2017年 Crit Care に発表された、人工呼吸患者の肺炎に対するDe-escalationのクロスオーバーStudy。
P : mechanically ventilated patients with suspected pneumonia
E : enhanced antimicrobial de-escalation (EAD)
EAD group had their antibiotic orders and microbiology results reviewed daily by a dedicated team comprised of a second-year critical care fellow, an ICU attending physician and an ICU pharmacist. Antibiotic de-escalation recommendations were made when appropriate based on microbiologic test results and clinical response to therapy.
C : routine antibiotic management (RAM)
There was no difference between groups in total antibiotic days *1 7.0 days (4.0, 9.0) versus 7.0 days (4.0, 8.8) (P = 0.616)); hospital mortality (25.2% versus 35.4% (P = 0.061)); or hospital duration (12.0 days (6.0, 20.0) versus 11.0 days (6.0, 22.0) (P = 0.918).
T : prospective cross-over trial
"Antimicrobial de-escalation was defined as a change in the initially prescribed antibiotic regimen resulting in one of the following: (1) a reduction in the number of antibiotics prescribed, (2) elimination of antibiotic coverage for a class of pathogens (e.g., stopping coverage for Staphylococcus aureus), and (3) changing the antibiotic regimen to a more narrow-spectrum regimen. For purposes of this investigation, antibiotics were ranked according to their activity spectrum against pneumonia pathogens, emphasizing Gram-negative bacteria (5, highest; 0, lowest) and Gram-positive bacteria (1, highest; 0, lowest). For combination regimens, rank was assigned according to the most potent drug. Therapy escalation was defined as the switch to or addition of a drug class or classes with a broader spectrum."
First, the study design did not allow the research team to supplant the ICU teams in terms of overall antibiotic decision-making. The study team could only make recommendations to the ICU teams on de-escalation. Furthermore, the EAD study team was only available during daytime hours and not during weekends or holidays. This may have had an impact on the study team’s ability to influence overall antibiotic management in patients with pneumonia during the time periods the study team was not available.
Second, the EAD team and the ICU teams comprised similar clinicians including intensivists and pharmacists with similar levels of training and experience. This may have contributed to our inability to detect any impact of the EAD program on antibiotic management or clinical outcomes. Based on prior experience, inclusion of an infectious disease specialist or microbiologist might have improved our ability to improve antibiotic utilization with the EAD program.
Third, we had a relatively small number of patients with VAP compared to COP and HAP. However, most of the patients with COP in our study had at least one healthcare-associated risk factor (prior hospitalization, admission from a nursing facility, immune suppression, or prior antibiotic exposure) placing them at higher risk for infection with potentially antibiotic-resistant bacteria.
Another limitation of our study is that the data were derived from a single center, and this necessarily limited the generalizability of our findings. As such, our results may not reflect what one might see at other institutions. For example, all of the ICUs at Barnes-Jewish Hospital are closed units with high-intensity multidisciplinary staffing providing continuous patient care. There is also a long history of antimicrobial stewardship being practiced within these ICUs. The organizational makeup of the ICUs may also have contributed to the negative findings of our study. The presence of high-intensity staffing models in ICUs has previously been suggested as a possible explanation for other negative trials performed in critically ill patients.
Moreover, our study was performed in two medical ICUs. It is possible that our findings might have differed had we selected other types of ICUs, due to differences in case mix, severity of illness, and practice patterns. Last, we did not directly integrate the use of a biomarker such as procalcitonin into the EAD program, which might have allowed further antimicrobial de-escalation and/or reductions in antibiotic duration.
*1:median (interquartile range