bluuebunny/crossref_metadata_2025 huggingface dataset:
1378. Impact of Cytomegalovirus Prophylaxis on Clinical Outcomes in Kidney Transplantation: A United States Renal Data System-Medicare Linked Database Study
Authors: Raval Amit D , Ganz Michael , Saravanan Priya , Tang Yuexin , Santos Carlos
Published: December 2021

Background

Guidelines recommends cytomegalovirus (CMV) prophylaxis by CMV serostatus/risk status, as the currently available antiviral agents may lead to myelosuppressive events in kidney transplant recipients (KTRs). Limited data exist for the United States (US) on the such clinical outcomes with CMV prophylaxis KTRs especially stratified by CMV risk strata. We examined the associations between clinical outcomes and CMV prophylaxis among adult KTRs stratified by CMV risk strata.

Methods

We employed a retrospective cohort design using the US Renal Data System registry-linked Medicare data (2011-2017). The cohort included 22,918 adult KTRs with continuous Medicare Part A & B coverage for ≥ 6-month pre and ≥ 12-month post KT and Part D coverage for ≥ 12-month post- KT. CMV prophylaxis was defined as ≥ 1 prescription fill or medical claim for valacyclovir or valganciclovir at prophylaxis doses within 28 days post-KT.

Results

CMV prophylaxis was utilized by 75% of the cohort. In no CMV prophylaxis group, 52.2% and 34.2% of high and intermediate risk KTRs received valganciclovir (as either pre-emptive or deferred therapy), respectively. Among high risk KTRs, CMV prophylaxis group had significantly lower proportions of KTRs with CMV infection, opportunistic infections (OIs) including bacterial, and fungal infections, and new onset of diabetes mellitus (NODAT) compared to no prophylaxis group. There were no differences in the rates of acute rejection or death; however, a trend towards lower rate of graft-failure at 12-month post-KT. Nearly 40% of high-risk KTRs had myelosuppressive events (leukopenia: 18%; neutropenia:15% thrombocytopenia :19%); however, their differences were non-significant except for thrombocytopenia by CMV prophylaxis status (Table 1). CMV infection and myelosuppressive event rates were higher in high-risk than intermediate/low risk KTRs irrespective of CMV prophylaxis status.

Conclusion

CMV prophylaxis was associated with lower rates of CMV infection, OIs, NODAT and graft failure compared to no prophylaxis, however, the burden of CMV infection, OIs and myelosuppression was greater in high-risk KTRs indicating further research is needed on factors associated with greater disease burden in high-risk KTRs.

Table 1

Disclosures

Amit D. Raval, PhD, Merck and Co., Inc. (Employee) Yuexin Tang, PhD, JnJ (Other Financial or Material Support, Spouse’s employment)Merck & Co., Inc. (Employee, Shareholder)
1379. Vaccination Rates among Liver Transplant Recipients at a Tertiary Care Hospital in Newark, NJ
Authors: Varughese Tilly , Song Michael , Sackey Joachim
Published: December 2021

Background

Transplant candidates and recipients are at increased risk of infectious complications of vaccine-preventable diseases due to their longstanding immunosuppressive regimens. We assessed the rates of vaccination in our liver transplant patients at University Hospital (UH) in Newark, NJ.

Methods

Retrospective chart-review including patients > 18 years old who underwent liver transplantation at UH for a 3-year period from 01/01/2017 to 07/20/2020. Data collected included demographics, clinical outcomes, eligibility and receipt of vaccinations before and after transplantation, protection titers after administration of hepatitis vaccinations and presence of an ID outpatient consultation. We looked at the following receipt of vaccinations: Prevnar-13, Pneumovax-23, Influenza, TDaP, Shingrix, Varivax, Havrix and Engerix/Heplisav. Characteristics of study participants was analyzed using descriptive statistics and Chi-Square/Fisher’s Exact tests were used to test associations.

Results

119 unique medical charts were reviewed and no patients were excluded. Of those patients who were eligible to receive Hepatitis A vaccination, only 44.8% were documented to receive vaccination and of those eligible to receive Hepatitis B vaccination, only 47.8% received it. Influenza vaccination pre-transplantation was 46% and 66.1% in post-transplant recipients. For the other vaccinations, during the pre-transplant period, 17.6 % of patients received Prevnar-13, 36.1% Pneumovax-23 and 20.2% TDaP and 26.1% received Shingrix. Patients who had ID consultation were significantly more likely to receive appropriate Hepatitis A and Hepatitis B vaccinations (p values 0.026 and 0.005).

Conclusion

We are not meeting national vaccination standards set by the American Society of Transplantation (AST) for optimal vaccination in this population. Our study can inform of possible solutions to increase vaccination rates in this population such as the simple addition of a smartphrase within EMR notes to remind providers to order appropriate vaccinations and eventually, a more long term solution of creation of a dedicated vaccination clinic and/or routine ID pre-transplant evaluations for all transplant candidates.

