bluuebunny/crossref_metadata_2025 huggingface dataset:
1389. Risk Factors and Clinical Outcomes of Tuberculosis Among Kidney Transplant Recipients in High Endemic Country: A Case–Control Study
Authors: Thitisuriyarax Saranya , Jutivorakool Kamonwan , Udomkarnjananun Suwasin , Townamchai Natavudh , Suwanpimolkul Gompol , Vanichanan Jakapat
Published: October 2019

Background

Tuberculosis (TB) is considered as a challenging issue in solid-organ transplant recipients because of high morbidity and mortality. Active TB after transplant can occur from reactivation of latent infection or newly acquired from community. Understanding risk factors and clinical information of TB may provide an appropriate prevention and treatment strategies in this specific patient population; however, most of data were from non-endemic countries.

Methods

A single-center, matched case–control study was conducted in our institute. Cases were defined as newly diagnosed proven or probable active TB in patients who underwent kidney transplant between April 1992 and October 2018. For each case, 5 controls were matched by age and sex. Risk factor associated with TB was determined using univariate and multivariate conditional logistic regression.

Results

Between study period, kidney transplant was performed in 787 patients. None of the recipients was screened or treated for latent tuberculosis. Twenty-seven patients (3.43%) were diagnosed with active TB including 20 proven and 7 probable cases. The overall incidence of TB in our population was 315 cases per 100,000 patients per year. Allograft rejection was significantly associated with active TB (P < 0.001). The median onset of infection was 17 months (IQR, 4–59 months) after transplantation and 3.4 months (IQR, 2.7–16.3 months) after episode of allograft rejection. Majority of patients (96.3%) were cured after complete treatment; however, those with TB remained having significant unfavorable outcomes including higher all-cause mortality and graft loss.

Conclusion

Incidence of TB in kidney transplant recipients is higher than normal population. Increasing risk of active TB after allograft rejection is probably due to mycobacterial reactivation following high-dose immunosuppression. Since TB is associated with poor post-transplant outcomes, screening, and treatment of latent infection may be beneficial even in endemic country.

Disclosures

All authors: No reported disclosures.
1391. Latent Tuberculosis Screening Cascade in Liver Transplant Candidates: A Single, Transplant Center Experience
Authors: Medvedeva Natalia , Cheung Harry , Wootton Elizabeth , Ventura Kara , Azar Marwan M , Malinis Maricar
Published: October 2019

Background

Screening for latent tuberculosis infection (LTBI) is an essential component of the pre-transplant evaluation and key in identifying patients at risk for TB reactivation post-transplantation. At our center, liver transplant candidates (LTC) are routinely referred to transplant infectious disease (TID) for pre-TID evaluation including LTBI screening. Our aim was to determine the effectiveness of our screening practices and identify barriers to LTBI treatment.

Methods

We conducted a medical chart review of actively wait-listed LTC as of February 18/2019. Data points collected included: TB risk factors, TID referral and completion of evaluation, intention to screen for LTBI (defined as placing an order), screening completion (with documentation of a test result), screening method (IGRA or PPD), screening test result, radiographic findings, and treatment initiation and completion, if applicable. A positive screen was defined as a positive IGRA or PPD result while a negative screen was defined as a negative result or an indeterminate result with lack of epidemiological risk factors and negative radiographic findings. The proportion of LTC who completed each step in the cascade of care for LTBI was determined.

Results

Of 102 LTC, 100 met inclusion criteria. Two were excluded due to past LTBI treatment. Of 100 LTC, 95 completed a pre-TID evaluation. For 94 (98.9%), there was intention to screen. Of those intended for screening, 91 (95.8%) successfully completed screening; 6 (6.6%) patients screened positive and 85 (93.4%) screened negative. All 6 LTC who tested positive were recommended for treatment. Five of 6 (83.3%) agreed to treatment, 3/6 (50.0%) started treatment, and all 3 completed treatment. Reasons for non-treatment included: deferral until completion of HCV treatment or hepatologist approval or patient refusal. Treatment regimens included rifampin (n = 1) and isoniazid (n = 2).

Conclusion

The prevalence of LTBI in our LTC cohort was low. Nonetheless, TID played a role in the successful completion of LTBI screening and identifying those appropriate for treatment in this vulnerable patient population. Barriers to successful LTBI screening and treatment completion are contingent on effective care coordination and addressing competing co-morbidities.

Disclosures

All authors: No reported disclosures.
1392. Tuberculosis Disease in Recipients of Organ-Transplantation, California 2010–2017
Authors: Katrak Shereen , Westenhouse Janice , BARRY Pennan , Flood Jennifer
Published: October 2019

Background

Tuberculosis (TB) disease in persons who have received organ transplantation causes high morbidity, but the epidemiology and clinical features of this problem remain poorly described.

Methods

Using California TB registry data from 2010–2017, we describe clinical features of all TB cases occurring in patients who previously received solid-organ transplantation. We compared TB cases with and without transplant, and examined mortality controlling for age.

Results

During 8 years of observation, the California TB Registry recorded 116 cases of post-transplant TB. A majority of patients with post-transplant TB were >45 year old (84%), nonwhite (90%), and born outside of the United States (84%). Of 116 cases, 48 (41%) had pulmonary disease, while 68 (59%) had extra-pulmonary or both pulmonary and extra-pulmonary disease, compared with 69% and 31%, respectively, in non-transplant-associated TB (P < 0.01). Common sites of extrapulmonary disease in transplant patients included pleura (19%), cervical lymph nodes (12%), and bone (12%). Controlling for age, transplant cases were nearly twice as likely to die as non-transplant-associated TB cases (OR = 1.92, CI = 1.13, 3.25). Among 49 post-transplant TB cases with a positive TB skin test (TST) or interferon-gamma release assay (IGRA), 12 (24%) had the test performed > 6 months prior to TB diagnosis.

