Pharmaceutical

Microbiology and
Parasitology

Antimicrobial (PHMP 211)

Drugs Our Lady of Fatima

University
College of Pharmacy
Ehrlich’s Magic Bullets
Fleming and Penicillin
Chemotherapy

The use of drugs to treat a disease

☐Selective toxicity: A drug that kills harmful
microbes without damaging the host
Antibiotic vs. Antimicrobial

Antibiotic: Chemical produced by a

microorganism that kills or inhibits the growth of
another microorganism

Antimicrobial agent: Chemical that kills or

inhibits the growth of microorganisms
Cidal vs. Static

Cidal: Chemical that kills organism

☐Bactericidal
☐Fungicidal

Static: Chemical that inhibits the growth of

microorganisms
☐Bacteriostatic
☐Fungistatic
Antibiotic Spectrum of Activity
No antibiotic is effective against all microbes.
BROAD SPECTRUM ANTIBIOTIC
 WIDESPREAD ACTIVITY AGAINST MANY
TYPES OF ORGANISM
 G+, G-, RICKETTSIA, MYCOBACTERIA
NARROW SPECTRUM ANTIBIOTIC
 NARROW ACTIVITY AGAINST ORGANISM
 G- ONLY
 G+ ONLY
Mechanisms of Antimicrobial Action

Bacteria have their own enzymes for:

☐Cell wall formation
☐Protein synthesis
☐DNA replication
☐RNA synthesis
☐Synthesis of essential metabolites
Mechanisms of Antimicrobial Action

Viruses use host enzymes inside host cells.

 OBLIGATE INTRACELLULAR PARASITES

Fungi and protozoa have own eukaryotic

enzymes.

The more similar the pathogen and host

enzymes, the more side effects the antimicrobials
will have.
 DNA TO MRNA MRNA TO PROTEIN

COPYING OF DNA TO DNA

Modes of Antimicrobial Action

 CELL WALL SYNTHESIS INHIBITORS
• MOA [Penicillins & Cephalosporins]
• Bind to penicillin-binding proteins (PBPs) which are involved in
cross-linking/transpeptidation of peptidoglycan layer thus
inhibiting peptidoglycan layer cross-linking/transpeptidation in cell
wall

1. Penicillins
2. Cephalosporins
3. Miscellaneous
TYPES OF PENICILLIN ANTIBIOTIC:
1. NATURAL PENICILLIN (g+)
A. PEN V  ORAL, “Vivig”
B. PEN G  IV, “iniinGect”
C. BENZATHINE PEN G  IM
2. ISOXAZOLYL PENICILLIN / ANTISTAPHYLOCOCCAL
Staphylococcus organism
Methicillin, Nafcillin, Cloxacillin and Fludocillin
3. AMINOPENICILLINS (EXTENDED SPECTRUM ANTIBIOTIC) (WITH G-)
AMPICILLIN
AMOXICILLIN
4. ANTIPSEUDOMONAL PENICILLIN (Pseudomonas aeruginosa)
Carboxypenicillin: Carbenicillin, Ticarcillin
Ureidopenicillin: Piperacillin, Mezlocillin, Azlocillin
Antibacterial Antibiotics
Inhibitors of Cell Wall Synthesis

Penicillin (over 50 compounds)

☐Share 4-sided ring (β-lactam ring)

Natural penicillins
☐Narrow range of action
☐Susceptible to penicillinase (β-lactamase) 
released by S.aureus to inhibit the beta –lactam ring
of penicillin  ineffectiveness of penicillin
☐BETA LACTAMASE RESISTANT ANTIBIOTIC 
ISOXAZOLYL ANTIBIOTIC/
ANTISTAPHYLOCOCCAL ANTIBIOTIC
Prokaryotic Cell Walls
Penicillinase (b Lactamase)

Figure 20.8
Semisynthetic Penicillins

Penicilinase-resistant penicillins
☐Carbapenems: very broad spectrum
☐Monobactam: Gram negative

Extended-spectrum penicillins

Penicillins + -lactamase inhibitors

Antibacterial Antibiotics
Inhibitors of Cell Wall Synthesis

Cephalosporins
☐2nd, 3rd, and
4th generations
more effective
against gram-
negatives
 CELL WALL SYNTHESIS INHIBITORS
Cephalosporins
Generation G (+) G (-)
1st +++ +
2nd ++ ++
3rd + +++
4th ++ +++
5 th
+++ +++
Antibacterial Antibiotics
Inhibitors of Cell Wall Synthesis

Polypeptide antibiotics
☐Bacitracin
☐Topical application
☐Against gram-positive
☐Vancomycin
☐Glycopeptide
☐Important "last line" against antibiotic resistant S.
aureus
☐MRSA  METHICILLIN RESISTANT
STAPHYLOCOCCUS AUREUS  VANCOMYCIN
Antibacterial Antibiotics
Inhibitors of Cell Wall Synthesis

