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Development and implementation of a short duration antibiotic therapy algorithm for uncomplicated gram-negative bloodstream infections

Published online by Cambridge University Press:  04 May 2021

Esther Y. GolnabiOpen the ORCID record for Esther Y. Golnabi[Opens in a new window],
Kathryn Dzintars,
Fidelia Bernice,
Pranita D. Tamma,
Sara E. Cosgrove and
Edina Avdic
Esther Y. Golnabi*
Affiliation:
Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, Maryland
Kathryn Dzintars
Affiliation:
Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, Maryland
Fidelia Bernice
Affiliation:
Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, Maryland
Pranita D. Tamma
Affiliation:
Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Sara E. Cosgrove
Affiliation:
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Edina Avdic
Affiliation:
Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, Maryland
*
Author for correspondence: Esther Y. Golnabi, E-mail: esther.golnabi@utsouthwestern.edu
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Abstract

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Type
Research Brief
Information
Infection Control & Hospital Epidemiology , Volume 42 , Issue 9 , September 2021, pp. 1136 - 1138
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Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of The Society for Healthcare Epidemiology of America

A growing body of literature indicates that clinical outcomes are similar for patients with uncomplicated gram-negative bloodstream infections (uGNBSI) receiving short courses (7 days) and long courses (14 days) of antibiotic therapy. Reference Yahav, Franceschini and Koppel1–Reference Von dach, Albrich and Brunel3 Shorter courses have the potential to reduce the risk of antibiotic-related adverse events, slow the development of antimicrobial resistance, and decrease hospital length of stay (LOS). Reference Corey, Stryjewski and Everts4

We developed a treatment algorithm to identify patients eligible to receive 7 days of antibiotic therapy for uGNBSI and investigated the impact of an antibiotic stewardship intervention using the algorithm on the clinical outcomes of patients with uGNBSI.

Methods

Algorithm

A treatment algorithm combining evidence-based literature and clinical experience was developed by the authors to identify hospitalized adult patients with Enterobacteriaceae BSIs eligible for a 7-day treatment course and conversion to oral therapy (Supplementary Material online). Patients were eligible for 7-day therapy if they had an uGNBSI, defined as meeting all of the following criteria by day 5 (with day 1 being the date of blood culture collection): no current or expected neutropenia (absolute neutrophil count [ANC] ≤ 500 cells/µL); no hematopoietic stem-cell transplantation in the previous 12 months; no ongoing therapy for graft-versus-host disease; no solid-organ transplant (SOT); adequate source control; no evidence of metastatic infection; no evidence or risk of endovascular infection (eg, prosthetic valve, vascular graft); no ongoing fevers or need for fluid resuscitation or vasopressors; and no persistently positive blood cultures, if repeat blood cultures were obtained.

Intervention

Between November 11, 2019 and March 31, 2020, all patients with gram-negative BSIs were routinely monitored and reviewed by an infectious diseases pharmacist between 8 a.m. and 5 p.m. on weekdays. Clinical teams of patients eligible for a 7-day treatment course were contacted by an infectious diseases pharmacist between days 2 and 5 to discuss algorithm-compliant recommendations. Additionally, the algorithm was made available to all prescribers through institution-specific treatment guidelines.

Study design

A quasi-experimental study was performed to assess the impact of the antibiotic stewardship intervention on clinical outcomes for patients with GNBSIs between the intervention period and the same period in the previous year (November 11, 2018 to March 31, 2019). Demographic data, pre-existing medical conditions, Pitt bacteremia score, intensive care unit status, and other notable clinical and treatment characteristics were compared between the 2 periods to ensure that the baseline and intervention populations were similar. The primary outcome was the total inpatient and outpatient duration of antibiotic therapy. Secondary outcomes included the duration of intravenous therapy and length of stay. Recurrent BSIs with the same organisms and 30-day mortality were used as balancing metrics to assess whether the algorithm was associated with patient harm. Only first episodes of uGNBSI were included in the analysis. Patients receiving hospice care and those who died within 7 days of their culture collection were excluded.

Statistical analysis

A χ2 test was used to compare proportions for categorical variables, and the Mann-Whitney U test was used to compare medians and interquartile ranges for continuous variables. Because of the limited number of events in the baseline and intervention periods, an interrupted time-series analysis was not pursued. P values ≤.05 were used to indicate statistical significance. Data analysis was conducted using Stata version 15.0 software (StataCorp, College Station, TX).

Results

There were 345 patients with GNBSIs during the study periods, 142 in the baseline period and 203 in the intervention period. Of these, 55 (39%) and 59 (29%) patients, respectively, met criteria for 7-day therapy. Common reasons for not meeting criteria for 7-day therapy were SOT (30%), inadequate source control by day 5 (28%), and an ANC < 500 cells/µL (18%) (Supplementary Material online).

Baseline characteristics for eligible patients were similar between the study periods (Table 1). The most common causative organisms were Escherichia coli (48%) and Klebsiella spp (33%). The most common bacteremia sources were urinary (43%) and intra-abdominal (23%). More baseline-period patients had a catheter source and more intervention-period patients had a biliary source. The median duration of therapy was shorter in the intervention period (8 days vs 10 days; P = .04), as were the duration of intravenous antibiotic therapy (4 days vs 7 days; P = .004) and LOS (4 days vs 7 days; P = .029). We detected no difference in recurrent bacteremia or 30-day all-cause mortality between the 2 groups.

