1391. Body Mass Index and Leptin Levels at Different Stages of the Tuberculosis Spectrum

Abstract Background Leptin is an adipose tissue-derived cytokine that plays a role in energy regulation and immune functions. High leptin levels and obesity have been associated with decreased risk of developing active TB. We aimed to characterize the association between body mass index (BMI) and leptin levels in patients at different stages of tuberculosis (TB). Methods Data from a cross-sectional cardiovascular risk study of 40 to 70 years old individuals enrolled in Lima, Peru, and Cincinnati, US, were analyzed. Four categories based on TB and treatment status were defined: no TB infection (QuantiFERON-TB test negative; n= 31), latent TB infection (LTBI; QuantiFERON-TB test positive; n= 43), active TB on treatment (in the continuation TB treatment phase; n= 30), and post-TB (within one year of TB treatment completion; n=16). BMI and plasma leptin levels were compared among the four groups using the Kruskal-Wallis test, followed by Dunn’s multiple comparison test if differences were found in the Kruskal-Wallis test. Multivariate ordered logistic regression models were used to assess factors associated with leptin levels, adjusted for potential confounders. Results The median age was 53 years, and 51% were female. BMI was different between study groups (p< 0.01), with LTBI individuals having the highest BMI compared to other groups; see Figure 1A. Leptin levels were marginally low in the group with active TB on treatment, but no significant differences were found between groups (p=0.44; see Figure 1B). In multivariate analysis, leptin was associated with female sex (OR 23, 95%CI, 9-58), BMI (OR, 1.5, 95%CI, 1.2-1.7), and coronary plaque ≥25% stenosis (OR, 0.29, 95%CI, 0.08-0.99). Body mass index (BMI) and plasma leptin levels in participants with negative QuantiFERON-TB test (QFN-), latent tuberculosis infection (LTBI), active tuberculosis on treatment (ATBT), and post-TB treatment (TB-treated). Significance was determined using the Kruskal-Wallis test, followed by Dunn’s multiple comparison test if the Kruskal- Wallis test p-value was <0.05. Conclusion LTBI individuals had a higher BMI compared to persons with active TB on treatment and post-TB. Higher leptin levels were associated with higher BMI, but we found no association between leptin and TB status in our cohort. Disclosures All Authors: No reported disclosures


Durlobactam, a Diazabicyclooctane (DBO) β-lactamase Inhibitor (BLI), Inhibits BlaC and Peptidoglycan (PG) Transpeptidases of Mycobacterium tuberculosis (Mtb): A Novel Approach to Therapeutics for Tuberculosis (TB)?
Background. Novel therapies for multidrug-resistant TB are needed and new BLIs could answer this call. Mtb encodes for BlaC, a class A β-lactamase. BlaC is inhibited by clavulanate (CLA) while the DBO avibactam (AVI) is an inefficient inhibitor (low k 2 /K value). Carbapenems are hydrolyzed slowly by BlaC (low kcat/Km value) making them "dual action" compounds that inhibit both BlaC and PG transpeptidases, the intended β-lactam targets. DBOs inhibit PG transpeptidases in other bacteria. To explore the therapeutic potential of new DBOs against Mtb, we compared the inhibitor activity of AVI, relebactam (REL), and durlobactam (DUR, formerly ETX2514) against BlaC and Mtb PG transpeptidases using a biochemical approach. We also investigated the ability of DUR to lower minimum inhibitory concentrations (MICs) of β-lactams against Mtb H37Rv.
Results. DUR alone had a MIC of 2 µg/mL with Mtb H37Rv (Table 1). BlaC formed AECs with all carbapenems and BLIs. BlaC had lower Ki app and higher k2/K with DUR than those with AVI and REL and comparable to those with CLA; however, with a period of pre-incubation, AVI fully inhibits BlaC ( Table 2). The carbapenems and DUR formed the most AECs with PG transpeptidases of the β-lactams and BLIs respectively; PG transpeptidases had lower Ki app values with DUR than those with AVI (Table 3). Conclusion. DUR alone has some antimicrobial activity against Mtb H37Rv. The likely mechanism that underlies this activity is inhibition of BlaC and several PG transpeptidases. Inhibition of enzyme targets with DUR was more potent and efficient than AVI and REL. DUR in combination with β-lactams lowered MICs but the DUR concentration used was higher than its MIC. Our findings support the exploration of novel BLIs against BlaC and PG transpeptidases with the ultimate goal of repurposing these drugs for the treatment of TB. Background. Leptin is an adipose tissue-derived cytokine that plays a role in energy regulation and immune functions. High leptin levels and obesity have been associated with decreased risk of developing active TB. We aimed to characterize the association between body mass index (BMI) and leptin levels in patients at different stages of tuberculosis (TB).

