Structure activity relationship (SAR) driven design and discovery of WCK 5107 (Zidebactam): novel β-lactam enhancer, potent against multidrug-resistant gram-negative pathogens

Bhavsar, Satish; Joshi, Sanjeev; Pawar, S.H.; Pavase, Laxmikant S.; Mishra, Amit; Jadhav, S.E.; Dabhade, Sanjay A.; Kayastha, Abhijeet K.; Yeole, Ravindra; Deshpande, P. K.; Bhagwat, Sachin; Patel, Mahesh

doi:10.1007/s00044-023-03135-6

Cited by 4 publications

(1 citation statement)

References 28 publications

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“…Cefepime, a fourth-generation cephalosporin, is known for its broad-spectrum antibacterial activity, which is significantly enhanced by zidebactam, a non-beta-lactam β-lactamase inhibitor [85]. Together, they target PBPs and inhibit β-lactamases, extending the spectrum of cefepime against β-lactam-resistant bacterial pathogens comprising MDR strains of A. baumannii [84,[86][87][88][89]. Research, including in vitro and in vivo studies, demonstrates that FEP-ZID can overcome resistance mechanisms that typically limit the efficacy of other antibiotics [90].…”

Section: Cefepime/zidebactammentioning

confidence: 99%

Unveiling the Secrets of Acinetobacter baumannii: Resistance, Current Treatments, and Future Innovations

Marino,

Augello,

Stracquadanio

et al. 2024

IJMS

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Acinetobacter baumannii represents a significant concern in nosocomial settings, particularly in critically ill patients who are forced to remain in hospital for extended periods. The challenge of managing and preventing this organism is further compounded by its increasing ability to develop resistance due to its extraordinary genomic plasticity, particularly in response to adverse environmental conditions. Its recognition as a significant public health risk has provided a significant impetus for the identification of new therapeutic approaches and infection control strategies. Indeed, currently used antimicrobial agents are gradually losing their efficacy, neutralized by newer and newer mechanisms of bacterial resistance, especially to carbapenem antibiotics. A deep understanding of the underlying molecular mechanisms is urgently needed to shed light on the properties that allow A. baumannii enormous resilience against standard therapies. Among the most promising alternatives under investigation are the combination sulbactam/durlobactam, cefepime/zidebactam, imipenem/funobactam, xeruborbactam, and the newest molecules such as novel polymyxins or zosurabalpin. Furthermore, the potential of phage therapy, as well as deep learning and artificial intelligence, offer a complementary approach that could be particularly useful in cases where traditional strategies fail. The fight against A. baumannii is not confined to the microcosm of microbiological research or hospital wards; instead, it is a broader public health dilemma that demands a coordinated, global response.

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