bluuebunny/crossref_metadata_2025 huggingface dataset:
276. Comparison of Ceftaroline in Combination with Either Vancomycin or Daptomycin for the Treatment of Methicillin-resistant Staphylococcus aureus Bacteremia
Authors: Welch Stephanie N , Meredith Jacqueline , Roshdy Danya , Medaris Leigh A , McCurdy Lewis
Published: January 2021

Background

Recent studies have suggested that combination therapy may be preferred to monotherapy for select patients with methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B); however, direct comparison between various combination regimens is lacking.

Methods

This was a multicenter, retrospective cohort study evaluating adult patients with MRSA-B who received vancomycin/ceftaroline (VAN+CPT) or daptomycin/ceftaroline (DAP+CPT) for at least 48 hours between April 1, 2017 and June 30, 2019. Patients with primary respiratory or central nervous system infections were excluded. The primary endpoint was rate of clinical success, defined as survival at 90 days, sterilization of blood cultures within 96 hours of combination therapy initiation, no perceived clinical failure requiring a change in MRSA-active therapy, and absence of recurrence. Secondary endpoints included time to culture clearance from combination therapy initiation, 30-day and in-hospital mortality, adverse events prompting antibiotic discontinuation, and hospital and intensive care unit length of stay.

Results

A total of 54 patients were included in the VAN+CPT group and 25 patients in the DAP+CPT group. Baseline characteristics were generally similar between groups, except patients in the VAN+CPT group were younger and more likely to have endocarditis. Bone/joint sources were more common in the DAP+CPT group. Initiation of combination therapy occurred 104.9 hours vs 140.0 hours from index culture collection in the VAN+CPT and DAP+CPT groups, respectively. Rates of clinical success were similar between groups (63.0% vs 64.0%, p=0.93). Time to culture clearance from combination therapy initiation was 50.9 hours in the VAN+CPT group compared to 48.6 hours in DAP+CPT (p=0.83). Rates of nephrotoxicity were higher in those who received VAN+CPT (16.7% vs 0%, p=0.04). Other secondary endpoints were similar between groups.

Conclusion

Rates of clinical success were similar between groups, though there was a significantly higher rate of nephrotoxicity noted in the VAN+CPT group. Our study supports that clinical outcomes may be similar between VAN+CPT and DAP+CPT, with greater safety concerns associated with VAN+CPT.

Disclosures

All Authors: No reported disclosures
279. Dalbavancin for Bloodstream Infections and Endocarditis: Real-World Outcomes From the DRIVE Registry
Authors: Gonzalez Pedro , Rappo Urania , McGregor Jennifer , DiPompo-Day Lisa , McCarthy Matthew W
Published: January 2021

Background

Dalbavancin, a long-acting lipoglycopeptide approved by the US FDA and EMA for acute bacterial skin and skin structure infections (ABSSSI) has potent activity against Gram-positive pathogens including MRSA. A total of 39 of 39 patients with baseline S aureus bacteremia from previous studies who received dalbavancin (1500 mg or 1000 mg followed by 500 mg 1 week later) had clearance of bacteremia (100%). We describe the clinical features and efficacy of dalbavancin in patients with bacteremia or endocarditis from a retrospective registry study of dalbavancin.

Methods

Dalvance Utilization Registry Investigating Value and Efficacy (DRIVE) was a phase 4 observational, multicenter, retrospective cohort study of the real-world use of dalbavancin in adults across the US. Data collected between 03/25/2017 and 11/27/2018 included patient, disease, and pathogen characteristics, antibiotic use, clinical outcome, and safety. Clinical outcome was assessed by chart review from last dalbavancin dose through 60 days. Success was defined as presumed or documented clinical or microbiological cure with no need for rescue IV antibiotic therapy. Failure was defined as presumed or documented clinical or microbiologic failure, or the need for rescue IV antibiotic therapy, or death. Outcome was indeterminate if there were insufficient data to determine status at 60 days.

Results

Of 1092 evaluable patients treated with dalbavancin for any indication, 32 had baseline bloodstream pathogen data and Gram-positive bacteremia (Figure). 29 of 32 patients were previously treated with antibiotics (91%) with a median duration of 8.5 days. The 3 patients with endocarditis were among those most heavily pretreated (9, 4, and 4 prior IV antibiotics each). Clinical success was achieved in 30/32 (94%); outcome was indeterminate in 2/32 (6%). Most common dalbavancin regimens were 1500 mg x 1 (50%) or 1500 mg weekly x 2 (13%). Negative blood cultures for baseline pathogen prior to dalbavancin were documented in 53% of patients. There were no adverse events assessed as related to dalbavancin.

Conclusion

Dalbavancin use in Gram-positive bacteremia appears well tolerated and effective in the real-world setting.

Disclosures

Pedro Gonzalez, MD, MT, AbbVie (Employee) Urania Rappo, MD, MS, PharmD, Allergan (before its acquisition by AbbVie) (Employee) Jennifer McGregor, RPh, AbbVie (Employee) Lisa DiPompo-Day, n/a, AbbVie (Employee) Matthew W. McCarthy, MD, Allergan (prior to its acquisition by AbbVie) (Consultant, Grant/Research Support)
281. Detecting bacterial sepsis among allogeneic HCT recipients with population-specific bedside tools
Authors: Lind Margaret , Pergam Steven A , Liu Catherine , Phipps Amanda , Mooney Stephen , Althouse Benjamin , Carone Marco
Published: January 2021

Background

Diagnosing sepsis among allogeneic hematopoietic cell transplant (aHCT) recipients remains challenging. Existing criteria, for use in hospitalized patients, have limited predictive accuracy among aHCT recipients and their use may lead to missed events or antibiotic overuse. We developed bedside bacterial sepsis prediction tools (criteria and decision tree [DT]) for aHCT recipients and compared them against Systemic Inflammatory Response Syndrome (SIRS), quick Sequential Organ Failure Assessment (qSOFA) and National Early Warning Score (NEWS) criteria.

