for FRCS & ICO part 1

1. Antibiotics
Dr. Ahmed Omara

2. Definitions
Antibiotics (Greek anti, “against”; bios, “life”): are chemical compounds used to
kill or inhibit the growth of infectious organisms.
Originally the term antibiotic referred only to organic compounds, produced by
bacteria or molds, that are toxic to other microorganisms.
Microbes kill each other with antibiotics
Intoduction

3. Intoduction

4. Antibiotic development 1929-72
Intoduction

5. Antibiotics only treat bacterial infections. Antibiotics are useless against viral infections (for
example, the common cold) and fungal infections (such as ringworm).
Intoduction

6. Selection of Antimicrobial Agent
Intoduction

7. Properties Influencing Frequency of Dosing
• Concentration dependent killing :e.g. aminoglycosides
Significant ↑ in rate of bacterial killing as the drug concentration ↑
Time-dependent killing e.g. β-lactams, glycopeptides, macrolides,
clindamycin & linezoid
Dependent on the % of time that blood concentrations remain above minimum
inhibitory concentration (MIC)
• Post-antibiotic effect (PAE): persistent suppression of microbial growth
after levels of antibiotic have fallen below MIC
Antibiotics with a long PAE – aminoglycosides and fluroquinolines
• Minimum bacterial concentration (MBC) is the lowest concentration of
antibiotic that kills 99.9% of bacteria
Intoduction

8. Intoduction

9. Intoduction

10. Classifying Antimicrobial Agents
• Mode of action
• BACTERICIDAL (kills the bug)
• BACTERIOSTATIC (stops the bug multiplying)
• Spectrum of activity
• BROAD (e.g. effective a variety of gram –ve & gram +ve bacteria)
• NARROW (e.g. effective only against gram –ve or gram +ve bacteria
• Mechanism of action / site of action;
• Inhibitors of cell wall synthesis; (β-Lactam, Vancomycin)
• Inhibitors of cell metabolism; (Sulfonamides, Trimethoprim)
• Inhibitors of protein synthesis; (Tetracyclines, Aminoglycosides, Macrolides, Clindamycin,
Chloramphenicol)
• Inhibitors of nucleic acid function or synthesis; (Floroquinolones, Rifampin)
• Inhibitors of cell membrane function; (Isoniazid, Amphotericin B)
Intoduction

11. Spectrum of Activity
Intoduction

12. Intoduction

14. Mechanism of action
Intoduction

15. Mechanism of action
Intoduction

16. Intoduction

17. Intoduction

18. Intoduction

19. Antimicrobial resistance
Increasing use of antimicrobials can lead to resistance
Mechanisms of bacterial resistance:
- Mutation (as seen in resistance to anti-tuberculous drugs such as rifampicin)
- Inheritance of “resistance” genes by:
 Conjugation via plasmid
Or
 Transduction through a bacteriophage.
Intoduction
Spore formation is NOT a mechanism of resistance

20. Antimicrobial resistance
Methods of bacterial resistance:
• Altering the antibiotic target, for example
- Changes of bacterial cell wall or membrane by failure of ribosomes to bind
erythromycin destruction
- Inactivation of the drug by enzymes, e.g. β-lactamase in penicillin resistance
or by acetylation of aminoglycosides
• Prevention of transport of the drug into the microbe
• Use of alternative enzymic pathways that are resistant to the drug, e.g.
enzymes resistant to sulphonamide and trimethoprim
Intoduction

21. 1. Inhibitors of cell wall synthesis
• Interfere with the synthesis of the bacterial cell wall
• Little or NO effect on bacteria that are NOT growing and dividing
Non β-lactamβ-lactam group
VancomycinPenicillins
BacitracinCephalosporins
Polymixin BCarbapenems
TelavancinMonobactams
Daptomycinβ-lactam inhibitors +
antibiotic combinations
Cidal
×× Cell wall

22. Penicillin
• Most widely effective and least toxic
• Produced from fungi
• Contain β lactam ring
• Limited use d.t. increased resistance
• Mechanism of action: …….....
Inhibit transpeptidase* i.e cross linking between peptides not occur →
Peptidoglycan of cell wall will NOT be formed.
Susceptible to β lactamase that is present in some bacteria e.g. Staph.
Cidal
×× Cell wall

