bluuebunny/crossref_metadata_2025 huggingface dataset:
2121. Isavuconazole (ISAV) as Primary Anti-Fungal Prophylaxis (PAP) in Patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS): An Open-Label, Prospective Study
Authors: Bose Prithviraj , McCue David , Wurster Sebastian , Wiederhold Nathan P , Kadia Tapan M , Borthakur Gautam , Ravandi-Kashani Farhad , Masarova Lucia , Konopleva Marina , Estrov Zeev , Takahashi Koichi , Yilmaz Musa , Rausch Caitlin R , Marx Kayleigh , Qiao Wei , Huang Xuelin , Bivins Carol A , Pierce Sherry A , Kantarjian Hagop M , Kontoyiannis Dimitrios P
Published: October 2019

Background

Mold-active antifungal prophylaxis (ppx) is recommended in neutropenic patients with newly diagnosed AML or MDS. ISAV is an extended spectrum triazole with superior tolerability, reliability of absorption, fewer drug–drug interactions, lack of QTc prolongation or need for therapeutic drug monitoring, approved for the treatment of invasive aspergillosis (IA) and mucormycosis. NCT03019939 is an investigator-initiated, phase 2 trial of PAP with ISAV in patients with AML/MDS.

Methods

Treatment-naïve adult patients with AML or MDS initiating remission-induction chemotherapy (RIC) received ISAV per the dosing recommendations in the United States label until recovery from neutropenia (neutrophils (ANC) ≥ 0.5 × 109/L) and attainment of complete remission (CR), occurrence of proven or probable invasive fungal infection (IFI, EORTC/MSG criteria), or for a maximum of 12 weeks. The primary endpoint was incidence of proven/probable IFI during the study period (up to 30 days from the last dose of ISAV).

Results

67 patients were enrolled (April 28, 2017 to February 14, 2019) and 60 patients were eligible for assessment (median age 67 years, 57 patients with AML, median ANC on enrollment was 660). Reasons for study completion were achievement of CR with ANC recovery (n = 35), completion of 12 weeks of PAP (n = 9), possible IFI (n = 7), investigator decision (n = 3), death (n = 2, 1 disease progression, 1 cardiac arrest), proven/probable IFI (n = 3), and mild transaminitis, possibly ISAV-related (n = 2). The median durations of neutropenia and ISAV ppx were 33 (7–86) and 31 (7–86) days, respectively. One microbiologically-proven (gluteal abscess due to Candida glabrata) and 2 cases of probable breakthrough IFIs (probable IA with positive galactomannan) occurred (IFI incidence 5%). ISAV trough serum concentrations were available in 31 patients on both day 8 (median 3.74 µg/mL, 2.03–7.65) and day 15 (median 4.10 µg/mL, 2.17–9.25), and were not significantly different.

Conclusion

ISAV is a safe and effective alternative for PAP in patients with newly diagnosed AML/MDS undergoing RIC, with a breakthrough (proven/probable) IFI rate of 5%. ISAV serum levels were adequate in patients with AML/MDS undergoing RIC. Pharmacological features make ISAV attractive for PAP in the era of recently approved or emerging small-molecule AML therapies.

Disclosures

All authors: No reported disclosures.
2122. Isavuconazonium for Invasive Fungal Therapy: Single-Center Pediatric Experience
Authors: Mongkolrattanothai Kanokporn , Mohandas Sindhu , Stach Leslie , Orbach Regina , Neely Michael
Published: October 2019

Background

Isavuconazole (ISZ), dosed as the pre-drug isavuconazonium (ISM), is active against a wide variety of clinically important fungal pathogens. ISM is approved for the treatment of invasive aspergillosis and mucormycosis in adults ≥18 years of age. We present our experience with ISM to treat proven or to prevent fungal infection in pediatric patients.

Methods

In a retrospective review of patients who received ISM at our institution between April 2016 and April 2019, we abstracted demographic information, primary diagnosis, indication for ISM therapy, ISZ serum concentrations if available, and outcomes.

Results

Of 16 patients who received ISM, 12 were < 18 years of age (range 6–17 years). Underlying conditions included leukemia (n = 8), lymphoma (n = 1), post BMT (n = 1), diabetes (n = 1), and cardiac transplant (n = 1). Nine (75%) had proven invasive fungal infection with aspergillosis (n = 2), zygomycosis (n = 3), mixed aspergillosis and zygomycosis (n = 2), mixed Rhizopus and Scedosporium (n = 1), and pathology only (n = 1). Five of these 9 patients received combination ISM and liposomal amphotericin initially, followed by monotherapy with ISM in 4 patients after a mean of 26 days (range 6–63), and continued dual therapy in the fifth. The other 4 received liposomal amphotericin with or without other azoles prior to changing to ISM monotherapy. ISM dosing was 10 mg/kg q8h on days 1 and 2, followed by q24 thereafter, up to a maximum of 372 mg/dose. There were 19 measured ISZ serum concentrations obtained from 8 patients after >1 week of verified inpatient dosing, ranging from 1.0 to 7.5 mg/L, above the MIC in all cases when known. Five (42%) patients died of underlying non-mycological causes, 1 (8%) died of progressive scedosporiosis, and 6 (50%) improved. The two patients receiving ISM prophylaxis did not suffer a breakthrough fungal infection. ISM was well tolerated with no dose-limiting, drug-related toxicities noted.

Conclusion

ISM is a well-tolerated therapeutic option in pediatric patients at risk for or with invasive mycosis. Only 1 of our 12 patients died from progressive fungal disease.