Conclusion

Our findings suggest that post-transplant TB disease is more likely to be extra-pulmonary and result in death than non-transplant-associated TB, and that opportunities may exist for preventing TB disease through screening and treatment for LTBI in this population.

Disclosures

All authors: No reported disclosures.
1401. Minimal Cerebrospinal Concentration of Miltefosine Despite Therapeutic Plasma Levels during the Treatment of Amebic Encephalitis
Authors: Monogue Marguerite L , Prokesch Bonnie C
Published: October 2019

Background

Miltefosine is an alkylphosphocholine compound used primarily for the treatment of leishmaniasis that also demonstrates in vitro and in vivo anti-amebic activity against Acanthamoeba species. As such, recommendations for treatment of amebic encephalitis generally include miltefosine therapy. Data support a minimum amebicidal concentration (MAC) of at least 16 μg/mL is required for most Acanthamoeba species. Given the high mortality associated with amebic encephalitis and a paucity of data regarding miltefosine levels in the plasma and cerebrospinal fluid (CSF) in vivo, we sought to determine whether a patient being treated with oral miltefosine at a higher-than-recommended dose obtained therapeutic plasma and CSF concentrations.

Methods

A patient with brain-biopsy-confirmed Acanthamoeba encephalitis was initiated on miltefosine 50mg by mouth every 6 hours (q6h), a higher frequency of therapy than recommended in the scant available literature (which suggests doses of 50 mg every 8 hours). Plasma and CSF miltefosine concentrations were collected on day 7 of treatment. CSF was collected via an external ventricular drain over a period of 1 hour. The quantification of miltefosine was performed using a Waters Xevo TQ-S triple quadrupole mass spectrometer coupled with a Waters Acquity UPLC I-class system.

Results

The trough plasma and CSF concentrations (taken 8 hours post-dose) were 16.2 and 0.007 µg/mL, respectively, resulting in a miltefosine plasma to CSF ratio of 2,440:1 µg/mL. The patient had no adverse reactions during the initial course of miltefosine therapy, though ultimately succumbed to the disease.

Conclusion

This is the first report to describe plasma and CSF concentrations after administration of miltefosine 50mg q6h for the treatment of amebic encephalitis. The administration of miltefosine 50mg q6h resulted in plasma concentrations at the suggested MAC for Acanthamoebaspp. However, the miltefosine CSF concentration was extremely low compared with the plasma level and did not reach amebicidal concentrations. While miltefosine human brain parenchyma concentrations have yet to be described in the literature, this case questions if oral miltefosine is adequate to veritably treat patients with amebic encephalitis.

Disclosures

All authors: No reported disclosures.
1421. Microbiology and Resistance of Diabetic Foot Osteomyelitis in a Teaching Hospital in Santiago, Chile
Authors: Valenzuela Pablo Tomas , E. Mühlhauser Margareta , Palma Sofia , Escobar Carola , Marin Magdalena
Published: October 2019

Background

Diabetic foot ulcers are a frequent complication of patients with diabetes mellitus, two-thirds of these can become infected and up to 50% can develop a deep infection and osteomyelitis, which usually requires surgical management and prolonged antibiotic therapy. Microbiology is characterized by a predominance of Gram-positive (Staphylococcus aureus and negative coagulase), followed by enterobacteria and non-fermentors such as P. aeruginosa, but it is variable and factors such as the type of patient, wound characteristics, use of antibiotics, and the environment. In Chile, there are no recent data on microbiology or resistance in diabetic foot osteomyelitis, which is fundamental for the rational use of antibiotics. The objective of this study was the description of this microbiology and resistance in a teaching hospital in Santiago, Chile.

Methods

Retrospective study conducted at the DIPRECA Hospital. Residual bone cultures taken from the operating room were analyzed, from patients hospitalized for diabetic foot osteomyelitis between January 1, 2013 and December 31, 2018. Sex, age, the microorganism isolated in bone and its resistance profile were analyzed. The study is approved by the Hospital Ethics Committee.

Results

We analyzed 285 cultures of 107 patients. The mean age was 71 ± 9 years and 82% corresponded to male patients. 26% of the cultures were polymicrobial. Gram-positive cocci corresponded to 68.4% and gram-negative bacilli to 31.6%. The main microorganism were E. faecalis 24.2%, S. aureus 21.8%, S. coagulase negative 18.9%, P. aeruginosa in 6.3%, K. pneumoniae in 6% and E. coli in 3.5%. In relation to resistance, E. faecalis were 98.2% sensitive to ampicillin, S. aureus were 55.5% sensitive to cefoxitin and 100% to vancomycin, S. coagulase negative were 41% sensitive to oxacillin and 100% vancomycin, P. aeruginosa were 73% sensitive to imipenem and 66% sensitive to meropenem, K. pneumoniae was 87% ESBL, 100% sensitive to imipenem and 73% to meropenem and E. coli was 63% ESBL and 100% sensitive to carbapenems.

Conclusion

Osteomyelitis of the diabetic foot was characterized as being mainly monomicrobial, by E. faecalis, Staphylococcus, P. aeruginosa, and K. pneumoniae, with a high prevalence of resistance to methicillin, ESBL and to a lesser extent resistance to carbapenems.

Disclosures

All authors: No reported disclosures.
1442. Effect of Reflex Urine Culturing on Rates of Cultures and Infections in an Acute Care Hospital, Emergency Department, and Two Long-Term Care Facilities
Authors: Lynch Chelsea , Appleby-Sigler Andrea , Bork Jacqueline , Dave Rohini , Claeys Kimberly C , Zhan Min , Agnes Kathy , Sanikop Molly , Heath Dori , Clark Arlene , Morgan Daniel
Published: October 2019

Background

Urine cultures are often positive in the absence of urinary tract infection (UTI) leading to unnecessary antibiotics. Reflex culturing decreases unnecessary urine culturing in acute care settings but the benefit in other settings is unknown.

