The document discusses anti-bacterial agents, specifically their classification, mechanisms of action, and therapeutic uses. It highlights the limitations such as drug resistance, toxicity, and potential for superinfections, along with the advantages of combining antimicrobial agents. Additionally, specific classes of antibiotics like sulphonamides and penicillins are detailed regarding their mechanisms, pharmacokinetics, and adverse effects.

1. ANTI-BACTERIAL AGENTS
(PCL 503)
2023/2024 SESSION
BY
DR. M.A. MAHDI
JUNE, 2024

2. 2
GENERAL CONSIDERATIONS
Chemotherapy can be defined as treatment of
infectious diseases with specific drugs which
kills or suppress growth of the
microorganism and spare the host cell.
Antibiotics are substances that are produced
by microorganisms in small concentrations
which are used to stop the growth and
development of other microorganisms (via
minimum inhibitory concentrations, MIC).
They are used to treat diseases caused by

3. 3
GENERAL CONSIDERATIONS
• Antimicrobial agents are referred to as
synthetic as well as natural substances that are
used to halt or kill microorganisms.
Limitations of the Use of Antibacterial Agents
a. Resistance to drugs
b. Hypersensitivity reaction
c. Toxicity
d. Superinfections

4. 4
GENERAL CONSIDERATIONS
Classification of antibacterial agents based on;
1.Type of action e.g. bactericidal (e.g
penicillin, aminoglycosides, polypeptides,
cephalosporins, vacomycin, nalidixic acid,
ciprofloxacin), bacteriostatic agents(e.g
tetracycline, sulphonamides,
chloramphenicol, erythromycin,
clidamycin).

5. 5
General Consideration
2. Spectrum of activity
Narrow Spectrum e.g. Penicillin G,
streptomycin, erythromycin
Broad spectrum e.g. tetracycline
chloramphenicol
Sources of Antibiotics
Fungi – Penicillin, cephalosporin, griseofulvin
Bacteria – Polymyxin B, colistin, bacitracin

6. 6
General Consideration
Actinomycetes

7. 7
• Aminoglycosides, macrolides, tetracyclines,
polyenes, chloramphenicol
• Mechanism of action e.g. cell wall synthesis
inhibitors(beta lactans e.g cephalosporine),
inhibitors of protein
synthesis(aminoglycosidese.g
gentamycin,macrolides), inhibitors of mRNA
synthesis(aminoglycosides),
antimetabolites(sulphonamide).

8. 8
GENERAL CONSIDERATIONS
• Factors to consider in selection of an
appropriate antibacterial agents are given
below;
Patient factors (age, history of allergies,
genetic abnormalities, pregnancy, host
defenses, hepatic dysfunction, renal
dysfunction, local factors).

9. 9
GENERAL CONSIDERATIONS
Drug factors (route of administration, spectrum of
activity, bactericidal effect, bacteriostatic effect, ability
to cross blood brain barrier, cost of antibacterial
agents)
Combination of Antimicrobial Agents
Advantages
1. To broaden spectrum of antibacterial activity in mixed
infections; intra-abdominal, hepatic, pelvic, brain
abscesses e.g. use of metronidazole and ceftriaxone for
treatment of brain abscess.

10. 10
GENERAL CONSIDERATIONS
2. To broaden spectrum of activity when the
etiology of a severe infection is not known;
combinations of ceftriaxone, vancomycin and
ampicillin used for empiric therapy of suspected
bacterial meningitis before selection of an
appropriate antibacterial agent and before culture
and sensitivity test results are obtained.

11. 11
GENERAL CONSIDERATIONS
3. To achieve synergism; e.g ampicillin +
gentamicin for enterococcal endocarditis,
carbenicillin + gentamicin due to infections by
Pseudomonas
4. To prevent emergence of resistant strains of
microorganisms; tuberculosis (TB), leprosy, HIV
infections

12. 12
GENERAL CONSIDERATIONS
5. To reduce duration of therapy; multi-drug
therapy in TB
6. To reduce adverse effects; amphotericin B and
flucytocine reduces incidence of nephrotoxicity
caused by amphotericin B
Disadvantages
1. Increased incidence and variety of adverse
effects e.g. vancomycin + tobramycin produce
exaggerated kidney failure

13. 13
GENERAL CONSIDERATIONS
2. Increased chances of superinfections
3. If inadequate doses of non-synergistic drugs
are used emergence of resistance may be
promoted.(Minimum Inhibitory Concentration;
MIC)
4. High cost of antibacterial agents.

14. 14
SULPHONAMIDES
This class of antibacterial agents were the first
antimicrobial agents effective against
pyogenic (pus-causing) bacterial infections.
All sulfonamides may be considered to be
derivatives of sulfanilamides (para-
aminobenzene sulphonamide) and are
synthetic compounds.

