Infection Prevention and Control

Video Transcript

Classification and Characteristics of Antibiotics

Welcome to this learning session on Classification and Characteristics of Antibiotics
Overview
Antimicrobials or anti-infective agents are chemicals that inhibit the growth of (or) destroy
microorganisms. Antibiotics include substances produced by fungi and bacteria which kill other
bacteria. They are also chemically synthesized, and these agents treat infections. Antimicrobial
agents kill microorganisms by affecting critical functions of the cell, like cell wall synthesis, protein
synthesis, and genetic material synthesis. The functions of a bacterial cell are different from that of a
human cell. Antimicrobials exploit these differences to exert their action.
Learning Objectives
By the end of this topic, you will be able to:
• Describe the spectrum of activity of antibiotics and
• Discuss the various classes of antibiotics.
Introduction
The spectrum of activity is the range of micro-organisms that are killed or inhibited by an antibiotic. It
also determines the effectiveness of the therapy. Antibiotics may be categorized as a broad and
narrow spectrum. Broad-spectrum antibiotics have comprehensive coverage and are effective
against both gram-negative and gram-positive bacteria. Some of these agents are effective against
anaerobes. Narrow spectrum antibiotics have a limited spectrum and are effective against specific
organisms or specific species or classes of micro-organisms.
Minimum Inhibitory Concentration
Minimum Inhibitory Concentration
The lowest concentration of an antibiotic that inhibits micro-organism growth in a broth culture after
overnight incubation is Minimum inhibitory concentration or MIC. MIC is a laboratory parameter that
helps determine if the micro-organism is sensitive or resistant to a particular antibiotic. Misuse of
antibiotics is quite common in the healthcare industry. Inappropriate antibiotic prescription and
inadequate dosing contribute significantly to the development of antibiotic resistance. Prescribers
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must be aware of the spectrum and the mechanism of commonly used antibiotics to treat infections
appropriately.
Classification of Antibiotics
Classification of Antibiotics
The antibiotics are grouped based on the mechanism of action into
• Antibiotics inhibiting protein synthesis
• Antibiotics inhibiting the nucleic acid synthesis
• Antibiotics inhibiting cell wall synthesis
• Antibiotics disrupting the cell membrane function
• Antibiotics blocking pathways and inhibiting metabolism
Beta-Lactum Antibiotics
Beta-Lactum Antibiotics
• Beta- Lactum antibiotics are the most commonly prescribed anti-microbials that share a
common structure: the 3-carbon and 1-nitrogen ring (beta-lactam ring).
• The mechanism of action is by inhibiting the synthesis of the peptidoglycan bacterial cell wall
constituent by acylating the transpeptidase involved in the cross-linking peptides to form
peptidoglycan.
• The classes of Beta- Lactum include
• Penicillin: This group includes natural penicillin, beta-lactamase–resistant agents,
aminopenicillins, and penicillinase-resistant penicillins.
• Cephalosporins: They are traditionally divided into five generations.
• Carbapenems: Carbapenem is coupled to a beta-lactam ring that confers protection against
most beta-lactamases.
• Monobactams: The beta-lactam ring stands alone and is not fused to another ring.
Penicillins
• Penicillins are a class of antibiotics that inhibit the growth of bacteria by inhibiting cell wall
synthesis. The classification of antibiotics is according to
• The route of administration – This includes oral and parenteral
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• The spectrum of activity and – The spectrum includes narrow spectrum, broad-spectrum,
intermediate spectrum, and extended-spectrum.
• Resistance to beta-lactamase enzymes – This includes nonresistance to B- Lactamase and
resistance to B-Lactamase.
• The chemical structure of all penicillins contains a beta-lactam ring which determines the
ability to inhibit cell wall synthesis. Beta-lactamases, specifically penicillinases, are enzymes
produced by bacteria that cleave the beta-lactam ring and destroy the drug. Such bacteria are
resistant to penicillins. Antibiotics like methicillin are not cleaved by beta-lactamases.
The cell wall is the principal stress-bearing and shape–maintained component, and its integrity is
essential to cell viability. The cell wall of gram-positive bacteria lacks an outer membrane. It is
surrounded by layers of a major component-peptidoglycan composed of linear chains of repeating
disaccharide units cross-linked via peptide side chains. The disaccharide subunit consists of N-Acetyl
Glucosamine (NAG) coupled with N-Acetyl Muramic (NAM). Penicillins block this cross-linking and
prevent cell wall synthesis.
Penicillin G is effective against gram-positive organisms, gram-negative cocci, and non-beta –
lactamase producing anaerobes. It is the drug of choice against streptococci, meningococci,
Clostridium species, and actinomyces and is ineffective against gram-negative rods.
Beta-lactamase-resistant penicillins are effective against beta-lactamase-producing staphylococci
and all penicillin-sensitive streptococci and pneumococci. It is the drug of choice against methicillin-
susceptible Methicillin-resistant Staphylococcus aureus. Beta-lactamase-resistant penicillins are not
effective against Methicillin-resistant Staphylococcus aureus, enterococci, and Listeria
monocytogenes.
Aminopenicillins are effective against gram-positive cocci spirochetes and have greater activity
against gram-negative rods than penicillin. They are the drug of choice for pneumococcal infections,
Shigella species, anaerobes, enterococci, and Salmonella species and are ineffective against
Klebsiella species, enterobacter, and other beta-lactamase producing organisms.
Carboxypenicillins have greater activity against gram negatives like pseudomonas species, Proteus
species, and Enterobacter species. They are not effective against beta-lactamase producers.
Cephalosporins
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• Cephalosporins are antibiotics with a mechanism of action similar to that of penicillin.