Methods

Adult aHCT recipients transplanted between September 2010–2019 with ≥ 1 potential infection (PI) within 100 days post-transplantation were randomly assigned to model/validation (7/3) cohorts. Tools included demographic and clinical factors and were built against a bacterial sepsis endpoint (gram-negative, Staphylococcus aureus, or Streptococcus species bacteremia). The tools were developed using best subset selection with rare event logistic regression (criteria) and classification tree (DT) algorithms. Criteria scores were estimated using a beta/10 integer weighting approach and tool predictive performances were compared against existing criteria.

Results

Between September 2010–2019, 1571 recipients with ≥ 1 PI contributed 7755 PIs and 238 sepsis events. The DT model included 7 terminal nodes based on 3 predictors: temperature, respiratory rate (RR), and sex. The criteria model contained 10 categories with 4 predictors: RR, temperature, pulse, and diastolic blood pressure (Figure 1). Our criteria and DT had AUCs of 71.1% (95% Confidence Interval (CI): 64.3, 77.9%) and 70.0% (CI: 63.7, 76.2%). SIRS had the highest AUC of existing criteria – 64.7% (CI: 57.1, 71.9%). Our criteria had the highest net benefit (for probabilities < 10%) and, at a 7+ cut-point, had a sensitivity of 73.8% (CI: 61.5–84.0%) and specificity of 55.0% (CI: 52.9, 57.1%) (Figure 2).

Conclusion

We developed aHCT recipient-specific bedside bacterial sepsis prediction tools with higher AUCs than existing criteria. Tools targeted to high-risk populations may lead to fewer missed sepsis events and, in turn, reduce sepsis related mortality among this high-risk population.

Disclosures

Steven A. Pergam, MD, MPH, Chimerix, Inc (Scientific Research Study Investigator)Global Life Technologies, Inc. (Research Grant or Support)Merck & Co. (Scientific Research Study Investigator)Sanofi-Aventis (Other Financial or Material Support, Participate in clinical trial sponsored by NIAID (U01-AI132004); vaccines for this trial are provided by Sanofi-Aventis)
288. Follow-Up Blood Cultures in Gram-Negative Bacteremia: How Do They Impact Outcomes
Authors: Elamin Azza , Khan Faisal , Abunayla Ali , Jagarlamudi Rajasekhar , Dash aditee
Published: January 2021

Background

As opposed to Staphylococcus. aureus bacteremia, there are no guidelines to recommend repeating blood cultures in Gram-negative bacilli bacteremia (GNB). Several studies have questioned the utility of follow-up blood cultures (FUBCs) in GNB, but the impact of this practice on clinical outcomes is not fully understood.

Our aim was to study the practice of obtaining FUBCs in GNB at our institution and to assess it’s impact on clinical outcomes.

Methods

We conducted a retrospective, single-center study of adult patients, ≥ 18 years of age admitted with GNB between January 2017 and December 2018. We aimed to compare clinical outcomes in those with and without FUBCs. Data collected included demographics, comorbidities, presumed source of bacteremia and need for intensive care unit (ICU) admission. Presence of fever, hypotension /shock and white blood cell (WBC) count on the day of FUBC was recorded. The primary objective was to compare 30-day mortality between the two groups. Secondary objectives were to compare differences in 30-day readmission rate, hospital length of stay (LOS) and duration of antibiotic treatment.

Mean and standard deviation were used for continuous variables, frequency and proportion were used for categorical variables. P-value < 0.05 was defined as statistically significant.

Results

482 patients were included, and of these, 321 (67%) had FUBCs. 96% of FUBCs were negative and 2.8% had persistent bacteremia. There was no significant difference in 30-day mortality between those with and without FUBCs (2.9% and 2.7% respectively), or in 30-day readmission rate (21.4% and 23.4% respectively). In patients with FUBCs compared to those without FUBCs, hospital LOS was longer (7 days vs 5 days, P < 0.001), and mean duration of antibiotic treatment was longer (14 days vs 11 days, P < 0.001). A higher number of patients with FUBCs needed ICU care compared to those without FUBCs (41.4% and 25.5% respectively, P < 0.001)

Microbiology of index blood culture in those with and without FUBCs

Outcomes in those with and without FUBCs

FUBCs characteristics

Conclusion

Obtaining FUBCs in GNB had no impact on 30-day mortality or 30-day readmission rate. It was associated with longer LOS and antibiotic duration. Our findings suggest that FUBCs in GNB are low yield and may not be recommended in all patients. Prospective studies are needed to further examine the utility of this practice in GNB.

Disclosures

All Authors: No reported disclosures
289. Impact of Clinician Specialty on the Use of Oral Antibiotic Therapy for Definitive Treatment of Uncomplicated Bloodstream Infections
Authors: Marcelin Jasmine R , Keintz Mackenzie R , Ma Jihyun , Stohs Erica J , Alexander Bryan , Bergman Scott , Van Schooneveld Trevor C
Published: January 2021

Background

No established guidelines exist regarding the role of oral antibiotic therapy (OAT) to treat uncomplicated bloodstream infections (uBSIs) and practices may vary depending on clinician specialty and experience.

