bluuebunny/crossref_metadata_2025 huggingface dataset:
1721. A Transcriptional Signature of Acute Aspergillus Infection Offers High Diagnostic Accuracy Despite the Presence of Immunosuppression
Authors: Steinbrink Julie M , Zaas Aimee K , Βncourt-Quiroz Marisol , Modliszewski Jennifer L , Corcoran David , McClain Micah T
Published: October 2019

Background

Invasive aspergillosis (IA) is a major cause of critical illness in immunocompromised (IC) patients. However, current fungal testing methods have significant limitations and there is a clear need for new diagnostic options. Disease-specific gene expression patterns in circulating host cells show promise as novel diagnostics; however, it is unknown whether such a “signature” exists for IA. Additionally, there is a need for better understanding of the effect of iatrogenic immunosuppression (present in most cases of IA) on such host response-driven biomarkers.

Methods

Male BALB/c mice were separated into an Aspergillus fumigatus inhalational exposure group and a placebo group. These two groups were each subdivided into three additional sets based on immunocompromised status (no immunosuppression, cyclophosphamide, and corticosteroids) for a total of six experimental groups. Mice were sacrificed 4 days post-infection. Whole blood was assayed for transcriptomic responses via microarray. Bayesian techniques were utilized to develop classifiers of IA and leave one out cross-validation was used to estimate predictive probabilities.

Results

Aspergillus infection triggers a powerful response in non-IC hosts, with 2996 genes differentially expressed between IA and controls. We generated a 146-gene expression classifier able to discriminate between non-IC mice with IA and uninfected non-IC mice with 100% accuracy. However, the presence of immunosuppressive drugs exhibited a strong confounding effect on the transcriptomic classifier that was derived in the absence of immunosuppression. After controlling for the genomic effects of immunosuppressive drugs, we were able to generate a 187-gene classifier with a sensitivity of 100% and specificity of 97% across all IC states.

Conclusion

The host transcriptomic response to IA is robust and highly conserved. Pharmacologic perturbation of the host immune response unsurprisingly has powerful effects on gene expression-based classifier performance and must be taken into account when developing novel diagnostics. When appropriately designed, host-derived peripheral blood transcriptomic responses to IA demonstrate the ability to accurately diagnose Aspergillus infection, even in the presence of immunosuppression.

Disclosures

All authors: No reported disclosures.
1751. The Impact of Prophylactic Systemic Antibiotics (PSA) on Cytomegalovirus (CMV) Infection: A Post-hoc Analysis of a Randomized Controlled Trial (RCT) in Hematopoietic Cell Transplantation (HCT) Recipients
Authors: Zamora Danniel , Xie Hu , Kimball Louise E , Golob Jonathan , Fredericks David , Liu Catherine , Petersen Finn , Leisenring Wendy , Boeckh Michael
Published: October 2019

Background

Prophylactic systemic antibiotics (PSA) during conditioning regimen-induced neutropenia after hematopoietic cell transplantation (HCT) reduce bacteremia but may disrupt the gut microbiota, potentially affecting viral immunity and risk for viral infections. Prior studies suggest a critical role of gut microbiota in the reconstitution of CMV-specific CD8+ T cells and in protection from respiratory viral infections after HCT (J Immunol 2007; 178: 5209; Blood 2018; 131:2978). To identify whether PSA is associated with differences in CMV infection outcomes after HCT, we conducted a post-hoc analysis of CMV infection in the only RCT of PSA exclusively performed in HCT recipients (Infection 1986; 14:115). In that trial, HCT patients received either PSA (ticarcillin/tobramycin/vancomycin or mezlocillin/ceftizoxime) or no systemic antibiotics during neutropenia (absolute neutrophil count <500/mm3).

Methods

A post-hoc analysis was performed of a previously conducted RCT in the pre-antiviral era (1984–1986) at the Fred Hutch. Patients received unscreened blood products and were tested weekly by CMV culture in throat, and disease was evaluated by tissue biopsy or bronchoalveolar lavage. CMV disease was confirmed by chart review. We compared the cumulative incidence of CMV at any site, CMV throat shedding, and CMV disease between randomization groups by day 100 post-transplant, treating death as a competing risk. Overall survival was also compared using Kaplan–Meier method.

