bluuebunny/crossref_metadata_2025 huggingface dataset:
241. Rural-urban differences in antibiotic prescribing for uncomplicated urinary tract infections
Authors: Clark Abbye W , Durkin Michael , Olsen Margaret A , Keller Matthew R , Ma Yinjiao , Butler Anne M
Published: January 2021

Background

Identification of inappropriate antibiotic prescribing patterns is critical for designing antimicrobial stewardship programs. We sought to examine whether the risk of receipt of an inappropriate outpatient antibiotic prescription varied by rural-urban status among women with an uncomplicated urinary tract infection (UTI).

Methods

Using the IBM MarketScan Commercial Database, we identified U.S. women 18–44 years diagnosed with a new uncomplicated UTI and prescribed an oral antibiotic with activity against common uropathogens from April 2011 through June 2015. We classified first-line agents (nitrofurantoin, trimethoprim-sulfamethoxazole, and fosfomycin) as appropriate, non-first-line agents (fluoroquinolones and β-lactams) as inappropriate, and antibiotic duration as appropriate when the days’ supply was consistent with Infectious Diseases Society of America 2011 guidelines. Rural-urban status was defined by residence in a metropolitan statistical area. We used modified Poisson regression to determine the association between rural-urban status and inappropriate antibiotic receipt, accounting for patient- and provider-level characteristics.

Results

Of 670,450 women with uncomplicated UTI, 46.7% of antibiotic prescriptions were written for inappropriate agents and 76.1% for inappropriate durations (Figures 1 and 2). Use of inappropriate agents or durations did not change appreciably over the study period (2011–2013 vs. 2014–2015). Of 507,737 prescriptions with inappropriate duration, 501,496 (98.8%) were written for a days’ supply longer than recommended. Compared to urban women, rural women had similar risk of receipt of an inappropriate agent (adjusted risk ratio 0.99, 95% CI, 0.98–1.00) but were more likely to receive a prescription for an inappropriate duration (adjusted risk ratio 1.10, 95% CI, 1.09–1.11).

Figure 1. Distribution of antibiotic agent by rural-urban status

Figure 2. Distribution of the antibiotic prescription days’ supply by antibiotic agent and rural-urban status

Conclusion

Regardless of rural-urban status, the majority of antibiotic prescriptions for uncomplicated UTI were written for inappropriate agents and durations. Rural women were more likely to receive prescriptions with inappropriately long durations. Antimicrobial stewardship interventions are needed to improve outpatient UTI antibiotic prescribing and reduce unnecessary exposure to antibiotics, particularly in rural settings.

Disclosures

Margaret A. Olsen, PhD, MPH, Merck (Grant/Research Support)Pfizer (Consultant, Grant/Research Support)
243. Temporal Trends in Appropriateness of Ambulatory Antibiotic Prescribing in South Carolina
Authors: Winders Hana R , Royer Julie , Justo Julie Ann , Bookstaver P B , Weissman Sharon , Ruegner Hannah , Al-hasan Majdi
Published: January 2021

Background

Previous studies have reported high levels of inappropriate ambulatory antibiotic prescribing in the United States. This population-based cohort study examines temporal trends in appropriateness of ambulatory antibiotic prescribing in South Carolina.

Methods

Aggregated pharmacy claims data for oral antibiotic prescriptions among South Carolina residents < 65 years old were matched with primary diagnosis codes from medical claims within 14 days of the pharmacy claim from 2012–2017. Appropriateness of antibiotics was defined as maybe indicated or not indicated based on diagnosis codes. Chi-square tests were used to examine overall temporal trend in appropriateness and the trends across age group and gender.

Results

During the 6-year period, 3,133,379 prescriptions were identified. Overall, 25.6% of antibiotic prescriptions filled were not indicated. This decreased from 27.9% in 2012 to 22.7% in 2017 (p < 0.001). The most common not indicated conditions were viral upper respiratory infections (39.1%), bronchitis (26.7%), and serous otitis (10.9%). The most common maybe indicated conditions were bacterial otitis (27.5%), acute bacterial tonsillitis (24.8%), and sinusitis (23.6%). While females filled more antibiotic prescriptions, they were less likely than males to have a not indicated condition (24.7% vs. 27.1%, p < 0.001). Prescribing for not indicated conditions was more likely in adults aged 40–64 (33.7%) than those aged 18–39 (23.5%) and < 18 (24.2%).

Conclusion

The observed decline in inappropriate ambulatory antibiotic prescribing from 2012 to 2017 in South Carolina represents welcomed news. Further improvements in ambulatory antibiotic stewardship efforts are needed particularly in men ≥ 40 years old with acute respiratory infections.

Disclosures

Julie Ann Justo, PharmD, MS, BCPS-AQ ID, bioMerieux (Speaker’s Bureau)TRC Healthcare (Speaker’s Bureau)
246. Antibiotic Prescribing Patterns for Residents in Assisted Living Facilities
Authors: Liao Chi-Yin , Crnich Christopher J , Ford II James
Published: January 2021

Background

Knowledge about antibiotic utilization in Assisted Living Facilities (ALFs) is limited. Studies have primarily focused on aggregate prescribing patterns, clinical indications for antibiotics, and the types of antibiotics prescribed. Information about individual resident prescribing patterns is limited. This project addresses the gap by using data from a convenient sample of ALFs.

