| dc.description.abstract | The rise of multidrug-resistant (MDR) Klebsiella pneumoniae poses a significant public
health threat, particularly in low- and middle-income countries where treatment options are
limited. This study investigates the potential of antibiotic combination therapy to reverse
resistance in MDR K. pneumoniae isolates collected from clinical samples in Bangladesh.
Using a combination of phenotypic assays and molecular techniques, five isolates were
screened for resistance to Ceftazidime, Amikacin, Meropenem, and Ciprofloxacin. Antibiotic
susceptibility testing and Minimum Inhibitory Concentration (MIC) assays confirmed
high-level resistance across multiple antibiotics, with partial reversal observed through dual
disk diffusion synergy testing. Notably, a combination of Ceftazidime and Gentamicin
demonstrated significant synergistic activity against isolate 87.
To understand the molecular basis of this synergy, key genes associated with antimicrobial
resistance, oxidative stress, membrane permeability, and DNA repair—including gyrA, phoQ,
soxS, ompF, rpoB, mutS, and sodB—were selected for future expression analysis via
RT-qPCR. Bioinformatics tools such as Venn diagram overlap analysis and STRING
interaction networks were employed to identify genes with dual roles in virulence and
resistance. Results suggest that the synergistic effect may involve disruption of redox
homeostasis and mismatch repair pathways, triggered by elevated reactive oxygen species
and increased membrane permeability.
This integrative approach combining phenotypic assays, gene expression profiling, and
computational analysis highlights the potential of strain-specific combination therapies in
overcoming drug resistance. Future work will expand this analysis to additional clinical
isolates and synergy pairs (Ceftazidime + Chloramphenicol, Norfloxacin, Vancomycin, and
Erythromycin) to further validate predictive markers with RT-qPCR and optimize treatment
strategies in resource-limited settings. | en_US |
