Question

What are antimicrobial agents? Discuss the differences between the major classes of antimicrobial agents, give examples of each, and describe what groups of bacteria are resistant to each and why.

Answer 1

Antimicrobial Agents - These are the drugs or chemical or agents which either kill or slow down the growth of microbes.

These are mainly classified in various classes based on chemical structure and mechanism of action as mentioned below.

A) Inhibition of cell wall synthesis agents

B) Inhibition of protein synthesis agents

C) Inhibition of bacterial nucleic acid synthesis agents

A) Inhibition of cell wall synthesis agents

Structurally, the bacterial cell wall is different from that of all other organisms by the presence of polysaccharide backbone, called peptidoglycan, which is composed of alternating N‐acetylmuramic acid and N‐acetylglucosamine residues in equal amounts and most of the eubacteria have peptidoglycan‐based cell walls except the mammalian cell. The bacterial cell wall offers structural completion to the cell; therefore, the most important process for avoiding bacterial growth is to stop cell wall synthesis by inhibiting the peptidoglycan layer of bacterial cell walls. The agents used to work against this function are called cell wall synthesis inhibitors.

• Penicillin

Class	Drugs/agent	Microbes affected
penicillinase susceptible	pen V & G	mostly gram-positive - Streptococcus pyogenes , Clostridium tetani e.t.c
penicillinase resistance	methicillin, oxacillin	Staphylococcus aureus
penicillinase susceptible with activity against gram-negative bacilli	ampicillin, amoxicillin, piperacillin	Enterococcus faecalis,E.coli,Helicobacter pylori,salmonella,shigella
penicillins with beta-lactamase inhibitors	amoxicillin-clavulanate	pseudomonas aeruginosa , Enterococcus faecalis,E.coli,Helicobacter pylori,salmonella,shigella

• cephalosporins

Class	Drugs/agent	Microbes affected
1st generation	cephazolin, cephalexin	Staphylococcus aureus , Staphylococcus epidermidis
2nd generation	cefuroxime, cefoxitin	Staphylococcus aureus , Staphylococcus epidermidis with gram negative activity
3rd generation	cefotaxime, ceftriaxone	Pseudomonas
4th generation	cefepime	same as all above

• Glycopeptide derivatives

Class	Drugs/agent	Microbes affected
Glycopeptide	vancomycin, teicoplanin, bleomycin	most gram positive bacteria

• Carbopenems

Class	Drugs	Microbes affected
Carbopenems	imipenem, meropenem	gram postive cocci,enterobacteriaceae , pseudomonas ,listeria , e.t.c

B) Inhibition of protein synthesis agents

Protein synthesis is one of the most important functions in the bacterial cell and humans as well. Therefore, to cure infectious disease caused by pathogenic bacteria, it is the most important target for the drugs, which are called protein synthesis inhibitor antibiotics. Since both human and bacterial cells synthesize proteins, due to the slow synthesis of human proteins, it has remained a comfortable task for the development of the selective antibiotics. Only the side effects from toxicity and resistance phenomenon are taken seriously during antibiotic development. protein synthesis inhibitors act to disturb any stage of the protein synthesis such as initiation and elongation stages (aminoacyl tRNA entry, proofreading, peptidyl transfer, ribosomal translocation and termination).

Class	Drugs/agent	Microbes affected
Aminoglycosides	gentamicin, tobramycin, amikacin	aerobic gram-positive bacteria such as Enterobacteriaceae and some are active against Pseudomonas
Macrolides	erythromycin, clarithromycin, azithromycin	Streptococcus Haemophjfus influenzae Mycopfasmapneumoniae
Tetracyclines	Tetracycline, Doxycycline	Rickettsiae, Chlamydiae, Mycoplasma., Spirochetes
Chloramphenicol	Chloramphenicol	Haemophjfus influenzae Salmonella
Lincomycins	clindamycin	Resistant gram positives like MRSA

C) Inhibition of bacterial nucleic acid synthesis agents

Class	Drugs/agent	Microbes affected
Fluoroquinolones l st generation	Norfloxacin, clprofloxacin ofloxacin	EntH<>bact• riaceH:, such as £.£0/i, KJebsie//a, 2. fnrerobacter,Salmone/la, Shigel/o,Praeu~Yerm/o
Auoroquinolones 2nd generation	Levofloxacin, lomefloxacin, moxifioxacin, sparfloxacin	Others: Neisser/o, HoemoptiAl$ Campylobacter, vibrio cholerae
Metronidazol	lntracellularlygenerates metabolic by·products that damage DNA	Anaerobic organisms
Rifampln	lnhibits RNA polymerase	Staphylocoa:us Mycobacrerjum tuberculosis