Procalcitonin to Guide 7 vs 14 Days of Antibiotics in Bloodstream Infections

Importance: The Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) trial showed that 7 days of antibiotics was noninferior to 14 days among patients with bacteremia. However, it is unknown whether patients with high serum procalcitonin (PCT) level at day 7 of therapy would benefit from a prolonged treatment course. Objective: To investigate whether an elevated serum PCT level at day 7 of bacteremia was associated with increased mortality among patients treated with 7 vs 14 days of antibiotics. Design, Setting, and Participants: This cohort study was a planned secondary analysis of the BALANCE trial from 2014 to 2023, a multicenter randomized clinical trial where serum was collected on day 7 of bacteremia and patients were followed up for 90 days after study enrollment. Serum samples were collected from patients 7 days after initiation of antibiotics; PCT levels were later quantified by an antibody-based assay and therefore were not available to clinicians. Data were analyzed from January to June 2025. Intervention: Patients were randomized to receive either 7 or 14 days of antibiotics. Antibiotic selection, dosing, and route were at the discretion of the treating team. Main Outcomes and Measures: The primary outcome was defined as death from any cause within 90 days of the positive index blood culture result. Secondary outcomes included death by any cause while admitted to the ICU, death by any cause while admitted to the hospital, number of days alive and not admitted to the ICU within 28 days of the index positive blood culture, number of days alive and not admitted to hospital within 28 days of the index positive blood culture, and the duration of mechanical ventilation. Results: A total of 125 patients (median age 63, [IQR, 58-79] years; 80 [64.0%] male) were included in this study. Sixty-five participants (52%) had low PCT levels (<250 pg/mL) and 60 (48%) had high PCT levels (≥250 pg/mL) on day 7. The high PCT group was older, had more comorbidities, and had a higher prevalence of community-acquired bacteremia. Ninety-day mortality was higher in the high vs low PCT group: 21.6% (13 of 60) vs 6.2% (4 of 65) (absolute risk difference [ARD] 15.5%; 95% CI, 3.6%-27.5%). Among patients with high PCT level, 90-day mortality was not different among participants with 7 vs 14 days of antbiotics (ARD, -19.9%; 95% CI, -1.7 to 41.7). Conclusions and relevance: In this cohort study, elevated PCT level on day 7 was associated with increased 90-day mortality. However, prolonging antibiotics beyond 7 days was not associated with improved mortality in patients with a residually high PCT level. Seven days of antibiotics appears sufficient for most patients with bloodstream infections independent of day 7 serum PCT level.