Discussion

We conducted a diagnostic test stewardship intervention, which included implementation of a guideline, clinician education, and audit with feedback, to reduce overuse of tracheal aspirate cultures in mechanically ventilated patients in a single, tertiary care PICU. Following the intervention, we demonstrated a sustained reduction in culture utilization up to two years after the initial intervention, with no increase in mortality, length of stay, PICU readmissions, or VAP diagnosis. Antibiotic use, as measured by the number of antibiotic courses per 100 ventilator days, also decreased during the postintervention period. This work adds to the published data supporting the role of tracheal aspirate culture diagnostic test stewardship in the ICU setting and introduces several novel findings.

Consistent with our findings, Sick-Samuels et al demonstrated a 41% decrease in tracheal aspirate culture orders from a baseline of 10.9 cultures per 100 ventilator days to 6.5 cultures per 100 ventilator days after implementing a tracheal aspirate culture algorithm, without a change in mortality, readmissions, or length of stay. ^{Reference Sick-Samuels, Linz and Bergmann19} Ormsby and colleagues similarly decreased tracheal aspirate culture utilization from a baseline of 10.7 cultures per 100 ventilator days to 7.1 cultures per 100 ventilator days through a series of interventions, including standardizing the process of collecting a tracheal aspirate culture, implementing lab rejection criteria for cultures collected within 72 hours, and through implementation of a consensus guideline for tracheal aspirate culture collection. ^{Reference Ormsby, Conrad and Blumenthal20} Of note, both studies had a substantially higher rate of tracheal aspirate culture utilization than our cohort, suggesting that even in settings with lower baseline tracheal aspirate culture utilization, including in the postacute care setting, tracheal aspirate culture diagnostic test stewardship appears safe and effective.

Further, and a relative strength of our study, we additionally systematically evaluated the appropriateness of tracheal aspirate cultures collected using our consensus guideline as a gold standard for adjudicating appropriateness. Reassuringly, we observed a decrease in “inappropriate” tracheal aspirate culture utilization, while the rate of “appropriate” testing increased following our intervention. Coupled with no observed changes in patient-centered outcomes including length of stay, mortality, and VAP diagnosis, this finding supports both the safety of such diagnostic test stewardship interventions as well as the ability of these interventions to specifically target unnecessary testing, including in the complex PICU environment. Additionally, we believe providing feedback on specific scenarios where cultures were inappropriately obtained facilitated uptake of our intervention. In a mixed-methods study conducted concurrently with this diagnostic test stewardship effort, we identified that practice variation as to what clinical scenarios triggered collecting a respiratory culture as well as collecting tracheal aspirate cultures as a “default” practice were drivers of culture overuse. By focusing our tracheal aspirate culture guideline and our monthly feedback on specific clinical scenarios where tracheal aspirate cultures are particularly low yield (for example, in the setting of isolated fevers or isolated secretion changes), we were able to at least partially address these barriers. ^{Reference Chiotos, Marshall and Kellom24}

We also demonstrated a reduction in antibiotic treatment of VAI following the intervention, lending additional support that diagnostic test stewardship is a promising antibiotic stewardship strategy in the PICU setting. ^{Reference Barlam, Cosgrove and Abbo25} This finding aligns with work done by Woods-Hill and colleagues, who performed a multicenter study evaluating the impact of blood culture stewardship across 14 PICUs, which demonstrated a significant reduction in broad-spectrum antibiotic use following the intervention. ^{Reference Woods-Hill, Colantuoni and Koontz26} Outside the PICU setting, the potential for diagnostic test stewardship interventions to reduce antibiotic overuse is also illustrated by urine culture diagnostic test stewardship efforts in adults. ^{Reference Trautner, Grigoryan and Petersen12–Reference Vaughn, Gupta and Petty14} Finally, greater utilization of tracheal aspirate cultures has been associated with greater antibiotic utilization, highlighting tracheal aspirate culture diagnostic test stewardship as a high-yield target for future PICU-based antibiotic stewardship efforts. ^{Reference Prinzi, Parker, Thurm, Birkholz and Sick-Samuels9,Reference Albin, Saravolatz, Petrie, Henig and Kaye18}

Finally, commonalities in the various consensus-based guidelines across reports highlight key targets for reducing tracheal aspirate culture overuse. First, cultures collected in the setting of isolated fever without any other symptoms localizing to the respiratory tract account for between 20% and 44% of tracheal aspirate culture orders, highlighting this as a potentially impactful target to reduce overall culture utilization rates. ^{Reference Chiotos, Marshall and Kellom24,Reference Sick-Samuels, Fackler, Berenholtz and Milstone27} Second, and likely related, tracheal aspirate cultures are obtained reflexively along with blood and urine cultures in the evaluation of fever or other instability in up to approximately one-third of patients. ^{Reference Albin, Saravolatz, Petrie, Henig and Kaye18,Reference Sick-Samuels, Fackler, Berenholtz and Milstone27} In a study conducted in an adult ICU, having a tracheal aspirate cultures obtained as part of a “pan culture” event increased the odds of receiving two or more days of broad-spectrum antibiotics by approximately 2.5-fold. ^{Reference Albin, Saravolatz, Petrie, Henig and Kaye18} Finally, repeat cultures collected within 72 hours are seldom informative but are nevertheless common, so implementation of lab-based rejection criteria or other automated decision support to avoid oversampling within a short interval may prove to be a low-burden, but impactful interventions. ^{Reference Ormsby, Conrad and Blumenthal20,Reference Sick-Samuels, Fackler, Berenholtz and Milstone27,Reference Feldman, Shah and Ahn28}

Our study has several important limitations. First, we implemented our intervention during the COVID-19 pandemic, which itself impacted culture rates and antibiotic use prior to our intervention, likely due to impacts on respiratory virus epidemiology and PICU case mix. ^{Reference Kanthimathinathan, Buckley and Davis29} We sought to overcome this limitation by analyzing an additional year of postintervention data and demonstrated no change in our centerline. Although culture utilization rates were trending upward at the end of this time, rates nevertheless remained substantially lower than the pre-COVID-19 baseline period. We also evaluated the appropriateness of tracheal aspirate cultures and showed a significant decrease in the proportion of cultures classified as inappropriate, an outcome measure less sensitive to pandemic effects and more specific to the intervention itself. Second, our study was performed in a single center and may not generalize to other settings. However, the consistency of our findings across at least two other studies strengthens generalizability, at least to other tertiary care PICUs. Finally, our assessment of tracheal aspirate culture appropriateness is limited to only scenarios where cultures were obtained, rather than scenarios where cultures were not obtained. Such an analysis was not feasible given that we were unable to systematically ascertain scenarios where a clinician decided not to obtain a culture.

Overall, our findings add to a growing body of literature supporting tracheal aspirate culture diagnostic test stewardship as an effective strategy to both reduce test overutilization and decrease antibiotic overuse stemming from overdiagnosis of VAI. Future studies should focus on optimal strategies for implementing tracheal aspirate culture stewardship interventions, which will likely include clinician-facing interventions such as guidelines coupled with lab-based interventions including rejection or reflex criteria.