Results
Patients
Three hundred fifty-five patients were assessed for inclusion; of these, 102 were preincluded. Five patients were excluded before randomization, and 97 patients were randomized (Fig. 2). Three patients were excluded after randomization: two patients from the PCT group and one patient from the CRP group. The reasons for exclusion were withdrawal of the consent form (two patients) and technical problems with measuring the markers (one patient). Therefore, 94 patients were included in the final analysis (Fig. 2).
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Figure 2.
Flowchart of inclusion of patients in the study. PCT = procalcitonin, CRP = C-reactive protein.
The average age for the entire studied population was 59.8 ± 16.8 years, and 60.6% of the patients were men. Overall, clinical patients and patients with nosocomial infections were predominant in both groups. No difference in severity scores and in frequency of septic shock was found between the two groups. The main characteristics of the patients included in the study are detailed in Table 1.
Sites of Infection and Microbiology
As shown in Table 1, pulmonary sepsis was the most common infection site in both groups. The proportion of sepsis confirmed through microbiological analysis did not differ significantly between the groups (48.9% for the CRP group vs 42.9% for the PCT group; p = 0.679). The most commonly isolated microorganisms in both groups were S. aureus, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Haemophilus influenzae.
Primary Outcome
The duration of antibiotic therapy for the first episode of infection was similar in both groups (Table 2), with a median of 7.0 (Q1–Q3, 6.0–8.5) days in the PCT group and 6.0 (Q1–Q3, 5.0–7.0) days in the CRP group (p = 0.06). The Cox analysis comparing the risk of having the first course of antibiotic therapy interrupted during the follow-up corroborated these findings, with a HR of 1.206 (95% CI, 0.774–1.3; p = 0.13) (Fig. 3). These results were similar even after adjusting for severity using the APACHE II (HR, 1.172 [95% CI, 0.747–1.838]), SAPS III (HR, 1.204 [95% CI, 0.771–1.879]), and SOFA (HR, 1.183 [95% CI, 0.756–1.851]) scores.
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Figure 3.
Cox analysis showing the risk of antibiotic therapy discontinuation in the first episode of infection for the procalcitonin group (dotted line) and C-reactive protein group (continuous line) (hazard ratio, 1.206 [95% CI, 0.774–1.3]; p = 0.13).
Secondary Outcomes
The number of days on antibiotic therapy during follow-up period was greater in the PCT group than in the CRP group; however, this difference was not significant (13 d vs 8 d, respectively; p = 0.183). The number of antibiotic-free days per 1,000 live days during follow-up was similar for both groups (357.10 vs 357.14; p = 0.998).
The remaining secondary outcomes are presented in Table 3. No significant difference was observed between the two studied groups regarding the rate of clinical cure and recurrence of the first episode of infection, prevalence of nosocomial infection during follow-up, ICU LOS, and hospital LOS. Death by any cause during the 28 days of follow-up was also similar for both groups (32.7% of the patients in the PCT group and 33.3% of the patients in the CRP group; p = 1.0; Table 3).
Protocol overruling occurred in only 13 patients: six (12.2%) patients in the PCT group and seven (15.5%) patients in the CRP group. In 17 (34.7%) patients of the PCT group and eight (17.8%) patients of the CRP group, the antibiotics were maintained for 7 days because of bacteremia and/or a SOFA score above 10 at inclusion (p = 0.037). However, with the exclusion of these 25 patients from the primary outcome analysis, no difference in the median duration of antibiotic therapy between the CRP and PCT groups was observed (p = 0.339).