In our study involving 2076 patients hospitalized for community-acquired pneumonia, initiation of antibiotic therapy within 4 hours of presentation varied significantly by site of treatment and was associated primarily with patient factors that reflect severity of illness at the time of presentation. Tachycardia (pulse ≥125/minute) and tachypnea (respiratory rate ≥ 30/minute), both identified as independent predictors of mortality for patients with pneumonia,[14
] were independently associated with initiation of timely antibiotic therapy. Suspected aspiration pneumonia, also associated with an increased risk of short-term mortality and frequently representing a marker of underlying neurologic impairment,[16
] was also an independent predictor of this outcome. These findings suggest that ED medical providers are appropriately using their clinical judgment to identify more severely ill patients likely to benefit most from rapid initiation of antibiotic therapy.
In our study, anemia (hematocrit <30%) was negatively associated with timely initiation of antibiotic therapy. This unexpected finding is inconsistent with our other observations that markers of severity of illness are postively associated with timely initiation of antibiotic therapy. Although the association between hematocrit and the study outcome could be explained if anemia was a confounder of factors previously shown to have a negative association with timeliness of antibiotic therapy (e.g., race and hospital size) or was associated with factors that could potentially impede timely initiation of therapy (e.g., time of presentation), we found no association between anemia and these types of variables.
Our observations that patient factors reflecting severity of illness are positively associated with timely initiation of antibiotic therapy are consistent with prior studies, which reported that tachycardia, tachypnea, and fever were independently associated with timely antibiotic therapy.[9
] Although not found to be associated with timely initiation of antibiotic therapy in our analysis, prior studies have identified patient race, prior receipt of antibiotics within 48 hours, and history of cerebrovascular disease as having independent associations with this process of care.[9
Our study failed to identify any provider or hospital level factors associated with timely inititation of antibiotic therapy. Prior studies have suggested that geographic location, time of initial presentation (7 am – 3 pm, 11 pm – 7 am), admission to a major teaching hospital, emergency department crowding, and larger hospital size were negatively associated with initiation of antibiotic therapy within 4 hours of presentation to the hospital.[9
] In addition, high nurse-to-bed ratios and receipt of first dose antibiotics within the ED have been previously found to be positively associated with timely initiation of antibiotic therapy.[9
Even the most intensive multi-faceted guideline implementation strategy used in the original EDCAP Trial did not significantly improve the performance rate for rapid initiation of antibiotic therapy, which was nearly 80% across all study sites.[13
] Of 12 previously published interventional studies designed to improve performance on this quality measure, 8 resulted in significant improvements in antibiotic timeliness.[13
] Interventions that focused exclusively on a single process of care, were multi-faceted in design, and involved multiple stakeholders in patient care (e.g., physicians, nurses, pharmacists) were most likely to be successful.
The limitations of our study should be acknowledged. First, demographic differences between patients who were and were not enrolled in the EDCAP trial and the fact that the majority of study sites were from urban areas may diminish the generalizability of our findings. However, the 80% enrollment rate was laudable for a large multicenter trial. Second, the associations between patient, provider, or hospital factors and timeliness of initial antibiotic therapy examined in our study might have been altered by the design of the EDCAP Trial to test the effectiveness of three intervention arms of incremental intensity in increasing the proportion of low-risk patients treated as outpatients. However, we did not observe any statistically significant differences in our outcome across intervention arm or any first-order interactions between intervention arm and the independent predictors of our study outcome. Third, because antibiotic timeliness as a quality measure has been hotly debated due to potential unintended consequences of this recommendation, the Center for Medicare and Medicaid Services and the Joint Commission now use a 6 hour benchmark to define antibiotic timeliness.[1
] Finally, that provider and system-level factors were not independently associated with this outcome in our analysis may reflect a lack of statistical power in this 32-site study, or a failure to collect the most relevant provider and hospital level factors.
In conclusion, in a cohort of inpatients at 32 hospitals participating in a quality improvement trial for pneumonia, we found that timely initiation of antibiotic therapy is related primarily to patient factors that reflect severity of illness at presentation. Although this study demonstrates an opportunity to improve performance on this quality measure in nearly one quarter of patients hospitalized for pneumonia, we failed to identify any provider or hospital level factors to target in such quality improvement efforts.