bluuebunny/crossref_metadata_2025 huggingface dataset:
222. Comparison of Outpatient Antibiotic Prescriptions in a High Prescribing State, 2016–2018
Authors: Evans Christopher D , Ouedraogo Youssoufou , Keaton Amelia , Staub Milner
Published: January 2021

Background

About 80% of antibiotic prescriptions are written in outpatient settings. Outpatient antibiotic use (AU) is highest in the Southern United States. Tennessee consistently has one of the highest AU rates in the country. Previous analyses found that 1,195 prescriptions were filled in Tennessee per 1,000 total population in 2016. Moreover, 50% of all outpatient antibiotic prescriptions were written by 9.3% of prescribers. We sought to assess Tennessee outpatient antibiotic prescribing trends, comparing 2016 with 2018 data.

Methods

The Tennessee IQVIA outpatient antibiotic prescription dataset from January 1 to December 31, 2018 was analyzed and compared to 2016 results. Orally administered antibacterial agents were included. Patients < 20 years old were classified as pediatric. County level population data were obtained from the Tennessee Department of Health. Antibiotic prescription rates were calculated as antibiotics prescribed per 1,000 population in the specified age group. Analysis was performed using SAS 9.4.

Results

The statewide AU rate decreased from 1,195 in 2016 to 1,074 in 2018 per 1,000 population. Consistent with the previous analysis, female patients (1,288), those over 65 years (1,459), and those < 2 years (1,372) had the highest rates of AU in 2018. Lower rates were observed in all age groups in 2018 except for the 3–9 years group. While narrow penicillins and macrolides remain the most frequently prescribed antibiotics, amoxicillin-clavulanate and ciprofloxacin fell out of the top five antibiotics used in adults, and amoxicillin-clavulanate fell out of the top five antibiotics used in pediatrics. Similar to 2016, 9.2% (3,098) of the providers contributed to 50% of the total prescriptions in 2016, and 2,090 of the 2,994 (69.8%) 2016 highest prescribing providers were also among the highest prescribers in 2018.

Conclusion

Despite a decline in outpatient antibiotic prescription volume, Tennessee remains one of the nation’s highest prescribing states. While a decline in broad spectrum antibiotic prescriptions may indicate a shift to more appropriate usage, these data do not include indication, excluding appropriate use assessment. Identifying and focusing antibiotic stewardship interventions for consistently high prescribers remains a priority for Tennessee.

Disclosures

All Authors: No reported disclosures
225. Evaluating Appropriateness of Antibiotic Prescribing in Pediatric Inpatients
Authors: Ray Michael J , McCracken Caitlin M , Tucker Kendall J , Yu Diana , Underwood Margaret , Wu Erin , Kastelic Kylee , Nolt Dawn , McGregor Jessina C
Published: January 2021

Background

Antibiotic appropriateness is the gold standard for informing antimicrobial stewardship efforts to optimize prescribing. The objectives of this study were to evaluate appropriateness of antibiotics for resistant gram-positive infections in pediatric inpatients and identify factors associated with inappropriate prescribing.

Methods

We included pediatric inpatients between July 2017 and July 2018 where an antibiotic typically used for resistant Gram-positive infections (per NHSN) was administered. We developed an algorithm based on laboratory data and diagnosis codes to categorize each antibiotic day of therapy as appropriate, inappropriate, or indeterminate. If indeterminate, we reviewed charts to assess appropriateness. We calculated total, appropriate, and inappropriate days of therapy (DOT) overall and per patient-day. We evaluated clinical characteristics and indications as potential predictors of inappropriate DOT using Chi-squared or Kruskal-Wallis tests.

Results

Among 591 included encounters, we assessed 708 total antibiotic courses. The algorithm allowed for classification of 422 encounters (71%) and the remaining 171 encounters (29%) were classified using manual record review. The most frequent antibiotics were vancomycin (68%) and clindamycin (29%). Patients received a median of 3 days of gram-positive agent therapy per visit, or 5 per every 10 patient-days. Most common indications for gram-positive therapy were surgical prophylaxis (28% of encounters) and empiric therapy (10%) (Figure 1). Of the 1,754 total days of therapy assessed, 94.8% were ruled appropriate. Thirty-one (4.4%) courses were classified as at least partially inappropriate among 27 unique encounters (4.6%). There was a median of 2 inappropriate days among those with any inappropriate therapy. The reason for inappropriate rulings for empiric or prophylaxis indications was most often “longer than necessary duration,” which was the case for 16 of 21 (76%) occurrences.

Figure 1. Appropriate and Inappropriate Days of Therapy (DOT) by Indication and Antibiotic

Conclusion

Inappropriate antibiotic use for Gram-positive infections was low in our patient population for the agents studied. We identified limiting the duration for patients receiving prophylactic or empiric therapy as a potential stewardship intervention target.

Disclosures

All Authors: No reported disclosures
228. Fluoroquinolone Prescribing for Diabetic Foot Infections following an FDA Drug Safety Communication for Aortic Aneurysm Risk
Authors: Li Catherine , Mercuro Nicholas J , Chapin Ryan , Gold Howard , McCoy Christopher
Published: January 2021

Background

Fluoroquinolones were commonly prescribed for hospitalized patients with diabetic foot infection (DFI) at our institution, included in 69% of empiric antibiotic regimens from 2011–2014. On December 20, 2018, the U.S. Food and Drug Administration (FDA) issued a Drug Safety Communication regarding the risk of aortic aneurysm with fluoroquinolones. The objective of this study was to assess the impact of the FDA Communication on antibiotic prescribing for DFI.

