Avium Complex Research Articles

Antibiotic Resistance in Mycobacterium Tuberculosis and Non-Tuberculous Mycobacteria

Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacteria (NTM) antibiotic resistance presents an important challenge to the treatment of mycobacterial infections. The therapeutic approaches are complicated by the resistance of both MTB and NTM to a variety of antibiotics. Resistance to first-line drugs such as isoniazid, rifampicin, ethambutol, and streptomycin has been consistently increasing in MTB, underscoring the necessity of effective treatment strategies. Conversely, the necessity of species-specific treatment regimens is underscored by the high resistance rates of NTM species, such as Mycobacterium avium complex, M. kansasii, and M. abscessus complex, to commonly used anti-tuberculosis pharmaceuticals. A combination of intrinsic and acquired factors are involved in the mechanisms of antibiotic resistance in these mycobacteria. Features such as biofilm formation, thick cell walls, and reduced drug uptake are responsible for intrinsic resistance in NTM, whereas acquired resistance can develop as a result of protracted antibiotic exposure. Understanding these resistance mechanisms is essential for the development of new therapies and the prevention of the increasing prevalence of drug resistance in mycobacterial infections. The significance of continuous surveillance, species-specific treatment protocols, and the development of novel antimicrobial agents to effectively manage mycobacterial diseases is emphasized by the prevalence of antibiotic resistance in MTB and NTM. This review article focuses on the molecular mechanisms that have resulted in the development of resistance in both MTB and NTMs, as well as the extent to which various classes of antimycobacterial drugs act.

The Long and Winding Road: Three-year Mortality Following Prescription of Multi-drug Antibiotic Treatment for Mycobacterium avium complex Pulmonary Disease in United States Medicare Beneficiaries with Bronchiectasis

Abstract Background/Aims Although increased mortality has been reported among people with Mycobacterium avium complex pulmonary disease (MAC-PD), data are limited on survival associated with various antibiotic regimens used to treat MAC-PD. We conducted a comparative analysis of 3-year mortality in Medicare beneficiaries with bronchiectasis using various MAC-PD regimens. Methods We included Medicare beneficiaries >65 years with bronchiectasis (01/2006–12/2014). We limited our cohort to new MAC-PD therapy users. MAC-PD therapy was defined as ≥60-day prescriptions for a macrolide plus ≥1 one other MAC-PD antibiotic. Guideline based therapy (GBT) included a macrolide, ethambutol +/- rifamycin. Using Cox proportional hazard models, we calculated adjusted hazard ratios (aHR) for death up to 3 years after therapy start between the following groups: 1) 2007 GBT vs. non-GBT; 2) 2020 GBT vs. non-GBT; and 3) macrolide-ethambutol-rifamycin (3-drug) vs. macrolide-ethambutol (2-drug). Results We identified 4,820 new MAC-PD therapy users, of whom 866 (17.9%) were deceased within 3 years of therapy initiation. Of 3,040 (63.1%) beneficiaries prescribed 2007 GBT, 472 (15.5%) were deceased by 3 years, compared to 394 (22.1%) of 1,780 (36.9%) prescribed non-GBT (aHR 0.82 [95%CI 0.72, 0.94]). We observed a similar trend for 2020 GBT vs non-GBT (aHR 0.81 [95%CI 0.70, 0.94]). Three-year-mortality was similar between those starting 3-drug vs. 2-drug regimens (aHR 0.89 [95%CI 0.74, 1.08]). Conclusions Among Medicare new MAC-PD therapy users, 3-year-mortality was higher in those prescribed non-GBT regimens compared to GBT regimens. Whether this finding suggests improved efficacy of GBT and/or differential characteristic of those using non-GBT regimens deserves further study.

Mycobacterium avium complex (MAC) infection in severely immunocompromised people living with HIV: Findings from a five-year cohort.

We sought to clarify the current incidence, risk factors and symptoms of disseminated Mycobacterium avium complex (dMAC) infection in admitted people living with HIV in a hospital in the Southeast of Spain. 5-years observational, retrospective and single-centre study. Demographic, clinical and analytical variables, along with microbiological, treatment and follow-up were collected. Five cases of dMAC infection in severely immunocompromised people living with HIV people living were found. dMAC was diagnosed in 22.7% of patients under 100 CD4. All patients presented with fever and clinical manifestations of pneumonia, lymphadenopathy, or gastrointestinal symptoms. Despite low CD4 levels and high viral loads in some cases, primary prophylaxis had not been previously administered. Until 2018, U.S. American guidelines recommended antimycobacterial prophylaxis for patients with low CD4 cell counts, a practice not adopted in Europe. Untreated dMAC infection is associated with high morbidity and mortality rates. dMAC infection represents a prevalent disease in severely immunosuppressed people living with HIV. dMAC requires a high index of suspicion in this population, in order to perform mycobacterial cultures from different samples.

