MICROBIOLOGY– 1.1B ANTIMICROBIAL DRUGS (DR.

DEVEZA)
OUTLINE
β- lactam antibiotics Other antibiotics
1. Inhibitors of Cell Wall Synthesis
Penicillins Bacitracin
2. Protein Synthesis Inhibitors
Cephalosporins Vancomycin
3. Inhibitors of Folic Acid Synthesis
Carbapenems
4. Inhibitors of Nucleic Acid Synthesis
Monobactam
- Interstitial nephritis
(methicillin)
DEFINITION OF TERMS
- Maculopapular rash
o Chemotherapy: The use of drugs to treat a disease.
(ampicillin)
o Antimicrobial drugs: Interfere with the growth of
microbes within a host.
2. Cephalosporins
o Antibiotic: Substance produced by a microbe that, in small
MOA & MOR: Same as penicillin
amounts, inhibits another microbe.
Adverse Effects:
o Selective toxicity: A drug that kills harmful microbes without
o Hypersensitivity (2%)
damaging the host.
o IV injections - phlebitis
o IM - pain
Background
1928- Fleming discovered penicillin, produced by Penicillium.
1ST GENERATION CEPHALOSPORINS
1940- Howard Florey and Ernst Chain performed first clinical trials of
penicillin. Cephalothin
Mechanism of Action of Penicillin Cephapirin •Effective: Gram (+) cocci
o Inhibits bacterial growth by interfering with the Cephradine •Not MRSA
transpeptidation reaction of bacterial cell wall synthesis. Cephalexin •DO NOT enter CNS
Cefazolin
Cefadroxil
2ND GENERATION CEPHALOSPORINS
Cefamandole • Effective: Gram (-) and
Cefuroxime Anaerobes
Cefonicid • DO NOT enter CNS
Ceforanide
Cefaclor
Cefoxitin
Cefotetan
Cefprozil
Cefmetazole
3RD GENERATION CEPHALOSPORINS
Cefotaxime • Effective: Gram (+)/ (-)
INHIBITORS OF CELL WALL SYNTHESIS Cefixime cocci, Gram (-) rods
1. Penicillins Cefpodoxime • Most enter CNS (not
o Penicillin G o Cloxacillin Cefoperazone cefoperazone)
o Penicillin V o Ampicillin Cefdinir
o Methicillin o Amoxicillin Ceftizoxime
o Nafcillin o Carbenicillin Ceftriaxone
o Oxacillin o Ticarcillin Ceftazidime
Ceftibuten
Mechanism of Action - 1st step: Binds to Penicillin- Cefditoren (new)
Binding Proteins (PBPs). 4TH GENERATION CEPHALOSPORINS
- 2nd step: Inhibits activity of
Cefepime •Broad-spectrum
transpeptidases enzyme
Cefpirome – outside US •Resistant to most Beta-
cross-linking of peptidoglycan
lactamases
chains.
5TH GENERATION CEPHALOSPORINS
- 3rd step: Activate autolysin
Mechanism of Resistance - Penicillinases (β-lactamases) Ceftaroline •MRSA
break lactam ring structure Ceftobiprole •Less on P. aeruginosa,
(e.g. Staphylococci). Acinetobacter, ESBL,
- Structural change PBPs Enterobacteriaceae
- Change in porin structure
Adverse Effects - Hypersensitivity: most
common (5-7%)
- GI distress
- Jarisch-Herxheimer reaction

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 MICROBIOLOGY– 1.1B ANTIMICROBIAL DRUGS (DR. DEVEZA)
3. Imipenem & Meropenem
2. Aminoglycosides
MOA: Same as penicillin
- 30s
- Resistant to Beta-lactamases
- Interfere with initiation codon functions
Coverage
- Block association of 50s ribosomal subunit (static)
o Gram (+) cocci
- Misreading of code (cidal)
o Gram (-) rods; Anaerobes
- Streptomycin; Neomycin; Kanamycin, Amikacin,
Gentamicin, Tobramycin, Sisomicin, Netilmicin
4. Aztreonam
- More active at alkaline pH
MOA: Monobactam inhibitor of transpeptidation
- Ototoxic and Nephrotoxic
- Resistant to Beta-lactamases
Coverage
o Gram (-) rods

5. Vancomycin
MOA
o Binding at the D-ala pentapeptide to sterically hinder the
transglycosylation reactions involved in elongation of
peptidoglycan chains.
Coverage
o MRSA (DOC); Gram (+) cocci Enterococci
3. Chloramphenicol
o Anaerobe Clostridium difficile (back-up drug)
- 50s
Adverse Effects
- Inhibit the activity of peptidyltransferase (static)
o Ototoxicity
- Blocks attachment of amino acids to the nascent
o Hypotension
- Adverse Effectcs: “Gray-baby” syndrome (Pale or blue
o Diffuse hyperemia (“red-man syndrome”)
skin, lethargic eyes).
PROTEIN SYNTHESIS INHIBITORS

