DNP 810 Module 2 Appraising and Grading the Evidence Example

How Strong Is the Case for Redosing Protocols? Appraising and Grading Five Sources on Delayed Second Antibiotic Doses

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Doctor of Nursing Practice Program, Aspen University

DNP 810: Evidence-based Practice for Quality Improvement

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Month Day, Year

How Strong Is the Case for Redosing Protocols? Appraising and Grading Five Sources on Delayed Second Antibiotic Doses

An evidence-based practice project must show not only that evidence exists but how strong it is and what it allows the project to claim. This paper appraises five sources relevant to the question of whether a nurse and pharmacist redosing protocol reduces late antibiotic redosing for septic patients held in the emergency department awaiting beds. It places each source on a hierarchy of evidence, appraises its design and quality, and grades the body of evidence as a whole.

The Hierarchy Used

Hierarchies of evidence rank designs by their ability to answer a particular type of question. For questions about the effectiveness of an intervention, a widely cited framework places systematic reviews of randomized trials at the top, followed by individual randomized trials, then observational studies with controls such as quasi-experimental and cohort designs, then descriptive studies, and finally expert opinion. The same framework notes that different questions, such as those about meaning or feasibility, call for different hierarchies (Evans, 2003). Because this project asks about effectiveness, the effectiveness hierarchy applies, while evidence about the size and consequences of the problem is judged by its own standards.

Evidence on the Intervention

Only one peer-reviewed study tested an intervention like the one proposed. At a tertiary academic emergency department, pharmacists were given authority to order follow-up antibiotic doses for high-risk boarded patients for up to 24 hours. In a pre-post comparison of 181 patients with a historical control group, major delays occurred in 13% of the intervention group and 48% of controls, with the largest reductions for six-hour and eight-hour dosing intervals; in-hospital mortality was also lower, 3% versus 11% (Payne-Cardona et al., 2021).

The design sits in the middle of the hierarchy: a quasi-experimental study without randomization or concurrent controls. Its strengths are a clear, operational outcome, a meaningful effect size and an intervention described well enough to replicate. Its weaknesses are the historical comparison, which cannot rule out other changes over time; a single academic site with dedicated emergency pharmacists, which may not reflect a community hospital; a modest sample; and a mortality difference that is surprising in size and may reflect differences between the groups rather than the intervention. Its quality is good for its design, but its level is limited.

Evidence on the Problem and Its Consequences

Three observational studies establish the problem. A retrospective cohort of 828 sepsis patients found major second-dose delays in 33%, strongly associated with shorter dosing intervals and emergency department boarding, and in exploratory analysis associated with higher mortality and mechanical ventilation (Leisman et al., 2017). As a single-site cohort using retrospective data, it demonstrates association, not causation, but its large sample, clear definitions and adjustment for several confounders make it a good-quality study at its level.

A cohort of 41,256 admissions from one emergency department found that the longer patients boarded, the more of them died in hospital: 2.5% of those boarding under two hours and 4.5% of those boarding 12 hours or more, with longer hospital stays, and the association persisted after adjustment (Singer et al., 2011). It does not address antibiotic timing directly but shows that boarding itself is a risk context.

Finally, a prospective study of 384 critically ill patients in 68 intensive care units found that 16% of patients treated for infection with beta-lactam antibiotics did not reach target drug exposure, and those patients were 32% less likely to have a positive clinical outcome (Roberts et al., 2014). It provides a mechanism: time-dependent antibiotics lose effect when concentrations fall below target, which a late dose would cause.

Guideline Evidence

The international sepsis guidelines recommend optimizing antimicrobial dosing strategies based on accepted pharmacokinetic and pharmacodynamic principles (Evans et al., 2021). Guidelines are developed by expert panels grading the underlying evidence, and this recommendation supports attention to dosing and timing, though it does not address redosing protocols specifically.