Optimal incubation duration of liquid cultures for assessing culture negative conversion in patients with Mycobacterium avium complex and Mycobacterium abscessus pulmonary diseases.

Mycobacterial liquid culturing typically requires six weeks or longer, primarily because of the slow growth rate of Mycobacterium tuberculosis. This study aimed to evaluate the potential of shortening the duration of mycobacterial liquid culturing in healthcare settings with high prevalence rates of non-tuberculous mycobacteria. We retrospectively analyzed the relationship between mycobacterial species and time to positive testing of liquid cultures from sputum samples using the Mycobacteria Growth Indicator Tube system over a 3.5-year period beginning in July 2020 at a university hospital in Japan. We analyzed 15,147 sputum culture samples and found a 1.1% positivity rate for Mycobacterium tuberculosis complex, while the rates for Mycobacterium avium complex and Mycobacterium abscessus were 17.6% and 2.1%, respectively. The median time to positivity was 17 days for Mycobacterium tuberculosis complex, 9 days for Mycobacterium avium complex, and 4 days for Mycobacterium abscessus. Comparing a 4-week culture period with an eight-week period, the positivity rates for Mycobacterium avium complex and Mycobacterium abscessus were 97.0% and 99.4%, respectively. In settings with a high incidence of non-tuberculous mycobacteria, the basic liquid culturing period can be safely shortened to 4 weeks without significantly compromising detection sensitivity, except for the samples that are highly suspected to contain tuberculosis, extremely slow-growing mycobacteria, smear-positive, or nucleic acid amplification testing positive.

Relationship between clarithromycin MICs and treatment responses in Mycobacterium avium complex pulmonary disease.

Mycobacterium avium complex pulmonary disease (MAC-PD) is a chronic lung condition with rapidly increasing prevalence worldwide. Macrolides like azithromycin and clarithromycin are the backbone of long-term antibiotic therapy for progressive MAC-PD. The impact of minimum inhibitory concentrations (MICs), especially within the susceptible range, for macrolides on treatment responses remains unclear. We analyzed adult patients who started treatment for MAC-PD between 1 March 2009 and 1 March 2022 at Seoul National University Hospital. Patients were categorized into four groups according to the clarithromycin MICs of their causative strains at treatment initiation. Logistic regression was employed to evaluate the impact of clarithromycin MICs on the microbiological cure rate. Companion drugs and their MICs, alongside clinical characteristics like age, sex, body mass index, cavity presence, acid-fast bacilli smear positivity, causative species, and erythrocyte sedimentation rate were adjusted in multivariable analysis. Four-hundred thirty-six patients (median age, 65 years; 34% men) were included. Microbiological cure rates were 51.8%, 51.9%, 50.0%, and 18.2% for patients with clarithromycin MICs ≤0.5, 1-2, 4-8, and ≥32 µg/mL, respectively (P=0.181). No significant differences in microbiological cure rates were observed across varying levels of clarithromycin MICs within the susceptible range (≤8 µg/mL). Relative to patients with clarithromycin-susceptible strains, patients with MICs ≥32 µg/mL had an odds ratio of 0.25 for achieving microbiological cure (95% confidence interval, 0.06-1.07; P=0.06). Treatment responses were comparable among patients with strains having clarithromycin MICs within the susceptible range, but were likely to be worse for patients with strains having MICs ≥32 µg/mL.

Long-term clinical course of Mycobacterium avium complex pulmonary disease patients with treatment failure.