Methods

Data on antibiotic prescriptions from 3 ALFs in Wisconsin were collected for a one-year period. Information included start and stop dates, clinical indication, and antibiotic prescribed. Antibiotic orders for the same resident were categorized as distinct events to capture treatment courses if 1) the days between the end date of the prior antibiotic and the initiation date of subsequent antibiotic orders were > 4 days, or 2) if the identified indications for the prior and subsequent antibiotic were different. Event-level indication was further defined based on (2). Descriptive statistics were used to understand antibiotic prescribing patterns at the individual and event level.

Results

A total of 207 antibiotic events among 110 assisted-living residents were identified. The patterns of antibiotic use at the resident and treatment course levels are described in tables 1 and 2, respectively. On average, each resident was received 1.9 (range:1 to 10) antibiotic treatment courses for an average of 24.8 (range: 1 to 237) total antibiotic days. The treatment duration of each treatment course averaged 14.5 days (range: 1 to 306). About 10 % of residents had 4 or more antibiotic events and days of therapy over 56 days. 43% of residents were prescribed an antibiotic without a clinical indication and 26% of the antibiotic events were not indicated. UTI was the most common indication for antibiotic treatment (31%) and ciprofloxacin was the most commonly prescribed antibiotic (22%).

Conclusion

The current study demonstrates multiple opportunities to improve antibiotic use in ALFs, including: 1) specification of indication for the antibiotic; 2) reducing unnecessary antibiotic treatments; 3) shortening durations of treatments; and 4) reducing use of broad-spectrum antibiotics. Studies on interventions that target these areas are needed.

Disclosures

All Authors: No reported disclosures
247. Validation of the Use of Oral Vancomycin Following Positive Admission Screening Testing for C. difficile
Authors: Yeturu Preethi , Parada Jorge P , Santarossa Maressa , Labuszewski Laurie , Lopez Jenna , Arimilli Seshank , Kapadia Heli , Albarillo Fritzie S
Published: January 2021

Background

Clostridioides difficile can cause a severe infectious colitis and is often associated with significant morbidity and mortality. C. difficile infection (CDI) is defined as the presence of diarrhea plus a positive stool test, whereas C. difficile colonization is defined as a positive stool test in the absence of diarrhea or the presence of diarrhea attributable to causes other than CDI. Widespread use of stool polymerase chain reaction (PCR) testing, especially within the first 3 days of admission, has become common at our institution and has been associated with increased number of positive C. difficile tests results. However, C. difficile colonization rates may be 15% or higher. Oral (PO) vancomycin (vanc) is first line therapy for the treatment of CDI. We sought to evaluate the appropriateness of use of PO vanc in patients who tested positive for C. difficile via stool PCR within 3 days of admission.

Methods

We reviewed the clinical history, presence of diarrhea, risk factors for diarrhea, treatment and use of an infectious disease (ID) consultation for all patients 18 years of age or older found to test positive for C. difficile by PCR on stool assays during the first 3 days of admission from 07/01/18 to 12/31/18.

Results

A total of 228 patients met inclusion criteria. 183 (80%) received PO vanc while 45 (20%) did not. 131 (71.6%) of patients who received PO vanc had diarrhea, 39 (21.3%) did not have diarrhea, 13 (7.1%) the presence of diarrhea was unknown. 41 of 143 (28.7%) of patients without ID consults received PO vanc despite not having diarrhea, while 11 of 40 (27.5%) patients seen by ID received PO vanc despite not having diarrhea (p=0.888).

Conclusion

Most patients who tested positive for C. difficile received PO vanc had documented diarrhea, meeting the definition of CDI. However, over 1 in 5 (21.3%) of patients who received PO vanc did not have diarrhea and may have been colonized rather than have true CDI. ID consultation did not decrease the number of patients without diarrhea who received PO vanc or prevent treatment of colonized patients. This work reveals there may be an opportunity for improvement regarding management of CDI vs. C. difficile colonization which may enhance antibiotic stewardship and the appropriate use of PO vanc.

Disclosures

All Authors: No reported disclosures
248. Why so Much Vancomycin and Piperacillin/Tazobactam Usage Given Known Risks of Nephrotoxicity
Authors: Son Andrea , Murphy Nina Naeger , Wadsworth Christina , Bogorodskaya Milana , Hecker Michelle
Published: January 2021

Background

Despite years of published data describing the increased risk of nephrotoxicity with use of vancomycin and piperacillin/tazobactam (VPT), this combination remains one of the most utilized antibiotic combinations at our institution. There is limited data describing the appropriateness of empiric use of this broad-spectrum regimen. Our primary objective was to evaluate the appropriateness of the anti-methicillin resistant Staphylococcus aureus (MRSA), anti-pseudomonal, and anti-anaerobic spectrum of activity for patients empirically treated with this combination. Our secondary objective was to evaluate the appropriateness of diagnostic evaluation in patients started on this combination.

Methods

A retrospective cohort study was performed on a random sample of unique patients prescribed the combination of VPT from October 2019 through March 2020. Demographic and clinical data were abstracted from the electronic medical record. Based on predetermined criteria, we evaluated the appropriateness of the spectrum of activity of empiric therapy and the diagnostic evaluation.

Results

Of 100 patients evaluated, 96 patients (96%) received VPT as empiric treatment. The indications for use are shown in Table 1. Pneumonia and soft tissue/bone/joint infections were the most common indications. The appropriateness of anti-MRSA, anti-pseudomonal, and anti-anaerobic therapy is shown in Table 2. In only 35% of patients was the full spectrum of activity appropriate. Of 47 patients treated empirically for pneumonia, 35 (74%) had an order for a respiratory culture and 7 (15%) for a nasal MRSA surveillance culture. Of 30 patients treated empirically for soft tissue//joint infections, wound cultures were obtained in 22 (73%). Nineteen patients underwent surgical intervention, of whom 17 (89%) had cultures obtained.