• They inhibit the synthesis of cell-wall by disrupting peptidoglycan synthesis.
• There are five generations of cephalosporins, namely the 1st generation effective mainly
against gram-positive organisms.2nd generation cephalosporins are effective against gram-
positive cocci and certain gram-negative bacilli.3rd generation drugs are active against gram-
positive species.4th generation drugs are effective against gram-positive cocci and gram-
negative bacilli, and the 5th generation cephalosporins are effective against Methicillin-
resistant Staphylococcus aureus, penicillin-resistant streptococci, and beta-lactamase-
producing Enterococcus faecalis.
• They penetrate well into the body fluids and the extracellular fluid of most tissues, especially
when inflammation is present. The cephalosporins are bactericidal for both the gram-positive
bacteria and the gram-negative bacteria.
The first-generation cephalosporins include cefadroxil, cefazolin, cephalexin monohydrate, and
cephalothin.
The second-generation cephalosporins are effective against all organisms inhibited by first-generation
cephalosporins, and some of these include cefamandole, cefuroxime, cefonicid, and cefaclor.
The following table describes the third-generation cephalosporins. They are effective against all
agents covered by second-generation cephalosporins with additional coverage against Citrobacter
species, beta-lactamase-producing Haemophilus species, and so on.
The fourth-generation cephalosporins are effective against all agents inhibited by third-generation
cephalosporins with good coverage against Pseudomonas aeruginosa, Enterobacteriaceae,
Staphylococcus aureus so on.
The fifth-generation cephalosporin is effective against MRSA and minimal activity against
enterococci.
Monobactams
The monobactams are effective against aerobic gram-negative bacilli, including Enterobacteriaceae
and Pseudomonas aeruginosa, and they are not effective against gram-positive bacteria and
anaerobes.
Carbapenem
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Carbapenem drugs like Doripenem and Meropenem are effective against gram-negative bacilli ad
several gram-positive organisms.
Beta-lactamase Inhibitors
• These drugs are inhibitors of penicillin hydrolyzing beta-lactamases (Ambler class A).
• They are used in combination with beta-lactam antibiotics to prevent the inactivation of beta-
lactamases.
• Ampicillin – Sulbactam and amoxicillin-clavulanate extend the spectrum of ampicillin to
include Enterobacteriaceae, methicillin-sensitive species, and beta-lactamase-producing
Hemophilus influenza and Streptococcus pneumonia. Piperacillin- Tazobactam broadens the
scope of ticarcillin and piperacillin to include most aerobic gram-positive and gram-negative
organisms.
Glycopeptides and Bacitracin
This class includes vancomycin, teicoplanin, and telavancin. Their mechanism of action is to inhibit
cell wall synthesis.
Bacitracin is mainly used for skin infections. It is a narrow-spectrum antibiotic with activity against
gram-positive cocci, which causes skin infections.
Colistin
Colistin is mostly effective against gram-negative bacteria and is a drug reserved for multi-drug
resistant isolates. Their mechanism of action includes Damaging the outer membrane of gram-
negative organisms.
Streptogramins
These are naturally occurring antibiotics and include Quinupristin/Dalfopristin with a mechanism of
inhibiting protein synthesis.
Oxazolidinones
Linezolid is the available oxazolidinone, and its mechanism of action includes protein synthesis
inhibition.
Lipopeptides
Cyclic lipopeptides are antibiotics derived from Streptomyces rose sports, and their mechanism of
action includes cell membrane damage and termination of protein and genetic material synthesis.
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Aminoglycosides
The spectrum of aminoglycosides is effective against aerobic gram-negative bacteria like
Pseudomonas aeruginosa, Enterobacteriaceae, Hemophilus influenza, and mycobacterium species.
Macrolides
Macrolides include erythromycin, azithromycin, and clarithromycin, and these act by inhibiting
bacterial protein synthesis. They are effective against Group A beta-hemolytic streptococci, penicillin-
susceptible streptococcus pneumoniae.
Nitroimidazole
Nitroimidazoles are commonly used for treating anaerobic infections and include drugs like
metronidazole and tinidazole.
Mechanism of action includes Inhibiting DNA synthesis and enzymes involved in energy production.
Clindamycin
Clindamycin is active against most anaerobes.
Quinolones
• First-generation quinolones like nalidixic acid are used only for urinary tract infections. The
other quinolones, ciprofloxacin, norfloxacin, moxifloxacin, and levofloxacin, attain significant
levels in tissue and the bloodstream.
• Mechanism of action includes Inhibiting DNA gyrase in gram-negative bacteria and
topoisomerase in gram-positive organisms.
Tetracyclines
• Tetracyclines are broad-spectrum antibiotics with clinical efficacy against intracellular
pathogens. They include tetracycline, doxycycline, minocycline, and tigecycline.
• Mechanism of action includes inhibition of protein synthesis.
Conclusion
We have reached the end of this session. Let us conclude:
The spectrum of activity is the range of micro-organisms that are killed or inhibited by an antibiotic.
Antibiotics may are classified as broad and narrow scope depending on the spectrum. Broad-
spectrum antibiotics have comprehensive coverage and are effective against both gram-negative and
gram-positive bacteria. Some of these agents are effective against anaerobes. Narrow spectrum
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antibiotics have a limited spectrum and are effective against anaerobes. A thin scope is effective
against specific organisms or specific species or classes of micro-organisms.