bluuebunny/crossref_metadata_2025_split huggingface dataset:
1778. Epstein–Barr Virus Genetic Diversity: Evaluation of BZLF1 Variants among Bone Marrow Transplant Patients and Individuals with Infectious Mononucleosis
Authors: Abdulnoor Mariana , Khodai-Booran Nasser , Schechter Tal , Paton Tara , Casallo Guillermo , Allen Upton D 
Published: October 2019

Abstract

Background
Epstein–Barr virus (EBV) is associated with several diseases, including infectious mononucleosis (IM) and malignant disorders, including post-transplant lymphoproliferative disorder (PTLD). The relationship between strains of the virus and disease manifestations or illness severity is of interest. Such strains have been defined by genetic variations in the major viral genes. Data involving the patterns of genetic diversity of the virus in different populations are required. We examined the genetic diversity of the BZLF1 gene, which is a major lytic gene of the virus.

Methods
We sequenced the BZLF1 gene of EBV following amplification from DNA that was extracted from blood obtained from pediatric bone marrow transplant (BMT) patients and children and young adults with IM. Sequencing was done by Sanger methodology (dideoxy DNA sequencing) and the sequences were aligned with a reference strain of EBV using Geneious software. The variant burden and types of single nucleotide variants (SNV) were compared across the 3 exons of the BZLF1 gene.

Results
We sequenced the BZLF1 gene using 21 patients with IM (median age 14, age range 2–19 years) and 11 who underwent bone marrow transplantation (median age 6, range 3–13 years). Three of 11 BMT patients developed post-transplant lymphoproliferative disorder (PTLD). Among the 3 exons, exon 1 had the greatest diversity across both study groups. There was a tendency for less diversity among PTLD samples, with no sample containing >1 single nucleotide variant (SNV) in contrast to the other samples. In samples that contained SNVs, there was a non-statistically significant trend for more SNVs to occur among the IM samples compared with PTLD samples (median 4.5 and 0, respectively; P > 0.05). Additionally, 2/11 (18.2%) BMT sequences contained more than 1 SNV compared with 7/21 (33.3%) IM sequences (P > 0.05).

Conclusion
There was a tendency for more genetic diversity among samples from patients with IM compared with bone marrow transplant patients, notably those with PTLD. Further studies will determine if this tendency is due to selective pressures in the transplant setting, including but not limited to the use of antiviral agents directed at the lytic phase of EBV.

Disclosures
All authors: No reported disclosures.
1781. Assessing the Utility of First-Contact Serum Ferritin as an Augur of Severe Thrombocytopenia in Dengue Fever
Authors: Lodha Abhijit R , Pillai Ashwin , Reddy Pavan , Munshi Nita 
Published: October 2019

Abstract

Background
Dengue fever is an arboviral infection with global public health concerns. Much of its impact on society is attributable to the economic ramifications on public health programs, particularly in developing countries. Hospitalization accounts for 4/5th of total direct expenditure on the disease. The identification of an inexpensive biomarker to help guide the decision to hospitalize would have great utility. Serum ferritin was selected as levels reflect both infective viral load and host immune response – factors that purportedly determine the likelihood of thrombocytopenia.

Methods
The study was conducted at α = 0.05 and β = 0.05. We included patients aged ≥12 years, of both sexes, with a definite serological diagnosis of dengue fever. We excluded patients with severe anemia (hemoglobin serum ferritin levels were measured at first medical contact. Patients were monitored with serial total blood counts, until platelet counts normalized. The primary endpoint was severe thrombocytopenia, defined as platelet count nadir <20,000/µL.

Results
We included 64 patients in the study. The receiver-operating-characteristics (ROC) curve for the association between serum ferritin levels and the primary end-point had an area-under-curve (AUC) of 0.846, implying a good test accuracy. The ideal cut-off for “high” serum ferritin was determined to be 876 ng/mL, with levels above that predicting severe thrombocytopenia with a sensitivity of 90% and specificity of 74.07%. The negative predictive value at this threshold was 97.56%. The primary endpoint was attained by 39.13% of patients with raised ferritin vs. 2.44% with lower values (P = 0.0002). The Odd’s ratio for developing severe thrombocytopenia was 25.71. This association was consistent irrespective of sex, the day of presentation, baseline hemoglobin, or primary or secondary dengue.

