Use of a Precision Antibiotic Therapy (PAT) Prediction Model to Identify Multidrug-Resistant (MDR) Enterobacteriaceae

Abstract Background Emergence of multidrug-resistant (MDR) Enterobacteriaceae complicates the selection of empiric antibiotic therapy. Software called Precision Antibiotic Therapy (PAT) (Teqqa, LLC; Jackson, WY) operationalizes a predictive model using patient factors to make real-time, personalized predictions of antibiotic susceptibility for each antibiotic, allowing prescribers to choose empiric therapy for patients at risk for resistant infections. The purpose of this study was to determine the performance of PAT software in identifying MDR Enterobacteriaceaebloodstream infections (BSI) as well as to determine optimal thresholds of predicted antibiotic susceptibility to choose a broader-spectrum antibiotic. Methods We conducted a retrospective cohort study including 475 unique patients with BSIs caused by Enterobacteriaceaefrom January 1, 2016 through December 31, 2016. First-line antibiotic therapy for BSI was defined as cefepime, piperacillin-tazobactam, levofloxacin, or aztreonam. Susceptibilities predicted by PAT were compared with known susceptibilities determined by routine laboratory testing. PAT thresholds for broadening antibiotics were assessed when predicted susceptibilities were 80%, 85%, 90%, and 95% using receiver-operating characteristic (ROC) curves. Performance characteristics were calculated for each threshold. Brier score calculations were then used to compare the accuracy of PAT predictions using the optimized predicted susceptibility threshold, to that of aggregate institutional susceptibility data. Results ROC curve analysis demonstrated an area under the curve of 0.82 for the 95% threshold. The sensitivity for the PAT prediction utilizing the 95% threshold was 91.7% with a specificity of 74.3%. The Brier score for the 2016 antibiogram to determine antibiotic therapy was 0.085, whereas the Brier score using PAT software was 0.071, representing a 16% improvement in accuracy. Conclusion PAT software demonstrated excellent capability to discriminate between Enterobacteriaceae BSIs resistant and susceptible to first-line therapy. A predicted susceptibility threshold of 95% should be used to indicate a need for escalation of empiric antibiotic therapy using PAT. Disclosures All authors: No reported disclosures.

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Antibiotic Prescribing Evaluation in an Outpatient Hemodialysis Clinic

Journal of Pharmacy Technology ◽

10.1177/875512250201800303 ◽

2002 ◽

Vol 18 (3) ◽

pp. 128-132 ◽

Cited By ~ 3

Author(s):

Harold J Manley ◽

Michael A Huke ◽

Mark A Dykstra ◽

Angela V Bedenbaugh

Keyword(s):

Antibiotic Therapy ◽

Empiric Therapy ◽

Prescribing Patterns ◽

Empiric Antibiotic Therapy ◽

Antibiotic Prescribing ◽

Gram Positive ◽

Hospital Infection Control ◽

Empiric Antibiotic ◽

Control And Prevention ◽

Gram Negative Organisms

Background Empiric vancomycin treatment is frequently used in hemodialysis (HD) patients because of ease of administration when methicillin-resistant Staphylococcus aureus (MRSA) infection is suspected. Differing rates of MRSA indicate that empiric antibiotic treatment should be based on a center-specific antibiogram. Objective To develop a center-specific antibiogram, evaluate antibiotic prescribing patterns, and determine areas of improvement in infection treatment. Methods The antibiogram was constructed from culture and susceptibility (C&S) data from January through December 1999. Evaluation of prescribing habits was based on 3 criteria: (1) Hospital Infection Control Practices Advisory Committee and Centers for Disease Control and Prevention guidelines; (2) vancomycin for 1 dose followed by appropriate antibiotic based on C&S results; and (3) C&S obtained with more than 1 dose of antibiotic. Results HD was provided to 161 patients during the study period. Antibiotics were empirically prescribed 104 times in 62 different patients. Cultures were obtained 122 times, and 67 different isolates were identified. Gram-positive organisms and gram-negative organisms accounted for 77.6% and 22.4% of isolates, respectively. Gram-positive organisms were identified as Staphylococcus spp. (53.8%); 17.9% of the staphylococcal isolates were MRSA strains. No isolates of vancomycin-resistant enterococcus were identified. Based on the antibiogram, empiric antibiotic therapy within our center should be 1 dose each of vancomycin and an aminoglycoside. Empiric vancomycin was used 71 times. When criterion I is used, 12 prescriptions (16.9%) were considered appropriate. When criterion II and adjustment for MRSA reported for our center were used, 46 (64.8%) vancomycin prescriptions were considered appropriate. Forty-one patients had more than 1 dose of antibiotic therapy, and 18 (43.9%) of those patients did not have C&S data obtained as prescribed by criterion III. Areas of prescribing improvement include obtaining a C&S in all suspected infections prior to empiric therapy and a more aggressive antibiotic switch based on C&S results. Conclusions Antibiograms can be used to determine appropriate empric antibiotic therapy and identify areas of improvement.

