Impact on antimicrobial consumption of procalcitonin-guided antibiotic therapy for pneumonia/pneumonitis associated with aspiration in comatose mechanically ventilated patients: a multicenter, randomized controlled study

Abstract

Background In comatose patients receiving oro-tracheal intubation for mechanical ventilation (MV), the risk of aspiration is increased. Aspiration can lead to chemical pneumonitis (inflammatory reaction to the gastric contents), or aspiration pneumonia (infection caused by inhalation of microorganisms). Distinguishing between the two types is challenging. We tested the interest of using a decisional algorithm based on procalcitonin (PCT) values to guide initiation and discontinuation of antibiotic therapies in intubated patients. Methods The PROPASPI (PROcalcitonin Pneumonia/pneumonitis Associated with ASPIration) trial is a multicenter, prospective, randomized, controlled, single-blind, superiority study comparing two strategies: (1) an intervention group where threshold PCT values were used to guide initiation and discontinuation of antibiotics (PCT group); and (2) a control group, where antibiotic therapy was managed at the physician’s discretion. Patients aged 18 years or over, intubated for coma (Glasgow score ≤ 8), with MV initiated within 48 h after admission, were eligible. The primary endpoint was the duration of antibiotic treatment during the first 15 days after admission to the ICU. Results From 24/2/2015 to 28/8/2019, 1712 patients were intubated for coma in the 5 participating centers, of whom 166 were included in the study. Data from 159 were available for intention-to-treat analysis: 81 in the PCT group, and 78 in the control group. Overall, 67 patients (43%) received antibiotics in the intensive care unit (ICU); there was no significant difference between groups (37 (46%) vs 30 (40%) for PCT vs control, p = 0.432). The mean duration of antibiotic treatment during the first 15 days in the ICU was 2.7 ± 3.8 days; there was no significant difference between groups (3.0 ± 4.1 days vs 2.3 ± 3.4 days for PCT vs control, p = 0.311). The mean number of days under MV was significantly higher in the PCT group (3.7 ± 3.6 days) than in controls (2.7 ± 2.5 days, p = 0.033). The duration of ICU stay was also significantly longer in the PCT group: 6.4 ± 6.5 days vs 4.6 ± 3.5 days in the control group (p = 0.043). After adjustment for SAPS II score, the difference in length of stay and duration of mechanical ventilation between groups was no longer significant. Conclusion The use of PCT values to guide therapy, in comparison to the use of clinical, biological (apart from PCT) and radiological criteria, does not modify exposure to antibiotics in patients intubated for coma. Trial registration Clinicaltrials.gov Identifier NCT02862314.

Change over time and agreement between clinical markers of disease resolution in dogs with aspiration‐induced lung injury

“…For example, acute‐phase protein monitoring helped in guiding the introduction of antibiotics in patients with aspiration pneumonia. However, it did not reduce the duration of antibiotic exposure compared to the control group, in which antibiotic treatment was guided by clinical resolution of symptoms 12 …”

“…For example, acute-phase protein kinetics may aid in determining the duration of antibiotic therapy and assist in identifying treatment failures. [12][13][14][15][16][17] However, acute-phase protein monitoring has not been as widely adopted in patients with pulmonary aspiration syndromes, which may be partly due to the mixed results when compared to patients with other causes of acute respiratory infections. 12,14,15,[18][19][20] For example, acute-phase protein monitoring helped in guiding the introduction of antibiotics in patients with aspiration pneumonia.…”

“…[12][13][14][15][16][17] However, acute-phase protein monitoring has not been as widely adopted in patients with pulmonary aspiration syndromes, which may be partly due to the mixed results when compared to patients with other causes of acute respiratory infections. 12,14,15,[18][19][20] For example, acute-phase protein monitoring helped in guiding the introduction of antibiotics in patients with aspiration pneumonia. However, it did not reduce the duration of antibiotic exposure compared to the control group, in which antibiotic treatment was guided by clinical resolution of symptoms.…”

“…However, it did not reduce the duration of antibiotic exposure compared to the control group, in which antibiotic treatment was guided by clinical resolution of symptoms. 12 Recent work in dogs suggests less reliance on serial TXR and more focus on acute-phase protein monitoring during disease recovery to direct treatment decisions. For example, reported high C-reactive protein (CRP) concentrations in dogs with bacterial pneumonia have led to others investigating CRP normalisation as a marker to guide antibiotic treatment durations.…”

“…In some patient populations with bacterial pneumonia, acute‐phase protein kinetics has shown promise in assessing clinical response during the initiation of treatment and later during disease recovery. For example, acute‐phase protein kinetics may aid in determining the duration of antibiotic therapy and assist in identifying treatment failures 12–17 . However, acute‐phase protein monitoring has not been as widely adopted in patients with pulmonary aspiration syndromes, which may be partly due to the mixed results when compared to patients with other causes of acute respiratory infections 12,14,15,18–20 .…”