Clinical Studies
Necessity of carbapenem use when prescribed per infectious diseases specialists

https://doi.org/10.1016/j.diagmicrobio.2017.02.013Get rights and content

Highlights

  • Necessity of infectious diseases physician carbapenem prescribing was examined.

  • Few patients prescribed carbapenems grew a cephalosporin-resistant organism.

  • More cephalosporin-resistant organisms were missed than were identified.

  • Physician judgment is insufficient to ensure optimal carbapenem use.

Abstract

Preauthorization strategies, including restricting broad-spectrum antimicrobials such as carbapenems to infectious diseases physicians (ID) are commonly employed by stewardship programs. The appropriateness, or “necessity” of empiric carbapenem therapy by ID, defined as an isolated organism sensitive to the carbapenem and resistant to cefepime, was evaluated over a 6 month span and included 84 patients. Additionally, 30 patients followed by ID who were not prescribed a carbapenem until final susceptibilities were included as a definitive therapy group. Differences in multi-drug resistant organism (MDRO) risk factors between groups were non-significant. Carbapenem therapy was necessary for only 6 (7%) empiric therapy patients, while four times as many definitive group patients required a carbapenem but did not receive one empirically. Overall, ID's ability to accurately gauge which patients required carbapenems appeared poor in this study. Alternative risk stratification strategies may better guide broad-spectrum antimicrobial use than ID judgment alone.

Introduction

Managing and maintaining robust antimicrobial stewardship programs in the era of increasing antimicrobial resistance is a continued challenge for clinicians. Globally, up to 16% of all Enterobacteriaceae isolated from hospitalized patients have been molecularly confirmed as extended-spectrum β-lactamase (ESBL) producers, with similar rates of multi-drug resistant Pseudomonas aeruginosa (Castanheira et al., 2015, Farrell et al., 2013). For patients at significant risk for infection with multi-drug resistant organisms (MDRO), patients may be appropriately initiated on broad-spectrum antimicrobial agents empirically, with subsequent de-escalation of therapy to the most narrow-spectrum agent with activity against the causative pathogen as culture results become available.

Guidelines by the Infectious Diseases Society of America (IDSA) advocate for antimicrobial preauthorization, whereby clinicians are required to obtain approval prior to prescribing certain antimicrobials designated as restricted by the stewardship team, hailing it as an effective method for reducing the initiation of inappropriate broad-spectrum antibiotics (Barlam et al., 2016). Previous studies have shown decreases in the overall use of broad-spectrum agents and their associated costs following the implementation of preauthorization interventions (Buising et al., 2008, Lewis et al., 2012, Metjian et al., 2008, Pakyz et al., 2009, White et al., 1997). However, a significant limitation of these studies is that the appropriateness of empiric broad-spectrum therapy pre- and post-implementation was not evaluated, with the overall utilization of broad-spectrum agents being less important clinically than the proportion of cases where broad-spectrum empiric therapy was truly indicated.

An alternative methodology recommended by IDSA guidelines is to restrict broad-spectrum antimicrobial use to certain indications outlined in institution-specific protocols (Barlam et al., 2016). However, since all patient scenarios necessitating use of a restricted antimicrobial cannot always be anticipated, many hospitals allow for use by infectious diseases physician (ID) approval to account for unique circumstances. Carbapenems have traditionally been regarded as first-line agents for the treatment of documented or suspected MDRO (Paterson, 2006). At Hartford Hospital, carbapenem use is restricted to urinary tract infection (UTI) for select high-risk patients (ESBL identified in the urine within 12 months), selected ventilator associated pneumonia (VAP) patients in the medical intensive care unit (ICU) per protocol, use in cystic fibrosis patients, and infectious diseases physician or infectious diseases pharmacist approval for any other indication. Despite the ubiquity among hospitals of an ID prior authorization strategy, no studies to date have investigated the appropriateness of carbapenem use as empiric therapy when per ID. The objective of this study was to assess the frequency at which ID accurately predict which patients require carbapenem therapy, specifically in cases where the primary pathogen is cephalosporin-resistant. This objective will be measured by answering two questions: 1) “How often does ID empirically prescribe a carbapenem to a patient who ultimately grows a bacterium that is resistant to extended-spectrum cephalosporins (i.e., cefepime)?” and 2) “How often does ID need to escalate therapy to a carbapenem after cultures reveal a bacterium resistant to extended-spectrum cephalosporins?” Time to de-escalation was also evaluated as a secondary outcome.

Section snippets

Study design and patient population

This retrospective, single-center, descriptive chart review included patients aged 18–88 years with medical or surgical admissions to Hartford Hospital from January 1st, 2014, to June 30th, 2014, inclusive, and was approved by the institutional review board of Hartford Hospital. Patients with one or more orders for an antibiotic of the carbapenem class (doripenem, ertapenem, imipenem-cilastatin, and meropenem) were screened for inclusion in one of two designated patient groups: the empiric

Patient population

During the study time frame, 235 patients received a carbapenem. Of those screened, 84 (35.7%) were included in the empiric therapy group and 30 (12.8%) were included in the definitive therapy group (Fig. 1). Ten different ID physicians were involved in the carbapenem prescribing for the included encounters. Although our hospital also allows for approvals per ID pharmacist, all patients meeting inclusion criteria were managed by ID physicians during the study time period.

The patients receiving

Discussion

Hospitals rely on comprehensive antimicrobial stewardship programs to enact appropriate prescribing of broad-spectrum antimicrobials, with a goal of optimizing clinical outcomes while minimizing the unintended harmful consequences of antimicrobial use. One such consequence of principle concern is the promotion of antimicrobial resistance, with the relationship between the overuse and misuse of broad-spectrum antimicrobials and bacterial resistance well-documented in the literature (Barbosa and

Conclusions

Preauthorization is recommended by the IDSA stewardship guidelines as an effective method for reducing unnecessary antibiotic use. However, in this study the ability of ID physicians to empirically discriminate between patients who do and do not require carbapenem therapy appears poor. Preauthorization strategies deserve further research evaluating their role as a means of restricting broad-spectrum antimicrobials, however more comprehensive antibiotic stewardship interventions focusing on risk

Conflict of interest

In the last 12 months K Goodlet has received grant support from Merck. M Nailor has received grant support or honorarium from Merck and Astellas.

Source of funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Acknowledgements

None.

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