bluuebunny/crossref_metadata_2025 huggingface dataset:
1653. Estimation of country-specific tuberculosis antibiograms using a wide and deep neural net on a large genomic dataset
Authors: Dixit Avika , Freschi Luca , Vargas Roger , Groeschel Matthias , Chen Michael , Tahseen Sabira , Kamal S M Mostofa , Ismail Nazir A , Farhat Maha
Published: January 2021

Background

Improved estimates of drug resistant tuberculosis (TB) burden are needed to aid control efforts. The World Health Organization (WHO) currently reports estimates for rifampin resistance (RR) or multidrug resistance (MDR) at the national level. Resistance rates to other first-line and second-line agents, e.g. ethambutol, pyrazinamide, and aminoglycosides, are rarely available, even at the country level. Our objective was to generate country and drug specific resistance prevalence estimates (antibiograms) using in silico phenotype prediction and curated public and surveillance Mycobacterium tuberculosis (MTB) genomic data.

Methods

We curated MTB genomes either by sequencing or from published literature and excluded genomes that did not meet our quality criteria (i.e. at least 10X depth in >95% of the genome). A machine learning model previously trained to predict phenotypic resistance in MTB with high accuracy, a wide and deep neural net (WDNN), was used to predict resistance to ten drugs. We corrected for resistance oversampling in genomic data by conditioning on RR and using country specific surveillance MDR/RR rates reported by the WHO.

Results

Of the 49,851 MTB genomes curated, 33,873 isolates met quality criteria. Of these, geographic data was available for 22,838 genomes. Antibiograms were generated for nine first- and second-line drugs for 36 countries. Among countries with at least 100 isolates, a high rate of resistance to fluoroquinolones and second line injectables was seen among isolates from the Republic of Moldova (15.4% [CI = 13.7-16.7%] moxifloxacin resistant, 6.3% [CI = 5.5-6.8%] kanamycin resistant, n = 330) and Russian Federation (9.3% [CI = 9.1-9.4] moxifloxacin resistant, 5.4% [CI = 5.3-5.5%] kanamycin resistant, n = 1011) (Figure 1).

Figure 1: Antibiograms created using genotypic data for isolates from Republic of Moldova (n=330, rifampin-resistance rate correction: 29%, range 26-31% among new tuberculosis cases);and Russian Federation (n=1011, rifampin-resistance rate correction 35%, range 34-35%, among new tuberculosis cases. rif: rifampin, inh: isoniazid, pza: pyrazinamide, emb: ethambutol, str: streptomycin, cap: capreomycin, amk: amikacin, kan: kanamycin, moxi: moxifloxacin

Conclusion

The estimation of antibiotic resistance prevalence in MTB for pyrazinamide, ethambutol and second-line agents can be aided by the use of in silico models of drug resistance. A high rate of resistance to second-line drugs precludes large scale roll out of short-course WHO regimens for treatment of MDR-TB for empiric use in certain countries. The use of whole genome sequencing for resistance surveillance can inform policy on optimal national regimen choice for TB treatment.

Disclosures

All Authors: No reported disclosures
1657. Musculoskeletal Tuberculosis in a Large Healthcare System
Authors: Denmeade Travis , Smith William , Kooken Banks , Leonard Michael
Published: January 2021

Background

Musculoskeletal tuberculosis (TB) is an important and elusive manifestation of extrapulmonary TB. This purpose of this study was to examine incidence and associated co-morbidities of confirmed cases of musculoskeletal TB at Atrium Health, a large non-profit health system in the Southeastern United States.

Methods

Retrospective case series of 12 adult patients with confirmed musculoskeletal TB between 2008-2019. Individuals younger than 18 years were excluded. The primary objective was to compare local incidence of musculoskeletal TB with that reported in the literature. Secondary objectives included analysis of patient co-morbidities for their correlation with the development of musculoskeletal manifestations of TB and requirement of surgical correction for underlying deformities from TB infection.

Results

237 patients were identified with confirmed TB infection from 2008-2019 in a retrospective cohort within the Atrium Health System. Of 237 patients, 94 (40%) had extrapulmonary disease and 12 (5%) had musculoskeletal manifestations defined as involvement of bone, joint space, or muscle and were included in this analysis. Six (50%) of the 12 patients were foreign born individuals who immigrated to the US. Three (33%) had concomitant pulmonary disease. Vertebral involvement (8, 66%) was most common and 1 (8%) patient noted to have infected total knee arthroplasty. Other sites included wrist, sternum, ribs and pelvis. Co-morbidities evaluated included HIV status 0%, diabetes (2, 17%), immunosuppressive medications (1, 8%), ESRD 0%, and rheumatologic disease 0%. Surgical intervention was necessary in 4 (33%) patients for both diagnostic and therapeutic interventions.

Conclusion

Of those tested for HIV 100% were negative but only 50% were tested showing a need for improved HIV testing. Very few had other co-morbid conditions including diabetes, use of immunosuppressive medications, ESRD status, or rheumatologic disease. Surgical intervention was needed in 33% of patients with musculoskeletal TB including several with a preoperative suspected diagnosis of malignancy. In this retrospective case series, the incidence of musculoskeletal TB was 5% in comparison to the 2-3% reported consistently in the US.

Disclosures

All Authors: No reported disclosures
1658. Particularities Of Pulmonary Tuberculosis Among Children
Authors: Hammami Fatma , Koubaa Makram , Chakroun Amal , Rekik Khaoula , Smaoui Fatma , Elleuch Emna , Marrakchi Chakib , Jemaa Mounir Ben
Published: January 2021

Background

The diagnosis of pulmonary tuberculosis (PTB) among children remains challenging due to the non-specific clinical symptoms, laboratory features and the difficulty of sampling for microbiological investigations. We aimed to study clinical, therapeutic and evolutionary features of PTB among children.

