Research progress on resistance mechanisms and clinical efficacy of tigecycline against Klebsiella pneumoniae

Abstract

Klebsiella pneumoniae (KP) is a Gram-negative, opportunistic pathogen known for causing hospital/community-acquired infections, with carbapenem-resistant Klebsiella pneumoniae (CRKP) being a major global health threat due to its resistance to last-resort antibiotics. Tigecycline is one of the most commonly used and accessible agents for CRKP treatment. However, the rapid spread of resistance genes via mobile genetic elements has led to an increase in bacterial resistance, thereby undermining the clinical efficacy. Additionally, controversy remains regarding the MIC breakpoint of tigecycline for KP, with either overestimation or underestimation of resistance rates, which complicates evaluation and selection of appropriate treatment regimens for clinicians. This review aims to elucidate the mechanisms of tigecycline resistance in KP strains, including the newly discovered mutants or resistance mechanisms mediated by efflux pumps and two-component regulatory systems. Subsequently, a global epidemiology of CRKP isolates with different tigecycline MIC values is conducted, finding that the resistance rates in Asia are higher than that in Europe and America. Furthermore, the latest clinical progresses of tigecycline in terms of dosage, combination regimen and adverse events are analysed.