Despite guideline-based therapy, some patients with Mycobacterium avium complex pulmonary disease (MAC-PD) experience treatment failure. We analyzed the clinical courses of 271 patients with treatment-refractory MAC-PD who discontinued therapy after at least 12 months. Patients were categorized into two groups-the retreatment group, who resumed antibiotics due to clinical or radiological deterioration, and the stable group, who did not require antibiotics. Of the study patients, 138 (51%) were in the retreatment group, whereas 133 (49%) were in the stable group. In the multivariate analysis models, an elevated erythrocyte sedimentation rate (adjusted hazard ratio [aHR] =1.01), the presence of a cavity (aHR = 1.75), and the number of lobes affected by bronchiectasis (aHR = 1.21) were associated with the need for retreatment. Our data indicated that approximately 50% of the patients with refractory MAC-PD who discontinued antibiotics eventually required retreatment, which was influenced by the extent of lung destruction or inflammation. These findings can aid in determining treatment strategies for patients with refractory diseases.

A histopathological study in road-killed European badgers (Meles meles) from the English midlands with isolation of novel non-tuberculous atypical mycobacteria

European badgers (Meles meles) play an important role in the epidemiology of bovine tuberculosis (caused by Mycobacterium bovis) in England, but little is known about the prevalence of atypical mycobacteriosis. Badgers are also known to be infected by other infectious agents, and the relationship between mycobacteriosis and concomitant infections needs further investigation. Overall, 88 badger carcasses from the Midlands of England collected between July 2016-August 2017 were selected for histopathological examination based on the degree of autolysis (mild), mycobacterial culture results and a balanced sex ratio. Mycobacteria were cultured from 44 badgers, of which 31 were mycobacteria belonging to the M. tuberculosis complex (MTBC) (based on IS6110 PCR and Hsp64 and/or rRNA PCR and sequencing) and 13 were non-tuberculous atypical mycobacteria (NTM). Mycobacteria were not cultured from the remaining 44 animals. Histologically, the most common findings were silica-laden macrophages (85%), granulomas (53%), sarcocystosis (47%), nephritis (31%), portal/periportal hepatitis (26%), ulcerative dermatitis (18%). Culturable mycobacteriosis was associated with higher prevalence of granulomas (p < 0.001) and lower prevalence of hepatitis (p = 0.003). NTM (M. nonchromogenicum, M. avium complex, M. hassiacum, M. malmoense, M. vaccae.) infections were associated with granulomatous pneumonia, and M. malmoense was associated with pyogranulomatous and ulcerative dermatitis. In conclusion, this study describes, for the first time, histological lesions associated with NTM in badgers, the histomorphology of which was similar to those caused by MTBC. In addition, the negative relationship between mycobacteriosis and periportal hepatitis may indicate a complex relationship between mycobacteriosis and other diseases, as previously observed with tuberculosis.

Abnormally high plasma concentrations of M-4, the active metabolite of edoxaban, at the onset of acute kidney injury in a patient receiving rifampin and clarithromycin: a case report

BackgroundEdoxaban, the only factor Xa inhibitor with active metabolites, is metabolized by carboxylesterase-1 to its main active metabolite, M-4, which is a substrate of organic anion transporting polypeptide 1B1 (OATP1B1) and is excreted in bile and urine. Because the area under the plasma concentration–time curve ratio of M-4 to parent compound is typically less than 10% in healthy subjects, M-4 is generally considered to exhibit negligible antithrombotic activity in patients treated with edoxaban. However, we identified a case in which drug interactions and kidney impairment led to a substantive increase in plasma M-4 concentrations.Case presentationThis case report involved a 68-year-old man with pancreatic cancer who was orally administered edoxaban tablets for prevention of thrombus formation in non-valvular atrial fibrillation, in addition to rifampin and clarithromycin (CAM) for treatment of mycobacterium avium complex lung disease. These medications were temporarily discontinued for a pancreaticoduodenectomy but were resumed 8 days post-surgery (POD8). On POD9, the patient developed acute kidney injury, and the trough concentrations of edoxaban and M-4 were 131.1 ng/mL and 115.8 ng/mL, respectively (M-4 ratio: 88.3%). On POD11, the M-4 trough concentration and M-4 ratio increased to 216.2 ng/mL and 186.2%, respectively. The plasma concentration of coproporphyrin-I, an endogenous biomarker of OATP1B1 activity, increased during this period.ConclusionsThis case suggests that in patients with impaired renal function taking edoxaban, co-administration of carboxylesterase-1 inducers such as rifampin and/or OATP1B1 inhibitors such as rifampin or clarithromycin may increase plasma concentrations of M-4 to clinically non-negligible levels.

