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Antimicrobial stewardship programs play an important role
in the development of institutional management guidelines in
hospitalized patients with serious infections.8 Modification of
national guidelines to tailor to the specific characteristics of an
institution is an important step in development of local guidelines. However, lack of national guidelines for management of
Gram-negative BSI emphasizes the need for antimicrobial
stewardship programs to develop institutional management
recommendations to guide empirical antimicrobial therapy
based on local data. The aim of the study was to develop institutional guidelines for empirical antimicrobial therapy of
Gram-negative BSI based on site of infection acquisition,
local bloodstream antibiogram, and acute severity of illness.
Methods
Setting
The study was conducted at Palmetto Health Richland and
Baptist hospitals in Columbia, SC, USA. The two hospitals
predominantly serve the population of Richland County and
surrounding counties in central South Carolina. Restricted
antimicrobial agents with Gram-negative activity at both
hospital formularies at the time of study included carbapenems, ceftaroline, and tigecycline. The Institutional Review
Board of the two hospitals approved the study and waived
informed consent.
Definitions
Gram-negative BSI was defined as the growth of any aerobic
Gram-negative bacillus in a blood culture. The source of BSI
was defined according to the Centers for Disease Control and
Prevention (CDC) criteria.9 The site of infection acquisition
was classified into community-acquired, health care-associated, and hospital-acquired as previously defined.10 Adequacy
of empirical antimicrobial therapy was defined based on dosing, route of administration, and in vitro antimicrobial susceptibility testing as previously defined.3 Briefly, empirical
antimicrobial therapy was considered adequate if (1) bloodstream isolate was susceptible to empirical agent based on in
vitro antimicrobial susceptibility results using Clinical and
Laboratory Standards Institute (CLSI) criteria; (2) empirical
antimicrobial agent was administered intravenously, with the
exception of fluoroquinolones which were considered appropriate if administered orally in hemodynamically stable
patients due to high bioavailability; and (3) patient received at
least the minimum recommended dose of an antimicrobial
agent according to the medication package insert for creatinine clearance at the time of BSI.
Case Ascertainment
All patients with BSI due to aerobic Gram-negative bacilli
from January 1, 2011, to December 31, 2012, were identified
Hospital Pharmacy 52(10)
through microbiology laboratory databases. Hospitalized
adult patients with first episodes of monomicrobial Gramnegative BSI were included in the study (n = 390). Patients
<18 years old (n = 62), polymicrobial BSI (n = 79), recurrent
episodes of BSI (n = 24), and patients who were treated outside the hospital (n = 23) were excluded.
Guideline Development and Assessment
Hospital-acquired and health care-associated sites of acquisition have been previously identified as risk factors for BSI due
to Gram-negative bacilli that inherently harbor antimicrobial
resistance genes such as Pseudomonas aeruginosa and chromosomally mediated AmpC-producing Enterobacteriaceae
(CAE), including Enterobacter, Citrobacter, and Serratia
species.11,12 The first step in guideline development was to confirm this finding in the local setting using a retrospective casecontrol design. Second, in vitro antimicrobial susceptibility
rates of bloodstream isolates for various antimicrobial agents
and combinations regimens were examined in each site of
acquisition. Antimicrobial agents with ≥90% in vitro susceptibility rates were retained. Third, patients were stratified by
acute severity of illness using the Pitt bacteremia score.13
Antimicrobial regimens were retained if susceptibility rates
were ≥90% for noncritically ill patients (Pitt bacteremia score
<4) and ≥95% for critically ill patients (Pitt bacteremia score
≥4). Minimum susceptibilities of 90% and 95% for recommended antimicrobial regimens in noncritically ill and critically ill patients, respectively, represented the 90th percentile
of responses to a large survey that was conducted among antimicrobial stewardship pharmacists.14 The preference for selection into institutional guidelines was given for monotherapy of
nonrestricted agents. If monotherapy of all nonrestricted agents
did not meet predefined susceptibility criteria in any category,
restricted antimicrobial agents and combination regimens were
included for selection in the respective category.
After management guidelines were developed, potential
to improve the adequacy of empirical antimicrobial therapy
and impact on utilization of broad-spectrum antibiotics was
evaluated. First, the adequacy of empirical antimicrobial
therapy for Gram-negative BSI in the historic cohort was
compared with projected adequacy if the guidelines were
fully implemented. Second, the proportion of patients who
received empirical antipseudomonal agents in the historic
cohort was compared with projected use after guidelines
implementation.
Statistical Analysis
Logistic regression was used to examine impact of site of
infection acquisition on risk of BSI due to P aeruginosa or
CAE. Demographics and clinical variables were collected
from electronic medical records in patients with BSI due to P
aeruginosa or CAE (cases) and other Gram-negative bacilli
Table of Contents for the Digital Edition of Hospital Pharmacy - November 2017
AKD—The Time Between AKI and CKD: What Is the Role of the Pharmacist?