Disclosures

All Authors: No reported disclosures
1380. Real-world Effectiveness and Complications of Valganciclovir (VGC) Prophylaxis for Kidney Transplant (KT) Recipients at High Risk for Cytomegalovirus (CMV) infection (CMV Donor (D)+/Recipient (R)-)
Authors: Roumpz Caroline G , Kohl Josh , Hughes Kailey L , Raval Amit D , Tang Yuexin , Clancy Cornelius J , Nguyen Minh-Hong
Published: December 2021

Background

CMV infection is common post-kidney transplant (KT). Valganciclovir (VGC) prophylaxis (Px) has lessened CMV infection among high-risk (CMV D+/R-) KT recipients (KTRs), but VGC can induce neutropenia. We quantified the burden of CMV infection among CMV D+/R- KTRs and healthcare resources required to manage these patients (pts).

Methods

Retrospective study of pts undergoing KT between Jan 2014-Dec 2018. Study and control groups (gps) were CMV D+/R- and R+ KTRs, respectively. Standard post-KT immunosuppression was tacrolimus and mycophenolate mofetil (MMF). D+/R- and R+ KTRs received VGC Px (900 mg/day) for 6 and 3 months (mos), respectively.

Results

Clinical characteristics did not differ between D+/R- (n=131) and R+ (n=140) pts. Median VGC Px duration was longer for D+/R- (183 vs 104 days, p< .01). Within the first 6 mos post KT, a higher proportion of D+/R- KTRs received ≥1-course of granulocyte-stimulating factor (G-CSF) (15% vs 6%, p=.02). VGC Px was stopped prematurely/intermittently in 20% and 10% of D+/R- and R+, respectively, due to neutropenia (p=0.02); corresponding data for stopping MMF for ≥1 mos were 32% and 21% (p=.05). 50% of D+/R- pts received < 3 mos Px. Leukopenia prompted hospitalization in 3% of D+/R- vs 0% of R+ pts (p=.05). CMV infections did not differ between gps (7% vs 6%, p=.80); however, VGC-resistant CMV was higher in D+/R- gp (3% vs 0%, p=.05). Between 6-12 mos post-KT, D+/R- KTRs had higher rates of CMV infection (24% vs 4%,p< .01), VGC resistance (5% vs 0%, p=.01), hospitalization due to CMV (11% vs 2%, p=.01), MD intervention (22% vs 2%,p< .01), and infectious disease (ID) referral (8% vs 2%,p= .04). 57% of CMV resistance was observed in pts who prematurely stopped VGC. Hospitalizations were longer for CMV infections in D+/R- KTRs (8 vs 1 d, p< .01). There was a trend toward higher rejection for D+/R- KTRs (13% vs 6%, p=.09).

Conclusion

Universal VGC Px in D+/R- KTR remains challenging and requires significant resources for monitoring and intervention for neutropenia, including MD involvement and ID referral. Intermittent/premature stop of VGC may have led to VGC-resistant CMV,and stop of MMF may have led to a trend of higher cellular rejection at 1 yr. There is critical need for new CMV agents with a better safety profile.

Disclosures

Amit D. Raval, PhD, Merck and Co., Inc. (Employee) Yuexin Tang, PhD, JnJ (Other Financial or Material Support, Spouse’s employment)Merck & Co., Inc. (Employee, Shareholder) Cornelius J. Clancy, MD, Merck (Grant/Research Support) Minh-Hong Nguyen, MD, Merck (Grant/Research Support)
1382. A Prospective Epidemiological Study BK Polyomavirus DNAuria and DNAemia within the First Year after Kidney Transplantation
Authors: Mongkolrattanakul Pannawat , Bruminhent Jackrapong , Siripoon Tanaya , Wiwattanathum Punlop , Worawichawong Suchin , Kantachuvesiri Susarak
Published: December 2021

Background

Screening and early detection for the preceding BK polyomavirus (BKV) DNAuria and DNAemia to prevent the occurrence of BK polyomavirus BKV-associated nephropathy (BKPyVAN) among kidney transplant (KT) recipients has not been universally utilized and never assessed in a setting where the resource is limited. Therefore, we aimed to investigate this entity’s incidence, risk factors, and outcome with this intervention at our institution.

Methods

A prospective study of KT recipients at a tertiary care transplant center in Bangkok, Thailand, was conducted between January 2019 and March 2020. All patients underwent preemptive monitoring of urine and plasma BKV DNA load, measured by quantitative real-time PCR at 1, 2, 3, 6, 9, and 12 months post-KT. Low- and high-level BKV DNAuria was defined as urine BKV DNA load of < and > 7log10 copies/mL, respectively. Low- and high-level BKV DNAemia was defined as plasma BKV DNA load of < and > 4log10 copies/mL, respectively. The incidences were calculated by Kaplan-Meier analysis. The chi-square or student’s T-test compared clinical characteristics between those with and without high-level BKV DNAuria as appropriate. Risk factors of high-level BKV DNAuria were analyzed using Cox proportional hazard model.