Methods

We conducted a retrospective study including all children aged ≤ 18 years diagnosed with PTB between 1995 and 2016.

Results

We encountered 67 children with PTB, among whom 37 (55.2%) were female. The median age was 15 years [1-18years]. According to residency, 36 patients came from rural area (53.7%). We noted 7 cases (10.4%) of miliary tuberculosis (TB). Three cases of pleural TB (4.5%), one case of lymph node TB (1.5%) and one case of neuromeningeal TB were associated to PTB. Induced sputum or gastric aspirate were positive for Mycobacterium tuberculosis in 67.9% of the cases. Serologic tests for human immunodeficiency virus was positive in one case (1.5%). The mean duration of antitubercular therapy was 8 ±2 months. The treatment regimen was based on a quadritherapy for the first 2 months, followed by a bitherapy for the rest of the period. Fixed dose drug combinations were prescribed in 17 cases (25.3%). The disease evolution was favourable in 65 cases (97%). Two patients were dead (3%). There were no relapsing cases.

Conclusion

Prompt diagnosis and treatment of PTB among children improve the prognosis. Screening for PTB among children exposed to adult tuberculosis is crucial in order to prevent the disease.

Disclosures

All Authors: No reported disclosures
1659. Pharmacokinetics/pharmacodynamics of the Novel Gyrase Inhibitor SPR719/SPR720 and Clinical Dose Selection to Treat Pulmonary Mycobacterium avium-complex Disease
Authors: Deshpande Devyani , Kuret Daniel , Cirrincione Kayle , Cotroneo Nicole , Melnick David , Lister Troy , Stokes Suzanne , Gumbo Tawanda
Published: January 2021

Background

Current therapy for pulmonary Mycobacterium avium-complex [MAC] disease achieves poor sustained sputum conversion rates and is poorly tolerated. SPR719, the active metabolite of SPR720, a novel gyrase inhibitor, has demonstrated low MICs against MAC. SPR720 is being developed as an oral therapy for use in combination with other antibiotics for the treatment of patients with pulmonary disease due to infection with MAC. Our objective was identify SPR719 pharmacokinetic/pharmacodynamic [PK/PD] parameters and optimal SPR720 dose for treatment of pulmonary MAC.

Methods

SPR719 was administered once daily for 28 days using a simulated human half-life of 3.3 hours in the hollow fiber system model of pulmonary intracellular MAC [HFS-MAC]. Bacterial burden, including for SPR719-resistant subpopulations, and drug concentrations, were measured via repetitive sampling of HFS-MAC units. A separate dose fractionation study in the HFS-MAC was used to identify the PK/PD index linked to effect. MAC burden versus SPR719 exposure was modeled using the inhibitory sigmoid maximal effect [Emax] model and resistance using the “antibiotic resistance arrow of time” model. Finally, we performed Monte Carlo Experiments to identify the optimal clinical dose of SPR720 monotherapy.

Results

The median HFS-MAC intracellular-to-extracellular SPR719 AUC0-24 ratio was 2300:1. The PK/PD parameter best linked to microbial kill was determined to be AUC0-24/MIC. SPR719 Emax was -1.5 log10 cfu/mL compared to day 0; 1.0 log10 cfu/mL reduction and acquired-resistance suppression were achieved by an AUC0-24/MIC of 2.0 and 11, respectively. SPR720 1,000 mg/day was predicted to achieve 1.0 log10 cfu/mL kill in 95%, and resistance suppression in 43%, of 10,000 simulated subjects.

Conclusion

SPR720 monotherapy is predicted to achieve exposures associated with bactericidal effect against pulmonary MAC in 95% of patients at doses that have recently been established to be safe and well tolerated. These data support the continued development of SPR720 for the treatment of pulmonary MAC.

Disclosures

Nicole Cotroneo, Spero Therapeutics (Employee) David Melnick, MD, Spero Therapeutics (Employee)Spero Therapeutics (Employee) Troy Lister, PhD, Spero Therapeutics (Employee) Suzanne Stokes, PhD, Spero Therapeutics (Employee, Shareholder) Tawanda Gumbo, MD, Praedicare Inc (Employee, Shareholder)
1662. The Prevalence of M. tuberculosis among Acid Fast Cultures from Military Health System Beneficiaries from Hawaii and Pacific Islands from January 2002 to November 2019
Authors: Crecelius Elena M , Lustik Michael , Horseman Timothy , Jones Milissa
Published: January 2021

Background

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is the leading infectious cause of death worldwide and the state of Hawaii (HI) has the second highest case rate of TB in the United States. The prevalence of TB among military health system (MHS) beneficiaries (active duty service members, retirees, dependents, civilians and eligible Pacific Island civilians) in HI has not been previously reported. Our analysis evaluates the prevalence of MTB among acid fast cultures (AFCs) tested at Tripler Army Medical Center (TAMC) on Oahu, HI and describes demographic factors associated with positive samples.

Methods

We analyzed AFC results from TAMC clinical diagnostic microbiology laboratory from January 2002 to November 2019. Demographic data were recorded for each individual with an AFC sample during the study period. Prevalence was calculated based on the number of MTB-positive AFCs per all AFCs over the study period. Multivariable logistic regression was used to evaluate associations between demographic factors and MTB-positive AFC results.

