Integrating rapid diagnostics and antimicrobial stewardship improves outcomes in patients with antibiotic-resistant Gram-negative bacteremia

Abstract Background Initiating early effective antimicrobial therapy is the most important intervention demonstrated to decrease mortality in patients with gram-negative bacteremia with sepsis. Rapid MIC-based susceptibility results make it possible to optimize antimicrobial use through both escalation and de-escalation. Method We prospectively evaluated the performance of the Accelerate Pheno™ system (AXDX) for identification and susceptibility testing of gram-negative species and compared the time to result between AXDX and routine standard of care (SOC) using 82 patient samples and 18 challenge organisms with various confirmed resistance mechanisms. The potential impact of AXDX on time to antimicrobial optimization was investigated with various simulated antimicrobial stewardship (ASTEW) intervention models. Results The overall positive and negative percent agreement of AXDX for identification were 100 and 99.9%, respectively. Compared to VITEK® 2, the overall essential agreement was 96.1% and categorical agreement was 95.4%. No very major or major errors were detected. AXDX reduced the time to identification by an average of 11.8 h and time to susceptibility by an average of 36.7 h. In 27 patients evaluated for potential clinical impact of AXDX on antimicrobial optimization, 18 (67%) patients could potentially have had therapy optimized sooner with an average of 18.1 h reduction in time to optimal therapy. Conclusion Utilization of AXDX coupled with simulated ASTEW intervention notification substantially shortened the time to potential antimicrobial optimization in this cohort of patients with gram-negative bacteremia. This improvement in time occurred when ASTEW support was limited to an 8-h coverage model.

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Prior colonization is associated with increased risk of antibiotic-resistant Gram-negative bacteremia in cancer patients

Diagnostic Microbiology and Infectious Disease ◽

10.1016/j.diagmicrobio.2014.01.022 ◽

2014 ◽

Vol 79 (1) ◽

pp. 73-76 ◽

Cited By ~ 8

Author(s):

Aaron S. Hess ◽

Michael Kleinberg ◽

John D. Sorkin ◽

Giora Netzer ◽

Jennifer K. Johnson ◽

...

Keyword(s):

Cancer Patients ◽

Antibiotic Resistant ◽

Gram Negative ◽

Increased Risk ◽

Gram Negative Bacteremia

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Bloodstream Infections Caused by Antibiotic-Resistant Gram-Negative Bacilli: Risk Factors for Mortality and Impact of Inappropriate Initial Antimicrobial Therapy on Outcome

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.2.760-766.2005 ◽

2005 ◽

Vol 49 (2) ◽

pp. 760-766 ◽

Cited By ~ 387

Author(s):

Cheol-In Kang ◽

Sung-Han Kim ◽

Wan Beom Park ◽

Ki-Deok Lee ◽

Hong-Bin Kim ◽

...

Keyword(s):

Risk Factors ◽

High Risk ◽

Mortality Rate ◽

Antimicrobial Therapy ◽

Treated Group ◽

Antibiotic Resistant ◽

Gram Negative ◽

Gram Negative Bacteremia ◽

Initial Antimicrobial Therapy ◽

Risk Source

ABSTRACT The marked increase in the incidence of infections due to antibiotic-resistant gram-negative bacilli in recent years is of great concern, as patients infected by those isolates might initially receive antibiotics that are inactive against the responsible pathogens. To evaluate the effect of inappropriate initial antimicrobial therapy on survival, a total of 286 patients with antibiotic-resistant gram-negative bacteremia, 61 patients with Escherichia coli bacteremia, 65 with Klebsiella pneumoniae bacteremia, 74 with Pseudomonas aeruginosa bacteremia, and 86 with Enterobacter bacteremia, were analyzed retrospectively. If a patient received at least one antimicrobial agent to which the causative microorganisms were susceptible within 24 h of blood culture collection, the initial antimicrobial therapy was considered to have been appropriate. High-risk sources of bacteremia were defined as the lung, peritoneum, or an unknown source. The main outcome measure was 30-day mortality. Of the 286 patients, 135 (47.2%) received appropriate initial empirical antimicrobial therapy, and the remaining 151 (52.8%) patients received inappropriate therapy. The adequately treated group had a 27.4% mortality rate, whereas the inadequately treated group had a 38.4% mortality rate (P = 0.049). Multivariate analysis showed that the significant independent risk factors of mortality were presentation with septic shock, a high-risk source of bacteremia, P. aeruginosa infection, and an increasing APACHE II score. In the subgroup of patients (n = 132) with a high-risk source of bacteremia, inappropriate initial antimicrobial therapy was independently associated with increased mortality (odds ratio, 3.64; 95% confidence interval, 1.13 to 11.72; P = 0.030). Our data suggest that inappropriate initial antimicrobial therapy is associated with adverse outcome in antibiotic-resistant gram-negative bacteremia, particularly in patients with a high-risk source of bacteremia.