Table 1. Indications for Empiric Vancomycin and Piperacillin/tazobactam Combination Therapy

Table 2: Appropriateness of Spectrum of Activity for Empiric Vancomycin and Piperacillin/tazobactam Combination Therapy

Conclusion

At our institution VPT use was usually empiric and unnecessarily broad for the syndrome being treated. Microbiologic testing was suboptimal and may have resulted in prolonged therapy. Although interventions aimed at de-escalating VPT are useful, interventions aimed at ensuring appropriate empiric use of this combination and ensuring appropriate diagnostic testing may be just as important.

Disclosures

All Authors: No reported disclosures
249. A metabolomic study of patients with A. baumannii bacteremia
Authors: Sun Hsin-Yun , Cheng Aristine , Chuang Yu-Chung , Wang San-Yuan , Kuo Ching-Hua , Tseng Yufeng , Chen Yee-Chun
Published: January 2021

Background

A. baumannii has become an emerging pathogen of healthcare-associated infection with significant mortality. The present study aimed to identify specific biomarkers to predict patient survival of A. baumannii bacteremia by metabolomics.

Methods

From July 2011 to November 2014, a total of 60 patients with A. baumannii bacteremia and available blood samples within 4 days of the onset (Day 0) of bacteremia were included for analysis. They were categorized into two groups depending on their survival at Day 14. Metabolomic profiles of the blood specimens collected at Day 0–4 of survival and death groups were compared to identify specific biomarkers to predict patient survival at Day 14. The patients were divided in the training (n=40) and validation (n=20) sets, and the logistic regression-based receiver-operation characteristic (ROC) was used to find the potential markers.

Results

The Day 14 mortality of the included patients was 20.0% (12/60). The partial least square-discriminate analysis (PLS-DA) scores plot separated the survival and death groups (Figure 1). Thirteen metabolites, L-Isoleucine, Ofloxacin, P-Hydroxybenzaldehyde, Hippurate, Indolelactic acid, Kynurenate, N-Acetyl-L-alanine, Sebacic acid, N-Acetylaspartylglutamic acid, Hematoporphyrin IX, and Urocanic acid reached the statistical significance (p < 0.05) and the accuracies of training and validation sets were greater than 0.8 and 0.6, respectively (Figure 2 and Table 1). Moreover, the Wilcoxon rank sum test results of those metabolites reached the statistical significance (Table 1).

Future 1: (A) PLS-DA scores plot for death and survival groups. (B) The loading plot of PLS-DA and the distribution of the thirty important metabolites with VIP values of >1.5.

Figure 2. Box plots showing significant changes of the 13 potential markers in the level of metabolites among the death and survival groups.

Table 2: Identified metabolites, p value, VIP, and the result of logistic regression.

Conclusion

Metabolomics had the potential to identify metabolites to predict survival in patients with A. baumannii bacteremia.

Disclosures

All Authors: No reported disclosures
250. Blood Stream Infections (BSI) in Pediatric Neuroblastoma High Risk: Emphasis on Viridans Group Streptococci (VGS) Bacteremia
Authors: Alali Muayad , Hageman Joseph
Published: January 2021

Background

Febrile neutropenia’s (FN) literature has focused on acute leukemia and undergoing allogeneic stem cell transplantation (SCT) as high risk factors for microbiological documented infection (MDI) and blood stream infection (BSI). Comprehensive studies on in pediatric Neuroblastoma high risk (NB-HR) who receive highly myelosuppressive therapy are lacking.

Methods

We conducted a retrospective medical record review of pediatric patients who received any oncology care at UCM Comer Children’s Hospitals.with a diagnosis of FN who had at least 1 blood culture obtained and one of the following underlying diagnoses (AML, lymphoblastic leukemia ALL), NB-HR, and other solid tumors (ST). SCT patients were excluded from study. We reviewed pathogens isolated from blood cultures (BCx) and determined whether they were pathogens or contaminants using IDSA guidelines. Comparative analyses of BSI rates between NB-HR and other underlying diagnoses were done.

Results

A total of 560 FN episodes (FNEs) were identified in 230 patients. FNEs occurred in NB-HR were 102 in 77 patients. Fifty-seven percent of patients developed one or more BSI or MDI during induction chemotherapy. The mean age was 11.0 (SD=6.5) years. True BSI occurred in 138 (24.6%) of FN episodes. The organisms that were most frequently isolated from were viridans group streptococci (VGS) (25%). The highest rate of BSI occurred among FNEs with AML (44/115, 37%) followed by NB-HR 26/110 (25%) Table1. Overall BSI rate in NB-HR group is higher than other solid tumors (25 vs 17%, P=0.03). In subset analysis, VGS bacteremia was highest among FNEs with AML and NB-HR compared with ALL (8.7 and 8.8 % vs 6%) P< 0.04 and P=0.02 respectively.

Notably, the gram positive/ gram negative (GP/GN ratio) in NB-HR compared with ST was significantly higher (OR =2.26, CI 95% 1.5–7.8, P< 0.01), this was likely due to a higher VGS rate (8.8% vs 2%, OR=4.2, P < 0.01). Rate of GN-BSI are same in each of ALL,HR-NB and ST.

Conclusion

Our large Neuroblastoma cohort showed that NB-HR during induction chemotherapy are higher risk for VGS bacteremia, compared with other solid tumors. Further prospective studies are needed to investigate infection related complication in this high risk group and possible improved morbidity and mortality.

