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What to D.O.

Procalcitonin Reduces Antibiotic Use with No Negative Outcomes

Pescatore, Richard DO

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doi: 10.1097/01.EEM.0000553473.11986.1f
    procalcitonin, antibiotics
    procalcitonin, antibiotics:
    procalcitonin, antibiotics

    The elderly patient presenting to the ED with nonspecific symptoms remains a diagnostic and therapeutic challenge. Often, these patients arrive with general complaints ranging from altered mental status to weakness, subjective ailments that are difficult to quantify or qualify in the space of a brief ED visit.

    They undergo extensive and relatively unremarkable evaluations, and finish their visits no better than when they arrived. Many physicians are loathe to discharge these patients because they typically carry multiple comorbidities and are known to be among those at the highest risk for near-term poor outcomes. (BMJ 2017;356:j239;

    A recurring difficulty in managing these patients is the interpretation of urinalyses. It is well known that urinary tract infections can cause malaise and mental status changes in elderly patients, but consistent clinical data suggest that the overwhelming percentage of “positive” UAs represent asymptomatic bacteriuria and are not truly indicative of UTI nor related to the patient's nonspecific complaints. (J Am Geriatr Soc 2018 Nov 22. doi: 10.1111/jgs.15679.)

    Society guidelines and our inpatient colleagues often remind us that antimicrobial treatment of asymptomatic bacteriuria offers no true benefit, but parsing which UAs represent constitution-influencing infection and which are simple asymptomatic bystanders is not a task easily achieved in the ED. (Clin Infect Dis 2005;40[5]:643; We appropriately fear the consequences of untreated and progressive infections in such a frail population, so we start empiric antibiotics in these patients. (CMAJ 2000;163[3]:273; Typically we use broad-spectrum intravenous agents, and therapeutic momentum drives continued dosing throughout a patient's stay until a urine culture returns negative or an intrepid geriatrician or infectious disease specialist cancels the scheduled ceftriaxone.

    Enter procalcitonin.

    A Failure to Ignore

    The latest diagnostic darling in inpatient circles, procalcitonin (the biologic precursor to calcitonin, naturally) rises quickly and reliably in bacterial infections. Dozens of trials have reliably demonstrated the test's strong performance in decision-making for antibiotic initiation or cessation, but in the most salient ED investigation—the ProACT Trial—procalcitonin failed miserably to limit unnecessary antibiotic utilization. (New Engl J Med 2018;379[3]:236;

    Notably, however, this failure seemed more a function of the same clinician fears of untreated infection than a shortcoming of the test itself, an idiosyncracy that was noted many times over in a slew of editorials following ProACT's publication. (N Engl J Med 2018;379[20]:1972.) As many respondents argued (and the trial authors seemed to agree), the combination of this reassuring objective test with a concerted effort to limit unnecessary antibiotic use, or an antibiotic stewardship program, could be more effective in harnessing the diagnostic value of procalcitonin.

    It would seem, then, that the management morass of abnormal urinalyses in the elderly patient with nonspecific symptoms represents an excellent opportunity for using procalcitonin testing. Clinical uncertainty has already impelled de facto antibiotic stewardship in every hospital across the country as well-meaning physicians strive to separate true infection from asymptomatic bacteriuria. Where clinical complacency exists—an afebrile, nontoxic-appearing patient in whom we wish to spare unnecessary antibiotic use—conflicts with the compulsion not to allow an indolent infection to run rampant. A procalcitonin-augmented strategy might satisfy both imperatives.

    Such a strategy is not new nor even lacking significant justification. Indeed, a brief examination of the existing literature reveals a compelling data set, but implementation has curiously lagged behind. A recent retrospective analysis found a negative predictive value of 91% for a low procalcitonin, arguing strongly for its use as an adjunct in not starting empiric antibiotics. (Am J Emerg Med 2018;36[11]:1993.) Even more compelling, a randomized trial of nearly 200 ED patients found that a procalcitonin-based algorithm reduced antibiotic exposure by 30 percent without negative effects on clinical outcomes. (BMC Med 2015;13:104;

    As is so often the case, the variations in care and discordance with data seen in the inconsistent management of abnormal urinalyses in the elderly are overwhelmingly a function of fear of bad outcomes in the setting of uncertainty. As I noted in my column about BNP (EMN 2018;40[7]:20;, synthesizing sensitive diagnostic testing with well-defined clinical questions is vital in pursuing individualized and optimized bedside care.

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