Case Presentation: A 55-year-old woman with no known past medical issues is admitted with a 1-week history of weakness and two days of fever and chills. Workup showed WBC count was 15600/µL, C-reactive protein of 14.3 mg/dL, procalcitonin of less than 0.05 ng/mL, and lactate of 0.7 mmol/L. Since procalcitonin was negative and there was no apparent source of infection, antibiotics were not initiated. Subsequently, two blood cultures returned positive for Methicillin-Resistant Staphylococcus aureus (MRSA) bacteremia. Repeat Procalcitonin also returned negative. The patient had no focal symptoms or signs to suggest a source of infection. A transesophageal echocardiogram, CT scan of the chest, abdomen, and pelvis did not reveal any potential source of infection. The patient was appropriately treated with IV vancomycin.

Discussion: The diagnostic significance of Procalcitonin (PCT) was not recognized until 1993 when Assicot et al. demonstrated a positive correlation between high serum levels of PCT and patients with findings for bacterial infection and sepsis [1]. Without systemic inflammation, PCT synthesis is restricted to thyroid neuroendocrine cells. This protein is not released into the blood until it cleaves into its mature form, calcitonin [2-5]. Thus, serum PCT is typically undetectable in healthy persons [4]. The extra-thyroid synthesis of PCT has been found to occur in the liver, pancreas, kidney, lung, intestine, and within leukocytes, where the synthesis of PCT is suppressed under normal conditions and gets induced and released into the bloodstream in bacterial infections [1]. PCT levels can be elevated in noninfectious conditions, such as trauma, burns, etc. [6-9]. PCT has proved to be a helpful tool in detecting bacterial infections due to its high specificity [1] and is adopted in stewardship programs as a valuable tool to determine the initiation or avoidance of antibiotics. Chirouze et al. [11] and Hoeboer et al. [12], through their studies, indicated that with lower threshold values , PCT has very high negative predictive value of 95 – 99%, hence a valuable test to rule out bacteremia. However, we should be careful in interpreting PCT results. The study by Goodlet et al. [10] showed that PCT was more sensitive for detecting gram-negative bacteremia than gram-positive bacteremia. This study showed that even if the strictest cutoff value of 0.1 ng/mL were applied, nearly 10% of bacteremia would still be missed, with the most common organism in these cases being Staphylococcus aureus. A study by Jona et al. used a PCT threshold of < 2 ng/mL to rule out bacteremia, and 20% of patients with a negative test had positive blood cultures, and the most common organism in this group was Staphylococcus aureus [14]. It is possible that in the studies, the high negative predictive value of PCT for true bacteremia could be because the incidence of infection in the study population could be low, resulting in a large number of true negatives compared to false negatives [10]. Interestingly, in the patient discussed above with true positive Methicilin-Resistant Staphylococcus aureus bacteremia, PCT was negative on two occasions despite using a lower threshold of 0.05 ng/ml.

Conclusions: Though Procalcitonin has a high negative predictive value to rule out bacteremia, as exemplified in this case, it could rarely be falsely negative in Staphylococcus aureus bacteremia. Physicians and antibiotic stewardship programs should be cautious and aware of this potential pitfall when interpreting PCT results.