Methods

This was a single-center quasi-experimental study of hospitalized patients initiated on antibiotics for DFI before (February-December 2018) and after (February-December 2019) the 2018 FDA Communication. Patients with concomitant infections or documented beta-lactam or fluoroquinolone allergies were excluded. The primary outcome was inpatient days of fluoroquinolone therapy. Secondary outcomes included days of beta-lactam therapy and Outpatient Parenteral Antibiotic Therapy (OPAT) enrollment. Variables were compared using the Pearson’s chi square, Fisher’s exact, and Mann Whitney U tests, as appropriate. A logistic regression was performed to identify predictors for inpatient receipt of fluoroquinolones.

Results

A total of 198 patients were included. Baseline characteristics were similar between groups (Table 1). After the FDA Communication, the median duration of inpatient fluoroquinolones decreased from 3 [0–5.5] to 0 [0–1] days (p< 0.001). The duration of antipseudomonal beta-lactams increased from 0 [0–2] to 2 [0–6] days (p< 0.001). OPAT enrollment increased from 16.5% to 29.7% (p=0.028), with a corresponding increase in peripherally inserted central catheter placement (15.5% to 25.7%, p=0.074). There was no difference in outpatient fluoroquinolone prescribing over time. Incidence of re-infection, readmission for DFI, and antibiotic adverse events were similar between groups (Table 2).

Table 1

Table 2

Conclusion

Inpatient fluoroquinolone prescribing for DFI decreased significantly following the 2018 FDA Communication, followed by an increase in antipseudomonal beta-lactam use and OPAT enrollment. FDA statements can influence institutional antibiotic prescribing and transitions of care decisions, representing an opportunity for education by Antimicrobial Stewardship programs.

Disclosures

All Authors: No reported disclosures
229. Hospitalists Antimicrobial Scorecard Improves Antibiotic Prescribing at a Community Teaching Hospital
Authors: Sessa Julia , Jacoby Helen , Blain Bruce , Avery Lisa
Published: January 2021

Background

Measuring antimicrobial consumption data is a foundation of antimicrobial stewardship programs. There is data to support antimicrobial scorecard utilization to improve antibiotic use in the outpatient setting. There is a lack of data on the impact of an antimicrobial scorecard for hospitalists. Our objective was to improve antibiotic prescribing amongst the hospitalist service through the development of an antimicrobial scorecard.

Methods

Conducted in a 451-bed teaching hospital amongst 22 full time hospitalists. The antimicrobial scorecard for 2019 was distributed in two phases. In October 2019, baseline antibiotic prescribing data (January – September 2019) was distributed. In January 2020, a second scorecard was distributed (October – December 2019) to assess the impact of the scorecard. The scorecard distributed via e-mail to physicians included: Antibiotic days of therapy/1,000 patient care days (corrected for attending census), route of antibiotic prescribing (% intravenous (IV) vs % oral (PO)) and percentage of patients prescribed piperacillin-tazobactam (PT) for greater than 3 days. Hospitalists received their data in rank order amongst their peers. Along with the antimicrobial scorecard, recommendations from the antimicrobial stewardship team were included for hospitalists to improve their antibiotic prescribing for these initiatives. Hospitalists demographics (years of practice and gender) were collected. Descriptive statistics were utilized to analyze pre and post data.

Results

Sixteen (16) out of 22 (73%) hospitalists improved their antibiotic prescribing from pre- to post-scorecard (χ 2(1)=3.68, p = 0.055). The median antibiotic days of therapy/1,000 patient care days decreased from 661 pre-scorecard to 618 post-scorecard (p = 0.043). The median PT use greater than 3 days also decreased significantly, from 18% pre-scorecard to 11% post-scorecard (p = 0.0025). There was no change in % of IV antibiotic prescribing and no correlation between years of experience or gender to antibiotic prescribing.

Conclusion

Providing antimicrobial scorecards to our hospitalist service resulted in a significant decrease in antibiotic days of therapy/1,000 patient care days and PT prescribing beyond 3 days.

Disclosures

All Authors: No reported disclosures
230. Impact of 10-day versus 5-day Duration Default on Length of Antibiotic Outpatient Prescriptions from the Emergency Department
Authors: Watts Amber M , Holt Shannon
Published: January 2021

Background

Antimicrobial stewardship programs (ASP) traditionally focus on inpatient care; however there is a growing effort to optimize antibiotic prescribing at transitions of care. Longer than necessary discharge prescriptions increase risk of antimicrobial resistance, C. difficile infection and adverse events. In order to minimize unnecessary antibiotic exposure, the health system updated the electronic medical record (EMR) outpatient antibiotic prescription default from 10 days to 5 days. The objective of this study was to assess the impact of a 10-day versus 5-day EMR antibiotic outpatient prescriptions default on length of therapy for patients discharged from the Emergency Department (ED).

Methods

This is a retrospective, single-system cohort study evaluating ED discharge prescriptions before and after transition from a default duration of 10 days to 5 days. Discharge prescriptions were collected and screened from December 2019 through January 2020 in the control group and March 2020 through April 2020 in the intervention group. Outpatient prescriptions were included for primary diagnoses of urinary tract infection (UTI), community-acquired pneumonia (CAP), skin and soft tissue infections (SSTI), diverticulitis, or dental infections. The primary outcome was the incidence of prescriptions written for a < 5 day duration.

