A Novel Antibiotic Agent, Cefiderocol, for Multidrug-Resistant Gram-Negative Bacteria

The threat of antibiotic resistance is an influencing factor in deteriorating public health. Therefore, new antibiotic development is necessary for continued successful treatment of infectious diseases. Cefiderocol is the first licensed injectable siderophore cephalosporin that chemically conjugates a siderophore and cephalosporin.Due to its high stability against various β-lactamases, it is widely used as an effective antibiotic for multidrug-resistant (MDR) gram-negative microorganisms, including Acinetobacter baumannii, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Enterobacteriaceae. Cefiderocol blocks microbial cell membrane synthesis. The binding site of cefiderocol is a penicillin-binding protein. Because of its siderophore-like properties, cefiderocol penetrates gram-negative bacterial periplasmic spaces, increasing its stability against β-lactamases. Unlike earlier cephalosporins, the siderophore of the cefiderocol moiety at position C-3 chelates with iron (ferric form) in the host and is then actively transported into the bacterial periplasmic space. This approach is known as a “Trojan horse” and improves cefiderocol stability against efflux pumps as well as porin channel mutations. Modification at the C-3 and C-7 side-chains produces powerful antibacterial properties against MDR gram-negative bacteria. The U.S. Food and Drug Administration (FDA) approved it as a new treatment option for adult patients with complicated urinary tract infection (cUTI) who have limited and no treatment options. Based on these observations, we conclude that cefiderocol is a potent treatment option for prospective bacterial infections. In this review, we summarize the future prospective use of cefiderocol for bacterial infections.

A Novel Antibiotic Agent, Cefiderocol, for Multidrug-Resistant Gram-Negative Bacteria

The threat of antibiotic resistance is an influencing factor in deteriorating public health. Therefore, new antibiotic development is necessary for continued successful treatment of infectious diseases. Cefiderocol is the first licensed injectable siderophore cephalosporin that chemically conjugates a siderophore and cephalosporin.Due to its high stability against various β-lactamases, it is widely used as an effective antibiotic for multidrug-resistant (MDR) gram-negative microorganisms, including Acinetobacter baumannii, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Enterobacteriaceae. Cefiderocol blocks microbial cell membrane synthesis. The binding site of cefiderocol is a penicillin-binding protein. Because of its siderophore-like properties, cefiderocol penetrates gram-negative bacterial periplasmic spaces, increasing its stability against β-lactamases. Unlike earlier cephalosporins, the siderophore of the cefiderocol moiety at position C-3 chelates with iron (ferric form) in the host and is then actively transported into the bacterial periplasmic space. This approach is known as a “Trojan horse” and improves cefiderocol stability against efflux pumps as well as porin channel mutations. Modification at the C-3 and C-7 side-chains produces powerful antibacterial properties against MDR gram-negative bacteria. The U.S. Food and Drug Administration (FDA) approved it as a new treatment option for adult patients with complicated urinary tract infection (cUTI) who have limited and no treatment options. Based on these observations, we conclude that cefiderocol is a potent treatment option for prospective bacterial infections. In this review, we summarize the future prospective use of cefiderocol for bacterial infections.

Delafloxacin, a New Miracle in Antibiotics Armamentarium for Bacterial Infections

The persistent antibiotics resistant issue has emerged as an influencing factor to deteriorate community health. So, new antibiotics development is urgent for the treatment of bacterial infections. Alternatively, delafloxacin is an eminent new fluoroquinolone, and chemically distinct from older fluoroquinolones. There is lack of proton substituent that indicates the poor acidic property of the drug. It also has a good intracellular penetration capacity that increases the intensity of the bactericidal property in acidic environment. Delafloxacin is a super active drug against the skin and soft tissue infections (SSTIs) and community-acquired respiratory tract infections. Delafloxacin also exhibits better efficacy against pathogens which are resistant to other fluoroquinolones, such as methicillin-resistant Staphylococcus aureus (MRSA). Delafloxacin received approval from the US Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSI). Phase III clinical trial among patients with community-acquired pneumonia (CAP) is ongoing to evaluate the effectiveness of delafloxacin. From the aforementioned arguments, delafloxacin will be a prominent candidate for the upcoming antibacterial agent. Similarly, delafloxacin can be a crucial drug to fight against ABSSI.

Omadacycline, a Magic Antibiotics for Bacterial Infections

Nowadays antibiotic resistance is a worldwide serious problem that mainly affects public health. Omadacycline is a unique antibiotic which has two available dosage forms such as intravenous (IV) and oral that development for community-acquired bacterial infectious disease treatment. It is a modified form of older tetracycline at C-9 aminomethyl substituent of 6-member core ring of tetracycline. Modification form shows its activity against efflux pump and ribosomal protein protection mechanism of tetracycline resistance. Generally, omadacycline is effective against methicillin-resistant S. aureus (MRSA), Streptococcus pneumoniae, vancomycin-resistant Enterococcus (VRE), Legionella and Chlamydia spp. Efficacy, safety and tolerability profile of omadacycline those compares with recent antibiotics shows that omadacycline is less resistant than others. One derivative from tetracycline derivatives is 9-neopentylaminomethylminocycline called omadacycline was discovered and ongoing phase III clinical experiments as a therapy for acute bacterial skin and skin structure infections (ABSSSI) as well as community-acquired bacterial pneumonia (CABP). Omadacycline seems to be a strong drug candidate for future promising new antibacterial agent that is effective against ABSSSI and CABP.