Results

119 and 125 allograft recipients were randomized to PSA and no prophylaxis, respectively. Baseline characteristics in both groups were balanced. CMV infection at any site and CMV throat shedding were greater in the PSA group (Figures 1 and 2); CMV disease was numerically reduced in the no PSA group (Figure 3). Overall survival by day 100 was not different between the groups (Figure 4).

Conclusion

CMV infection risk appeared to be increased in recipients of PSA with a significant anaerobic spectrum. While current PSA regimens have narrower spectrum activity, these results provide the rationale to study if changes in gut microbiota play a role in CMV reactivation and adaptive immunity after HCT.

Disclosures

All authors: No reported disclosures.
1756. Role of Human bocavirus Respiratory Tract Infection in Hematopoietic Cell Transplant Recipients
Authors: Ogimi Chikara , Martin Emily T , Xie Hu , Campbell Angela P , Waghmare Alpana , Kuypers Jane , Jerome Keith , Leisenring Wendy , Englund Janet A , Boeckh Michael
Published: October 2019

Background

Limited data exist regarding the impact of human bocavirus (BoV) in hematopoietic cell transplant (HCT) recipients. We examined incidence and disease spectrum of BoV respiratory tract infection (RTI) in HCT recipients.

Methods

In a longitudinal surveillance study of viral RTIs among allogeneic HCT recipients, pre-HCT and weekly post-HCT nasal washes and symptom surveys were collected through day 100, then every 3 months, and whenever respiratory symptoms occurred through 1-year post-HCT. Samples were tested by multiplex semi-quantitative PCR for RSV, parainfluenza virus 1–4, influenza A/B, adenovirus, human metapneumovirus, rhinovirus, coronavirus, and BoV. Plasma samples from BoV+ subjects were analyzed by PCR. In addition, we conducted a retrospective review of HCT recipients with BoV detected in bronchoalveolar lavage or lung biopsy.

Results

Among 469 patients in the prospective cohort, 21 distinct BoV RTIs (3 pre-HCT and 18 post-HCT) were observed by 1-year post-HCT in 19 patients (median 42 years old, range 0–67) without apparent seasonality. BoV was more frequently detected in the latter half of the first 100 days post-HCT (Figure 1). The frequencies of respiratory symptoms in patients with BoV detected did not appear to be higher than those without any virus detected, with the exception of watery eyes (P < 0.01) (Figure 2). Univariable models among patients with BoV RTI post-HCT showed higher peak viral load in nasal samples (P = 0.04) and presence of respiratory copathogens (P = 0.03) were associated with presence of respiratory symptoms; however, BoV detection in plasma was not (P = 0.8). Retrospective review identified 6 allogeneic HCT recipients (range 1–64 years old) with BoV detected in lower respiratory tract specimens [incidence rate of 0.4% (9/2,385) per sample tested]. Although all 6 cases presented with hypoxemia, 4 had significant respiratory copathogens or concomitant conditions that contributed to respiratory compromise. No death was attributed mainly to BoV lower RTI.

Conclusion

BoV is infrequently detected in respiratory tract in HCT recipients. Our studies did not demonstrate convincing evidence that BoV is a significant pathogen in either upper or lower respiratory tracts. Watery eyes were associated with BoV detection.

Disclosures

All authors: No reported disclosures.
1764. Use of Intravesical BCG for Treatment of Bladder Cancer in a Renal Transplant Recipient, with Subsequent Resolution of Chronic BK Viremia
Authors: Kit Chan Yu , Jasmine Chung Shimin , Khor Vincent , Huei Li Gan Valerie , Chen Kenneth , Hwai Liang Loh Alwin , Kee Terence
Published: October 2019

Background

BK virus-induced nephropathy in renal transplantation is well recognized but its oncogenic potential is less appreciated.

Methods

We report a case of high-grade urothelial tumor in a renal transplant recipient with chronic BK viremia in the absence of BK nephropathy successfully treated with intravesical Bacillus Calmette-Guerin (BCG) instillation. Following BCG therapy, there was also spontaneous clearance of BK viremia.

