Catalase-Containing Silica Particles as Ultrasound-Based Hydrogen Peroxide Sensors to Determine Infected From Noninfected Fluid Collections in Humans.

Malone, Christopher D; Fetzer, David T; Lux, Jacques; Mattrey, Robert F · AJR Am J Roentgenol · 2019

cross_sectional · Level IV

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Abstract

<b>OBJECTIVE.</b> Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) plays a key role in neutrophil oxidative defense against infection. Catalase-containing silica nanoshells are nanoparticles that generate O<sub>2</sub> microbubbles imaged with ultrasound in the presence of elevated H<sub>2</sub>O<sub>2</sub>. We aimed to determine whether ultrasound-detectable O<sub>2</sub> microbubbles produced by catalase-containing silica nanoshells can determine whether fluid collections drained from patients are infected. <b>SUBJECTS AND METHODS.</b> During this HIPAA-compliant, institutional review board-approved study, 52 human fluid samples were collected from clinically required image-guided percutaneous drainage procedures. Catalase-containing silica nanoshells were added to the fluid samples during imaging in real time using a Sequoia-512 15L8-S linear transducer (Siemens Healthcare). Production of detectable microbubbles was graded subjectively as negative (noninfected) or positive (infected) with low, moderate, or high confidence by a single observer blinded to all clinical data. The truth standard was microbiology laboratory culture results. Performance characteristics including ROC curves were calculated. <b>RESULTS.</b> Microbubble detection to distinguish infected from noninfected fluids was 84% sensitive and 72% specific and offered negative and positive predictive values of 89% and 64%, respectively. The AUC was 0.79. Six of nine false-positive samples were peritoneal fluid collections that were all collected from patients with decompensated cirrhosis. <b>CONCLUSION.</b> The presence of elevated H<sub>2</sub>O<sub>2</sub> indicated by microbubble formation in the presence of catalase-containing silica nanoshells is sensitive in distinguishing infected from noninfected fluids and offers a relatively high negative predictive value. False-positive cases may result from noninfectious oxidative stress. Catalase-containing silica nanoshells may constitute a novel point-of-care test performed at time of percutaneous drainage, potentially obviating placement of drains into otherwise sterile collections and minimizing risk of secondary infection or other complication.