Dr. Ndayisaba Corneille provides an overview of bacterial cell structure and function, as well as sites of action and mechanisms of common antibacterial drugs. The document begins by describing the capsule, cell wall, cell membrane, ribosomes, and genetic material of bacterial cells. It then discusses classes of antibiotics that target cell wall synthesis, including beta-lactams and glycopeptides. Further sections cover inhibitors of folic acid metabolism, cell membrane destroyers, inhibitors of protein synthesis, quinolones, and other newer antibiotic classes. In each case, specific drugs are named and their mechanisms of action are explained at a basic level. The document aims to inform readers about the essential components of bacterial cells and how

1. Dr. NDAYISABA CORNEILLE
CEO of CHG
MBChB,DCM,BCSIT,CCNA
Supported BY
ANTIBIOTICS INTRODUCTION

2. Bacterial Cell: Functions
 Capsule: Gram–ve bact. (offers natural
resistance)
 Cell wall: made of:
 Gram +ve: Peptidoglycan – well
developed
2

3. • Gram –ve: Peptidoglycan- less
developed, ( 2 layers) outer layer has
Lipopolysaccharides- Resist hydrophilic
molecules
 Cell membrane: phospholipids, proteins &
CHO
 Ribosomes: 70s with two sub-units (30 s &
50s)
3

4.  Genetic material: program for whole cell
 Folic acid pathway: for nucleic acid
synthesis
 PABA to folic acid to folinic acid to DNA
4

5. Sites of action of antibacterials:
5

6. Cell Wall Synthesis inhibitors
1) Beta Lactams
 Penicillins
 Cephalosporins
 Monobactams
 Carbapanems
2) Non- Beta Lactams
— Vancomycin
— Cycloserine D
— Bacitracin
— Fosfomycin
6

7. Bacterial Cell Wall Structure
7

8. Structure of Peptidoglycan
8

9. Bacterial cell Wall: Synthesis
 Three stages
 1) Synthesis of monomer molecules
 Fosfomycin or Fosmidomycin (inhibits early stage)
 Cycloserine D (inhibits L- Alanine racemase)
 Bacitracin (interferes with bactroprenol)
 2) Polymerization of the monomers
 Vancomycin
 3) Cross linking of peptide chains
 Beta lactam antibiotics (inhibits transpeptidase)
9

10. CEPHALOSPORINS
10

11. Cephalosporin: Classification
 Classifies according to generations in
which they were discovered
 First Generation
 Second Generation
 Third Generation
 Fourth Generation
Dr Ndayisaba Corneille

12. Cephalosporins: Classification
 First generation
 Cefadroxil
 Cephalexin
 Cephradine
 Cefazolin
 Cephalothin
 Cephapirin
 Second generation
 Cefaclor
 Cefonicid
 Cefprozil
 ceforanide
 Cefamandole
 Cefmetazole
 Cefoxitin
 Cefotetan
 Cefuroxime( Zinnat) 12

13. Cephalosporins: Classification
 Third Generation
 Cefixime
 Ceftizoxime
 Cefpodoxime
 Ceftriaxone
 Cefoperazone
 Ceftazidime
 Cefotaxime
 Moxalactam
 Fourth generation
 Cefepime
13

14. Cephalosporins: critical
considerations
 Assessment
 Assess for history of allergies
 Interventions
 Orally administered forms should be given with food to
decrease GI upset, even though this will delay absorption.
 Evaluation
 Some cause Antabuse -like reaction when taken with
alcohol.
 Allergic reactions & convulsions
14

15. MONOBACTAMS: Aztreonam
15

16. CARBAPANEMS
16
IMIPENEM
MEROPENEM

17. NON BETA LACTAM
Cell wall synthesis
inhibitors
17

18. Non beta lactam antibiotics
 Cycloserine
 Vancomycin
 Bacitracin
 Fosfomycin
18

19. Antibacterial Antibiotics
Inhibitors of Cell Wall Synthesis
 Polypeptide antibiotics
 Bacitracin
 Topical application Against gram-positives
 Vancomycin & Teicoplanin
 Glycopeptide
 Treat Methicillin-resistant S. aureus
 Bacteriostatic – Not bactericidal
 Never develop resistance while on treatment.
 RED MAN syndrome – slow infusion
 Can be nephro and oto-toxic
19

