Sage Journals: Discover world-class research

Abstract

Background:

The optimal timing for the de-escalation of broad-spectrum antibiotics with activity against Pseudomonas aeruginosa and resistant Gram-negative rods (GNRs) in critically ill adults remains unknown.

Research Question:

We tested the hypothesis that cultures will identify GNRs that ultimately demonstrate resistance to ceftriaxone within 48 hours, potentially allowing safe de-escalation at this time point.

Study Design and Methods:

We conducted a secondary analysis of data from the Isotonic Solutions and Major Adverse Renal Events Trial: a pragmatic, cluster-randomized, multiple-crossover trial comparing balanced crystalloids versus saline for intravenous fluid administration in 15,802 critically ill adults at 5 intensive care units (ICUs) at Vanderbilt University Medical Center in Nashville, TN, USA. The primary endpoint was the time-to-positivity of respiratory and blood cultures that ultimately demonstrated growth of GNRs resistant to ceftriaxone. Multivariable logistic regression modeling was used to examine risk factors for the growth of cultures after 48 hours.

Results:

A total of 524 respiratory cultures had growth of GNRs, of which 284 (54.2%) had resistance to ceftriaxone. A total of 376 blood cultures grew GNRs, of which 70 (18.6%) had resistance to ceftriaxone. At 48 hours, 87% of respiratory cultures and 85% of blood cultures that ultimately grew GNRs resistant to ceftriaxone had demonstrated growth. Age, gender, predicted risk of inpatient mortality and prior use of antibiotics did not predict the growth of cultures after 48 hours.

Interpretation:

Among a cohort of critically ill adults, 13% of respiratory cultures and 15% of blood cultures that ultimately grew GNRs resistant to ceftriaxone did not demonstrate growth until at least 48 hours after collection. Further work is needed to determine the ideal time for critically ill adults to de-escalate from broad-spectrum antibiotics targeting Pseudomonas aeruginosa and extended-spectrum β-lactamase-producing gram-negative pathogens.

Keywords

antimicrobial stewardship critical care Pseudomonas aeruginosa bacteremia ceftriaxone

Get full access to this article

View all access options for this article.

References

Pollack

Srinivasan

. Core elements of hospital antibiotic stewardship programs from the Centers for Disease Control and Prevention. Clin Infect Dis. 2014;59(suppl_3):S97–S100.

Timsit

J-F

Harbarth

Carlet

. De-escalation as a potential way of reducing antibiotic use and antimicrobial resistance in ICU. Intensive Care Med. 2014;40(5):1580–1582.

Heenen

Jacobs

Vincent

. Antibiotic strategies in severe nosocomial sepsis: why do we not de-escalate more often? Crit Care Med. 2012; 40(5):1404–1409.

Silva

BNG

Andriolo

Atallah

ÁN

Salomão

. De-escalation of antimicrobial treatment for adults with sepsis, severe sepsis or septic shock. Cochrane Database Syst Rev. 2010;12.

Moustos

Staphylaki

Christidou

Spandidos

Neonakis

. Major pathogen microorganisms except yeasts can be detected from blood cultures within the first three days of incubation: a two-year study from a university hospital. Exp Ther Med. 2017;14(6):6074–6076.

Pardo

Klinker

Borgert

Trikha

Rand

Ramphal

. Time to positivity of blood cultures supports antibiotic de-escalation at 48 hours. Ann Pharmacother. 2014;48(1):33–40.

Melling

Noto

Rice

Semler

Stollings

. Time to first culture positivity among critically ill adults with methicillin-resistant Staphylococcus aureus growth in respiratory or blood cultures. Ann Pharmacother. 2019;54(2):131–137.

Garnacho-Montero

Gutiérrez-Pizarraya

Escoresca-Ortega

Fernández-Delgado

López-Sánchez

. Adequate antibiotic therapy prior to ICU admission in patients with severe sepsis and septic shock reduces hospital mortality. Crit Care. 2015;19(1):302.

Lambregts

Bernards

van der Beek

Visser

de Boer

. Time to positivity of blood cultures supports early re-evaluation of empiric broad-spectrum antimicrobial therapy. PloS One. 2019;14(1):e0208819.

10.

Scheer

Fuchs

Gründling

, et al. Impact of antibiotic administration on blood culture positivity at the beginning of sepsis: a prospective clinical cohort study. Clin Microbiol Infect. 2019;25(3):326–331.

11.

Harris

Bramley

Jain

, et al. Influence of antibiotics on the detection of bacteria by culture-based and culture-independent diagnostic tests in patients hospitalized with community-acquired pneumonia. Open Forum Infect Dis. 2017;10(1):ofx014.

12.

Liu

Ohl

Johnson

Williamson

Beardsley

Luther

. Frequency of empiric antibiotic de-escalation in an acute care hospital with an established Antimicrobial Stewardship Program. BMC Infect Dis. 2016;16(1):751.

13.

Semler

Self

Wanderer

, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018; 378(9):829–839.

14.

Clinical and Laboratory Standards Institute (CLSI). M45 Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria. 3rd ed. https://clsi.org/standards/products/microbiology/documents/m45/. Accessed March 5, 2020.

15.

Clinical and Laboratory Standards Institute (CLSI). M100 Performance Standards for antimicrobial susceptibility testing. 29th ed. https://clsi.org/standards/products/microbiology/documents/m100/. Accessed March 5, 2020.

16.

Kollef

Sherman

Ward

Fraser

. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest. 1999;115(2):462–474.

17.

Ibrahim

Sherman

Ward

Fraser

Kollef

. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest. 2000;118(1):146–155.

18.

Eliopoulos

Paterson

Rice

. Empirical antibiotic choice for the seriously ill patient: are minimization of selection of resistant organisms and maximization of individual outcome mutually exclusive? Clin Infect Dis. 2003;36(8):1006–1012.

19.

Metlay

Waterer

Long

, et al. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019; 200(7): e45–e67.

20.

Schlueter

James

Dominguez

Tsu

Seymann

. Practice patterns for antibiotic de-escalation in culture-negative healthcare-associated pneumonia. Infection. 2010;38(5):357–362.

21.

Brusselaers

Vogelaers

Blot

. The rising problem of antimicrobial resistance in the intensive care unit. Ann Intensive Care. 2011;1(1):47.

22.

Leone

Garcin

Bouvenot

, et al. Ventilator-associated pneumonia: breaking the vicious circle of antibiotic overuse. Crit Care Med. 2007;35(2):379–385.

23.

Niederman

. De-escalation therapy in ventilator-associated pneumonia. Curr Opin Crit Care. 2006;12(5):452–457.

24.

Höffken

Niederman

. Nosocomial pneumonia: the importance of a de-escalating strategy for antibiotic treatment of pneumonia in the ICU. Chest. 2002; 122(6):2183–2196.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.14 MB

Time to First Culture Positivity for Gram-Negative Rods Resistant to Ceftriaxone in Critically Ill Adults