Antimicrobial Stewardship: Philosophy Versus Practice

Ashley, Elizabeth S. Dodds; Kaye, Keith S.; DePestel, Daryl D.; Hermsen, Elizabeth D.

doi:10.1093/cid/ciu546

Cited by 45 publications

(34 citation statements)

References 87 publications

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“…17–20,22 Although the most appropriate outcomes have not yet been established, they have been the subject of considerable discussion in the field recently. 21,23,24 The present study adds to the literature by providing one of the broadest assessments of potential stewardship outcomes to date. Our findings are instructive in that they demonstrate a number of complexities of proposed outcome measures.…”

Section: Discussionmentioning

confidence: 94%

Long-Term Outcomes of an Antimicrobial Stewardship Program Implemented in a Hospital with Low Baseline Antibiotic Use

Jenkins

Knepper²,

Shihadeh³

et al. 2015

Infect. Control Hosp. Epidemiol.

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Objective To evaluate the long-term outcomes of an antimicrobial stewardship program (ASP) implemented in a hospital with low baseline antibiotic use Design Quasi-experimental, interrupted-time series study Setting 525-bed public safety-net hospital Intervention Implementation of a formal ASP in July 2008 Methods We conducted a time-series analysis to evaluate the impact of the ASP over a 6.25-year period (July 1, 2008 – September 30, 2014) while controlling for trends during a 3-year preintervention period (July 1, 2005 – June 30, 2008). The primary outcome measures were total antibacterial and antipseudomonal use in days of therapy (DOT) per 1000 patient-days (PD). Secondary outcomes included antimicrobial costs and resistance, hospital-onset C. difficile infection, and other patient-centered measures. Results During the preintervention period, total antibacterial and antipseudomonal use were declining (−9.2 and −5.5 DOT/1000 PD per quarter, respectively). During the stewardship period, both continued to decline, although at lower rates (−3.7 and −2.2 DOT/1000 PD, respectively), resulting in a slope change of 5.5 DOT/1000 PD per quarter for total antibacterial use (P = .10) and 3.3 DOT/100 PD per quarter for antipseudomonal use (P = .01). Antibiotic expenditures declined markedly during the stewardship period (−$295.42/1000PD per quarter, p=.002). There were variable changes in antimicrobial resistance and few apparent changes in C. difficile infection and other patient-centered outcomes. Conclusion In a hospital with low baseline antibiotic use, implementation of an ASP was associated with sustained reductions in total antibacterial and antipseudomonal use and declining antibiotic expenditures; however, this study highlights limitations of commonly used stewardship outcome measures.

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Section: Discussionmentioning

confidence: 94%

Long-Term Outcomes of an Antimicrobial Stewardship Program Implemented in a Hospital with Low Baseline Antibiotic Use

Jenkins

Knepper²,

Shihadeh³

et al. 2015

Infect. Control Hosp. Epidemiol.

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“…They can be used as an extension of the antibiogram, inform institutional clinical pathway design, and influence physicians to choose the correct agent, dose, route, and dosing interval. These are important metrics of antimicrobial use processes that can be evaluated by ASPs to track and optimize antimicrobial utilization [ 28 ]. Since the execution of the current study, the antimicrobial management team provides practitioners at our institution with Monte Carlo simulation data in addition to the annual antibiogram to help guide empiric therapy for both P. aeruginosa and Enterobacteriaceae.…”

Section: Discussionmentioning

confidence: 99%

Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy

et al. 2015

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Pseudomonas aeruginosa is a common pathogen implicated in nosocomial infections with increasing resistance to a limited arsenal of antibiotics. Monte Carlo simulation provides antimicrobial stewardship teams with an additional tool to guide empiric therapy. We modeled empiric therapies with antipseudomonal β-lactam antibiotic regimens to determine which were most likely to achieve probability of target attainment (PTA) of ≥90%. Microbiological data for P. aeruginosa was reviewed for 2012. Antibiotics modeled for intermittent and prolonged infusion were aztreonam, cefepime, meropenem, and piperacillin/tazobactam. Using minimum inhibitory concentrations (MICs) from institution-specific isolates, and pharmacokinetic and pharmacodynamic parameters from previously published studies, a 10,000-subject Monte Carlo simulation was performed for each regimen to determine PTA. MICs from 272 isolates were included in this analysis. No intermittent infusion regimens achieved PTA ≥90%. Prolonged infusions of cefepime 2000 mg Q8 h, meropenem 1000 mg Q8 h, and meropenem 2000 mg Q8 h demonstrated PTA of 93%, 92%, and 100%, respectively. Prolonged infusions of piperacillin/tazobactam 4.5 g Q6 h and aztreonam 2 g Q8 h failed to achieved PTA ≥90% but demonstrated PTA of 81% and 73%, respectively. Standard doses of β-lactam antibiotics as intermittent infusion did not achieve 90% PTA against P. aeruginosa isolated at our institution; however, some prolonged infusions were able to achieve these targets.