4. Macrolides
-Inhibit translocation of peptidyl-tRNA (static)
1. Tetracyclines -Erythromycin, Azithromycin, Clarithromycin,
- 30s Roxithromycin
Block the attachment of aminoacyl tRNA to acceptor site 5. Lincosomides
(static). - Clindamycin & Lincomycin
- Prevent interaction of new amino acids to the nascent - Mechanism of Action: same as macrolides
peptide chain - Clindamycin: First known drug to cause
- Coverage: Susceptible G (+) & (-) pseudomembranous colitis
- Adverse Effect: Discoloration of teeth (not recommended
in fetus and < 6 years)
- Doxycycline; Minocycline; Demeclocycline
- DOC against Rickettsiae, Chlamydia and Mycoplasma
pneumoniae

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 MICROBIOLOGY– 1.1B ANTIMICROBIAL DRUGS (DR. DEVEZA)

INHIBITORS OF FOLIC ACID SYNTHESIS

1. Sulfonamides SUMMARY OF MOA
2. Trimethoprim MOA Antimicrobial Agents
3. Pyrimethamine Penicillin, Cephalosporins,
Inhibition of bacterial Carbapenems, Monobactams,
- Sulfonamides cell wall synthesis Vancomycin, Aztreonam, Imipenem,
inhibit Bacitracin
Dihydropteroate Aminoglycosides, Chloramphenicol,
Synthase Inhibition of bacterial Macrolide (Erythromycin),
- Trimethoprim protein synthesis Tetracyclines, Clindamycin
and Inhibition of nucleic acid Quinolones, Rifampin
Pyrimethamine synthesis
inhibit Inhibition of folic acid Sulfonamides, Trimethoprim,
Dihydrofolate synthesis Pyrimethamine
Reductase
ADDITIONAL INFO FROM THE VIDEO (Optional)
Antibiotics can either be
o Bactericidal- destroys the bacteria
o Bacteriostatic- inhibits the growth of bacteria
INHIBITORS OF NUCLEIC ACID SYNTHESIS
1. Fluoroquinolones Antibiotics that DISRUPT CELL MEMBRANE FUNCTION
- Mechanism of Action: Bactericidal analogs of nalidixic acid - Disrupts phospholipid bilayer Polymyxins
that interfere with bacterial DNA synthesis - Alters cell membrane by making it Polyenes (antifungal)
- Ciprofloxacin, Lomefloxacin, Ofloxacin, Clinafloxacin, more permeable which disrupts its
Gatifloxacin, Gemifloxacin, Levofloxacin, Moxifloxacin, osmotic balance, causing the leakage
Sparfloxacin, Nalidixic acid of cellular molecules and an increase
in water uptake leading to cell death.
ANTI-TUBERCULOSIS DRUGS Antibiotics that INHIBIT CELL WALL SYNTHESIS
Rifampicin - Mechanism of Action: Inhibits DNA- dependent -Bactericidal Penicillin
RNA polymerase (inhibit bacterial RNA synthesis) Cephalosporins
- Mechanism of Resistance: Change in enzyme Bacitracin
- Adverse Effects: Proteinuria, hepatitis, “flu-like” Antibiotics that INHIBIT DNA/ RNA SYNTHESIS
syndrome, induction of P450, thrombocytopenia, - Prevents RNA/DNA synthesis and Quinolones (inhibit
red-orange metabolites therefore protein synthesis DNA)
Isoniazid - Mechanism of Action: Inhibits mycolic acid Nalidixic acids (inhibit
synthesis DNA)
- Mechanism of Resistance: Rifamycin ((inhibit
- high level resistance – deletions in katG gene RNA)
(encodes catalase needed for INH Antibiotics that INHIBIT PROTEIN SYNTHESIS
bioactivation); - Bacteriostatic 50S:
- low-level resistance deletions in inhA gene - Ribosomes carry out protein Erythromycin
(encodes acyl carrier protein). synthesis which translates mRNA to Chloramphenicol
- Adverse Effects: Hepatitis (age-dependent), older proteins.
peripheral neuritis (use Vitamin B6), hemolysis in - Target either the 30S or 50S subunit 30S:
G6Pd deficiency, SLE in slow acetylators (rare) of the ribosome. Tetracycline
Ethambutol - Mechanism of Action: Inhibits synthesis of Streptomycin
arabinogalactan (cell wall component) Gentamycin
- Adverse Effects: Dose-dependent retrobulbar Antibiotics that INHIBIT FOLIC ACID METABOLISM
neuritis, visual-acuity and red-green discrimination - Para-aminobenzoic acid (PABA): Sulfonamides
(color blindness) precursor to folate which is important Trimethoprim
Pyrazinamide - Mechanism of Action & Resistance: Unknown, but in synthesis of adenine and thymine.
metabolically activated by bacteria – strains lacking - humans do not metabolize folic acid
the bioactivating enzyme are resistant so it is okay to take up these antibiotics.
- Adverse Effects: Polyarthralgia, myalgia,
hepatitis, rash, hyperuricemia REFERENCES:
Streptomycin - Aminoglycoside -PPT by Dr. DANILO D. DEVEZA JR.
- Mechanism of Action: Protein synthesis inhibition -Jawetz,Melnick & Adelberg’s Medical Microbiology 28 th Edition
- Adverse Effects: Deafness, vestibular dysfunction, -Basic and Clinical Pharmacology by Katzung 14th Edition
nephrotoxicity -Video by Armando Hasudungan

3 Transcribed by: JENNIE