Results

The study included 3060 of 9651 (32%) prescriptions in the control group and 1610 of 4938 (33%) prescriptions in the intervention group. The mean age was 38 years old with 61% female. The most common primary diagnoses were SSTI (n=1633, 35%) and UTI (n=1633, 32%). The mean duration for discharge prescriptions was similar between groups (8.44 vs. 8.30 days). The incidence of outpatient antibiotic prescriptions for < 5 days was not significantly different between groups (10.72% vs 10.56%, p=0.996). There was an improvement in duration of therapy, with more prescriptions < 5 days for SSTI (2.96% vs. 7.64%, p=0.860) and dental infections (3.30% vs. 10.86%, p=0.808).

Conclusion

Implementation of a shorter default duration for antibiotic outpatient prescriptions from the ED did not significantly increase the incidence of prescriptions written for < 5 days. There was an improvement in duration for SSTI and dental infections after implementation.

Disclosures

All Authors: No reported disclosures
235. In outpatient clinics serving Veterans, antibiotic prescriptions precede a minority of antibiotic-associated adverse events
Authors: Wilson Brigid , Bej Taissa A , Banks Richard , Briggs Janet , Song Sunah , Jump Robin , Jump Robin , Perez Federico
Published: January 2021

Background

An estimated 30% of antibiotic prescriptions in outpatient settings may be inappropriate. Antibiotic exposure increases an individual’s risk of Clostridioides difficile infection (CDI) and acquiring drug-resistant pathogens. To quantify the increased risk of CDI and drug-resistant pathogens posed by antibiotics prescribed in outpatient visits, we examined a two-year cohort of patients seen in primary care clinics at VA Community-Based Outpatient Clinics (CBOC) associated with a large VA Medical Center.

Methods

Among patients with an in-person visit at 13 CBOCs in 2018–2019, we examined rates of antibiotic-associated adverse events (AEs), defined as community-onset CDI or acquisition of resistant Gram-negative bacteria (R-GNB), in the 90 days following those visits. For each visit, we used administrative databases to determine if systemic antibiotics were prescribed, if there was an associated infectious diagnosis, and the subsequent occurrence of AEs. We summarized quarterly rates of prescribed antibiotics and AEs, characterized patients with and without AEs, and estimated the risk ratio of AE for an antibiotic prescription.

Results

Following 236,665 primary care visits, we observed 62 and 225 AEs due to CDI and R-GNB, respectively (0.12% combined rate) among 278 patients (5 with both). Patients who developed CDI or R-GNB had a higher Charlson Comorbidity Index (3.6 ± SD 3.0 and 2.68 ± SD 2.7, respectively) compared to those without AEs (0.72 ± SD 1.3; Table). The rate of new antibiotic prescriptions was 4% in visits without and 10% in visits with a subsequent AE, yielding a risk ratio of 2.5 (95% CI: 1.7–3.7). The rates of both antibiotic prescribing and AE were steady over the examined two-year period (Figure).

Table

Figure

Conclusion

Among all patients with a CBOC visit between 2018–2019, an AE, defined as CDI or R-GNB acquisition, was observed following only 0.1% of primary care visits. Among patients who experienced an AE, only 10% of primary care visits preceding those events included a new antibiotic prescription. While this analysis does not address antibiotics during inpatient stays or prescribed by specialty clinics, these findings suggest that among Veterans, outpatient antibiotic exposure may have only a modest contribution to the risk of AE.

Disclosures

Robin Jump, MD, PhD, Accelerate (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member) Federico Perez, MD, MS, Accelerate (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)
236. Incorporating Clinical Guidance into Computerized Prescriber Order Entry May Reduce Fluoroquinolone Utilization for the Treatment of Diverticulitis at a Rural Community Health System
Authors: Tirupathi Raghavendra , Miller Benton , Logsdon Jarett
Published: January 2021

Background

Fluoroquinolones are associated with many adverse effects. As a result, many hospitals are investigating methods to reduce fluoroquinolone use. Computerized prescriber order entry (CPOE) provides an opportunity to develop and implement clinically guided order sets that discourage the use of fluoroquinolones. To date, there are few studies investigating the effect of clinically guided order sets on medication utilization. This study aims to investigate the hypothesis that incorporating clinical guidance and leveraging antimicrobial stewardship into a CPOE diverticulitis order set would reduce fluoroquinolone use in the treatment of diverticulitis.

Methods

A diverticulitis order set was revised to provide guided antibiotic selection based on a patient’s penicillin allergy. Patients were split into two groups based on admission date relative to the implementation date of the revised order set. Fluoroquinolone use was compared between both groups. The primary outcome was the percentage of patients who were ordered a fluoroquinolone-containing regimen during their stay. The secondary outcome was the percentage of regimens that contained a fluoroquinolone. A subgroup analysis was conducted exclusively on patients whose antibiotics were ordered with the diverticulitis order set.

Results

494 patients were included in the study. 316 patients in the pre-order set group, 178 patients in the post-order set group. 56% of patients in the pre-group received a fluoroquinolone in their regimen versus 46% of patients in the post-group (RR=0.82; 95% CI 0.68–0.99, p = 0.028). 49% of regimens in the control group contained a fluoroquinolone versus 39% of regimens in the experimental group (RR=0.78; 95% CI 0.64–0.95; p = 0.012). 77.5% of patients in the control subgroup received a fluoroquinolone in their regimen versus 42.4% of patients in the experimental subgroup (RR=0.55; 95% CI 0.36–0.84, p = 0.0062). Fluoroquinolone days of therapy decreased from 90.6 to 58.6 from 2018–2019. Clostridioides difficile infections also decreased during this time frame.

