Aztreonam-Avibactam Activity Against Multidrug-Resistant Klebsiella pneumoniae Complex

Background

The Klebsiella pneumoniae complex (KPC) is a group of opportunistic pathogens that pose a serious threat to public health. In recent years, the infection rate of multidrug-resistant (MDR) Klebsiella pneumoniae has significantly increased, leading to extremely limited treatment options. Particularly, strains producing carbapenemases exhibit resistance to multiple antibiotics, presenting a major challenge for clinical treatment. To address this issue, researchers are continuously exploring new antibiotic combinations in hopes of finding effective treatment solutions.

Aztreonam-avibactam (AZA) is a novel antibiotic combination consisting of the widely used β-lactam antibiotic aztreonam and the new β-lactamase inhibitor avibactam. Aztreonam is resistant to metallo-β-lactamases (MBLs), while avibactam can inhibit various β-lactamases, including extended-spectrum β-lactamases (ESBLs) and class A carbapenemases. Therefore, AZA is considered a promising drug for treating infections caused by multidrug-resistant Klebsiella pneumoniae.

Source of the Paper

This paper was authored by Alicja Sękowska, affiliated with the Department of Microbiology at Nicolaus Copernicus University and the Department of Clinical Microbiology at University Hospital No. 1 in Bydgoszcz, Poland. The paper was submitted on October 21, 2024, accepted on December 21, 2024, and published in 2025 in The Journal of Antibiotics.

Research Process and Results

Study Subjects and Samples

The study included a total of 204 strains of the Klebsiella pneumoniae complex, comprising 187 strains of K. pneumoniae, 16 strains of K. variicola, and 1 strain of K. quasipneumoniae. These strains were collected from clinical samples at University Hospital No. 1 in Bydgoszcz over a two-year period. All strains were identified using mass spectrometry (MALDI-TOF MS), with some strains further confirmed through sequencing.

Antimicrobial Susceptibility Testing

The study used the gradient strip method to test the susceptibility of the strains to AZA. The results showed that all 204 strains were susceptible to AZA. Specifically, the minimum inhibitory concentration (MIC) range for ESBL-positive strains was 0.032 to 0.75 μg/ml, while for carbapenemase-producing strains, the MIC range was 0.016 to 2 μg/ml. Among these, the MIC50 for VIM- and ESBL-positive strains was 0.094 μg/ml, and the MIC90 for ESBL-positive strains was 0.125 μg/ml.

Resistance Analysis

Among the 204 strains, 152 (74.5%) produced carbapenemases, including types such as KPC, NDM, VIM, OXA-48, and OXA-181. Of these, 150 were K. pneumoniae, and 2 were K. variicola. The study also found that 41 strains (20.1%) were multidrug-resistant (MDR), 133 strains (65.2%) were extensively drug-resistant (XDR), and 30 strains (14.7%) were pandrug-resistant (PDR). AZA demonstrated excellent in vitro activity against these resistant strains, particularly against PDR strains, with MIC50 and MIC90 values of 0.19 μg/ml and 0.38 μg/ml, respectively.

Data Analysis and Conclusions

The results indicate that AZA exhibits significant in vitro antibacterial activity against the Klebsiella pneumoniae complex, particularly against carbapenemase-producing and multidrug-resistant strains. This finding provides a new option for clinical treatment, especially in cases where existing antibiotics have limited efficacy. The widespread use of AZA may help control the spread of infections caused by multidrug-resistant Klebsiella pneumoniae.

Research Highlights

1. Broad Antibacterial Activity: AZA demonstrates excellent antibacterial activity against various resistant phenotypes of the Klebsiella pneumoniae complex, particularly against carbapenemase-producing and pandrug-resistant strains.
2. Novel Antibiotic Combination: AZA combines the advantages of aztreonam and avibactam, effectively inhibiting various β-lactamases, especially showing resistance to metallo-β-lactamases.
3. Potential for Clinical Application: The study provides strong support for the clinical application of AZA, particularly in treating infections caused by multidrug-resistant Klebsiella pneumoniae.

Significance and Value of the Research

The scientific value of this study lies in its systematic evaluation of AZA’s antibacterial activity against the Klebsiella pneumoniae complex, particularly its potential application against multidrug-resistant strains. The results offer clinicians a new treatment option, especially in cases where existing antibiotics are ineffective. Additionally, the study emphasizes the importance of continuous monitoring of antibiotic resistance to address the evolving challenges of bacterial resistance.

Additional Valuable Information

The study also notes that while AZA exhibits excellent in vitro antibacterial activity, its potential resistance mechanisms in clinical applications must be considered. For example, some strains producing carbapenemases or cephalosporinases may develop resistance to AZA. Therefore, future research should further explore the resistance mechanisms of AZA and develop corresponding strategies.

As a novel antibiotic combination, AZA offers new hope for treating infections caused by multidrug-resistant Klebsiella pneumoniae. Its broad application prospects and significant antibacterial activity make it an important direction for future antibiotic development.