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Automated Alerts Coupled with Antimicrobial Stewardship Intervention Lead to Decreases in Length of Stay in Patients with Gram-Negative Bacteremia

Infection Control and Hospital Epidemiology ◽

10.1086/674849 ◽

2014 ◽

Vol 35 (2) ◽

pp. 132-138 ◽

Cited By ~ 40

Author(s):

Jason M. Pogue ◽

Ryan P. Mynatt ◽

Dror Marchaim ◽

Jing J. Zhao ◽

Viktorija O. Barr ◽

...

Keyword(s):

Length Of Stay ◽

Blood Culture ◽

Antimicrobial Stewardship ◽

Positive Blood Culture ◽

Medical Center ◽

Intervention Group ◽

Gram Negative ◽

Gram Negative Bacteremia ◽

Appropriate Therapy ◽

The Impact

Objective.To assess the impact of active alerting of positive blood culture data coupled with stewardship intervention on time to appropriate therapy, length of stay, and mortality in patients with gram-negative bacteremia.Design.Quasi-experimental retrospective cohort study in patients with gram-negative bacteremia at the Detroit Medical Center from 2009 to 2011.Setting.Three hospitals (1 community, 2 academic) with active antimicrobial stewardship programs within the Detroit Medical Center.Patients.All patients with monomicrobial gram-negative bacteremia during the study period.Intervention.Active alerting of positive blood culture data coupled with stewardship intervention (2010-2011) compared with patients who received no formalized stewardship intervention (2009).Results.Active alerting and intervention led to a decreased time to appropriate therapy (8 [interquartile range (IQR), 2-24] vs 14 [IQR, 2-35] hours; P = .014) in patients with gram-negative bacteremia. After controlling for differences between groups, being in the intervention arm was associated with an independent reduction in length of stay (odds ratio [OR], 0.73 [95% confidence interval (CI), 0.62-0.86]), correlating to a median attributable decrease in length of stay of 2.2 days. Additionally, multivariate modeling of patients who were not on appropriate antimicrobial therapy at the time of initial culture positivity showed that patients in the intervention group had a significant reduction in both length of stay (OR, 0.76 [95% CI, 0.66-0.86]) and infection-related mortality (OR, 0.24 [95% CI, 0.08-0.76]).Conclusions.Active alerting coupled with stewardship intervention in patients with gram-negative bacteremia positively impacted time to appropriate therapy, length of stay, and mortality and should be a target of antimicrobial stewardship programs.

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Impact of antimicrobial stewardship and rapid microarray testing on patients with Gram-negative bacteremia

European Journal of Clinical Microbiology & Infectious Diseases ◽

10.1007/s10096-017-3008-6 ◽

2017 ◽

Vol 36 (10) ◽

pp. 1879-1887 ◽

Cited By ~ 24

Author(s):

K. R. Rivard ◽

V. Athans ◽

S. W. Lam ◽

S. M. Gordon ◽

G. W. Procop ◽

...

Keyword(s):

Antimicrobial Stewardship ◽

Gram Negative ◽

Gram Negative Bacteremia

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Impact of a Pharmacist-Led Antimicrobial Stewardship Program on the Number of Days of Antimicrobial Therapy for Uncomplicated Gram-Negative Bacteremia in a Community Hospital

Cureus ◽

10.7759/cureus.14635 ◽

2021 ◽

Author(s):

Tetsuya Fukuda ◽

Kentaro Tanuma ◽

Satoru Iio ◽

Jympei Saito ◽

Makoto Komura ◽

...

Keyword(s):

Antimicrobial Stewardship ◽

Antimicrobial Therapy ◽

Community Hospital ◽

Antimicrobial Stewardship Program ◽

Gram Negative ◽

Stewardship Program ◽

Gram Negative Bacteremia

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Antibiotic-Resistant Bacteremia in Young Children Hospitalized With Pneumonia in Bangladesh Is Associated With a High Mortality Rate

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab260 ◽

2021 ◽

Vol 8 (7) ◽

Author(s):

Mohammod Jobayer Chisti ◽

Jason B Harris ◽

Ryan W Carroll ◽

K M Shahunja ◽

Abu S M S B Shahid ◽

...

