Optimizing the Management of Uncomplicated Gram-Negative Bloodstream Infections: Consensus Guidance Using a Modified Delphi Process

Abstract Background Guidance on the recommended durations of antibiotic therapy, the use of oral antibiotic therapy, and the need for repeat blood cultures remain incomplete for gram-negative bloodstream infections. We convened a panel of infectious diseases specialists to develop a consensus definition of uncomplicated gram-negative bloodstream infections to assist clinicians with management decisions. Methods Panelists, who were all blinded to the identity of other members of the panel, used a modified Delphi technique to develop a list of statements describing preferred management approaches for uncomplicated gram-negative bloodstream infections. Panelists provided level of agreement and feedback on consensus statements generated and refined them from the first round of open-ended questions through 3 subsequent rounds. Results Thirteen infectious diseases specialists (7 physicians and 6 pharmacists) from across the United States participated in the consensus process. A definition of uncomplicated gram-negative bloodstream infection was developed. Considerations cited by panelists in determining if a bloodstream infection was uncomplicated included host immune status, response to therapy, organism identified, source of the bacteremia, and source control measures. For patients meeting this definition, panelists largely agreed that a duration of therapy of ~7 days, transitioning to oral antibiotic therapy, and forgoing repeat blood cultures, was reasonable. Conclusions In the absence of professional guidelines for the management of uncomplicated gram-negative bloodstream infections, the consensus statements developed by a panel of infectious diseases specialists can provide guidance to practitioners for a common clinical scenario.

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289. Impact of Clinician Specialty on the Use of Oral Antibiotic Therapy for Definitive Treatment of Uncomplicated Bloodstream Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.332 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S144-S145

Author(s):

Jasmine R Marcelin ◽

Mackenzie R Keintz ◽

Jihyun Ma ◽

Erica J Stohs ◽

Bryan Alexander ◽

...

Keyword(s):

Social Media ◽

Soft Tissue ◽

Infectious Diseases ◽

Antibiotic Therapy ◽

Bloodstream Infections ◽

Definitive Treatment ◽

Oral Antibiotic ◽

Soft Tissue Infections ◽

Gram Positive ◽

Oral Antibiotic Therapy

Abstract 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

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194. Description of Positive Blood Culture Results not Identified by Verigene Informs Empiric Antibiotic Selection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.269 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S116-S117

Author(s):

Connor Deri ◽

Whitney Nesbitt ◽

George Nelson ◽

Jessica Keefe

Keyword(s):

Antibiotic Therapy ◽

Resistance Mechanism ◽

Bloodstream Infections ◽

Blood Cultures ◽

Aerobic Bacteria ◽

Gram Positive ◽

Antibiotic Selection ◽

Gram Negative ◽

Empiric Antibiotic ◽

Gram Negative Organisms

Abstract Background Bloodstream infections are a leading cause of mortality amongst hospitalized patients. Optimizing time to pathogen identification and receipt of appropriate antibiotic therapy significantly decreases mortality, morbidity, and length of hospitalization. Rapid diagnostic tests, such as Verigene, assist in the early identification of bacteria and resistance determinants from positive blood cultures; however, Verigene assays are limited to the detection of 13 gram-positive and 9 gram-negative bacteria. Methods The purpose of this study was to describe gram-negative and gram-positive aerobic bacteria identified from positive blood cultures with no Verigene target detected and to use the susceptibilities to create an antibiogram to assist in empiric antibiotic selection. A total of 2325 positive blood cultures resulted between January 2017 and October 2018 underwent Verigene testing. Results Of the 2325 isolates, 383 (16.5%), had no Verigene organism or resistance mechanism detected. Of these, there were 239 (62.4%) gram-positive isolates, 141 (36.8%) gram-negative isolates, and 3 yeast isolates with 96 unique organisms. Seventy-six (19.8%) of the organisms identified by standard culture, but not Verigene testing, are included on Verigene panel. We analyzed nine common antibiotics active against gram-negative organisms to determine percent susceptibilities against the isolated aerobic pathogens: amikacin (92.1%), cefepime (93.5%), ceftazidime (94.0%), ceftriaxone (79.7%), ciprofloxacin (88.5%), gentamicin (91.9%), levofloxacin (86.9%), piperacillin–tazobactam (83.8%), and tobramycin (85.5%). Additionally, four antibiotics active against gram-positive organisms were analyzed for gram-positive susceptibilities: cefotaxime (91.8%), ceftriaxone (98.1%), levofloxacin (82.5%), and vancomycin (91.8%). Conclusion The results of this study provide clinicians with antibiotic susceptibilities against organisms that were not identified through Verigene to better guide timely and appropriate antibiotic therapy against gram-negative and gram-positive aerobic bacteria. Disclosures All authors: No reported disclosures.