Methods

An IRB-exempt web-based survey was emailed to Nebraska Medicine clinicians caring for hospitalized patients, and widely disseminated using social media. The survey was open access and once disseminated on social media, it was impossible to ascertain the total number of individuals who received the survey. Chi-squared analysis for categorical data was conducted to evaluate the association between responses and demographic groups.

Results

Of 275 survey responses, 51% were via social media, and 94% originated in the United States. Two-thirds of respondents were physicians, 16% pharmacists, and infectious diseases clinicians (IDC) represented 71% of respondents. The syndromes where most were comfortable using OAT routinely for uBSI were urinary tract infection (92%), pneumonia (82%), pyelonephritis (82%), and skin/soft tissue infections (69%). IDC were more comfortable routinely using OAT to treat uBSIs associated with vertebral osteomyelitis and prosthetic joint infections than non-infectious diseases clinicians (NIDC), but NIDC were more likely to report comfort with routine use of OAT to treat uBSIs associated with meningitis and skin/soft tissue infections. IDC were more likely to report comfort with routine use of OAT for uBSIs due to Enterobacteriaceae and gram-positive anaerobes, while NIDC were more likely to be comfortable with routinely using OAT to treat uBSIs associated with S. aureus, coagulase-negative staphylococci and gram-positive bacilli. In one clinical vignette of S. aureus uBSI due to debrided abscess, 11% of IDC would be comfortable using OAT vs 28% of NIDC; IDC were more likely to report routinely repeating blood cultures (99% vs 83%, p< 0.05).

Figure 1: Clinician comfort using oral antibiotic therapy to treat uncomplicated bacteremia due to specific syndromes

Figure 2: Clinician comfort using oral antibiotic therapy to treat uncomplicated bacteremia due to specific organisms

Conclusion

Considerable variation in comfort using OAT for uBSIs among IDC vs NIDC exists, highlighting opportunities for IDC to continue to demonstrate their value in clinical practice. Understanding the reasons for variability may be helpful in creating best practice guidelines to standardize decision making.

Disclosures

All Authors: No reported disclosures
291. Impact of Surveillance and Offered Infectious Diseases Consults for Staphylococcus aureus Bacteremia on Quality of Care Indicators
Authors: Jhaveri Khushali , Ramdeen Sheena
Published: January 2021

Background

Staphylococcus aureus bacteremia (SAB) remains the leading cause of bloodstream infections and is associated with 20–40% mortality. Past studies demonstrated that Infectious Diseases (ID) consultation is associated with better adherence to quality of care indicators (QCIs), including follow-up blood cultures, echocardiography, early source control, and appropriate choice and duration of antibiotics. A 2014 quality improvement project at Medstar Washington Hospital Center (MWHC) by Narsana et al. showed significantly better adherence to SAB QCIs among patients with ID consults and a non-significant trend towards lower mortality. In 2015, MWHC instituted a policy advocating ID consultation for all SAB patients, and active surveillance was performed by the ID Section to offer prompt consults prospectively. Our study aimed to assess the impact of this policy and the proactively offered ID consults on adherence to SAB QCIs and mortality rates amongst patients with SAB with and without ID consults.

Methods

We retrospectively reviewed 557 patients diagnosed with SAB between July 1st, 2015 - June 30th, 2018. Data included follow-up blood cultures, echocardiography, presence of a focal source of infection, use of appropriate antibiotics, measurement of vancomycin levels, duration of therapy, death during hospitalization, and presence of an ID consultation. Chi-Square and Fisher exact tests, and t-test and Wilcoxon rank sum test were used to analyze categorical and continuous variables, respectively.

Results

A total of 513 patients were included in the analysis, 88% (n=453) of whom had ID consultations. Patients with ID consultations were more likely to have a focal source of infection (84% vs. 50%, p < 0.0001), echocardiography (97% vs. 56%, p < 0.0001), use of a beta-lactam antibiotic for methicillin-susceptible S. aureus (90% vs 65%, p < 0.0001), and a longer duration of therapy (33 vs 9 days, p< 0.0001). Mortality was lower among patients with ID consults (16% vs. 23%, p=0.1495), but the difference was not statistically significant.

Table 1

Conclusion

Our study demonstrates that ID consultation is associated with better adherence to SAB QCIs, with a trend towards lower mortality. Hospital systems should support mandatory ID consultation for patients with Staphylococcus aureus bacteremia.

Disclosures

All Authors: No reported disclosures
293. Influence of a Pharmacist Led Treatment Algorithm for the Management of Staphylococcus Bacteremia
Authors: Lomanno Jessica , Elarabi Salwa , Fleisher Jorge
Published: January 2021

Background

Staphylococcus bacteremia is a major healthcare burden and currently there is no widely recommended treatment algorithm. Our institution adopts all elements of antimicrobial stewardship including rapid diagnostic testing. Despite these efforts, management of staphylococcus bacteremia continues to be problematic. The objective of this project is to evaluate implementation of a pharmacist-driven algorithm to guide treatment selection for staphylococcus bacteremia.

Methods

This is a single center, IRB-approved cohort study with a retrospective and prospective phase. The algorithm was designed in collaboration with the infectious disease (ID) service. Retrospective data was collected from June 2019 through September 2019. The algorithm was implemented on October 1, 2019 and prospective data was collected through January 2020. Prospectively a pharmacy resident identified positive blood cultures and recommended treatment based on the algorithm. Patients 18 years of age or older with a positive blood culture for staphylococcus were included. Patients were excluded if treatment was initiated at an outside hospital. The primary outcome is algorithm adherence. Secondary outcomes include days to negative blood culture, days to de-escalation, length of hospital stay and whether ID was consulted.

