Procalcitonin as a Biomarker for Predicting Amputation Level in Lower Extremity Infections.

Inflammatory markers are essential tools in the decision-making process for lower extremity infections. When coupled with objective findings, clinicians can more accurately diagnose and treat these entities. Typically, markers such as the white blood cell count, erythrocyte sedimentation rate, and C-reactive protein are used to initially assess these patients or monitor the progression of medical or surgical therapy. Procalcitonin is a newer inflammatory marker that is specific for an infectious process. Originally, procalcitonin was used to monitor antibiotic therapy and sepsis for patients in the intensive care setting, but it has now been expanded to other facets of medicine. The utility of procalcitonin has been described for diagnosing infection or osteomyelitis in diabetic foot ulcers. However, limited research has compared inflammatory marker levels and the level of amputation. A retrospective inpatient medical record review was performed of 156 consecutive patient occurrences during 25 months in which surgical intervention was required for a lower extremity infection and an initial procalcitonin level had been obtained. This initial procalcitonin value was then compared with the level of amputation at the final surgical intervention. A highly statistically significant difference was found when comparing those who underwent a below-the-knee or above-the-knee amputation (median procalcitonin 1.72 ng/mL) and those who did not (median procalcitonin 0.105 ng/mL; p < .001). Therefore, patients with higher initial procalcitonin values were more likely to undergo below-the-knee or above-the-knee amputation or require aggressive surgical intervention. Thus, the procalcitonin level can provide valuable initial information to the clinician.

Rapid diagnosis of bloodstream infections using a culture-free phenotypic platform.

BACKGROUND: Bloodstream infections (BSIs) are a life-threatening acute medical condition and current diagnostics for BSIs suffer from long turnaround time (TAT). Here we show the validation of a rapid detection-analysis platform (RDAP) for the diagnosis of BSIs performed on clinical blood samples METHODS: The validation was performed on a cohort of 59 clinical blood samples, including positive culture samples, which indicated confirmed bloodstream infections, and negative culture samples. The bacteria in the positive culture samples included Gram-positive and Gram-negative pathogenic species. RDAP is based on an electrochemical sandwich immunoassay with voltage-controlled signal amplification, which provides an ultra-low limit of detection (4 CFU/mL), allowing the platform to detect and identify bacteria without requiring culture and perform phenotypic antibiotic susceptibility testing (AST) with only 1-2 h of antibiotic exposure. The preliminary diagnostic performance of RDAP was compared with that of standard commercial diagnostic technologies. RESULTS: Using a typical clinical microbiology laboratory diagnostic workflow that involved sample culture, agar plating, bacteria identification using matrix-assisted laser desorption ionization time-of-flight (MALDI TOF) mass spectrometry, and AST using MicroScan as a clinical diagnostic reference, RDAP showed diagnostic accuracy of 93.3% and 95.4% for detection-identification and AST, respectively. However, RDAP provided results at least 15 h faster. CONCLUSIONS: This study shows the preliminary feasibility of using RDAP to rapidly diagnose BSIs, including AST. Limitations and potential mitigation strategies for clinical translation of the present RDAP prototype are discussed. The results of this clinical feasibility study indicate an approach to provide near real-time diagnostic information for clinicians to significantly enhance the treatment outcome of BSIs.

Effective treatment of bloodstream infections (BSIs), a life-threatening acute medical condition, requires rapid diagnosis. Current diagnostic methods involve culturing the bacteria from the patient's blood, which requires typically 16­48 h to produce a diagnosis. Here, we demonstrate the feasibility of using a culture-free platform to perform rapid diagnosis of BSIs. We tested the diagnostic platform on a cohort of clinical blood samples. The bacteria contained in the samples covered a representative range of bacteria that cause BSIs. The culture-free platform produced diagnosis in about 15 hours faster than standard commercial diagnostic technologies and  the diagnostic results were in good agreement with that of standard technologies. The results of this study indicate an approach to providing near real-time diagnostic information for clinicians to significantly enhance the treatment outcome of BSIs.