Ceftazidime-avibactam treatment dilemma of bla KPC−2-containing Klebsiella pneumoniae due to the development of co-existence of mixed strains carrying bla KPC−2 or bla KPC−33 in lung transplant recipients

• Main Authors: Zichen Lei (Author), Ziyao Li (Author), Yulin Zhang (Author), Lingbing Zeng (Author), Yongli Wu (Author), Feilong Zhang (Author), Xinrui Yang (Author), Xinmeng Liu (Author), Qi Liu (Author), Yiqun Ma (Author), Binghuai Lu (Author)
• Format: Book
• Published: BMC, 2024-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/s12941-024-00743-x; 1476-0711
• Keywords: Mixed strains carrying different bla KPC variants; bla KPC−2; bla KPC−33; Ceftazidime/Avibactam; Carbapenem-resistant Klebsiella pneumoniae; Lung transplant recipients; Therapeutics. Pharmacology; RM1-950; Infectious and parasitic diseases; RC109-216; Microbiology; QR1-502
• Source: Annals of Clinical Microbiology and Antimicrobials, Vol 23, Iss 1, Pp 1-11 (2024)

Abstract Background Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant threat to immunocompromised populations, including lung transplant recipients. This study investigates mixed CRKP strains carrying either bla KPC−2 or bla KPC−33 following ceftazidime-avibactam (CAZ/AVI) exposure, particularly in the context of lung transplantation. Mixed CRKP strains with shifting resistance phenotypes were frequently identified in patients exposed to CAZ/AVI. We aimed to elucidate the transitional state of bla KPC variants by selecting CAZ/AVI-sensitive and -resistant CRKP strains from a lung transplantation patient. Methods The bla KPC-variant-carrying CRKP strains were collected from lung transplant recipients exposed to CAZ/AVI in less than two years. Antibiotic susceptibility testing (AST) was conducted using microbroth dilution, and whole-genome sequencing (WGS) was used to identify genotypes and resistance mechanisms. Limiting dilution, drop-plate, and in vitro induction experiments determined bla KPC-variant changes during CAZ/AVI administration. qPCR primers/probes were designed to identify bla KPC−2 mutations. Results Among 104 lung transplant recipients infected by bla KPC-harboring CRKP strains and receiving CAZ/AVI, 10 (9.6%) experienced changing resistance phenotypes. The limiting dilution method found that Patient 10's CRKP strains carried either bla KPC−2 or bla KPC−33. The drop-plate experiment showed differing growth patterns on CAZ/AVI mediums. The in vitro induction experiment demonstrated shifting from bla KPC−2 to bla KPC−33. Conclusions The study identified a "transitional state" of the mixed CRKP strains carrying either bla KPC−2 or bla KPC−33 in CAZ/AVI-exposed patients. Molecular diagnostics are crucial for identifying mixed strains and the transitional state of bla KPC variants, guiding treatment decisions in this complex landscape.