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70. Impact of the Accelerate Pheno™ System on Clinical and Antimicrobial Outcomes among Inpatients with Gram-Negative Bacteremia at a 528-bed Community Teaching Hospital

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.272 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S152-S153

Author(s):

William P DePasquale ◽

Mary L Staicu ◽

Sean Stainton ◽

Maryrose R Laguio-Vila ◽

Mindee Hite ◽

...

Keyword(s):

Blood Culture ◽

Antibiotic Therapy ◽

Median Time ◽

Blood Cultures ◽

Oral Antibiotic ◽

E Coli ◽

Oral Antibiotic Therapy ◽

Secondary Outcomes ◽

Klebsiella Spp ◽

Historical Controls

Abstract Background Traditional methods in blood culture analysis require 24-72 hours to yield identification (ID) and antimicrobial susceptibility testing (AST) results, which may contribute to the use of empiric broad-spectrum antibiotic therapy. Hence, the primary objective of this study was to determine the impact of rapid blood culture analysis with the Accelerate Pheno™ system (AXDX) on time to antibiotic de-escalation. Methods This was a single center, case-control analysis of adult inpatients with E. coli or Klebsiella spp. bacteremia. Cases were prospectively identified by the antimicrobial stewardship team between August and October 2020 after the implementation of AXDX in July 2020. Subjects were matched to historical controls (July 2018-July 2020) based on age (± 3 years), gender, source of infection, and identified organism. The primary outcome was time to antibiotic de-escalation and time to oral antibiotic therapy from the time of positive blood cultures. Secondary outcomes included hospital length of stay, 30-day mortality, 30-day readmission, and 60-day C. difficile infection. Outcomes were compared using descriptive and inferential statistics. Results Of 33 cases identified, 30 (91%) were matched with historical controls. E. coli bloodstream infection was identified in 24 (80%) subjects while Klebsiella spp. was identified in 6 (20%) subjects. The average age was 66 years (SD ± 19) and there was an even distribution of males and females in both groups. Other demographics were similar between groups. The median time to species identification [14 hours (IQR 13 – 18) vs 34 hours (29 – 39), p< 0.001) and AST [20 hours (19 – 37) vs 45 hours (38 – 51), p< 0.001] from laboratory registration was significantly shorter in cases. The average time to antibiotic de-escalation was 1.7 (±1.2) days for cases compared to 2 (±1.3) days for controls (p=0.460). Median time to oral antibiotic therapy from positive blood cultures was 2.9 (1.8 – 4.7) days for cases and 3.4 (2.5 – 5.1) days for controls (p=0.166). There were no significant differences in the secondary outcomes. Conclusion AXDX did not appear to have a significant impact on time to antibiotic de-escalation and time to oral antibiotic therapy. However, time to organism ID and AST results were significantly shorter in the AXDX cohort. Disclosures All Authors: No reported disclosures

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1001. Evaluation of the Clinical Efficacy and Safety of Oral Antibiotic Therapy for Streptococcus spp. Bloodstream Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.838 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S297-S298 ◽

Cited By ~ 1

Author(s):

Amy Kang ◽

Cynthia Bor ◽

Jamie Chen ◽

Michelle Gandawidjaja ◽

Emi Minejima

Keyword(s):

Antibiotic Therapy ◽

Oral Therapy ◽

Bloodstream Infections ◽

Hospital Length Of Stay ◽

Common Source ◽

Oral Antibiotic ◽

Efficacy And Safety ◽

Oral Antibiotic Therapy ◽

Definitive Therapy ◽

Step Down

Abstract Background Despite the severity and frequency of bloodstream infections (BSI), the effectiveness of oral definitive therapy remains unknown. The objective of this study was to evaluate the efficacy and safety of step down oral antibiotics for the treatment of Streptococcus spp. BSI. Methods This was a retrospective cohort study of adult, hospitalized patients with Streptococcus spp. BSI between June 2015 and June 2017. Patients were excluded if received <48 hours of antibiotic therapy or therapy was started >48 hours from first positive culture. Patients were grouped by receipt of step down oral antibiotic therapy (PO group) vs. full course IV therapy (IV group) and compared for demographics, clinical course, and outcomes. The primary outcome was 30-day mortality and hospital length of stay (LOS). The secondary outcomes included 30-day recurrence of BSI and adverse events (AEs). Results One hundred ninety-five patients met inclusion criteria; median age was 51 year old, 68% were male, 57% were Hispanic, and 71% had community-onset BSI. Sixty-four (33%) were treated with step down oral therapy. The most common source of bacteremia was pneumonia (21%); 8% had endocarditis. Comorbidities were similar between the groups, with diabetes being most common (IV 22% vs. PO 19%, P = 0.29). Severity of illness measured by need for ICU admission, initial lactate level, and SOFA score was similar between the two groups. S. viridans was the most frequent pathogen isolated (IV 28% vs. PO 27%, P = 0.87). Ceftriaxone (39%) for the IV group and levofloxacin (30%) for the PO group were the most common definitive therapy prescribed. PO group received 4 days of IV therapy prior to transition to orals. The IV group had significantly higher mortality rate (11% vs. 2%, P = 0.02) and longer LOS (median 9 days [IQR 5–18] vs. 5 days [4–7.75], P ≤ 0.01) compared with the PO group. 30-day recurrence (IV 2% vs. PO 5%, P = 0.40) and AEs (IV 2% vs. PO 3%, P = 0.60) were similar between the two groups. Conclusion In Streptococcus spp. BSI, step down oral antibiotic therapy was associated with a significantly shorter LOS compared with IV only therapy without compromise of clinical outcomes. Larger prospective trials evaluating step down oral therapy are warranted to confirm our results. Disclosures All authors: No reported disclosures.