Results

From January 2002 to November 2019 there were 4768 AFCs resulted at TAMC with 49 MTB-positive AFC, leading to a cumulative prevalence of 1.03 percent (Figure 1). After controlling for other factors, Asian-Pacific Islanders had nearly 15 times higher odds of having a positive AFC than whites (OR=14.96, 95% CI 5.03, 44.55, p=< 0.001) and active duty personnel had 2.6 times the odds of having a positive AFC than dependents, civilians and retirees (OR=2.6, 95% CI 0.94, 7.22, p=0.067).

Figure 1. The Prevalence of M. tuberculosis (MTB) among Acid Fast Cultures (AFC) from Military Health System Beneficiaries from Hawaii and Pacific Islands from January 2002 to November 2019.

Conclusion

The low prevalence of MTB among AFCs performed at our institution over nearly 16 years suggests that living in the state of HI does not appear to confer high rates of TB to MHS beneficiaries. Persons with Asian-Pacific Islander ethnicity have higher odds of positive AFC which corroborates prior studies regarding risk factors for MTB. Further analysis is needed to further define risk factors associated with positive AFC among MHS beneficiaries in HI. Follow-up analysis is underway to describe the clinical course of the persons with MTB-positive AFC from this study.

Disclosures

All Authors: No reported disclosures
1663. The Significance of Acid Fast Cultures in Peritoneal Dialysis-associated Infections: A Non-tuberculous Mycobacteria Case Series
Authors: Lusby Heather , Cannella Anthony
Published: January 2021

Background

Non-tuberculosis mycobacteria (NTM) are a group of Mycobacterium that are defined as species other than Mycobacterium tuberculosis complex and Mycobacterium leprae. Rapid growing NTM’s grow on culture media as early as 5-7 days. NTM’s are considered a rare cause of peritoneal dialysis (PD) associated infections.

Methods

We highlight four cases of PD catheter associated infections due to rapid growing NTMs to covey the importance of these bacteria in the setting of PD associated infections.

Results

All of our cases all were on PD due to their end stage renal disease (ESRD). Case 1 is a 55-year-old man who was on PD due to IgA nephropathy. He had ulceration around catheter site and abdominal pain for 3 months prior to presentation. Catheter site and peritoneal fluid were both positive for Mycobacterium abscessus. Case 2 is a 59-year-old woman with who was on PD due to Alport syndrome. She presented with fever and pain around PD catheter site. Cultures were positive for Mycobacterium fortuitum. Case 3 is a 68-year-old woman who was on PD due to diabetic nephropathy. She presented after increased drainage around PD-catheter site after 2 months duration. Cultures from catheter site grew Mycobacterium porcinum. Case 4 is a 73-year-old male with who was on PD due to diabetic nephropathy. He presented due to erythema around his PD catheter site. Catheter site cultures were positive for M. abscessus. Each case was treated based upon culture data and for varied length of time, which can be further seen in Table 1.

Table 1

Conclusion

Typical organisms that cause peritonitis and PD exit site infections are from skin flora contamination. The International Society of Peritoneal Dialysis recommends anaerobic and aerobic cultures to be obtained in suspected peritonitis. Expected culture negative rate are typically about 10-20%. NTM’s can be often missed and diagnosed as a culture negative infection if routine acid-fast bacilli (AFB) cultures are not obtained. Also, NTMs are likely to be under represented since these are not considered reportable. A high index of suspicion would mandate culturing for NTMs as a potential cause of PD catheter associated infection. With having 4 cases all in Florida, we would like to stress the importance of ordering AFB cultures in PD catheter associated infections.

Disclosures

All Authors: No reported disclosures
1666. Yield of Tuberculosis Contact Tracing among Veterans after Outpatient Exposure
Authors: Yang Janet , Fritz Carman , Kundu-Raychaudhuri Smriti , Dailey Jeffrey , Bang Heejung , Nguyen Hien , Maniar Archana
Published: January 2021

Background

Tuberculosis contact tracing (TBCT) is essential to detecting transmission. High priority contacts for TBCT include children less than 5 and those with prolonged, close contact with a tuberculosis (TB) case. Other populations considered high priority include those with certain comorbidities. While data are limited, there is evidence for transmission in outpatient settings with short duration/casual contact. We describe the yield of TBCT among a high priority cohort after exposure in to active TB in VA clinics.

Methods

Between 2016-2019, VA Northern California performed 4 episodes of TBCT in the outpatient setting. In TBCT 1, the index case was an AFB smear positive healthcare worker (HCW) with 30-minute patient appointments. In TBCT 2-4, the index cases were patients, 2 of whom were AFB smear positive. TBCT included patients seen by the HCW (TBCT 1) and those with appointments one hour before or after the index patient in the same clinic (TBCT 2-4). Contacts were offered interferon-gamma release-assay (IGRA). Staff contacts were tested by purified protein derivative (PPD). Comorbidities, prevalent and new cases with positive TB testing were calculated and compared between different groups.

Results

Fifty-one percent of veteran contacts had comorbidities placing them in a high priority group for TBCT. Among the 593 patients who had an IGRA during TBCT, 40 (6.7%) tested positive. Twenty-six (4.4%) had no known history of prior positive TB test of whom 6 reported a previous TB exposure history. Veterans exposed to the HCW did not have a higher prevalence of IGRA positivity or a new positive IGRA compared to TBCT 2-4 (5.5% vs 8.0%, p-value 0.22 and 3.4% vs. 5.3%, p-value 0.26). Among the 130 staff tested in TBCT 1-4, one (0.7%) converted during TBCT 1.