Table 1: Average fluoroquinolone days of therapy per 1000 patient days

Figure 1: Percentage of Diverticulitis Orders by Antibiotic Regimen: Pre- and Post-Order Set Change. CFP=cefepime, Metro=metronidazole, PIP-TZ=piperacillin-tazobactam, AM-SB=ampicillin-sulbactam, CIP=ciprofloxacin, Levo=levofloxacin, FQ=fluoroquinolone

Figure 2: Fluoroquinolone days of therapy per 1000 patient days from 2016–2020.

Conclusion

Our findings support the hypothesis that incorporating clinical guidance into a CPOE order set would reduce fluoroquinolone use for the treatment of diverticulitis.

Figure 3: Indicence of Clostridioides difficile infection per 1000 patient days

Disclosures

All Authors: No reported disclosures
244. The Double-Edged Sword of Cost Effectiveness in Evaluating Antimicrobial Stewardship Interventions
Authors: Zmerli Omar , Chamieh Amanda , Saliba Sanaa , Afif Claude , Azar Eid
Published: January 2021

Background

The multiple classical benefits of reducing antimicrobial consumption extend beyond the impact on rates of antimicrobial resistance and infections to include a cost-saving effect of 100,000$-300,000$ per intervention as estimated by the CDC. However, the recent introduction of novel antimicrobial molecules with a high price tag and the fall in the prices of older agents presents a substantial challenge in maintaining cost-effectiveness.

Methods

We retrieved from the antimicrobial stewardship program(ASP) database the consumption of the Gram-negative broad-spectrum antibacterial agents (GNBS): imipenem, meropenem, ertapenem, piperacillin-tazobactam, amikacin, colistin, ceftazidime, ceftolozane-tazobactam and cefepime from January 2015-August 2019 at Saint George Hospital(SGH), a 333-bed tertiary care center in Lebanon. The yearly cost of all antibacterials consumed during this period were obtained from SGH billing records. GNBS consumption was calculated as Daily Defined Doses (DDD)/1000 Patient Days(PD) per WHO guidelines.

Results

The carbapenem consumption significantly dropped from a peak of 205 DDD/1000PD in 2015 to 33 DDD/1000PD in 2019. This drop was not accompanied by an increase in the consumption of other GNBS. The total use of GNBS dropped by 54% from 288 DDD/1000PD in 2015 to 132 DDD/1000PD by August 2019. Currently, SGH serves a yearly average of 82,000 patient-days. Hence, this reduction in total GNBS consumption corresponds to 12,792 fewer daily defined doses of antimicrobial therapy per year.

The average annual cost of all antibacterials at SGH is 1,100,000 $ (U.S. Dollars), ranging from 955679 $ to 1340109 $ for the period 2015–2019. (Table 1)

Consumption of Gram-negative Broad-Spectrum Antimicrobial Agents and Cost of Antibiotics at Saint George Hospital, Lebanon

Conclusion

The striking decrease in GNBS consumption, namely carbapenems, was not mirrored with a reduction of total antibacterial cost. Although novel antimicrobials carry great potential, they come at a significant increase in overall cost. Modeling ASP interventions solely around cost-effectiveness will limit the better placement of these new agents in institutional therapeutic guidelines. Strict continuous analysis of consumption, antimicrobial resistance, and cost within an ASP provides a proactive and vigilant approach to navigate through the complexity of difficult to treat bacterial infections.

Disclosures

All Authors: No reported disclosures
245. The impact of patient safety report and sentinel events on the prescribing and practice habits of infectious disease physicians
Authors: Kollu Vidya S , Zaidi Zareen , Cho Jonathan J , Abbott Andrew , Archibald Lennox , Kalyatanda Gautam
Published: January 2021

Background

Adverse events associated with antimicrobials range from mild to severe and may cause distress or harm to patients, and anxiety for prescribers. The basic tenets of prescribing antimicrobials are based on knowledge of the disease, pharmacokinetics, and pharmacodynamics of the prescribed agent, and effectiveness of the therapy. Inappropriate prescribing can increase costs and may cause reactions or the emergence of resistance. There is a paucity of published data on the prescribing habits of physicians after a sentinel event or patient safety report. Thus, we carried out this study to ascertain whether patient safety reports and sentinel events influence physician antimicrobial prescribing practices

Methods

We invited Infectious Disease physicians at the University of Florida to participate in a survey of their perception of risks and prescribing habits after a sentinel event. Participants were interviewed using a standardized questionnaire. Data were analyzed using Epi Info statistical software. Thematic analyses were performed on the open-ended interview questions.

Results

Of 17 faculty and fellows who participated in the survey, 5 (29.4%) had been practicing infectious disease for 1–3 years, 3 (17.6%) for 4–6 years, 2 (11.7%) for 7–9 years, and 7 (41.1 %) for >nine years. Two (11.7%) had a patient safety report filed against them. All participants had experienced at least one sentinel event involving an antimicrobial agent. Sixteen (94%) changed their practice after sentinel events; 8 (47%) increased the frequency of ordering laboratory tests, and 7 (41%) indicated they might change to more expensive antimicrobials with better safety profiles. Eight (47%) participants endorsed hypervigilance when using antibiotics

Conclusion

We found that sentinel events affect physicians’ prescribing practices and monitoring of antimicrobial therapy. The most frequent changes included closer follow-up and obtaining more laboratory tests. However, some participants avoided certain antimicrobial agents or used more expensive therapies with better safety profiles. Although physicians use evidence-based medicine to alter their prescribing habits, serious adverse events can have an impact on the way we practice

Disclosures

Jonathan J. Cho, MD, Novartis (Shareholder)
255. Ticagrelor Aids Platelet-Mediated Clearance in a Refractory Staphylococcus aureus Endovascular Infection with Septic Emboli
Authors: Ulloa Erlinda , Uchiyama Satoshi , Nizet Victor , Sakoulas George
Published: January 2021

Background

The pore-forming alpha-toxin produced by Staphylococcus aureus (SA) decreases the viability and increases the clearance of platelets, a critical element of innate immune defense in endovascular infection. Our group recently identified that ticagrelor (TICA) blocks alpha-toxin-induced platelet clearance, protecting mice in a lethal systemic SA infection model. Here, we describe a case report in which TICA, added to antimicrobial therapy of a persistent methicillin-susceptible SA (MSSA) bacteremia associated with a septic aortic thrombus, resulted in immediate bacteremia clearance. We further explore TICA synergy with antibiotics and human platelets in vitro.

