken and sent to the specialized examination center. Mycobacterium abscessus was diagnosed in all of the patients. According to drug sensitivity results, targeted antibiotic agent treatment was implemented for 12 months. Local proper conservative debridement was conducted as needed. When the patients were discharged from the hospital, they were advised to continual oral medication for six months. After three to nine years of follow-up, no recurrence was found. On the basis of this, a corresponding standard treatment was proposed. Conclusions: Mycobacterium abscessus infection after fat grafting should be diagnosed and treated accurately. Our experience and proposed treatment may be beneficial.

Incidence possibility of pulmonary Mycobacterium abscessus infection in an endemic area: onion diagram with overlapping analysis

Background Mycobacterium abscessus is a new emerging mycobacterial infection with drug resistance problem. An endemic area of this infection is Thailand, a tropical country in Indochina. The incidence of this infection is not well estimated. Materials and methods In the present study, the authors reappraised on the available epidemiological data in an endemic area aiming at finding incidence possibility of pulmonary M. abscessus infection. The path probability assessment was done, and the onion diagram was finally constructed. In additional, overlapping analysis was also performed. Results The incidence possibility of pulmonary M. abscessus infection in this endemic area is equal to 0.15% of overall suspected cases of nontuberculous mycobacterial infections. Conclusion In our setting, there is considerably high possibility of pulmonary M. abscessus infection among suspected cases of nontuberculous mycobacterial infections.

Outcomes of pulmonary Mycobacterium abscessus infection.

Treatment of Mycobacterium abscessus pulmonary disease (PD) is challenging with frequent side effects and uncertain rates of success. We performed a retrospective review of all patients at our center with at least one respiratory sample positive for M. abscessus between 2014 and 2019. Electronic health records were reviewed to determine factors associated with M. abscessus infection and clinical outcomes. Thirty-seven patients were identified including 24 with cystic fibrosis (CF), 10 with bronchiectasis, two with chronic obstructive PD (COPD), and one with asthma. American Thoracic Society/Infectious Diseases Society of America criteria for nontuberculous mycobacteria PD were met in 21/37 (56.8%) of cases. Evidence of Aspergillus lung disease was noted in 18 (75.0%) CF patients compared with 3 (23.1%) non-CF patients (P = 0.005). Induction therapy for M. abscessus was given to 22/37 (59.5%) patients (18/24 [75%] with CF and 4/13 [30.8%] without CF). Median duration of induction therapy was 6 weeks (range 3-12). Maintenance antibiotic therapy was prescribed to 17/22 (77.3%) of treated patients. Culture conversion was seen in 15/24 (62.5%) of CF patients compared with 3/13 (23.1%) in the non-CF group (P = 0.034). Culture conversion occurred in 10/22 (45.5%) of treated patients compared with 8/15 (53.3%) untreated patients. Three patients (8.1%) died during follow-up: one with CF and two with COPD. Culture conversion following isolation of M. abscessus from respiratory samples not only is more common in CF than in patients without CF but also frequently occurs spontaneously in both groups. Targeted treatment for M. abscessus did not clearly impact rates of culture conversion.

Effect of Coptis chinensis on Biofilm Formation and Antibiotic Susceptibility in Mycobacterium abscessus.

Mycobacterium abscessus infections are notoriously difficult to be treated and newer treatment options are required. Coptis chinensis (C. chinensis) and its main compound berberine are frequently used to treat bacterial and viral infections. In this study, the susceptibility of M. abscessus to C. chinensis extract and berberine was assessed by minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) evaluation. The effects of C. chinensis and berberine on biofilm formation and antibiotic susceptibility in M. abscessus were observed. C. chinensis at concentrations of MIC (1.5 mg/mL) and 2 × MIC (3.0 mg/mL) and berberine at ½ × MIC (0.125 mg/mL) demonstrated a strong inhibition of biofilm formation. Concentration of C. chinensis at ½ × MIC resulted in a significant reduction in MICs of trimethoprim/sulfamethoxazole (TMP/SXT), clarithromycin (CLA), and linezolid (LZD). Similarly, ½ × MIC berberine had a significant effect on the MIC reductions of nine antibiotics including TMP/SXT, CLA, and LZD. Notably, the resistance level MIC of LZD against M. abscessus was reversed to a susceptible level by treatment with either C. chinensis or berberine. Therefore, C. chinensis and berberine have the potential to produce a synergistic antimycobacterial effect, reduce biofilm formation, and decrease antibacterial resistance to LZD in M. abscessus.