Disclosures

All Authors: No reported disclosures
251. High prevalence of the cefazolin inoculum effect in methicillin-susceptible Staphylococcus aureus causing bloodstream infections in a hospital network in Houston, TX
Authors: Pinargote-Cornejo Paulette M , Gomez-Villegas Sara I , De la Hoz Alejandro , Miller William R , Pedroza Claudia , Arias Cesar A
Published: January 2021

Background

Anti-staphylococcal β-lactams, such as anti-staphylococcal penicillins (AsPen) or cefazolin are the drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections. However, cefazolin has seen increasing use due to its better tolerance, lower cost, ease of administration and possibly better outcomes when compared to AsPen. Nevertheless, its efficacy may be compromised by the cefazolin inoculum effect (CzIE), defined as an increase in the minimum inhibitory concentration (MIC) of cefazolin to ≥16mg/L when a high inoculum (5x107 CFU/ml) is present. Previous studies have suggested that the prevalence of the CzIE varies geographically, with high prevalence in some Latin American countries. Prospective data evaluating the presence of the CzIE in deep-seated MSSA infections across the United States are lacking.

Methods

We performed a prospective observational study of MSSA bacteremia in a network of 13 hospitals in Houston, TX. Patients ≥ 18 years old, with a positive blood culture with MSSA, with at least one follow-up blood culture confirming clearance of the bacteremia, who received cefazolin or nafcillin as definitive therapy (72 hours or longer after culture results known) and whose original isolate was available for evaluation of the CzIE, were included. Patients with polymicrobial BSI, or those who received another antibiotic with activity against MSSA in the definitive therapy period were excluded. Cefazolin MICs were determined by broth microdilution at standard and high inoculum.

Results

We report the results of 50 patients enrolled from February 15, 2020-April 30, 2020. The baseline characteristics of each group are outlined in Table 1. A total of 37/50 (74%) received cefazolin as definitive therapy, and complicated bacteremia was seen in 27/50 (54%). A total of 16/50 (32%) of the MSSA isolates exhibited the CzIE. Two patients in our cohort died: both of whose isolates exhibited the CzIE and received cefazolin as definitive therapy.

Conclusion

We report a high prevalence of the CzIE in MSSA BSIs in a major US urban hospital network. Further evaluation of the clinical implications of the CzIE is urgently needed.

Disclosures

William R. Miller, MD, Entasis Therapeutics (Scientific Research Study Investigator)Merck (Grant/Research Support)Shionogi (Advisor or Review Panel member) Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator) MeMed (Scientific Research Study Investigator) Merck (Grant/Research Support)
252. Increased incidence rates of positive blood cultures shortly after chemotherapy treatment initiation among individuals treated for solid malignant tumours
Authors: Roen Ashley O , Terrones-Campos Cynthia , Mocroft Amanda , Andersen Michael Asger , Helleberg Marie , Niemann Carsten Utoft , Daugaard Gedske , Specht Lena , Reekie Joanne , Lundgren Jens
Published: January 2021

Background

Cancer treatments suppress immune function and are associated with increased risk of infections, but the overall burden of serious infectious diseases in treated patients has not been clearly elucidated.

Methods

All patients treated for solid malignant tumours with curative intent radiotherapy (RT) and/or standard first line chemotherapy (C) at the Department of Oncology at Rigshospitalet between 01/1/2010 to 31/12/2016 were included. Patients were followed from treatment initiation to new cancer treatment, end of follow up or death whichever came first. We calculated incidence rates (IR) of positive blood culture (PBC) per 1000 person years follow up using Kaplan-Meier methods, and examined the proportion who died within 30 days of PBC.

Results

13,275 individuals were included, 4,372 (33%), 6,349 (48%), and 2,554 (19%) treated with RT, C, or concomitant RT&C, respectively, contributing 21,493 person years follow-up. 6,930 (52%) were female, the median (IQR) age was 63 (53, 70), and the most common cancer diagnoses were breast (n = 2,593 [19%]), colorectal (n=1,422 [11%]), and stomach (n=1,246 [9%]).

Overall, 564 individuals (4%) experienced 746 unique episodes of PBC, 188, 408, and 150 events in 143, 311 and 110 individuals treated with RT, C, and RT&C, of which 49 (26%), 104 (25%), 38 (25%) died within 30 days of PBC, respectively. IR of PBC significantly varied by treatment: 13.0 (95% confidence interval 11.1, 15.4), 43.9 (39.3, 49.0) and 32.0 (26.5, 38.5) per 1000 person-years follow up in the RT, C and RT&C groups, respectively (IR ratio = 3.36 (2.75, 4.10) and 2.45 (1.91, 3.14) for C and RT&C compared to RT, respectively) and time since treatment (figure). Escherichia coli (n=185, 25%), Staphylococcus aureus (n=102, 14%), Klebsiella pneumoniae (n=76, 10%), Enterococcus faecium (n=48, 6%), and Enterococcus faecalis (n= 37, 5%) were the top 5 microorganisms identified and did not vary by treatment category, p = 0.11, there were 31 (4%) cases of Candida.

Incidence rate of positive blood culture (PBC) by time since treatment initiation (0–3 months, 0–6 months and >6 months) and the proportion who died within 30 days of PBC by treatment type among individuals treated for solid malignant tumours with radiotherapy [RT], chemotherapy [C] and concomitant RT&C at Department of Oncology at Rigshospitalet, University of Copenhagen between 01/1//2010 to 31/12/2016.

Conclusion

PBCs are seen more often within 3 – 6 months after C than after RT alone. PBCs are not common, but when they occur, mortality is high. More precise risk factors for PBC and prophylactic means and empiric treatments in selected high-risk patients should be investigated.