Internal Evidence

Evidence-based practice also weighs internal evidence, the organization's own data. The hospital's audit of 150 sepsis admissions, which found major delays in 38%, is descriptive evidence of modest quality: it was retrospective, relied on charted administration times and was completed by one reviewer. It nonetheless matters because it shows that the published problem exists locally at a similar rate, with the same pattern by dosing interval and boarding time. To strengthen it before it serves as a baseline, a second reviewer will abstract a random 20% of charts, and disagreements will be resolved against the medication administration record's scan times, which are more reliable than manual entries.

Staff experience is a further form of internal evidence. Emergency nurses and pharmacists interviewed during the audit consistently described the same gap, the absence of an active order for the second dose, which supports the causal pathway the intervention targets.

Grading the Body of Evidence

Viewed as a whole, the studies agree that second-dose delays are common and predictable, that they occur most often in boarders and with short dosing intervals, and that inadequate antibiotic exposure is associated with worse outcomes. Evidence that the proposed intervention reduces delays comes from a single quasi-experimental study with a large effect. The body of evidence is therefore strong for the existence and plausibility of the problem, and low to moderate for the effectiveness of the specific intervention.

That grade has direct consequences for the project. It justifies implementing and evaluating the protocol as quality improvement, since the risk is low and the potential benefit is meaningful, but it does not justify claiming that the protocol will reduce mortality. The project will measure delays as its primary outcome and monitor mortality only descriptively.

Conclusion

Appraising five sources on a hierarchy of effectiveness evidence shows a well-documented problem and a promising but thinly tested intervention. The strongest direct evidence is a single pre-post study, supported by cohort data on delay and boarding and by pharmacokinetic evidence on the harm of low drug exposure. Grading the evidence honestly sets the limits of what the project can claim and strengthens the case for careful local evaluation.

References

Evans, D. (2003). Hierarchy of evidence: A framework for ranking evidence evaluating healthcare interventions. Journal of Clinical Nursing, 12(1), 77-84. https://doi.org/10.1046/j.1365-2702.2003.00662.x

Evans, L., Rhodes, A., Alhazzani, W., Antonelli, M., Coopersmith, C. M., French, C., Machado, F. R., Mcintyre, L., Ostermann, M., Prescott, H. C., Schorr, C., Simpson, S., Wiersinga, W. J., Alshamsi, F., Angus, D. C., Arabi, Y., Azevedo, L., Beale, R., Beilman, G., . . . Levy, M. (2021). Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock 2021. Critical Care Medicine, 49(11), e1063-e1143. https://doi.org/10.1097/CCM.0000000000005337

Leisman, D., Huang, V., Zhou, Q., Gribben, J., Bianculli, A., Bernshteyn, M., Ward, M. F., & Schneider, S. M. (2017). Delayed second dose antibiotics for patients admitted from the emergency department with sepsis: Prevalence, risk factors, and outcomes. Critical Care Medicine, 45(6), 956-965. https://doi.org/10.1097/CCM.0000000000002377

Payne-Cardona, M., San Luis, V. A., Aazami, R., Dermendjieva, M., Erin, M., Kirkwood, J., Tong, C., Marks, G., Smith, E. A., Torbati, S. S., & Gilmore, J. F. (2021). Pharmacist driven antibiotic redosing in the emergency department. The American Journal of Emergency Medicine, 50, 160-166. https://doi.org/10.1016/j.ajem.2021.07.039

Roberts, J. A., Paul, S. K., Akova, M., Bassetti, M., De Waele, J. J., Dimopoulos, G., Kaukonen, K.-M., Koulenti, D., Martin, C., Montravers, P., Rello, J., Rhodes, A., Starr, T., Wallis, S. C., & Lipman, J. (2014). DALI: Defining antibiotic levels in intensive care unit patients: Are current beta-lactam antibiotic doses sufficient for critically ill patients? Clinical Infectious Diseases, 58(8), 1072-1083. https://doi.org/10.1093/cid/ciu027

Singer, A. J., Thode, H. C., Jr., Viccellio, P., & Pines, J. M. (2011). The association between length of emergency department boarding and mortality. Academic Emergency Medicine, 18(12), 1324-1329. https://doi.org/10.1111/j.1553-2712.2011.01236.x