Disclosures

All authors: No reported disclosures.
2137. Impact of Accelerate Pheno™ Rapid Blood Culture Detection System with Real-time Notification vs. Standard Antibiotic Stewardship on Clinical Outcomes in Bacteremic Patients
Authors: Pearson Courtney , Lusardi Katherine , McCain Kelsey , Painter Jacob , Lakkad Mrinmayee , Rosenbaum Eric R , Daniels Kay , Van Serena , Bariola J Ryan , Dare Ryan K
Published: October 2019

Background

Accelerate Pheno™ blood culture detection system (AXDX) provides identification (ID) and antimicrobial susceptibility testing (AST) within 8 hours of growth in blood culture. We previously reported length of stay (LOS), time to optimal therapy (TTOT), and antibiotic days of therapy (DOT) decrease following AXDX implementation alongside an active antimicrobial stewardship program (ASP). It is unclear whether real-time notification (RTN) of results further improves these variables.

Methods

A single-center, quasi-experimental before/after study of adult bacteremic inpatients was performed after implementation of AXDX. A 2017 historical cohort was compared with two 2018 intervention cohorts. Intervention-1: AXDX performed 24/7 with results reviewed by providers or ASP as part of their normal workflow. Intervention 2: AXDX performed 24/7 with RTN to ASP 7 days per week 9a-5p and overnight results called to ASP at 9a. Interventions 1 and 2 were utilized on an alternating weekly basis during the study (February 2018–September 2018). Historical ID/AST were performed using VITEK® MS and VITEK®2. Exclusion criteria included polymicrobial or off-panel isolates, prior positive culture, and patients not admitted at the time of AST. Clinical outcomes were compared with Wilcoxon rank-sum and χ 2 analysis.

Results

540 (83%) of 650 positive cultures performed on AXDX had on-panel organisms. 308 (57%) of these cultures and 188 (77%) of 244 reviewed historical cultures met inclusion criteria. Baseline illness severity and identified pathogens were similar between cohorts. Clinical outcomes and antimicrobial DOT are reported in Tables 1 and 2.

Conclusion

Following our implementation of AXDX, clinical outcomes including LOS, TTOT, total DOT, BGN DOT, and frequency of achieving optimal therapy were significantly improved compared with a historical cohort. Addition of RTN for AXDX results in the setting of an already active ASP did not further improve these metrics. However, compared with historical arm, AXDX with RTN did significantly impact specific subsets of antibiotic use while AXDX alone did not. This may be due to earlier vancomycin de-escalation. These results support the benefit of integration of AXDX into healthcare systems with an active ASP even without the resources to include real-time notification.

Disclosures

All authors: No reported disclosures.
2138. Follow-up Investigation of Antibody Titers and Diagnostic Antibody Cut-Off Values in Scrub Typhus Patients in Korea
Authors: Kim Dong-Min , Kim Choon-Mee , Ra Yun Na
Published: October 2019

Background

Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi. There have been few follow-up studies assessing antibody titers using serologic tests from various commercial labs.

Methods

A prospective investigation to assess antibody titers of scrub typhus patients and seroprevalence for health checkup individuals were evaluated. The antibody titers of former patients diagnosed with scrub typhus at least 1 year and a maximum of 13 years were also investigated. The following tests were performed simultaneously: (i) immunofluorescence antibody assays (IFAs) that detect immunoglobulin(Ig) M and IgG, (ii) IFA that detects total Ig by a commercial lab, (iii) antibody tests using two commercially available kits.

Results

In prospective analyses with cutoff values set to ≥1:16 for IgM, ≥1:256 for IgG based on the KCDC’s criteria, and ≥1:40 for total Ig. The antibody positive rates of 102 confirmed scrub typhus patients were 44%, 35.3%, and 57.6%, respectively, in the first week after symptom onset. Among 91 former patients recovered, the follow-up IgM, IgG, and total Ig positivity rates were 38.5% (35/91), 22% (20/91), and 76.9% (70/91), respectively. In overall cohort of 216 health checkup subjects, 4.2% (9/216) IgM and 0% (0/216) IgG seroprevalence was observed.

Conclusion

The IFA from KCDC and commercial lab, and rapid commercial kits cannot differentiate between former patients recovered from scrub typhus and current scrub typhus. In Korea and other countries where low antibody cut-off titer values have been used as criteria for diagnosing and reporting scrub typhus, upward adjustments of cut-off values may be necessary.

Disclosures

All authors: No reported disclosures.
2141. Potential for Harm From Rapid Campylobacter Antigen Test: Quality Improvement Process Reveals 84% False-Positive STAT! Campy Stool Antigen Results
Authors: Farrell John J , Mathis Jessica , Knapp Sarah J
Published: October 2019

Background

The Immunocard STAT! Campy is known to have a poor correlation with Campylobacter culture, and bloody stools are thought to be the most common cause of false-positive tests. A CDC investigation of 11 cases of Campylobacter in premature infants with non-bloody stools between March and April, 2018 at the Children’s Hospital of Illinois identified a pseudo-outbreak secondary to false-positive stool antigen tests.

Methods

Beginning May 1, 2018, Immunocard STAT! Campy (Meridian BioScience) positive stools from 14-hospitals in the OSF network were sent to the OSF System lab for confirmation prior to resulting in the medical record (MR). Stool was placed into Cary Blair media and a STAT! Campy stool antigen test was repeated in the OSF System Lab. BioFire GI Panel (GIP) PCR was performed on STAT! Campy positive stools, and results reported in the MR.

Results

Between May 1, 2018 and April 30, 2019, 3,639 stools were submitted for culture. 372 tested positive by the STAT! Campy rapid antigen test and were referred for confirmation. Repeat rapid antigen tests were negative for 56% (208/372) of stools and were finalled in the MR as negative without GIP testing. GIP PCR was performed on 164 samples from 163 patients (mean age = 18). 43% (71/164) of GIP were completely negative; 16% (27/164) positive STAT! Campy antigens were confirmed by the GIP (84% were false positive). Pathogens detected by the GIP included: 30 viral infections (50% Norovirus), 27 cases of C. difficile, and 19 pathogenic E. coli (Table 1). Multiple pathogens were detected in 15% (25/163) patients (1 patient was positive for 4 pathogens). One case of Salmonella was not detected by GIP. One patient tested negative by the GIP but remained symptomatic and C. difficile was detected on repeat testing 10 days later.