Disclosures

All Authors: No reported disclosures
253. Is Echocardiogram always indicated in Bacteremia?
Authors: Grinberg Sagy , Nagarakanti Sandhya , Ma’ayah Audai Ibrahim , Tchao Yee , Bishburg Eliahu
Published: January 2021

Background

Echocardiography (ECHO) is a commonly used test; and is part of the Duke’s criteria for diagnosing endocarditis (IE). Our objectives were to analyze utilization and results of ECHO in pts with bacteremia growing organisms not typically associated with IE, and to evaluate whether ECHO contributed to a diagnosis of IE.

Methods

A retrospective review in a 680-bed tertiary care hospital from 2013–2019. Adult pts with bacteremia with at least 2 positive blood cultures for an organism not typically associated with IE such as Streptococcus viridans, Staphylococcus spp. and enterococcus, and who underwent ECHO were included. Data was collected on demographics, blood cultures, timing of ECHO and its’ findings. Modified Duke’s criteria was used to diagnose IE.

Results

Ninety four pts were included. Mean age 62 yrs. (range 23-91yrs). 50 (53%) were men. DM noted in 49(52%), CAD in 37(39%), CHF in 54 (57%), chronic kidney disease in 22(23%), hemodialysis in 19(20%), history of IE in 9 (10%). Transthoracic ECHO in 34 (36%), transesophageal ECHO in 28(30%), 32(34%) had both. Identifiable sources of bacteremia were urinary tract infection in 9 (10%), pneumonia 5 (5%), PICC line 5 (5%), wound/tissue infection 3 (3%).Clinicians did not specify the indication for ECHO in any of the cases. Unidentified source of bacteremia noted in 72(77%). Bacteremia was community acquired in 70(74%). Mean days of positive blood cultures 5.6 days (range 1–34 days). Gram (-) organism isolated in 44(47%), Gram (+) in 50(53%), of these, 50 (54%) had an implanted devices/indwelling catheter: 39 cardiac implantable device, 12 indwelling/tunneled catheter. The overall yield of ECHO in bacteremia was 11/94 (12%). ECHO in Gram (-) bacteremia had yield of 9% (4/44 pts) of them only 1 met possible IE by Duke’s criteria. Gram (+) bacteremia had an ECHO yield of 14% (7/50pts); of them 4 met possible IE Duke’s criteria. None of the cases met definite criteria for IE.

Conclusion

Yield of ECHO for the diagnosis of IE in pts with bacteremia with organisms other than Streptococcus viridans, staphylococci or enterococci was low even in the presence of implanted devices or indwelling catheters. Better criteria for ECHO utilization will reduce its use and potentially increase its yield.

Disclosures

All Authors: No reported disclosures
256. Serratia Marcescens Bacteremia and Endocarditis: A Treatment Assessment from an Academic Medical Center
Authors: Slain Douglas , Howard Catessa , Cooper Clinton G
Published: January 2021

Background

Serratia Marcescens (SM) is often an opportunist that has been associated as a cause of healthcare-associated infection and in some people who inject drugs (PWID). Decisions about the treatment of SM infections are difficult given the small clinical studies available and concerns for multidrug resistance. SM has the ability to produce inducible AmpC b-lactamase and may acquire extended-spectrum b-lactamase (ESBL). Evidence-based guidance is lacking in terms of identifying preferred antimicrobial therapy of SM bacteremia and endocarditis. Compared to other reports, our hospital has one of the largest SM data sets to compare.

Methods

This observation study included adult patients admitted to our hospital (2016–2019) with SM bloodstream infections, including endocarditis. Patients were excluded from the analysis, if they had a concomitant infection with another gram-negative organism. Our evaluation was designed to: compare outcomes associated with different antibiotic regimens, evaluate how care differed in PWID patients versus others, and identify factors associated with obtaining infectious diseases expert consultations (ID Consult).

Results

Forty-three patients met study inclusion/exclusion. Twenty-eight patients (65.1%) had ID Consults. Twenty-four (55.8%) were PWID. Endocarditis was diagnosed in 30.2% of patients. The most common regimen was cefepime +/- aminoglycoside, followed by a carbapenem +/- aminoglycoside. Combination therapy was only recommended during ID Consult. Piperacillin-tazobactam was used in 11.6% of patients. No regimen displayed an efficacy or safety advantage over another. Most patients (90.7%) cleared their blood stream within 48 hours of antibiotic start. Phenotypic susceptibility testing did not identify either ESBL or AmpC production in any of the isolates, including recurrences. Multi-drug resistance was not appreciated. Significant factors associated with obtaining ID Consult were: PWID (p=0.004), endocarditis (p=0.0002), sepsis (p=0.022), surgical intervention (p=0.003).

Conclusion

We could not identify an advantage with any particular antibiotic treatment regimen in this study. Induction of AmpC or selection of ESBL organisms was not displayed by any of the organisms.

Disclosures

All Authors: No reported disclosures
257. Staphylococcus aureus Bacteremia: Does Intravenous Drug Use Impact Quality of Care and Clinical Outcomes?
Authors: McClellan Kristen , Hilsendager Cami , Luke Strnad
Published: January 2021

Background

Individuals with intravenous drug use (IDU) have higher risk for Staphylococcus aureus bacteremia (SAB) and increased management complexity. The goal of this study was to compare differences in SAB characteristics, adherence to standard of care metrics, and clinical outcomes in those with and without IDU.