Results

Among 99 evaluable KT recipients, a mean (SD) age was 42 (11) years, 64.6% were male, and 69.6% received an induction immunosuppressive therapy. Within 12 months post-KT, the incidences of low-level BKV DNAuria, high-level BKV DNAuria, low-level BKV DNAemia, and high-level BKV DNAemia were 22.63%, 13.14%, 9.49%, and 5.11%, respectively. High panel reactive antibody (PRA) was associated with high-level BKV DNAuria at 6 and 12 months, (HR 1.02 [95% CI (1.00-1.04)], P=0.019) and (HR 1.02 [95% CI (1.00-1.04)], P=0.023), respectively. Underlying diabetes mellitus was associated with high-level BKV DNAuria (HR 3.49 [95% CI (1.28-9.51)], P=0.015) at six months; however, not at 12 months. There was no allograft rejection directly related to a reduction of immunosuppression for BKV infection observed.

Conclusion

BKPyV infection is also prevalent among KT recipients in a resource-limited setting, however, without unfavorable consequence. Those with high-level PRA and underlying diabetes could be at risk of high-level BKV DNAuria after KT.

Disclosures

All Authors: No reported disclosures
1383. Universal Strongyloides Screening in a Heart Transplant Program in South Carolina: Just How Endemic Is It?
Authors: Adekunle Ruth , Jandhyala Deeksha , Lewis Jessica
Published: December 2021

Background

Strongyloides stercoralis is endemic in sub-Saharan Africa, Southeast Asia, Latin America, and the southeastern United States, particularly Appalachia, where Strongyloides seroprevalence approaches 2%. SC is considered a state in which Strongyloides is endemic, however the degree of endemnicity is not known. Here we define the epidemiology of chronic strongyloidiasis in our state, through data obtained via universal screening of heart transplant candidates at our center.

Methods

This single center retrospective study was performed at a 700 bed academic medical center that is the only comprehensive transplant center in SC. All adult patients who underwent heart transplant evaluation 1/1/2019 - 12/31/2020 were included. Routine pre-transplant evaluation by Transplant Infectious Diseases (TxID) was implemented in the heart transplant program in 2015 and universal screening with Strongyloides IgG began in late 2018. We assessed demographics, risk factors for exposure to Strongyloides, treatment, and outcomes for seropositive subjects.

Results

During the study period, 218 patients underwent heart transplant evaluation. Adherence to universal screening was 96.8% (211/218). 187 subjects (88.6%) had negative screening results (≤ 0.9 IV) and 24 subjects (11.4%) had equivocal or positive screening results (≥ 1.0 IV). Demographics and risk factors for the 24 equivocal/positive subjects are presented in Table 1.

15 equivocal/positive subjects (66.7%) received ivermectin and 9 (33.3%) did not. The majority of untreated patients were declined for transplant (8/9) and did not have a TxID evaluation (6/9). One untreated patient was waitlisted for transplant and has received ivermectin since being identified in this study. There were no episodes of hyperinfection or disseminated infection in the cohort.

Table 1. Demographics and risk factors for subjects with equivocal or positive Strongyloides IgG

Conclusion

Universal screening of adult heart transplant candidates at SC’s only transplant center detected a Strongyloides seroprevalence rate of 11.4%. The majority of subjects with equivocal/positive Strongyloides IgG were born in the US and did not have other known risk factors (residence in the Appalachian region of SC, military service, overseas travel). These data suggest a high level of endemnicity of strongyloidiasis in SC.

Disclosures

All Authors: No reported disclosures
1387. Impact of Cytomegalovirus Prophylaxis on Healthcare Resource Use and Costs among Kidney Transplant Recipients: A United States Renal Data System-Medicare Linked Database Study
Authors: Raval Amit D , Ganz Michael , Saravanan Priya , Tang Yuexin , Santos Carlos
Published: December 2021

Background

Cytomegalovirus (CMV) management requires a balance between reducing the risk of CMV infection and avoiding anti-viral toxicities. Limited information is available on the impact of CMV prophylaxis on the healthcare resource use (HCRU) and costs among adult kidney transplant recipients (KTRs) in the United States. Therefore, we examined HCRU and cost associated with CMV prophylaxis stratified by the CMV risk categories among KTRs at 1-year post-KT.

Methods

We identified a cohort of 22,918 adults first-time KTRs during 2011–2017 using the US Renal Data System registry-linked Medicare data. Additional inclusion criteria were to have continuous coverage in Medicare Part A & B for ≥ 6-month pre- and ≥ 12-month post KT and Medicare Part D for ≥12-month post-KT. CMV prophylaxis was confirmed as ≥ 1 prescription fill for valacyclovir/(val)ganciclovir prophylaxis doses within 28 days post-KT.

