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Assessing antibiotic stewardship opportunities in the management of uncomplicated Enterobacterales bacteremia

Published online by Cambridge University Press:  25 September 2026

Chad Michael DittmarOpen the ORCID record for Chad Michael Dittmar[Opens in a new window],
Alexander Coughlin,
Melissa O’NealOpen the ORCID record for Melissa O’Neal[Opens in a new window],
Nicholas PiccicaccoOpen the ORCID record for Nicholas Piccicacco[Opens in a new window] and
Kristen GreeneOpen the ORCID record for Kristen Greene[Opens in a new window]
Chad Michael Dittmar*
Affiliation:
Pharmacy, Tampa General Hospital , Tampa, USA
Alexander Coughlin
Affiliation:
Pharmacy, The Johns Hopkins Hospital, Baltimore, USA
Melissa O’Neal
Affiliation:
Pharmacy, Tampa General Hospital , Tampa, USA
Nicholas Piccicacco
Affiliation:
Pharmacy, Tampa General Hospital , Tampa, USA
Kristen Greene
Affiliation:
Pharmacy, Tampa General Hospital , Tampa, USA
*
Corresponding author: Chad Michael Dittmar; Email: cdittmar11@gmail.com

Abstract

In this study of adult patients with uncomplicated Enterobacterales bloodstream infections, the median duration of antibiotic therapy was 12.3 days (IQR 9.6, 15). Compared to current literature, most patients had opportunities for shorter durations of therapy. Opportunities exist for antimicrobial stewardship programs to optimize antibiotic use for these infections.

Information

Type
Concise Communication
Information
Antimicrobial Stewardship & Healthcare Epidemiology , Volume 6 , Issue 1 , 2026, e298
Creative Commons
Creative Common License - CCCreative Common License - BYCreative Common License - NCCreative Common License - ND
This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided that no alterations are made and the original article is properly cited. The written permission of Cambridge University Press or the rights holder(s) must be obtained prior to any commercial use and/or adaptation of the article.
Copyright
© The Author(s), 2026. Published by Cambridge University Press on behalf of The Society for Healthcare Epidemiology of America

Introduction/Background

Bloodstream infections (BSIs) account for more than 500,000 infections annually in North America and contribute significantly to healthcare burden and poor patient outcomes. Reference Goto and Al-Hasan1 Enterobacterales spp. are common pathogens causing BSIs and confer a mortality rate >30%. Reference Goto and Al-Hasan1,Reference Kang, Kim and Park2 Initial management has centered around longer courses of intravenous (IV) antibiotic therapy; however, studies have assessed the safety and efficacy of oral therapy due to benefits of reducing length of stay (LOS), central-line-associated complications, and healthcare costs. Reference Bouwman, Pierce and Emberger3

Recent advancements in Enterobacterales BSI literature demonstrate oral antibiotics are non-inferior to IV antibiotics and shorter durations are non-inferior to longer durations for uncomplicated BSIs. Reference Heil, Bork and Abbo4 In a study by Yahav et al, 604 patients with uncomplicated gram-negative rod (GNR) BSIs were treated for either a 7-day or 14-day duration; no significant difference in mortality was seen, underscoring 7 days of therapy (DOT) was non-inferior to 14 days. Reference Yahav, Franceschini and Koppel5 Similarly, Tamma et al evaluated 30-day all-cause mortality for patients with uncomplicated GNR BSIs who transitioned to oral therapy. They found patients transitioned to oral antibiotics did not have a significant difference in 30-day mortality when compared to those who received exclusively IV therapy. Reference Tamma, Conley and Cosgrove6 Patients receiving oral therapy also had a significantly shorter LOS. Reference Tamma, Conley and Cosgrove6 These studies provide evidence to support 7-day durations for uncomplicated Enterobacterales BSIs and the use of oral antibiotics.

This emerging data can lead to significant cost savings and shorter inpatient LOS without compromising safety and efficacy. Despite this, providers may be hesitant to implement these changes into clinical practice. The purpose of this study is to evaluate current prescribing patterns and strategies for managing uncomplicated Enterobacterales BSIs at our institution.

