Infectious Diseases II

According to current evidence, PCT should not routinely be measured in patients without signs and

symptoms of infection. The decision to initiate patients on antibiotics without signs and symptoms of

infection using PCT alone would probably lead to antimicrobial overuse and possible adverse effects

associated with antimicrobial therapy. In a PCT study of critically ill patients, 1200 patients were

randomized to either a PCT alert strategy or a standard of care. For those randomized to intervention, a

PCT concentration greater than 1.0 mcg/L generated an alert that mandated clinical intervention, which

included microbiological cultures, additional radiologic assessment, and/or initiation or expansion of

antimicrobial coverage. Overall, this strategy did not lead to an improvement in mortality or time to

appropriate antibiotics. In contrast, patients experienced a greater need for mechanical ventilation,

prolonged ICU LOS, and prolonged antibiotic use.

In critically ill patients with signs and symptoms of infection, a baseline PCT (at the time of the

symptoms) should not be used to determine whether antibiotics should be initiated. The compliance rate

for withholding antibiotics for a low PCT in this scenario has consistently been low. The compliance

rate in clinical practice is likely even lower than that in clinical studies; however, this has not been

evaluated. If a baseline PCT is obtained, it should be used to trend the PCT for the possible early

discontinuation of antibiotics. In a study of patients with signs and symptoms of infection to determine

whether a PCT-guided strategy would limit the initiation of antibiotics, no difference in antibiotic

use was seen. However, this was probably because only 36% of clinicians were compliant with the

recommendation to withhold antimicrobials when the PCT was low. This is in stark contrast with the

86% compliance rate with the recommendation to initiate antibiotics when the PCT was high.

Critically ill patients with signs and symptoms of infection should have a baseline PCT obtained for

trending purposes. A low PCT (or substantial decrease from baseline) during antibiotic treatment

should be used to shorten the duration of antimicrobial therapy. This could be accomplished through

either eliminating unnecessary antibiotics in patients who are not infected or shortening the course

of therapy for patients who are infected. This strategy has been proven safe and effective in a wide

spectrum of critically ill patients. Several studies have evaluated the utility of a PCT-guided strategy

for determining the appropriate time to discontinue and/or de-escalate antibiotics. These studies

consistently show that PCT guidance for discontinuing antimicrobial therapy led to decreases in

antibiotic use without an untoward outcome effect. This has been shown in various ICU populations, in

patients with different severity of illness, and in those with proven infections. The largest PCT study of

critically ill patients (n=1575) was published in 2016. It demonstrated a significant decrease in the use

of antimicrobials (median 5 days vs. 7 days) and 28-day mortality (20% vs. 25%; p=0.012). A recent

meta-analysis showed that use of PCT to guide discontinuation of antimicrobial therapy may have a

short-term mortality benefit.

A recent prospective study showed that the inability to decrease PCT by at least 80% by day 4 was an

independent predictor of mortality.

PCT for antibiotic cessation. In certain scenarios, PCT concentrations may be affected. For example,

some clinicians recommend using different cutoffs (e.g., greater than 0.5 mcg/L) in patients with stage

5 chronic kidney disease or requiring dialysis. Furthermore, in some studies, the PCT cutoff is greater

than 1.0 mcg/L among patients with recent surgery.

this could represent bacterial co-infection, could be a marker of severity of acute respiratory distress

syndrome, or respiratory failure could cause immune dysregulation that increases the production of

cytokines. Due to the unclear cause of elevated PCT in COVID-19, it is not advisable to use the PCT

level by itself to guide antibiotic therapy.