Methods

This was a quasi-experimental study performed at a health system consisting of an acute care hospital, an emergency department (ED), and two long-term care (LTC) facilities. Reflex urine criterion was a urine analysis with > 10 white blood cells/high-power field. Urine cultures performed per 100 bed days of care (BDOC) were compared pre- (August 2016 to July 2017) vs. post-intervention (August 2017 to August 2018) using interrupted time series regression. Catheter-associated UTI (CAUTI) rates were reviewed to determine potential CAUTIs that would have been prevented.

Results

In acute care, pre-intervention, 894 cultures were performed (3.6 cultures/100 BDOC). Post-intervention, 965 urine cultures were ordered and 507 cultures were performed (1.8 cultures/100 BDOC). Reflex culturing resulted in an immediate 49% decrease in cultures performed (P < 0.001). The CAUTI rate 2 years pre-intervention was 1.8/1000 catheter days and 1.6/1000 catheter days post-intervention. Reflex culturing would have prevented 4/14 CAUTIs. In ED, pre-intervention, 1393 cultures were performed (5.4 cultures/100 visits). Post-intervention, 1959 urine cultures were ordered and 917 were performed (3.3 cultures/100 visits). Reflex culturing resulted in an immediate 47% decrease in cultures performed (P = 0.0015). In LTC, pre-intervention, 257 cultures were performed (0.4 cultures/100 BDOC). Post-intervention, 432 urine cultures were ordered and 354 were performed (0.5 cultures/100 BDOC). Reflex culturing resulted in an immediate 75% increase in cultures performed (P < 0.001). The CAUTI rate 2 years pre-intervention was 1.0/1000 catheter days vs. 1.6/1,000 catheter days post-intervention. Reflex culturing would have prevented 1/13 CAUTIs.

Conclusion

Reflex culturing canceled 16%-51% of cultures ordered with greatest impact in acute care and the ED and a small absolute increase in LTC. CAUTI rates did not change although reflex culturing would have prevented 29% of CAUTIs in acute care and 8% in LTC.

Disclosures

All authors: No reported disclosures.
1444. Urine Screening Prior to Surgical Valve Replacement: Should It Be Performed?
Authors: LeVee Alexis , Beaulac Kirthana , Doron Shira
Published: October 2019

Background

Screening for and treatment of asymptomatic bacteriuria (ASB) is controversial prior to surgical valve replacement (SVR). The theoretical concern that the bacteria can translocate to the surgical site, causing infective endocarditis (IE), has not been well-described. At our institution, screening for and treatment of ASB is routine prior to SVR. This study aims to identify whether an association exists between ASB and post-op infections in patients undergoing SVR.

Methods

A single-center retrospective study was conducted for patients who had SVR between 2016 and 2018. Pre-op urinalyses (UAs) and cultures, symptoms of UTI, and antibiotic therapy were collected during the 60-day pre-op period. Infections, antibiotic therapy, development of resistance, 30-day readmission rates, and 30- and 90-day mortality rates were collected up to 3 months post-op. Statistical analysis was performed using the Chi-square and Fisher exact tests.

Results

Of the 358 patients who underwent SVR, pre-op UAs were performed in 329 (92%) patients; of whom, 296 (91%) were asymptomatic. Amongst those asymptomatic, 14 (5%) cultures were positive and 11 (79%) positive cultures were treated. Patients with ASB had no difference in post-op infection (1/14 [7%] vs. 32/282 [11%]; P = 1), 30-day readmission rate (1/14 [7%] vs. 44/282 [16%]; P = 0.7), or 90-day mortality rate (0/14 [0%] vs. 4/282 [1%]; P = 1) compared with those with negative urine cultures. Patients who were treated for ASB also showed no difference in these same outcomes compared with those not treated. IE was a complication in 3 of 358 (1%) cases, and none of these patients had ASB or symptomatic UTI prior to surgery. Antibiotic treatment prior to surgery was associated with acquisition of a multi-drug-resistant organism (9/68 [13%] vs. 15/290 [5%]; P = 0.02). There was a trend toward increased 30-day readmission rate (15/68 [22%] vs. 43/290 [15%]; P = 0.15) and development of resistance (1/68 [1%] vs. 0/290 [0%]; P = 0.19) in patients who received pre-op antibiotics.

Conclusion

In this study, ASB prior to SVR was not related to post-op infection, and treatment of ASB did not prevent future infection. Antibiotic treatment prior to SVR was associated with the development of MDROs. Urine screening prior to SVR should be avoided.

Disclosures

All authors: No reported disclosures.
1445. Antimicrobial Activity of Novel β-Lactamase Inhibitor Combinations Tested against Organisms Causing Complicated Urinary Tract Infections in United States Medical Centers
Authors: Sader Helio S , Carvalhaes Cecilia G , Shortridge Dee , Huband Michael D
Published: October 2019

Background

High-dose extended-infusion cefepime-tazobactam (FEP-TAZ) is in clinical development at 2g/2g q8 hours administered over 90 minutes. We evaluated the potency and spectrum of activity of FEP-TAZ, ceftolozane–tazobactam (C-T), ceftazidime–avibactam (CAZ-AVI), and comparators tested against gram-negative bacilli (GNB) causing complicated urinary tract infections (cUTIs) in United States (US) hospitals.