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Association between preadmission oral antibiotic therapy and cerebrospinal fluid findings and sequelae caused by Haemophilus influenzae type b meningitis

The Pediatric Infectious Disease Journal ◽

10.1097/00006454-198611000-00005 ◽

1986 ◽

Vol 5 (6) ◽

pp. 626-632 ◽

Cited By ~ 55

Author(s):

SHELDON L. KAPLAN ◽

E. OʼBRIAN SMITH ◽

CATHY WILLS ◽

RALPH D. FEIGIN

Keyword(s):

Cerebrospinal Fluid ◽

Haemophilus Influenzae ◽

Antibiotic Therapy ◽

Haemophilus Influenzae Type ◽

Oral Antibiotic ◽

Haemophilus Influenzae Type B ◽

Type B ◽

Oral Antibiotic Therapy

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Variability in Oral Antibiotic Step-Down Therapy in the Management of Gram-Negative Bloodstream Infections

International Journal of Antimicrobial Agents ◽

10.1016/j.ijantimicag.2021.106451 ◽

2021 ◽

pp. 106451

Author(s):

Joshua T. Thaden ◽

Pranita D. Tamma ◽

Yohei Doi ◽

Nick Daneman

Keyword(s):

Bloodstream Infections ◽

Oral Antibiotic ◽

Gram Negative ◽

Step Down

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Effectiveness of early switching from intravenous to oral antibiotic therapy in Staphylococcus aureus prosthetic bone and joint or orthopedic metalware-associated infections

BMC Musculoskeletal Disorders ◽

10.1186/s12891-021-04191-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Hélène Boclé ◽

Jean-Philippe Lavigne ◽

Nicolas Cellier ◽

Julien Crouzet ◽

Pascal Kouyoumdjian ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Therapy ◽

Treatment Failure ◽

Cox Model ◽

University Hospital ◽

Empiric Antibiotic Therapy ◽

Oral Antibiotic ◽

Intravenous Antibiotic ◽

Oral Antibiotic Therapy ◽

Intravenous Antibiotic Therapy

Abstract Background The optimal duration of intravenous antibiotic therapy in Staphylococcus aureus prosthetic bone and joint infection has not been established. The objective of this study was to compare the effect of early and late intravenous-to-oral antibiotic switch on treatment failure. Patients and methods We retrospectively analyzed all adult cases of S. aureus prosthetic bone and joint or orthopedic metalware-associated infection between January 2008 and December 2015 in a French university hospital. The primary outcome was treatment failure defined as the recurrence of S. aureus prosthetic bone and joint or orthopedic metalware-associated infection at any time during or after the first line of medical and surgical treatment within 2 years of follow-up. A Cox model was created to assess risk factors for treatment failure. Results Among the 140 patients included, mean age was 60.4 years (SD 20.2), and 66% were male (n = 92). Most infections were due to methicillin-susceptible S. aureus (n = 113, 81%). The mean duration of intravenous antibiotic treatment was 4.1 days (SD 4.6). The majority of patients (119, 85%) had ≤5 days of intravenous therapy. Twelve patients (8.5%) experienced treatment failure. Methicillin-resistant S. aureus infections (HR 11.1; 95% CI 1.5–111.1; p = 0.02), obesity (BMI > 30 kg/m2) (HR 6.9; 95% CI1.4–34.4, p = 0.02) and non-conventional empiric antibiotic therapy (HR 7.1; 95% CI 1.8–25.2; p = 0.005) were significantly associated with treatment failure, whereas duration of intravenous antibiotic therapy (≤ 5 or > 5 days) was not. Conclusion There was a low treatment failure rate in patients with S. aureus prosthetic bone and joint or orthopedic metalware-associated infection with early oral switch from intravenous to oral antibiotic therapy.

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