Results

CMV prophylaxis was utilized in 86%, 82%, and 32% of high, intermediate, and low-risk KTRs with an average cost of prophylaxis per KTRs of &16,241, &9481, and &8,648, respectively. In no prophylaxis groups, valganciclovir was utilized in 52%, 34%, and 36% of KTRs (as either pre-emptive or deferred therapy) with an average cost of &6,719, &2,722, and &431 among high, intermediate, and low-risk KTRs, respectively. Among high-risk KTRs, CMV prophylaxis group had a significantly higher prescription drug cost (&26,060 vs. &13,433) but a lower average direct healthcare medical cost (&84,914 vs. &101,268), mainly due to lower all-cause hospitalization cost (&56,758 vs. &69,852) (Table 1). CMV prophylaxis group had lower rates of all-cause rehospitalization, and CMV-and opportunistic infection (OIs)-related hospitalization compared to no prophylaxis (Table 2). In high-risk KTRs, nearly 32% had myelosuppressive events-related hospitalization, and 15% filled granulocyte colony-stimulating factors with an average cost of &4,695 per treated KTR.

Conclusion

CMV prophylaxis had a higher cost of medications but had a lower medical cost with including all-cause and CMV-related hospitalizations. Myelosuppressive events were frequent and resource-intensive especially in high and intermediate-risk KTRs.

Disclosures

Amit D. Raval, PhD, Merck and Co., Inc. (Employee) Yuexin Tang, PhD, JnJ (Other Financial or Material Support, Spouse’s employment)Merck & Co., Inc. (Employee, Shareholder)
158. Impact of Fluoroquinolone Cascade Reporting of Urine Samples on Antibiotic Prescribing Rates in a Network of Urgent Care Clinics
Authors: Weichman Brittani , Bushman Amanda , Rosa Rossana M
Published: December 2021

Background

Cascade reporting is a type of selective reporting in which susceptibility results of certain antibiotics (either with broader spectrum or cost) are only reported if an organism is resistant to other prespecified agents. This strategy has been successfully deployed in inpatient settings but its impact in outpatient settings is less well characterized. Therefore, we aimed to evaluate the impact of cascade reporting of the antimicrobial susceptibility of fluoroquinolones on prescribing rates of select antibiotics in a network of urban Urgent Care clinics.

Methods

On July 2019, the susceptibility reporting policies for urine cultures growing Enterobacterales were changed to routinely reporting a limited antibiotic panel including first and second generation cephalosporins, nitrofurantoin and trimethoprim-sulfamethoxazole (TMP-SMX), and fluroquinolone (FQ) reporting was changed to a release only in case of resistance to all agents in the limited panel. Third and fourth generation cephalosporins and carbapenems were reported only in case of resistance to all narrower spectrum agents and FQs. We then compared monthly antibiotic use in prescriptions per 1000 patient-encounters for the pre-intervention (June 2018-June 2019) and post-intervention (August 2019-December 2020) periods using an interrupted times series analysis.

Results

Immediately following the change to cascade reporting, FQ prescribing decreased by 38% (incidence rate ratio [IRR] 1.38; 95% confidence interval [CI] 0.50-0.77 p< 0.0001) and no change in trend was subsequently seen (IRR 1.01, 95% CI 0.98-1.04; p=0.59) (Figure 1).Cephalexin prescribing did not immediately change following the intervention (IRR 1.20, 95% CI 1.00-1.33; p=0.05) but subsequently showed a trend towards increase use (IRR 1.04, 95% CI 1.02-1.06; p< 0.0001) (Figure 1). No immediate or trend changes in the prescribing rates of TMP-SMX or nitrofurantoin were identified (Figure 1).

Conclusion

In a network of Urgent Care clinics, cascade reporting of FQ susceptibility in urine cultures growing Enterobacterales resulted in a sustained decrease in FQ prescribing without major shifts towards prescribing of other agents. Cascade reporting should be considered as a feasible antimicrobial stewardship strategy in this outpatient setting.

Disclosures

All Authors: No reported disclosures
1388. Epidemiology and Treatment Outcomes of Nontuberculous Mycobacterial Infections at a Community Teaching Hospital in the Southeastern United States
Authors: Vivian Tsai Y , Derrick Caroline , Yunusa Ismaeel , Weissman Sharon , Al-hasan Majdi N , Justo Julie Ann , Brandon Bookstaver P
Published: December 2021

Background

Gaps in evidence concerning the epidemiology of nontuberculous mycobacterial (NTM) organisms and their associated treatment outcomes are evident in the literature. The aim of this study was to describe NTM species distribution and susceptibility profile and associated treatment outcomes among adult patients at a tertiary referral hospital in the Southeastern United States.

