Ceftazidime-Avibactam (C/A) Resistant, Meropenem Sensitive KPC-Producing Klebsiella pneumoniae in ICU Setting: We Are What We Are Treated with?

The continuous spread of carbapenem-resistant Klebsiella pneumoniae (CP-Kp) strains presents a severe challenge to the healthcare system due to limited therapeutic options and high mortality. Since its availability, ceftazidime/avibactam (C/A) has become a first-line option against KPC-Kp, but C/A-resistant strains have been reported increasingly, especially with pneumonia or prior suboptimal blood exposure to C/A treatment. A retrospective, observational study was conducted with all patients admitted to the Intensive Care Unit (ICU) dedicated to COVID-19 patients at the City of Health & Sciences in Turin, between 1 May 2021 and 31 January 2022, with the primary endpoint to study strains with resistance to C/A, and secondly to describe the characteristics of this population, with or without previous exposure to C/A. Seventeen patients with colonization or invasive infection due to Klebsiella pneumoniae, C/A resistance, and susceptibility to meropenem (MIC = 2 mu g/L) were included; the bla(KPC) genotype was detected in all isolates revealing D179Y mutation in the bla(KPC-2) (bla(KPC-33)) gene. Cluster analysis showed that 16 out of the 17 C/A-resistant KPC-Kp isolates belonged to a single clone. Thirteen strains (76.5%) were isolated in a 60-day period. Only some patients had a previous infection with non-mutant KPC at other sites (5; 29.4%). Eight patients (47.1%) underwent previous large-spectrum antibiotic treatment, and four patients (23.5%) had prior treatment with C/A. The secondary spread of the D179Y mutation in the bla(KPC-2) during the COVID-19 pandemic needs to be addressed constantly by an interdisciplinary interaction between microbiologists, infection control personnel, clinicians, and infectious diseases consultants to properly diagnose and treat patients.

Automated summary

The continuous spread of carbapenem-resistant Klebsiella pneumoniae (CP-Kp) strains poses a significant challenge to healthcare systems. Ceftazidime/avibactam (C/A) has been a first-line treatment, but C/A-resistant strains are increasing, especially among pneumonia patients or those with prior suboptimal blood exposure to C/A. A retrospective study was conducted on patients admitted to an ICU for COVID-19, with the primary purpose of studying C/A-resistant strains and describing the characteristics of the population. The study found a single clone of C/A-resistant KPC-Kp isolates with a D179Y mutation in the bla(KPC-2) gene.