Antimicrobial Drugs

Antimicrobial Drugs
• Antimicrobial drugs Interfere with the
growth of microbes within a host
• Antibiotic
– Substance produced by a microbe that, in
small amounts, inhibits another microbe
• Selective toxicity
– A drug that kills harmful microbes without
damaging the host
 Properties of an ideal antibiotic
• broad spectrum
• soluble in body fluids
• stable toxicity
• Nonallergenic
• reasonable cost
• selectively toxic
• not likely to induce bacterial resistance
 Microorganism that produce
clinically useful antibiotics
• Bacillus
• Streptomyces
• Cephalosporium
• Penicillium
Postantibiotic Effect
Persistent suppression of bacterial growth after limited ex-
poser to an antimicrobial agent.

PAE = T-C
T = the time required for the viable count in the test (invitro) cultuture
to increase tenfold above the count observed immediately before drug re
moval and C is the time required for the count in untreated culture to
increase tenfold above the count observed immediately after completion
of the same procedure used on the test culture.
The PAE reflects the time required for bacteria to return to logarithmic
growth.
In vivo PAE are usually much longer than in vitro due to PALE
 Antimicrobial activity
Inhibit Cell wall synthesis
Penicillins, Cephalosporins, Monobactam,
Carbapenem. Vancomycin

Inhibit protein synthesis

Aminoglycides, tetracyclines, chloramphenicol,
Macrolide

Inhibit nucleic acid synthesis

Sulphoamide ,Trimethoprim ,Quinolones
Penicillin group:
Penicillin Ampicillin
Nafcillin Amoxicillin
Ticarcillin
Oxacillin
Cloxacillin
Dicloxacillin

Clinical uses:
Treatment of sensitive microorganism.

ADR: anaphylactic shock

First-generation:
-Cephadroxil
-Cephazolin
-Cephalexin
-Cephalothin
-Cephapirin
-Cephradine

Second –gneration:
-Cefachlor -Loracarbef
-Cefamandole -ceforanide
-Cefonicid -Cefoxitin
-Cefuroxime -Cefmetazole
-Cefprozil
Third-Geheration:
-Cefoperazone -Cefixime
-Cefotaxime -Cefpodoxime proxetil
-Ceftizoxime -Cefdinir
-Ceftazidime -Cefditoren pivoxil
-Ceftriaxzone -Ceftibuten
-Moxalactam

Fourth-Generation
-Cefepime

Monobactam beta-lactam
Aztreonam
Beta-lactamase inhibitor:
-Clavulanic acid
-Sulbactam
-Tazobactam

Carbapenem{
-Ertapenem
-Imipenem
-Meropenem

Other cell wall-acyive agents:

-Vancomycin -Teicoplanin -Daptomycin
-Bacitracin -Fosphomycin -Cycloserine
Penicillins resistant to staphylococcal beta
lactamase:
-Methicillin
-Nafcillin
-Isoxazolyl penicillins

Extended-spectrum penicillins
-Aminopenicillins
-Carboxypenicillins
-ureidopenicillins
Beta-Lactam & Other Cell Wall & Membrane-
Active Antibiotics.

Beta-lactam compound:
-Penicillins
-Cephalosporins
-Monobactams
-carbapenems
-β lactamase inhibitor
 Antibacterial Antibiotics
Inhibitors of Cell Wall Synthesis
• Penicillin
– Natural penicillins
– Semisynthetic penicillins
• Penicilinase-resistant penicillins
• Extended-spectrum penicillins
• Penicillins + -lactamase inhibitors
• Carbapenems
• Monobactam
 Antibacterial Antibiotics
Inhibitors of Cell Wall Synthesis
• Cephalosporins
– 2nd, 3rd, and 4th generations more effective against
gram-negatives
• Polypeptide antibiotics
– Bacitracin
• Topical application
• Against gram-positives
– Vancomycin
• Glycopeptide
• Important "last line" against antibiotic resistant S.
aureus
 Antibacterial Antibiotics
Inhibitors of Protein Synthesis
• Chloramphenicol
– Broad spectrum
• Binds 50S subunit, inhibits peptide bond
formation
• Aminoglycosides
– Streptomycin, neomycin, gentamycin
• Broad spectrum
– Changes shape of 30S subunit
 Antibacterial Antibiotics
Inhibitors of Protein Synthesis
• Tetracyclines
– Broad spectrum
• Interferes with tRNA attachment
• Macrolides
– Gram-positives
• Binds 50S, prevents translocation
• Erythromycin
– Gram-positives
• Binds 50S, prevents translocation
 Definitions
• MIC Minimal inhibitory
concentration
• MBC Minimal bactericidal
concentration
 Antibiotic Resistance
• A variety of mutations can lead to
antibiotic resistance.
• Mechanisms of antibiotic resistance
1. Enzymatic destruction of drug
2. Prevention of penetration of drug
3. Alteration of drug's target site
4. Rapid ejection of the drug
• Resistance genes are often on plasmids
or transposons that can be transferred
between bacteria.
 Antibiotic Resistance
• Misuse of antibiotics selects for
resistance mutants. Misuse includes:
– Using outdated, weakened antibiotics
– Using antibiotics for the common cold and
other inappropriate conditions
– Use of antibiotics in animal feed
– Failure to complete the prescribed regimen
– Using someone else's leftover prescription
 Effects of
Combinations of Drugs
• Synergism occurs when the effect of
two drugs together is greater than the
effect of either alone.
• Antagonism occurs when the effect of
two drugs together is less than the
effect of either alone.