Body Mass Index and Leptin Levels at Different Stages of the Tuberculosis Spectrum
Methods. Data from a cross-sectional cardiovascular risk study of 40 to 70 years old individuals enrolled in Lima, Peru, and Cincinnati, US, were analyzed. Four categories based on TB and treatment status were defined: no TB infection (QuantiFERON-TB test negative; n= 31), latent TB infection (LTBI; QuantiFERON-TB test positive; n= 43), active TB on treatment (in the continuation TB treatment phase; n= 30), and post-TB (within one year of TB treatment completion; n=16). BMI and plasma leptin levels were compared among the four groups using the Kruskal-Wallis test, followed by Dunn's multiple comparison test if differences were found in the Kruskal-Wallis test. Multivariate ordered logistic regression models were used to assess factors associated with leptin levels, adjusted for potential confounders.
Significance was determined using the Kruskal-Wallis test, followed by Dunn's multiple comparison test if the Kruskal-Wallis test p-value was <0.05.
Conclusion. LTBI individuals had a higher BMI compared to persons with active TB on treatment and post-TB. Higher leptin levels were associated with higher BMI, but we found no association between leptin and TB status in our cohort. Background. Wisconsin is one of a handful of states in which laboratory identification of nontuberculous mycobacteria (NTM) from clinical samples is reportable to public health. The aims of this study were to characterize the demographic features of Wisconsin adults with NTM, assess the relative abundance of NTM species recovered, and describe trends in NTM isolation over the study period.

Nontuberculous Mycobacteria Isolated from Wisconsin Residents
Methods. We conducted a retrospective cohort study of Wisconsin residents 18 years of age and older from whom NTM isolates were recovered and reported to the Wisconsin Electronic Disease Surveillance System (WEDSS) between 2010 and 2018. Isolates of M. gordonae were excluded. For the analysis of NTM frequency, multiple reports from the same individual were enumerated as separate isolates when non-identical or collected from different sites. Because NTM were usually reported into WEDSS without clinical data, this study couldn't discern the clinical significance of the isolates.
Results. A total of 9,032 NTM isolates from 7,722 adults were analyzed. The average annual number of reported NTM cases was 950 (21.7/100,000 adults) during 2011-2018. Table 1 shows the demographic characteristics of individuals with NTM isolates, stratified by specimen collection site and NTM species. M. avium complex (MAC) accounted for 75.7% of respiratory isolates. An important pathogenic NTM, M. xenopi, accounted for 8.9% of non-MAC respiratory isolates. As shown in Table 2, M. chelonae, a rapidly growing mycobacteria (RGM), was the most common species isolated from skin and soft tissue, head, ears, nose and throat, and eye specimens. MAC was the most common isolate from other tissue sites. Table 1. Demographic characteristics of individuals with NTM isolates.
Categorization was based upon the initially recovered sample when multiple samples were obtained from a given individual. "Respiratory" samples included sputum, bronchoalveolar lavage, and tracheal aspirate specimens. IQR, interquartile range. RGM, rapidly growing mycobacteria (M. chelonae and the M. abscessus, M. chelonae-abscessus, and M. fortuitum groups). SST, skin and soft tissue. Table 2. Most common NTM species isolated from non-respiratory sites.
Conclusion. Consistent with prior studies, MAC is the predominant NTM isolated from respiratory specimens in Wisconsin. RGM are important minority respiratory pathogens, and predominate as skin and soft tissue NTMs. We highlight M. xenopi as an important pathogen in Wisconsin compared to other parts of the United States. In contrast to recent reports of increasing incidence of NTM disease, we found a stable annual incidence of NTM isolation between 2010 and 2018.
Disclosures. Background. Adherence in the treatment of latent tuberculosis infection (LTBI) is closely related to reactivation and infection control in the population. However, there has been little research on which populations are at higher risk of loss to follow-up. The aim of this study is to investigate how the adherence of LTBI patients in the United States (US) differs by region of origin.
Methods. A retrospective, observational study was conducted from 2001 to 2020. LTBI patients were identified from the Cuyahoga County Tuberculosis Clinic in Cleveland, Ohio. Only patients who were informed of the diagnosis of LTBI were included. Patients were discharged from the Tuberculosis outpatient clinic upon completion of treatment or when the physician decided to discontinue treatment. We defined loss to follow-up as a case where LTBI was diagnosed but the patient was not formally discharged. Patients whose treatment was interrupted due to side effects were not considered loss to follow-up. Odds ratios were calculated using a multivariable regression model with patients from North America as the reference group.