23. ×× Cell wall

24. Treponema
pallidum
×× Cell wall

25. Penicillin
ExamplesGroup
* Benzylpenicillin (Acid sensitive = NOT oral)
* Phenoxymethylpenicillin
(Acid resistant = Given oral)
Narrow spectrum – penicillinase
(= β-lactamase) sensitive
* Methicillin:
[ Poor oral availability (only parenteral)]
* Oxacillin: Good oral availability
* Cloxacillin
* Dicloxacillin
Narrow spectrum – penicillinase
(= β-lactamase) resistant
* Ampicillin (Oral)
* Amoxicillin (Oral)
Broad spectrum – penicillinase (=
β-lactamase) sensitive
(= Aminopenicillins)
* Carbenicillin: [Poor oral availability]
Active against gram +ve & gram –ve bacteria
Active against Pseudomonas aeruginosa, Klebsiella
* Ticarcillin
* Mezlocillin
* Pipercillin
Extended spectrum – penicillinase
(= β-lactamase) sensitive
(= Carboxypenicillins)
×× Cell wall

26. ×× Cell wall

27. Cephalosporin
• Semi-synthetic antibiotics [derived from fungus Cephalosporium ]
• Contain β lactam ring
• Mechanism of action: ……………
Susceptible to β lactamase that is present in some bacteria e.g. Staph
Cidal
Cross-allergies with penicillins are common
×× Cell wall

28. 4 Generations of cephalosporins
• 1st generation: Cephalexin, cephalothin, Cephadroxil (mostly GP, some GN)
Poor penetration to BBB
• 2nd generation : Cefaclor, Cefuroxime, Cefoxitin (some GP and some GN,
*anaerobes)
• 3rd generation : Cefixime, Cefpodoxime, Ceftriaxone, Cefdinir (good
Streptococcal coverage, mostly GN)
and ceftazidime (no GP, mostly GN, Pseudomonas)
Good penetration to BBB
• 4th generation : Cefepime, Cefpirome
(most GP, most GN, Pseudomonas) ×× Cell wall

29. ×× Cell wall

30. ×× Cell wall

31. ×× Cell wall

32. ×× Cell wall

33. ×× Cell wall

34. Vancomycin
• Glycopeptide*
• Spectrum: very good for G +ve
Staph (including MRSA)*
Strept
Bacillus
- Propionobacterium acne
- Cl. Difficile
Indications:*
- Keratitis
- Endophthalmitis (intra-vitreal injection)
Side effect: Ototoxic - Nephrotoxic
MRSA
×× Cell wall

35. Carbapeneme
Spectrum:
• Gram +ve except MRSA
• Gram –ve
• Anaerobes
×× Cell wall

36. Other inhibitors of cell wall
BacitracinPolymixin B
G +ve
+
Nisseria
Hemophilus
Actinomyces
G –ve
Hemophilus
Enterobacter
E-coli
Klebsiella
pseudomonas
Mechanism of action: They are cyclic peptides
that adsorb to negatively charged lipids in the
cell membrane, leading to disorganization of
the membrane and loss of cell function.
Conjunctivitis - BlepharitisUsed : Conjunctivitis
S.E. : They lack selectivity, which can lead to
nephrotoxicity and neurotoxicity
×× Cell wall

37. Other inhibitors of cell wall
BacitracinPolymixin B
G +ve
+
Nisseria
Hemophilus
Actinomyces
G –ve:
• Hemophilus
• Enterobacter
• E-coli
• Klebsiella
• pseudomonas
Spectrum
They are cyclic peptides that adsorb to
negatively charged lipids in the cell
membrane  disorganization of the
membrane and loss of cell function.
Mechanism
of action
Conjunctivitis - BlepharitisConjunctivitisUses
They lack selectivity, which can lead
to nephrotoxicity and neurotoxicity
S.E.
×× Cell wall

38. 2. PROTEIN
SYNTHESIS
INHIBITORS
Inhibit either the 30s or 50s ribosomal subunit
- Aminoglycosides (bactericidal)
– Tetracyclins
– Macrolides
– Chloramphenicol Bacteriostatic
– Clindamycin

41. Protein Synthesis Inhibitors
• 50S ribosome inhibitors
-Macrolides e.g. Erythromycin
-Lincosamides e.g. clindamycin, lincomyin
• 30S ribosome inhibitors
-Aminoglycosides
-Tetracyclines
Mnemonics
Buy AT 30s & Cell
for 50s

42. 1. AmiNOglycosides
• NO protein synthesis [ by inhibition of 30s ribosome]
• NO pregnancy [Teratogenic]
• Negative Organisms killer
• NOt active against anaerobes
• Nephrotoxic - Ototoxic
Scheme

43. 1. Aminoglycosides
Spectrum: effective against gram -ve aerobic bacteria
[Gentamycin & tobramycin kill staph. ]
Distribution: (water soluble = very polar)
Poor penetration to BBB / Cornea
[ Good penetration if inflamed tissue e.g. meningitis]
= NOT used orally but parenteral [may be used in endopthalmitis]
= Used topically for external eye infections e.g. conjunctivitis - keratitis
bactericidal
Penetration into cell requires an oxygen-dependent transport
So, anaerobes are resistant