Table 1.

Baseline Characteristics and Clinical Outcomes in Patients Who Met Criteria for 7-Day Therapy for Gram-Negative Bloodstream Infections in the Baseline and Intervention Periods

Note. IQR, interquartile range; MDR, multidrug resistant; ICU, intensive care unit, MALDI-TOF, matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy.

a Based on values documented from 48 h prior to positive blood culture collected to day 1 of therapy. If multiple values were available during emergency and/or hospital admission, the most abnormal value recorded was included in the analysis.

b In both periods, MALDI-TOF was utilized for organism identification, and approximately a month after intervention period was started, GenMark Dx ePlex blood culture identification (GenMark Diagnostics, Carlsbad, CA) was implemented for organism identification.

c Baseline: E. coli (n=6), K. pneumoniae (n=1); Intervention: E. coli (n=5), K. pneumoniae (n=1), Enterobacter (non-cloacae complex) (n=1), P. mirabilis (n=1)

d Adjusted body weight was used for patients whose recorded weight is ≥30% above ideal body weight.

Discussion

Our intervention applying an algorithm for uGNBSIs resulted in shorter durations of both overall and intravenous antibiotic therapy as well as hospital LOS, without increases in recurrent bacteremia or 30-day mortality. The reduction in LOS was likely due to early transitions to oral step-down therapy, facilitating earlier discharge. Our study adds to the growing body of evidence suggesting that short-course therapy is safe and effective for uGNBSIs. Reference Yahav, Franceschini and Koppel1–Reference Von dach, Albrich and Brunel3

Our study is not generalizable to every patient with a GNBSI. We excluded patients with non-fermenting GNBSIs because of limited evidence for 7 days of therapy in non- Enterobacteriaceae BSIs; only ∼10% of patients in other uGNBSI duration studies consisted of these organisms. Reference Yahav, Franceschini and Koppel1,Reference Swamy and Sharma5 We also excluded patients with immunocompromising conditions, again due to limited evidence for safety in this population. However, Chotiprasitsakul et al Reference Chotiprasitsakul, Han and Cosgrove2 showed that the presence of immunocompromising conditions was not associated with clinical failure in patients with uGNBSI receiving short durations of therapy. Catheter source was more common in the baseline period and biliary source in the intervention period. Given that our institution guidelines previously recommended a 7-day course for catheter-associated GNBSI after removal, this imbalance was not likely a driver of duration differences observed between the 2 periods. The study was additionally limited by its single-center design, lack of a contemporaneous control group, retrospective nature, and small sample size.

Implementation of a treatment algorithm for 7-day therapy in patients with uGNBSIs was successful in reducing antibiotic exposure and LOS. Bolstered by several comparative effectiveness studies, including randomized controlled trial data, we believe that short-course therapy for uGNBSI is ripe for stewardship interventions.

Acknowledgments

The authors thank the clinical pharmacists at The Johns Hopkins Hospital for their assistance with antimicrobial stewardship interventions. The contents of the manuscript and research are entirely the responsibility of the authors and do not represent the official view of MSHP.

Financial support

Dr. Bae received the 2019 Maryland Society of Health System Pharmacists (MSHP) Trainee Research Grant from MSHP to support her attendance and poster presentation at IDWeek 2020.

Conflicts of interest

All authors report no conflicts of interest relevant to this article.

Supplementary material

To view supplementary material for this article, please visit https://doi.org/10.1017/ice.2021.166

Footnotes

PREVIOUS PRESENTATION. These data were presented as a poster at IDWeek 2020 on October 22, 2020, conducted virtually.

References

Yahav, D, Franceschini, E, Koppel, F, et al. Seven versus 14 days of antibiotic therapy for uncomplicated gram-negative bacteremia: a noninferiority randomized controlled trial. Clin Infect Dis 2019;69:1091–1098.CrossRefGoogle ScholarPubMed
Chotiprasitsakul, D, Han, JH, Cosgrove, SE, et al. Comparing the outcomes of adults with enterobacteriaceae bacteremia receiving short-course versus prolonged-course antibiotic therapy in a multicenter, propensity score-matched cohort. Clin Infect Dis 2018;66:172–177.CrossRefGoogle Scholar
Von dach, E, Albrich, WC, Brunel, AS, et al. Effect of C-reactive protein-guided antibiotic treatment duration, 7-day treatment, or 14-day treatment on 30-day clinical failure rate in patients with uncomplicated gram-negative bacteremia: a randomized clinical trial. JAMA 2020;323:2160–2169.CrossRefGoogle ScholarPubMed
Corey, GR, Stryjewski, ME, Everts, RJ. Short-course therapy for bloodstream infections in immunocompetent adults. Int J Antimicrob Agents 2009;34 suppl 4:S47–S51.CrossRefGoogle Scholar
Swamy, S, Sharma, R. Duration of treatment of gram-negative bacteremia: are shorter courses of antimicrobial therapy feasible? Infect Dis Clin Pract 2016;24:155–160.CrossRefGoogle Scholar
Figure 0

Table 1.Baseline Characteristics and Clinical Outcomes in Patients Who Met Criteria for 7-Day Therapy for Gram-Negative Bloodstream Infections in the Baseline and Intervention Periods

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