Treatment Algorithm

Results

A total of 64 patients were identified in the retrospective cohort and 46 in the intervention group. There were no significant differences in baseline characteristics. Algorithm adherence increased from 45% to 72% upon implementation (p=0.006). The algorithm resulted in a shorter time to de-escalation from 2.1 to 1.3 days (p=0.04). There were no statistically significant differences in days to negative blood culture, 2.3 vs. 2.2 days, or in average length of stay, 12.1 vs. 10.6 days in the retrospective and intervention groups, respectively. ID was consulted on 50% of patients in the retrospective cohort and 48% in the intervention group.

Conclusion

Implementation of a staphylococcus bacteremia treatment algorithm optimizes management. Additional layers of pharmacy involvement also result in a shorter time to de-escalation. These results highlight the importance of continuity of antimicrobial stewardship efforts.

Disclosures

All Authors: No reported disclosures
295. Is Herd Immunity from Pneumococcal Conjugate Vaccines Changing the Clinical Features of Invasive Pneumococcal Disease in Adults?
Authors: McGeer Allison , Plevneshi Agron , Hassan Kazi
Published: January 2021

Background

Numerous factors that affect the presentation and severity of pneumococcal disease. Several studies in the pre-PCV era demonstrated that organism characteristics, including serotype, are associated with variability in disease presentation and severity. We undertook an analysis of population based surveillance for invasive pneumococcal disease (IPD) to assess whether herd immunity from PCVs will change the presentation and severity of IPD in adults

Methods

TIBDN has performed population-based surveillance for IPD in Toronto and Peel region (pop’n 4.5M) since 1995. All sterile site isolates of S. pneumoniae are reported to a central study laboratory, isolates are serotyped, and clinical and vaccination data are collected via patient and physician interview and chart review. Population data are obtained from Statistics Canada. Backwards stepwise logistic regression assessed patient characteristics, illness features, and isolate factors associated with clinical presentation and case fatality.

Results

Between 1995 and 2018, 8815 episodes of IPD were identified in adults. Patients infected with PCV10not7 serotypes were younger, more likely male and without underlying illness. Patients with infections due to non-vaccine types were more likely to be immunocompromised. Case fatality in IPD declined from 177/754 in 1995/6 to 113/554 in 2017/8; OR 0.67, 95%CI0.51-0.86, P< .0001) and in all serotype groups (Figure). In multivariable models adjusted for host factors, relative to infections caused PCV7 serotypes, those caused by PCV10not7 were less likely to be fatal (OR 0.65, 95%CI 0.46–0.91); those caused by PCV13not10 were more likely to be fatal (OR 1.6, 95%CI 1.3–1.9). Bacteremic pneumonia as a proportion of presentations is highest in IPD due to PCV10not7 and PCV13not10 serotypes (85% and 83%, respectively), and lowest in IPD due to non-vaccine serotypes and PCV20not15 (59% and 68%, P< .0001). Meningitis is least common in IPD due to PCV10not7 serotypes (2.6%), and highest in cases due to non-vaccine types and PCV20not15 (9.0% and 8.0%, respectively, P< .0001).

FIgure

Conclusion

In our population, herd immunity from PCVs will result in a higher proportion of adult IPD occurring in immunocompromised cases, and a shift from bacteremic pneumonia to bacteremia without focus and meningitis.

Disclosures

Allison McGeer, MD, FRCPC, GlaxoSmithKline (Advisor or Review Panel member, Research Grant or Support)Merck (Advisor or Review Panel member, Research Grant or Support)Pfizer (Research Grant or Support)
296. IV-to-PO Antibiotic Step-down Therapy for Treatment of Uncomplicated Streptococcal Bloodstream Infections
Authors: Ramos-Otero Gerardo P , Brett Meghan , Ryan Keenan L , Sarangarm Preeyaporn , Walraven Carla
Published: January 2021

Background

Beta-lactams are the drug of choice for uncomplicated Streptococcal bloodstream infections (BSIs). However, due to the low bioavailability of oral beta-lactams, it’s unclear whether de-escalation from IV to PO therapy is safe and effective. Our objective was to compare the efficacy and safety of step-down IV-to-PO antibiotic therapy to IV-only treatment of uncomplicated Streptococcal BSIs.

Methods

This was a retrospective study at a level-1, academic medical center in New Mexico of patients ≥ 18 years of age treated for uncomplicated Streptococcal BSI between January 2017 and December 2019. The primary outcome was clinical failure in patients receiving IV-only therapy compared to IV-to-PO step-down therapy. Clinical failure was defined as having at least one of the following: persistent bacteremia, 30-day reinfection at any site or new-onset sepsis, 30-day BSI recurrence, or 30-day all-cause mortality. Secondary outcomes include 30-day all-cause readmission, 30-day antibiotic-related side effects, 30-day C. difficile-associated diarrhea and hospital length of stay (HLOS).

Results

A total of 98 patients were included: 51 in the IV-to-PO group and 47 in the IV-only therapy group. The median age for both groups was 61 years; 65% patients were male, and 72% were Caucasian. BSIs were predominantly associated with respiratory infections (24.5%). Streptococcus pneumoniae (29.6%) was the most common pathogen. Nine patients (19.1%) in the IV-only group and none in the IV-to PO group experienced a clinical failure. 30-day reinfection at any site or new-onset sepsis (88.9%) was the primary cause of clinical failures. Fourteen patients (14.3%) were readmitted due to any cause within 30 days, 6 patients (11.8%) from the IV-to-PO and 8 (17%) from the IV-only group. Patients in the IV-to-PO group had a shorter duration of therapy than patients in the IV-only group (13 vs. 15 days, p=0.001), and decreased HLOS (5 vs. 12 days, p< 0.001). Clinical failure was not statistically different when assessed for co-morbidities, source of infection, Pitt bacteremia score, documented BSI clearance, ICU admission or pathogen.