Conclusion
In appropriately selected patients, serum ferritin is a reliable indicator of severe dengue fever, helping identify patients likely to require more careful observation.

Disclosures
All authors: No reported disclosures.
1985. Impact of Suppressing Ciprofloxacin Susceptibility Results on Antibiotic Utilization and Hospital-acquired Clostridioides difficile Infection
Authors: White Bryan P , Chastain Daniel B , Kinney Karen , Thompson Katie , Kelley Jerry , McCloskey Cindy B 
Published: October 2019

Abstract

Background
Fluoroquinolones (FQs) are broad-spectrum antibiotics associated with multiple adverse effects and an increased risk of Clostridioides difficile infections (CDI). Previous data suggest that suppression of FQ susceptibility results decreased FQ use. The purpose of this study was to examine the impact of suppressing ciprofloxacin susceptibility on antibiotic use, susceptibility, and CDI.

Methods
This was a single-center quasi-experimental study of the effect of the suppression of ciprofloxacin susceptibility on pan susceptible urine isolates for Klebsiella sp. and E. coli starting in March 2018 in the 11 months before and after the intervention. Monthly antibiotic utilization in days of therapy (DOT)/1,000 patient-days for levofloxacin, ciprofloxacin, ceftriaxone, trimethoprim/sulfamethoxazole (TMP/SMZ), fosfomycin, and nitrofurantoin, hospital-acquired CDI (HA-CDI) rates as defined by CDC, and Pseudomonas aeruginosa susceptibility was compared with interrupted time series analysis using Stata MP 12.1 before and after the intervention to compare the level, intercept, and rate, slope, of a trend line.

Results
There was no change in the level or rate of ciprofloxacin DOT (0.27, 95% CI: −0.94 to 1.48–3.49; 95% CI: −10.89 to 3.90) and levofloxacin DOT (−5.87, 95% CI: −17.79 to 6.06; −0.98, 95% CI −2.86 to 0.90) with the intervention, respectively. Level of P. aeruginosa susceptibility to ciprofloxacin level (8.13, 95% CI: 0.00 to 16.26) had a trend toward increasing and rate (1.65, 95% CI: 0.44 to 2.87) increased after the intervention. Ceftriaxone DOT level decreased after the intervention (P = 0.01), but the rate did not change. Cephalexin (P = 0.01) and nitrofurantoin (P = 0.01) DOT levels increased after the intervention without changes in rates. There was no change in the level or rate of HA-CDI, fosfomycin, or TMP/SMZ DOTs.

Conclusion
Suppressing ciprofloxacin susceptibility results on pan susceptible Klebsiella sp. and E. coli urine isolates was associated with increased P. aeruginosa susceptibility to ciprofloxacin and increased cephalexin and nitrofurantoin DOTs. No changes were seen in FQ use or HA-CDI rates.

Disclosures
All authors: No reported disclosures.
1987. Impact of Updated IDSA Clostridium difficile Guidelines on the use of Fidaxomicin in a Large Health System
Authors: Bariola J Ryan , Khadem Tina 
Published: October 2019

Abstract

Background
Fidaxomicin (fidax) is approved for treatment of Clostridioides difficile infection. In February 2018 IDSA/SHEA released updated guidelines suggesting expanded use of fidax, recommending it or oral vancomycin (po vanc) in severe or non-severe initial episodes or for most recurrences. In April 2018, University of Pittsburgh Medical Center (UPMC) relaxed system-wide guidelines to allow for fidax use in the first recurrence of C. difficile or later, with earlier use allowed by ID or GI specialists or with local Pharmacy and Therapeutics Chair approval. Hospitals could continue to be more restrictive if desired. We reviewed changes in fidax, po vanc, and IV/PO metronidazole (metro) use at UPMC hospitals after guideline changes.

Methods
For the reviewed antibiotics, hospital-level usage was evaluated at 15 UPMC hospitals before/after system-level changes. Usage was measured as days of therapy per 1,000 patient-days (DOT/1,000 PD). Sites were further grouped by the level of restrictions: Standard (following new system guidelines) or more restrictive (additional restrictions remained in place locally). Hospitals were also grouped by type of local stewardship programs (ASP): Robust (included an Infectious Diseases trained clinical pharmacist or ID physician with specific time dedicated to antibiotic review) or Non-Robust.

Results
Figure 1 shows before/after changes in usage at all hospitals. Figure 2 shows changes in Standard vs. More Restrictive hospitals, and Figure 3 shows changes in Robust vs. Non-Robust hospitals.

