Sub-Inhibitory N-Acetylcysteine and L-Glutamine Partially Restore Ceftriaxone Susceptibility in Multidrug-Resistant Klebsiella pneumoniae and Pseudomonas aeruginosa

Abstract

Background: Klebsiella pneumoniae and Pseudomonas aeruginosa are Gram-negative pathogens commonly recovered from hospital surfaces, where multidrug resistance (MDR) restricts treatment options. N-acetylcysteine (NAC) and L-glutamine have each been proposed as non-antibiotic adjuvants capable of restoring antibiotic activity against resistant bacteria.

Methods: A total of 50 surface swabs were collected from medical-device surfaces in a Sebha hospital; 18 yielded Gram-negative isolates identified as K. pneumoniae (n = 12) or P. aeruginosa (n = 6). These isolates were tested by Kirby-Bauer disk diffusion against six antibiotics before and after 4-hour exposure to sub-inhibitory (0.5 mg/mL) NAC or L-glutamine, with each isolate serving as its own control. Inhibition zones were interpreted using CLSI 2024 breakpoints; paired comparisons used the Wilcoxon signed-rank test and Fisher's exact test. Results: Baseline resistance was 100% for ampicillin, cefoxitin and ertapenem, 89% for ceftriaxone and ceftazidime, and 11% for co-trimoxazole. Mean ceftriaxone zone diameter increased from 11.8 mm to 18.0 mm after NAC exposure (p = 0.005) and to 17.6 mm after glutamine exposure (p = 0.009), converting 6 of 18 isolates from resistant to susceptible under each adjuvant (p = 0.018 and p = 0.041, respectively). Neither adjuvant produced a significant change in susceptibility to ampicillin, cefoxitin, ertapenem, ceftazidime or co-trimoxazole; a single ampicillin conversion was observed, after glutamine exposure only. Conclusion: Sub-inhibitory NAC and L-glutamine each partially restored ceftriaxone susceptibility in these environmental isolates without a comparable effect on the other antibiotics tested. The findings point to a narrow, ceftriaxone-specific resensitization rather than a broad antimicrobial-potentiating action for either compound.