Delay of Active Antimicrobial Therapy and Mortality among Patients with Bacteremia: Impact of Severe Neutropenia

Abstract

Increasing bacterial antimicrobial resistance has prompted physicians to choose broad-spectrum antimicrobials in order to reduce the likelihood of inactive empirical therapy. However, for bacteremic patients already receiving supportive care, it is unclear whether delay of active antimicrobial therapy significantly impacts patient outcomes. We performed a retrospective cohort study of patients with monomicrobial bloodstream infections at a large urban hospital in the United States from 2001 to 2006. We assessed the impact of delay of active antimicrobial therapy on mortality by using multivariable logistic regression modeling with and without propensity score methodology. We evaluated 1,523 episodes of monomicrobial bacterial bloodstream infections at our institution. Nine hundred eighty-three bacteremic episodes (64.5%) were treated with an active antimicrobial agent within 24 h of the index blood culture; the remaining 540 episodes (35.5%) were considered to have delay of active antimicrobial therapy. In adjusted analysis, among patients in the nonintensive-care-unit setting with an absolute neutrophil count (ANC) of <100 cells/l, delay was associated with increased mortality (odds ratio [OR], 18.0; 95% confidence interval [CI], 2.84 to 114.5; P < 0.01); among intensive-care-unit patients with an ANC of <100 cells/l, the effect of delay on mortality was nearly significant (OR, 5.56; 95% CI, 0.85 to 36.3; P ‫؍‬ 0.07). However, for patients who were nonneutropenic (ANC, >500 cells/l) or had ANCs of 100 to 500 cells/l, delay was not associated with increased mortality. While the delay of active antimicrobial therapy was not significantly associated with higher mortality for most patients in this cohort, patients with severe neutropenia appeared to be vulnerable.

<i>Pseudomonas aeruginosa</i> Bacteremia among Immunocompetent and Immunocompromised Patients: Relation to Initial Antibiotic Therapy and Survival

“…We performed a subgroup analysis using the Kaplan-Meier method, and the log-rank test showed a significant influence of initial antibiotic therapy in immunocompromised patients, whereas it did not show any therapeutic benefit in immunocompetent patients. Similar findings that support our results were observed in neutropenic and non-neutropenic patients with bacteremia (29,30). Therefore, considering these observations, initial antibiotic therapy for P. aeruginosa bacteremia should be highlighted in patients with immunocompromised status.…”

Prognosis of acute respiratory distress syndrome in neutropenic cancer patients

“…In this group of patients, no death occurred until the first week in ICU, whereas the mortality was ,35% during this period for the others. These results suggest that an earlier implementation of an effective therapy may result in improved outcome [22]. Cancer patients with prolonged neutropenia, exposure to broad-spectrum antibiotics and those requiring mechanical ventilation have higher risk for S. maltophilia infection [23].…”

“…In fact, antibiotics active on P. aeruginosa are not always efficient on documented infections with S. maltophilia or ESBL-producing strains, and their combination with antibiotics such as TMP-SMX [23] or colistin may either extend their spectrum or act synergistically [25]. Our data suggest that, first, when considering that data on antibiotic resistance is dynamic and varies from ward to ward [26], broad-spectrum antibiotic treatment must be initiated promptly [22] and, secondly, the monitoring of patient colonisation status in order to permit a surveillance-assisted initiation of empirical antibiotics should be evaluated in such patients [27].…”

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

“…The majority of studies within the meta-analysis were of low quality due to a number of deficiencies, including small study size, using an initial index time of an arbitrary time point such as emergency department arrival, and indexing of outcome to delay in time to the first antimicrobial (regardless of activity against the putative pathogen) [82,83]. Other negative studies not included in this meta-analysis are compromised by equating bacteremia with sepsis (as currently defined to include organ failure) and septic shock [84][85][86][87]. Many of these studies are also compromised by indexing delays to easily accessible but nonphysiologic variables such as time of initial blood culture draw (an event likely to be highly variable in timing occurrence).…”