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“…De-escalation of antibiotic therapy, or the changing of therapy with an empirical antibiotic to one with a narrower-spectrum antibiotic, is often advocated to reduce the use of broad-spectrum antibiotics in the hospitalized patient (3,29). It is generally considered safe, has been associated with improved outcomes in several observational studies, and is recommended in the 2013 Surviving Sepsis Campaign guidelines (9,10,30).…”

Section: Discussionmentioning

confidence: 99%

A Simulation Study Reveals Lack of Pharmacokinetic/Pharmacodynamic Target Attainment in De-escalated Antibiotic Therapy in Critically Ill Patients

Carlier

Roberts

Stove

et al. 2015

Antimicrob Agents Chemother

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f De-escalation of empirical antibiotic therapy is often included in antimicrobial stewardship programs in critically ill patients, but differences in target attainment when antibiotics are switched are rarely considered. The primary objective of this study was to compare the fractional target attainments of contemporary dosing of empirical broad-spectrum ␤-lactam antibiotics and narrower-spectrum antibiotics for a number pathogens for which de-escalation may be considered. The secondary objective was to determine whether alternative dosing strategies improve target attainment. We performed a simulation study using published population pharmacokinetic (PK) studies in critically ill patients for a number of broad-spectrum ␤-lactam antibiotics and narrower-spectrum antibiotics. Simulations were undertaken using a data set obtained from critically ill patients with sepsis without absolute renal failure (n ‫؍‬ 49). The probability of target attainment of antibiotic therapy for different microorganisms for which de-escalation was applied was analyzed. EUCAST MIC distribution data were used to calculate fractional target attainment. The probability that therapeutic exposure will be achieved was lower for the narrower-spectrum antibiotics with conventional dosing than for the broad-spectrum alternatives and could drastically be improved with higher dosages and different modes of administrations. For a selection of microorganisms, the probability that therapeutic exposure will be achieved was overall lower for the narrower-spectrum antibiotics using conventional dosing than for the broad-spectrum antibiotics. P rovision of antibiotic therapy that is timely and of an appropriate spectrum is one of the mainstays of treatment (1, 2). This has led to the widespread use of broad-spectrum antibiotic therapy for the empirical treatment of infections. After identification of the causative microorganism, antibiotic therapy is typically adapted to the susceptibility profile of the microorganism, with a preference to change therapy to narrower-spectrum agents in order to decrease selective pressure for resistant pathogens. This process is called antibiotic de-escalation and is considered an important element in antibiotic stewardship programs (3-5).Although the timing and adequacy of the antibiotic therapy remain crucial, recent data hint at the importance of antibiotic dosing and exposure on clinical outcome (6). Changes in the physiology of the critically ill alter the pharmacokinetics (PKs) of ␤-lactam antibiotics, with many patients being at risk of being underdosed (7,8). Attainment of PK/pharmacodynamic (PD) targets associated with efficacy is also dependent on the susceptibility of the pathogen and varies across antibiotic classes, an element that is rarely considered (8).Although de-escalation of antibiotic therapy is a key element in many antibiotic stewardship programs, the possible change in PK/PD target attainment in de-escalation has not yet been considered. De-escalation has been associated with improved outcomes in ...

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Antimicrobial Stewardship: Philosophy Versus Practice

Cited by 45 publications

References 87 publications

Long-Term Outcomes of an Antimicrobial Stewardship Program Implemented in a Hospital with Low Baseline Antibiotic Use

Long-Term Outcomes of an Antimicrobial Stewardship Program Implemented in a Hospital with Low Baseline Antibiotic Use

Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy

A Simulation Study Reveals Lack of Pharmacokinetic/Pharmacodynamic Target Attainment in De-escalated Antibiotic Therapy in Critically Ill Patients

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