Results

In July 2011, Mr. LYY, a 57-year-old Chinese man with end-stage renal failure secondary to chronic glomerulonephritis underwent uncomplicated deceased donor renal transplantation. One year later, he developed persistent high-level BK viremia despite reduction in immunosuppression. He was also treated with a course of ciprofloxacin from January to October 2013, and intravenous immunoglobulin (IVIG) in February 2013, but high-level BK viremia persisted. In spite of this, his graft function was preserved. He was subsequently placed on BK surveillance alone. Chronic BK viremia persisted for the next 5 years with stable graft function. See Figure 1. In February 2018, an incidental urinary bladder nodule was picked up on computed tomography (CT) scan performed for evaluation of urosepsis. Follow-up flexible cystoscopy in May 2018 showed a 1.5 cm papillary tumor over the left superior bladder wall. Transurethral resection of bladder tumor (TURBT) was performed and histopathological examination revealed high-grade papillary urothelial carcinoma. In addition, the biopsy specimen was stained positive for SV40, suggesting the possible association between chronic BK virus replication in the bladder and oncogenesis. Relook TURBT in July 2018 revealed a persistent erythematous patch over the posterior bladder wall. Given the cystoscopic findings, Mr. LYY received a weekly instillation of intravesical BCG for 6 weeks. He tolerated the intravesical BCG treatment with no local or systemic complications. Interestingly, his serum BK viral loads dropped below lower limits of detection thereafter and continued to remain so for the next 4 months.

Conclusion

We postulate that the intravesical BCG therapy triggered an immune response that targeted not only the tumor but also the BK virus infection, resulting in successful clearance of chronic BK viremia.

Disclosures

All authors: No reported disclosures.
1771. Donor-derived Ureaplasma Infection Increases Mortality in Lung Transplant Recipients
Authors: Roberts Scott C , Bharat Ankit , Kurihara Chitaru , Bhorade Sangeeta M , Ison Michael G
Published: October 2019

Background

Infection with Ureaplasma species has been linked to fatal hyperammonemia syndrome (HS) in lung transplant (LTx) recipients (R). In this retrospective cohort, we sought to characterize the epidemiology of Ureaplasma spp in both candidates and donors and describe outcomes of antimicrobial therapy in preventing and treating HS.

Methods

We performed a retrospective cohort study of patients who received LTx at Northwestern Memorial Hospital from July 2014 to October 2018. Candidate testing for Ureaplasma spp. was performed with urine culture and PCR testing before LTx but after listing. Positive candidates were treated with levofloxacin for 14 days prior to undergoing LTx. Donor testing was performed with bronchoalveolar lavage (BAL) culture and PCR testing at organ implantation. From July 2014 to February 2017 LTxR were treated according to result; from February 2017 to October 2018 LTxR received empiric levofloxacin and azithromycin at the time of LTx until testing returned negative. HS was defined as new-onset altered mental status (AMS) after LTx with ammonia > 100; if no ammonia was tested, LTxR was classified as not developing HS. Summary and comparative statistics were performed using IBM® SPSS Statistics version 25.0.

Results

66 patients who underwent LTx and had candidate screening, donor screening, or both were included. 81.8% (n = 54) of patients had negative screening tests in donor and candidate pre-LTx, 7.5% (n = 5) had positive Ureaplasma spp. testing pre-LTx, and 12.1% (n = 8) had positive donor BAL testing at the time of LTx. One had positive candidate and donor screening (see Table 1). 3 patients developed HS a median of 6 days post-transplant; 2 died with HS as attributed cause. None received empiric therapy. LTxR with confirmed donor-derived infection were more likely to have mortality at 1 year when compared with LTxR with negative testing and candidates with positive testing pre-LTx (P = 0.019). LTxR with donor-derived infection were more likely to have AMS, higher peak ammonia, and require renal replacement therapy, although none reached significance (Table 2).

Conclusion

Donor-derived Ureaplasma spp. in LTxR was associated with increased mortality at one-year. Pre-transplant screening and treatment had no effect on the outcome. There is high concern for donor transmission and we advocate testing in all LTxR.

Disclosures

All authors: No reported disclosures.
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

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

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

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

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

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

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

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

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

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.
2016. Antibiotic Misuse of Rural Residents and Pilot Project of Antibiotic Take-Back Program
Authors: Wang Weiyi , Wang Xiaomin , Cai Jingjing , Yao Tingting , Zhou Xudong
Published: October 2019

Background

Self-medication with antibiotics (SMA) is a major form of antibiotic misuse behaviors contributing to increasing antimicrobial resistance (AMR). The main source of SMA usually comes from in-home leftover antibiotics which usually disposed as household waste without classification. Therefore, an antibiotic take-back program (ATBP) is urgently needed.