Conclusion
Fidax use remained low, but an increase was seen after the release of the guidelines and relaxation of system restrictions, mainly in hospitals without additional restrictions in place. PO vanc also increased across the system, possibly indicating better adherence to updated guidelines regarding less metro use for C. difficile treatment. Although minimal decrease, if any, was seen with metro itself. This could have been compounded by the recent fluid shortage as well as other common uses for metro. Dissemination of new guidelines to providers should be a key function of ASPs as well as monitoring for changes in usage after implementation of local changes. Further studies are needed to define any differences in practice patterns and clinical outcomes related to changes in guidelines.

Disclosures
All authors: No reported disclosures.
1989. Impact of Pharmacist-Led β-Lactam Allergy Clarification Interview on Optimizing Preoperative Antibiotic Prophylaxis
Authors: Kwiatkowski Shaina , Mulugeta Surafel , Davis Susan L , Kenney Rachel , Kalus James , Walton Leslie , Patel Nisha 
Published: October 2019

Abstract

Background
Patients with reported β-lactam allergies (BLA) are often given alternative perioperative antibiotic prophylaxis, increasing risk of surgical site infections (SSI), acute kidney injury (AKI), and Clostridioides difficile infection (CDI). The purpose of this study was to implement and evaluate a pharmacist-led BLA clarification interview in the preoperative setting.

Methods
This single-center, IRB-approved, quasi-experimental study compared surgical patients with a BLA between November 2017 and March 2018 (pre-intervention) vs. November 2018 and March2019. From November 2018 to March 2019, a pharmacist performed BLA clarification phone interviews for patients scheduled for a surgical procedure. Based on the allergy history and decision algorithm, first-line antibiotics, alternative antibiotics, or an allergy testing referral were recommended and documented in the EHR. The allergy label was updated as well. The primary outcome was the use of β-lactams preoperatively. Secondary outcomes included 30-day SSI and CDI, AKI, allergic reactions, allergy labels updated or removed, time to incision, and vancomycin doses administered.

Results
87 patients were included in the study; 50 (57%) and 37 (43%) in the pre- and post-group, respectively. Most common surgeries: orthopedic 41 (47%), neurosurgery 17 (20%). In the post-group, all EHR BLA labels were updated after interview. 23 patients were referred for allergy testing, 12 (52%) completed BLA testing, and 7 BLA allergies were removed. 76% of pharmacy antibiotic recommendations were accepted (figure). Cefazolin use significantly increased from 28% to 65% post-intervention, P = 0.001; vancomycin use also increased from 19 (38%) to 22 (59%), P = 0.047. Time to incision decreased by a median of 8 minutes (P = 0.484). SSI occurred in 5 (10%) patients in the pre-group only, P = 0.051. All of these were associated with alternative antibiotics. Incidence of AKI and CDI were similar between the groups (P > 0.05). No allergic reactions occurred in either group.

Conclusion
Clarifying reported BLA in the perioperative setting significantly increased β-lactam preoperative use without negative clinical sequelae.

Disclosures
All authors: No reported disclosures.
1994. Impact of Pharmacist-initiated MRSA Nasal PCR Protocol on Pneumonia Therapy in a Community Teaching Hospital
Authors: Pham Selena , Sturm Abby , Dumkow Lisa , Jacoby Joshua , Egwuatu Nnaemeka 
Published: October 2019

Abstract

Background
Methicillin-resistant Staphylococcus aureus (MRSA) nasal PCR testing can rapidly detect MRSA colonization via nasopharyngeal swab. With a high negative predictive value for MRSA pneumonia, this test may help minimize the duration of anti-MRSA therapy and associated adverse drug events. This study aimed to evaluate the impact of a pharmacist-initiated MRSA nasal PCR protocol on pneumonia therapy in a community teaching hospital.

Methods
This retrospective, quasi-experimental study evaluated adult patients with pneumonia before and after the implementation of a pharmacist-initiated MRSA nasal PCR protocol. The GeneXpert MRSA/SA Nasal Complete Assay was utilized for PCR testing. Prior to protocol implementation the MRSA nasal PCR was not routinely used to assist in pneumonia treatment decisions. Following protocol implementation, pharmacists ordered MRSA PCR testing after an order for anti-MRSA pneumonia therapy; however, prescriber approval was required to discontinue therapy following negative result. The primary outcome of this study was to compare the duration of anti-MRSA therapy between the pre-PCR group (June 1–November 1, 2017) and PCR group (June 1–November 1, 2018). Secondary comparisons included the duration of antipseudomonal therapy, time from IV to PO interchange, adverse events, and clinical outcomes between groups.