44. 1. Aminoglycosides
• Mechanism of action : 30s ribosome inhibitor
Cause misreading of m-RNA code and affect permeability.
Stop protein synthesis initiation
bactericidal
Better for ……..Antibiotic
SerratiaGentamycin
PseudomonasTobramycin
Pseudomonas + mycobacteriaAmikacin
T.B + strept viridansStreptomycin
AcanthamoebaNeomycin - paraneomycin

45. Side effects of aminoglycosides*
Ototoxicity: (irreversible)
• Affection of cochlear cells : tinnitus – pressure sensation
• Affection of vestibular cells: Nystagmus, vertigo, nausea & vomiting
Nephrotoxicity: Acute tubular necrosis (reversible)
Neuromuscular toxicity: blockage of presynaptic A.Ch release  respiratory
suppression
Amikacin is less nephrotoxic than gentamycin*
Can be used -with monitoring- in renal failure

46. Gentamycin
Side effectRoute/use
Corneal epithelial toxicityTopical gentamicin
(in microbial keratitis)
Retinal toxicity*Intra-vitreal gentamicin

47. Neomycin
One of the most toxic aminoglycosides
• Routes:
o Oral: poor penetration [ Used locally in GIT]
e.g. preparation of bowel before surgery or hepatic encephalopathy
o Topical: skin & external ear
o I.V.: rarely used
• Side effect : Allergy is very common + …………
Neomycin is used in ophthalmology for acanthameoba

48. Tetracycline
Having a nucleus of four cyclic rings
Spectrum:
• G +ve / G –ve
+
• Rickettsia [ Typhus – Q fever ]
• Chalmydia
• Mycoplasma pneumoniae
• Mechanism of action :
Inhibit protein synthesis: by binding to 30s ribosomes
Prevent attachment of aminoacyl-t-RNA to the mRNA ribosome complex.
Bacteriostatic

49. Tetracycline members
• Tetracycline
• Oxytetracycline
• Doxycycline
• Domeclocycline
• Minocycline
Most of them excreted in kidney, so contraindicated if renal failure !!
Except, doxycycline (excreted mainly by GIT ! )

50. Tetracycline: Ophthalmological uses
• Anti-collagenase action
TTT of sterile (non-infected) corneal ulcer [corneal melting]
in which stromal necrosis is thought to be d.t. collagenase activity
• Topically for trachoma
But systemic erythromycin is the drug of choice !

51. Uses:
“On empty stomach”

52. Side effects
Change in dentation: discoloration & dysgenesis [ contraindicated before 8 years ]
d.t. formation of tetracyclin – calcium phosphate complex

53. Macrolides
Mechanism of action : Macrolides bind to 50s ribosome and interfere with translocation
Taken on empty stomach
Specterum
Mostly G +ve and a few G-ve bacteria e.g. Hemophilus,
+ atypical bacteria (Legionella, Chlamydia, Mycoplasma)
[Narrow spectrum antibiotics similar to penicillin]
[Good alternative for patients with penicillin allergy]
bacteriostatic
Poor penetration to BBB & BAB
Erythromycin is bacteriocidal in high dose

54. Macrolides
Erythromycin is highly active against:
• Str. Pyogenes
• Str. Pneumaniae
• N. gonorrhoeae
• C. diphtheriae
Azithromycin [Very long half-life (>24 h)]
Clarithromycin
• Used for H. pylori infection

56. Specterum & uses of macrolides

57. CHLORAMPHENICOL
Spectrum
• Gram +ve & Gram -ve organisms + anerobes
+ Chalmydia, mycoplasma, Rickettsia
NOT active against Pseudomonas
Mechanism of action
• Binds to 50s ribosome
• Inhibit the transfer of elongated peptide chain to the newly attached aminoacyl -tRNA at
ribosome mRNA complex.
bacteriostatic
Lipid soluble, So
Good penetration to BBB & BAB & cornea 
Good for topical use & CNS infections

58. Side effects
[Dose dependent]
These side effects are for topical & systemic !!!
Restricted for life-threatening infections where no alternative exists
such as Haemophilus influenzae meningitis or typhoid fever
• Bone marrow depression (Reversible)
• Aplastic anemia [idiosyncrasy] (irreversible) (very rare)
• Grey baby syndrome
NOT used at pregnancy & lactation

59. Clindamycin
Spectrum: G +ve + anaerobes
Mechanism of action: inhibitor of 50s ribosome
Use:
• Anaerobic bacteria e.g Bacteroides fragilis (infections associated with
trauma or surgery)
• MRSA
• Toxoplasma
Side effects: pseudo-membraneous colitis d.t. overgrowth of cl. Difficile
Bacteriostatic
TTT of pseudomembraneous colitis: oral vancomycin or metronidazole

