Aztreonam Acts as a Synergist for Ceftazidime/Avibactam Against Carbapenem-Resistant Enterobacteriaceae (CRE) of Various Carbapenemase Phenotypes in Southwestern China

Xuelian Ruan,1,* Zhiyu Gong,1,* Moqiyi Zeng,1 Ziqing Zhong,1 Yongling Chen,1 Fangyi Wei,1 Chong Lei,1 Yuanyuan Zhu,1 Xue Qin,1 Meng Li1,2 1Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Key Laboratory of Clinical Laboratory Medicine of Guangxi Department of Education, Nanning, Guangxi, People’s Republic of China; 2Guangxi Health Commission Key Laboratory of Fungi and Mycosis Research and Prevention, Nanning, Guangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Meng Li, Email [email protected] Xue Qin, Email [email protected]: Carbapenem-resistant Enterobacteriaceae (CRE) presents a significant challenge due to its role in severe and multidrug-resistant infections.Purpose: This study aims to evaluate aztreonam (ATM) as a synergistic agent with ceftazidime/avibactam (CZA) for treating CRE strains with different carbapenemase phenotypes.Methods: A total of 87 non-repeated clinical CRE strains were collected from various clinical specimens at The First Affiliated Hospital of Guangxi Medical University. Carbapenemase genotypes and phenotypes were identified using polymerase chain reaction (PCR) and NG-Test Carba 5 methods. The synergistic effect of CZA combined with ATM was assessed via the checkerboard MIC and disk stacking methods.Results: The clinical analysis revealed that underlying pulmonary disease, pneumonia, urinary catheter, and central intravenous catheter were associated with poor prognosis in CRE infections (p< 0.05). All 87 CRE strains showed high resistance to most antibiotics, especially cefazolin, ceftriaxone, piperacillin/tazobactam, ertapenem, and meropenem, with a rate of 100.00%. For strains with a single carbapenemase gene, NG-Test Carba 5 demonstrated 100.00% accuracy. Notably, The combination of CZA and ATM showed synergy in 95.40% (83/87) of the CRE strains overall, with specific rates of 100.00% (4/4) in strains lacking detectable carbapenemase genes, 94.29% (33/35) in those with blaNDM, and 100.00% (3/3) in those with blaNDM plus blaKPC-2 or blaKPC-2 plus blaIMP-4.Conclusion: In conclusion, ATM significantly enhances CZA’s activity against CRE strains in Guangxi, achieving a high synergy rate across diverse isolates, regardless of the carbapenemase genes present.Keywords: combination therapy, synergist, ceftazidime/avibactam, aztreonam, carbapenem-resistant Enterobacteriaceae