Conclusion

After extensive TBCT, the prevalence of latent TB among short duration/casual contacts of TB was 6.7%, similar to the baseline prevalence of latent TB of 6% in California. In this high priority population for TBCT, no difference was seen when there was face-to-face contact versus a shared waiting room with the index case. Staff conversion rate was extremely low. While decisions to perform TBCT in outpatient settings need to be individualized, the yield of TBCT in this population of veterans was low.

Disclosures

All Authors: No reported disclosures
1671. Diagnosis and management of Escherichia coli bacteriuria at a Veterans Affairs hospital
Authors: Shah Niyati H , Decker Brooke K , Decker Brooke K , Sgro Gaetan , Boudreaux-Kelly Monique Y , Corredera Erica
Published: January 2021

Background

The IDSA recommends against screening for and treating ASB in all patients except for those pregnant or undergoing urologic procedures. Nevertheless, antibiotic treatment of ASB is widespread. We conducted a retrospective analysis of physician practices in diagnosis and management of Escherichia coli (E. coli) ASB in a male Veteran population, and compared outcomes in ASB patients treated or not treated with antibiotics.

Methods

Patients with an E. coli positive urine culture during an ED visit or inpatient admission from 01/2017 to 12/2017 were screened. Patients admitted to the intensive care unit or diagnosed with a sexually transmitted infection, pyelonephritis, prostatitis, or epididymitis/orchitis were excluded. A total of 163 patients were included. Demographics, clinical comorbidities and severity of illness, and outcomes were compared in ASB patients managed with or without antibiotics. ANOVA and Chi-square or Fisher’s exact tests were utilized for comparing measurements.

Results

ASB was present in 92/163 patients. The majority (74%) of these patients were given antibiotics. Regardless of qSOFA score or alternate infection, there were no significant differences in outcomes between ASB patients treated or not treated with antibiotics: 3-month mortality (15% vs 21%; p = 0.53), emergence of newly resistant bacterial pathogens (7% vs 13%; p = 0.43), recurrent urinary tract infections (61% vs 50%; p = 0.72), clearance of urinary pathogens (75% vs 58%; p = 0.45), length of hospital stay (7 vs 6 days, p = 0.67). Factors that were predictive of physician treatment of ASB included patient comorbid conditions such as benign prostatic hyperplasia, pyuria, and the absence of hematuria. The incidence of adverse events with antibiotic treatment of ASB was low.

Conclusion

The rate of antibiotic treatment of E. coli ASB in male veterans is high. Outcomes do not differ among ASB patients managed with or without antibiotics. Future studies examining outcomes in patients prescribed antibiotics for multiple episodes of ASB may yield differences, particularly in emergence of resistant pathogens. Focusing on patients with comorbid conditions who are not critically ill would be a high yield target for provider education to reduce ASB treatment.

Disclosures

All Authors: No reported disclosures
1674. Epidemiology of Urinary Tract Infections in the Renal Transplant Population in a Large Urban Midwestern Hospital: A Retrospective Cohort Study
Authors: Kumar Rebecca Nirmal , Zembower Teresa , Stosor Valentina
Published: January 2021

Background

Renal Transplant Recipients (RTR) are at high risk for Urinary Tract Infections (UTIs). However, the best empiric option for treatment is not well defined, because the prevalence of extended spectrum beta-lactamase (ESBL) Enterobacteriaceae and carbapenem resistant Enterobacteriaceae (CRE). The primary purpose of this study was to describe the prevalence of multidrug resistant UTIs in a contemporary cohort of RTR at a large Midwestern tertiary care hospital. Secondary outcomes evaluated frequency of key symptoms and physical exam findings, as well as characteristics of patients who developed multidrug resistant organisms, morbidity, and mortality.

Methods

This was a single-center retrospective cohort study. Patients were included if they were 18 years or older and underwent their transplant between July 11, 2019 and November 26, 2018. Statistical analysis was performed using Fischer’s Exact T-test for comparison of the patients with and without ESBL UTIs. Significance was defined by a p< 0.05

Results

Two hundred fifty-two patients were evaluated (median age 54.4, 38.3% female gender), 36 patients developed UTIs, and no patients had CRE organisms. ESBL UTI prevalence was 7/252 (2.8%) among the total RTR population and 7/36 (19.4%) among the population of RTR who developed UTIs. Mortality rates did not differ significantly between patients with and without ESBL UTI (0% and 6.9%, respectively, p=.489) (Table 1). Additional clinical characteristics of the patients that developed ESBL UTIs were also obtained (Table 2).

Table 1: Comparison of non-ESBL UTI and ESBL UTI

Table 2: Characteristics of Patients with ESBL UTI

Conclusion

Prevalence of ESBL UTIs among RTR are low at a tertiary Midwestern hospital.

Disclosures

All Authors: No reported disclosures
1675. Epidemiology of Urinary Tract Infections in the United States, 2009 - 2018
Authors: Foster Kendra , Polgreen Linnea A , Faine Brett , Polgreen Philip M
Published: January 2021

Background

Urinary tract infections (UTIs) are one of the most common bacterial infections. There is a lack of large epidemiologic studies evaluating the etiologies of UTIs in the United States. This study aimed to determine the prevalence of different UTI-causing organisms and their antimicrobial susceptibility profiles among patients being treated in a hospital setting.

Methods

We used the Premier Healthcare Database. Patients with a primary diagnosis code of cystitis, pyelonephritis, or urinary tract infection and had a urine culture from 2009- 2018 were included in the study. Both inpatients and patients who were only treated in the emergency department (ED) were included. We calculated descriptive statistics for uropathogens and their susceptibilities. Multi-drug-resistant pathogens are defined as pathogens resistant to 3 or more antibiotics. Resistance patterns are also described for specific drug classes, like resistance to fluoroquinolones. We also evaluated antibiotic use in this patient population and how antibiotic use varied during the hospitalization.