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Empiric antibiotic therapy in a child with cancer and suspected septicemia

Pediatric Reports ◽

10.4081/pr.2012.e2 ◽

2012 ◽

Vol 4 (1) ◽

pp. 2 ◽

Cited By ~ 4

Author(s):

Desiree Caselli ◽

Olivia Paolicchi

Keyword(s):

Antibiotic Therapy ◽

Supportive Therapy ◽

Empiric Therapy ◽

Infectious Complications ◽

Empiric Antibiotic Therapy ◽

Beta Lactam ◽

Blood Tests ◽

Empiric Antibiotic ◽

Lactam Antibiotic ◽

Life Threatening

Improved outcome in the treatment of in childhood cancer results not only from more aggressive and tailored cancer-directed therapy, but also from improved supportive therapy and treatment of life-threatening infectious complications. Prompt and aggressive intervention with empiric antibiotics has reduced the mortality in this group of patients. Physical examination, blood tests, and blood cultures must be performed, and antibiotic therapy must be administered as soon as possible. Beta-lactam monotherapy, such as piperacillin-tazobactam or cefepime, may be an appropriate empiric therapy of choice for all clinically stable patients with neutropenic fever. An anti-pseudomonal beta-lactam antibiotic plus gentamicin is recommended for patients with systemic compromise.

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The Role of Adjunctive Therapies in Septic Shock by Gram Negative MDR/XDR Infections

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2017/2808203 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Stefano Busani ◽

Erika Roat ◽

Giulia Serafini ◽

Elena Mantovani ◽

Emanuela Biagioni ◽

...

Keyword(s):

Septic Shock ◽

Antibiotic Therapy ◽

Multidrug Resistant ◽

Blood Purification ◽

Empiric Antibiotic Therapy ◽

Alternative Strategies ◽

Immune Paralysis ◽

Empiric Antibiotic ◽

The Relationship

Patients with septic shock by multidrug resistant microorganisms (MDR) are a specific sepsis population with a high mortality risk. The exposure to an initial inappropriate empiric antibiotic therapy has been considered responsible for the increased mortality, although other factors such as immune-paralysis seem to play a pivotal role. Therefore, beyond conventional early antibiotic therapy and fluid resuscitation, this population may benefit from the use of alternative strategies aimed at supporting the immune system. In this review we present an overview of the relationship between MDR infections and immune response and focus on the rationale and the clinical data available on the possible adjunctive immunotherapies, including blood purification techniques and different pharmacological approaches.

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127. Living on the Edge: The Impact of MIC Distributions on Empiric Antibiotic Selection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.329 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S176-S177

Author(s):

Karri A Bauer ◽

Levita K Hidayat ◽

Kenneth Klinker ◽

Mary Motyl ◽

C Andrew DeRyke

Keyword(s):