Thiostrepton: A Novel Therapeutic Drug Candidate for Mycobacterium abscessus Infection.

Mycobacterium abscessus is a rapid-growing, multidrug-resistant, non-tuberculous mycobacterial species responsible for a variety of human infections, such as cutaneous and pulmonary infections. M. abscessus infections are very difficult to eradicate due to the natural and acquired multidrug resistance profiles of M. abscessus. Thus, there is an urgent need for the development of effective drugs or regimens against M. abscessus infections. Here, we report the activity of a US Food and Drug Administration approved drug, thiostrepton, against M. abscessus. We found that thiostrepton significantly inhibited the growth of M. abscessus wild-type strains, subspecies, clinical isolates, and drug-resistant mutants in vitro and in macrophages. In addition, treatment of macrophages with thiostrepton significantly decreased proinflammatory cytokine production in a dose-dependent manner, suggesting an inhibitory effect of thiostrepton on inflammation induced during M. abscessus infection. We further showed that thiostrepton exhibits antimicrobial effects in vivo using a zebrafish model of M. abscessus infection.

Mycobacterium abscessus, an Emerging and Worrisome Pathogen among Cystic Fibrosis Patients.

Nontuberculous mycobacteria (NTM) have recently emerged as important pathogens among cystic fibrosis (CF) patients worldwide. Mycobacterium abscessus is becoming the most worrisome NTM in this cohort of patients and recent findings clarified why this pathogen is so prone to this disease. M. abscessus drug therapy takes up to 2 years and its failure causes an accelerated lung function decline. The M. abscessus colonization of lung alveoli begins with smooth strains producing glycopeptidolipids and biofilm, whilst in the invasive infection, “rough” mutants are responsible for the production of trehalose dimycolate, and consequently, cording formation. Human-to-human M. abscessus transmission was demonstrated among geographically separated CF patients by whole-genome sequencing of clinical isolates worldwide. Using a M. abscessus infected CF zebrafish model, it was demonstrated that CFTR (cystic fibrosis transmembrane conductance regulator) dysfunction seems to have a specific role in the immune control of M. abscessus infections only. This pathogen is also intrinsically resistant to many drugs, thanks to its physiology and to the acquisition of new mechanisms of drug resistance. Few new compounds or drug formulations active against M. abscessus are present in preclinical and clinical development, but recently alternative strategies have been investigated, such as phage therapy and the use of β-lactamase inhibitors.

Medical management of atraumatic Mycobacterium abscessus cutaneous infection: A case report

Treatment for cutaneous infection from Mycobacterium abscessus is fraught with poorly established evidence. Given its antibiotic multi-resistance, surgical intervention is often recommended. We report a case of cutaneous M. abscessus infection that was successfully managed with medical therapy alone. A 55-year-old immunocompetent woman from the Bellarine peninsula in Victoria, Australia presented to our hospital with a 2-week history of a non-healing ulcer on her left forearm. The patient had no history of trauma or procedures to the skin. On presentation, the patient had a punch biopsy, which was culture positive for M. abscessus. The isolate was susceptible to clarithromycin and amikacin, had intermediate susceptibility to ciprofloxacin, cefoxitin and linezolid and was resistant to doxycycline, imipenem, cotrimoxazole and moxifloxacin. The tigecycline MIC was 0.25 μg/ml. The patient received a total of 12 weeks of oral clarithromycin 500 mg twice daily, 4 weeks of intravenous amikacin 500 mg daily, 6 weeks of intravenous tigecycline 100 mg over 24 hours via Baxter pump, and 4 weeks of oral clofazimine 100 mg daily. The patient made a good clinical recovery and had her medical therapy ceased after 12 weeks. M. abscessus cutaneous infection in an immunocompetent individual without antecedent trauma or surgery is rare. Our case illustrates the successful treatment of a deep M. abscessus cutaneous ulcer with relatively short duration macrolide-based antibiotic therapy without any surgical intervention.

Mycobacterium abscessus infection in the stomach of patients with various gastric symptoms.

