Abstract
Antibiotic resistance occurs when microorganisms resist the drugs used against the infection caused by them and neutralize their effects over time using various mechanisms. These mechanisms include preventing drug absorption, changing drug targets, drug inactivating, and using efflux pumps, which ultimately cause drug resistance, which is named pan-drug-resistant (PDR) infection if it is resistant to all antimicrobial agents. This type of drug resistance causes many problems in society and faces the health system with difficulties; therefore their treatment is crucial and encourages doctors to develop new drugs to treat them. PDR Gram-negative bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli are among the most significant resistant bacteria to many antimicrobial agents, and only a limited range of antibiotics, especially synergistically are effective on them. For the therapy of PDR A. baumannii, tigecycline in combination with colestimethate, imipenem, amikacin, and ampicillin-sulbactam are the most effective treatments. The utilization of β-lactamase inhibitors such as ceftolozane-tazobactam, ceftazidime-avibactam, or imipenem-cilastatin-relebactam has the most efficacy against PDR P. aeruginosa. The PDR K. pneumoniae has been treated in the last decades with tigecycline and colistin, but currently, nitrofurantoin, fosfomycin, and pivmecillinam seem to be the most effective agent for the therapy of PDR E. coli. While these drugs impressively struggle with PDR pathogens, due to the daily increase in antibiotic resistance in microorganisms worldwide, there is still an urgent need for the expansion of novel medicines and methods of combating resistance.