Results

There were 640,285 individuals who met the inclusion criteria. Females make up 82% of the study population and 45% were age 65 or older. The most common uropathogen was Escherichia Coli (64.9%) followed by Klebsiella pneumoniae (8.3%), and Proteus mirabilis (5.7%). 22.2% of patients were infected with a multi-drug-resistant pathogen. We found that E. Coli was multi-drug resistant 23.8% of the time; Klebsiella pneumoniae was multi-drug resistant 7.4%; and Proteus mirabilis was multi-drug resistant 2.8%. The most common antibiotics prescribed were ceftriaxone, levofloxacin, and ciprofloxacin. Among patients that were prescribed ceftriaxone, 31.7% of them switched to a different antibiotic during their hospitalization. Patients that were prescribed levofloxacin and ciprofloxacin switched to a different antibiotic 42.8% and 41.5% of the time, respectively.

Conclusion

E. Coli showed significant multidrug resistance in this population of UTI patients that were hospitalized or treated within the ED, and antibiotic switching is common.

Disclosures

All Authors: No reported disclosures
1676. Evaluation of Antibiotic Overuse for Asymptomatic Bacteriuria in a Hospital with Low Baseline Antibiotic Use
Authors: Kernan Bailey , Shihadeh Katherine C , Jenkins Timothy C
Published: January 2021

Background

In 2019, the Infectious Diseases Society of America published guidelines for the management of asymptomatic bacteriuria (ASB) with recommendations to avoid antimicrobial therapy in most patients. Denver Health has existing guidance for the management of patients with a urinary tract infection (UTI) and in August of 2019, implemented specific guidance for the management of ASB. As an institution, Denver Health has a Standardized Antimicrobial Administration Ratio (SAAR) of 0.8-0.9, suggesting a strong antimicrobial stewardship program with a ratio of < 1. The purpose of this study is to assess if signs and symptoms were present in patients prescribed an antibiotic for UTI.

Methods

We retrospectively identified hospitalized patients at least 18 years old who were prescribed an antibiotic with “UTI” as the indication from March 1st to August 31st, 2019. Patients with catheter-associated UTIs were excluded. A random sample of 50 cases was manually reviewed for signs and symptoms of infection. Signs were considered fever, defined as at least 38oC or leukocytosis, defined as at least 10 k/uL WBC. Symptoms collected were based on documentation of patient reported dysuria, frequency, or urgency, or findings of hematuria. The primary outcome was proportion of patients prescribed an antibiotic for UTI in the absence of signs or symptoms. Prescribing patterns for choice and duration of antimicrobials were also surveyed.

Results

A total of 382 antibiotics were prescribed for UTI during the study period. Of the 50 cases reviewed, median age was 65.8 years, with 11% being male. Overall, 29 patients (58%) had no documented symptoms while being treated for UTI. Additionally, 22 patients (44%) had no documented fever, leukocytosis, or urinary symptoms. The most commonly prescribed antibiotics were cefdinir, fosfomycin, and nitrofurantoin. Tables 1 and 2 include additional findings.

Table 1 Symptomology and Type of UTI

Table 2 Antimicrobial Choice and Duration

Conclusion

Despite a well established stewardship program, nearly half of patients prescribed an antibiotic for UTI did not have signs or symptoms consistent with infection. This suggests many patients were treated for ASB, without necessity. Among hospitals with comparatively low antibiotic use, ASB may be a high-yield opportunity to reduce unnecessary antibiotic use.

Disclosures

All Authors: No reported disclosures
1679. Evaluation of the Treatment of Urinalyses and Urine Cultures in Multiple Sclerosis Patients
Authors: Griffith Nicole C , Hill Brandon , Tingen S Ross , Crowe J Cameron
Published: January 2021

Background

Patients with Multiple Sclerosis (MS) experience lower urinary tract dysfunction (LUTD) that in some cases, may necessitate catheterization. Discerning asymptomatic bacteriuria (ASB) from urinary tract infection (UTI) in MS patients is complicated by LUTD, leading to potentially inappropriate antimicrobial use. The purpose of this study was to evaluate the antimicrobial treatment practices of positive urine cultures in patients with MS.

Methods: A single-center, retrospective study. Positive cultures in patients with diagnosed MS (ICD10: G35) were included. The primary outcome was the proportion of patients that were appropriately treated with or without antimicrobial therapy. Secondary endpoints included antimicrobial selection and urinalysis obtainment and positivity.

Results

236 cultures from 139 patients were evaluated. Frequency, nocturia, dysuria, and foul-smelling urine were reported by patients in 54 (23%), 10 (4%), 25 (11%), and 14 (6%) of cases, respectively. Treatment was inappropriate in 81/201 (40%) of treated cultures. The agent selected was considered too broad in 35/201 (17%) instances. Of those, fluoroquinolones were the agents utilized in 33/35 (94%) cases. A urinalysis was sent in 200 (85%) cases, with 197/200 (99%) positive for at least one of four pre-defined positivity criteria.

Conclusion

Urinalyses and urine cultures are obtained frequently in patients with MS, often independent of patient symptomatology. Multiple sclerosis patients may be treated for ASB at higher rates than the general population, and traditional urinary symptoms may not be appropriate indicators of infection. Empiric therapy for UTI is frequently utilized in this population, often resulting in too broad of antimicrobial therapy.