Comparative analysis of non-tuberculous mycobacterial lung disease and lung colonization: a case-control study

BackgroundNon-tuberculous mycobacteria (NTM) are common opportunistic pathogens, and the most common infection site is lung. NTM are found commonly in the environment. Many patients have NTM lung colonization (NTM-Col). NTM lung disease (NTM-LD) have no specific sympotms, though it is hard to differentiate NTM-LD and NTM-Col under this circumstance. The aim of this study is to explore the differences between NTM-LD and NTM-Col for future clinical diagnosis and treatment.MethodsWe retrospectively enrolled patients who had a history of NTM isolated from respiratory specimens in Peking Union Medical College Hospital (PUMCH) from January 1st, 2013 to December 31st, 2022. Patients were classified into NTM-LD group and NTM-Col group. Demographic characteristics, clinical manifestations, laboratory tests and imaging findings of the two groups were compared. Comparative analysis was also performed in peripheral blood lymphocyte subsets among three groups.ResultsA total of 127 NTM-LD patients and 37 NTM-Col patients were enrolled. Proportion of patients with bronchiectasis was higher in NTM-LD group than in NTM-Col group (P = 0.026). Predominant NTM isolates were Mycobacterium avium complex (MAC). NTM-LD group had a higher proportion of Mycobacterium intracellulare (P = 0.004). CD4+ T cells counts was lower in NTM-LD group (P = 0.041) than in NTM-Col group. Imaging finding of bronchiectasis (P = 0.006) was higher in NTM-LD group than in NTM-Col group. Imaging findings of bronchiectasis (OR = 6.282, P = 0.016), and CD4+ T cell count (OR = 0.997, P = 0.012) were independent associated factors for differential diagnosis between NTM-LD and NTM-Col.ConclusionNTM isolates from both NTM-LD and NTM-Col patients were predominantly MAC, with a higher Mycobacterium intracellulare isolation rate in NTM-LD group. Imaging findings of bronchiectasis and lower peripheral blood CD4+ T cell count may be helpful to separate the diagnosis of NTM-LD from NTM-Col.

Assays for Assessing Mycobacterium avium Immunity and Evaluating the Effects of Therapeutics.

In Europe and North America, the prevalence of pulmonary nontuberculous mycobacteria (NTM) is increasing. Most pulmonary NTM infections are caused by the Mycobacterium avium complex (MAC). Sadly, the treatment of pulmonary MAC is suboptimal with failure rates ranging from 37% to 58%. Therefore, there is a need to develop new therapeutics. Developing new immunotherapies and studying their interaction with standard or new drugs requires reliable assays. Four different assays including CFSE-based flow cytometry, in vitro protection assays, IFN-γ ELISPOT, and murine infection models were optimized using a reference strain of MAC (ATCC 700898) to help with the development of immunotherapies for MAC. Expansion of proliferating and IFN-γ producing human T cells is optimal after 7 days of stimulation with MAC at a multiplicity of infection (MOI) of 0.1, achieving a stimulation index of 26.5 ± 11.6 (mean ± SE). The in vitro protection assay for MAC works best by co-culturing T cells expanded for 7 days with MAC (MOI 1)-infected autologous macrophages. Aerosol MAC infection of mice allows measurement of the effects of the BCG vaccine and clarithromycin. IFN-γ ELISPOT assays with live MAC (MOI 3) stimulation of splenocytes from mice immunized with BCG help identify differences between unimmunized mice and mice immunized with BCG. In conclusion, multiple assays are available for use to identify MAC-specific effector T cells, which will help in the development of new therapeutics or vaccines against pulmonary MAC.

Exploring the pangenome landscape of Mycobacterium avium complex: insights into phylogeny and lifestyle

Exploring the pangenome landscape of Mycobacterium avium complex: insights into phylogeny and lifestyle

Demographic, Behavioural, and Biological Factors Seen in Men Who Have Sex with Men with Salmonella spp.: A Systematic Review