Methods

A retrospective chart review was conducted on cases of SAB between January 1, 2016 and December 31, 2017 at a 500-bed teaching hospital. Inclusion criteria was age > 18 years and ≥ one blood culture positive for S. aureus. Patients were excluded if they transferred hospitals, had care withdrawn or died within 48 hours of diagnosis or had a ventricular assist device infection. Records were reviewed for substance use, SAB characteristics, standards of care, and outcomes. Data were analyzed using SPSS software. The study was approved by the Institutional Review Board.

Results

In 248 patients with SAB, 28.2% had documented IDU. Median age was 37 (IDU) and 57 (non-IDU). In the IDU group, 75.7% had the formal diagnosis of opioid use disorder and 78.9% of stimulant use disorder. IDU was associated with hepatitis C and houselessness while non-IDU was associated with diabetes, hemodialysis, and cancer. Those with IDU had higher rates of MRSA, endocarditis, and spinal infections, but did not have higher rates of polymicrobial infections or venous thrombosis. There was no difference in appropriate repeat blood cultures, antibiotic management, and ID consultation. Length of stay and against medical advice (AMA) discharges were higher in those with IDU. There was no difference in 90-day recurrence or readmission, but 90-day mortality was higher in the non-IDU group.

Conclusion

There was no difference in adherence to SAB quality of care metrics between groups with and without IDU. Despite the IDU group being younger with fewer comorbidities, 90-day readmissions were not different between groups. This bears further analysis but may represent the influence of therapy completion, AMA discharges, and unmeasured social determinants of health.

Disclosures

All Authors: No reported disclosures
262. A Systematic Review and Meta-Analysis of the Impact of Delayed Appropriate Antibiotic Therapy on Mortality in Patients with Gram-Positive Bacteremia
Authors: Liu Steve , Moua Paochee , Monjor Selam , Zasowski Evan J
Published: January 2021

Background

Antibiotic resistance is common and frequently leads to unintentional delays in appropriate antibiotic therapy. The detrimental impact of delayed therapy is well-accepted, but the majority of evidence focuses on gram-negative infections. A review and synthesis of the evidence evaluating the impact of delayed appropriate antibiotic therapy in serious gram-positive infections does not exist. Such data would define the scope of the problem in this important patient population where antibiotic resistance is common. The objective of this systematic review and meta-analysis was to assess the impact of delayed appropriate antibiotic therapy on mortality in patients with gram-positive bacteremia.

Methods

Pubmed and Embase were searched from inception to March 30, 2020 to identify clinical studies of patients with bacteremia due to staphylococci, enterococci, or streptococci that reported the association between delayed appropriate antibiotic therapy and mortality. Three independent reviewers screened search results. Study quality was assessed via Newcastle-Ottawa Assessment Scale. Meta-analyses evaluating association between delayed therapy and mortality were conducted via random effects models in Review Manager 5.3. The primary analysis included unadjusted effect estimates from studies reporting unadjusted data. Secondary analysis included adjusted effect estimates from studies adjusting for confounding.

Results

Of 3684 search results, 16 cohort studies encompassing 4173 bacteremias were included. Ten studies involved S. aureus, 5 enterococci, and 2 S. pneumoniae. One-third (33.7%) of the 3659 patients in the primary analysis received delayed appropriate antibiotic therapy. The primary meta-analysis of 15 studies reporting unadjusted data showed a statistically significant association between delayed therapy and mortality (figure 1). Results from secondary analysis using adjusted point estimates from 9 studies were similar (figure 2).

Figure 1. Forrest plot of meta-analysis of unadjusted association between delayed therapy and mortality

Figure 2. Forrest plot of meta-analysis of covariate adjusted association between delayed therapy and mortality

Conclusion

Delayed appropriate therapy was common and associated with increased mortality in patients with gram-positive bacteremia. These findings underscore the need for continued antimicrobial stewardship efforts to ensure expeditious appropriate antibiotic therapy for patients with gram-positive bacteremia.

Disclosures

All Authors: No reported disclosures
268. Clinical Characteristics and Mortality Associated with Culture Positivity in Adult Inpatients with Sepsis: A 15-Year Cohort Study of 48,706 Patients at a Tertiary Medical Center in Taiwan
Authors: Chiang Hsiu-Yin , Chen Pei-Shan , Chi Chih-Yu , Kuo Chin-Chi
Published: January 2021

Background

Culture-negative (CN) sepsis occurs in 30~60% of sepsis patients. Understanding CN sepsis is crucial for treatment optimization. We used an electronic medical records (EMR)-based surveillance proposed by Rhee et al. to identify patients with sepsis meeting Sepsis-3. We aimed to describe the trend of sepsis and mortality, and to study the characteristics and mortality associated with culture positivity.

Methods

This cohort study included adult (>=18 years) inpatients with first-time sepsis who were admitted to our hospital during 2003–2017 (Figure 1). Sepsis was identified using clinical indicators of presumed infection and concurrent acute organ dysfunction. Culture-positive (CP) sepsis were those whose blood grew non-commensal organisms for > = 1 blood draw and those whose blood grew commensal organisms for > = 2 blood draws. Mortality were ascertained by the National Cause of Death Database. Multivariable Cox proportional hazard model was used to evaluate the effect of culture positivity on all-cause mortality.

Figure 1. Selection Process of the Study Population (N = 48,706).