Development of gastric diseases such as gastritis, peptic ulcer and gastric cancer is often associated with several biotic and abiotic factors. Helicobacter pylori infection is such a well-known biotic factor. However, not all H. pylori-infected individuals develop gastric diseases and not all individuals with gastric diseases are infected with H. pylori. Therefore, it is possible that other gastric bacteria may contribute to the formation and progression of gastric disease. The aim of this study was to isolate prevalent gastric bacteria under microaerobic condition and identify them by 16S rRNA gene sequence analysis. Analysis of gastric biopsies showed infection of Mycobacterium abscessus (phylum Actinobacteria) to be highly prevalent in the stomachs of subjects included. Our data show that of 129 (67 male and 62 female) patients with gastric symptoms, 96 (51 male and 45 female) showed the presence of M. abscessus in stomach tissues. Infection of M. abscessus in gastric epithelium was further confirmed by imaging with acid fast staining, immunohistochemistry and immunofluorescence. Our imaging data strongly suggested that M. abscessus is an intracellular colonizer residing inside the gastric epithelial cells rather than in macrophages. Additionally, phylogenetic analysis of the mycobacterial hsp65 gene showed that the nearest match to the M. abscessus strains isolated from our study subjects is the M. abscessus strain ATCC 19977. Surprisingly, the subjects studied, the prevalence of M. abscessus infection in stomach is even higher than the prevalence of H. pylori infection. This, to the best of our knowledge, is the first study showing the colonization of M. abscessus in human gastric mucosa among patients with various gastric symptoms. This study could provide usher in a new opportunity to understand the role of less studied gastric bacteria in the development of gastric diseases.

Atypical Mycobacterial Infections After Plastic Surgery Procedures Abroad: A Multidisciplinary Algorithm for Diagnosis and Treatment.

The recent rise in medical tourism, especially for cosmetic procedures, has been mirrored by an increase in the incidence of infections with Mycobacterium abscessus, which is an atypical mycobacterium that is ubiquitous in aquatic environments. M. abscessus soft tissue infections arise from the use of improperly sterilized water and surgical equipment during surgical procedures, and these infections have devastating consequences if not promptly treated. M. abscessus infections are notoriously difficult to diagnose and properly treat, and therefore, we illustrate a typical case presentation and provide a comprehensive diagnostic and treatment algorithm. Of the patients who have presented to our hospital for treatment of cutaneous M. abscessus infections, a representative patient's story was included to illustrate the typical presentation and treatment timeline. The current literature on M. abscessus infections was reviewed, and this literature and the clinical experience of our plastic surgery and infectious disease teams were used in the creation of a diagnostic and treatment algorithm for M. abscessus infections. M. abscessus infections can have an incubation period of months, and the classic presenting signs include purulent drainage, violaceous nodules, and subcutaneous abscesses at the site of a recent surgery. A key finding is persistence of the infection despite debridement and empiric antibiotic treatment. Cultures grown on mycobacterial-specific growth media are considered the diagnostic criterion standard, but high clinical suspicion is enough to warrant the initiation of treatment. Treatment itself consists of surgical drainage and debridement in combination with multidrug antibiotic regimens that typically include amikacin, a macrolide, and a carbapenem or cephalosporin antibiotic, with the option for macrolide and fluoroquinolone maintenance therapy. M. abscessus cutaneous infections present with unique history and physical examination findings and often require complex diagnostic workups and treatment plans. Increased provider awareness of the management and potential complications of M. abscessus is crucial to the improvement patient outcomes, as is a multidisciplinary approach that incorporates primary care providers, pathologists, plastic surgeons, and infectious disease specialists.

1360. Disseminated Mycobacterium abscessus Infections in Patients with Neutralizing Anti-interferon-gamma Autoantibodies Treated with Rifabutin-based Combination Regimens