Pseudomonas Aeruginosa ◽

Critically Ill ◽

Critically Ill Patients ◽

Antibiotic Susceptibility ◽

Empiric Therapy ◽

First Line ◽

Similar Frequency ◽

Empiric Antibiotic ◽

The Impact ◽

Susceptibility Breakpoint

Abstract Background Due to variability in the precision of an MIC, concern may exist in optimizing PK/PD using standard doses when the MIC is at the susceptibility breakpoint (SBP). This is notable when treating infections in critically ill patients. Evaluating MIC distributions among commonly used antibiotics and accounting for isolates at the SBP represents an additional enhancement to inform empiric therapy. The aim of the study was to evaluate antibiotic susceptibility for commonly used β-lactams against Pseudomonas aeruginosa (PA) in a syndromic antibiogram, incorporating MIC distribution. Methods 20 US institutions submitted yearly up to 250 consecutive targeted Gram-negative pathogens from hospitalized patients as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) in 2016-2019. MICs were determined by broth microdilution and interpreted using 2021 CLSI breakpoints. The syndromic antibiogram included PA from a blood or respiratory source based on patient location. Based on CLSI guidance, an empiric antibiotic susceptibility threshold of ≥ 90% was deemed optimal. Results 2,500 PA blood (n=680) and respiratory (n=1,820) isolates were evaluated; piperacillin/tazobactam (P/T), cefepime (FEP), meropenem (MEM), and ceftolozane/tazobactam (C/T) susceptibilities were 69.6%, 74.2%, 75.3%, and 95%, respectively (Figure 1). Isolates with MICs at the SBP were observed in 12.1%, 18.7%, 7.5%, and 6.5% for P/T, FEP, MEM, and C/T, respectively. Susceptibilities were lower when stratified by ICU, 64.8%, 71.2%, 70.7%, and 93.7% for P/T, FEP, MEM, and C/T, respectively with a similar frequency of SBP isolates (Figure 2). Figure 1. Syndromic antibiogram evaluating P. aeruginosa blood and respiratory isolates. Figure 2. Syndromic antibiogram evaluating Pseudomonas aeruginosa blood and respiratory isolates stratified by ICU. *MIC breakpoints used to determine susceptibility included: P/T MIC ≤ 16/4 µg/ml, FEP ≤ 8 µg/ml, MEM ≤ 2 µg/ml, C/T ≤ 4 µg/ml Conclusion Our analysis demonstrated that first line antipseudomonal agents, P/T and FEP, have susceptibility rates lower than the CLSI recommended threshold. A significant portion of the MICs within the susceptible range are at the SBP. Due to the frequency of baseline resistance and challenge in achieving adequate PK/PD in critically ill patients, clinicians may be concerned with relying on certain antibiotics when the MIC is at the SBP. Antimicrobial stewardship programs should consider incorporating MIC distributions into syndromic antibiograms to better inform empiric therapy recommendations. Disclosures Karri A. Bauer, PharmD, Merck & Co., Inc. (Employee, Shareholder) Levita K. Hidayat, PharmD BCIDP, Merck & Co., Inc. (Employee, Shareholder) Kenneth Klinker, PharmD, Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co., Inc. (Employee, Shareholder) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder)

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Influence of Antibiotic Susceptibility Testing on Antibiotic Choice in Hospital-Acquired and Ventilator-Associated Pneumonia

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.1204 ◽

2020 ◽

Vol 41 (S1) ◽

pp. s520-s521

Author(s):

Taissa Zappernick ◽

Robbie Christian ◽

Sharanie Sims ◽

Brigid Wilson ◽

Federico Perez ◽

...

Keyword(s):