Background: The sexual transmissibility of enteric pathogens, including Salmonella spp., has been described in men who have sex with men (MSM). However, the factors seen in MSM with Salmonella spp. are poorly understood. Method: We aimed to systematically review the literature to explore any factors seen in MSM with Salmonella spp. (MSM). We searched six databases—Medline, PubMed, CINAHL, Embase, Emcare, and Global Health—in April 2024 for manuscripts which contained primary peer-reviewed data in English and the measurement of any risk factors observed in MSM with Salmonella spp. This review was registered on PROSPERO (CRD42023472864). Results: Eleven manuscripts were included in the final review and highlighted demographic (living with HIV), behavioural (oral–anal sex, receptive and penetrative anal sex, hand licking to stimulate their partner, group sex, non-condom use), and biological (co-infection with CMV, Mycobacterium avium complex, Strongyloides stercoralis, Blastocystis hominis, Klebsiella spp. Herpes simplex virus, Cytomegalovirus, Cryptosporidium, Histoplasmosis, Shigella spp.; previous infection with Treponema pallidum, Neisseria gonorhoeae, Chlamydia trachomatis and hepatitis B; and antimicrobial treatment failure) factors seen in MSM with Salmonella spp. Conclusion: Despite a limited number of manuscripts and individuals, this review highlighted some potential demographic, behavioural, and biological factors implicated in the transmission of Salmonella spp. in MSM. These data will provide insights for future guidelines, public health control strategies, and research.

Facial cutaneous tuberculosis infected by non-tuberculous mycobacteria

BackgroundCutaneous infections caused by non-tuberculous mycobacteria (NTM) are extremely rare, particularly when they are localized to the facial area. This condition presents significant diagnostic challenges due to its unusual presentation and the need for precise microbiological identification.Case PresentationA two-year-old male patient presented with a progressively enlarging reddish-brown mass on the left side of his face. Despite the absence of systemic symptoms, the lesion’s growth warranted investigation due to its growth. Ultrasonography showed a hypoechoic mass in the dermis, indicating an underlying abscess. The subsequent aspiration resulted in pale yellow pus, which upon testing and culture, confirmed the presence of Mycobacterium avium complex infection, a species of NTM. This case exemplifies the synergy between imaging modalities and microbiological analysis, highlighting the crucial role of both in achieving favorable clinical outcomes in patients with suspected cutaneous NTM infections. Ultrasound can expedite diagnosis, improve treatment planning, and enhance patient care by enabling targeted interventions and monitoring response to therapy in these scenarios. However, it is the combination of pathogen-specific diagnostics that ensures accurate etiological attribution and appropriate antimicrobial stewardship.ConclusionAlthough rare, facial cutaneous infections caused by NTM still deserve thorough investigation to determine the exact cause. Ultrasound is used to identify cutaneous lesions, measure their extent, and guide surgical procedures. The ultimate diagnosis is based on microbiological confirmation.

Variability of macrolide-resistant profile in Mycobacterium avium complex pulmonary disease.

This single-center retrospective study aimed to analyze the variability of macrolide resistance (MR) in 68 patients with Mycobacterium avium complex pulmonary disease. Among 25 patients treated without macrolides, 13 (52%) reverted to macrolide-susceptible (MS) profiles. Only one (2%) of 43 patients who continued macrolide treatment showed this change. We compared 30 MR isolates with recent specimens. Among them, seven shifted to MS (five attributed to clonally related strains; two resulting from reinfection or polyclonal infection).

