Catalase-containing silica particles as ultrasound-based hydrogen peroxide sensors to determine infected from noninfected fluid collections in humans

OBJECTIVE. Hydrogen peroxide (H₂O₂) plays a key role in neutrophil oxidative defense against infection. Catalase-containing silica nanoshells are nanoparticles that generate O₂ microbubbles imaged with ultrasound in the presence of elevated H₂O₂. We aimed to determine whether ultrasound-detectable O₂ microbubbles produced by catalase-containing silica nanoshells can determine whether fluid collections drained from patients are infected. SUBJECTS AND METHODS. 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. RESULTS. 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. CONCLUSION. The presence of elevated H₂O₂ 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.