Conclusion

C. difficile and Norovirus were the most common pathogens detected in stools that yielded false positive STAT! Campy results. These findings have important patient care and infection control implications. Currently neither FDA nor CDC requires Campylobacter culture (or other laboratory methods) of confirmation of positive Campylobacter stool antigen tests. Missed and incorrect diagnoses represent a significant risk of harm for patients (particularly C. difficile or Shiga toxin-infected patients, Table 1), and outbreaks in institutional settings.

Disclosures

All authors: No reported disclosures.
2148. Performance of the BioFire FilmArray Gastrointestinal Panel in a Clinical Setting of Infectious Diarrhea
Authors: Aguirre-García Gloria Mayela , Moraila-Baez Alejandra , Camacho-Ortiz Adrian
Published: October 2019

Background

Infectious diarrhea remains as one of the leading causes of morbidity and mortality worldwide among all age groups. Conventional methods for diagnosis are time consuming and expensive. The BioFire FilmArray gastrointestinal panel (FA-GIP) tests for 22 enteric pathogens, provides results in a few hours and improves healthcare costs. The impact on antibiotic stewardship is unknown.

Methods

We conducted a retrospective cohort, multi-center study to evaluate FA-GIP clinical performance in hospitalized patients with acute diarrhea. Patients from 3 hospitals from the Christus Muguerza health group were included between January 2017 and August 2018. The FA-GIP was ordered by the treating physician and was not influenced by the study. Duration of antibiotic therapy, length of hospital stay, and therapy modification were assessed. The comparison group consisted of patients with acute diarrhea in which no FA-GIP was ordered.

Results

Data from 130 patients with FA-GIP and 107 patients with conventional methods were collected. Pathogens were detected by FA-GIP in 72.3% of the cases. The median of duration of antibiotic therapy in FA-GIP group was 5 days (IQR 0–8) vs. 3 days (IQR 0–6) in conventional methods group, (P < 0.05). The mean length of stay was 3.3(SD ± 2.4) in FA-GIP group vs. 1.9 (SD ± 1.0) in the control group (P < 0.05). Patients in FA-GIP group had more days with diarrhea, lower hemoglobin levels, and higher creatinine levels at admission (Table 1). The most frequent pathogens detected were enteropathogenic Escherichia coli in 24.4%, norovirus in 19.1%, Clostridium difficile in 17.0% and Campylobacter jejuni in 15.9% (Table 2). Therapy modification after FA-GIP results was made in 51.1% of the patients with a detected pathogen, and in 42.8% of patients with no pathogen detected in FA-GIP the antibiotic was stopped.

Conclusion

Patients in the FA-GIP group had a more complex clinical scenario upon admission, they also had a longer duration of antibiotic therapies and longer length of stay. Although antibiotic therapy was positively influenced by the FA-GIP result, and no pathogen detection leads to withdrawal of unnecessary antibiotics.

Disclosures

All authors: No reported disclosures.
2161. Organism-Specific Turn Around Time Improvement in Urinary Specimens as a Result of Microbiological Laboratory Automation
Authors: Farooq Nouman , Emrick Alanna , Gonzalez-Ortiz Carolyn , Sellers David , Tabak Ying P , Vankeepuram Latha , Kurtz Stephen , Levent Fatma
Published: October 2019

Background

University Medical Center in Lubbock, TX is one of few medical centers using Becton Dickinson (BD) Kiestra Total Laboratory Automation (TLA) system since May 2015. The impact on organism-specific turn around time (TAT) in urinary specimens after implementation of TLA was evaluated.

Methods

After approval from the Quality Improvement Review Board, a retrospective analysis of microbiological data from urinary specimens in BD research database was performed. Before vs. after implementation (2013 vs. 2016) TAT was compared. Ten clinically relevant organisms were analyzed. Statistical analysis was performed with SAS software version 9.2. Data were analyzed using Chi-squared test. A P-value of < 0.05 was considered statistically significant.

Results

Overall, 2282 specimens from 2013 and 2306 specimens from 2016 were analyzed. Compared with before vs. after implementation of TLA, an overall improvement in TAT was observed (expressed as mean hours for each organism): Enterococcus faecalis (55.2 vs. 38.8), Enterococcus faecium (68.4 vs. 43.8), Escherichia coli (44.2 vs. 41.0), Klebsiella pneumoniae (45.0 vs. 44.0), Proteus mirabilis (44.8 vs. 38.6), Pseudomonas aeruginosa (58.9 vs. 37.7), Staphylococcus aureus (49.2 vs. 36.0), Streptococcus agalactiae (49.2 vs. 31.4), Streptococcus pneumoniae (51.7 vs. 61.8), Streptococcus pyogenes (62.6 vs. 26.6). It was also observed that improvement in TAT was more pronounced for Gram-positive organisms than Gram-negative organisms. P-value was < 0.01 for all organisms except Streptococcus pneumoniae (0.7985) and Streptococcus pyogenes (0.2562). The number of specimens with these two organisms was too small to be considered significant.

Conclusion

Automation of microbiology laboratory leads to significant TAT improvement in urinary specimens, making early data availability to clinicians. This improves efficiency as well as supporting earlier antibiotic switch, antimicrobial stewardship and optimal patient care in treating urinary tract infections.

