Aggressive versus conservative initiation of antimicrobial treatment in critically ill surgical patients with suspected intensive-care-unit-acquired infection: a quasi-experimental, before and after observational cohort study

doi:10.1016/S1473-3099(12)70151-2

The Lancet Infectious Diseases

Volume 12, Issue 10, October 2012, Pages 774-780

https://doi.org/10.1016/S1473-3099(12)70151-2 Get rights and content

Summary

Background

Antimicrobial treatment in critically ill patients can either be started as soon as infection is suspected or after objective data confirm an infection. We postulated that delaying antimicrobial treatment of patients with suspected infections in the surgical intensive care unit (SICU) until objective evidence of infection had been obtained would not worsen patient mortality.

Methods

We did a 2-year, quasi-experimental, before and after observational cohort study of patients aged 18 years or older who were admitted to the SICU of the University of Virginia (Charlottesville, VA, USA). From Sept 1, 2008, to Aug 31, 2009, aggressive treatment was used: patients suspected of having an infection on the basis of clinical grounds had blood cultures sent and antimicrobial treatment started. From Sept 1, 2009, to Aug 31, 2010, a conservative strategy was used, with antimicrobial treatment started only after objective findings confirmed an infection. Our primary outcome was in-hospital mortality. Analyses were by intention to treat.

Findings

Admissions to the SICU for the first and second years were 762 and 721, respectively, with 101 patients with SICU-acquired infections during the aggressive year and 100 patients during the conservative year. Compared with the aggressive approach, the conservative approach was associated with lower all-cause mortality (13/100 [13%] vs 27/101 [27%]; p=0·015), more initially appropriate therapy (158/214 [74%] vs 144/231 [62%]; p=0·0095), and a shorter mean duration of therapy (12·5 days [SD 10·7] vs 17·7 [28·1]; p=0·0080). After adjusting for age, sex, trauma involvement, acute physiology and chronic health evaluation (APACHE) II score, and site of infection, the odds ratio for the risk of mortality in the aggressive therapy group compared with the conservative therapy group was 2·5 (95% CI 1·5–4·0).

Interpretation

Waiting for objective data to diagnose infection before treatment with antimicrobial drugs for suspected SICU-acquired infections does not worsen mortality and might be associated with better outcomes and use of antimicrobial drugs.

Funding

National Institutes of Health.

Introduction

Until recently, the use of antimicrobial drugs was thought by physicians to be relatively risk free, which resulted in a tendency to give these drugs at the smallest suspicion of infection. However, excessive antimicrobial use is now known to be associated with resistance and other associated effects. Consequently, the decision to start treatment in a possibly (but not certainly) infected critically ill patient is made based on a balance between three considerations: the certainty of the diagnosis,1, 2, 3, 4, 5 the risk of delaying treatment,6, 7, 8, 9, 10, 11, 12 and the environmental damage caused by the use of antimicrobial drugs,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 including the selection of resistant organisms.

Two possibilities for the timing of the start of antimicrobial treatment in critically ill patients exist:26, 27 starting treatment immediately after obtaining cultures, knowing that many uninfected patients will receive unnecessary treatment; or withholding antimicrobial treatment until an infection is confirmed by objective data, knowing that some patients might have potentially harmful delays in treatment. There is no standardised approach to the timing of the start of antimicrobial therapy. We postulated that delaying the administration of broad-spectrum antimicrobial drugs until the initial return of objective evidence of infection would not significantly worsen mortality and would be potentially beneficial in terms of reduction of antimicrobial use and the induction of resistance.

Section snippets

Study design

Patients aged 18 years or older who were admitted to the University of Virginia (Charlottesville, VA, USA) surgical intensive care unit (SICU) were prospectively followed up until discharge from Sept 1, 2008, to Aug 31, 2010. Patients not on a surgical service and patients with burns were excluded. The 16-bed SICU at the University of Virginia is managed by five board-certified intensivists. All orders are written by the SICU team, and a clinical pharmacist reviews all drug orders, including

Results

762 patients were admitted to the ICU during the first year (aggressive approach) of the study, 101 (13%) of whom acquired 247 discrete sites of infection in the ICU. During the second year (conservative approach), 100 (14%) of 721 admitted patients acquired an infection, with 237 sites of infection. The two study groups were balanced for baseline characteristics (table 1). The incidences of infection were similar, with 32·0 infections per 100 admissions and 26·0 infections per 1000

Discussion

It is challenging to correctly time the start of antimicrobial treatment in patients who are critically ill. First, patients often exhibit signs and symptoms of infection that are the consequence of non-infectious causes.²⁹ Second, the diagnosis of infection still generally depends upon the growth of pathogens from culture over 48–72 h. In our study, we showed that patients managed under an aggressive treatment protocol had a more rapid start of treatment, a lower chance of receiving initially

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ArticlesAggressive versus conservative initiation of antimicrobial treatment in critically ill surgical patients with suspected intensive-care-unit-acquired infection: a quasi-experimental, before and after observational cohort study

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Section snippets

Study design

Results

Discussion

Chest

Chest

Chest

Chest

J Hosp Infect

Adv Drug Deliv Rev

Lancet Infect Dis

J Hosp Infect

Am J Infect Control

Causes and consequences of fever complicating critical surgical illness

Surg Infect (Larchmt)

Antibiotic management of suspected nosocomial ICU-acquired infection: does prolonged empiric therapy improve outcome?

Intensive Care Med

Ventilator-associated pneumonia: diagnosis, treatment, and prevention

Clin Microbiol Rev

Empirical antimicrobial therapy of septic shock patients: adequacy and impact on the outcome

Crit Care Med

Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis

Crit Care Med

Efficacy of adequate early antibiotic therapy in ventilator-associated pneumonia: influence of disease severity

Intensive Care Med

Articles
Aggressive versus conservative initiation of antimicrobial treatment in critically ill surgical patients with suspected intensive-care-unit-acquired infection: a quasi-experimental, before and after observational cohort study