Mass Spectrometry–Based Detection of Beta Lactam Hydrolysis Enables Rapid Detection of Beta Lactamase Mediated Antibiotic Resistance

• Published in: Laboratory medicine Vol. 53; no. 2; pp. 128 - 137
• Main Authors: Suhandynata, Raymond T, Lund, Kyle, Caraballo-Rodríguez, Andrés M, Reed, Sharon L, Dorrestein, Pieter C, Fitzgerald, Robert L, Bevins, Nicholas J
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 07.03.2022
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotics; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Drug resistance; Humans; Hydrolysis; Ions; Mass spectrometry; Science; Scientific imaging; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods; Urinary tract infections; Urine; mass-spectrometry; beta lactamase; antibiotic resistance; ESBL; antibiotic resistance testing; urinary tract infection; beta lactam hydrolysis
• ISSN: 0007-5027; 1943-7730
• DOI: 10.1093/labmed/lmab068

Abstract Objective Antibiotic resistance by beta lactamase expression is a serious and growing threat. We aimed to determine whether beta-lactamase activity is detectable in urine specimens to enable faster identification of resistance. Methods Urine specimens from patients with extended spectrum beta lactamase (ESBL)-expressing urinary infections were incubated with beta lactam antibiotics. Beta lactam hydrolysis was determined by mass spectrometry methods. Results Ceftriaxone hydrolysis was observed in 45 of 45 ESBL-containing specimens from patients not treated with a beta lactamase inhibitor before specimen collection. Ceftriaxone hydrolysis was not observed in 108 of 108 non-ESBL-containing specimens. Spiking studies show that beta lactam hydrolysis can be observed within 30 minutes. Beta lactam hydrolysis is evidenced by mass spectrometry preceded by either liquid chromatography or matrix-assisted laser desorption ionization specimen processing methods. Conclusion Clinically significant beta lactamase activity is detectable directly from urine specimens. The described methods would enable the detection of beta lactam resistance 24 to 48 hours sooner than culture based methods.