Methods

A retrospective cohort study of adult patients with NTM infections from January 1, 2010 to June 30, 2020 was performed. Included patients had a positive culture for NTM species and clinical suspicion of infection. Patients were excluded if they had concurrent positive culture for M. tuberculosis (MTB) or monomicrobial culture for M. gordonae. Study endpoints included predictors for favorable treatment outcome, species distribution, and susceptibility at baseline. Favorable treatment outcome was defined as physician-guided cessation of therapy due to clinical improvement. Univariate followed by multivariate regression analysis was used to analyze favorable predictors.

Results

A total of 250 and 78 patients were included in microbiologic and outcomes cohorts, respectively. Among treated patients, 47 (60%) had a favorable treatment outcome. The outcomes cohort consisted primarily of non-Hispanic Caucasians (71%) with pulmonary infection (67%). The most common isolates observed were Mycobacterium avium complex (MAC) (67%) and M. abscessus (18%). Being self-pay, underweight, history of MTB treatment, and concurrent asthma were more common in those with unfavorable treatment outcomes. The significant favorable predictors included antibiotic change not due to escalation or de-escalation of therapy and private insurance. Among MAC isolates, clarithromycin and amikacin were highly susceptible; however, M. abscessus has reduced susceptibility to first-line agents such as amikacin, clarithromycin, and cefoxitin (Table 1).

Table 1. Baseline Susceptibility

Conclusion

Considering the long incubation time, knowledge of prevalence, antimicrobial susceptibility patterns, and outcomes could guide empirical antimicrobial selection for NTM infections. This is particularly useful for M. abscessus infections where most isolates carry significant resistance to one or more first-line agents.

Disclosures

Julie Ann Justo, PharmD, MS, BCPS-AQ ID, bioMerieux (Speaker’s Bureau)Merck & Co. (Advisor or Review Panel member)Therapeutic Research Center (Speaker’s Bureau)Vaxart (Shareholder) P. Brandon Bookstaver, Pharm D, ALK Abello, Inc. (Grant/Research Support, Advisor or Review Panel member)Biomerieux (Speaker’s Bureau)Kedrion Biopharma (Grant/Research Support, Advisor or Review Panel member)
1389. Nontuberculous Mycobacterial Infections of the Upper Extremity
Authors: Polveroni Thomas M , Scott Kelly , Renfree Kevin J , Vikram Holenarasipur R , Mead-Harvey Carolyn
Published: December 2021

Background

Although uncommon, nontuberculous mycobacterial infections (NTMI) of the upper extremity cause significant morbidity based on their natural history, delay in diagnosis, prolonged duration of antimicrobial therapy often combined with surgical debridement, and functional loss. Herein we describe our experience with such infections.

Methods

Records for adult patients from two academic, tertiary facilities with culture-proven NTMI involving the upper extremity were retrospectively reviewed. Demographic information, co-morbidities, laboratory and microbiological evaluation, management, and outcomes were extracted. Patients were analyzed based on pathogen identified and immune suppression.

Results

77 patients were identified. The mean age was 59 years and 65% of patients were male. 48% reported a preceding injury, with the hand being most frequently involved (58%). 41% were considered immune compromised; 19% of them were organ transplant recipients. Mean symptom duration prior to presentation was 203 days. Mean time to culture identification was 33 days, and 25 different species of NTM were identified (subcategorized as rapid or slow growers). 77% had solitary lesions, with cutaneous/subcutaneous location as the most common site. All patients underwent surgical debridement with four undergoing amputation to control infection. 69% received combination antimicrobial therapy for a mean duration of 184 days. Immunosuppressed patients were treated with antimicrobial therapy for a longer duration (mean 243 vs 155 days). One-third of patients experienced complications and/or recurrence regardless of organism type.

Conclusion

NTMI of the upper extremity is often misdiagnosed leading to significant delays in appropriate management. Knowledge of its protean manifestations and early consideration in the differential diagnosis of chronic, painful swelling of the hand or wrist, nodular or inflammatory lesions, or septic arthritis is crucial. A low threshold for surgical or biopsy with specimens sent for histopathology as well as microbiologic analysis is warranted. A combined approach with surgical debridement and prolonged combination antimicrobial therapy is necessary for optimal outcomes; however, adverse reactions from such therapy are commonly encountered.

Disclosures

All Authors: No reported disclosures
1390. 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)?
Authors: Nguyen David , Bethel Christopher , Taracilla Magdalena A , Li Qing , Dousa Khalid M , Kurz Sebastian G , Nguyen Liem , Kreiswirth Barry N , Boom Wilem , Bonomo Robert A
Published: December 2021

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 k2/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.

Methods

Mass spectrometry was performed to capture acyl-enzyme complexes (AECs) of purified BlaC and PG transpeptidases (PonA1, LdtMt1, LdtMt2, LdtMt3, and LdtMt5) with β-lactams and BLIs. Steady-state enzyme kinetics were determined using nitrocefin as a substrate. MICs with amoxicillin (AMX), meropenem (MER), CLA, and DUR alone and in combination against Mtb H37Rv were assessed using a microdilution method.