Disclosures

All authors: No reported disclosures.
2162. Comparison of Plazomicin Disk Diffusion vs. Gradient Diffusion Susceptibility Testing Results Against Drug-Resistant Clinical Enterobacteriaceae Isolates
Authors: Lepak Alexander , Lepak Alexander , Grajcevci Luriane , Banach Joyce , Meyer Katherine , Chen Derrick
Published: October 2019

Background

Plazomicin, a novel aminoglycoside, is active against carbapenem-resistant Enterobacteriaceae (EB) and is not inhibited by most aminoglycoside modifying enzymes that affect gentamicin and tobramycin. We investigated the activity of plazomicin against resistant EB clinical isolates and compared disk diffusion (DD) vs. gradient diffusion (GD) results.

Methods

EB isolates that were carbapenem resistant and/or resistant to both gentamicin and tobramycin were retrieved from the UW Health clinical isolate repository. Each isolate was tested against plazomicin using both DD (MAST Group Ltd. Plazomicin disk 30 µg) and GD (Liofilchem Plazomicin MIC Test Strip 0.16–256 µg/mL) methods according to manufacturer instructions and using FDA clinical breakpoints for interpretation.

Results

51 isolates were tested: 21 E. coli, 9 P. mirabilis, 7 E. cloacae, 6 K. pneumoniae, 3 K. oxytoca, 3 S. marcescens, 1 K. aerogenes, and 1 C. freundii. Specimen sites included: 29 blood, 8 urine, 8 soft tissue or bone, 5 intra-abdominal, and 1 sputum. Previous phenotypic AST results demonstrated 19 (37%) were CRE, of which 5 were also gentamicin and tobramycin resistant, and 32 (63%) were tobramycin and gentamicin resistant but carbapenem susceptible. Plazomicin zone diameters and minimal inhibitory concentrations (MIC) for all isolates are shown in the figure (data jittered to show frequency). There was a significant correlation between increased MIC and smaller zone diameters (Pearson coefficient −0.443, P = 0.001). However, while all 51 isolates were susceptible by DD breakpoints, only 46 (92%) were susceptible by GD breakpoints. All 5 discordant results were P. mirabilis which had an MIC of 4 µg/mL (intermediate) but zone diameters of 20–21 mm (susceptible).

Conclusion

Concordance between plazomicin DD and GD susceptibility was only 92%. All 5 discordant results were P. mirabilis. Surveillance studies demonstrate >80% of P. mirabilis have MIC of 2–4 mg/L. Given the DD breakpoint is 16 mm, our data suggest DD was overly active in our sample set. Comparison of DD and GD to reference broth microdilution against a larger set of isolates is warranted to determine which method is optimal; however, our data suggest DD may result in categorical errors for P. mirabilis.

Disclosures

Alexander Lepak, MD, Paratek Pharmaceuticals: Research Grant; Tetraphase Pharmaceuticals: Research Grant.
2167. Evaluation of Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy for Rapid and Reagent-Free Identification of Burkholderia spp.
Authors: Lam Lisa M T , Ismail Ashraf , Sedman Jacqueline , Vallières Émilie
Published: October 2019

Background

Burkholderia cepacia complex including B. gladioli are opportunistic pathogenic bacteria affecting the immunocompromised population. For prognosis and appropriate treatment, rapid and accurate species identification is particularly important for those diagnosed with cystic fibrosis (CF). Conventional biochemical identification techniques are insensitive and problematic for identifying Burkholderia spp., leading to common misidentification or inconclusive results. Recent studies have successfully employed attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy for rapid, reagent-free and cost-effective microbial identification. In the present study, identification of Burkholderia spp. by this technique is investigated.

Methods

A total of 59 isolates belonging to 7 species of Burkholderia were included in this study; all these isolates had been well-characterized by VITEK 2, 16S rRNA sequencing, random amplification of polymorphic DNA (recA typing) and/or matrix-assisted laser desorption/ionization time of flight mass spectrometry. ATR-FTIR spectra were acquired directly from colonies on 5% blood agar plates.

Results

A spectral database containing ATR-FTIR spectra of over 4300 bacterial isolates, encompassing over 70 genera and 190 species, was updated to include spectra of 39 isolates collected in this study and employed in the identification of the other isolates (n = 20). All isolates were correctly identified as Burkholderia by a multitier search approach. For Burkholderia species identification, spectra belonging to 39 isolates representative of all 7 species were used to construct a spectral database employed to identify the other 20 isolates [B. anthina (n = 2), B. gladioli (n = 8), B. multivorans (n = 7), and B. vietnamiensis (n = 3)]. Compared with VITEK 2 (30% correct species identification), ATR-FTIR spectroscopy correctly identified all but one isolate, resulting in overall correct species identification of 95%. Prospectively (10 months), 5 of 1100 isolates collected were identified as Burkholderia spp. by ATR-FTIR spectroscopy in concordance with VITEK 2.

Conclusion

ATR-FTIR spectroscopy can provide the means of rapid Burkholderia spp. identification for appropriate treatment of those diagnosed with CF.

Disclosures

All authors: No reported disclosures.
2181. Yield and Impact of Molecular Diagnostics for Pathogen Detection in Pediatric Patients: 16/18S rRNA PCR and Noninvasive Assays
Authors: Chun Angela , Heald-Sargent Taylor , Malczynski Michael , Muller William J , Qi Chao , Seed Patrick C , Mithal Leena B , Mithal Leena B
Published: October 2019

Background

Molecular diagnostic tests can identify bacterial and fungal pathogens from clinical samples. Nucleic acid detection tests include 16S and 18S rRNA gene PCR (16/18S PCR) and plasma next-generation sequencing (NGS). Other assays (fungal galactomannan and 1,3-β-d-glucan) detect structural factors. Our objective was to assess the utilization, yield, and impact of molecular diagnostics in pediatric patients who had samples sent for 16/18S PCR.

Methods

Sterile site fluid or tissue specimens were collected as part of standard care at Lurie Children’s Hospital, cultured, and sent to Northwestern Memorial Hospital for 16/18S PCR as clinically indicated. Medical records were reviewed for diagnostics, antibiotics, and clinical course.