Methods

Antibiotic susceptibility of an MSSA strain from a patient treated with TICA for refractory bacteremia was tested by MIC and checkerboard assays in MHB or RPMI at standard (105 CFU/mL) or high (107 CFU/mL) inocula using TICA, ertapenem (ETP), cefazolin (CZ), or nafcillin (NAF) alone vs. ETP+CZ ± TICA. Killing assays with human platelets ± TICA against SA were also performed.

Results

SA bacteremia secondary to a septic aortic thrombus (>4 mm) with multiple secondary pyogenic foci refractory to standard CZ and subsequent salvage CZ+ETP for 5 days rapidly cleared within 24 h after the addition of TICA. Thrombocytopenia resolved concurrently. Discontinuation of TICA on day 12 led to rebound thrombocytopenia, and TICA was restarted, once again resulting in resolution of thrombocytopenia. TICA alone lacked in vitro activity against SA, nor was TICA synergistic with ETP+CZ. In contrast, addition of a physiological achievable concentration of TICA dramatically sensitized SA to human platelet killing (p< 0.001) in vitro.

Figure 1

Figure 2

Figure 3

Conclusion

In a complex case of aortic plaque rupture with septic thrombus, multiple septic emboli, and refractory MSSA bacteremia, addition of TICA to antimicrobial therapy yielded unanticipated immediate clinical and microbiological success. The profound therapeutic effect of TICA in vivo was corroborated by the enhanced staphylocidal activity of human platelets in vitro in the presence of physiological concentrations of the antiplatelet agent. TICA warrants further study as adjunctive treatment of refractory SA bacteremia due to a primary endovascular focus when thrombocytopenia is present.

Disclosures

Victor Nizet, MD, Centauri Therapeutics (Advisor or Review Panel member)Cidara Therapeutics (Advisor or Review Panel member)InhibRx (Advisor or Review Panel member)Roche Pharmaceutical (Advisor or Review Panel member)
258. A Comparison of Cefprozil and Fluoroquinolones for Gram-Negative Bacteremia
Authors: Nolen Rebecca C , Shor Emily M , Lucido Anthony , Hodges Georgeanne , Metzger Alex , Wu Julia , Unverferth James , Busch Lauren
Published: January 2021

Background

Beta lactams and fluoroquinolones (FQ) have been evaluated as step-down therapy options for Gram-negative bacteremia (GNB), but the preferred oral step-down antibiotic remains unclear.

Methods

This retrospective, non-inferiority, cohort study included adult patients who received oral step-down therapy with cefprozil or FQ (ciprofloxacin, levofloxacin) for GNB caused by Proteus spp, Klebsiella spp, or E. coli at SSM Health St. Louis between 1/1/2016 and 2/28/2020. The primary outcome was treatment failure, defined as all-cause mortality or recurrent infection within 30 days of initial bacteremia episode. Assuming an 85% success rate, to achieve 80% power with a noninferiority margin of 15%, 71 patients were required in each arm. Multivariate logistic regression was used to evaluate factors for treatment failure. Factors evaluated for inclusion in the multivariate model were oral antibiotic, age >65 years, urinary source, Pitt bacteremia score >2, ICU admission, and IV antibiotics for >5 days prior to step-down.

Results

A total of 174 patients were included— 103 received cefprozil and 71 received FQ. Most baseline characteristics were similar between groups. Patients in the cefprozil group had more ICU admissions (21.3% vs. 7%; p=0.01), had a higher mean Pitt bacteremia score (1.6 vs 0.7; p< 0.001), and received a longer duration (days) of IV antibiotics prior to step-down therapy (5.2 vs 4.1; p< 0.001). Mean total treatment duration (days) was similar between groups (13.1 vs 13.2; p=0.75). Cefprozil 500 mg PO BID was administered in 84.5% of cefprozil patients. Treatment failure occurred in 3.88% (4/103) of cefprozil patients compared to 1.41% (1/71) of FQ patients (mean difference -2.47%; 95% CI -7.52% to 2.58%). The rate of adverse drug reactions was significantly higher in the FQ arm (2.9% vs 12.6%; p=0.016). In the univariate model, E. coli bacteremia, Pitt bacteremia score >2, and IV antibiotic duration >5 days met pre-defined criteria (p< 0.2) for inclusion in the multivariate model. In the multivariate analysis, these factors were not found to be significant.

Conclusion

Cefprozil was non-inferior to FQ in regard to treatment failure. Cefprozil is an efficacious alternative to FQ for oral step-down treatment of GNB and was associated with significantly fewer adverse effects.

