Duration of antibiotic therapy for critically ill patients with bloodstream infections: A retrospective cohort study

Abstract

Background: The optimal duration of antibiotic treatment for bloodstream infections is unknown and understudied.

Methods: A retrospective cohort study of critically ill patients with bloodstream infections diagnosed in a tertiary care hospital between March 1, 2010 and March 31, 2011 was undertaken. The impact of patient, pathogen and infectious syndrome characteristics on selection of shorter (≤10 days) or longer (>10 days) treatment duration, and on the number of antibiotic-free days, was examined. The time profile of clinical response was evaluated over the first 14 days of treatment. Relapse, secondary infection and mortality rates were compared between those receiving shorter or longer treatment.

Results: Among 100 critically ill patients with bloodstream infection, the median duration of antibiotic treatment was 11 days, but was highly variable (interquartile range 4.5 to 17 days). Predictors of longer treatment (fewer antibiotic-free days) included foci with established requirements for prolonged treatment, underlying respiratory tract focus, and infection with Staphylococcus aureus or Pseudomonas species. Predictors of shorter treatment (more antibiotic-free days) included vascular catheter source and bacteremia with coagulase-negative staphylococci. Temperature improvements plateaued after the first week; white blood cell counts, multiple organ dysfunction scores and vasopressor dependence continued to decline into the second week. Among 72 patients who survived to 10 days, clinical outcomes were similar between those receiving shorter and longer treatment.

Conclusion: Antibiotic treatment durations for patients with bloodstream infection are highly variable and often prolonged. A randomized trial is needed to determine the duration of treatment that will maximize cure while minimizing adverse consequences of antibiotics.

Keywords: Antibacterials; Antibiotic stewardship; Bacteremia; Bacterial infections; Critical care.

Figures

Figure 1)

Duration of antibiotic therapy. The duration of antibiotic therapy is displayed for each of the 100 patients with bacteremia. The total duration of antibiotic therapy was defined by the number of consecutive days of antibiotics active against the culprit pathogen, after the index date of blood culture collection. The bars are segmented according to the patient’s survival status, and timing of death in relation to initiation and completion of antibiotic therapy. This figure illustrates the potential for immortal time bias among patients who have the opportunity for longer treatments

Figure 2)

Time profile of temperatures among critically ill patients with bloodstream infection. There was a significant decrease in temperatures in the first seven days (reduction of 0.16°C per day, 95% CI 0.11 to 0.20; P

Figure 3)

Time profile of white blood cell counts among critically ill patients with bloodstream infection. White blood cell count declined over the 14-day interval, although there was substantial variation in time profiles among individuals

Figure 4)

Time profile of multiple organ dysfunction scores among critically ill patients with bloodstream infection. Multiple organ dysfunction scores declined over the 14-day interval, although there was substantial variation in time profiles across individuals

Figure 5)

Time profile of vasopressor requirements among critically ill patients with bloodstream infection. Vasopressor use declined over the 14-day period (OR 0.9/day, 95% CI 0.93 to 0.98; P=0.018), with no significant plateau after seven days