Antibiotics effective
against Mycobacteria:
interfere with mycolic acid
synthesis or incorporation
ANTITUBERCULOSIS /
ANTIMYCOBACTERIAL
(Mycobacterium
tuberculosis)
☐Isoniazid (INH)
☐Ethambutol
ANTIMYCOBACTERIAL DRUGS
ANTITUBERCULOSIS

DRUGS MOA
RIFAMPICIN INHIBIT DNA DEPENDENT RNA POLYMERASE
(DNA SYNTHESIS)
ISONIAZID (INH) INHIBITS MYCOLIC ACID SYNTHESIS (CELL
WALL)
PYRAZINAMIDE UNKNOWN MOA, BACTERICIDAL
ETHAMBUTOL INHIBITION OF ARABINOSYL TRANSFERASE
(RESPONSIBLE FOR THE FORMATION OF
ARABINOSYL GALACTAN  COMPONENT OF
MYCOBACTERIAL CELL WALL)
STREPTOMYCIN AMINOGLYCOSIDE
INHIBITS THE PROTEIN SYNTHESIS
Antibacterial Antibiotics
Inhibitors of Protein Synthesis

Broad spectrum, toxicity problems

Examples:
☐Chloramphenicol (bone marrow)
☐Aminoglycosides: Streptomycin, Neomycin,
Gentamicin (hearing, kidneys)
MYCIN  STREPTOMYCES ORGANISM
MICIN  MICROMONOSPORA ORGANISM
☐Tetracyclines (DOXYCYCLINE  DOC FOR
LEPTOSPIROSIS) (Rickettsias & Chlamydia; GI tract)
☐Macrolides: Erythromycin (gram +, used in children)
PROTEIN SYNTHESIS INHIBITORS

Ribosomes  used for protein synthesis

 30s and 50s ribosomal subunit
buy AT 30  AMINOGLYCOSIDE AND
TETRACYCLINE
CEL @ 50  (CHLORAMPHENICOL,
ERYTHROMYCIN: MACROLIDE,
LINCOSAMIDE)
Antibacterial Antibiotics
Injury to the Plasma Membrane

Polymyxin B (Gram negative)

☐Topical
☐Combined with bacitracin and neomycin
(broad spectrum) in over-the-counter
preparation
Antibacterial Antibiotics
Inhibitors of Nucleic Acid Synthesis

Rifampicin
☐Inhibits RNA synthesis
☐Antituberculosis
Quinolones and fluoroquinolones
☐Ciprofloxacin
☐Inhibits DNA gyrase/ TOPOISOMERASE II
(DNA SUPERCOILING)
☐Urinary tract infections
QUINOLONES

1st Generation
• Nalidixic acid (prototype)
• Cinoxacin, Rosoxacin, Oxolinic Acid

2nd Generation
• Ciprofloxacin, Lomefloxacin, Ofloxacin (tulo), Norfloxacin, Enoxacin
3rd Generation
• Levofloxacin, Gatifloxacin, Sparfloxacin, Grepafloxacin, Gemifloxacin
4th Generation
• Trovafloxacin, Alatrofloxacin, Moxifloxacin
Antibacterial Antibiotics
Competitive Inhibitors

Sulfonamides (Sulfa drugs)

☐Inhibit folic acid synthesis
☐Broad spectrum
SULFONAMIDES

Sulfonamides – weakly acidic

Short-Acting
☐Sulfisoxazole
☐Sulfacytine
☐Sulfamethizole
Intermediate-Acting
☐Sulfamethoxazole
☐Sulfadiazine
☐Sulfapyridine
Long-Acting
Sulfadoxine
 NUCLEIC ACID SYNTHESIS INHIBITORS
MOA of Antimetabolites:
1. CELL WALL SYNTHESIS INHIBITOR  PEN,
CEPHALOSPORIN, BACITRACIN, VANCOMYCIN,
ISONIAZID, ETHAMBUTOL
2. PROTEIN SYNTHESIS INHIBITOR 
AMINOGLYCOSIDE,
TETRACYCLINE,CHLORAMPHENICOL,
MACROLIDE, LINCOSAMIDE
3. INJURY IN PLASMA MEMBRANE  POLYMIXIN B
4. NUCLEIC ACID SYNTHESIS  SULFONAMIDES,
TRIMETHOPRIM, RIFAMPIN/RIFAMPICIN
 Antifungal Antibiotics

Fungi are
eukaryotes
Have unique sterols
(ERGOSTEROL) in
their cell walls
Pathogenic fungi are
often outside the
body
ANTIFUNGAL DRUGS

