Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Apr 23;6(6):ofz194.
doi: 10.1093/ofid/ofz194. eCollection 2019 Jun.

Antimicrobial Resistance or Delayed Appropriate Therapy-Does One Influence Outcomes More Than the Other Among Patients With Serious Infections Due to Carbapenem-Resistant Versus Carbapenem-Susceptible Enterobacteriaceae?

Thomas P Lodise  1 , Ariel Berger  2 , Arman Altincatal  2 , Rosa Wang  2 , Tarun Bhagnani  2 , Patrick Gillard  3 , Nicole G Bonine  3
Affiliations

Antimicrobial Resistance or Delayed Appropriate Therapy-Does One Influence Outcomes More Than the Other Among Patients With Serious Infections Due to Carbapenem-Resistant Versus Carbapenem-Susceptible Enterobacteriaceae?

Thomas P Lodise et al. Open Forum Infect Dis. .

Abstract

Background: The relative contribution of antimicrobial resistance versus delayed appropriate treatment to the clinical and economic burden of Enterobacteriaceae infections is not well understood.

Methods: Using a large US hospital database, we identified all admissions between July 2011 and September 2014 with evidence of serious Enterobacteriaceae infection. The "index date" was the earliest date on which a culture positive for Enterobacteriaceae was drawn. Infections were classified as carbapenem-resistant (CRE) or carbapenem-susceptible (CSE). Receipt of antimicrobials with activity against all index pathogens on the index date or ≤2 days thereafter was deemed as "timely"; all other instances were "delayed." Associations between CRE status and delayed appropriate therapy on outcomes were estimated using inverse probability weighting and multivariate regression models (ie, logistic model for discharge destination and composite mortality [in-hospital death or discharge to hospice] or generalized linear model for duration of antibiotic therapy, hospital length of stay [LOS], and costs).

Results: A total of 50 069 patients met selection criteria; 514 patients (1.0%) had CRE. Overall, 67.5% of CSE patients (vs 44.6%, CRE) received timely appropriate therapy (P < .01). Irrespective of CRE status, patients who received delayed appropriate therapy had longer durations of antibiotic therapy and LOS, higher costs, lower likelihood of discharge to home, and greater likelihood of the composite mortality outcome (P for trend < .01).

Conclusions: Delayed appropriate therapy is a more important driver of outcomes than CRE, although the 2 factors are somewhat synergistic. Better methods of early CRE identification may improve outcomes in this patient population.

Keywords: Enterobacteriaceae; antibacterial drug resistance; antibiotic resistance; carbapenems; cost of illness.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Full diagram of sample selection. LOS indicates length of stay. aIncluding chronic infection (N = 1468), gangrene (N = 1468), necrotizing fasciitis (N = 186), osteomyelitis or related bone infection, or both (N = 1307), and pregnancy (N = 266). bWith exception of patients who expired relatively early in the course of admission (these patients were assumed to be “victims” of inappropriate empiric therapy and were therefore retained).
Figure 2.
Figure 2.
Time to receipt of appropriate therapy, by CRE status. CRE indicates carbapenem-resistant Enterobacteriaceae; CSE, carbapenem-susceptible Enterobacteriaceae.
See this image and copyright information in PMC

References

    1. Solomkin JS, Mazuski JE, Bradley JS, et al. . Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis 2010; 50:133–64. - PubMed
    1. Nicolle LE, Bradley S, Colgan R, et al. ; Infectious Diseases Society of America; American Society of Nephrology; American Geriatric Society Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis 2005; 40:643–54. - PubMed
    1. Friedman ND, Kaye KS, Stout JE, et al. . Health care–associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med 2002; 137:791–7. - PubMed
    1. American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005; 171:388–416. - PubMed
    1. Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2013. http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013..., 2013. Accessed April 26, 2019.