Results

Of 48,706 adult inpatients with first-time sepsis, 41,304 (84.8%) were CN. The sepsis rate increased from 4.6% to 8.7%, while in-hospital mortality significantly decreased from 30.2% to 14.5% (Figure 2). Patients with CN sepsis tended to be younger, male, less diabetes, liver cirrhosis but more cardiovascular disease, and received systemic antibiotic within 14 days prior (Table 1). Serum biochemical profiles of procalcitonin, hs-CRP, and lactate were significantly lower in CN sepsis. Mechanical ventilation and respiratory site of infection were more likely to be presented in CN sepsis. Overall, the mortality (in-hospital, 7-day, 30-day, 1-year) was lower in CN sepsis. After adjusting for confounders, culture positivity was significantly associated with 7-day mortality (aHR 1.21; 95% CI 1.08, 1.37) (Table 2).

Figure 2. The Trend of Sepsis Rate (A) and In-hospital Mortality (B) of Adult Inpatients with Sepsis, 2003–2017 at CMUH.

Table 1. Baseline Demographic and Clinical Characteristics of the Adult Inpatients with Sepsis, 2003–2017 at the CMUH (N = 48,706).

Table 2. Hazard Ratio (95% Confidence Interval) for Mortality Associated with Culture-Positive Sepsis.

Conclusion

Sepsis rate increased while the mortality decreased, indicating the improvement of sepsis management in the past 15 years. The clinical characteristics of CN and CP sepsis were comparable, except for the lower inflammatory markers found in CN sepsis. Patients with CP sepsis had 21% higher risk of 7-day mortality. Next, we will link with National Health Insurance Database to examine admission history and antibiotic use in other institutions.

Disclosures

All Authors: No reported disclosures
269. Clinical Characteristics and Outcomes of Persistent Staphylococcus aureus Bacteremia
Authors: Yang Eunmi , Chung Hyemin , Seo Hyeonji , Kim Haein , Kim Jinyeong , Park Sunghee , Sung Heungsup , Kim Mi-Na , Jung Jiwon , Kim Min Jae , Chong Yong Pil , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Woo Jun Hee , Kim Yang Soo
Published: January 2021

Background

Staphylococcus aureus bacteremia (SAB) is a leading cause of bacteremia and persistent SAB is associated with poor outcomes. We evaluated key clinical characteristics and outcomes associated with persistent SAB.

Methods

We reviewed patients enrolled in a prospective cohort of adult patients with S. aureus bacteremia at a tertiary hospital from August 2008 to December 2018. Clinical characteristics, outcomes, and microbiologic characteristics of patients with persistent bacteremia (≥ 3 d) were evaluated.

Results

Of the total 969 patients, 617 (63.7%) patients had persistent bacteremia. The median duration of bacteremia with persistent bacteremia was 5 days. The most common sources of persistent bacteremia were central venous catheter-related infection (33.4%) and bone and joint infection (14.9%). Methicillin resistant S. aureus (MRSA) isolates were analyzed in 372 (60.3%) patients and metastatic infections were 217 (35.2%) with persistent bacteremia. In the multivariate analysis, APACHE Ⅱ score (adjusted odds ratio [aOR], 1.07; 95% confidence interval [CI], 1.03–1.10), Charlson comorbidity index score (aOR, 1.14; 95% CI, 1.04–1.25), liver cirrhosis (aOR, 2.47; 95% CI, 1.44–4.23), and S. aureus pneumonia (aOR, 3.04; 95% CI, 1.29–7.18) were independently associated with 30-d mortality. In persistent MRSA bacteremia, ST5-SCCmecⅡ was 59.7% (222/372) and agr dysfunction was 64.8% (241/372). After adjusting for confounding factors, APACHE Ⅱ score (aOR, 1.08; 95% confidence interval [CI], 1.04–1.12), liver cirrhosis (aOR, 3.09; 95% CI, 1.56–6.14), and S. aureus pneumonia (aOR, 4.37; 95% CI, 1.40–13.67) were independently associated with 30-d mortality.

Table 1. Demographic and Clinical characteristics of Patients With Persistent Bacteremia

Table 2. Microbiologic Characteristics and Genotypes in MRSA Isolates Responsible for Persistent Bacteremia

Fig 1. Duration of Staphylococcus aureus bacteremia

Conclusion

In persistent bacteremia, clinical factors, including APACHE Ⅱ score, Charlson comorbidity index score, liver cirrhosis, and S. aureus pneumonia contribute to 30-d mortality.

Disclosures

All Authors: No reported disclosures
271. Clinical Outcomes Treating Gram-Negative Bacteremia with Oral Beta-Lactams vs. Trimethoprim-Sulfamethoxazole or Fluoroquinolone Step-Down Therapy
Authors: Sinclair Emily , Frens Jeremy J , Zeigler Dustin , Mccarthy Megan , Sharma Roopali
Published: January 2021

Background

Recently, studies about gram-negative bacteremia have shown that shorter courses and early step-down therapy with oral agents have equivalent outcomes compared to longer courses with intravenous therapy. The question remains, however, as to which oral agents may be most appropriate for oral conversion therapy. At Cone Health it has been common practice to de-escalate to oral beta-lactams due to local susceptibility patterns and safety concerns with fluoroquinolones. This study retrospectively evaluated the 30-day clinical outcomes of patients treated with oral beta-lactams as step-down therapy vs. fluoroquinolones and trimethoprim-sulfamethoxazole (TMP-SMX).

Methods

In this IRB approved, retrospective review, 200 patients with gram-negative rod bacteremia were screened. Sixty-seven patients were excluded due to inpatient mortality (17), transfer to another facility (7), hospice care (6), or receipt of intravenous antibiotics only (37). The most common organism isolated was E. coli at 57% (75/133) and a majority of cases had a genitourinary source, 79/133 (59%). The primary endpoints were 30-day readmission and mortality. Secondary endpoints included total length of antibiotic therapy and length of IV therapy.

