Practice Repor t on Designing Treatment Regimens for Carbapenem-Resistant Klebsiella pneumoniae Based on Collateral Sensitivity
Objective:To explore the influence of antibiotic combination regimen based on collateral sensitivity(CS)on the clinical outcomes and drug resistance progression of carbapenem-resistant Klebsiella pneumoniae(CRKP),thereby providing insights for the treatment of clinical drug-resistant bacteria.Methods:Case 1:Results from drug sensitivity tests for CRKP urinary tract infections indicated resistance to amikacin.Considering the presence of CS between amikacin and β-lactams antibiotics,we adjusted the treatment to a combination regimen involving two β-lactams,mecillinam combined with amoxicillin sodium and clavulanate potassium,and subsequently evaluated the therapeutic effects of this combination.Case 2:According to the development of drug resistance of CRKP and CS observed among aminoglycosides,tetracyclines,and β-lactams,we designed a sequential administration mode and selected synergistic drug combinations for simultaneous administration,such as piperacillin sodium and tazobactam sodium combined with doxycycline,meropenem combined with amikacin,as well as mecillinam combined with amoxicillin sodium and clavulanate potassium.The therapeutic effects and changes in drug resistance associated with these regimens were analyzed.Results:In Case 1,mecillinam combined with amoxicillin sodium and clavulanate potassium was found to be effective in the treatment of CRKP urinary tract infections,with its synergistic effect likely arising from the presence of the CS effect.The therapeutic effects of CS in Case 2 and the inhibition of drug resistance are influenced by drug types and the methods of sequential and simultaneous administration.Notably,when a CS effect exists between the two antibacterial drugs,the therapeutic effects of drugs are enhanced.From the perspective of drug resistance,transitioning from aminoglycosides to β-lactams can mitigate the development of drug resistance.Conclusion:The design of drug regimens that utilizing the CS effects of antibiotics may represent a viable strategy to enhance the therapeutic effects and inhibit drug resistance.
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