Conclusion

IV-to-PO step-down therapy appears to be a safe and effective alternative for treating uncomplicated Streptococcal BSIs in patients who are otherwise clinical stable.

Disclosures

Keenan L. Ryan, PharmD, PhC, Theravance (Advisor or Review Panel member)
298. Multicenter retrospective cohort study of the clinical significance of Staphylococcus lugdunensis isolated from a single blood culture set
Authors: Hauser Naomi , Kim Justin , Luethy Paul , Schmalzle Sarah , Bork Jacqueline
Published: January 2021

Background

Staphylococcus lugdunensis is a coagulase negative Staphylococcus (CoNS) species with the potential to cause aggressive infection. Guidance surrounding S. lugdunensis bacteremia (SLB) is lacking, especially in the case of a single positive set of blood cultures.

Methods

We performed a multicenter, retrospective observational cohort review of adult patients with SLB from at least one blood culture set within the University of Maryland Medical System from November 2015-November 2019. Objectives were to (1) describe baseline characteristics, (2) compare available criteria for evaluating clinical significance, and (3) evaluate the clinical outcomes among patients with SLB in 1 vs ≥2 positive blood culture sets. Descriptive statistics with Chi-squared and Mann-Whitney U tests were carried out.

Results

There were 5,548 CoNS-positive blood culture sets, 49 (0.88%) with S. lugdunensis comprising 36 adult patients (24 with 1 positive set and 12 with ≥2 positive sets). Patients with ≥2 positive sets were more likely to be on hemodialysis (HD) (p=0.029) and to have an HD catheter present (p=0.10) (Table 1). Thirty-five of the 36 patients fulfilled at least one of the following: systemic inflammatory response syndrome (SIRS), Souvenir criteria, or clinical criteria (infectious focus on imaging and/or second positive culture site) (Table 2). Twenty-eight (78%) patients were treated with antimicrobial therapy and/or central line removal. SIRS criteria were met more often among patients with 1 positive set (p=0.05). Patients with ≥2 positive sets were more often treated with antibiotics for longer than 2 weeks (p=0.02). The mean time of positive cultures to discharge was 11 days and was longer for patients with only one set of positive blood cultures (13 vs. 6 days), although this difference was not statistically significant (p=0.29) (Table 3).

Conclusion

SLB was rare and occurred more frequently as a single set of positive blood cultures. Though limited by sample size, this study found similar patient characteristics, clinical significance and outcomes between patients with one set and those with ≥2 sets of blood cultures positive for S. lugdunensis. Given the potential severity of SLB, it seems prudent to treat S. lugdunensis in a single blood culture, but larger studies are needed.

Disclosures

All Authors: No reported disclosures
301. Penicillin Versus Cefazolin or Anti-staphylococcal Penicillins for Penicillin-Susceptible Staphylococcus aureus Bacteremia
Authors: Aldhaeefi Mohammed , Pearson Jeffrey , Kanjilal Sanjat , Dionne Brandon
Published: January 2021

Background

Staphylococcus aureus bacteremia is a significant cause of mortality. Penicillin (PCN) may have a role in the treatment of penicillin-susceptible Staphylococcus aureus (PSSA) bacteremia as it has a narrower spectrum of activity than cefazolin and is better tolerated than antistaphylococcal penicillins (ASPs). The aim of this study is to evaluate the safety and effectiveness of PCN versus cefazolin or ASPs in the treatment of PSSA bacteremia.

Methods

This is a single-center, retrospective study at a tertiary academic medical center. All patients with a PSSA blood culture from January 1, 2012 to September 1, 2019 were screened. Patients were excluded if they were treated with a definitive antibiotic (defined as antimicrobial therapy received 72 hours after positive blood culture) other than the study comparators, or if they received combination antibiotic therapy >72 hours from the initial positive blood culture result. The primary outcome was 60-day clinical failure, which was a composite endpoint of change in antibiotic after 72 hours of definitive therapy, recurrence of PSSA bacteremia, infection-related readmission, or all-cause mortality.

Results

Of 277 patients with PSSA bacteremia, 101 patients were included in the study; 62 (61%) were male and 11 (11%) had a β-lactam allergy. At baseline, 40 patients (40%) had hardware, 25 (25%) had an intravenous line, 6 (6%) were on dialysis, and 4 (4%) had active IV drug use, with similar distribution across antibiotic groups. Penicillin was the most common antibiotic used (Table 1). There was a significant difference among groups with respect to the 60-day clinical failure (log-rank p=0.019). In terms of unadjusted 60-day clinical failure, penicillin had similar outcomes to cefazolin (95% CI -0.29 to 0.104, p=0.376), however, it had statistically significant better outcomes in comparison to the ASPs, nafcillin or oxacillin (95% CI 0.023 to 0.482, p=0.031) (Table 1).

Table 1. 60-day outcomes of PSSA bacteremia

Conclusion

Penicillin is effective and safe in the treatment of PSSA bacteremia and may be preferable to antistaphylococcal penicillins

Disclosures

All Authors: No reported disclosures
302. Peripheral IV catheters, a common source of healthcare-associated Staphylococcus aureus bacteremia
Authors: Young Heather , Aragon Deborah , Knepper Bryan C , Hussain Cory , Jenkins Timothy C
Published: January 2021

Background

Healthcare-associated S. aureus bacteremia (HA-SAB) has traditionally been attributed to surgical site infections (SSI) or central line-associated bloodstream infections. However, peripheral IV catheters (pIV) are increasingly recognized as cause of HA-SAB. This study evaluates risk factors for HA-SAB due to pIV.

