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Department of Clinical Pharmacy
University of Michigan College of Pharmacy
Infectious Diseases Clinical Pharmacist
Ann Arbor, Michigan
Jason M. Pogue, PharmD, has disclosed that he has received consulting fees from Entasis, GlaxoSmithKline, Merck, Qpex, Shionogi, Utility, and Venatorx.
I am a firm believer that the 2 most important interventions a stewardship team can make to improve outcomes in critically ill patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-acquired bacterial pneumonia (VABP) are (1) employing strategies to minimize time to appropriate therapy and (2) optimizing dosing.
Mapping the Fastest Route
My focus here is on time to appropriate therapy. This means developing empiric treatment pathways and wide-reaching strategies that ensure your sickest patients have a high probability of getting appropriate therapy in the time before patient-specific interventions have been identified, while also limiting unnecessary broad-spectrum antibiotic usage.
To help accomplish this, I am a big fan of unit-specific respiratory combination gram-negative antibiograms. These tell me the combination of antibiotics—on a population level—most likely to have in vitro activity against the flora of a given ICU. We have found that optimal empiric regimen often varies among ICUs within a health system—or even within a given hospital—and, for some units, combination therapy offers little benefit over monotherapy. These data can be used to develop empiric therapy recommendations for critically ill patients with HABP/VABP.
One Size Does Not Fit All
However, it is important that these combination antibiograms are not overapplied within an institution. Just because a combination antibiogram suggests that meropenem and tobramycin should be used empirically for HABP/VABP in the ICU, that does not mean this should be the empiric HABP recommendation hospital wide.
The microbiology of HABP in floor patients is poorly described and more likely to be susceptible to single antimicrobial agents, and the consequences of inappropriate empiric therapy are much less in a hemodynamically stable population. Therefore, a risk-stratification approach needs to be applied to the empiric therapy guideline, and most floor patients in most institutions should receive empiric gram-negative monotherapy.
Although it is important to develop these strategies within an institution, it is perhaps even more important to pair them with real-time, patient-specific stewardship to further optimize outcomes, particularly in critically ill ICU patients with pneumonia. It is vital to work closely with frontline ICU pharmacists and physicians to take into consideration microbiological histories, recent antimicrobial exposures, and drug allergies to optimize therapy on an individual level.
For example, if a hemodynamically unstable patient with pneumonia has just received 2 weeks of piperacillin/tazobactam, I don’t care what the empiric pathway states—piperacillin/tazobactam is a poor empiric antibiotic selection.
Don’t Avoid Novel Agents
Similarly, if a patient has a medical history of recently treated Pseudomonas aeruginosa pneumonia, it is critical that healthcare professionals have a clear understanding of the commonality of coresistance among traditional antipseudomonal β-lactams. In these cases, you should be quick to use novel therapies. To me, the risk related to delays in time to appropriate therapy significantly outweighs those of a short empiric course of a novel therapy. Besides, novel agents can always be de-escalated if the cultures demonstrate a susceptible isolate.
I think the best stewardship programs empower ICU healthcare professionals to appropriately use novel agents—particularly in the empiric setting—to fully optimize patient outcomes. In my own experience, the ICU pharmacists I worked closely with knew much better than I did—at that critical time zero—which patients needed novel agents empirically. I supported them using these agents when appropriate, with a clear understanding that use would be paired with the results of microbiological cultures and de-escalation if definitive treatment was not required.
Recognize Limits and Always Consider Individual Patient and Setting Factors
Finally, it is important to recognize and acknowledge that no matter how strong our empiric therapy process is, given the high global rates of antimicrobial resistance, in a fair number of patients we are going to “miss” with our empiric selection. In these patients where empiric therapy was inappropriate, real-time positive culture alerts to stewardship personnel—ideally paired with rapid diagnostic tests—can minimize delays in therapy. It is crucial that frontline healthcare professionals and stewardship personnel are aware what rapid diagnostic tests do—and do not—detect so that appropriate modifications are made based on the information.
Probably the best example of this is with P aeruginosa. Resistance to β-lactams in this organism is primarily linked to up- or downregulation of chromosomal mechanisms. Therefore, for example, the absence of a carbapenemase gene does not rule out carbapenem resistance, and patient-specific (eg, microbiological and antibiotic history, clinical response, and severity of illness) and hospital-specific (eg, unit-specific antibiogram) characteristics should drive antimicrobial decisions.
What strategies do you use to minimize time to appropriate therapy? How often do you consult with pharmacists and other team members in treatment decisions? Please answer the polling question and join the conversation by posting a comment in the discussion section.