Results

From 1/2016–8/2018, 236 samples were sent for 16 and/or 18S PCR from 183 patients. 83% had a concurrent ID consult. 16S PCR was done on 215 samples, 42 (20%) were positive, and 36 yielded species identification (Table 1). Antibacterial agents were administered prior to specimen collection in 73% and did not affect likelihood of positive 16S PCR. 18S PCR was sent on 163 samples; 12 (7.4%) were positive (Table 2) of which 10 were from immunocompromised hosts. 40% of patients were on antifungals prior to sample acquisition. 16/18S PCR impacted antimicrobial decision-making in 70 cases (30%). A pathogenic fungus was detected by PCR but not culture in 2 cases. Time to positivity of fungal culture was 1–15 days. Fungal culture was positive in 5 cases with-negative 18S PCR. Seventeen patients had positive serum 1,3-ß-D-glucan and/or galactomannan: 3 of which had positive 18S PCR, 5 with fungal growth, 5 presumed infection based on imaging, 1 Nocardia, and 3 noninfectious etiology. Plasma NGS was sent on 45 cases, was positive in 34, and affected clinical management in 10.

Conclusion

16S PCR can identify bacterial pathogens in the setting of negative culture and impact clinical care. Abscess, bronchial/pleural fluid, and brain/organ tissue were high yield specimens. 18S PCR can provide expeditious fungal identification in cases of suspected invasive disease, but fungal culture and serum molecular testing increase diagnostic yield. No single fungal test is comprehensive. Plasma NGS had relatively high yield and clinical impact in selected patients.

Disclosures

All authors: No reported disclosures.
2182. Harnessing Direct-from-Blood MALDI-TOF (DBM) and Local Blood Stream Infection (BSI) Antibiogram Data to Direct Optimal Therapy for Gram-Negative Rod (GNR) Bacteremia
Authors: Tischendorf Jessica , Lepak Alexander , Lepak Alexander
Published: October 2019

Background

GNR bacteremia is common in the hospital environment. Drug-resistance challenges thoughtful use of, and timely de-escalation to, regimens that limit carbapenem use. DBM accurately provides rapid identification of bacteremia pathogens, but lacks antibiotic susceptibility testing (AST) results to aid clinicians in refining therapy. We investigated whether integrating DBM identification and local BSI antibiogram data could be used to identify carbapenem-sparing regimens with predicted efficacy of ≥ 95% prior to traditional AST results.

Methods

We identified GNR blood culture results in adults from January 1, 2018 to December 31, 2018. The first isolate per bacteremia episode per patient was analyzed. AST was performed by MicroScan. We categorized isolates into 1 of 3 groups based on the most common resistance mechanisms in our population (i.e. CTX-M ESBL, AmpC): 1] Escherichia spp. and Klebsiella spp. (EK), 2] S. marscecens, P. mirabilis, E. (Klebsiella) aerogenes, C. freundii, M. morganii, E. cloacae complex, and C. non-freundii (SPEC-MEC), and 3] P. aeruginosa (PA). We compiled susceptibility rates to common antibiotics for GNR sepsis and compared results using Chi-square.

Results

381 GNR isolates were recovered in blood cultures from adult patients in 2018: EK 264 (69%), SPEC-MEC 66 (17%), PA 36 (9%), other 15 (4%). Susceptibility results in common GNR sepsis agents are shown in Figure 1 (*P < 0.05 between groups). Within each organism group, susceptibility was highest in the following scenarios: 1] EK: PTZ and MEM (P < 0.05 vs. FEP, TOB, CIP, and ATM), 2] SPEC-MEC: FEP, TOB, and MEM (P < 0.05 vs. PTZ and ATM), and 3] PA: comparably similar (> 90%) for PTZ, FEP, TOB, and MEM.

Conclusion

Integration of DBM and antibiogram data identified species-specific carbapenem-sparing regimens that would predict ≥ 95% of patients with GNR bacteremia are on effective therapy prior to traditional AST results. In appropriate patients, this could lead to a significant reduction in carbapenem duration and avoid broad-scale carbapenem use while also optimizing time to effective therapy. This is a readily adaptable process for other centers to improve care of patients with GNR bacteremia. Our data suggest using β-lactam alternatives for GNR bacteremia, especially EK, should be done with caution.

Disclosures

Alexander Lepak, MD, Paratek Pharmaceuticals: Research Grant; Tetraphase Pharmaceuticals: Research Grant.
2188. Provider Education and Rapid Antigen Detection Test Use in Private and Academic Pediatric Clinics
Authors: Dahl Steven , Hurley Emily A , Lee Brian R , Newland Jason , Bradley-Ewing Andrea , Donis De Miranda Evelyn , Pina Kimberly A , Mackenzie Alexander , Goggin Kathy , Myers Angela , Myers Angela
Published: October 2019

Background

Rapid antigen detection testing (RADT) is needed to differentiate Group A Streptococcal (GAS) pharyngitis from viral pharyngitis. Guidelines do not recommend RADT in patients with viral symptoms or in children <3 years old without GAS exposure. Reduction in unnecessary RADT use may impact inappropriate antibiotic use by decreasing prescriptions in children likely colonized with GAS. We examined the impact of guideline concordant education of appropriate RADT and antibiotic use in pharyngitis on providers’ (physician and APRN) use of RADT in an academic and private pediatric primary care clinic.

Methods

Retrospective chart review of 1,085 healthy children, age 1–5 years old, seen in clinics between September 2015 and March 2019 (355 pre- and 730 post-education; 211 academic and 874 private). Education occurred in 3/2017. Cases selected had either complaint of sore throat, RADT, or diagnosis of GAS pharyngitis or pharyngitis. Data collected included the presence of viral symptoms (e.g., cough, rhinorrhea), RADT/GAS culture results, diagnosis, and prescribed antibiotics. RADT was deemed unnecessary for all children < 3 years old without GAS exposure, in patients with ≥ 2 viral symptoms, or in patients ≥ 3 years old without pharyngitis.

