Robiul Islam, Shyamal C. Das, Daniel Pletzer
Klebsiella pneumoniae is a major cause of hospital-acquired pneumonia and a critical global threat due to its escalating multidrug resistance. This review highlights current advancements in therapeutic strategies, including double and triple drug combinations, and evaluates their clinical efficacy and limitations. We discuss the global dissemination of resistance determinants such as blaKPC, blaNDM and mcr genes, and the complex mechanisms, including porin mutations, efflux pump overexpression and enzymatic degradation. The regional variation in these mechanisms undermines treatment success. Evidence for antibiotic combination therapy, including the double (colistin/meropenem) and triple (polymyxin B/meropenem/rifampicin) regimens, is analysed, along with controversies regarding their superiority over monotherapy. Finally, we highlight inhaled antibiotic delivery, particularly dry powder inhalers, as a promising strategy to achieve targeted, effective pulmonary drug concentrations and reduced systemic toxicity. Despite progress, significant barriers remain, including formulation stability, regulatory hurdles and the continued shortage of clinical trials. Future research should prioritize optimizing inhaled drug therapies and innovative delivery platforms to combat multidrug-resistant K. pneumoniae lung infections.