Table 2.
Procalcitonin Randomized Controlled Trials for Infections in Critically Ill Adult Patients
| First Author (Year) [Reference] Trial Name |
Setting (Country) |
Number and Type of Infection | PCT Algorithm | Exclusion Criteria | Antibiotic Reduction Outcomes | Clinical Outcomes |
|---|---|---|---|---|---|---|
| Nobre (2008) [17] | 1 Medical-Surgical ICU (Switzerland) | 79 patients with severe sepsis/septic shock | Discontinuation only: stop antibiotics if PCT decreased 90% from initial value, but not before day 3 (if baseline <1 µg/L) or day 5 (if baseline ≥1) | Organisms or conditions requiring prolonged duration of therapy, severe viral or parasitic infections, antibiotics started ≥48 hours before enrollment, severely immunocompromised, withholding of life support | 4 day reduction in median duration of antibiotic therapy (P = .003) | No different in mortality and recurrent infection; reduced ICU LOS by 2 days (P = .03) |
| Hochreiter (2009) [28] | 1 Surgical ICU (Germany) | 110 patients with suspected or confirmed sepsis | Discontinuation only: stop antibiotics if PCT <1 µg/L or decrease to 25%–35% of initial value over 3 days | Antibiotics started before ICU admission, therapy limitation due to goals of care | Mean 5.9 vs 7.9 days (P < .001) | No difference (treatment success, ICU LOS, SOFA score, hospital mortality) |
| Schroeder (2009) [29] | 1 Surgical ICU (Germany) | 27 patients with severe sepsis | Discontinuation only: stop antibiotics if PCT <1 µg/L or decrease to <35% of initial value over 3 days | Antibiotics started before ICU admission | Mean 6.6 vs 8.3 days (P < .001) | No difference (SAPS II or SOFA score, ICU stay, hospital mortality) |
| Stolz (2009) [26] ProVAP |
7 ICUs in 3 hospitals (Switzerland, United States) | 101 patients with ventilator-associated pneumonia | Discontinuation only: after 72 hours, antibiotic cessation strongly encouraged (<0.25 µg/L), encouraged (0.25–0.5 or decrease by ≥80%), discouraged (≥0.5 or decrease by <80%), strongly discouraged (>1) | Pregnant, enrolled in another trial, immunosuppressed, coexisting extrapulmonary infection requiring antibiotics for >3 days | 13 vs 9.5 antibiotic-free days alive 28 days after ventilator-associated pneumonia onset (overall 27% reduction in antibiotic therapy, P = .038) | No difference (mechanical ventilation-free days, ICU-free days alive, hospital LOS, 28-day mortality) |
| Boudama (2010) [30] PRORATA |
5 medical ICUs and 2 surgical ICUs (France) | 621 patients with suspected infection | Initiation and Discontinuation: antibiotics strongly discouraged (<0.25 µg/L), discouraged (0.25–0.5), encouraged (0.5–1), strongly encouraged (≥1) (daily PCT measurements). Discontinuation also if PCT decreased ≥80% from peak | Pregnancy, bone marrow transplant, or neutropenic, infections requiring long-term antibiotics, poor chance of survival, and do-not-resuscitate orders | Mean 11.6 vs 14.3 days of therapy (P < .0001) | No difference in noninferiority analysis (28-day and 60-day mortality), but trend towards increased 60-day mortality (+3.8%). No difference in infection relapse or superinfection, mechanical ventilation, ICU and hospital LOS |
| Annane (2013) [49] | 8 ICUs (France) | 58 patients with culture-negative severe sepsis | Initiation and Discontinuation: withhold or stop antibiotics (<0.25 µg/L); antibiotics strongly discouraged (0.25–0.5), recommended (0.5–5), strongly recommended (≥0.5). Higher cutoffs used for postsurgical patients |
Pregnancy, severe burns, trauma, cardiac arrest, postorthopedic surgery, neutropenic, withholding of life-supportive therapies, indisputable clinical infection, antibiotic exposure ≥48 hours before ICU admission | Nonsignificant trend: 67% vs 81% of patients on antibiotics at day 5 (P = .24) | No difference in day 5 mortality, ICU or hospital LOS or mortality, SOFA score at day 3 or 5 (but study terminated early due to low incidence of eligible patients) |
| Shehabi (2014) [31] ProGUARD |
11 ICUs (Australia) | 394 patients with suspected sepsis | Discontinuation only: stop antibiotics if PCT <0.1 µg/L, or 0.1–0.25 and infection is highly unlikely, or subsequent PCT declines >90% from baseline (daily PCT measurements) |
Antibiotics for surgical prophylaxis or proven infection requiring >3 weeks of therapy, fungal or viral infections, immunosuppressed, cardiac surgery or trauma or heat stroke within 48 hours, medullary thyroid or small cell lung cancer, not expected to survive, pregnancy | Nonsignificant trend: median 9 vs 11 days of antibiotic therapy (P = .58) | No difference (ventilation time, ICU and hospital LOS, hospital and 90-day mortality) |
| de Jong (2016) [32] SAPS |
ICUs at 15 hospitals (Netherlands) | 1546 patients with suspected or proven infection | Discontinuation only: stop antibiotics if PCT decreased to ≥80% of peak value, or ≤0.5 µg/L (daily PCT measurements) | Antibiotics for prophylaxis only or gut decontamination, expected ICU stay <24 hours, severe immunosuppression, severe viral or parasitic or tuberculosis infections, moribund, chronic infection (eg, endocarditis) | Median antibiotic consumption of 7.5 vs 9.3 daily defined doses (P < .0001), median treatment duration 5 vs 7 days (P < .0001) | Decreased 28-day mortality (20% vs 25%, P = .0122) and 1-year mortality (36% vs 43%, P = .0188). No difference in hospital and ICU LOS or requirement for additional antibiotics within 28 days. But 5% vs 3% rate of reinfection by same pathogen (P = .0492) |
| Bloos (2016) [50] SISPCT |
33 ICUs (Germany) | 1089 patients with severe sepsis or septic shock | Discontinuation or “Alert”: PCT measured on days 0, 1, 4, 7, 10, and 14. On day 4: change antibiotics or intensify source control efforts if PCT not decreased by ≥50% from baseline value. Other days: stop antibiotics if PCT <1 or decreased by ≥50% from previous value. (2 × 2 factorial study design with sodium selenite administration and PCT arms) | Pregnancy or lactation, selenium intoxication, infections with long recommended treatment durations, immunocompromised, imminent death or treatment limitations | 4.5% reduction in antibiotic exposure per 1000 ICU days (823 days vs 862 days) (P = .02) | No difference in 28-day mortality (25.6% vs 28.2%, P = .34), no differences in procedures for infection source control or diagnosis |
Abbreviations: ICU, intensive care unit; PCT, procalcitonin; LOS, length of stay; SAPS II, Simplified Acute Physiology Score II; SOFA, Sequential Organ Failure Assessment score.