Results

Overall, RADT use decreased from pre to post intervention (72.1% vs. 23.4% of patients, P ≤ 0.0001). Unnecessary RADT use decreased overall (50.4% vs. 16.2%, P ≤ 0.0001), in all clinics (private: 56.2% vs. 16.0%, P ≤ 0.0001; academic: 38.1% vs. 17.4%, P = 0.0012), and with all providers (physician: 41.6% vs. 18.3%, P ≤ 0.0001; APRN: 58.8% vs. 14.1%, P ≤ 0.0001). Unnecessary RADT use decreased for children <3 years old (28.1% vs. 7.4%, P ≤ 0.0001) and ≥2 viral symptoms (65.7% vs. 16.5%, P ≤ 0.0001).

Conclusion

Unnecessary RADT use decreased in the post-education period overall (34%), in children <3 years old (21%), and in patients with ≥ 2 viral symptoms (49%). Reductions were also seen in both academic (21%) and private (40%) clinics as well as with both physicians (23%) and ARPNs (45%). Limitations include lack of a control group and sample size variance by the clinic. We observed positive trends in RADT reduction following provider education in private and academic settings; however, further research including control and optimal sample size is needed to confirm any direct impact.

Disclosures

All authors: No reported disclosures.
2208. Development and Evaluation of Predictive Models for Estimating Infection Susceptibility to Empiric Treatment Regimens Among Patients with Pneumonia in Intensive Care Units
Authors: Dewart Courtney M , Hade Erinn , Gao Yuan , Rahman Protiva , Lustberg Mark , Pancholi Preeti , Stevenson Kurt , Hebert Courtney
Published: October 2019

Background

Predictive models for empiric antibiotic prescribing often estimate the probability of infection with multidrug-resistant organisms. In this work, we developed models to predict coverage of specific treatment regimens to better target antibiotics to high- and low-risk patients.

Methods

We established a retrospective cohort of adults admitted to the ICU in a 1,300-bed teaching hospital from November 1, 2011 to June 30, 2016. We included patients with a diagnosis of pneumonia and positive respiratory culture collected during their ICU stay. We collected demographics, comorbidities, and medical history from the electronic health record. We evaluated three penalized regression methods for predicting infection susceptibility to 11 treatment regimens: least absolute selection and shrinkage operator (LASSO), minimax concave penalty (MCP), and smoothly clipped absolute deviation (SCAD). We developed models for susceptibility prediction at two stages of the diagnostic process: for all pathogenic bacteria and for infections with Gram-negative organisms only. We selected final models based on higher area under the receiver operating characteristic (AUROC), acceptable goodness of fit, lower variability of the AUROCs in the cross-validation run, and fewer predictors.

Results

Among 1,917 cases of pneumonia, 54 different pathogens were identified. The most frequently isolated organisms were: Pseudomonas aeruginosa (16.6%), methicillin-resistant Staphylococcus aureus (16.1%), and Staphylococcus aureus (13.5%). Frequently selected variables included age, Elixhauser score, tracheostomy status, recent antimicrobial use, and prior infection with a carbapenem-resistant organism. All final models used MCP or SCAD methods. Point estimates for the AUROCs in the training set ranged from 0.70 to 0.80, and estimates in the internal validation set ranged from 0.64 to 0.77.

Conclusion

MCP and SCAD outperformed LASSO. For some regimens, models predicted infection susceptibility with fair accuracy. These models have potential to help antibiotic stewardship efforts to better target appropriate antibiotic use.

Disclosures

All authors: No reported disclosures.
2214. Comparison of Cefepime–Zidebactam (WCK 5222), Ceftazidime–Avibactam, and Ceftolozane–Tazobactam Tested Against Gram-Negative Organisms Causing Pneumonia in United States Hospitals in 2018
Authors: Sader Helio S , Carvalhaes Cecilia G , Mendes Rodrigo E , Castanheira Mariana , Flamm Robert K
Published: October 2019

Background

Zidebactam (ZID) is a bicyclo-acyl hydrazide antibiotic with a dual mechanism of action: selective Gram-negative PBP2 binding and β-lactamase inhibition. We evaluated the frequency and antimicrobial susceptibility (S) of Gram-negative bacilli (GNB) isolated from patients with pneumonia in US hospitals.

Methods

All 3,086 clinical isolates were consecutively collected from patients hospitalized with pneumonia (1/patient) in 29 US medical centers in 2018, and the GNB (n = 2,171) were S tested against cefepime (FEP)-ZID (1:1 ratio) and comparators by reference broth microdilution methods. The FEP S breakpoint of ≤8 mg/L (CLSI, high dose) was applied to FEP-ZID for comparison purposes. An FEP-ZID S breakpoint of ≤64 mg/L has been proposed for non-fermentative GNB based on pharmacokinetic/pharmacodynamic target attainment and was applied. Enterobacterales (ENT) isolateswere screened for β-lactamase genes by whole-genome sequencing.

