Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy for Bloodstream Infections Secondary to Enterobacter, Serratia, and Citrobacter Species.

Caroline Derrick,P Brandon Bookstaver,Majdi N Al-Hasan,Brad Crane,Trisha Branan,Virginia Fleming,S Travis King,Sandy Estrada,David Cluck,Brian Odle,Christopher M Bland,Julie Ann Justo,Kayla R Stover,Jenna Swindler,V Paul Dimondi,Shawn H Macvane,Kathey Fulton Rumley ,Liang Zhiqiang ,Scott E Kincaid ,Benjamin B Britt ,Bruce M Jones ,Kelly E Pillinger

doi:10.3390/antibiotics9050254

Abstract

Objectives: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species. Methods: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection. Results: A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51–1.72) in multivariable Cox proportional hazards regression analysis. Conclusions: These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents.

Highlights

Antimicrobial resistance is an increasingly prevalent problem and a substantial contributor to the global disease burden and patient mortality [1]
bloodstream infections (BSIs) have led many clinicians to advise against the use of third-generation cephalosporins in infections with these pathogens, regardless of in vitro susceptibility [12]
In an era of increasing antimicrobial resistance and reporting of antimicrobial utilization and resistance to the National Healthcare Safety Network, antimicrobial stewardship programs have been searching for safe strategies to reduce unnecessary utilization of carbapenems and antipseudomonal beta-lactams

Summary

Introduction

Antimicrobial resistance is an increasingly prevalent problem and a substantial contributor to the global disease burden and patient mortality [1]. Among the chromosomally-mediated beta-lactamases, the AmpC family represents one of the most commonly encountered resistance enzymes [2] These beta-lactamases are characteristically found in Enterobacter, Serratia, or Citrobacter spp. Expression of these enzymes is a complex process regulated by transcription factors (AmpR) and regulatory enzymes (AmpD), which work to promote or reduce enzyme production, respectively Induction of these enzymes may occur following exposure to certain beta-lactams. Prior data suggest the on-therapy emergence of 3GC resistance can occur despite initial in vitro susceptibility Complicating this controversy is a relative dearth of clinical evidence to guide the treatment of non-Enterobacter AmpC-producing organisms [5,6,7,8,9]

Objectives

Methods

Discussion

Conclusion