Disclosures

All Authors: No reported disclosures
1681. Female Urinary Metagenomic Analysis and Natural Language Processing Enhances the Infectious Diagnostic Yield in Precision Medicine
Authors: Valencia C Alexander , Baugher David , Larsen Alexander , Chen Alvin , Icenhour Crystal
Published: January 2021

Background

In this study, we assessed the diagnostic yield of metagenomics urine sample testing in patients with urological symptoms.

Methods

We conducted metagenomic analysis on 69 consecutive unbiased female patients, by sequencing their DNA using the KAPA HyperPlus library construction with next-generation sequencing (Nextseq500, Illumina) and reads were analyzed using Xplore-Patho®, an analytical system that permits the detection of 37,000+ microorganisms, including over 12,000 known pathogens, and examined report summaries written by infectious disease experts to obtain a diagnostic yield. In addition, infectious disease expert analysis was contrasted with a natural language (NLP) pathogen detection system to investigate its accuracy.

Results

In the expert data summaries, a total of 95% of the patients tested had at least one pathogen identified by metagenomics as a potential explanation of their urological symptoms and these results were binned into four categories: 1) 51% of infection likely, 2) 4% of infection possible, 3) 26% of low-grade infection likely and 4) 14% of low-grade infection possible. Data from healthy controls was used in conjunction with an NLP pathogen detection pipeline and compared to infectious disease expert summaries. The NLP pathogen algorithm detected that at least 97% of samples had one pathogen which was more than 5 standard deviations from the abundance of that pathogen in healthy controls, and least 84% had 2 or more pathogens. These diagnostic percentages were consistent with the infectious disease expert summaries. The NLP algorithm had access to a large database derived from PubMed articles and it was found that several relevant uropathogens were not mentioned in report summaries. For example, one well-documented uropathogen was present in 13 samples, but was not mentioned in any report summaries.

Conclusion

In conclusion, this study demonstrated the high diagnostic yield in females with urological symptoms following metagenomic analysis and the ability of NLP to enhance the sensitivity of reportable pathogens.

Disclosures

All Authors: No reported disclosures
141. Implementation of Veterans Affairs Outpatient Antimicrobial Stewardship Interventions for Asymptomatic Bacteriuria and Acute Respiratory Infections, a Stepped Wedge Randomized Study
Authors: Mortrude Grace , Rehs Mary , Sherman Katherine , Gundacker Nathan , Dysart Claire
Published: January 2021

Background

Outpatient antimicrobial prescribing is an important target for antimicrobial stewardship (AMS) interventions to decrease antimicrobial resistance in the United States. The objective of this study was to design, implement and evaluate the impact of AMS interventions focused on asymptomatic bacteriuria (ASB) and acute respiratory infections (ARIs) in the outpatient setting.

Methods

This randomized, stepped-wedge trial evaluated the impact of educational interventions to providers on adult patients presenting to primary care (PC) clinics for ARIs and ASB from 10/1/19 to 1/31/20. Data was collected by retrospective chart review. An antibiotic prescribing report card was provided to PC providers, then an educational session was delivered at each PC clinic. Patient education materials were distributed to PC clinics. Interventions were made in a step-wise (figure 1) fashion. The primary outcome was percentage of overall antibiotic prescriptions as a composite of prescriptions for ASB, acute bronchitis, upper-respiratory infection otherwise unspecified, uncomplicated sinusitis, and uncomplicated pharyngitis. Secondary outcomes included individual components of the primary outcome, a composite safety endpoint of related hospital, emergency department or primary care visit within 4 weeks, antibiotic appropriateness, and patient satisfaction surveys.

Figure 1

Results

There were 887 patients included for analysis (405 pre-intervention, 482 post-intervention). Baseline characteristics are summarized in table 1. After controlling for type 1 error using a Bonferroni correction the primary outcome was not significantly different between groups (56% vs 49%). There was a statistically significant decrease in prescriptions for bronchitis (20.99% vs 12.66%; p=0.0003). Appropriateness of prescriptions for sinusitis (OR 4.96; CI 1.79–13.75; p=0.0021) and pharyngitis (OR 5.36; CI 1.93 – 14.90; p=0.0013) was improved in the post-intervention group. The composite safety outcome and patient satisfaction survey ratings did not differ between groups.

Table 1

Conclusion

Multifaceted educational interventions targeting providers can improve antibiotic prescribing for indications rarely requiring antimicrobials without increasing re-visit or patient satisfaction surveys.

Disclosures

All Authors: No reported disclosures
1683. Hospital Admission Patterns in Adult Patients with Complicated Urinary Tract Infections (cUTIs): Identification of Potentially Avoidable Hospital Admissions Across United States (US) Hospitals
Authors: Lodise Thomas , Chopra Teena , Nathanson Brian , Sulham Katherine
Published: January 2021

Background

There is an increase in hospital admissions for cUTI in the US despite apparent reductions in the severity of admissions. However, there are scant data on cUTI hospital admission rates from the emergency department (ED) stratified by age, infection severity, and presence of comorbidities. This study described US hospitalization patterns among adults who present to the ED with a cUTI. We sought to quantify the proportion of admissions that were potentially avoidable based on presence of sepsis and associated symtpoms as well as Charlston Comorbidity Index (CCI) scores.

Methods

A retrospective multi-center study using data from the Premier Healthcare Database (2013-18) was performed. Inclusion criteria: (1) age ≥ 18 years, (2) primary cUTI ED/inpatient discharge diagnosis, (3) positive blood or urine culture between index ED service days -5 to +2. Transfers from acute care facilities were excluded. Based on ICD-9/10 diagnosis codes present on admission, incidence of hospital admissions were stratified by age (≥ 65 years vs. < 65 years), presence of sepsis (S), sepsis symptoms but no sepsis codes (SS) (e.g., fever, tachycardia, tachypnea, leukocytosis, etc.), and CCI.

