An Innovative Laboratory Technique Showcasing the Synergy among CeftazidimeAvibactam and Aztreonam in Combating Infections caused by Enterobacterales producing Metallo-beta-lactamases: A Prospective Study

Abstract

Introduction: Combination therapy with CeftazidimeAvibactam (CAZ-AVI) and Aztreonam (ATM) has been studied in the context of infections caused by Enterobacterales that produce Metallo-Beta-Lactamases (MBL). The development of combination therapy is a crucial factor in combating MBLproducing Enterobacterales. As most isolates from Intensive Care Unit (ICU) patients produce a variety of beta-lactamases, offering resistance to a broad range of antibiotics, they need to be treated with the CAZ-AVI and ATM combination. This study addresses a pressing public health issue-the rise of multidrugresistant bacteria, particularly MBL-producing Enterobacterales. By investigating the synergy between CAZ-AVI and ATM, the study aims to provide valuable insights to guide clinical practice, improve patient outcomes, and contribute to the global effort to combat antibiotic resistance. Aim: To demonstrate the synergy between CAZ-AVI and ATM in patients with infections caused by MBL-producing Enterobacterales. Materials and Methods: A prospective study was conducted in the Department of Microbiology at Symbiosis Medical College for Women (SMCW) and Symbiosis University Hospital and Research Centre (SUHRC), Symbiosis International (Deemed University), Lavale, Pune, Maharashtra, India. The study duration was six months, from January 2023 to June 2023. All isolates meeting the inclusion criteria were processed to demonstrate synergy between CAZ-AVI and ATM. Isolates from the Enterobacteriaceae family with resistant breakpoints for carbapenemase, ceftazidimeavibactam, and aztreonem, as determined by the Phoenix automated system, were included in the study. Restoration of the ATM breakpoint was observed following the addition of CAZ/AVI to ATM. Breakpoints provided by the BD Phoenix system were compared to the results obtained from CAZ/AVI and ATM disc diffusion/stacking, E-strip/disc methods, in terms of susceptibility and resistance. Results were simultaneously compared with the broth disc elution test, considered the gold standard. Results: Sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) were calculated for the E-test/disc and disc stacking methods. The disc stacking synergy test demonstrated a PPV of 96.88% and an NPV of 62.5%. By using the E-test/disc, the ATM/CAZ-AV synergy test revealed a PPV of 97.22% and an NPV of 83.33% when CAZ/ AVI was added to ATM. Comparatively, disc stacking was less sensitive than the broth disc elution. Conclusion: In the majority of MBL-producing Enterobacterales that are ATM-resistant, the CAZ/AVI+ATM combination showed strong synergy. In the microbiology laboratory, the E-test/disc and disc stacking approaches are rapid, repeatable, and reliable methods for checking clinically significant synergy.

Keywords

• carbapenemases
• combination therapy
• disc elution
• disc stacking