Results

Of the 133 patients included, 101 (76%) received an oral beta-lactam and 32 (24%) received either a fluoroquinolone or TMP-SMX. In the beta-lactam group 22/101 (21.8%) were re-admitted within 30-days compared to 5/32 (15.6%) in the fluoroquinolone and TMP-SMX group (p=0.412). Each group had one patient re-admitted due to recurrence of bacteremia. The majority of patients in the beta-lactam group were re-admitted for a non-infectious reason (82%). Only 1 (1%) patient in the beta-lactam group died within 30 days of discharge compared to 2 (6%) in the fluoroquinolone group (p=0.165). Average total length of therapy in the beta-lactam group was 12.8 days compared to 14 days in the fluoroquinolone and TMP-SMX group (p=0.065). Average length of IV therapy was 3 days in the beta-lactam group and 4 days in the fluoroquinolone and TMP-SMX group (p=0.99).

Conclusion

At our institution, we have not noted any significant difference in 30-day bacteremia recurrence or mortality between those who receive oral beta-lactams or fluoroquinolones/TMP-SMX.

Disclosures

All Authors: No reported disclosures
272. Clinical Outcomes with Continuation of Combination Antibiotic Therapy versus De-escalation to Monotherapy for Patients with MRSA Bacteremia
Authors: Nichols Courtney , Sobhanie Mahdee , Wardlow Lynn , Coe Kelci E
Published: January 2021

Background

Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with increased morbidity and mortality. Previous studies have demonstrated lower mortality with combination therapy (CT) compared to monotherapy (MT) for MRSA bacteremia; however, there is a lack of evidence to favor continued CT over de-escalation to MT for completion of treatment after clearance of bacteremia.

Methods

This was a single-center, retrospective study at The Ohio State University Wexner Medical Center in patients with MRSA bacteremia from November 2011 to July 2019. The primary composite outcome included inpatient infection-related mortality, 60-day readmission and 60-day bacteremia recurrence in patients receiving daptomycin and ceftaroline CT for greater than 10 days against those who received three to ten days of CT and were then de-escalated to either daptomycin, ceftaroline, or vancomycin MT. Statistical analysis used simple and multivariate logistic regression models to estimate crude and adjusted odds ratios and the 95% confidence interval to assess the relationship between the composite outcome for the MT and CT groups, while controlling for proven cofounders.

Results

A total of 286 patients with MRSA bacteremia were identified with 146 patients omitted based on exclusion criteria. The study population included 66 in the CT group and 74 in the MT group. Of those in the MT group 20 received ceftaroline, 29 received daptomycin, and 25 received vancomycin. Median age was 46 years (IQR 34.5–61), 60% required intensive care unit stay (n=84), and patients were 51% female (n=71) and 78% white (n=109). Bacteremia source was primarily intravenous drug use (40%) or line-related (16%). No significant difference was observed in the primary composite outcome (21% CT group vs 24% MT group; p=0.66). Within this outcome, there was no significant difference in readmission within 60 days (20% CT group vs 18% MT group; p=0.75), bacteremia recurrence within 60 days (3% CT group vs 7% MT group; p=0.45), or inpatient infection-related mortality (2% CT group vs 5% MT group; p=1.00).

Conclusion

No significant difference was found in the composite clinical outcome for MRSA bacteremia patients with continued CT versus those who were switched to MT.

Disclosures

All Authors: No reported disclosures
274. Comparison of Cefazolin Susceptibilities of Enterobacterales with an Automated Susceptibility Testing Platform versus In Vitro Antimicrobial Testing
Authors: Noval Mandee , Heil Emily , Williams Paula , Johnson J Kristie , Claeys Kimberly C
Published: January 2021

Background

The Clinical and Laboratory Standards Institute (CLSI) revised breakpoints for cefazolin (CFZ) may be difficult to implement with current automated susceptibility testing (AST) platforms and Enterobacterales may be falsely reported as susceptible to CFZ. The possibility remains that CFZ may then be inappropriately used as definitive therapy.

Methods

This was a retrospective observational cohort of adult patients with Enterobacterales bloodstream infections (BSI) reported CFZ susceptible per Vitek®2 (bioMerieux, Durham NC). The primary outcome was the percentage of CFZ susceptible Enterobacterales isolates using three different susceptibility testing methods: Vitek®2 automated testing, ETEST® (bioMerieux, Durham NC), and disk diffusion. Secondary outcomes included treatment failure defined as a composite outcome of 30-day all-cause inpatient mortality, 30-day recurrent BSI, 60-day recurrent infection, or infectious complications.

Results

In 195 isolates reported CFZ susceptible per Vitek®2, 84 (43.1%) were CFZ susceptible using E-test vs.119 (61%) using disk diffusion (Figure 1). Rates of treatment failure were similar in both CFZ and non-CFZ groups (33.3% vs. 38.5% respectively; p=0.57). Both groups had high rates of ID consult involvement (>60%) and source control (>80%) with urinary tract being the most reported source. No difference was noted in 30-day all-cause mortality, secondary infectious complications, 30-day readmissions, or 60-day recurrent infections. A subgroup analysis of patients receiving CFZ vs. ceftriaxone suggests treatment failure was significantly less likely to occur in the setting of source control (adjusted OR 0.06; 95% CI, 0.13–0.32) and ID consult

Figure 1: CFZ Susceptibilities by Testing Method

Conclusion

There was a large discrepancy among testing methods; additional confirmatory CFZ susceptibility testing beyond AST platforms should be considered prior to definitive use of CFZ for systemic Enterobacterales infections.

Disclosures

All Authors: No reported disclosures