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

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.

Fluoroquinolone Versus Nonfluoroquinolone Treatment of Bloodstream Infections Caused by Chromosomally Mediated AmpC-Producing Enterobacteriaceae

“…In this study, fluoroquinolones had a numerically lower rate of composite clinical failure than comparators (12.9% vs. 24%), but this difference was not statistically significant. The rates of clinical failure in our groups were lower than a similar study by Derrick et al (17.9% vs. 33.8%), which described overall treatment failure in patients with AmpC-producing Enterobacterales who received either third-generation cephalosporins or comparator therapy [25]. In addition, 90-day readmission rates were low (10.9% overall) but were numerically higher in the beta-lactam group (6.5% vs. 16.7%).…”

Gram-Negative Bloodstream Infection: Implications of Antimicrobial Resistance on Clinical Outcomes and Therapy

“…Previous literature demonstrated the effectiveness of cefepime in comparison to carbapenems for the treatment of BSI due to these bacteria [ 19 ]. In this Special Issue, Derrick and colleagues suggest that ceftriaxone may be a treatment option in patients with low-inoculum BSI due to Enterobacter cloacae and other CAE [ 20 ]. This is conceivable, since low-inoculum sources of GN-BSI are associated with lower mortality [ 21 , 22 ].…”

“…This is conceivable, since low-inoculum sources of GN-BSI are associated with lower mortality [ 21 , 22 ]. This multicenter cohort study is the first to report the effectiveness of ceftriaxone for BSI due to CAE [ 20 ]. The study has major antimicrobial stewardship implications, since it allows de-escalation of antimicrobial therapy from carbapenems or cefepime to ceftriaxone in patients with uncomplicated CAE BSI secondary to urinary tract source without obstruction or central venous catheter infection after catheter removal [ 20 ].…”

“…This multicenter cohort study is the first to report the effectiveness of ceftriaxone for BSI due to CAE [ 20 ]. The study has major antimicrobial stewardship implications, since it allows de-escalation of antimicrobial therapy from carbapenems or cefepime to ceftriaxone in patients with uncomplicated CAE BSI secondary to urinary tract source without obstruction or central venous catheter infection after catheter removal [ 20 ]. The results should not be extrapolated to patients with more complex sources of GN-BSI, such as pulmonary infections or multi-loculated intra-abdominal abscesses, due to the increased risk of resistance development and mortality [ 21 , 22 , 23 , 24 ].…”

The Clinical Evaluation of Third-generation Cephalosporins As Definitive Therapy for <i>Enterobacter</i> spp. and <i>Klebsiella aerogenes</i> Bacteremia

“…Previous studies have also shown no significant difference in clinical outcomes of bacteremia when 3GCs were used for definitive therapy compared to non-3 GC therapy (i.e. extended-spectrum penicillin antibiotics, fluoroquinolones, 4CGs, and carbapenems) (9). In addition, there is evidence that the administration of broad-spectrum antimicrobial agents may contribute to the establishment of resistance.…”