Proteína C reativa versus procalcitonina para orientar a duração da terapia antimicrobiana em pacientes sépticos internados em centrode terapia intensiva

Abstract

Procalcitonin (PCT) guidance has been proved to safely shorten the duration of the antibiotic therapy in septic patients. C-reactive protein (CRP) has not been tested in this context. We sought to evaluate if CRP was as useful as PCT to guide antibiotic therapy in intensive care patients with severe sepsis or septic shock. Randomized noninferiority clinical trial (NCT00934011) conducted at two University Hospitals inBrazil. Patients with severe sepsis or septic shock admitted at one of two intensive care units (ICU) of the Universidade Federal de Minas Gerais were assessed for inclusion, and randomized to one of the two groups: PCT group and CRP group. According to the group of randomization, antibiotic were stopped when the initial levels of PCT and CRP had decreased atleast 90% and 50%, respectively. Antibiotic interruption did not occur before Day 4, if baseline PCT levels were < 1ng/ml or baseline CRP levels were <100mg/L; and before Day 5, if baseline PCT levels were g 1ng/ml or baseline CRP levels were 3 100mg/L. The main endpoint was "duration of antibiotic therapy" for the first episode of infection. The secondary endpoint were "total days under antibiotictherapy", "antibioticfree days per 1000 days alive" during follow up, "all-cause 28-day morta|ity", "|ength of stay in the hospital", "|ength of stay in the |CU". Patients were followed up for 28 days, or until death, if it occurred in the interim. As results, 94 patients were randomized: 49 patients to the PCT group and 45 patients to the CRP group. Overall, the mean age was 59.8 (SD: 16.8) years, and 57 (60.6%) patients weremale. Fifty-six out of the 94 (59.6%) patients had septic shock, without significant difference between the groups (p=O.53). Median Apache II and SOFA score, both measured on inclusion, were 21 (0.1-0.3: 14-26) points and seven (Q1-Q3: 4-10) points, respectively, and no difference between the groups was observed (p=O.828 e p=O,400). Median CRP levels on inclusion were similar for patients of the PCT group (242; Q1-Q3:133.7 - 313.2 mg/L) and for those of the CRP group (186.1; O.1-Q3: 74.4 - 299 mg/L), p=0.403. Similarly, the median PCT levels on inclusion were similar among patients of the PCT groups and those of CRP group (3.87; Q1-Q3: 1.56-19.96ng/ml vs. 3.81; Q1-Q3: 1.37-18.60 ng/ml; p=0.691). The median duration of antibiotic therapy for the first episode of infection was similar in the two groups: 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; HR: 1.206 (95% CI: 0.774-1.30), p=0.060, and remained so after adjusting for severity (SOFA score, Apache II or S/-\PS III). The median of total days under antibiotic therapy during follow-up was higher in patients of the PCT group than in those of the CRP group (13 vs. 8 days, p=0.183). Finally, the number of antibioticfree days per 1000 days alive was similar among thetwo groups (357.14, Q1-Q3: 33.3-509.2 in the CRP group vs. 357,1, Q1-Q3: 0-541 in the PCT group; p=0.998). The length of stay (LOS) was similar between PCT group and CRP group for the ICU (14 vs 12 days, p=0.164) and the hospital (36 in PCT vs 25 days, p=0.175). Protocol overruling occurred in only nine (9.57%) patients, without significant difference between the groups. Twenty-one patients died in each group(p=0.836). Conclusion: In this study, we found that CRP might be as useful as PCT to reduce the antibiotic use in septic patients admitted to the ICU, with no apparent harm.