Results

187,789 patients met inclusion criteria. The mean (SD) age was 59.7 (21.9), 40.4% were male, 29.4% had sepsis, 16.7% had at least 1 SS symptom (but no S), and 53.9% had no evidence of S or SS. The median [IQR] CCI was 1 [0, 3]. 119,668 out of 187,789 (63.7%) were admitted to hospital. Among inpatients, median [IQR] length of stay (LOS) and total costs were 5 [3, 7] days and $7,956 [$4,834, $13,960] USD. Incidence of hospital admissions by age, presence of S/SS, and CCI score are shown in the Table. 18.9% of admissions (22,644/119,668) occurred in patients with no S/SS and a CCI ≤ 2. Their median [IQR] LOS and total costs were 3 [2, 5] days and $5,575 [$3,607, $9,133].

Incidence of Hospital Admission by Age, Charlson comorbidity index (CCI), Presence of Sepsis (S), and Presence of Sepsis Symptoms (SS)

Conclusion

Nearly 1 in 5 cUTI hospital admissions may be avoidable. Given the resources associated with the management of inpatients with cUTIs, these findings highlight the critical need for healthcare systems to develop well-defined criteria for hospital admission based on presence of comorbid conditions and infection severity. Preventing avoidable hospital admissions has the potential to save the healthcare system substantial costs.

Disclosures

Thomas Lodise, PharmD, PhD, Paratek Pharmaceuticals, Inc. (Consultant) Teena Chopra, MD, MPH, Spero Therapeutics (Consultant, Advisor or Review Panel member) Brian Nathanson, PhD, Spero Therapeutics (Independent Contractor) Katherine Sulham, MPH, Spero Therapeutics (Independent Contractor)
1685. Inappropriate Treatment of Asymptomatic Bacteriuria in Elderly Patients: A Quality Improvement Study
Authors: Cornelius Tuhina , Patel Kiran K , Rubinson Michael , Aslam Nadia , Rana Ashish , Abandeh Foad
Published: January 2021

Background

Asymptomatic bacteriuria is often misdiagnosed as Urinary Tract Infection (UTI) in elderly patients. Studies suggest that 15-30% of males and 25-50% of females have asymptomatic bacteriuria. We wanted to estimate the percentage of elderly patients who are treated for UTI at our facility and if treatment was appropriate. The goal was to provide the staff with an educational opportunity and help decide if more antibiotic restriction policies would be beneficial.

Methods

A retrospective study of patients > 65 years of age who were started on antibiotics for presumed UTI at a single medical center between 7/2018 and 12/2018. Reviewed data included demographics, admitting diagnosis, presence or absence of symptoms of UTI and urine culture results. The data was presented at educational conferences and at antimicrobial stewardship meetings in our facility.

Results: 234 patients were started on antibiotics on the basis of pyuria on admission. Of these, only 47% (n=110/234) had symptoms suggestive of UTI. Positive urine cultures were more common in symptomatic patients (n=93/110) compared with asymptomatic patients (n=47/80).

In addition, ninety patients had a change in mental status on presentation and were started on antibiotics for suspected UTI. Approximately one third of these patients had eventual negative urine cultures.

Conclusion: Elderly patients with pyuria and asymptomatic bacteriuria represent a diagnostic challenge due to their inability to vocalize signs or symptoms of UTI. In addition, a percentage of patients who are asymptomatic and admitted for another reason were often started on antibiotics inappropriately on the basis of pyuria alone. Studies have shown that treating asymptomatic bacteriuria does not add a mortality benefit or lower risk of infection. The CDC emphasizes the importance of assessing for clinical symptoms of UTI before treatment is considered.

Our study highlights the importance of provider education in the management of asymptomatic bacteriuria in elderly patients. We also feel that antibiotic restriction policies may limit use of antibiotics for asymptomatic bacteriuria. This would in turn improve patient outcomes and decrease incidence of clostridium difficile associated colitis.

Disclosures

All Authors: No reported disclosures
1686. Microbiology of Community-Onset Urinary Tract Infections in the United States, 2012-2017
Authors: Preston Leigh Ellyn , McDonald Clifford , Olubajo Babatunde , McCarthy Natalie , Reddy Sujan , Wolford Hannah , Hatfield Kelly M , Sheriff Edward , Jernigan John A , Kourtis Athena P , Baggs James
Published: January 2021

Background

Community-onset urinary tract infections (coUTIs) are one of the most common indications for antibiotic prescribing. It is important to understand patient demographic factors associated with microorganisms causing coUTI and their antibiotic resistance profiles, to tailor antibiotic prescribing practices. We analyzed microbiology data to understand factors associated with coUTI in the United States (US).

Methods

CoUTIs were identified in the Premier Healthcare Database and Cerner Health Facts among patients treated at participating healthcare facilities in the US between 2012-2017. Cases were defined by urine cultures yielding a bacterial organism and were collected in outpatient settings or within three days of hospitalization. Only the first specimen for each encounter was included in the analysis. Data on the organisms isolated, patient’s age, sex, and US census regions of the submitting facilities were described and compared using chi-square tests for associations. Encounters were classified as inpatient (INPT), observation (OBS), emergency department (ED), and outpatient (OTPT) based on the setting in which the culture was submitted.