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).

Table 1. Minimum Inhibitory Concetrations for Mycobacterium tuberculosis H37Rv

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.

Disclosures

Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)
1391. Body Mass Index and Leptin Levels at Different Stages of the Tuberculosis Spectrum
Authors: Askar Wajih , Feria Manuel G , Jose Shinsmon , Madan Rajat , Huaman Moises A
Published: December 2021

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
1392. Nontuberculous Mycobacteria Isolated from Wisconsin Residents, 2010-2018
Authors: Vonasek Bryan J , Gusland Daniele Y , Hash Kevin P , Tans-Kersten Julie L , Gibbons-Burgener Suzanne N , Misch Elizabeth A
Published: December 2021

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.

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.

*’Respiratory specimens’ was inclusive of sputum, bronchoalveolar lavage, and tracheal aspirate specimens. CNS, central nervous system. HENT, head, ears, nose, or throat. SST, skin and soft tissue.

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

All Authors: No reported disclosures
1393. Loss to Follow-up Rate in the Treatment of Latent Tuberculosis by Region of Origin
Authors: Yoshii Hikari , Bark Charles
Published: December 2021

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.

Results

Of 4018 LTBI patients, 1171 (28.7%) were lost to follow-up, of which 950/2314 (41.0%) were from North America. Compared with LTBI patients from North America, significantly lower loss to follow-up rates were observed for those from Middle East and North Africa 30/170 (17.7% OR 0.52, 95% Confidence Interval (CI) 0.31-0.89), South Asia 60/692 (8.7% OR 0.41, 95% CI 0.21-0.78), and Sub-Saharan Africa 69/526 (13.1% OR 0.22, 95% CI 0.14-0.36).

Conclusion

The analysis showed that a high loss to follow-up rate was observed in the patient groups from North America, Europe and Central Asia, and Latin America & the Caribbean. LTBI patients from North America had a significantly higher loss to follow-up rate than those from Middle East and North Africa, South Asia, and Sub-Saharan Africa, respectively. Further research is needed to determine how to intervene in the poorly adherent patient population, such as LTBI patients from North America, Europe and Central Asia, and Latin America & the Caribbean.

Disclosures

All Authors: No reported disclosures
1394. Autochthonous Leprosy in Missouri
Authors: Patel Paragkumar , Rojas-Moreno Christian , Nelson Taylor , Zaesim Araya , Dyer Jon
Published: December 2021

Background

Introduction: Leprosy (Hansen’s disease) is a chronic granulomatous infection of the skin/peripheral nerves caused by Mycobacterium leprae. Of 216 new cases reported in the US in 2019, 70% were in FL, LA, TX, HI, CA, GA and NY. Leprosy is considered a zoonosis in the southern US with the nine-banded armadillo as a reservoir. There have been no reported autochthonous leprosy cases in Missouri.

Methods

Case: 55 y/o previously healthy male noted a new rash on his arm 2 years ago. Over time it spread to his extremities/torso. Skin biopsy showed a granulomatous infiltrate, suspected granuloma annulare, but it progressed despite appropriate therapy. He noted progressive numbness of the affected areas of skin and several regional nerve distributions. In the weeks prior to his initial visit he noted facial swelling, eyelid and ear induration, worsening fatigue, diffuse arthralgia, and some vision changes. His travel history is limited to Canada, Colorado and a brief vacation to the Texas/Mexico border (no notable outdoor exposure during the latter trip; no travel outside the country). He lives in rural Missouri where he is exposed to armadillos. His dogs frequently kill them and often bring them into the yard, rolling around on/in the dead carcasses which he disposes of. He typically wears gloves when handling them and has never consumed them. On exam he had diffuse purplish-red nummular infiltrated anesthetic papules and plaques diffusely distributed over the trunk and extremities. Distinct left ulnar neuropathy was noted. He exhibited leonine facies and infiltration of the bilateral helices. Repeat biopsy showed a granulomatous infiltrate with abundant acid-fast bacilli. DNA sequencing confirmed M. leprae. He was preventatively treated with prednisone and methotrexate to minimize immune reaction, and two weeks later began a regimen of monthly rifampin, minocycline, and moxifloxacin with an anticipated duration of 24 months.

Results

Diagnosis

lepromatous leprosy with pre-treatment immune reaction. This is potentially the first case of autochthonous leprosy in Missouri. Providers should include Hansen’s disease in the differential diagnosis of patients with dermal eruption and cutaneous neurological symptoms to avoid delays in diagnosis/care.