Antibiotic Therapy ◽

Antibiotic Susceptibility ◽

Susceptibility Testing ◽

Empiric Antibiotic Therapy ◽

Ventilator Associated Pneumonia ◽

Antibiotic Susceptibility Testing ◽

Bacterial Identification ◽

Respiratory Sample ◽

Empiric Antibiotic ◽

Hospital Acquired

Background: The survival of patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) is largely determined by the timely administration of effective antibiotic therapy. Guidelines for the treatment HAP and VAP recommend empiric treatment with broad-spectrum antibiotics and tailoring of antibiotic therapy once results of microbiological testing are available. Objective: We examined the influence of bacterial identification and antibiotic susceptibility testing on antibiotic therapy for patients with HAP or VAP. Methods: We used the US Veterans’ Health Administration (VHA) database to identify a retrospective cohort of patients diagnosed with HAP or VAP between fiscal year 2015 and 2018. We further analyzed patients who were started on empiric antibiotic therapy, for whom microbiological test results from a respiratory sample were available within 7 days and who were alive within 48 hours of sample collection. We used the antibiotic spectrum index (ASI) to compare antibiotics prescribed the day before and the day after availability of bacterial identification and antibiotic susceptibility testing results. Results: We identified 4,669 cases of HAP and VAP in 4,555 VHA patients. The median time from respiratory sample receipt in the laboratory to final result of bacterial identification and antibiotic susceptibility testing was 2.22 days (IQR, 1.31–3.38 days). The most common pathogen was Staphylococcus aureus (n = 994), with methicillin resistance in 58% of those isolates tested. The next most common pathogen was Pseudomonas spp (n = 946 isolates). The susceptibility of antipseudomonal antibiotics, when tested, was as follows: 64% to carbapenems, 74% to cephalosporins, 75% to β-lactam/β-lactamase inhibitors, 69% to fluoroquinolones, and 95% to amikacin. Lactose-fermenting gram-negative bacteria (296 Escherichia coli and 360 Klebsiella pneumoniae) were also common. Among the 3,094 cases who received empiric antibiotic therapy, 607 (20%) had antibiotics stopped the day after antibiotic susceptibility results became available, 920 (30%) had a decrease in ASI, 1,075 (35%) had no change in ASI, and 492 (16%) had an increase in ASI (Fig. 1). Among the 1,098 patients who were not started on empiric antibiotic therapy, only 154 (14%) were started on antibiotic therapy the day after antibiotic susceptibility results became available. Conclusions: Changes in antibiotic therapy occurred in at least two-thirds of cases the day after bacterial identification and antibiotic susceptibility results became available. These results highlight how respiratory cultures can inform the treatment and improve antibiotic stewardship for patients with HAP/VAP.Funding: This study was supported by Accelerate Diagnostics.Disclosures: None

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Using the Association Between Antibiotic Susceptibility and Genetic Relatedness to Rescue Old Drugs for Empiric Use

10.1101/19006106 ◽

2019 ◽

Author(s):

Derek R MacFadden ◽

Bryan Coburn ◽

Karel Břinda ◽

Antoine Corbeil ◽

Nick Daneman ◽

...

Keyword(s):

Escherichia Coli ◽

Antibiotic Susceptibility ◽

Genetic Relatedness ◽

Model Performance ◽

Empiric Therapy ◽

Empiric Antibiotic Therapy ◽

Phenotypic Data ◽

Oral Agents ◽

Empiric Antibiotic ◽

Treatment Adequacy

AbstractBackgroundRising rates of antibiotic resistance have led to the use of broader spectrum antibiotics and increasingly compromise empiric therapy. Knowing the antibiotic susceptibility of a pathogen’s close genetic relative(s) may improve empiric antibiotic selection.MethodsUsing genomic and phenotypic data from three separate clinically-derived databases of Escherichia coli isolates, we evaluated multiple genomic methods and statistical models for predicting antibiotic susceptibility, focusing on potentially rapidly available information such as lineage or genetic distance from archived isolates. We applied these methods to derive and validate prediction of antibiotic susceptibility to common antibiotics.ResultsWe evaluated 968 separate episodes of suspected and confirmed infection with Escherichia coli from three geographically and temporally separated databases in Ontario, Canada, from 2010-2018. The most common sequence type (ST) was ST131 (30%). Antibiotic susceptibility to ciprofloxacin and trimethoprim-sulfamethoxazole were lowest (<=72%). Across all approaches, model performance (AUC) ranges for predicting antibiotic susceptibility were greatest for ciprofloxacin (0.76-0.97), and lowest for trimethoprim-sulfamethoxazole (0.51-0.80). When a model predicted a susceptible isolate, the resulting (post-test) probabilities of susceptibility were sufficient to warrant empiric therapy for most antibiotics (mean 92%). An approach combining multiple models could permit the use of narrower spectrum oral agents in 2 out of every 3 patients while maintaining high treatment adequacy (∼90%).ConclusionsMethods based on genetic relatedness to archived samples in E. coli could be used to rescue older and typically unsuitable agents for use as empiric antibiotic therapy, as well as improve decisions to select newer broader spectrum agents.SummaryRapid genomic approaches that capitalize on the association between genetic relatedness and phenotype can improve our selection of antibiotics, allowing us to rescue older drugs for empiric use and better select newer and broader spectrum agents.

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