15. 15
SULPHONAMIDES
Types of Sulphonamides
Sulphonamides of clinical significance include;
a. Systemic acting agents
1. Short acting (4-8 hr) e.g. sulphadiazine,
sulphisoxazole
2. Intermediate acting (8-12 hr) e.g.
sulphamethoxazole
3. Long acting (> 7 days) e.g. sulphadoxine

16. 16
SULPHONAMIDES
b. Local acting
1. Sulphacetamide
2. Silver Sulphadiazine
3. Mafenide
c. Others
4. Sulphasalazine (act both locally and
systemically)

17. 17
SULPHONAMIDES
Mechanism of Action
The precursor for the synthesis of folic acid
required for cell growth and development is
para-aminobenzoic acid (PABA).
Sulphonamides are structural analogues of
PABA
Sulphonamides inhibits folate synthetase
enzyme required for the synthesis of
dihydrofolic acid

18. 18
SULPHONAMIDES
Sulphonamides are not effective in the presence
of pus because it is rich in PABA, purines and
thymidine.
Sulphonamides do not affect mammalian cells
because it lacks folate synthetase enzyme hence
folic acid is not synthesized in humans. It is
supplemented in diet as vitamin.
Bacterial Resistance to Sulphonamides
Many bacteria develop or have the capacity to

19. 19
SULPHONAMIDES
develop resistance to sulphonamides which could be
due to:
1. decreased affinity of folate synthetase
2. an efflux mechanism by the bacteria that expels the
drug out of the cell
3. alternate metabolic pathway developed by the bacteria
4. increase in production of PABA by the bacteria
Note ; find out the role of tetrahydrofolic acid in cell
growth

20. 20
SULPHONAMIDES
Pharmacokinetics
The absorption of sulphonamides is nearly
complete from the gastrointestinal tract.
Extent of binding to plasma albumin ranges
between 10-95% among different members. The
highly bound drug are longer acting
Distribution of sulphonamides e.g. sulfadiazine in
the body is wide including the CNS and fetal
circulation across the placenta.

21. 21
SULPHONAMIDES
The initial pathway of metabolism of
sulphonamides is by acetylation at N4
by
acetyltransferase found in the liver.
The acetylated sulphonamide retain the toxic
potential of the parent compound. It is less
soluble in acidic urine than the parent drug
hence can precipitate and cause crystalluria.
 In renal failure the metabolite and parent drug
accumulate in the blood increasing toxicity.

22. 22
SULPHONAMIDES
Part of the parent compound is excreted in the
urine as a metabolite and part of it as intact. The
process of excretion is glomerular filtration,
active tubular secretion, and tubular reabsorption.
Adverse Effects
1. Crystalluria, haematuria, obstruction to urinary
tract. These can be treated by taking excess fluid
and alkalinization of the urine.
2. Epigastric pain, nausea and vomiting

23. 23
SULPHONAMIDES
3. About 2-5% of patients are hypersensitive to
sulphonamides characterized by rashes, urticaria,
and drug fever.
4. Acute hemolytic anemia is caused by
sulphonamides in patients with glucose-6-
phosphate dehydrogenase deficiency.
5. Kernicterus (preventable brain damage that
happens in newborn with jaundice) is caused by
high levels of bilirubin in neonates which occur

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SULPHONAMIDES
due to displacement of the bilirubin from plasma
protein binding sites.
The risk of contact sensitization develops on
topical application of sulphonamides
Drug Interactions
The ability of sulphonamides to displace from
plasma protein binding and inhibit the
metabolism of phenytoin, tolbutamide,
methotrexate and oral anticoagulants prolong

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SULPHONAMIDES
the duration of action of these drugs.
Therapeutic Uses
Suppressive therapy of chronic urinary tract
infection
Combined with trimethoprim
sulfamethoxazole is used in treatment of P.
Jirovecii infection, Norcardiosis
Combined with pyrimethamine sulfadoxine is

26. 26
SULPHONAMIDES
used in prophylaxis of malaria.
Treatment of conjunctivitis using
sulfacetamide
Prevention of burn wounds by silver
sulfadiazine
Treatment of rheumatic fever using
sulfadiazine

27. 27
SULPHONAMIDES
Cotrimoxazole
• It is an approved fixed-dose combination of
sulphamethoxazole and trimetoprime in a ratio of 5:1
respectively.
• The two drugs share common pharmacokinetic profile
and the combination is effective at a plasma
concentration of 20:1.
• The individual drugs have bacteriostatic effect but the
combination has cidal effect. Also chances of bacterial
resistance is greatly reduced.