Methods

In 2018, 3,023 GNBisolates (1/patient) were consecutively collected and susceptibility tested against FEP-TAZ (TAZ at fixed 8 mg/L) and comparators by reference broth microdilution methods. Percentage of isolates inhibited at ≤8 mg/L (CLSI, cefepime high dose) and at ≤16 mg/L (pharmacokinetic/pharmacodynamic [PK/PD] susceptible [S] breakpoint based on extended infusion and high dosage) were evaluated.

Results

FEP-TAZ (99.9% inhibited at ≤16 mg/L; Table), CAZ-AVI (99.9%S), and meropenem (MEM; 99.5%S) were the most active agents against Enterobacterales (ENT). An ESBL phenotype (CLSI criteria) was observed in 12.5%, 12.9%, and 3.6% of E. coli (EC), K. pneumoniae (KPN), and P. mirabilis (PM), respectively. FEP-TAZ and CAZ-AVI exhibited complete activity against EC, whereas C-T and piperacillin–tazobactam (PIP-TAZ) were active against 91.5% and 88.1% of ESBL-phenotype EC isolates, respectively. The most active agents against KPN were FEP-TAZ (99.6% inhibited at ≤16 mg/L), CAZ-AVI (100.0%S), and amikacin (AMK; 99.4%S). All PM isolates were S to FEP-TAZ (highest MIC, 0.12 mg/L), C-T, CAZ-AVI, MEM, PIP-TAZ and AMK. FEP-TAZ was highly active against E. cloacae (n = 94; MIC90, 0.5 mg/L; 98.9% inhibited at ≤16 mg/L) and Citrobacter spp. (n = 91; MIC90, 0.12 mg/L; highest MIC, 0.5 mg/L). Against P. aeruginosa (PSA), FEP-TAZ inhibited 97.6% of isolates at ≤16 mg/L, with spectrum of activity similar to CAZ-AVI (96.4%S), C-T (99.4%S) and AMK (97.6%S), and greater than MEM (85.5%S) and PIP-TAZ (87.3%S).

Conclusion

FEP-TAZ showed potent activity against ENT and PSA isolated in US hospitals in 2018, with overall spectrum (ENT + PSA) similar to CAZ-AVI and greater than C-T, PIP-TAZ, and MEM when FEP-TAZ proposed PK/PD S breakpoint of ≤16 mg/L was applied. FEP-TAZ may represent a valuable option for treating cUTIs caused by resistant GNB.

Disclosures

All authors: No reported disclosures.
1446. The Impact of Enterobacteriaceae Isolate Breakpoints on Prescriber Treatment Choices for Discordant Pattern Urinary Tract Infections
Authors: Lee Philip , Guo Yi , Szymczak Wendy , Soma Vijaya L , Nori Priya
Published: October 2019

Background

Our institution revealed Enterobacteriaceae with discordant cefazolin (CEF)-resistant / ampicillin-sulbactam (SAM) susceptible patterns (CRASS-P). This discordance could be from the multiple MIC cephalosporin breakpoint adjustments from CLSI. SAM has higher resistance for gram-negative bacteria compared with cephalosporins such as CEF which is confirmed by our antibiogram. We sought to understand if narrow-spectrum antibiotic choices for CRASS-P urinary tract infections (UTIs) led to clinical cure (CC).

Methods

We conducted a retrospective review from January 2018 to February 2019 of all CRASS-P Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae isolates from urine cultures. Patients with any symptom related to a UTI, urinalysis with >10 white blood cells/high-powered field, urine culture with >10,000 colony-forming units/mL, and receipt of an antibiotic were included. CC was defined as symptom resolution within 48 hours with no return to care within 28 days of the positive urinary culture. “Group A” included patients prescribed narrow-spectrum antibiotics such SAM, CEF, or an oral cephalosporin (OC) vs. broad-spectrum antibiotics such as ceftriaxone, quinolones or sulfa-medications (“Group B”).

Results

There were 960/1356 (70.8%) CRASS-P urinary isolates and 244 patients met inclusion criteria. Of 244 patients, 72 were in Group A and 172 were in Group B. There was no difference in the diversity of the 3 uropathogens, P = 0.34 (Table 1). Median age was 69±20.3 and 67.5±23.9 years for Group A and Group B, respectively, P = 0.23. Females accounted for 73.6% and 77.9% in Group A and B, respectively, P = 0.51. Overall, patients reached CC in 98.6% (71/72) of Group A patients, compared with 92.4% (159/172) of Group B patients, P = 0.07. Antibiotics used in treatment are outlined in Figure 1. UTI was associated with bacteremia for 2 patients in Group A and 4 patients in Group B (P = 0.84). Both patients in Group A reached CC and used AMC for treatment. However, 1 out of 4 patients did not achieve CC in Group B.

Conclusion

The use of SAM or OC can spare the broad-spectrum antibiotics use for CRASS-P UTIs as there was no statistical difference in CC between the two groups. The use of SAM with CRASS-P bacteremia secondary to UTI is possible; however, future studies are needed.

Disclosures

All authors: No reported disclosures.
1453. Cephalexin and Cefadroxil Are Not Therapeutic Equivalents for Uncomplicated Cystitis (uUTI): Further Analysis of Cefazolin Surrogate Susceptibility Testing Criteria
Authors: Jones Ronald N , Nguyen Hien M
Published: October 2019

Background

Cephalexin (CLEX) and cefadroxil are first-generation oral cephalosporins (OC’s) with similar antimicrobial spectrums, side-effects, and high urine concentrations; and are US-FDA approved for uUTI. Some stewardship programs are replacing CLEX (4 × daily) with cefadroxil (2 × daily) for dosing convenience. The US Committee on Antimicrobial Susceptibility Testing (USCAST) and CLSI recommend a cefazolin (CZOL) UTI surrogate breakpoint (≤16 mg/L; ≥15 mm) to predict susceptibility (S) for 7 OC’s against indicated Enterobacteriaceae. Direct cefadroxil antimicrobial S testing (AST) does not exist in US breakpoint interpretive documents, limiting specific results.

