Antibiotics were firstly used for the treatment of critical infections in the
1940s. They could save patients’ lives and increased life spans by improving the
outcome of serious infections. Antibiotics are the most commonly used drugs in a
healthcare environment. However, antibiotics are not correctly prescribed, due to
improper antibiotic selection, not suitable dosing, inappropriate treatment duration, and
wrong treatment in nonbacterial conditions. Consequently, the rapid emergence of
resistant bacteria occurs worldwide because they could adapt and compete with
environmental stress. There are 4 primary mechanisms of resistance to counter the
antibiotics: (i) modification of the target, (ii) enzymatic inhibition of the antibiotics,
(iii) active efflux of the antibiotics, and (iv) changing membrane permeability.
Carbapenem-resistant Pseudomonas aeruginosa (CR-PA), CR Acinetobacter
baumannii (CR-AB), and CR Enterobacteriaceae were declared by World Health
Organization (WHO) as the three most important pathogens that pose the greatest
threat to human health. Moreover, they are also multidrug-resistant (MDR) and usually
resist almost all of the most effective antibiotics, including carbapenem and fourthgeneration
cephalosporin. There is an urgent need to develop new strategies to combat
antibiotic resistance and preserve the existing antibiotics. Numerous approaches,
including host-directed, antibiotic-adjuvant combination, and antibiotic-antibiotic
combination therapy, have been put forward to bring about antibiotic efficacy against
MDR pathogens.
Keywords: Antibiotic-Adjuvant Combination, Antibiotic-Antibiotic Combination,
Gram-Negative Pathogens, Host-Directed, Multidrug-Resistant.