Methods

This study evaluated patients with uncomplicated Enterobacterales BSIs between January 1, 2024, and December 31, 2024. Adult patients were included if they had an uncomplicated infection, positive blood culture(s) for prespecified Enterobacterales organism (Escherichia coli, Klebsiella spp., Citrobacter spp., Enterobacter spp., Serratia spp., or Proteus spp), and were able to transition to oral antibiotics. An uncomplicated infection was defined as a monomicrobial BSI confirmed or strongly suspected to be secondary to a urinary tract infection (UTI), intra-abdominal (IAI) or biliary infection, catheter-related BSI, pneumonia (without structural lung disease, empyema/abscess, or cystic fibrosis), or skin and soft tissue infection. Infections not meeting this definition were considered complicated and thus excluded. An uncomplicated infection presumed source control where appropriate and clinical improvement (ie, afebrile, hemodynamic stability, absence of leukocytosis) within 72 hours of effective antibiotics. Patients who were unable to take medications by mouth, failed swallow evaluation, had active gastrointestinal bleeding or recurrent emesis, or with documented allergies to susceptible oral antibiotics were considered to have an inability to transition to oral antibiotics. Patients were excluded if they had polymicrobial BSI, complicated infection, inability to obtain source control, solid organ transplant within the last year, received antibiotics >24 hours from the time of first positive blood culture, inability to transition to oral antibiotics, or expired within 48 hours from the first positive blood culture. This study was approved by the University of South Florida’s institutional review board (IRB #: STUDY008473).

The primary outcome was the total duration of antibiotic therapy (inpatient and prescribed outpatient (if applicable)). The duration of outpatient therapy was determined by electronic prescription data; adherence to outpatient prescriptions upon discharge was assumed. Secondary endpoints included time to oral therapy, hospital LOS, and 30-day hospital readmission with an infection related to the same organism. Time to oral therapy only included patients with confirmed susceptibility to oral therapy. Data was analyzed using descriptive statistics.

Results

We assessed 189 patients for study eligibility, and a total of 100 patients were included. Median age was 65 years with a qPitt bacteremia score of 1, and 51% of patients were male (Table 1). UTIs were the most common source of infection (60%) followed by IAI or biliary source (25%). The most common pathogens were E. coli (66%) and Klebsiella spp. (21%). Most patients (81%) had cultures with at least one susceptible oral antibiotic, and 62 (77%) of these patients were transitioned to oral therapy. Of patients transitioned to oral therapy, 36 patients (36/62, 58%) were transitioned to oral therapy at discharge.

Table 1.

Study results

A table summarizing patient demographics, infection characteristics, and distribution of oral antibiotics.
Table 1. Long description

A table with 25 rows and 4 columns. The table is divided into three sections: Patient demographics, Infection characteristics, and Distribution of oral antibiotics. Patient demographics include Age, Gender, Race, Diabetes, End Stage Renal Disease, Cirrhosis, qPitt bacteremia score, Active cancer treatment, and Solid organ transplant. Infection characteristics include Infection source and Pathogen. Distribution of oral antibiotics lists different antibiotics and the number and percentage of patients receiving each. Row 1: Age, yr, median (IQR), 65 (50.6, 73.5). Row 2: Gender, male, n (%), 51 (51 percent). Row 3: Caucasian, n (%), 62 (62 percent). Row 4: Black or African American, n (%), 22 (22 percent). Row 5: Hispanic or Latino, n (%), 15 (15 percent). Row 6: Asian, n (%), 1 (1 percent). Row 7: Diabetes, n (%), 23 (23 percent). Row 8: End Stage Renal Disease, n (%), 10 (10 percent). Row 9: Cirrhosis, n (%), 8 (8 percent). Row 10: qPitt bacteremia score, median (IQR), 1 (0, 2). Row 11: Active cancer treatment, n (%), 14 (14 percent). Row 12: Solid organ transplant, n (%), 9 (9 percent). Row 13: Infection source. Row 14: UTI, n (%), 60 (60 percent). Row 15: IAI or biliary source, n (%), 21 (21 percent). Row 16: Catheter-related, n (%), 6 (6 percent). Row 17: Pneumonia, n (%), 5 (5 percent). Row 18: Skin and soft tissue, n (%), 4 (4 percent). Row 19: Pathogen. Row 20: Escherichia coli, n (%), 66 (66 percent). Row 21: Klebsiella spp., n (%), 21 (21 percent). Row 22: Proteus spp., n (%), 5 (5 percent). Row 23: Enterobacter spp., n (%), 4 (4 percent). Row 24: Serratia spp., n (%), 4 (4 percent). Row 25: Distribution of oral antibiotics (n = 62). Row 26: Ciprofloxacin, n (%), 37 (60 percent). Row 27: Sulfamethoxazole-trimethoprim, n (%), 6 (10 percent). Row 28: Levofloxacin, n (%), 6 (10 percent). Row 29: Amoxicillin-clavulanate, n (%), 5 (8 percent). Row 30: Cefpodoxime, n (%), 4 (6 percent). Row 31: Cefdinir, n (%), 2 (3 percent). Row 32: Cephalexin, n (%), 2 (3 percent).