Methods

This is a retrospective, case-control study of adult patients hospitalized at Denver Health Medical Center with HA-SAB (SAB presenting with hospital-onset [≥3 days after hospitalization] or community-onset attributed to recent hospitalization [discharge ≤7 days prior]). The time period ranged from Jan 1, 2016 to Nov 30, 2019. Cases were reviewed by an infectious diseases physician to determine the source of SAB. PIV-related SAB was defined as phlebitis, cellulitis, and/or drainage at the site of a previous pIV AND no other source or another less likely source based on progress notes and microbiology results. Three controls were matched to each pIV-related SAB case based on the age of the patient (±5 years) and the date the pIV was placed (±3 days). Patients who were admitted for elective procedures, to psychiatry, to obstetrics, and those who died within 2 days of pIV placement were excluded.

Results

There were 376 episodes of SAB during the study period; 313 were community-onset while 63 were HA-SAB (50 hospital-onset and 13 community-onset attributed to hospitalization). PIV was the most common cause of HA-SAB (n=20, 29.4%); other common causes were SSI (n=10, 15.9%), source present at admission (n=8, 12.7%), and pneumonia (n=7, 11.1%). The median age of patients with pIV-related SAB was 53 years (SD 15.6), and 85% were male. The median duration of pIV was 5 days (SD 2.8). Twenty percent was MRSA.

As compared to controls, pIV in immunocompromised individuals and those placed by emergency medical services (EMS) were more likely to develop SAB (OR 11.8, 95% CI 2.5–56.5 and OR 6.9, 95% CI 6.9–24.0, respectively). Age, gender, pIV location, and duration of pIV were not associated with development of SAB.

Conclusion

PIV placed by EMS are more likely to cause SAB than those placed in the hospital. Facilities should consider changing these pIV promptly upon admission to the hospital and work with EMS to improve pIV placement technique.

Disclosures

All Authors: No reported disclosures
303. Physiological Changes Due to Bloodstream Infection in Intensive Care Unit Patients Differ According to Transplant Status
Authors: Zimmet Alex , Lake Douglas , Zimmet Amanda M , Gadrey Shrirang M , Bell Taison , Moorman Randall , Moore Christopher
Published: January 2021

Background

Transplant recipients are at increased risk of bloodstream infection (BSI), which often leads to critical illness. Due to immunosuppression, BSI in these patients may manifest with different pathophysiology compared to non-transplant recipients. We aimed to identify different trends in the pathophysiology of critically ill patients with BSI based on transplant status.

Methods

We reviewed data from patients admitted to the medical and surgical/trauma intensive care units (ICUs) at the University of Virginia Medical Center from 2011 to 2015. We included both solid organ and hematopoietic stem cell transplant recipients. We performed univariate logistic regression modeling to evaluate trends in different physiological features in both transplant and non-transplant recipients in the 96 hours surrounding a positive blood culture. We then performed multivariate logistic regression modeling to identify features independently associated with a positive blood culture in the next 24 hours in transplant recipients.

Results

We analyzed 9,954 ICU patient-admissions (including 505 transplant recipients), with a total of 144 patient-years of physiological data, 1.3 million hourly measurements, and 15,577 blood culture instances. Of the 1,068 blood culture instances in transplant recipients, 125 (12%) were positive, compared to 1,051 of 14,509 (7%) blood culture instances in non-transplant recipients. Critically ill transplant recipients with BSI had greater abnormalities in vital signs, oxygen requirement, markers of organ damage, APACHE score, and Charlson Comorbidity Index (CCI) compared to non-transplant recipients (Figure 1). Trends in many of these features also differed based on transplant status. The multivariable logistic regression model of BSI in transplant recipients included, in decreasing strength of association: total bilirubin, systolic blood pressure, fraction of inspired oxygen, number of intravenous lines, and CCI. This model had an AUC of 0.75.

Figure 1. Trends in pathophysiological abnormalities in 9,954 critically ill patients with BSI based on transplant status, 2011–2015. Each graph demonstrates the average value of the physiological variable over time relative to the acquisition of a positive blood culture. Blue curves depict trends in transplant recipients, while red curves depict trends in non-transplant recipients. We assessed 108 physiological features and show the 24 features with the greatest change around the time of blood culture.

Conclusion

Critically ill transplant recipients have a higher prevalence of BSI and different pathophysiological manifestations of BSI compared to non-transplant recipients. This may have implications regarding early detection and treatment of BSI in these patients.

Disclosures

Randall Moorman, MD, Advanced Medical Predictive Devices, Diagnostics, and Displays (Board Member, Shareholder)
305. Prevalence of Ceftriaxone Susceptible, Piperacillin-tazobactam Non-susceptible Escherichia coli Bacteremia in Patients with Hematologic Malignancy
Authors: Spitznogle Sarah L , Rausch Caitlin R , Bhatti Micah M , Shelburne Samuel A , Aitken Samuel L
Published: January 2021

Background

Piperacillin-tazobactam (TZP) is common empiric and targeted therapy for gram-negative bacteremia in patients with hematologic malignancy. Resistance to TZP tends to occur concurrently with ceftriaxone (CRO) resistance; however, the prevalence of TZP nonsusceptibility in CRO susceptible Escherichia coli (E. coli) in patients with hematologic malignancy is unknown. Therefore, we sought to determine the prevalence of TZP nonsusceptible, CRO susceptible E. coli bacteremia at a cancer center.

