Phenyllactic Acid as a Marker of Antibiotic-Induced Metabolic Activity of Nosocomial Strains of Klebsiella pneumoniae In Vitro Experiment.
Maria Getsina, Ekaterina Chernevskaya, Ekaterina Sorokina, Tatiana Chernenkaya, Natalia Beloborodova
Abstract
Open AccessKlebsiella pneumoniae (K. pneumoniae) is a major nosocomial pathogen with increasing antibiotic resistance. Treatment failures and high mortality rates in sepsis caused by K. pneumoniae are associated with difficulties in choosing an adequate antibacterial therapy in the presence of resistance to all available antibiotics, based on the results of susceptibility tests. This study aimed to identify "weak points" in the metabolism of K. pneumoniae, to be able to use these features in the future. Ten nosocomial K. pneumoniae strains were incubated with fourteen broad-spectrum antibiotics representing major drug classes. Aromatic metabolites were analyzed using gas chromatography-mass spectrometry after 24 h exposure. Phenyllactic acid (PhLA), comprising 86% of detected phenylcarboxylic acids, served as the metabolic activity marker. Antibiotics demonstrated multidirectional effects on aromatic compound metabolism. Doxycycline, nitrofurantoin, rifampicin, and tigecycline significantly suppressed metabolic activity, confirmed by decreased PhLA levels. Conversely, meropenem, cephalosporins (ceftriaxone, cefepime, cefotaxime, and ceftazidime), ciprofloxacin, and amikacin stimulated PhLA production, suggesting that bacterial metabolic activity was maintained despite the presence of antibiotics. PhLA is a promising biomarker for quantifying K. pneumoniae's metabolic response to antibiotics. This potentially introduces a novel approach for future investigations into resistance mechanisms and has the potential to increase the effectiveness of therapies for multidrug-resistant K. pneumoniae infections by providing an additional analytical tool to traditional susceptibility testing methodologies.