Disclosures

All Authors: No reported disclosures
259. A Prospective, Stewardship-Driven IV to PO Conversion in Uncomplicated Bacteremia
Authors: Quan Asia , Marks Gregory , Tran Hai P , Shane Rita , Ben-Aderet Michael , Sutterwala Fayyaz S , Grein Jonathan , Smith Ethan , Rapp Jeffrey
Published: January 2021

Background

Recent data has shown a transition to oral (PO) antibiotics (ABX) for definitive treatment of uncomplicated bacteremia has similar efficacy compared to continuation of intravenous (IV) ABX, and reduces hospital length of stay (LOS). The purpose of this study was to evaluate the safety and efficacy of an antimicrobial stewardship pharmacist-driven, IV to PO ABX transition in clinically stable patients with uncomplicated bacteremia, and to determine the impact on hospital LOS.

Methods

This was a prospective, interventional study with concurrent controls, conducted at Cedars-Sinai Medical Center between November 2019 and April 2020. For patient recruitment, a report of all positive inpatient blood cultures was reviewed daily. For patients meeting study criteria, the treating provider was contacted to recommend an IV to PO ABX transition. The treating provider was responsible for making the final determination on ABX therapy. Patients continuing IV ABX served as the comparator group to those transitioning to PO.

The primary outcome of interest was a composite of: 30-day, all-cause mortality, 30-day readmission due to infectious- or ABX-related complications, or 30-day recurrent infection with the same organism recovered. The second outcome of interest was overall hospital LOS and hospital LOS after the definitive ABX regimen was established.

Results

A total of 117 patients were evaluated; 69 patients met criteria for inclusion in the study (46 PO ABX / 23 IV ABX). Overall, baseline characteristics were similar between the groups. No difference was observed in the 30-day composite outcome (1 in each group), but the median, overall hospital LOS was three days shorter in the PO group. Furthermore, hospital LOS after the definitive ABX regimen was established was four days shorter in the PO group. Based on the differences in hospital LOS observed, the intervention was estimated to have resulted in approximately $819,200 cost-avoidance during the study period.

Conclusion

Similar to prior studies, our findings support the safety and effectiveness of an IV to PO ABX transition in clinically stable patients with uncomplicated bacteremia. Antimicrobial stewardship pharmacists can be leveraged to facilitate such a transition.

Disclosures

All Authors: No reported disclosures
260. A Rare Case of Severe Group B Streptococcal Infection with Toxic Shock-like Syndrome and Diffuse Metastatic Infection
Authors: Ayyash Ali M , Tran Ly , Ervin Charlie , Sampath Rahul , Campanile Teresa
Published: January 2021

Background

The incidence of invasive Group B streptococcal (GBS) infection has been increasing in the past decade and is currently at 10.9 cases per 100,000 population. GBS toxic shock-like syndrome is rare, with few cases reported over the past decade. The presumed etiology is the production of an uncharacterized pyrogenic toxin by certain strains.

Methods

We present a unique case of invasive GBS infection complicated by severe GBS-mediated toxic shock-like syndrome (TSLS) and diffuse metastatic infection.

Results

A 62-year-old obese male with diabetes mellitus presented with pain, swelling, and redness of the right shoulder and ankle for one week after a fall. Vitals were remarkable for tachycardia to 106 BPM and fever of 101°F with labs showing a leukocytosis to 23,500 u/L. The patient was started on ceftriaxone IV but continued to develop worsening fever, leukocytosis, encephalopathy, diffuse extremity pain, and whole-body macular erythema at 48 hours. Blood cultures grew GBS and TSLS was suspected. Adjunct clindamycin was started. MRI of the extremities demonstrated abscesses of the right levator scapulae, posterior scalene, brachioradialis, and right ankle. MRI of the spine showed epidural abscesses at L3-L5 and septic arthritis of the spinal facets at L4-L5. Operative abscess removal with joint washouts were performed by neurosurgery and orthopedics, and the patient symptomatically improved within 2 weeks on IV ceftriaxone. He was subsequently continued on cefazolin for 10 weeks and did well at follow-up.

Right elbow showing a characteristic flat, macular erythema of toxic shock-like syndrome.

Left arm with macular erythema.

MRI showing spinal epidural abscesses at L3-L5 spinal levels (arrows).

Conclusion

Invasive metastatic Group B Streptococcus infection in non-pregnant adults presenting with TSLS is rare. To our knowledge, there has never been a case of GBS infection causing TSLS with rapidly developing florid metastatic infection including epidural abscess development, septic arthritis, and musculoskeletal abscesses. This case highlights the wide range of infectious possibilities associated with severe GBS infection.

Disclosures

All Authors: No reported disclosures
261. A Single-Center Case Series of Methicillin-Resistant S. aureus Bacteremia with Elevated Minimal Inhibitory Concentrations to Vancomycin
Authors: Mills Alexandra , Dupper Amy , Chacko Kieran , Nadkarni Devika , Caban Ana Berbel , Fox Lindsey , Obla Ajay , Van Bakel Harm , Altman Deena
Published: January 2021

Background

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious nosocomial pathogen, and is listed as a “High Priority Pathogen” by the WHO due to concerns of antimicrobial resistance and lack of novel therapeutics. Even in vancomycin-susceptible MRSA, increased rates of treatment failure occur in the setting of an increased minimum inhibitory concentration (MIC) to vancomycin, which is considered the gold-standard of therapy. We performed a case series of 25 patients infected with MRSA with an elevated MIC to vancomycin. Additionally, we describe the use of combination therapy with beta-lactams for the management of these highly complex cases.

Methods

We conducted a retrospective case series of 25 patients hospitalized at MSH between 8/2014–5/2019 who were treated for MRSA bacteremia where the isolate had an MIC ≥ 2. Data was centralized into the REDCap program. Clonal typing of bacteria and analysis of clinical features were performed in SAS and R.