Disclosures

All Authors: No reported disclosures
1395. Epidemiology of Non-Tuberculous Mycobacteria Infection Among Immunocompromised Children: A Single Center Experience
Authors: Kang Ye jin , Sue Paul K , Filkins Laura , Chery Giselle S
Published: December 2021

Background

Nontuberculous mycobacteria (NTM) infection is associated with high rates of morbidity and mortality among immunocompromised adults. However, sparse data exists regarding clinical outcomes among immunocompromised (IC) children with NTM infection. We sought to characterize clinical features and outcomes among IC children at our institution with microbiologically confirmed NTM disease.

Methods

Retrospective review of cases of microbiologically confirmed NTM infection among IC children between January 2017 and December 2020. Children (≤21y.o) with microbiologically confirmed NTM disease and known primary or secondary immunodeficiency diagnosed between January 1, 2017 and December 20, 2020 were included in the study. All subjects with a positive NTM microbiologic stain or culture but no subsequent treatment for NTM infection were excluded. Demographic and clinical characteristics were assessed and risk factors for mortality were evaluated.

Results

Of 147 mycobacterial cultures sent during the study period, 72 subjects had a positive microbiologically confirmed NTM species, with 10 subjects meeting all inclusion and no exclusion criteria. Median age was 16 years old, with 40 percent being female and 50 percent of Hispanic ethnicity. NTM disease was distributed among patients with primary immunodeficiency (30%), solid organ transplantation (20%), hematopoietic stem cell transplant (20%), rheumatologic disease on immunosuppressive therapy (10%), and hematologic malignancy (10%). Bacteremia was common, with blood cultures positive in 70% of cases, and M. abscessus (50%) and M. avium complex (30%) the most frequently implicated pathogens. Hospital acquired infection was common (60%). 2 year mortality following invasive NTM infection was high at 40%.

Conclusion

While rare, NTM infections are associated with significant morbidity and mortality among immunocompromised children. Additional investigations are needed to assess for risk factors associated with NTM and severe NTM disease.

Disclosures

Laura Filkins, PhD, Avsana Labs (Board Member, Scientific advisory board member)Biofire Diagnostics (Grant/Research Support)
1397. Modern Lineages of Mycobacterium tuberculosis Were Recently Introduced in Western India and Demonstrate Increased Transmissibility
Authors: Dixit Avika , Kagal Anju , Ektefaie Yasha , Freschi Luca , Lokhande Rahul , Groeschel Matthias , Tornheim Jeffrey A , Gupte Nikhil , Pradhan Neeta N , Kadam Deelip , Gupta Amita , Golub Jonathan , Farhat Maha , Mave Vidya
Published: December 2021

Background

Mycobacterium tuberculosis (Mtb) transmissibility may vary between lineages (or variants) and this may contribute to the slow decline of tuberculosis incidence. The objective of our study was to compare transmissibility across four major lineages (L1-4) of Mtb in Pune, India.

Methods

We performed whole-genome sequencing (WGS) of Mtb isolated from sputum culture of adult patients with pulmonary TB. We performed genotypic susceptibility testing for both first- and second-line drugs using a previously validated random forest predictor. We identified single nucleotide polymorphisms and generated a multiple sequence alignment excluding drug resistance conferring mutations to avoid skewing the phylogeny due to convergent evolution in these regions. We used Bayesian molecular dating to generate phylogenies and compared tree characteristics using a two-sample Kolmogorov-Smirnov (KS) test.

Results

Of the 642 isolates from distinct study participants that underwent WGS, 612 met quality criteria. The median age of participants was 31 years (range 18-74), the majority were male (64.7%) and sputum smear-positive (83.3%), and 6.7% had co-infection with HIV (Table 1). There was no significant difference in baseline characteristics between lineages. The majority of isolates belonged to L3 (44.6%). The majority (61.1%) of multidrug-resistant (MDR, resistant to isoniazid and rifampin) isolates belonged to L2. In phylogenetic analysis, we found evidence of higher transmissibility of L2 as indicated by shorter branch lengths (i.e., less time had elapsed between transmission and sampling) and more genetic similarity (smaller pairwise single nucleotide polymorphism [SNP] distances) among L2 isolates as compared to other lineages (Figure 1). Branching times for L2 and L4 were smaller than L1 and L3 indicating recent introduction into the region (p < 0.001 [KS test]).

Figure 1: Lineage-wise distribution of A) phylogenetic tree branch lengths (log) and B) pairwise single nucleotide polymorphism (SNP) distance, using 612 tuberculosis isolates from Pune, India. P values calculated using two-sample Kolmogorov-Smirnov test.

Table 1: Demographic characteristics of study participants included in the study, by lineage.

Conclusion

Modern Mtb lineages (L2 and L4) were relatively recently introduced in western India, as compared to older lineages (L1 and L3), with the more drug-resistant L2 showing higher transmissibility. These findings highlight the need for early detection and treatment initiation to interrupt transmission with important implications for antimicrobial stewardship and heightened surveillance of TB resistance rates.