Methods

We reanalyzed and compared the CZOL surrogate testing for cefadroxil, CLEX and 5 other OC’s using AST data previously reported (Schuetz et al., 2013; IHMA). Broth microdilution AST was used against 205 isolates: E. coli (92; 40% with β-lactamase), K. pneumoniae (62), P. mirabilis (31; 10% with β-lactamase), and other enteric bacilli (20). A CZOL surrogate S breakpoint (≤16 mg/L) was used to infer S for OC’s.

Results

CZOL X cefadroxil cross-S accuracy rate was only 91.6% (unacceptable; < 95%) and the false resistance was 1.0% (acceptable). Cross-S accuracy was ≥ 97.0% for all tested OC’s except cefadroxil and cephradine (80.1%). CZOL spectrum vs. tested, indicated species (81.0%) was essentially identical for CLEX, cefprozil, cefaclor and loracarbef (80.0–81.0%). In contrast, cefdinir, cefpodoxime, and cefuroxime axetil S rates were underestimated 5.3 to 10.7% by the surrogate test. CLSI and USCAST did not list cefadroxil or cephradine for CZOL surrogate uUTI prediction; however the current (2019) US-FDA website document states “cefadroxil may be deduced from testing CZOL” regardless of clinical indication.

Conclusion

Cefadroxil -S for guiding uUTI therapy cannot be accurately predicted by CZOL results at ≤16 mg/L (unacceptable surrogate accuracy and compromised spectrum/potency). Furthermore, direct cefadroxil AST does not exist in United States due to lack of breakpoint criteria (CLSI, USCAST) and reagent materials (MIC products or disks). CLEX or other OC’s remain preferred, more active (table) uUTI treatment choices having quality direct or surrogate AST guidances.

Disclosures

All authors: No reported disclosures.
1477. A Randomized Phase 2 Study of Cefepime Combined with the Novel Extended Spectrum β-Lactamase Inhibitor Enmetazobactam in Hospitalized Adults with Complicated Urinary Tract Infections (cUTI) Including Acute Pyelonephritis (AP)
Authors: Carmeli Yehuda , Knechtle Philipp , Hardenberg Jeff , Knecht Mathias
Published: October 2019

Background

Third-generation cephalosporin (3GC)-resistant Enterobacteriaceae has been classified as critical priority pathogens. The novel extended-spectrum β-lactamase (ESBL) inhibitor enmetazobactam (formerly AAI101; EMT) in combination with cefepime (FEP) is currently being developed as a carbapenem-sparing treatment of serious Gram-negative infections in settings with a high prevalence of 3GC-resistant Enterobacteriaceae. We report here the results from a phase 2 study that assessed safety, tolerability, and pharmacokinetics of FEP-EMT in patients with cUTI/AP.

Methods

Forty-five patients were enrolled in a randomized, multicenter, double-blind study of hospitalized adults with cUTI/AP. Patients received dosing regimens of FEP or FEP-EMT IV therapy q8h by 2 hours infusion (table) for 7 to 10 days with a 28-day follow-up. Efficacy was evaluated in the microbiological-modified ITT (µMITT) population. Safety was monitored in patients who received at least 1 dose of study drug. Clinical cure was designated as the resolution of cUTI symptoms present at study entry. Plasma and urine PK were determined from all patients.

Results

The study drugs were well tolerated in each cohort, with similar % adverse events and no new or unexpected safety concerns (table). Two discontinuations were due to allergic dermatitis. The microbiological- and clinical responses at test-of-cure for the combined FEP-EMT group were 83.3% (20/24) and 95.8% (23/24) compared with responses in the combined FEP group of 73.3% (11/15) and 93.3% (14/15), respectively (table). The most common baseline pathogens were Escherichia coli (66.7%) and Klebsiella pneumoniae (23.1%): 28.2% of isolates produced ESBLs with eradication rates for the combined FEP-EMT group of 85.7% (6/7) and for the combined FEP group of 75.0% (3/4). FEP and EMT PK were best described by a 2-compartment, linear PK model. Both agents exhibited half-lives of 2.3 hours. Creatinine clearance had a significant covariate effect on FEP and EMT, consistent with predominant renal excretion of both agents.

Conclusion

Results from this phase 2 study justify advancement to phase 3 studies to evaluate the safety and efficacy of FEP-EMT in patients with cUTI/AP.

Disclosures

All authors: No reported disclosures.
1480. Plasma and Urine Pharmacokinetic Analysis of Gepotidacin (GSK2140944) Following BID Oral Dosing in a Phase IIa Study for Treatment of Uncomplicated Urinary Tract Infections
Authors: Zimmerman Eric I , Dumont Etienne , Perry Caroline R , Tiffany Courtney , Scangarella-Oman Nicole , Raychaudhuri Aparna , Hossain Mohammad
Published: October 2019

Background

Uncomplicated urinary tract infections (uUTIs) are very common, with approximately 11% of women >18 years of age experiencing at least 1 episode of acute cystitis per year [Foxman, 2000]. Multidrug resistance has now emerged at the community level and has made treatment approaches for UTIs more difficult [Hooton, 2012; Flamm, 2014; Sanchez, 2016]. Gepotidacin (GEP), a first-in-class, novel triazaacenaphthylene antibacterial has demonstrated in vitro activity against uropathogens, including E. coli. With its unique ability to selectively inhibit bacterial DNA replication by a means not utilized by any currently approved human therapeutic agent, GEP warrants further study as a potential opportunity to address an unmet medical need by providing a new and effective oral treatment option for acute cystitis.