20. Non Beta lactams:
Mechanisms
20

21. 2. Inhibitors of Folic Acid
Metabolism
21

22. Classification of Drugs
Step 1: Inhibit (DHFS)
 Sulphonamides
 Dapsone
 Methtrexate
 Tremetrexate
 Step 2: Inhibit (DHFR)
 Pyrimethamine
 Trimethoprim
22

23. i. Sulfonamides
1) Topical sulphonamides
 Sulphacetamide
 Silver sulphadiazine
 Silver sulphacetamide
 Mefanide
2) Systemic sulphonamides
a) Short acting systemic
 Sulfadiazine
 Sulfisoxazole
 Sulfamethizole
 Sulphadimidine
b) Long acting
 Sulphasalazine
 Sulfamethoxazole
c) Very long acting
 Sulphadoxine
 Sulphamethopyrazine
23

24. Antifolates: Mechanism of Action
24

25. Destroyers of Cell membrane
1.Used for Bacterial
Infections
 Polymixins
 Colistin (Polymixin E)
 Mainly active on gram
–ve bacteria rich in
 Phosphatidyl
ethanolamine (PEA)
to which polymixins
Bind
2 Used for Fungal
Infections
 Nystatin
 Amphotericin B
Imidazole antifungals
 Fluconazole
 Ketoconazole
 Clotrimazole
 Itraconazole
 Bifonazole
 Micinazole etc 25

26. III. Inhibitors of Protein synthesis
At the 30S Subunit
“Buy AT 30”
 Aminoglycosides
 Tetracyclines
At the 50S Subunit
“CELLS at 50 M”
 Amphenicols
 Chloramphenicol
 Macrolides
 Erythromycin
 Lincosamides
 Lincomycin
 Clindamycin
 Linezolid
 STREPTOGRAMINS
 Quinupristin
 dalfopristin
 Muprocin 26

27. Bacterial Protein synthesis
27

28. Subunits/function of a
Ribosome
28
50S subunit
30S subunit
tRNA/amino
acid complex

29. From DNA to Protein synthesis
29

30. Specific Mechanism of Action
Drugs MOA
Macrolides, lincosamides,
streptogramins
Prevents transfer of the growing
polypeptide chain from the "A"
site to the "P" site.
Ketolides Blocks protein synthesis by
binding to domain II and V of
the 23S rRNA of the 50S
subunit
Tetracyclines Reduces affinity of tRNA for
the mRNA ribosome complex
30

31. Specific Mechanism of Action
Drugs MOA
Chloramphenicol Prevents binding of amino acid
containing tRNA to the “A” transferase
site
Oxazolidinones (Linezolid) Binds to a site on the 50S ribosomal
subunit near its interface with the 30S
unit prevents the formation of a 70S
initiation complex
Glycylcyclines (Tigicycline) Binds to the 30S subunit & blocks
entry of tRNA into the A site of the
ribosome
31

32. Antibiotics: Tetracyclines
Short acting ( OTC)
 Oxytetracycline
 Tetracycline
 Chlortetracycline
Intermediate acting
(DM)
 Demeclocycline
 Methacycline
Long Acting (DM)
 Doxycycline
 Minocycline
32

33. 33
Tetracycline
OH
H3C OH
O
N
OH
C
O OH
OH
CH3
H3C
ONH2

34. Antibiotics: Aminoglycosides
“GIANT” commonly
Used
 Gentamicin
 I?
 Amikacin (Amikin)
 Neltimycin
 Tobramycin
“PINKS” Rarely Used
 Paramomycin
(Aminosidine)
 I?
 Neomycin
 Kanamycin
 Streptomycin
34
Ototoxicity, Renal toxicity, NMJ blockade

35. Aminoglycoside Structure
35

36. Antibiotics: Macrolides
14 CARBON
“RED COF” we use
them for red cough
 Erythromycin
 Clarithromycin
 Roxithromycin
 Fluorithromycin
 Oleandomycin
 Dirithromycin
15 CARBON
 Azithromycin
16 CARBON
 Rokitamycin
 Micamycin
 Troleandomycin
 bactericidal action
36

37. Macrolide Structure
37

38. Macrolide Structure
38

39. Macrolides
Mechanism of Action
 Inhibits protein synthesis by reversibly
binding to the 50S ribosomal subunit
 Suppression of RNA-dependent protein
synthesis
 Macrolides typically display bacteriostatic
activity, but may be bactericidal when
present at high concentrations against very
susceptible organisms
 Time-dependent activity 39