DRUGS
AMPHOTERICIN B  SYSTEMIC FUNGAL INFECTION
 BINDS WITH ERGOSTEROL CAUSING
LEAKAGE OF THE CELL MEMBRANE
GRISEOFULVIN  INHIBITS THE MICROTUBULE
SYNTHESIS (DNA SYNTHESIS)
AZOLE ANTIFUNGAL  INHIBITING 14-ALPHA DEMETHYLASE
KETOCONAZOLE, (LANOSTEROL  ERGOSTEROL)
FLUCONAZOLE,
ITRACONAZOLE
FLUCYTOSINE  INHIBITS DNA AND RNA SYSNTHESIS
5-FU (5-FLUOROURACIL)  CONVERTED TO FLUCYTOSINE (DNA
AND RNA SYNTHESIS)
Antiviral Drugs

Viruses are composed of nucleic acid, protein

capsid, and host membrane containing virus
proteins
Viruses live inside host cells and use many host
enzymes  OBLIGATE INTRACELLULAR
MICROORGANISM
Some viruses have unique enzymes for
DNA/RNA synthesis or protein cutting in virus
assembly
Figure 20.16a
Antiviral Drugs
Nucleoside and Nucleotide Analogs

Figure 20.16a
Analogs Block DNA Synthesis
Antiviral Drugs
Enzyme Inhibitors

Inhibit assembly
☐Indinavir (HIV)
Inhibit attachment
☐Zanamivir (Influenza)
Inhibit uncoating  PROTEIN CAPSID
☐Amantadine (Influenza)
Antiviral Drugs
Enzyme Inhibitors

Interferons prevent spread of viruses to new

cells (Viral hepatitis)
Natural products of the immune system in viral
infections
 Antiprotozoan Drugs

Protozoa are eukaryotic

cells
Many drugs are
experimental, and their
mode of action is unknown
Metronidazole – inhibit glucose uptake
Trichomonas vaginalis  TRICHOMONIASIS
Entamoeba histolytica  AMOEBIASIS
Giardia lamblia  GIARDIASIS
Anaerobic bacteria
 ANTIPROTOZOALS PNEUMOCYSTOSIS  COTRIMOXAZOLE
TOXOPLASMOSIS  SULFADIAZINE
PYRIMETHAMINE
LEISHMANIASIS  SODIUM STIBOGLUCONATE
PLASMODIUM TRYPANOSOMIASIS
SPECIES MALARIA AMERICAN  NIFURTIMOX
AMOEBIASIS AFRICAN  MELARSOPROL
Antihelminthic Drugs/ ANTHELMINTHIC DRUG

Helminths are
macroscopic
multicellular
eukaryotic
organisms:
tapeworms,
roundworms,
pinworms,
hookworms
ANTHELMINTHICS
NEMATODES  ROUNDWORM
TREMATODES  FLATWORM /FLUKEWORM
CESTODES  TAPEWORM
Measuring Antimicrobial Sensitivity

E Test
MIC: Minimal inhibitory concentration
Measuring Antimicrobial Sensitivity: Disk Diffusion
Antibiotic Resistance

Figure 20.20
Antimicrobial Resistance

Relative or complete lack of effect of

antimicrobial against a previously susceptible
microbe
Increase in MIC
Mechanisms of Antibiotic Resistance

oEnzymatic destruction of drug

oPrevention of penetration of drug
oAlteration of antibiotic or target site
oRapid ejection of the drug
Antibiotic Selection for Resistant Bacteria
What Factors Promote Antimicrobial Resistance?

Exposure to sub-optimal levels of antimicrobial

Exposure to microbes carrying resistance genes
Inappropriate Antimicrobial Use

Prescription not taken correctly

Antibiotics for viral infections
Antibiotics sold without medical supervision
Spread of resistant microbes in hospitals due to
lack of hygiene
Inappropriate Antimicrobial Use

Lack of quality control in manufacture or

outdated antimicrobial
Inadequate surveillance or defective
susceptibility assays
Poverty or war
Use of antibiotics in foods
Antibiotics in Foods

Antibiotics are used in animal feeds and sprayed

on plants to prevent infection and promote
growth
Multi drug-resistant Salmonella typhi has been
found in 4 states in 18 people who ate beef fed
antibiotics
Consequences of Antimicrobial Resistance

Infections resistant
to available
antibiotics
Increased cost of
treatment
Multi-Drug Resistant TB
MRSA “mer-sah”

Methicillin-Resistant Staphylococcus aureus

Most frequent nosocomial (hospital-acquired)
pathogen
Usually resistant to several other antibiotics
Proposals to Combat Antimicrobial Resistance

Speed development of new antibiotics

Track resistance data nationwide
Restrict antimicrobial use
Direct observed dosing (TB)
Proposals to Combat Antimicrobial Resistance

Use more narrow spectrum antibiotics

Use antimicrobial cocktails