Sub-Inhibitory Meropenem Restores Ceftazidime Susceptibility in Resistant Klebsiella pneumoniae: A Phenotypic Insight Into Collateral Sensitivity and Molecular mechanism.
Abstract
Antibiotic resistance continues to outsmart modern medicine, especially in hospital settings
where infections are often resistant to multiple drugs.mystudy dives into this challenge by
investigating the combined effect of two beta-lactam antibiotics—Ceftazidime and
Meropenem—to understand how they might complement each other against resistant bacterial
strains. Rather than viewing combination therapy as random trial and error, I approached it
through both computational and experimental methods.
Using R-based genomic data extrapolation, I identified resistance genes and mapped resistant
pathways to locate synergy points—molecular intersections where two drugs might double down
on a pathogen’s defenses.myexperimental pipeline involved culturing clinical samples,
confirming species via phoE PCR, and performing AST using both disc diffusion and
checkerboard MIC assays. The results were encouraging: I observed synergistic activity between
Ceftazidime and Meropenem in several resistant strains.
Mechanistically, although both are beta-lactams, they target slightly different penicillin-binding
proteins (PBPs). This complementary action helps bypass certain resistance mechanisms like
beta-lactamase production or efflux pumps, increasing their overall efficacy when
combined.myfindings offer a fresh perspective on beta-lactam synergy and highlight the need for
smarter, tailored antibiotic pairings in an age of rising resistance.
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