Results

Using data from 637 acute care hospitals, urine samples from 3,291,561 encounters were included, with 776,653 (25.7%) INPT, 1,063,219 (34.8%) ED, 107,760 (3.5%) OBS, and 1,092,658 (35.8%) OTPT. The pathogens most frequently associated with coUTIs were Escherichia coli (57.3%), Klebsiella pneumoniae (9.7%), Enterococcus faecalis (5.1%), Proteus mirabilis (4.9%), and Pseudomonas aeruginosa (2.9%). Female sex, age < 65y and OTPT and ED settings were associated with higher relative frequency of E. coli (all p < 0.0001). Male sex, INPT setting and age >65 y were associated with higher relative frequency of P. aeruginosa, P. mirabilis and E. faecalis (all p < 0.0001, Figure). K. pneumoniae was found at higher relative frequency in those >45y, and in INPT and OBS settings (all p < 0.0001).

Figure. Distribution of pathogens most frequently associated with community onset urinary tract infections

Conclusion

Understanding patient factors associated with the microbiology of coUTIs is an important step in developing treatment recommendations and antibiotic stewardship efforts. Further analyses will include assessing the impact of major antibiotic resistance phenotypes, geographic and healthcare settings.

Disclosures

All Authors: No reported disclosures
1690. Oral Fosfomycin for the Treatment of Bacterial Prostatitis
Authors: Kamath Meghan , Johns Scott T , Ma Ariel , Mehta Sanjay
Published: January 2021

Background

Bacterial prostatitis (BP) is notoriously difficult to treat. Few antibiotics penetrate the prostate well, and antibiotic resistance can further restrict options. A small body of recent literature suggests fosfomycin, a bactericidal antibiotic that can treat multidrug resistant (MDR) organisms and has little cross-resistance, may both effectively penetrate the prostate and treat BP. This study sought to add to the limited literature on the efficacy and safety of fosfomycin for BP.

Methods

Patients treated for BP with fosfomycin between November 2009 and May 2019 at the San Diego VAMC were retrospectively examined. Patients were excluded if they died within 6 months of completion of fosfomycin or if fosfomycin was used for less than half of the treatment course. If fosfomycin was used to treat a urinary tract infection (UTI), an infectious disease physician determined if the UTI may have been undiagnosed BP. Outcomes were clinical and microbiological cure at 6 months and adverse events to fosfomycin reported during the trial period.

Results

The study included 29 patient cases. All but one had chronic BP. Most initially presented outpatient (66%). Almost all had prior occurrences of BP treated with antibiotics (90%). The most common pathogen was E. coli (73%), and 87% of all pathogens were MDR. The most common fosfomycin dosing regimen was 3g PO q48h (66%), with 3g PO q24h as the next most common (21%). Less than half of patient cases received fosfomycin courses > 28 days (38%), while the remaining received courses < 14 days (62%). At 6 months, 48% achieved clinical cure and 44% achieved microbiological cure. When comparing those who received courses > 28 days vs. courses < 14 days, clinical cure was achieved in 55% vs. 44% and microbiological cure in 56% vs. 39%, respectively. Adverse events were reported in 6 unique patients (27%), mostly diarrhea with one instance of nausea.

Conclusion

Fosfomycin may be a safe and effective alternative for the treatment of chronic BP. Treatment courses longer than 4 weeks may be more effective than courses shorter than 2 weeks with a similar rate of adverse events. This study also highlights inpatients as a relevant BP population and a need for provider education on identifying BP and prescribing optimal durations of therapy.

Disclosures

All Authors: No reported disclosures
142. Implementing an Antimicrobial Stewardship Program in the Outpatient Setting
Authors: Nielsen Travis B , Santarossa Maressa , Probst Beatrice D , Labuszewski Laurie , Lopez Jenna , Barsanti-Sekhar Mary C , Albarillo Fritzie S
Published: January 2021

Background

Antimicrobial-resistant infections lead to increased morbidity, mortality, and healthcare costs. Among the most facile modifiable risk factors for developing resistance is inappropriate prescribing. The CDC estimates that 47 million (or ≥30% of) outpatient antibiotic prescriptions in the United States are unnecessary. This has provided impetus for expanding our antimicrobial stewardship program (ASP) into the outpatient setting. Initial goals included the following: continuous evaluation and reporting of antibiotic prescribing compliance; minimize underuse of antibiotics from delayed diagnoses and misdiagnoses; ensure proper drug, dose, and duration; improve the percentage of appropriate prescriptions.

Methods

To achieve these goals, we first sent a baseline survey to outpatient prescribers, assessing their understanding of stewardship and antimicrobial resistance. Questions were modeled from the Illinois Department of Public Health (IDPH) Precious Drugs & Scary Bugs Campaign. The survey was sent to prescribers at 19 primary care and three immediate/urgent care clinics. Compliance rates for prescribing habits were subsequently tracked via electronic health records and reported to prescribers in accordance with IRB approval.

Results

Prescribers were highly knowledgeable about what constitutes appropriate prescribing, with verified compliance rates highly concordant with self-reported rates. However, 74% of respondents reported intense pressure from patients to inappropriately prescribe antimicrobials. Compliance rates have been tracked since December 2018 and comparing pre- with post-intervention rates shows improvement in primary care since reporting rates to prescribers in August 2019.

Conclusion

Reporting compliance rates has been helpful in avoiding inappropriate antimicrobial therapy. However, the survey data reinforce the importance of behavioral interventions to bolster ASP efficacy in the outpatient setting. Going forward, posters modeled off of the IDPH template will be conspicuously exhibited in exam rooms, indicating institutional commitment to the enumerated ASP guidelines. Future studies will allow for comparison of pre- and post-intervention knowledge and prescriber compliance.

Disclosures

All Authors: No reported disclosures