Results

GNB represented 70.3% of the collection, and the most common GNB were P. aeruginosa (PSA; 34.9% of GNB), K. pneumoniae (10.9%), E. coli (9.7%), S. marcescens (7.7%), and S. maltophilia (XM; 6.4%). FEP-ZID was highly active against PSA (MIC50/90, 2/8 mg/L; 98.8% and 99.9% inhibited at ≤8 and ≤16 mg/L, respectively; highest MIC, 32 mg/L), including resistant subsets (table). Among comparators, colistin (99.6%S), ceftazidime–avibactam (CAZ-AVI; 95.2%S), and ceftolozane–tazobactam (C-T; 94.5%S) were the most active compounds against PSA. FEP-ZID inhibited all ENT at ≤4 mg/L, including ESBL-producers (MIC90, 0.25 mg/L) and carbapenem-resistant ENT (MIC90, 4 mg/L). The most active comparators against ENT were CAZ-AVI (99.9%S), amikacin (98.5%S), and meropenem (MEM; 98.3%S). FEP-ZID inhibited 75.0% and 97.9% of XM isolates at ≤8 and ≤16 mg/L, respectively (highest MIC, 64 mg/L). The only other compounds active against XM were co-trimoxazole (MIC50/90, ≤0.12/2 mg/L; 95.7%S) and levofloxacin (MIC50/90, 1/2 mg/L; 70.7%S). FEP-ZID inhibited 71.0% and 98.9% of A. baumannii isolates at ≤8 and ≤64 mg/L,, respectively.

Conclusion

FEP-ZID showed potent in vitro activity against GNB causing pneumonia in US hospitals and may represent a valuable therapeutic option for these difficult-to-treat infections

Disclosures

All authors: No reported disclosures.
2219. Evaluation of Medicare Claims to Assess Burden of Pertussis Disease in Persons Aged ≥65 Years
Authors: Havers Fiona , Wu Xiyuan , Wernecke Michael , Kelman Jeffrey A , Spiller Michael , Hariri Susan
Published: October 2019

Background

Pertussis in adults may be underdiagnosed and underreported; there is limited information on the incidence and severity of pertussis in older adults. We compared pertussis diagnoses identified using medical claims data with national surveillance data to examine the use of claims data as a source for disease burden estimates.

Methods

We examined claims data in persons aged ≥65 years in the United States enrolled in Medicare A and B from January 1, 2008 to December 31, 2017. We identified provider-diagnosed pertussis through pertussis-related ICD9/ICD10 diagnostic codes (033.XX, 484.3, A37.XX). We examined whether any were categorized as inpatient claims and if there were claims for laboratory tests within 30 days of the initial pertussis claim. We estimated claims-based pertussis incidence using person-time for all Medicare A/B enrollees and compared incidence estimates to those reported by the Nationally Notifiable Diseases Surveillance System (NNDSS) for the same period and age group.

Results

Among 27,269,361 Medicare beneficiaries, 24,355 (0.09%) had claims with pertussis diagnostic codes. Of these, 1,875 (7.7%) had claims associated with inpatient hospitalizations; 7,964 (33%) had laboratory testing performed. The mean annual incidence of claims-based pertussis was 11.5/100,000 person-years (range: 9.37 to 14.3/100,000 person-years) (figure). In contrast, 6,722 pertussis cases in persons aged ≥65 years were reported to NNDSS. Among the 5,101 cases whose hospitalization status was known, 783 (15%) were hospitalized. Mean annual reported pertussis incidence was 1.5/100,000 person-years (0.67 cases to 2.63 cases/100,000 person-years) in this age group.

Conclusion

Many more Medicare beneficiaries with pertussis-related claims were identified than pertussis cases in persons ≥65 years reported to public health authorities, suggesting pertussis is likely diagnosed more frequently in older adults than national incidence estimates indicate. A smaller proportion of Medicare beneficiaries with pertussis-related claims were hospitalized compared with reported cases and a majority did not have laboratory testing performed. It is unknown what proportion of pertussis-associated claims represent true pertussis disease.

Disclosures

All authors: No reported disclosures.
2224. Reducing Antibiotic Overuse in Adult Lower Respiratory Tract Infections Using Novel Host–Response-Based Diagnostics
Authors: Shani Liran , Halabi Salim , Shiber Shachaf , Paz Meital , Moscoviz Einat , Neuberger Ami , Petersiel Neta , Grupper Mordechai , Kirshner Dani , Haber Daniel , Kronenfeld Gali , Samuel Mastboim Niv , Gottlieb Tanya , Stein Michal , Rudich Nurit , Sitry Naama , Guetta Claire S , Pri-or Ester , Lishtzinsky Ynon , Yanai Shirly , Maor Yasmin , Oved Kfir , Eden Eran , Drescher Michael , Paul Mical
Published: October 2019

Background

Antibiotic overuse in LRTI is a major healthcare care problem, contributing to antimicrobial resistance. A novel assay that integrates blood levels of three immune-proteins TRAIL\IP-10\CRP was developed to assist in differentiating bacterial from viral disease. The assay exhibited high performance in blinded validation studies focusing on children. We performed a preliminary analysis of the ongoing OBSERVER study, evaluating the assay’s potential to reduce antibiotic misuse in adult patients presenting with suspicion of LRTI.

Methods

OBSERVER (NCT03011515) is an EU Horizon 2020 funded study (grant No. 684589), the first to validate the signature in adult LRTI patients. For every participant recruited at the emergency departments of three hospitals in Israel, we collected medical history, physical examination, routine lab, imaging, and respiratory multiplex PCR data. The assay outcomes are bacterial, viral or equivocal. Reference standard outcome of bacterial, viral, indeterminate or noninfectious, was assigned by expert panel majority adjudication. Indeterminates were excluded from the analysis.

Results

In this preliminary analysis, we included the first 218 patients with locked data (Figure 1). Age ranged from 18 to 96 years (mean 59.5). Clinical syndromes included: 21% pneumonia, 13% acute bronchitis, 6% COPD exacerbation, 32% upper respiratory tract infection and 16% unspecified LRTI or viral infections. The assay demonstrated high diagnostic performance for distinguishing bacterial from viral disease (Figure 2). Assay equivocal rate was 8%. In this cohort, antibiotics were prescribed to 41 of 105 patients with viral reference outcomes indicating an overuse rate of 39%, of these, 34 yielded viral index test outcomes, supporting the potential of the assay to reduce overuse by ~83%.