Methods

All participants received oral GEP 1500 mg BID for 5 days (total of 10 doses) and PK sampling was performed on Days 1–5.

Results

GEP was rapidly absorbed with median Tmax values of 1.50 to 1.92 hours. Steady-state was attained by Day 3 with moderate accumulation in plasma following BID dosing (1.4 fold), which is consistent with an effective elimination half-life of 6.6 hours. Steady-state urine trough levels were high and remained above an MIC of 4 µg/mL over 12 hours. Approximately 20% of the dose was excreted in urine over the 12-hour dosing interval on Day 1, which increased to 31% on Day 4. Urinary AUC24hr (11945 µg hours/mL) was higher than the free plasma AUC24hr (39.4 µg hours/mL). Slightly higher GEP plasma and urine exposures were observed in uUTI patients compared with Phase I healthy subjects.

Conclusion

Oral dosing of 1500 mg BID produces urine GEP exposures that exceed free plasma exposures by ~300-fold. Urine concentrations were also higher than the GEP MIC90 values for common UTI pathogens, such as E. coli (MIC90 = 4 µg/mL), suggesting that GEP warrants further clinical study for the treatment of uUTI.

Disclosures

All authors: No reported disclosures.
1488. Effects of Clostridium difficile Infection in Hospitalized Patients with Inflammatory Bowel Disease, National Inpatient Sample Study 2016
Authors: Chen Bing , Mahmoud Omar , Liu Bolun
Published: October 2019

Background

Patients with inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn’s disease (CD) have been shown to have increased Clostridium difficile infection (CDI) rates. In this study, we aimed to determine the effects of concurrent CDI in the outcomes of hospitalized patients with IBD.

Methods

In this retrospective cohort study, we analyzed the 2016 National Inpatient Sample (NIS) database of hospitalized patients with a first or secondary diagnosis of IBD and CDI using their respective ICD-10 codes. Primary outcomes of interest were all-cause mortality, hospital length of stay, total cost for hospital stay, and rate of colectomy. Multivariate regression was used to adjust for age, gender, race, hospital bed size, and Charlson comorbidity index. We used STATA 14 for analysis.

Results

There were a total of 3,306 patients admitted with IBD and CDI, of which 1,864 had a diagnosis of UC and 1,460 had a diagnosis of CD. 58.02% of the cases were female and the mean age was 52.5 years old. The mean age of patients in the CD group (48.97 [47.79–50.15]) was lower than the UC group (55.16 [54.01–56.31]). The results of in-hospital outcomes are shown in Tables 1 and 2.

Conclusion

We observed a significant increase in all-cause mortality, hospital length of stay, and total cost for hospital stay in IBD patients with concurrent CDI. There was no statistical difference in the rate of colectomy. In the subgroup analysis, there was a statistically non-significant increase in all-cause mortality in the CD group and a statistically significant increase in all-cause mortality in the UC group. Thus, in our study, IBD patients, especially UC patients, with concurrent CDI had a worse prognosis but they did not have more colectomies.

Disclosures

All authors: No reported disclosures.
1491. Active Norovirus Surveillance in Children Under 5 Years with Diarrhea after Rotavirus Vaccine Introduction in Argentina (2017–2019)
Authors: Gentile Angela , Stupka Juan , Degiuseppe Juan I , del Valle Juárez María , Florencia Lucion Maria , Agustina Pirker María , Turco Marisa , Sabbaj Rosa Liliana , Soledad Areso María
Published: October 2019

Background

Acute diarrhea is one of the leading causes of infant morbidity and mortality. Argentina introduced massive rotavirus vaccination in 2015. In several countries, this introduction has changed the distribution of enteropathogens. The decrease in the prevalence of rotavirus has been described at the expense of an increase in Norovirus (NoV) activity worldwide. The aim of this study was to analyze the role of NoV in acute diarrhea cases in outpatient children under 5 years of age and their epidemiological profile.

Methods

A prospective and cross-sectional study in <5 years outpatients attended for acute diarrhea in Children’s Hospital “Dr. Ricardo Gutiérrez” in Buenos Aires, Argentina, between July 2017 and March 2019 was conducted. Active epidemiological surveillance was performed with a specific case reporting form. Stool samples were tested for NoV (RT-qPCR). Clinical and epidemiological data were recorded.

Results

A total of 252 patients were enrolled and 235 stools samples were tested. Median of age was 22.3 months (IQR: 11–30), 58.7% were male. The most frequent symptoms were fever and vomiting in 63.1% and 53%, respectively; 52% had watery diarrhea, 45.2% had moderate diarrhea according to Vesikari Scale, 95.6% were normohydrated and 22% had a household member with diarrhea. There were no immunocompromised children. A 72% had received rotavirus vaccine, 86% of them with full scheme. From samples tested, 27% (n = 63) were NoV positive. NoV was found throughout the year and the frequency of detection was higher in January and June (summer and winter in Argentina). Regarding genetic diversity the most frequent genogroup was GII (65%; 41/63) and genotype GII.P16-GII.4 Sydney (48%; 20/41). Bacterial co-infection was observed in 35%. Compared with negative cases, NoV were younger (18 vs. 20 months; P < 0.001) and were associated with higher prevalence of rotavirus vaccination (88% vs. 66%; P = 0.001). No statistically difference was found regarding to gender, clinical outcome and severity.

Conclusion

NoV was detected at high frequency (27%) in children presenting moderate acute diarrhea, mainly in those who received rotavirus vaccine. Regarding sporadic acute diarrhea cases in children, it is important to consider NoV as a frequent etiological agent.

