Measurement of Serum Procalcitonin

Abstract

THE ADVENT OF ANTIBIOTICS LED TO DRAMATIC REductions in mortality and medical complications from bacterial respiratory tract infections. Although the armamentarium of diagnostic and therapeutic approaches has increased exponentially since that time, the effect of these advances on patient outcomes is less dramatic. Nevertheless, the goal of care remains constant: to match the patient’s illness with a treatment approach that optimizes recovery while causing no harm. Harm exists in at least 2 forms: patient-specific, from an adverse event due to a diagnostic test or a treatment, and population-based, from the development of bacterial resistance promoted by the misuse or overuse of antibiotics. Lower respiratory tract infections (LRTIs) are a pervasive public health problem and cause more disease and death in the United States than any other infection. Patients and their physicians share a goal of improving symptoms from LRTIs as quickly as possible, often viewing antibiotics as the most expeditious intervention to achieve this goal. This one-sizefits-all approach for patients with illnesses ranging from acute bronchitis to community-acquired pneumonia (CAP) fails to consider the basic questions of who would benefit (or be harmed) from antibiotic therapy, and if treated, what is the optimal duration. Answering these questions requires an accurate assessment of which patients have bacterial infections and how their illness might progress with or without treatment. Many conventional bacterial detection techniques used in LRTIs, such as sputum Gram stains and cultures, lack sufficient diagnostic accuracy and turnaround time to inform real-time decisions. In the setting of a severe LRTI with evidence of organ derangement, assessing the benefits and risks of treatment often favors empirical antibiotic therapy. However, such clinical scenarios are uncommon; the vast majority of patients have mild to moderate illness, rendering this assessment of cause and response more challenging. Clinical decision rules based on bedside clinical and laboratory data could help physicians improve antibiotic management for such patients and optimize the duration of therapy. The ultimate clinical value of such rules is a function of diagnostic accuracy, effectiveness in changing clinician behavior, safety for patients, and both individual and societal cost. In this issue of JAMA, Schuetz and colleagues build on prior work bystudyingtheeffectivenessandsafetyofusinganovel decision rule to guide antibiotic therapy of patients diagnosed with LRTIs ranging from acute bronchitis to exacerbationofchronicobstructivepulmonarydisease(COPD)toCAP. In their current study, theauthors evaluated1359patientspresenting to emergency departments in 6 tertiary care hospitals who were randomized to receive care guided by evidencebased LRTI guidelines (control group) or by an experimental algorithm that used serum procalcitonin (PCT) to quantify the likelihood of a bacterial infection and gauge the response to therapy. PCT is released in response to bacterial infection and correlates with illness burden and severity; furthermore, it is rarely elevated in patients with viral infection. The algorithm specified 1 of 4 antibiotic treatment recommendations, rangingfromstronglydiscouragetostronglyrecommend,based on the measured PCT levels. For hospitalized patients, repeat PCT measurements guided continuation of antibiotic therapy. In contrast to many effectiveness trials that seek to change clinician behavior through the implementation of decision rules, compliance with treatment recommendations in this trial were commendably high (79.4% in the control group and 90.8% in the PCT group). Overall, the PCT-guided strategy led to reduced antibiotic exposure by an average of 3 days (8.7 vs 5.7 days) and led to 8.2% less antibioticrelated adverse effects (28.1% vs 19.8%), with slightly lower overall adverse event rates in the PCT group (15.4% vs 18.9%). Although similar outcomes were observed for patients with acute bronchitis, COPD exacerbation, and CAP, the paths to reducing antibiotic exposure differed in a predictable fashion. For acute bronchitis, decreased antibiotic exposure was principally from nontreatment, whereas for CAP it was principally from reduction in duration of therapy. Even though this PCT-guided decision rule holds promise for the management of patients with LRTI, several issues must be carefully considered before broadly translating this research into clinical practice. First, the study had a high proportion of patients with pneumonia (68.1%), more than half of whom were considered high risk (pneumonia severity index risk classes IV or V). In such patients, the high likelihood of bacterial disease and high disease acuity render PCT guidance unlikely to alter the decision to initiate antibiotic