Methods

This is a retrospective cohort study of adult (age > 18) patients with E. coli bacteremia admitted to the Leukemia or Stem Cell Transplant (SCT) services at The University of Texas MD Anderson Cancer Center (MDACC) between 8/2016 and 7/2019. Isolates were categorized according to current CLSI resistance breakpoints. A first isolate was defined as the first positive blood culture and subsequent episodes of bacteremia were defined as any E. coli isolate obtained at least 24 hours after the first negative blood culture.

Results

The overall prevalence of TZP resistant CRO susceptible E. coli from 404 isolates was 7.7% and varied by service. There was a higher prevalence in the Leukemia service compared to SCT, 9.8% vs 2.5%, respectively (p < 0.01). 46% of isolates were CRO nonsusceptible, of which 91% were extended-spectrum beta-lactamase (ESBL) producers, identified by Vitek 2 or Accelerate Pheno. The TZP MIC50 was 4ug/ml, MIC90 was 128ug/ml, with an MIC range of 3ug/ml to ≥ 256ug/ml. The TZP MIC distribution varied based upon CRO phenotype. In CRO susceptible isolates the MIC50 and MIC90 were 4ug/ml and 64ug/ml, respectively, compared to 8ug/ml and 128ug/ml in CRO nonsusceptible isolates (p < 0.01). TZP resistance was more common in CRO nonsusceptible isolates (31.6% vs 12.0%, p < 0.01) and was more frequent with subsequent episodes of bacteremia compared to the first (39.5% vs 20.1%, p < 0.01).

Conclusion

In patients with hematologic malignancy and E. coli bacteremia, TZP resistance is common with significant variations by CRO phenotype. TZP resistance becomes more common with subsequent episodes of bacteremia compared to the first. The clinical implications and genetic cause of this phenotype is currently unknown and warrants further investigation.

Disclosures

All Authors: No reported disclosures
306. Rapid Detection Of Bloodstream Infections, Including Molecular Characterization, From Whole Blood
Authors: Kadoom Aram , Lockhart Daniel , Kadoom Yassar , Fauci Sonia La , Rodgers Andrew , Turner James , Bennett Helen , Jay Paul , Thaker Sumi , Mullen William
Published: January 2021

Background

Diagnosis of bloodstream infections (BSI) and treatment with appropriate antimicrobials is dependent upon fast and accurate information about the microorganism(s). The long time taken for a blood culture result, microbial identification and antimicrobial susceptibility testing (AST), can lead to poor antimicrobial stewardship. Many antimicrobial change decisions are based on the results of a Gram stain, with this being the first result available. Having results from a rapid test, direct from blood, which can confirm BSI and characterize the causative pathogen(s) would provide an improvement in antimicrobial stewardship and patient care.

Methods

SepsiSTAT® is a rapid molecular test, developed by Momentum Bioscience Ltd, for the detection of BSI, with a time-to-result of < 4 hours. It uses whole blood to detect viable microorganisms whilst also providing molecular characterization. Microorganisms are extracted from the sample using a proprietary process involving capture on magnetic microbeads. This is followed by Enzymatic Template Generation and Amplification (ETGA®) for ultra-sensitive, universal detection of viable bacterial and fungal species, based on detecting microbial DNA polymerase activity. Simultaneously, molecular characterization also provides genus/species identification. The detection limits of SepsiSTAT® were evaluated for a broad panel of microorganisms, representing 80% of BSI reported to Public Health England (2018 report).

Results

These results show a median detection limit (n=5) of < 10 cfu/mL in blood for microorganisms representing 77.4% of reported BSI, including key organisms such as E. coli, S. epidermidis and C. albicans. Notably, S. aureus, P. aeruginosa, E. faecalis, P. mirabilis and S. marcescens were all detected at < 1 cfu/mL.

Conclusion

SepsiSTAT® can detect microbes in low numbers, with a turnaround time substantially faster than traditional blood culture. Future development will aim to shorten time-to-results to < 3 hours, further benefiting patient outcomes and antimicrobial stewardship. Future studies in a clinical setting will seek to further demonstrate the efficacy and rapid turnaround time of the SepsiSTAT® test.

Disclosures

All Authors: No reported disclosures
307. Rapid Resistance Development to Three Antistaphylococcal Therapies in Daptomycin-tolerant Staphylococcus aureus Bacteremia
Authors: Miller Christopher R , Monk Jonathan , Berti Andrew David
Published: January 2021

Background

We report a patient case of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia which over 30 days developed resistance to all three primary antistaphylococcal antibiotics. Index blood cultures displayed susceptibility to vancomycin (VAN, MIC=1), ceftaroline (CPT, MIC=0.5) and daptomycin (DAP, MIC=0.5). The patient was maintained on VAN/CPT with negative blood cultures by hospital day 7. The regimen was later modified to DAP/piperacillin-tazobactam. One month after initial presentation, during the same encounter, blood cultures were again positive for MRSA, now displaying intermediate resistance to VAN (MIC=2) and CPT (MIC=2), and resistance to DAP (MIC=4).

Methods

Isolates were collected from the initial bacteremia episode (B325) and the recurrence (B326). In-vitro one-compartment pharmacokinetic/pharmacodynamic modeling was performed on each isolate to determine which antibiotics or combinations would effectively eradicate cultures. Regimens examined included DAP (10mg/kg), DAP/cefazolin (CFZ), VAN/CFZ and penicillin/clavulanate. Draft whole-genome sequences are pending for each clinical isolate using hybrid assembly (Unicycler v0.4.2) of MinION and Illumina (150bp PE) reads.