BackgroundThis prospective study aimed to describe the treatment and safety outcomes of rifabutin-based combinations which has been shown to be synergistic in vitro, for patients with refractory M. abscessus infections and neutralizing anti-IFNγ antibodies.MethodsPatients failing at least two standard macrolide-based regimens were recruited from hospitals across Taiwan since August 2017. They received rifabutin (RFB > 300 mg/day) initially with azithromycin (AZR 500 mg/day) and at least one parenteral agent and were monitored thereafter clinically on a monthly basis and by 3–6 monthly PET-CT imaging.ResultsOf 12 referred patients, only four had complete evaluations. The median age was 41 years and follow-up duration was 543 (range 307–668) days. All patients had lung and lymph node disease, two also had liver, bone and joint involvements and all were HLA-DR 16:02, HLA-DQ 05:02 positive. Prior to starting RFB–AZR, they had received at least four successive antimycobacterial regimens, but showed progression of existing lesions (2) or new lesions (2). Following RFB–AZR, all four patients experienced adverse reactions, including reactive dermatoses (2), fevers (2), leukopenia (2), thrombocytopenia (1), hearing loss (1), acute kidney injury (1), which necessitated withdrawal of rifabutin (4), short-term steroid use (2), and replacement of tenofovir with entecavir for chronic hepatitis B (1). All patients recovered fully from these adverse effects. Rifabutin was successfully restarted on first attempt (3) and on third attempt (1). The longest symptom-free interval on RFB–AZR was 331 days and the lowest maintenance dose was RFB 150–AZR 250 thrice weekly. Follow-up PET-CT confirmed good resolution of previous hot spots (mean SUVmax −4.5) except for the patient who did not tolerate RFB 300 due to fever and nausea on the first re-challenge, whose PET-CT detected a slight increase in mean SUVmax +0.6 and was hospitalized for dry cough on daily AZR–ciprofloxacin. The latter eventually tolerated a lower daily dose RFB 150–AZR 250 and became asymptomatic.ConclusionRifabutin is an oral agent that can be effectively combined with azithromycin in long-term maintenance regimens against M. abscessus in immunodeficient adults. Adverse effects are frequent early on; however, rechallenge appears to be safe and outcomes favorable. Disclosures All authors: No reported disclosures.

PRESENTATION OF MYCOBACTERIUM ABSCESSUS INFECTION FOLLOWING A SARCOIDOSIS DIAGNOSIS: A CASE REPORT

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Sarcoidosis is an idiopathic, multiorgan, inflammatory disease characterized by the presence of noncaseating granulomas. Although mycobacterial infection has long been a candidate as a causative agent in sarcoidosis, only recently has strong evidence supported a causal connection. Mycobacterium abscessus is a rapidly growing mycobacterium (RGM), found worldwide in the environment. It is increasingly being recognized as a cause of human disease, including pulmonary infections. Clinical features of progressive RGM lung disease include bilateral lung involvement and fibrocavitary disease. Here, we describe a case of Mycobacterium abscessus infection detected two years after sarcoidosis. CASE PRESENTATION: A 63 year old Chinese female, who worked as a farmer, presented with episodes of hemoptysis for 33 years, which was treated empirically with azithromycin on multiple occasions, resulting in good response according to the patient. She sought medical advice in the United States several times for the past 5 years. Workup during that period included: Quantiferon, ANA, ANCA, Anti-GBM, which were negative, chest CT remarkable for diffuse tree-in-bud opacities in the left lung, bronchoscopy with bronchoalveolar lavage (BAL) and pathology demonstrating noncaseating granulomas. She was started on steroids resulting in resolution of fever and hemoptysis. The patient stopped steroids and was lost to follow up. She remained asymptomatic until two years later when hemoptysis recurred. During that time, she was taking antibiotics from China. Repeat chest CT showed several scattered nodular and cavitary densities throughout the left lower lobe in a tree-in-bud morphology (Figure 1). Repeat rheumatological, vasculitis, and fungal panels were negative. Quantiferon TB Gold and MTB PCR were negative. Based on these results, as well as the previous biopsy demonstrating noncaseating granuloma, and the previous response on steroids, she was restarted on high dose steroids. Chest CT repeated 3 days after steroids demonstrated decrease in size and number of the pulmonary nodules. Bronchial washings and BAL samples were positive for M. abscessus. Steroids were tapered, and she was referred to infectious disease for treatment of pulmonary M. abscessus. She received Doxycycline with complete resolution of her symptoms. DISCUSSION: Although the patient's clinical and CT findings were not typical for sarcoidosis, the histopathology and improvement with steroids supported the diagnosis. However, noncaseating granulomas are nonspecific; as it can be seen in various conditions. The histological similarity between sarcoidosis and atypical mycobacterial infection raises the possibility that this patient’s Mycobacterial infection had previously evaded detection. CONCLUSIONS: Mycobacterial infection should be investigated in all patients with sarcoidosis as it could be a causative agent an infection that evaded detection. Reference #1: James DG, Sharma OP. From Hutchinson to now: a historical glimpse. Current opinion in pulmonary medicine. 2002;8(5):416-23. Reference #2: Brownell I, Ramirez-Valle F, Sanchez M, Prystowsky S. Evidence for mycobacteria in sarcoidosis. American journal of respiratory cell and molecular biology. 2011;45(5):899-905. Reference #3: Primm TP, Lucero CA, Falkinham JO, 3rd. Health impacts of environmental mycobacteria. Clinical microbiology reviews. 2004;17(1):98-106. DISCLOSURES: No relevant relationships by Meily Arevalo, source=Web Response No relevant relationships by Cinthya Carrasco Barcenas, source=Web Response My spouse/partner as a Speaker/Speaker's relationship with Salix Please note: $1001 - $5000 Added 03/13/2019 by Ebtesam Islam, source=Web Response, value=Speaker fee No relevant relationships by John Makram, source=Web Response No relevant relationships by Haneen Mallah, source=Web Response No relevant relationships by Ximena Solis, source=Web Response No relevant relationships by Wasawat Vutthikraivit, source=Web Response