Results

In total, 25 patients developed MRSA bacteremia with a vancomycin MIC ≥ 2. The majority of cases involved infection from vascular access, arteriovenous fistula/graft, and septic joint/osteomyelitis. All 25 patients were initially treated with vancomycin, with modification of therapy varying widely depending on clinician. The most common vancomycin-alternative was daptomycin (14/25 patients, alone and in combination). Combination therapy with vancomycin or daptomycin and a beta-lactam was used in 9 cases (36% of cases). Average number of days to clearance was 18.3 (range 1–69 days). Univariate and multivariate analyses revealed significant correlation MRSA bacteremia with vancomycin MIC ≥ 2 and admission from a nursing home or skilled nursing facility (p=0.02), history of MRSA colonization (p=0.006), and persistent bacteremia (bacteremia >7 days)(p< .0.001).

Conclusion

With few novel therapeutics under development, management of MRSA bacteremia with a rising MIC to vancomycin is a clinical challenge for practitioners. In our case series we found that treatment is largely patient and practitioner-dependent, and far from standardized. Further definition of the clinical risk factors for development and novel therapeutic strategies will enable understanding of how to best manage these challenging infections.

Disclosures

All Authors: No reported disclosures
263. An Evaluation of Quality Indicators for the Management of Staphylococcus aureus Bacteremia: A Nested Case-Control Study
Authors: Simms Andrew , Schweizer Marin L , Ohl Michael , Perencevich Eli N , Goto Michihiko
Published: January 2021

Background

Community-acquired Staphylococcus aureus bacteremia (CA SAB) is a common infection with high mortality. Ten Oever et al. recently used expert consensus methods to develop a set of 25 quality indicators for SAB care in five domains (i.e., follow up blood cultures, echocardiography, non-antibiotic interventions including source control, antibiotic treatment, and other management aspects). Associations between these quality indicators and patient outcomes have not been evaluated. We assessed associations between proposed quality indicators and all-cause 30-day mortality among patients with CA SAB.

Methods

We conducted a nested case-control study within a described national multicenter cohort of patients with SAB in the Veterans Health Administration (VHA). The cohort included 2,093 patients who were: 1) admitted to acute care hospitals between 1/2012 and 12/2014 for CA SAB (the first positive blood culture before or within 48 hours of admission with no recent healthcare exposure); 2) survived at least 96 hours after the SAB onset. We identified paired cases (who died within 30 days) and controls (who survived an equal time), matched 1:1 for age (+/- 5 years), gender, admission year and month, and methicillin susceptibility of isolates. We reviewed charts to extract information for quality indicators. We estimated associations between quality indicators and mortality using logistic regression, adjusting for patient demographics and comorbidity.

Results

164 patients (82 cases and 82 controls) were included. The median patient age was 68.5 (IQR: 62–80) years, and 74 (45.1%) had methicillin-resistant isolates. All patients received at least one domain of quality indicator (median: 3 [IQR: 2–4]). When analyzed individually, only two domains (follow-up blood cultures: OR 0.27 [95% CI: 0.11–0.68]; source control: OR: 0.13 [0.05–0.31]) were associated with mortality. There was a dose-response relationship in which more domains received was associated with decreased mortality (Figure).

Association Between the Number of Satisfied Quality Indicator Domains and All-Cause 30-day Mortality

Conclusion

Among patients with CA-SAB, the number of satisfied quality indicator domains was associated with 30-day mortality with a dose-response relationship. This finding supports the relevance of these quality indicators for SAB management.

Disclosures

All Authors: No reported disclosures
264. Anti-platelet Therapy Significantly Reduces Inpatient Mortality in Patients with Staphylococcus aureus Bacteremia
Authors: Caffrey Aisling , O’Neill Emily T , Lopes Vrishali , Ulloa Erlinda R , Sakoulas George , Nizet Victor , LaPlante Kerry
Published: January 2021

Background

There is a growing body of evidence which suggests that P2Y12 inhibitors may have antibacterial properties in vivo. To our knowledge, this has not been previously examined using real world clinical data from patients with specific infections.

Methods

Our retrospective cohort study included patients admitted to Veterans Affairs hospitals between 2010–2018 with blood cultures positive for S. aureus and treated with appropriate antibiotics within 48 hours of culture collection. We included patients treated with P2Y12 inhibitors for at least the 30 days prior to admission and continued use for at least 5 days after admission. Non-users included patients without P2Y12 inhibitor use in the year prior to admission through discharge. We compared clinical outcomes during the S. aureus bacteremia admission among P2Y12 users and non-users using propensity score matched Cox proportional hazards regression models.

Results

We identified 371 P2Y12 inhibitor users (clopidogrel, prasugrel, ticagrelor, cangrelor) and 13,298 non-users. Mean age was 70 years and 69 years, respectively. Over 98% were male in both the groups, and the overall inpatient mortality rate was 8.7%. We were able to match 199 users and non-users, which were well matched in terms of baseline covariates. Inpatient mortality was significantly lower among P2Y12 inhibitor users (hazard ratio [HR] 0.08, 95% confidence interval [CI] 0.01–0.64), and 30-day mortality was non-significantly lower (HR 0.57, 95% CI 0.31–1.03). There was no difference between the groups in readmission or re-infection within 30 days of discharge.