Disclosures

All Authors: No reported disclosures
1398. Gland Tuberculosis: A Rare Localization of Tuberculosis
Authors: Hammami Fatma , Koubaa Makram , Chakroun Amal , Rekik Khaoula , Marrakchi Chakib , Smaoui Fatma , Jemaa Mounir Ben
Published: December 2021

Background

Tuberculosis (TB) is a multisystem disease that might affect all organs. Gland TB is characterized with a misleading clinical presentation which often mimic a neoplastic process. The aim of our work was to study the clinical, therapeutic and evolutionary features of gland TB.

Methods

We conducted a retrospective study including all patients hospitalized for gland TB in the infectious disease department between 1999 and 2020.

Results

We encountered 28 cases among which 24 were females (85.7%). The mean age was 39±14 years. A rural origin was noted in 15 cases (53.5%). Two patients were previously treated for TB (7.1%). Systemic symptoms of TB included fever (60.7%), asthenia (53.5%), loss of appetite (46.4%) and weight loss (25%). There were 18 cases of breast TB (64.3%), 4 cases of salivary gland TB (14.3%) and 3 cases of ovarian TB (10.7%). Two cases of pituitary TB (7.1%) and one case of adrenal TB (3.6%) were noted. Multifocal TB was noted in 7 cases (25%). Lymph node (17.8%), pulmonary (14.2%) and peritoneal (7.1%) TB were associated with gland TB. Tuberculin skin test was positive in 19 cases (67.8%). The diagnosis was based on histopathological proof in 23 cases (82.1%), microbiological proof in 4 cases (14.3%) and clinically confirmed in one case (3.6%). The median duration of antitubercular therapy was 10 [9-15] months. Patients received fixed-dose combination in 11 cases (39.2%). Adverse effects of antitubercular therapy were noted in 10 cases (35.7%) represented by gastrointestinal symptoms (14.3%), increase in hepatic enzyme levels (14.3%) and skin reactions (7.1%). The disease evolution was favorable in 26 cases (92.9%). Relapse was noted in two cases (7.1%).

Conclusion

Gland TB included different sites. The presence of systemic symptoms of TB and the diagnosis of TB elsewhere in the body helped through the diagnosis process which requires high index of suspicion. It was mainly based on histological evidence.

Disclosures

All Authors: No reported disclosures
1399. Clarithromycin–Rifampin-based Treatment for Non-tuberculous Mycobacterial Infections in Immunocompromised Patients Who Require Concomitant CYP-Metabolized Medications
Authors: Gonzalez-Bocco Isabel H , Aleissa Muneerah M , Cheng Matthew , Manne-Goehler Jennifer , Marty Francisco M
Published: December 2021

Background

Non-tuberculous mycobacteria (NTM) are causes of pulmonary and extrapulmonary disease that frequently affect immunocompromised hosts (ICH). Current treatment guidelines recommend a macrolide-based, multi-drug regimen that includes rifampin. Rifampin is a potent cytochrome P450 (CYP) 3A inducer, which often results in drug-drug interactions in ICH receiving multiple CYP substrates. One way to mitigate rifampin’s CYP induction is to utilize clarithromycin, a CYP inhibitor, as the accompanying macrolide. We evaluated the incidence of NTM treatment-related adverse events (AEs) in patients who received a clarithromycin-based regimen compared to patients who received an azithromycin-based regimen.

Methods

We conducted a retrospective review of NTM infection in 30 immunocompromised adults. All participants had a positive culture for a NTM and had received a rifamycin (rifampin or rifabutin) with a macrolide (azithromycin or clarithromycin) for treatment at Brigham and Women’s Hospital between 01/01/2011-10/18/2020 or Dana-Farber Cancer Institute between 06/03/2015-07/01/2020. The primary outcome was the incidence of NTM treatment-related AEs in patients who received a clarithromycin-based regimen compared to those who received an azithromycin-based regimen.

Results

There were no significant differences in the reasons for discontinuation of NTM treatment or 90-day mortality between groups. The number of AEs possibly related to NTM treatment were similar in patients who received a clarithromycin-based regimen and those who received an azithromycin-based one (10/13 vs. 14/17; p=0.73). The most common AE was liver function test abnormalities (Table 1). Additionally, the proportion of patients requiring dose adjustments for interacting medications and patients with out-of-range tacrolimus levels were similar between the two groups (23.1% vs. 29.4%; p=0.76 and 8.0% vs. 6.0%; p=1.00, respectively).

Table 1: Adverse events

Conclusion

A clarithromycin-based regimen for NTM treatment was safe and well tolerated in our patient population. This combination provides a good alternative for patients requiring medications that are CYP substrates, or those who cannot tolerate azithromycin.

Disclosures

Matthew Cheng, MD, GEn1E Lifesciences (Advisor or Review Panel member)Kanvas Biosciences (Board Member, Shareholder)nplex biosciences (Advisor or Review Panel member)