Results

DAP/CFZ combination reduced viability of both B325 and B326 below limit of detection by 12 hours and maintained efficacy for 72 h. DAP, initially effective in reducing B326 cell concentrations below limit of detection, allowed regrowth by 36 h. All other modeled therapies were less effective. Interestingly, DAP took significantly longer to kill B325 relative to S. aureus collected contemporaneously from other patients. For DAP-containing regimens, the time to 3-log viability reduction (MDK99.9) was five-fold longer in B325 compared to similar clinical isolates with the same DAP MIC. Comparative genomics of sequential isolates is pending, although single nucleotide polymorphisms in vraT and mprF were identified in B326 compared to B325.

Conclusion

Delayed kill kinetics of B325 when exposed to DAP may indicate antibiotic tolerance, which could partially account for B325’s rapid transition to a multi-drug resistant organism. DAP/CFZ therapy appears to be the most active combination against both antibiotic-tolerant and multidrug resistant S. aureus strains.

Disclosures

All Authors: No reported disclosures
308. Re-purposing Beta-lactam Antibiotics as Fluoroquinolone Sparing Stepdown Therapy for the Treatment of Enterobacteriales Bloodstream Infections
Authors: Davis Matthew , McManus Dayna , Ruggero Michael , Topal Jeffrey E
Published: January 2021

Background

Oral antimicrobial therapy for Enterobacteriales bloodstream infection (EB-BSI) is advantageous to reduce the risk of central line complications, cost of care, and length of stay. Fluoroquinolones (FQ) given their high bioavailability have been utilized as the standard for stepdown therapy (SDT) for EB-BSI. Given the recent increased warnings around FQ use including Clostridioides difficile infection (CDI) and the increasing FQ resistance alternative oral options for treatment are warranted. Recent literature has suggested beta-lactams (BLM) may be an option for EB-BSI. To enhance the antimicrobial stewardship goal of reducing FQ use, our team began recommending de-escalation to a BLM for EB-BSI and the objective of this study is to evaluate the outcomes of this approach.

Methods

This study was a retrospective chart review of patients with EB-BSI due to ceftriaxone sensitive monomicrobial E. coli, Klebsiella spp., or P. mirabilis who received a BLM or a FQ as SDT. Patients were excluded if < 18 years of age; pregnant; ANC < 1000 cells/µL; had endocarditis, a bone/joint, or a CNS infection; discharged to hospice or expired prior to discharge; anaphylactic BLM allergy; or prior kidney transplant. SDT was defined as a switch to a definitive oral antibiotic after empiric IV therapy. The primary outcome was clinical cure defined as completion of therapy without signs of infection (increase in WBC > 2000 cells/mL if WBC was ≥ 12,000 cells/mL, fever (>38°C), or change in antibiotic due to failure). Secondary outcomes included 30 day re-admission rates, reinfection rate defined as positive culture within 30 days of completion of therapy, antibiotic associated adverse events defined as side effects leading to discontinuation and/or CDI within 90 days from start of treatment.

Results

A total of 159 patients were included in the study (Figure 1). The BLM patients had a higher median age (78 vs 72, p=0.008), higher median PITT bacteremia score (2 vs 1, p=0.037), were less likely to be immunosuppressed (9% vs 25%, p=0.045), and had shorter median duration of therapy (13 vs 14, p=0.034). There was no difference in the primary or secondary outcomes (Table 2).

Conclusion

BLM may enhance stewardship efforts as a FQ sparing option for treatment of EB-BSI; however, prospective studies in this area are warranted.

Disclosures

All Authors: No reported disclosures
309. The Impact of Addiction Medicine Consultation on Discharges Against Medical Advice in Patients with Opioid Use Disorder and Staphylococcus Aureus Bacteremia
Authors: Spivack Stephanie , Mueller Daniel , Axelrod Peter , D’Orazio Joseph
Published: January 2021

Background

People who inject drugs (PWID) are at risk for infectious complications of their injection practices, including Staphylococcus aureus (SA) bacteremia. Prolonged hospitalization is sometimes required; however, rates of discharges against medical advice (AMA) are elevated in this patient population. Inadequate control of pain and opioid withdrawal are commonly cited. Our aim was to assess the effectiveness of addiction medicine consultation for preventing AMA discharges.

Methods

We performed a retrospective chart review of adult PWID admitted to an urban hospital with SA bacteremia between August 2016 and May 2018. Demographics, HIV and HCV status, and presence or absence of addiction medicine consultation were recorded. We assessed whether discharges were planned or AMA; the number of hospitalizations at 30 days, 90 days, and 1 year from index admission; and death within one year. EpiInfo6 was used for data analysis.

Results

A total of 360 patients with SA bacteremia were reviewed. Of these, 101 reported intravenous opioid use at admission. Average age was 37 years, and 64% were male. HIV and HCV were present in 13% and 82% of patients, respectively. Addiction medicine was consulted on 29 patients. Of these, 4/29 (13.8%) left AMA, compared to 27/72 (37.5%) of patients without an addiction consult (RR = 0.3678 [95% CI = 0.1412 - 0.9583], p = 0.02).

Patients receiving addiction medicine consultation averaged 0.17 readmissions within 30 days of their index admission, compared to 0.39 readmissions in the group without addiction medicine consult (p = 0.27). Readmissions at 90 days and 1 year were also lower but not statistically significant. At 1 year, 6 deaths were observed; 2 who had addiction medicine consultation and 4 who did not.

Conclusion

Consultation with an addiction medicine specialist significantly reduced the number of patients discharged AMA in a high-risk cohort of PWID presenting with SA bacteremia. Numerically fewer readmissions occurred after consultation, though this difference was not statistically significant. Mortality in both groups was low. There were high rates of HIV and HCV in this patient population, suggesting a particularly vulnerable patient population, which warrants further study.

Disclosures

All Authors: No reported disclosures