Results
210 patients were included (pre-PCR n = 138, PCR n = 72). Vancomycin was the anti-MRSA therapy ordered for all patients in both groups. In the PCR group, the median time from vancomycin order to PCR order was 2.8 hours (0–45.6 hours), while median time from PCR order to PCR result was 4.4 hours (0.6–31.5 hours). The PCR result was negative for 63 patients (87.5%) and 56 (88.9%) vancomycin orders were discontinued within 24 hours of the negative result. The mean duration of vancomycin therapy was significantly shorter in the PCR group (2.5 vs. 1.4 days, P < 0.001) as well as duration of IV therapy (5 vs. 3.9 days, P = 0.003). There was no difference between groups in duration of antipseudomonal therapy (P = 0.425), acute kidney injury (P = 0.332), 30-day readmission (P = 0.137), or 30-day mortality (P = 0.179).

Conclusion
A pharmacist-led MRSA nasal PCR protocol significantly decreased the duration of anti-MRSA therapy and IV antibiotic duration in patients with pneumonia.

Disclosures
All authors: No reported disclosures.
2000. Utilization of a ‘Never Event’ Framework to Classify Antimicrobial Appropriateness
Authors: Liu Jiajun , Mercuro Nicholas , Davis Susan L , Yarnold Paul , Patel Twisha S , Petty Lindsay A , Pais Gwendolyn M , Kaye Keith S , Scheetz Marc H 
Published: October 2019

Abstract

Background
Contemporary strategies can be leveraged to predict antimicrobial overuse, yet little information is gained on the appropriateness of antibiotics prescribed. Classifying appropriateness is complicated by the lack of a standard definition for appropriateness. Thus, we created and implemented a novel ‘antibiotic never event’ (NE) framework to systematically classify the most inappropriate usages of vancomycin and correlated these NE to abnormal consumption trends (i.e., antibiotic outbreaks).

Methods
Vancomycin use was categorized by an algorithm using data query from the electronic medical records. Extracted data included vancomycin use, relevant patient demographics, and microbiological data. Electronic classifications placed each vancomycin therapy into type 1 (use for non-susceptible organism after susceptibility finalization) or type 2 (use exceeding 48h after susceptibility report when a safe de-escalation is possible) NE. Patients were categorized as cases or controls (no NE) at Northwestern Memorial Hospital (NM) and Henry Ford Hospital (HF) between January 2014 and October 2017. A manual chart review was performed. Sensitivity (SEN), specificity (SPEC), PPV, and NPV were calculated for NE prediction. Vancomycin use was quantified during the same period. Linear models with prediction intervals (PI) were generated to identify potential outbreaks, which were linked to monthly NE counts defined as a binary factor.

Results
A total of 220 NE cases were electronically identified for vancomycin at NM (n = 197) and HF (n = 23). Random cases were matched 1:1 (NM = 200) and 1:5 (HF = 115) to controls for manual review. At NM and HF, 35 and 24 true positives were identified, respectively. Thus, overall SEN and SPEC were 93.7% and 75.1% and PPV and NPV were 45.7% and 98.1%, respectively. Linear models revealed 11 potential outbreak periods at HF and 5 at NM. A PI of 80% showed a combined SEN below 10% and SPEC above 90%, respectively.

Conclusion
The methodology was generalizable across two centers. In the pilot review, our method was highly sensitive and an effective screening tool for NE identification. Antibiotic consumption trends did not correlate with NE. In summary, the NE classification was sensitive in assessment of antibiotic appropriateness, whereas consumption alone does not predict NE.

