Table 1.
Procalcitonin Randomized Controlled Trials for Respiratory Tract Infections in Adult Patients
| First Author (Year) [Reference] Trial Name |
Setting (Country) |
Number and Type of Infection | PCT Algorithm | Exclusion Criteria | Antibiotic Reduction Outcomes | Clinical Outcomes |
|---|---|---|---|---|---|---|
| Christ-Crain (2004) [20] | 1 hospital (Switzerland) | 243 patients with LRTI | Initiation only: antibiotics strongly discouraged (<0.1 µg/L), discouraged (0.1–0.25), encouraged (0.25–0.5), strongly encouraged (≥0.5). Repeat PCT after 6–24 hours if antibiotics withheld | Severely immunocompromised, cystic fibrosis, active tuberculosis, hospital-acquired pneumonia | 47% reduction in antibiotic use (P < .0001) | No difference (including hospital mortality or long- term mortality at mean 5.3 months, hospital or ICU LOS, laboratory outcomes) |
| Christ-Crain (2006) [21] ProCAP |
1 hospital (Switzerland) | 302 patients with CAP | Initiation and Discontinuation: antibiotics strongly discouraged (<0.1 µg/L), discouraged (0.1–0.25), encouraged (0.25–0.5), strongly encouraged (≥0.5). Repeat PCT after 6–24 hours if antibiotics withheld, and at days 4, 6, and 8 | Severely immunocompromised, cystic fibrosis, active tuberculosis, hospital-acquired pneumonia | 52% relative risk of antibiotic exposure and median 5 vs 12 days of antibiotic treatment (P < .001 for both) | No difference (including mortality, ICU admission, treatment success, laboratory outcomes) |
| Stolz (2007) [22] |
1 hospital (Switzerland) | 208 patients with COPD exacerbation | Initiation only: antibiotics discouraged (<0.1 µg/L), discouraged if clinically stable (0.1–0.25), encouraged (>0.25). Repeat PCT after 6–24 hours if antibiotics withheld | Immunosuppression, asthma, cystic fibrosis, infiltrates on chest radiograph, psychiatric illness | 56% relative risk of antibiotic exposure; 40% vs 72% overall antibiotic use (P < .0001 for both) | No difference (including death, treatment success, hospital LOS, ICU admission, improvement in FEV1 at 14 days and 6 months, 6 month rehospitalization rate, mean time to next exacerbation) |
| Briel (2008) [25] | 53 outpatient physicians in (Switzerland) | 458 outpatients with acute respiratory tract infections | Initiation and Discontinuation: antibiotics strongly discouraged (≤0.1 µg/L), discouraged (0.1–0.25), encouraged (>0.25). Repeat PCT after 6–24 hours if antibiotics withheld | Antibiotics within prior 28 days, psychiatric disorders, severe immunosuppression, cystic fibrosis, active tuberculosis, need for immediate hospitalization | 72% decrease in antibiotic use (95% CI, 66%–78%) | No difference in activity restriction at 14 days, or ongoing symptoms or relapsing infection at 28 days |
| Kristoffersen (2009) [45] | 3 hospitals (Denmark) | 223 patients with LRTI | Initiation only: antibiotics discouraged (<0.25 µg/L), encouraged (0.25–0.5), and strongly encouraged (≥0.5). Single PCT measurement | None described | Mean 5.1 vs 6.8 days of antibiotic therapy (P = .007) | No difference (including hospital LOS, ICU admission, hospital mortality) |
| Schuetz (2009) [23] ProHOSP |
6 hospitals (Switzerland) | 1359 patients with LRTI | Initiation and Discontinuation: antibiotics strongly discouraged (≤0.1 µg/L), discouraged (0.1–0.25), encouraged (0.25–0.5), strongly encouraged (≥0.5). Repeat PCT after 6–24 hours if antibiotics withheld, and at days 3, 5, 7, and discharge | Active intravenous drug use, severe immunosuppression, life-threatening comorbidities, hospital-acquired pneumonia, chronic infection requiring antibiotics | Mean 5.7 vs 8.7 days of antibiotic therapy (relative change, −34.8%; 95% CI, −40.3% to −28.7%) | No difference (composite of 30-day adverse outcomes including death, ICU admission, and disease-specific complications, and recurrent LRTI); less frequent antibiotic-associated adverse events (19.8% vs 28.1%) |
| Burkhardt (2010) [24] | 15 primary care practices (Germany) | 550 patients with mild respiratory tract infection | Initiation only: no antibiotics (<0.25 µg/L) or yes antibiotics (≥0.25) | Recent antibiotics, chronic liver disease, recent major surgery, autoimmune or systemic inflammatory disorders, dialysis, medullary C-cell carcinoma | 21.5% vs 36.7% of patients received antibiotics | No difference in significant health impairment after 14 days |
| Long (2011) [46] |
1 hospital (China) | 172 patients with low- risk CAP (discharged from ED) | Initiation only: antibiotics strongly discouraged (≤0.1 µg/L), discouraged (0.1–0.25), encouraged (>0.25). Repeat PCT after 6–12 hours if antibiotics withheld | Pregnancy, antibiotics started ≥48 hours before enrollment, immunocompromised, withholding of life-support, active tuberculosis | 55% relative risk of antibiotic exposure (P = .003); median 5 vs 7 days of antibiotic treatment (P < .001) | No difference (all survived at 4 weeks, with similar clinical and laboratory outcomes) |
| Tang (2013) [47] |
1 hospital (China) |
225 patients with asthma exacerbation | Initiation only: antibiotics strongly discouraged (≤0.1 µg/L), discouraged (0.1–0.25), encouraged (>0.25). Repeat PCT after 6–8 hours if initial PCT <0.25 | Recent antibiotics, other bacterial infections, pneumonia on chest radiograph, other chronic respiratory disease, severe organ dysfunction | 46.1% vs 74.8% of patients received antibiotics (P < .001) | No difference (including asthma control, secondary ED visits, hospital readmission, additional steroids or antibiotics, FEV1) |
| Branche (2015) [48] | 1 hospital (United States) | 300 patients with nonpneumonic LRTI | Initiation only: antibiotics strongly discouraged (≤0.1 µg/L), discouraged (0.1–0.25), encouraged (0.25–0.5), strongly encouraged (≥0.5). PCT intervention arm coupled with viral PCR testing. | Definitive infiltrates on chest radiograph, immunosuppression, hypotension, ICU requirement, ≥15% peripheral bands, conditions known to increase PCT, antibiotics before admission | No difference overall, but less antibiotics in algorithm-adherent patients (2.0 vs 4.0 days; P = .004) | No difference in adverse events (no deaths in either arm; same median hospital LOS and number of posthospitalization healthcare visits) |
Abbreviations: CAP, community-acquired pneumonia; CI, confidence interval; COPD, chronic obstructive pulmonary disease; ED, emergency department; FEV1, forced expiratory volume at 1 second; ICU, intensive care unit; LOS, length of stay; LRTI, lower respiratory tract illness; PCR, polymerase chain reaction; PCT, procalcitonin.