61. Inhibitors of nucleic
acid function or
synthesis
• Floroquinolone
• Rifampin
• Metronidazole

62. Quinolones
Analogues of nalidixic acid
Mostly fluorinated = Fluoroquinolones (except nalidixic acid) to  activity
Spectrum:
• G –ve
• Some G +ve ( heamophilus, pseudomonas, Enterobacteria, staph)
• Chalamydia
• Rickettsia
• Mycoplasma
Bacteriocidal

63. Quinolones
Mechanism of action:
Inhibitors of DNA Gyrase (= Topoisomerase II) [a bacterial enzyme that winds and unwinds
DNA (required for supercoiling the bacterial genome)]  inhibition of DNA synthesis and
transcription
Bacteriocidal

64. Generations of Quinolones
• 4th generation has enhanced activity against G +ve
ExamplesGeneration
Nalidixic acid1st generation
Ciprofloxacin
Ofloxacin
Norfloxacin
2nd generation
Levofloxacin3rd generation
Gatifloxacin
Moxifloxacin
Besifloxacin
Travofloxacin
4th generation

66. Ophthalmic uses
• Conjunctivitis
• Keratitis
• Prophylaxis in penetrating trauma
Oral ciprofloxacin produce high levels in vitreous as they are with
intravitreous therapy.
So, It is used as part of endophthalmitis protocols.

67. Uses

68. Side effects
Cartilage damage in children is experimental finding
‫بس‬ ‫يحصل‬ ‫خايفين‬ ‫يعني‬..‫واللي‬ ‫للحوامل‬ ‫ممنوع‬‫بيرضعوا‬

69. Metronidazole
Spectrum
• Anaerobes (e.g. bacteroides)
• Protozoa:
Amoeba (drug of choice)
Trichomonas vaginalis (drug of choice)
Giardia (drug of choice)
Mechanism of action:
Inhibition of microbial DNA synthesis [by forming toxic metabolites]
USE in ophthalmology: Orbital cellulitis in combination with cefuroxime.
Good penetration (Can pass BBB)

70. NOT
in
pregnan
cy

71. Disulifram reaction

72. Inhibitors of cell
metabolism
• Sulfonamides
• Trimethoprim

73. Sulfonamides
Mechanism of action:
Inhibition of folic acid synthesis
Example:
Sulfacetamide
Spectrum:
G +ve / G –ve
+
Toxoplasmosis
Chalamydia
Actinomyces
Pneumocystits
Bacteriostatic
Trimethoprim
• Has similar activity to
sulphonamides
• Give synergistic effect in
combination with
sulphonamides
(= Cotrimoxazole)

74. Uses
Rarely used now d.t. resistancy
• Conjunctivitis
• Blepharitis
• Toxoplasmosis

75. Side effects
• Hypersensitivity (Steven Jhonson syndrome)*
• Nephrotoxicity
• Haemopoeitic disturbances
• Transient myopia*

76. Cotrimoxazole
(sulfamethoxazole plus trimethoprim)

77. Anti – T.B. drugs

78. Anti-mycobacterials
optic neuritis

79. The Top Ten Rule
1. All cell wall inhibitors are Beta-lactams (penicllins,
cephalosporins etc) except vancomycin.
2. All penicllins are water soluble except nafcillin.
3. All protein synthesis inhibitors are bacteriostatic, except
for the aminoglycosides
4. All cocci are gram positive, except Neisseria spp.
5. All bacilli are gram negative, except anthrax, tetanus,
botulism and diphtheria bugs
6. All spirochaetes are gram negative

80. The Top Ten Rule
7. Tetracylcines and macrolides are used for intracellular
bacteria
8. Beware pregnant women and tetracylcines,
aminoglycosides, fluoroquinolones and sulfonamides.
9. Antibitoics beginning with 'C' are particularly associated
with pseudomembranous colitis i.e. Cephalosporins,
Clindamycin and Ciprofloxacin.
10. While the penicillins are the most famous for causing
allergies, a significant proportion of people with penicillin
allergies may also react to cephalosporins. These should
therefore also be avoided.

81. Antibiotics for Selected Bacteria

82. Use of prophylactic antibiotic in patient with cardiac murmur
Needed with:
• DCR
• Orbital floor fracture
As they are associated with septicemia d.t. the amount of bleeding & high
load of bacterial commensals in sinus & nasal cavity
NOT needed with:
• Cataract operation
• Trabeculectomy
• Ptreygium operation
As they are relatively clean procedure