7660 Navigating Hypercalcemia: MAC Treatment Hurdles and the Unforeseen Impact of Vitamin D Supplementation

Abstract Disclosure: S. Noguchi: None. S. Lai: None. A. Rajpal: None. Introduction: Hypercalcemia is a recognized complication in granulomatous disorders such as sarcoidosis and tuberculosis, resulting from increased 1 alpha-hydroxylase activity in macrophages leading to excessive conversion to 1,25(OH)2 vitamin D (calcitriol). Mycobacterium avium complex (MAC) is an infectious granulomatous disease often suspected in immunocompromised individuals, including those with human immunodeficiency virus (HIV). Additionally, vitamin D deficiency is prevalent in the general population, prompting supplementation. We hereby present a patient with advanced HIV and disseminated MAC who developed severe calcitriol-induced hypercalcemia in the setting of high dose vitamin D supplementation. Case description: A 48-year-old male with advanced HIV (CD4 count &amp;lt;20 cells/mm^3) presented for evaluation of abdominal pain and constipation, and was found to have severe hypercalcemia of 14.8 mg/dL. Five months prior, he had restarted anti-retroviral therapy (ART) after having been out of care for over a year and was diagnosed with disseminated MAC for which he was on azithromycin and ethambutol. Cultures drawn during this admission were negative for MAC. Hypercalcemia was possibly due to paradoxical immune reconstitution inflammatory syndrome (IRIS) and with appropriate management his calcium level rapidly normalized to 9.7 mg/dL and remained stable until the recent admission. He represented one year later with a calcium level of 13.8 mg/dL with suppressed parathyroid hormone levels, which was refractory to bisphosphonate therapy, therefore was empirically initiated on dexamethasone. By day 4, his calcium levels improved significantly and was discharged on a taper regimen. Cultures collected this admission later revealed ongoing MAC infection, which raised concern for treatment failure and calcitriol-induced hypercalcemia. Calcitriol levels were elevated at 105 pg/mL, which further supported this hypothesis. Additionally, prior to admission he had been prescribed ergocalciferol 50,000 units weekly for 8 weeks, after which he was transitioned to 2,000 units daily. This likely exacerbated the calcitriol-induced hypercalcemia by providing sudden availability of substrate, 25-OH vitamin D, for the activated macrophages. Conclusion: ART has reduced the incidence of opportunistic infections such as MAC, however mortality remains high. Vigilant monitoring for complications, particularly life-threatening calcitriol-induced hypercalcemia and timely use of corticosteroids, is crucial. This case also highlights the need for careful oversight in high-dose vitamin D supplementation for individuals with granulomatous disease and vitamin D dysregulation. Presentation: 6/2/2024

Amikacin Liposomal Inhalation Suspension for Non-Tuberculous Mycobacteria Lung Infection: A Greek Observational Study.

Background and Objectives: Intravenous amikacin, recommended for severe or recurrent M. avium complex (MAC) infections and as initial treatment for M. abscessus lung disease, is often limited by serious adverse effects such as renal and auditory toxicities. Inhaled Amikacin Liposome Inhalation Suspension (ALIS) enhances pulmonary drug deposition while minimizing systemic adverse effects, and it has recently been introduced as an add-on therapy for refractory MAC infections or when other standard treatments are inadequate. This study aims to retrospectively describe the outcomes of Greek patients with difficult-to-treat non-tuberculous mycobacterial (NTM) lung disease following the addition of ALIS to guideline-based therapy. Materials and Methods: Seventeen consecutive patients (median age: 66 years) treated with ALIS as an add-on therapy to a standard regimen at "Sotiria" General Hospital of Chest Diseases (Athens, Greece) from 2020 to 2023 were enrolled in this study. These patients had recurrent or refractory NTM lung disease and/or limited treatment options due to prior treatment-related adverse effects. Clinical, radiological, and microbiological data on treatment response and overall outcomes after ALIS initiation were recorded for each patient. Results: By the end of 2023, 14 out of 17 patients had either successfully completed or were continuing their ALIS therapy. At 6 months, 85.7% (12/14) showed clinical, microbiological, and radiological improvement. However, 25% (3/12) of treated patients, primarily those with monomicrobial or combined M. abscessus lung disease, experienced disease relapse after therapy completion. The most frequent adverse effects related to ALIS were mild and localized to the respiratory tract, with only one patient discontinuing therapy due to hypersensitivity pneumonitis. Conclusions: Adding ALIS to standard regimens was effective and safe in a small group of Greek patients with refractory or recurrent NTM lung disease, particularly those who had discontinued intravenous aminoglycosides due to significant adverse effects, with notable responses observed in MAC lung disease. Further research is needed to validate these findings in clinical practice and to investigate ALIS's role in NTM lung disease caused by other species.

Multicenter study of the performance of NTM Elite agar for the detection of nontuberculous mycobacteria from patients with cystic fibrosis.

