Classes of Antibiotics:

Beta-lactam antibiotics are the most widely used class of drugs for the treatment of bacterial infections. They include penicillin and its derivatives, such as methicillin and amoxicillin. The beta-lactam ring portion of the antibiotic targets the penicillin-binding proteins (PBP), found in the bacterial cell membrane, which function in the synthesis of the cell wall. Binding of the antibiotic to the PBPs prevents the PBPs from performing their essential role and results in the death of the bacterial cell.

Gram positive bacteria acquire resistance to beta-lactam antibiotics through the production of a protein called PBP2a, which is able to avoid the inhibitory effects of the antibiotics. This is the mechanism by which MRSA is able to persist despite treatment with multiple beta-lactam antibiotics.

The genes for beta-lactamase enzymes are probably the most international in distribution: random mutations of the genes encoding the enzymes have given rise to modified catalysts with increasingly extended spectra of resistance. The archetypical plasmid-encoded beta-lactamase, TEM, has spawned a huge tribe of related enzyme families, providing ample proof this adaptability. The beta-lactamase genes are ancient and have been found in remote and desolate environments, which implied that novel beta-lactamases with altered substrate ranges occur in the environment. (Davies, “origins and Evolution of Antibiotic Resistance” Microbiology and Molecualr Biology Reviews, 2010, p. 417-433)

–Amoxicillin: is used to treat a wide variety of bacterial infections. It is a penicillin-type antibiotic that works by stopping the growth of bacterial. Amoxicillin is a widely utilized beta-lactam antimicrobial drug approved by the U.S. Food and Drug Administration (FDA) for use in the primary care setting. Amoxicillin is an aminopenicillin created by adding an extra amino group to penicillin to battle antibiotic resistance. This drug is indicated for the treatment of infections caused by susceptible isolates of selected bacteria, specifically those that are beta-lactamase–negative, including ear, nose, and throat infections, Helicobacter pylori eradication, lower respiratory and urinary tract infections, acute bacterial sinusitis, and skin and structure infections.

Amoxicillin is effective against a wide range of gram-positive bacteria, offering additional coverage against some gram-negative organisms compared to penicillin. Amoxicillin’s spectrum of activity includes coverage against Streptococcus species, with heightened efficacy against Listeria monocytogenes and Enterococcus spp. Furthermore, amoxicillin also demonstrates effectiveness against Haemophilus influenzae, select Escherichia coli strains, Actinomyces spp., Clostridium species, Salmonella spp., Shigella spp., and Corynebacteria spp.

Fluoroquinolones:

–Ciprofloxacin: is a member of the fluorquinolone drug class that is sued to treat various Gram-engative bacteria such as Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae and E coli and Gram-positive bacteria such as Staphylococcus auereus. (Chegini, “Bacteriophages: The promising therapeutic approach for enhancing ciprofloxacin efficacy against bacterial infection” J Clin Lab Anal, 2023).

Gepotidacin: This antibiotic is in phase III (GSK). It could become the first novel oral antibotic treatment for uncomplicated urinary tract infections in over 20 years. Gepotidacin provides activity against most srains of E. coli, including isolates that are highly reistant to current antibiotics. It binds to two different enzymes, which would reuqire the bacteria to develop mutations in both enzymes to become resistant . GSK also ahs an exclusive licence with Spero Therapeutics for another antibiotic to treat complicated urinary tract infections called tebipenem pivoxil hydrobromide (tebipenem HBr). This drug belogs to a class of antibiotic agents called carbapenems, which are typically reserved for sever bacterial infections of suspecte mutlidrug-resistant bacterail infections.

Macrolide antibotics: such as erthyromycine were introduced to content with the problem of methicillin resistance and are widely used for the treatment of Gram-positive infections. The macrolides and related antibiotics act by binding at different sites in the peptide exit tunnel of the 50S ribosome subunit. Resistance can occur by modificaiton of the RNA or protein components of the tunnel.

Streptomycin: was introduced in 1944 for the treatment of tuberculosis. Mutant strains of Mycobacterium tuberculosis resistant to therapeutic concentrations of the antibiotic were found to arise during patient treatment.

Combination of antibiotics:

Antibiotic combination therapy is the application of two or more antibiotics and is widely sued in clinical settings to prevent the evolution of resistance. Compared to monotherpiees, such therapies can improve treatment efficiency, expand antibiotic coverage or reduce health damage ot humans. For example, beta-lactams are used in combination with aminoglycosides and fluoroquinolones for the treatment of gram-negative bacteria of sepsis and severe Pseudomonas infections.

Antibiotic adjuvants:

Antibiotic adjuvants can provide an alternative and complementary strategy that can target antibiotic resistance or enhcnace antibiotic action to restore or improve the antimicrobial activity of commonly used antibiotic. The adjuvants commonly used can be classified into beta-lactamase inhibitors, efflux pump inhibitors and outer membrane permeabilizers.

Antibiotic Resistance:

The gut microbioa in healthy adults is a reservoir for multiple ARGs. A major parte of the gut reistome has its origin in soil and water habitates, and some in food. As these populations had little exposure to antibiotics, their ubiquitous ARGs such as tetracylcine and several beta-lactam resistance genes are environmentally derived. Only a small fraction of ARGs pose a threat to human health. (Staley, “Long- and short-term effects of fecal microbiota transplantation on antibiotic reistance genes: results form a randomized placebo-controlled trial” (2024)