Conclusion

The TRAIL/IP-10/CRP assay demonstrated high diagnostic performance for differentiating between bacterial and viral disease. Medical literature shows that there is a big gap between guidelines antibiotic prescription recommendations and reported prescribing rates (~25% vs. 40%-50%) for suspected LRTI in adults. The use of this new assay, which has a specificity of 93% and NPV of 99%, can help to close the gap and improve adherence to the guidelines.

Disclosures

All authors: No reported disclosures.
2231. Safety of Nebulized Colistin as Adjunctive Treatment of Lower Respiratory Tract Infections
Authors: Nadeem Komal , Raja Karan , Patel Mitesh , Philips Mona
Published: October 2019

Background

Systemic antibiotics used in treatment of drug-resistant lower-respiratory tract infections (LRTI) may have poor lung penetration or narrow therapeutic indices. Nebulized administration of colistin allows direct instillation of active agent to maximize concentrations at the site of infection. Theoretically, local administration also avoids treatment-limiting toxicities and adverse drug reactions (ADR). Current literature supports efficacy of nebulized colistin as adjunctive treatment for LRTI. However, there is a paucity of data surrounding safety and tolerability of this administration technique.

Methods

The electronic medical record (EMR) was queried to identify patients treated with nebulized colistin between January 1, 2016 and December 31, 2018. The following data were collected from the EMR and hospital ADR reporting systems: demographics, treatment regimen, serum creatinine (SCr), concomitant nephrotoxins, infecting pathogen, treatment-emergent ADRs, and drug toxicities. The primary outcome was prevalence of renal (acute kidney injury [AKI]), neurologic (seizure, visual disturbance), or respiratory (bronchospasm) ADRs secondary to colistin nebulization therapy. AKI was defined according to the RIFLE criteria.

Results

Thirty-two patients were administered nebulized colistin during the study period. Approximately 19% of patients had a baseline renal impairment. Cultures were positive in 29 patients of which 11 organisms were resistant to all tested antimicrobials. The most common infecting pathogen was A. baumanii (n = 15) followed by K. pneumoniae (n = 9). The median duration of therapy was 4.6 days. Seventeen patients (53.1%) were exposed to concomitant nephrotoxins. Three patients experienced AKI of which two received simultaneous furosemide and one had underlying renal dysfunction and received concomitant vancomycin. The one observed neurologic reaction, seizure, occurred in a patient with underlying epilepsy. No patients had documented visual disturbances or bronchospasm.

Conclusion

The results of our study are consistent with the principle that localized administration of colistin results in a lower incidence of systemic adverse events. Nebulized colistin is a safe adjunct for managing LRTI. Renal, pulmonary, and neurologic reactions in this study were likely not treatment-related.

Disclosures

All authors: No reported disclosures.
2245. Oral 5-Day Lefamulin for Outpatient Management of Pneumonia Outcomes Research Team (PORT) Risk Class III/IV Community-Acquired Bacterial Pneumonia (CABP): Post Hoc Analysis of the Lefamulin Evaluation Against Pneumonia (LEAP) 2 Phase 3 Study
Authors: Schranz Jennifer , Alexander Elizabeth , Fitts David , Mariano David , Meads Andrew , Sandrock Christian , Moran Gregory J , Gelone Steven P
Published: October 2019

Background

Site-of-care decisions (e.g., admission vs. outpatient) in CABP management can be challenging for healthcare providers. Here we describe a post hoc analysis of adults with CABP managed as outpatients in the LEAP 2 double-blind, noninferiority, Phase 3 trial.

Methods

LEAP 2 compared the efficacy and safety of oral lefamulin (LEF) 600 mg every 12 hours for 5 days vs. oral moxifloxacin (MOX) 400 mg every 24 hours for 7 days in adults with PORT Risk Class II-IV. Descriptive statistics were generated to characterize demographics, baseline characteristics, efficacy, and safety outcomes in the subpopulation of outpatients in LEAP 2.

Results

Overall, 42% (310/736) of patients started treatment as outpatients (41% [151/368] LEF and 43% [159/368] MOX). Age, gender, and BMI were generally similar in both treatment groups. 44% (66/151) LEF and 40% (64/159) MOX outpatients had PORT Risk Class III or IV, and 21% in both groups (31/151 LEF and 34/159 MOX) had CURB-65 score 2 or 3. Comorbidities included smoking history (43% LEF vs. 34% MOX), hypertension (26% vs. 30%), COPD/asthma (14% vs. 18%), and diabetes mellitus (7% vs. 11%). Early clinical response (ECR) responder rates and investigator’s assessment of clinical response (IACR) success rates at the test of cure (TOC) visit were high and similar in both groups among all, PORT Risk Class III/IV, and CURB-65 score 2 or 3 outpatients (Table 1). In the PORT Risk Class III/IV subset, 86% LEF vs. 80% MOX patients were both an ECR responder and IACR success at TOC. In the CURB-65 score 2 or 3 subset, 87% LEF vs. 74% MOX patients were both an ECR responder and IACR success at TOC. Treatment-emergent adverse event (TEAE) rates were similar in both groups (Table 2). Consistent with overall study results, the difference between groups in related TEAEs was driven by gastrointestinal disorders (20% LEF vs. 5% MOX), specifically diarrhea (15% vs. 1%). Rates of TEAEs leading to discontinuation were low and similar in both groups. No LEF outpatient had an SAE or was admitted during the study, compared with 5 (3%) SAEs, including 2 deaths, in the MOX group.

Conclusion

These study data suggest that PORT Risk Class III or IV patients can be effectively managed as outpatients with 5 days of oral LEF as an alternative to fluoroquinolones for the treatment of CABP.

Disclosures

All authors: No reported disclosures.