The performance of a novel selective agar was evaluated against the performance of conventional mycobacterial cultures, i.e., a combination of the mycobacterial growth indicator tube (MGIT) with Löwenstein-Jensen (LJ), for the detection of nontuberculous mycobacteria (NTM) in sputum samples from people with cystic fibrosis (pwCF). Two hundred eighty-three sputum samples (231 fresh sputum and 52 spiked sputum) from 143 pwCF were collected. They were inoculated without prior decontamination on NTM Elite agar (30°C ± 2°C for 28 days) and inoculated on both MGIT and LJ (35°C-37°C for 6-8 weeks) after N-acetyl-L-cysteine-2% sodium hydroxide decontamination. NTM were identified by Matrix-Assisted Laser Desorption Ionization/Time of Flight Mass Spectrometry and/or PCR, and whole-genome sequencing. A total of 67 NTM were recovered overall by the combination of all culture media. NTM Elite agar allowed the recovery of 65 NTM (97%), compared to 22 for the conventional MGIT and LJ media combination (32.8%), including 22 NTM for MGIT (32.8%) and 3 NTM with the LJ medium (4.5%). For Mycobacterium abscessus complex, the sensitivity of NTM Elite agar was 95% compared with a sensitivity of 30% for the conventional MGIT and LJ media combination. Overall, 17.3% of cultures on NTM Elite agar were contaminated with other micro-organisms vs 46.3% on MGIT and 77% on LJ. This study shows that the novel selective agar (NTM Elite agar) significantly outperforms the conventional MGIT and LJ media combination in terms of sensitivity, selectivity, and ease of culture, without the requirement of an L3 laboratory.IMPORTANCENontuberculous mycobacteria (NTM) are significant pulmonary pathogens in patients with pre-existing structural lung conditions such as cystic fibrosis, bronchiectasis, or chronic obstructive pulmonary disease. Mycobacterium avium complex and Mycobacterium abscessus complex (MABSC) are the most frequently isolated organisms. Compared to the recommended culture method for NTM, which combines solid and liquid culture media, NTM Elite agar enables a faster/easier diagnosis and speeds up identification and susceptibility testing as the final reading is at 28 days instead of 6-8 weeks for the conventional mycobacterial cultures. In addition, for the NTM Elite agar, no decontamination stage before inoculation is necessary, unlike the conventional mycobacterial cultures. NTM Elite agar is derived from a formulation of medium adapted to rapidly growing mycobacteria (RGM). The medium enables the growth of RGM while suppressing other flora. It is supported with published clinical data showing the benefits of this medium.

More Than Just Stool: Hypereosinophilic Syndrome Presenting as Persistent Diarrhea in a Patient With Ulcerative Colitis

We highlight a case of non-infectious diarrhea that progressed despite supportive care, prompting further workup. A 50-year-old man presented with 1 week of voluminous diarrhea, nausea, emesis, and abdominal pain. His history included ulcerative colitis, primary sclerosing cholangitis, Clostridioides difficile treated via total colectomy with ileoanal pouch, treated disseminated Mycobacterium avium complex, and international travel. On physical exam he had normal vital signs, diffuse abdominal tenderness without peritoneal signs, and a rash. Lab work revealed leukocytosis with eosinophilia, hyponatremia, and elevated creatinine. Lactate, inflammatory markers, stool studies, and computed tomography of his abdomen were normal. Tissue biopsies of the duodenum, ileum, and rectal pouch collected during colonoscopy and push enteroscopy revealed prominent mucosal eosinophilia, confirming the diagnosis of hypereosinophilic syndrome (HES). Treatment with steroids led to significant improvement in all symptoms and blood eosinophilia. This case highlights the importance of aggressive workup of diarrhea with peripheral eosinophilia, especially in patients with ulcerative colitis: waiting 6 months to confirm the diagnosis via blood work would delay treatment. Notably, infection with Strongyloides stercoralis was ruled out in this case prior to treatment. This is an important step in the workup and management of HES to prevent progression of Strongyloidiasis.

S4413 Hepatic Lesions Secondary to Disseminated Mycobacterium avium Complex: A Diagnostic Challenge in a Patient With Advanced HIV Complicated by Kaposi Sarcoma Inflammatory Cytokine Syndrome

S4413 Hepatic Lesions Secondary to Disseminated Mycobacterium avium Complex: A Diagnostic Challenge in a Patient With Advanced HIV Complicated by Kaposi Sarcoma Inflammatory Cytokine Syndrome

Total syntheses of mavintramycin A and its structural analog, cytosaminomycin C, and evaluation of their antibacterial activities against Mycobacterium avium and Mycobacterium intracellulare

Mavintramycin A is a new aminohexopyranose nucleoside antibiotic with potent anti-Mycobacterium avium complex (MAC) activity against M. avium and M. intracellulare. Herein, we report the total syntheses of mavintramycin A and its structural analog cytosaminomycin C, which is a known anticoccidial antibiotic. Furthermore, the anti-MAC activities of mavintramycin A, cytosaminomycin C, and their corresponding p-methoxybenzyl-protected analogs were evaluated. Notably, the developed synthetic route enables ready access to various analogs of mavintramycin A for structure-activity relationship studies.