Disclosures

All authors: No reported disclosures.
1498. Assess Risk Factors, Mortality, and Healthcare Utilization Associated with Clostridioides difficile Infection (CDI) in 4 Latin American Countries
Authors: Yu Holly , Flaster Nestor , Casanello Adrian , Curcio Daniel
Published: October 2019

Background

In contrast to Europe and North America, little is known about Clostridioides difficile infection (CDI) in Latin America, especially about risk factors, mortality, and healthcare utilization.

Methods

We conducted a retrospective, case–control study at eight hospital centers in Brazil, Mexico, Argentina, and Chile. Hospital databases and medical records were used to identify nosocomial CDI cases from January 1, 2014 to December 31, 2017. CDI cases were patients with diarrhea and a positive CDI testing ≥72 hours after hospital admission. Two controls with no CDI diagnosis and diarrhea were matched to each CDI case and were required to (1) have a length of hospital stay (LOS) ≥ 3 days, (2) be admitted ±14 days from the case, and (3) share the same ward. Risk factors associated with CDI were assessed by conditional logistic regression. Mortality and healthcare utilization were compared between cases and controls.

Results

A total of 1,443 patients (≥18 years old) who met eligibility criteria were selected (481 cases and 962 controls). Comparing cases to controls, the mean age and gender representation were similar (age: 58.7 vs. 56.7 years, P = 0.269; male: 56.3% vs. 53.4%, P = 0.293), but comorbidity was higher (mean Charlson Comorbidity index: 4.3 vs. 3.6, p

Conclusion

Antibiotic exposure, existing medical conditions, and recent hospital admission are CDI major risk factors in Latin America. CDI also increased in-hospital death risk and LOS. These findings are consistent with published literature in developed countries.

Disclosures

All authors: No reported disclosures.
1503. Engraftment of Investigational Microbiome Drug, SER-262, in Subjects Receiving Vancomycin Is Associated with Reduced Rates of Recurrence after Primary Clostridium Difficile Infection (CDI)
Authors: Ford Christopher , Litcofsky Kevin , McGovern Barbara , Pardi Darrell , Nathan Richard , Hansen Val , Brennan Robert , Pullman John , Bernardo Patricia , Tomlinson Amelia , Horgan Kevin , Bryant Jessica , Walsh Emily , Rodriguez Michelle , Rogalin Henry , Wang Elaine , Henn Matt
Published: October 2019

Background

CDI is a 2-hit process requiring C. difficile spores and antibiotic-mediated dysbiosis, a low diversity state of the gut microbiome. Recurrent CDI (rCDI) is common and may be related to inadequate antibiotic concentrations (e.g., metronidazole; MET) or persistent dysbiosis (e.g., vancomycin; VAN). SER-262 is an oral investigational microbiome drug rationally designed to reduce rCDI by restoring colonization resistance.

Methods

SERES-262-001 was a Phase 1b randomized placebo (PBO)-controlled single and multidose study. Subjects with primary CDI (n = 96) were enrolled in 8 cohorts (SER-262: PBO, 5:1). Subjects were dosed after MET (n = 57) or VAN (n = 39) per investigator discretion. Engraftment of SER-262 strains was evaluated using strain-specific molecular probes in fecal samples; microbial diversity was measured via whole metagenomic shotgun sequencing. Endpoints included safety and rCDI rates up to 8 weeks posttreatment and strain engraftment at 1, 4, 8, 12, and 24 weeks.

Results

SER-262 safety was comparable to PBO. Although overall rCDI rates were similar in SER-262 (n = 80) and PBO (n = 16) subjects (18.8% vs. 12.5%, respectively), in a post-hoc analysis we observed reduced rates of rCDI in the VAN+SER-262 arm compared with MET+SER-262 (6.3 vs. 27.1%, respectively, P = 0.02, Figure 1). Overall, 8 of 12 SER-262 strains showed significant engraftment relative to PBO. However, greater SER-262 strain engraftment was observed in VAN-treated subjects compared with MET-treated subjects (P < 0.001, Figure 2). To better understand the impact of dysbiosis on engraftment, we evaluated baseline microbial diversity by prior antibiotic received and observed that the diversity of Bacteroidetes and Firmicute species was lower in VAN-treated subjects compared with MET-treated subjects (P < 0.001, Figure 3).

Conclusion

In this first phase 1b study of a fermented microbiome drug in subjects with primary CDI, SER-262 was safe and well-tolerated. The higher efficacy rates of SER-262 in reducing rCDI among VAN-treated subjects may be due to low baseline microbial diversity, which creates an ecologic niche for greater engraftment of dose species. Treatment of C. difficile with VAN, followed by restoration of colonization resistance with SER-262, is a promising 2-pronged therapeutic paradigm to reduce rCDI.

Disclosures

All authors: No reported disclosures.
1505. Shorter-Course Antibiotic Treatment for Pediatric Ventilator-Associated Tracheitis Is Safe and Effective
Authors: Grabic Mirela , Lake Jason G , Debelnogich Jelena , Krucylak Christina , Newland Jason
Published: October 2019

Background

Ventilator-associated tracheitis (VAT) is a common infection in children cared for in pediatric intensive care units (PICU). Short-course antibiotic treatment (5 days) has been shown to be effective. In October 2016, we implemented a PICU VAT guideline for short-course therapy. We assessed the impact of this intervention.

Methods

We conducted a retrospective cohort study of PICU patients diagnosed with VAT from October 2016 to June 2018. The antimicrobial stewardship program (ASP) identified potential patients through daily chart review. Only those patients with a clinician diagnosis and who were receiving antibiotics for VAT, either enterally or parenterally, were included. Frequencies and proportions were calculated. Chi-square or Fisher exact tests were used to compare proportions.