In silico and in vitro evaluation of tetrahydropyridine compounds as efflux inhibitors in Mycobacterium abscessus

Herein, we evaluated tetrahydropyridine (THP) compounds (NUNM) as antimicrobials and inhibitors of the efflux mechanism in M. abscessus. subsp. abscessus. The modulation factor (MF) of efflux inhibitors was calculated from the minimum inhibitory concentrations (MICs) of amikacin (AMI), ciprofloxacin (CIP) and clarithromycin (CLA) in the absence and presence of subinhibitory concentrations of the NUNM compounds and canonical inhibitors carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and verapamil (VP). The kinetics of the intracellular accumulation of the fluorimetric substrate ethidium bromide (EtBr) was evaluated and calculated by the relative final fluorescence (RFF). In addition, molecular modeling simulations for the MmpL5 and Tap efflux transporters with ligands (CLA, NUNM, CCCP, VP and EtBr) were performed to better understand the efflux mechanism. We highlight the NUNM01 compound because it reduced the MICs of AMI, CIP and CLA by 4-, 4- and 16-fold, respectively, had the highest effect on EtBr accumulation (RFF = 3.1) and showed a significant in silico affinity for the evaluated proteins in docking simulations. Based on the analyses performed in vitro and in silico, we propose that NUNM01 is a potential pharmacophore candidate for the development of a therapeutic adjuvant for M. abscessus infections.

Safety and Tolerability of Clofazimine in a Cohort of Children With Odontogenic Mycobacterium abscessus Infection.

Mycobacterium abscessus infections can be challenging to treat. Clofazimine has excellent in vitro activity against M abscessus, but reports of its use, particularly in children, have been limited. In this study, clofazimine was given to 27 children during an outbreak of odontogenic mycobacterial infections and seemed to be well tolerated as part of a multidrug regimen.

Outcomes in Lung Transplant Recipients With Mycobacterium abscessus Infection: A 15-Year Experience From a Large Tertiary Care Center

BackgroundMycobacterium abscessus (M abscessus) infection is a serious complication post–lung transplant (LTx). We examined determinants of outcomes in LTx recipients infected with M abscessus. MethodsElectronic records of all patients who underwent LTx in a single transplant center between 2000 and 2015 were screened for isolation of M abscessus before or after LTx. ResultsTwenty-six cases of M abscessus isolation were identified. Twenty-four had M abscessus isolation post-LTx. Two had M abscessus isolated from a surgical site, while the others were pulmonary isolates. Out of these 22 with pulmonary isolates, 12 had clinical disease. In 73% of patients, treatment had to be temporarily held or switched due to intolerance and toxicity. There was a statistically significant worsening in survival in those who developed clinical disease compared to matched controls. Among the 12 patients with clinical pulmonary disease, use of clofazimine was significantly associated with a favorable outcome. Six patients had M abscessus isolation pretransplant. Four developed M abscessus recurrence at a median of 2 months post-LTx. Two recurrences were surgical site infections, and 2 were pulmonary infections. ConclusionM abscessus infection is difficult to treat as tolerance to medications used is poor. M abscessus pneumonia is associated with worse survival post-LTx. Use of clofazimine is associated with 1-year infection-free survival.