Differential effect of exogeneous glutathione on susceptibility of non-β-lactam antibiotics in clinical isolates of OXA-type carbapenemase-producing Acinetobacterbaumannii.

Acinetobacter baumannii (A. baumannii) is a Gram-negative bacterial pathogen that causes infections in the lungs, bloodstream, urinary tract, and wounds. This bacterium has become one of the most challenging pathogens for healthcare institutions worldwide. A big problem in treating these infections is that oxacillinase (OXA)-type carbapenemase-producing A. baumannii often resists many antibiotics that are not β-lactams, including almost all β-lactams. Glutathione is a tripeptide (l-glutathione, l-cysteine, and l-glycine) antioxidant synthesized in most Gram-negative bacteria and eukaryotic cells. Exogenous glutathione has been evaluated for antibacterial properties and various clinical implications. A previous study showed that exogenous glutathione significantly enhanced the susceptibility of β-lactam antibiotics in OXA-type carbapenemase-producing A. baumannii. However, the effect of exogenous glutathione on non-β-lactam antibiotics was unclear. In this study, the antibacterial activity of exogenous glutathione against A. baumannii was determined at various concentrations. Additionally, the effect of exogenous glutathione on several non-β-lactam antibiotics, including chloramphenicol, ciprofloxacin, erythromycin, novobiocin, kanamycin, and tetracycline, was evaluated on four OXA-type carbapenemase-producing strains of A. baumannii: bla, bla, bla, and bla. The results showed that exogenous glutathione significantly inhibited bacterial growth at concentrations greater than 10 mM, achieving complete growth inhibited at 16 mM. Interestingly, at the subinhibitory concentration of 10 mM, exogenous glutathione increased susceptibility (more sensitive) to chloramphenicol, novobiocin, and tetracycline by as much as 256-fold. Conversely, it decreased susceptibility (more resistant) to ciprofloxacin, erythromycin, and kanamycin by up to 32-fold at the same subinhibitory concentration. These findings highlight the need for caution when using glutathione in combination with antibiotics, especially for treating A. baumannii infections.