Methods

A pilot ATBP was launched in Liantang Village, Zhejiang Province from January to March, 2019. A total of 50 households were randomly selected for the baseline survey. A questionnaire was used to investigate their knowledge and antibiotic use behaviors. Health education leaflets and posters were distributed to each household. A village Wechat group was set up for health communication. Residents were encouraged to hand over those unused or expired antibiotics at home to the village clinic to redeem a commodity. The pilot ATBP was implemented for 30 days. The type, name, and amount of antibiotics were collected as after intervention data.

Results

All of 50 households finished the questionnaire. Although 27 (52.9%) agreed that keeping antibiotics at home would potentially increase risk of SMA, there were still 32 (64.0%) residents reported that they kept antibiotics at home and 25 (49%) residents indicated that their leftover antibiotics usually disposed as household waste. After the 30-day intervention, 10 (20.0%) households handed their in-home antibiotics or medicine to the village clinic. In total, 32 boxes of medicine including 17 (53.1%) boxes of antibiotics were recycled. All of 32 boxes of medicine could be classified into 19 specific types, of which there were 8 (42.1%) types of antibiotics, belonging to four broad categories: Cephalosporins, Penicillins, Macrolides, and Nitroimidazoles. In addition, there were also antifungal drug, antiviral agent, anti-inflammatory drug, and paracetamol tablets handed over by the villagers as antibiotics.

Conclusion

Using leaflets and social media to promote health education can reduce the risk of keeping antibiotics at home. Rural residents could not identify commonly used antibiotics even after health education. To conduct a broader intervention to recycle antibiotics, further study needs to focus on improving the antibiotic identification among the rural residents.

Disclosures

All authors: No reported disclosures.
2024. A Multifaceted Intervention to Improve Oral Antimicrobial Prescription at the Emergency Department at a Japanese Tertiary Care Center
Authors: Tagashira Yasuaki , Honda Hitoshi
Published: October 2019

Background

The emergency department (ED) is one of the most important settings where antimicrobials are frequently prescribed in developed countries, and at least 30% of antimicrobials prescribed at the ED are inappropriate. Some studies revealed that various factors, especially the physician-related factors were associated with inappropriate antimicrobial use. Implementing effective strategies to modify prescribing practice is needed to optimize antimicrobial therapy at the ED.

Methods

We implemented a multifaceted intervention to patients discharged with oral antimicrobial agents in the ED at a Japanese tertiary care center from October 2018 to March 2019. The intervention included (1) an educational didactic session to physicians, (2) an evidence-based tool book regarding antimicrobial use for common diagnoses, (3) antimicrobial order sets for common diagnoses, (4) monthly reports of the appropriateness of antimicrobial use, and (5) post-prescription review and feedback by an infectious diseases physician. The proportion of appropriate discharge antimicrobial prescription at ED, and changes in the prescription density, measured as the number of prescription per 1,000 patient visits between pre- and post-intervention were evaluated.

Results

The total number of patient visits at the ED during the study period was 52,274. With the intervention, the mean monthly discharge antimicrobial prescription decreased from 42.7 to 34.2 per 1,000 visits (proportional reduction 0.20; P < 0.01). Overall, appropriate prescription rate significantly increased from 47.7% (742/1,555) to 77.4% (421/544) (P < 0.01). The rate of unnecessary and inappropriate discharge antimicrobial prescription accounted from 27.5% (428/1,555) and 21.7% (337/1,555) to 8.5% (46/544) and 10.7% (58/544), respectively. A substantial improvement in discharge antimicrobial prescription against intra-abdominal infections and odontogenic infections during the intervention period was observed (changes in the proportion of appropriate prescription was 0.37 [P < 0.01] and 0.51 [P < 0.01], respectively.

Conclusion

An evidence-based, multifaceted intervention led to decreasing unnecessary prescription and optimizing physicians’ antimicrobial prescriptions at the ED.

Disclosures

All authors: No reported disclosures.
2055. Action: A Year in the Lives of Consultant Pharmacists Working on Antimicrobial Stewardship in Long-Term Care Facilities
Authors: Chung Philip , Neukirch Alex , Ortmeier Rebecca J , Bergman Scott , Rupp Mark E , Van Schooneveld Trevor C , Ashraf M Salman
Published: October 2019

Background

The CDC recommends consultant pharmacists (CP) support antimicrobial stewardship (AS) activities in long-term care facilities (LTCF) by reviewing antimicrobial appropriateness. We initiated a project training CP from a regional long-term care pharmacy to support AS implementation in LTCF.