Letter to the Editor
Antithrombotic Therapy Post Endovascular Stenting for Superior Vena Cava Syndrome
Pharmaceutical Pipeline Update
Janus Kinase Inhibitors for the Treatment of Rheumatoid Arthritis
Formulary Drug Reviews
Etelcalcetide
Treatment of Hypertriglyceridemia-Induced Acute Pancreatitis With Insulin, Heparin, and Gemfibrozil: A Case Series
Evaluation of Antimicrobial Stewardship–Related Alerts Using a Clinical Decision Support System
Compatibility, Stability, and Efficacy of Vancomycin Combined With Gentamicin or Ethanol in Sodium Citrate as a Catheter Lock Solution
Development of Institutional Guidelines for Management of Gram-Negative Bloodstream Infections: Incorporating Local Evidence
Underutilization of Aldosterone Antagonists in Heart Failure
Stability of Procainamide Injection in Clear Glass Vials and Polyvinyl Chloride Bags
Development of a Local Health-System Pharmacy Resident Society
Challenges and Solutions to New Manager Onboarding
Hospital Pharmacy - November 2017 - 649
Hospital Pharmacy - November 2017 - 650
Hospital Pharmacy - November 2017 - 651
Hospital Pharmacy - November 2017 - 652
Hospital Pharmacy - November 2017 - 653
Hospital Pharmacy - November 2017 - 654
Hospital Pharmacy - November 2017 - 655
Hospital Pharmacy - November 2017 - 656
Hospital Pharmacy - November 2017 - 657
Hospital Pharmacy - November 2017 - 658
Hospital Pharmacy - November 2017 - 659
Hospital Pharmacy - November 2017 - 660
Hospital Pharmacy - November 2017 - AKD—The Time Between AKI and CKD: What Is the Role of the Pharmacist?
Hospital Pharmacy - November 2017 - 662
Hospital Pharmacy - November 2017 - Letter to the Editor
Hospital Pharmacy - November 2017 - Pharmaceutical Pipeline Update
Hospital Pharmacy - November 2017 - Janus Kinase Inhibitors for the Treatment of Rheumatoid Arthritis
Hospital Pharmacy - November 2017 - Formulary Drug Reviews
Hospital Pharmacy - November 2017 - Etelcalcetide
Hospital Pharmacy - November 2017 - 668
Hospital Pharmacy - November 2017 - 669
Hospital Pharmacy - November 2017 - 670
Hospital Pharmacy - November 2017 - 671
Hospital Pharmacy - November 2017 - 672
Hospital Pharmacy - November 2017 - Treatment of Hypertriglyceridemia-Induced Acute Pancreatitis With Insulin, Heparin, and Gemfibrozil: A Case Series
Hospital Pharmacy - November 2017 - 674
Hospital Pharmacy - November 2017 - 675
Hospital Pharmacy - November 2017 - 676
Hospital Pharmacy - November 2017 - Evaluation of Antimicrobial Stewardship–Related Alerts Using a Clinical Decision Support System
Hospital Pharmacy - November 2017 - 678
Hospital Pharmacy - November 2017 - 679
Hospital Pharmacy - November 2017 - 680
Hospital Pharmacy - November 2017 - 681
Hospital Pharmacy - November 2017 - 682
Hospital Pharmacy - November 2017 - Compatibility, Stability, and Efficacy of Vancomycin Combined With Gentamicin or Ethanol in Sodium Citrate as a Catheter Lock Solution
Hospital Pharmacy - November 2017 - 684
Hospital Pharmacy - November 2017 - 685
Hospital Pharmacy - November 2017 - 686
Hospital Pharmacy - November 2017 - 687
Hospital Pharmacy - November 2017 - 688
Hospital Pharmacy - November 2017 - Development of Institutional Guidelines for Management of Gram-Negative Bloodstream Infections: Incorporating Local Evidence
Hospital Pharmacy - November 2017 - 690
Hospital Pharmacy - November 2017 - 691
Hospital Pharmacy - November 2017 - 692
Hospital Pharmacy - November 2017 - 693
Hospital Pharmacy - November 2017 - 694
Hospital Pharmacy - November 2017 - 695
Hospital Pharmacy - November 2017 - Underutilization of Aldosterone Antagonists in Heart Failure
Hospital Pharmacy - November 2017 - 697
Hospital Pharmacy - November 2017 - 698
Hospital Pharmacy - November 2017 - 699
Hospital Pharmacy - November 2017 - 700
Hospital Pharmacy - November 2017 - 701
Hospital Pharmacy - November 2017 - Stability of Procainamide Injection in Clear Glass Vials and Polyvinyl Chloride Bags
Hospital Pharmacy - November 2017 - 703
Hospital Pharmacy - November 2017 - 704
Hospital Pharmacy - November 2017 - 705
Hospital Pharmacy - November 2017 - 706
Hospital Pharmacy - November 2017 - Development of a Local Health-System Pharmacy Resident Society
Hospital Pharmacy - November 2017 - 708
Hospital Pharmacy - November 2017 - 709
Hospital Pharmacy - November 2017 - Challenges and Solutions to New Manager Onboarding
Hospital Pharmacy - November 2017 - 711
Hospital Pharmacy - November 2017 - 712
Hospital Pharmacy - November 2017 - 713
Hospital Pharmacy - November 2017 - 714
Hospital Pharmacy - November 2017 - 715
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