Conclusion

Among patients with S. aureus bacteremia, those treated with P2Y12 inhibitors in the days leading up to admission and continuing through the initial period of antibiotic treatment, had a 92% lower risk of inpatient mortality. Identifying adjunctive therapies which improve clinical outcomes among patients with S. aureus bacteremia is highly important in order to improve patient outcomes and to increase the understanding of the pathophysiology of the disease. Prospective clinical studies are needed to further define the potential benefits of P2Y12 inhibitors in S. aureus bacteremia and possibly other infection types.

Disclosures

Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support) Erlinda R. Ulloa, MD, MSc, Cidara Therapeutics (Consultant) Victor Nizet, MD, Centauri Therapeutics (Advisor or Review Panel member)Cidara Therapeutics (Advisor or Review Panel member)InhibRx (Advisor or Review Panel member)Roche Pharmaceutical (Advisor or Review Panel member) Kerry LaPlante, PharmD, Merck (Advisor or Review Panel member, Research Grant or Support)Ocean Spray Cranberries, Inc. (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc. (Research Grant or Support)
267. Characteristics and Trends of Serratia Blood Stream Infections
Authors: Elabd Hatem , Eagleston Anjuli , Brandt Dominique , Blatt Stephen
Published: January 2021

Background

Serratia is an opportunistic pathogen known to cause an array of infectious presentations including UTIs, pneumonia, wound infections, skin and soft tissue infections, surgical site infections and although rare, endocarditis and bacteremia. The aim of the proposed study is to identify the characteristics of patients with community-acquired Serratia blood stream infection over a five-year period within the TriHealth inpatient population within the Cincinnati, Ohio Region. The study will also examine antibiotic resistance patterns among patients with Serratia bloodstream infections.

Methods

This is a retrospective cohort study of 107 adult patients admitted to two community hospitals from January 2014 to December 2018 with a positive blood culture for Serratia species. A complete data set of 100 patients was analyzed for complications, antibiotic resistance, in-hospital mortality, 90-day mortality, readmission within 90 days and length of Hospital Stay (LOS). Descriptive statistics was performed using frequencies for discrete variables and median (IQR) for continuous variables.

Results

Patients admitted with a positive Serratia blood culture were 38% female with a median (IQR) age of 54.5 years (40.25–71.75) and predominantly white (85%). Forty percent had hepatitis C (HCV) infection and 42% had a history of IV drug use. Most patients were living at home (77%), 18% in long term care and 91% were infected with Serratia marcescens. The most common complications were endocarditis (12%) and osteomyelitis (10%). Extended spectrum beta-lactamase (ESBL) production was confirmed in 13%. In-hospital mortality was 2%, 90-day mortality 2%, readmission 23% and median (IQR) LOS 7(3.25–14.75).

PATIENT CHARACTERISTICS AND OUTCOMES (part 1)

PATIENT CHARACTERISTICS AND OUTCOMES (part 2)

PATIENT CHARACTERISTICS AND OUTCOMES (part 3)

Conclusion

This study demonstrates that a high proportion of patients admitted with Serratia bacteremia are IV drugs users and that they have a high prevalence of coexistent HCV infection. Endocarditis and metastatic foci of infection are relatively common. Appropriate empiric antibiotic management should take into account the significant incidence of ESBL production resulting in a prolonged LOS and a high readmission rate.

Disclosures

All Authors: No reported disclosures
270. Clinical Outcomes of Ceftriaxone versus Penicillin G for Complicated Viridans Group Streptococci Bacteremia
Authors: Wo Stephanie , Dubrovskaya Yanina , Siegfried Justin , Papadopoulos John , Jen Shin-Pung
Published: January 2021

Background

Viridans group streptococci (VGS) is an infrequent yet significant cause of bloodstream infections, and complicated cases may require prolonged antibiotic therapy. Ceftriaxone (CTX) and penicillin G (PCN G) are both considered first line options for VGS infections, but comparisons between these agents are limited. We evaluated the clinical outcomes amongst patients treated with CTX and PCN G for complicated VGS bacteremia.

Methods

This was a single-center, retrospective study of adult patients with ≥1 positive VGS blood culture who were treated with either CTX or PCN G/ampicillin (both included in PCN G arm) between January 2013 and June 2019. The primary outcome was a composite of safety endpoints, including hospital readmission due to VGS or an adverse event (AE) from therapy, Clostridioides difficile infections, treatment modification or discontinuation due to an antibiotic-related AE, and development of extended-spectrum beta lactamase resistance. Secondary outcomes included the individual safety endpoints, VGS bacteremia recurrence, hospital readmission, and all-cause mortality.

Results

Of 328 patients screened for inclusion, 94 patients met eligibility criteria (CTX n= 64, PCN G n=34). Median age was 68 years (IQR 56–81) and 68% were male. Study patients did not present with critical illness, as reflected by a median Pitt bacteremia score of 0 in the CTX and 1 in the PCN G arms, P=0.764. Streptococcus mitis was the most common VGS isolate and infective endocarditis (IE) was the predominant source of infection. CTX was not significantly associated with increased risk of the primary outcome (14% vs. 27%; P= 0.139). The driver of the composite outcome was hospital readmission due to VGS bacteremia or therapy complications. Results were similar in the subgroup of patients with IE (12.5% vs. 23.5%). No secondary endpoints differed significantly between groups. On multivariate analysis, source removal was a protective factor of the primary outcome (OR 0.1; 95% CI 0.020–0.6771; P= 0.017).

Conclusion

Despite potential safety concerns with the prolonged use of CTX in complicated VGS bacteremia, this study did not demonstrate a higher rate of treatment failure, adverse events, or resistance. These findings warrant further exploration.

Disclosures

All Authors: No reported disclosures