Results

ASP identified 251 potential patients, 105 (42%) of whom met inclusion criteria. The median age was 7 years (range: 0–21). Twenty-eight (27%) were tracheostomy dependent. The most commonly prescribed antibiotics were cefepime (43%), ceftriaxone (17%), and vancomycin (14%). Median antibiotic duration was 13 days (range: 1–29); 57 (52%) received > 5 days and 48 (44%) received 5 days. Only 3 (6%) patients who received 5 days of antibiotics required retreatment within 10 days of their initial course vs. 11 (19%) who received > 5 days (P = 0.09). A diagnosis of ventilator-associated pneumonia (VAP) within 10 days of completing VAT treatment was made in 2 (4%) patients who received 5 days vs. 3 (5%) of patients who received > 5 days (P = 1.0). C. difficile infection within 90 days occurred in 2 (4%) patients who received > 5 days vs. 1 (2%) who received 5 days (P = 1.0).

Conclusion

Short-course antibiotic therapy for VAT was not associated with retreatment for VAT or subsequent diagnosis of VAP. Development of C. difficile was similar between groups. Adherence to the guideline was approximately 50%, perhaps due to physician perception of disease severity. Additional work is needed to refine the diagnosis of VAT and assess the interaction between illness severity and treatment duration.

Disclosures

All authors: No reported disclosures.
1511. Effect of Discharge Antibiotic Route on Clinical Outcomes in Children with Methicillin-Resistant Staphylococcus aureus (MRSA) Osteomyelitis with Bacteremia
Authors: Olson Jared , Hamdy Rana F , Hsu Alice J , Tamma Pranita , Tamma Pranita , Gerber Jeffrey , Dona Daniele , Hersh Adam
Published: October 2019

Background

Children with osteomyelitis transitioned to oral step-down therapy experience similar outcomes to those treated with outpatient parenteral antibiotic therapy (OPAT). Compared with OPAT, oral therapy has lower costs and avoids catheter complications. However, few studies have specifically compared patient outcomes between those receiving oral therapy vs. OPAT for osteomyelitis with associated bacteremia caused by MRSA.

Methods

We performed a retrospective cohort study comparing early oral therapy (EOT), defined as transition to oral therapy at or prior to discharge vs. use of OPAT at discharge. We identified hospitalized children <19 years of age with MRSA osteomyelitis with bacteremia between 2007 and 2014 from three children’s hospitals. The primary outcome was treatment failure within 6 months of discharge, defined as unplanned change in antibiotic after discharge, development of chronic osteomyelitis, need for an operative procedure after discharge, or recrudescence of bacteremia. The secondary outcome was treatment-related events, defined as documented adverse drug events in the medical record and/or central venous catheter complications. Between-group comparisons were made using Fisher exact test for binomial distributions and the Wilcoxon rank-sum test for continuous variables.

Results

We included 61 patients with MRSA osteomyelitis with bacteremia. Twenty-five patients (41%) received EOT and 36 (59%) received OPAT. Duration of bacteremia and hospital length of stay was similar between groups (Table 1). Clindamycin was the most commonly used antibiotic in both the EOT (24/25; 96%) and OPAT (22/36; 61%) groups. Clinical failure occurred in 1/25 (4%) children receiving EOT and in 5/36 (14%) in the OPAT group (95% CI of difference: −29 to 6%; P = 0.38, Table 1). Treatment-related adverse events occurred in 1/25 (4%) children receiving EOT compared with 9/36 (25%) receiving OPAT (95% CI of difference: −49 to –7%; P = 0.04, Table 1).

Conclusion

Children receiving EOT for MRSA osteomyelitis with bacteremia did not experience higher rates of clinical failure and had fewer treatment-related complications compared with OPAT. Oral step-down therapy can be considered for children with MRSA osteomyelitis with bacteremia.

Disclosures

All authors: No reported disclosures.
1514. Factors Associated with an Infectious Diseases Consultation for Pediatric Staphylococcus aureus Bacteremia
Authors: Curley Tara E , Ansusinha Emily , Hamdy Rana F
Published: October 2019

Background

Staphylococcal aureus bacteremia is associated with substantial morbidity in children. An infectious diseases consultation is associated with decreased mortality in adults with S. aureus bacteremia, but this has not yet been shown in a pediatric population.

Methods

This was a retrospective cohort study of children <18 years old hospitalized at Children’s National Medical Center with S. aureus bacteremia between January 1, 2012 and December 31, 2016. We excluded children with polymicrobial infections, those with a concurrent culture-proven infection, and those transferred with incomplete records. Structured manual chart review was used to collect demographic information, underlying comorbidities, type of admission (ICU or non-ICU), epidemiologic classification (hospital- or community-onset), primary source of infection, and methicillin resistance (MRSA or MSSA). A multivariable logistic regression analysis was performed to identify factors associated with having an infectious diseases consultation.

Results

We identified 171 episodes of S. aureus bacteremia; 27.5% occurred in infants <12 months old, 65.5% occurred in males, 38% occurred in ICU patients, and 18.1% were methicillin-resistant S. aureus (MRSA). The most common primary sources of infection were musculoskeletal (38%), catheter-related (18.1%), and skin/soft-tissue infections (17%). The majority (70.2%) received an infectious diseases consultation. In univariable analysis, ID consultation was more frequent among infections with the following characteristics: non-neonates (74.2% vs. 45.8%; P = 0.007), community-acquired (78.7% vs. 45.5%; P < 0.01), no underlying comorbidities (97.0% vs. 53.3%; P < 0.001), musculoskeletal (98.5%) or endovascular (100%) source of infection, and MRSA (100%). In a multivariable logistic regression analysis, musculoskeletal infections, endovascular infections, and MRSA had significantly higher odds of receiving an infectious diseases consultation.

Conclusion

Children with S. aureus bacteremia were more likely to receive an infectious diseases consultation if presenting with musculoskeletal infections, endovascular infections, or MRSA.

Disclosures

All authors: No reported disclosures.