40. Clindamycin
Clindamycin is a semisynthetic derivative of
lincomycin which was isolated from
Streptomyces lincolnesis in 1962; clinda is
absorbed better with a broader spectrum
40

41. V. Inhibitors of Nucleic Acid
synthesis
Quinolones (Q) ‘CAPPON’
 Cinoxacin
 Acrosoxacin
 Pepamindic acid
 Piromindic Acid
 Oxolinic acid
 Nalidixic acid
Fluoroquinolones(FQs)
First Generation -ve
 Norfloxacin,
Second Generation + & -
 Ciprofloxacin
 Levofloxacin
 Perfloxacin
 Ofloxacin
Third Generation inc on +
 Sparfloxacin
 Gatifloxacin
Fourth generation
 Moxifloxacin (-ve & anaerob)
41

42. Quinolones: MOA
42

43. New Groups of Antibiotics
 Streptogramins
 Quinupristin/dalfopristin
 Oxazolidinones
 Linezolid
 Ketolides
 Telithromycin
 Lipopeptides
 Daptomycin
43

44. Oxazolidinones
 Linezolid (Lizolid®) is the first available agent which
received FDA approval in April 2000; available PO
and IV
 Developed in response to need for agents with
activity against resistant gram-positives (MRSA,
GISA, VRE)
 Linezolid is a semisynthetic oxazolidinone which is
a structural derivative of earlier agents in this class
44

45. Linezolid Structure
45

46. LINEZOLID
Mechanism of Action
 An oxazolidinone.
 Interferes with initiation of protein synthesis –
attaches to 50S ribosome.
 Bacteriostatic versus staphylococci and
enterococci.
46

47. LINEZOLID
Spectrum of Activity
 Gram-positive bacteria:
 Streptococci
 including drug resistant S. pneumoniae
 Staphylococci
 including methicillin resistant S. epidermidis (MRSE)
and S. aureus (MRSA)
 Enterococci
 including E. fecalis
 including vancomycin resistant E. faecium (VRE)
47

48. LINEZOLID
Clinical Uses
 Treatment of vancomycin resistant
enterococcal (VRE) disease:
 e.g., bacteremia with 600 mg IV/PO
q 12 hours
48

49. Quinupristin/Dalfopristin-1
 Streptogramins, derived from pristinamycins.
 Inhibit protein synthesis by irreversible
binding to 50S ribosome; resistance due to
methylation of binding site.
 Bacteriostatic versus enterococci.
 Administered by slow infusion through central
venous catheter.
 Eliminated by biliary excretion.
49

50. Quinupristin/Dalfopristin-2
 Adverse effects: pain and phlebitis at the injection
site; arthralgias & myalgias; hyperbilirubinemia;
nausea & diarrhea.
 Active in vitro against a wide variety of gram-
positive bacteria.
 except Enterococcus fecalis
 Used for treatment of vancomycin resistant
Enterococcus faecium (VRE) disease:
 e.g., bacteremia with 7.5 mg/kg IV q 8 hours
50

51. Synercid® Structure
51

52. V. Inhibitors of Nucleic Acid
synthesis
Rifamycins
 Rifampicin
 Rifabutin
 Rifapentin
Nitrofurans
 Nitofurantoin
 Furadantoin
Nitroimidazoles
 Metronidazole
 Secnidazole
 Tinidazole
52

53. Antituberculosis
 First line anti-TB
agents
 Isoniazid
 Rifampicin
 Ethambutol
 Pyrazinamide
 Second line agents
 Cycloserine
 Streptomycin
 Rifabutin
 Ethionamide
 Prothionamide
 Capreomycin
53

54. Treatment of resistant gram +
bacteria
Resistant
gram positive agents
MRSA VRE
PCN-R
S. pneumoniae
Vancomycin
(>99% susceptible)
Linezolid
Flouroquinolones
Vancomycin
Linezolid
Streptogramins
Glycylcylines
Tetracyline
Streptogramins
(E.faecium only)
Tetracyline
Ketolides
Linezolid
Streptogramins
54
DOC →
Alternatives →
Maybe susceptible →

55. END
BY
DR NDAYISABA CORNEILLE
MBChB,DCM,BCSIT,CCNA,Cyber Security
contact: amentalhealths@gmail.com ,
ndayicoll@gmail.com
whatsaps :+256772497591 /+250788958241
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