Antimicrobials and antimicrobial

classification

Lina Cavaco
Rene Hendriksen
Susanne Karlsmose Pedersen
Outline
• Antimicrobial/Antibiotic- definitions
• Use of antimicrobials
• Antimicrobial resistance- definitions
• Antimicrobials – origin
• Antimicrobials classification
– Antimicrobial classes
– Bactericidal vs Bacteriostatic
– Spectrum of antimicrobials

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What is an antibiotic/antimicrobial
• Antibiotic is a substance produced by a microorganism, that
has the capacity, to selectively inhibit or kill other
microorganisms (Paul Vuillemin, 1941)

• Antimicrobial is a broader term - referring to any substance

that can affect microbial life, including synthetic and semi-
synthetic compounds and substances without selective toxicity
(e.g. biocides)

• Some of the most toxic substances in the world 0.001-4 mg/L

have an effect, but in therapeutic doses they do not harm the
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Use of antimicrobials in humans

• Antimicrobials are (should be) used in humans mainly to kill or

inhibit harmful bacteria that cause infection and disease

• The CDC estimates that about one-third of the 150 million outpatient
prescriptions for antibiotics every year are unnecessary

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Use of antimicrobials in animals
• Therapeutic use:
– To treat sick animals

• Prophylactic / Metaphylactic use:

– To prevent infection in animals

• Growth promoters (used as a supplement in animal feed in sub-

therapeutic concentrations, which is prohibited in the EU):
– To improve feed utilization, production and enhance economic returns to
farmers
– Control of chronic diseases in intensively-reared animals

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Antimicrobial resistance is a relative term

Resistance Susceptibility
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What is antimicrobial resistance
• Real world - clinical definition
Resistance is the ability of a bacterial strain to survive or grow during
antimicrobial treatment

• Research - genetic definition

Resistance is defined by the presence of a genetic change
(mutation or gene) = resistance determinant

• Laboratory - microbiological definition:

Resistance is the ability to survive or grow in higher antibiotic
concentrations than most other bacterial strains of the same species

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 Classification of antimicrobials
• Based on chemical structure
• Based on target organisms
– Antiviral
– Antibacterial
– Antifungal
– Antiparasitic
• Based on antimicrobial activity
– Bactericidal
– Bacteriostatic
• Spectrum of activity
– Narrow Note: Sulfonamides are both
– Broad antibacterial and antiparasitic

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Origin of antimicrobial classes
Class Antimicrobial agents Producing organisms Year of
isolation

ß-lactams Natural penicillins Penicillium notatum, P. chrysogenum, 1929,

Cephalosporium acremonium 1940
Cephalosporin C Streptomyces cattleya
Gluconobacter spp. 1945-53
Imipenem Chromobacterium violaceum 1976
Aztreonam 1981

Glycopeptides Vancomycin Amycolapsis orientalis Mid-

Teicoplanin, avoparcin Amycolapsis coloradensis subsp labeda 1950s,
1975
Macrolides Erythromycin Streptomyces erythraeus 1952
Spramycin Streptomyces ambofaciens 1955
Lincosamides Lincomycin Streptomyces lincolnensis 1963
Streptogramins Streptogramins A and B Streptomyces diastaticus 1953
Virginiamycins A and B Streptomyces virginiae 1955
Tetracyclines Chlortetracycline Streptomyces aureofaciens 1948
Oxytetracycline Streptomyces rimosus
Phenicols Chloramphenicol Streptomyces venezuelae 1947
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Origin of antimicrobial classes -
cont
Class Antimicrobial agents Producing organisms Year of
isolation
Aminoglycosides Streptomycin Streptomyces griseus 1943
Neomycin Streptomyces fradiae 1949
Kanamycin Streptomyces kanamyceticus 1957
Gentamicin Micromonospora purpurea 1963
Tobramycin Streptomyces tenebrarius 1967
Aminocyclitols Spectinomycin Streptomyces spectabilis 1961
Pleuromutilins Tiamulin Pleurotus spp.
Polypeptide Polymyxin B Bacillus polymyxa (aerosporus) 1947
antibiotics Polymyxin E (colistin) Bacillus polymyxa subsp colistinus 1949
Bacitracin Bacillus licheniformis 1943
Sulfonamides Prontosil, sulfametoxazole, etc. Synthetic 1935

Trimethroprim Trimethroprim Synthetic 1956

Quinolones Nalidixic acid Synthetic 1962

Fluoroquinolones Ciprofloxacin, Levofloxacin, etc. Synthetic 1973

Oxazolidones Linezolid Synthetic 1987,1996

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Bactericidal vs bacteriostatic
drugs
Bactericidal drugs are recommended in:
• Life threatening infections where
the immune system is unable to
remove bacteria (e.g.
endocarditis)
• Immuno-compromised patients

Some drugs may be

bactericidal or bacteriostatic
depending on
– Drug concentration
– Presence of other drugs
– Bacterial species
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Bactericidal vs Bacteriostatic antimicrobials
Class Origin Activity
Aminoglycosides Streptomyces, Micromonospora spp. Bactericidal
Cephalosporins Cephalosporium spp. Bactericidal
Macrolides Various Actinomycetes Bacteriostatic
Penicillins Penicillium sp Bactericidal
Phenicols Streptomyces venezuelae Bacteriostatic
Quinolones Synthetic Bactericidal
Rifamycins Amycolapsis mediterranei Bactericidal
Sulfonamides Synthetic Bacteriostatic
Tetracyclines Streptomyces spp. Bacteriostatic

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 Bacteriostatic antimicrobials
• Tetracyclines

• Sulphonamides

• Macrolides

• Chloramphenicol

• Trimethroprim
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Antimicrobial effect
vs PK/PD parameters
Pharmacodynamics (PD)
– Mechanisms for killing or inhibiting growth
– Time-dependent/concentration-dependent
– MIC - Minimum inhibitory concentration
– MBC - Minimum bactericidal concentration

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Antimicrobial effect
vs PK/PD parameters

Pharmacokinetics (PK)
– Depend on route of administration, formulation, drug
absorption, distribution, elimination, bioavailability
• Cmax (g/mL) - maximal concentration in plasma
• Tmax (h) - time at Cmax
• t1/2 (h) - half-life
• AUC LOQ (g.h/mL) area under curve

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Determine MIC and MBC of
bacteriostatic drugs
MIC MBC

0.12 0.25 0.5 1 2 4 8 16 Control

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 Use of associations of antimicrobials
• Increase efficacy
• Increase spectrum
• Synergic effect
• Not always beneficial, some combinations might be reducing
efficacy:
– E.g. bactericidal drug need microbial growth to act
– Bacteriostatic drug stop growth
– = Antagonism

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 On behalf of the EURL-AR team:
Thank you very much!

www.antimicrobialresistance.dk

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