The primary outcome was 12.3 days (9.6, 15) (Figure 1). Patients were transitioned to oral therapy after a median of 4 days (3.2, 5.3), and the median hospital length of stay was 7.5 days (4, 14.8). No patients were readmitted within 30 days for a recurrent infection with the same organism. The most common oral antibiotics prescribed were ciprofloxacin (37/62, 60%), levofloxacin (6/62, 10%), and trimethoprim/sulfamethoxazole (6/62, 10%), followed by oral beta-lactams (Table 1).

Figure 1.

Median duration of antibiotic therapy.

A bar graph showing the number of patients by days of antibiotic therapy.

Discussion

In this study of uncomplicated Enterobacterales BSIs, most patients were treated longer than recommended by current literature, and there was significant variability in infection treatment. This data demonstrates DOTs for uncomplicated Enterobacterales BSI often exceed 7 days at our institution, despite publications demonstrating no additional benefit to longer DOTs. Reference Yahav, Franceschini and Koppel5 Additionally, this data underscores how transitions to oral therapy often occurred at discharge. This highlights opportunities for antimicrobial stewardship (AS) intervention, including education on shortening durations for qualifying patients, transitioning to oral therapy earlier, and ensuring discharge prescriptions are reconciled appropriately. It is worth highlighting that when transitioning to oral antibiotics, fluoroquinolones and TMP/SMX were frequently prescribed. This raises the possibility that, in circumstances where fluoroquinolones and TMP/SMX are resistant, providers may be hesitant to transition to susceptible oral cephalosporins or may be unfamiliar with data supporting their efficacy as oral options. Despite growing evidence of supporting literature for these uncomplicated BSIs, opportunities still exist for providers and AS to optimize antibiotic use for these infections.

Our study should be interpreted in the context of its assumptions and limitations. Since it was not feasible to ensure adherence upon hospital discharge, it was assumed every patient adhered to the entire duration of outpatient antibiotic prescription, if applicable. Therefore, this study does not account for the possibility of non-adherence after hospital discharge. Additionally, we did not compare DOTs for patients followed by an Infectious Diseases (ID) consult service versus those who were not. Furthermore, as hospital LOS is multifactorial, antibiotic utilization will not exclusively impact this outcome, and strict associations cannot be made.

Our study highlights opportunities to provide updates on contemporary data surrounding treatment of uncomplicated Enterobacterales BSIs. Education efforts should involve key stakeholders, including physicians, advanced practice providers, and pharmacists, who are involved in the ordering and reconciliation of antimicrobial therapy. Systematically, institutions may consider implementing auto stop dates for a 7-day duration when ordering antibiotics for uncomplicated BSIs to ensure an appropriate DOT and prevent prolonged treatment. Additionally, these efforts can also highlight the importance of considering patient age, comorbidities, and severity of illness which may influence patient outcomes. Future studies may consider analyzing the cost differential for patients who were treated with only IV antibiotics compared to those transitioned to oral therapy.

In summary, this study demonstrates real-world variability in the implementation of new literature and treatment of uncomplicated Enterobacterales BSIs. These findings underscore the opportunity for antimicrobial stewardship teams to provide education, make interventions according to published guidelines, and reduce costs for patients and healthcare system. Future studies should analyze the impact of educational interventions, ID consults, and additional institutional guidance on the treatment of these infections.

Acknowledgements

AC conducted the initial literature search, developed the study’s methods, and submitted the study for IRB approval. CD conducted data collection, data analysis, and manuscript preparation. NP, KG, and MO oversaw the process and provided feedback as preceptors.

Financial support

None reported.

Competing interests

All authors report no conflicts of interest relevant to this article. Research transparency and reproducibility. Contact corresponding author.

References

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Tamma, PD, Conley, AT, Cosgrove, SE, et al. Association of 30-day mortality with oral step-down vs continued intravenous therapy in patients hospitalized with Enterobacteriaceae bacteremia [published correction appears in JAMA Intern Med. 2019 Nov1;179(11):1607. doi: 10.1001/jamainternmed.2019.5480.]. JAMA Intern Med 2019;179:316–323. doi:10.1001/jamainternmed.2018.6226 CrossRefGoogle Scholar
Figure 0

Table 1.Study resultsTable 1 long description.

Figure 1

Figure 1.Median duration of antibiotic therapy.