Keyword(s):

Mortality Rate ◽

Young Children ◽

High Mortality ◽

Diarrhoeal Disease ◽

Salmonella Typhi ◽

Antibiotic Resistant ◽

Gram Negative ◽

Empiric Antibiotics ◽

Risk Of Death ◽

Gram Negative Bacteremia

Abstract Background Pneumonia is a leading cause of sepsis and mortality in children under 5 years. However, our understanding of the causes of bacteremia in children with pneumonia is limited. Methods We characterized risk factors for bacteremia and death in a cohort of children admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) between 2014 and 2017 with radiographically confirmed pneumonia. Results A total of 4007 young children were hospitalized with pneumonia over the study period. A total of 1814 (45%) had blood cultures obtained. Of those, 108 (6%) were positive. Gram-negative pathogens predominated, accounting for 83 (77%) of positive cultures. These included Pseudomonas (N = 22), Escherichia coli (N = 17), Salmonella enterica (N = 14, including 11 Salmonella Typhi), and Klebsiella pneumoniae (N = 11). Gram-positive pathogens included Pneumococcus (N = 7) and Staphylococcus aureus (N = 6). Resistance to all routinely used empiric antibiotics (ampicillin, gentamicin, ciprofloxacin, and ceftriaxone) for children with pneumonia at the icddr,b was observed in 20 of the 108 isolates. Thirty-one of 108 (29%) children with bacteremia died, compared to 124 of 1706 (7%) who underwent culture without bacteremia (odds ratio [OR], 5.1; 95% confidence interval [CI], 3.3–8.1; P < .001). Children infected with bacteria resistant to all routinely used empiric antibiotics were at greater risk of death compared to children without bacteremia (OR, 17.3; 95% CI, 7.0–43.1; P < .001). Conclusions Antibiotic-resistant Gram-negative bacteremia in young children with pneumonia in Dhaka, Bangladesh was associated with a high mortality rate. The pandemic of antibiotic resistance is shortening the lives of young children in Bangladesh, and new approaches to prevent and treat these infections are desperately needed.

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Rapid identification of gram-negative bacteremia and impact on antipseudomonal antibiotic consumption with antimicrobial stewardship at a community hospital system

Journal of the American College of Clinical Pharmacy ◽

10.1002/jac5.1013 ◽

2018 ◽

Vol 2 (1) ◽

pp. 26-31

Author(s):

Maggie J. Box ◽

Jennifer M. Lee ◽

Courtney D. Ortiz ◽

Kristine N. Ortwine ◽

Caitlin A. Richardson ◽

...

Keyword(s):

Antimicrobial Stewardship ◽

Community Hospital ◽

Antibiotic Consumption ◽

Rapid Identification ◽

Hospital System ◽

Gram Negative ◽

Gram Negative Bacteremia

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2006. Evaluation of Rapid Blood Culture Identification with Antimicrobial Stewardship Treatment Recommendations at a Community Health System in Patients with Gram-negative Bacteremia: Adequacy, Adherence, and Outcomes

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1686 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S673-S674

Author(s):

Erin Deja ◽

Jeremy J Frens

Keyword(s):

Blood Culture ◽

Antimicrobial Stewardship ◽

Treatment Algorithm ◽

Resistance Mechanism ◽

Treatment Recommendations ◽

Gram Negative ◽

Gram Negative Bacteremia ◽

Adequate Coverage ◽

Culture Identification ◽

Organism Identification

Abstract Background Sepsis mortality is greatly affected by the timely receipt of appropriate antibiotics. FilmArray Blood Culture Identification (BCID) is used at Cone Health to identify organisms in blood cultures within one to 2 hours after growth detected. The Cone Health antimicrobial stewardship (AMS) team has created treatment recommendations for each organism and resistance mechanism identifiable by BCID. Results and antibiotic recommendations are communicated in real time to providers by clinical pharmacists. The purpose of this evaluation was to validate the adequacy of antibiotics recommended by the BCID treatment algorithm for Gram-negative rods (GNR); assess proper implementation of the BCID notification procedure; and evaluate its effect on AMS. Methods Patients with GNR BCID results in January and April 2018 were retrospectively identified. Information collected for each patient included: demographics, location, organism, admission antibiotics, pharmacist compliance with BCID procedure, recommendation acceptance rate, organism susceptibility, changes to antibiotics post-BCID and final cultures, extended-spectrum β-lactamase (ESBL) incidence, length of antibiotic therapy, and patient outcome. Results A total of 101 patients were evaluated. The BCID treatment algorithm recommendations covered 97% of identified organisms (Figures 1–4). Resistant isolates were ESBL producers. Pharmacist antibiotic recommendations matched the treatment algorithm 66% of the time. Providers accepted 90% of pharmacist recommendations. Twenty-two percent of antibiotics were not de-escalated after BCID results without identifiable reason. Conclusion The BCID treatment algorithm provided adequate coverage for nearly all identified organisms, except ESBLs. However, patients with ESBL organisms all survived to hospital discharge. Pharmacists are following the BCID protocol in a majority of cases. One-third of recommendations deviated from the algorithm but only 17% did not have documented reasoning. Providers are very receptive to pharmacist input, with only 8% of recommendations rejected without documented reasoning. Finally, nearly a quarter of empiric antibiotics were not de-escalated despite organism identification, which represents opportunity for improvement. Disclosures All authors: No reported disclosures.

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