Methods

CP were trained to evaluate the appropriateness of all systemic antimicrobial therapy (AT) and provide prescriber feedback during their monthly drug regimen review (DRR). An electronic database was developed to facilitate data reporting. Antimicrobial use (AU) and adverse events (AE) from 32 LTCF were analyzed for 2018 using descriptive statistics.

Results

A total of 5327 courses of AT with a median duration of 7 days (IQR 5–10) were reviewed. The majority of AT was started in the LTCF (55%) but was also initiated in hospitals (24%), clinics (11%) and emergency departments (2%). Of 2926 AT started in LTCF, 36% were based on nurse evaluation (NE) while 33% began after prescriber evaluation (PE). Fluoroquinolones (FQ) and first-generation cephalosporins were the most commonly prescribed agents (Table 1). Treatment or prophylaxis of urinary tract infections accounted for 40% of AU (Figure 1). Diagnostic testing was associated with 37% of AT courses. Urine cultures were the most frequent test performed (81%). Overall, 41% of AT was determined to be inappropriate resulting in > 800 feedback letters sent to prescribers. Unnecessary antibiotic starts (based on revised Mc Geer or Loeb’s criteria) were identified as the most common reason (Figure 2). AT appropriateness varied depending on the setting in which it was initiated. A majority (87%) of AT initiated in hospitals was found to be appropriate with 56% and 46% appropriate for ED and clinic starts. Appropriateness of LTCF initiated AT was 49% (59% after PE and 42% after NE). AE were associated with 3% of AT with allergic reactions and Clostridioides difficile infections occurring with 0.4% and 0.7% of AT, respectively. AE were most frequently associated with folate antagonists (5%) and FQ (3%).

Conclusion

This study demonstrates many AU improvement opportunities exist in LTCF and CP can play an important role in identifying them if trained in AS principles. CP should review all AU for appropriateness and provide data to inform AS efforts in LTCF.

Disclosures

All authors: No reported disclosures.
2066. Development and Implementation of Prescribing Algorithms for Antibiotics on Discharge from the Emergency Department
Authors: Stoll Kristin , Feltz Erik , Ebert Steven C
Published: October 2019

Background

In the emergency department (ED), rapid decision-making and frequent distractions are often challenging to implementing effective antimicrobial stewardship. The purpose of this project is to improve guideline adherence and promote optimal use of outpatient antibiotic therapy for community-acquired infections.

Methods

Prescribing algorithms were developed to integrate clinical practice guideline recommendations with emergency department-specific antibiogram data. Algorithms for treating community-acquired pneumonia (CAP), skin and soft-tissue infections (SSTI), and urinary tract infections (UTI) were made available throughout the ED. Outcomes were evaluated through a chart review of patients prescribed empiric outpatient antibiotics for CAP, SSTI, or UTI by ED providers. Patients were excluded if they were <18 years old, pregnant, or taking antibiotics prior to arrival. The primary outcome was rate of adherence to clinical practice guidelines, defined as the selection of an appropriate antibiotic agent, dose, and duration of therapy for each patient discharged. Secondary outcomes included the rate of fluoroquinolone use, as well as all-cause 30-day returns to the ED or urgent care.

Results

When compared with patients discharged from the ED prior to algorithm implementation (N = 325), the post-implementation group (N = 172) received more antibiotic prescriptions that were completely guideline adherent (57.0% vs. 11.7%, P < 0.01). Post-implementation discharge orders demonstrated improvement in the selection of an appropriate agent (86.6% vs. 45.5%, P < 0.01), dose (89.0% vs. 77.2%, P < 0.01), and duration of therapy (63.4% vs. 39.1%, P < 0.01). Additionally, fluoroquinolone prescribing rates in this population were reduced (2.9% vs. 12.3%, P < 0.01). In the post-implementation patients who presented at least 30 days prior to analysis (N = 124), a reduction in all-cause 30-day returns to the ED or urgent care was observed (12.9% vs. 21.5%, P < 0.05).

Conclusion

Implementation of antibiotic prescribing algorithms improved guideline adherence in the outpatient treatment of CAP, SSTI, and UTI. By developing prescribing algorithms, pharmacists may reduce the unnecessary use of broad-spectrum antibiotics and prevent patient returns to the ED.

Disclosures

All authors: No reported disclosures.