Disclosures
All authors: No reported disclosures.
2010. A Significant Reduction in Empiric Vancomycin Days of Therapy for Suspected MRSA Pneumonia in Adult Non-ICU Patients After Implementation of a Rapid MRSA Nasal PCR Test with Antimicrobial Stewardship Intervention
Authors: Markoski Nikola , Wang Sheila K , Bertram Christie , Hoff Brian M , Sutton Sarah , Zembower Teresa , Qi Chao , Rhodes Nathaniel J , Scheetz Marc H , Postelnick Michael J 
Published: October 2019

Abstract

Background
Methicillin-resistant Staphylococcus aureus (MRSA), when implicated in respiratory tract infections, can be associated with significant morbidity and mortality. The prevalence of severe MRSA pneumonia may be as high as 10%; however, recent evidence suggests that MRSA is much less prevalent as a cause of community-acquired pneumonia (CAP) among community-dwelling patients and may be as low as 0.1%. Nonspecific features of pneumonia in non-ICU patients (viral co-infection, multi-lobar infiltrates) often lead clinicians to cautiously initiate empiric anti-MRSA therapy. Recommendations of when to safely de-escalate empiric treatment prior to known respiratory cultures are not established. To decrease anti-MRSA therapy in non-ICU pneumonia patients with a low probability of MRSA pneumonia, we employed a nasal screening paired with antimicrobial stewardship intervention.

Methods
A retrospective, single-center, pre-post interventional study was conducted at Northwestern Memorial Hospital (NMH), in Chicago, IL, to assess the duration of empiric vancomycin for suspected MRSA pneumonia in non-ICU patients before (January 2019) and after (March 2019) the implementation of a rapid MRSA nasal PCR test. During the post-implementation period, an NMH Antimicrobial Stewardship (AS) member identified and assessed the daily (M-F) use of empiric vancomycin for pneumonia in non-ICU patients. When vancomycin use criteria were not met, the AS pharmacist requested the team order a BD MRSA Nasal PCR test (NPV: 97.2%) to classify patients as either possible MRSA pneumonia or unlikely MRSA pneumonia. Results of a negative MRSA Nasal PCR with an ongoing clinical disposition not suggestive of MRSA pneumonia prompted the AS pharmacist to recommend de-escalation of vancomycin.

Results
See table.

Conclusion
The use of a rapid MRSA nasal PCR test with active antimicrobial stewardship intervention significantly reduced the duration of empiric vancomycin in hospitalized non-ICU patients with suspected MRSA pneumonia.

Disclosures
All authors: No reported disclosures.
2015. Minimal Impact of Blood Culture Contaminants on Patient Care Decisions May Limit Cost-Effectiveness of Interventions to Reduce Contamination Rates
Authors: Augusto. Terrero Salcedo David , Powers-Fletcher Margaret , Smulian Alan G 
Published: October 2019

Abstract

Background
High blood culture (BC) contamination rates have been associated with increased healthcare cost, antimicrobial use, and extended length of stay. Interventions using blood culture diversion devices (BCDD) reduce contamination rates, but often increase equipment costs compared with traditional collection techniques. Cost savings will only be achieved, therefore, if contaminated BCs do in fact lead to expensive care decision. The purpose of this study was to define the actual impact of contaminated BCs on patient care as a means of determining the cost-effectiveness of implementing BCDD at our institution.

Methods
A retrospective review of all contaminated BCs collected in our Emergency Department (ED) from July 2018 to December 2018 was completed. Data including antimicrobial therapy, admission status, laboratory orders, and co-morbidities for patients with contaminated cultures, as defined by the College of American Pathologist (CAP), were recorded. Laboratory costs included rapid molecular assays performed for patients admitted from the ED, as well as technologist effort and media costs for BC work-up.

Results
During this study period, out of a total of 4,176 blood draws, there were 118 BCs (2.8%) that met the CAP definition of contamination. Of all contaminated cultures, only 12.7% (n = 15) of patients were treated because of a positive BC, while 68.6% were given antibiotics due to other comorbidities; A total of 22 patients (18.6%) did not receive any antibiotics during the encounter. The most common therapy for treated contaminants was vancomycin (14/15, 93.34%) for an average of 5.2 days. No patients with contaminated BCs were admitted to the hospital because of a positive result; 92.3% of patients with contaminated BCs were admitted, however, for a different diagnosis. Based on average treatment and laboratory costs, the total costs per contaminant were estimated at $170 USD.

Conclusion
Contamination of BCs collected in the ED does not routinely lead to antimicrobial therapy or hospital admissions at our institution. This minimal impact of BC contaminants on patient care decisions and healthcare costs limits the cost-effectiveness of interventions such as BCDD at our institution. These findings may be specific to our institution based on our clinical practice and unique patient population.

Disclosures
All authors: No reported disclosures.