28. 28
SULPHONAMIDES
Mechanism of Action
• Cotrimoxazole produces sequential blockade
i.e. two (2) drugs block two (2) different steps in folic
acid synthesis pathway. Sulphamethoxazole inhibits
folate synthetase (required for production of
dihydrofolic acid) while trimethoprim (also combined
with dapsone in the treatment of pneumocystis
pneumonia) inhibits folate reductase (required for
production of tetrahydrofolic acid).
Pharmacokinetics

29. 29
SULPHONAMIDES
Cotrimoxazole is administered both orally and
parenterally. Its distribution to various tissues is wide
including the CSF and sputum.
 Cotrimoxazole is metabolized in the liver and
excreted mainly in urine, hence dose reduction is
needed in patients with renal insufficiency.
Adverse Effects
Common adverse effects of sulphonamides are skin
rashes and gastrointestinal disturbances including
nausea, vomiting, glossitis and stomatitis. Exfoliative
dermatitis, erythema multiforme and Stevens-Johnson

30. 30
SULPHONAMIDES
syndrome are rare. Megaloblastic anemia rarely occur in
alcoholics and malnourished persons. Also bone marrow
suppression with leukopenia, neutropenia and
thrombocytopenia occur.
Therapeutics Uses
1. Urinary tract infections: useful for chronic and recurrent
UTIs especially in women
2. Bacterial respiratory tract infections: effective for acute
and chronic bronchitis due to S. pneumonia and H.
influenzae.
3. Bacterial diarrheas: Used for GI infections due to E. coli,
Shigella, Salmonella. Flouroquinolones are

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SULPHONAMIDES
preferred agents.
4. Typhoid fever: clotrimoxazole is effective but fluoroquinolones or
third generation cephalosporins are preferred
5. Pneumocystis jirovecii infection: High doses of clotrimoxazole
used in immunocompromised patients. It is also used for P. jirovecii
Pneumonia
6. Nocardiosis (infectious disease affecting lungs or whole body):
used in the treatment of infections due to Nocardia spp.
7. Chancroid (STD characterized by painful sores on genitalia):
caused by H. ducreyi drug of choice is azithromycin. Cotrimoxazole
is equally effective. Ceftriaxone and ciprofloxacin are alternative
agents

32. 32
PENICILLINS
They include penicillins, cephalosporins,
carbapanems and monobactams
All drugs in this group have a β-lactam ring
Penicillins discovered by Alexander fleming was
the first antibiotic developed and used clinically
In addition to the β-lactam ring (site of action of
penicillinase), it is comprised of a thiozolidine
moiety.

33. 33
PENICILLINS
Mechanism of action; β-lactam antibiotics act by
inhibiting the synthesis of peptidoglycan by
preventing the cross linking of adjacent
pentapeptide strands. The cell wall becomes less
rigid resulting in lysis.
Mechanism of resistance to penicillins;
i. Production of β-lactamases which destroys β-
lactam e.g. S. aureus, E. coli, gonococci, H.
influenzae.

34. 34
PENICILLINS
ii alteration of penicillins binding protiens (DD-
transpeptidases) e.g. S. pneumoniae
iii decreased ability of antibacterial agent to
penetrate to its site of action
Pharmacokinetics;
Penicillin G is administered via i.v or i.m
routes due to destruction in the stomach by
gastric acid

35. 35
PENICILLINS
Widely distributed in the body excluding the
brain (except during meningitis when adequate
amount reaches the CSF)
Excretion is in urine by active tubular
secretion
Action of penicillins can be prolonged by
giving concurrently with probenecid
Duration of action of penicillin G is prolonged

36. 36
PENICILLINS
by combining with water-soluble procaine
(procaine penicillin G) or benzathine (benzathine
penicillin G) to obtain aqueous suspension.
Adverse Reactions
Hypersensitivity reactions; rashes, urticaria,
fever, dermatitis, bronchospasm, angioedema,
joint pain, serum sickness, anaphylactic
reaction

37. 37
PENICILLINS
Adverse Reactions;
Pain at i.m injection site, Jarisch-Herxheimer
reaction (exacerbation of the signs and symptoms
of syphilis during penicillin therapy) manifested
by fever, chills, myalgia, hypotension, circulatory
collapse, etc. It is treated with aspirin and
corticosteroids
Therapeutic Uses
The use of penicillin G has declined due to risk of

38. 38
PENICILLINS
anaphylaxis and availability of better antibacterial agents
i. Pneumococcal infection: in meningitis, pneumonia or
other serious infections cephalosporins are drug of
choice. Penicillin G is used as an alternative
ii. Streptococcal infections: pharingitis, otitis
media,scarlet fever, rheumatic fever respond to
ordinary doses of penicillin G
iii. Meningococcal infections: meningitis and other
infections may be treated with high doses

39. 39
PENICILLINS
iii Gonorrhea: Due to resistance third generation
cephalosporins, ceftriaxone or cefixime are drugs
of choice for uncomplicated gonococcal
infections.
iv Syphilis: benzathine penicillin is the drug of
choice.
v Diptheria: Procaine penicillin has adjuvant value
and prevent carrier state. Antitoxin therapy is of
prime importance.

40. 40
PENICILLINS
vi Clostridial infection (Tetanus and gas gangrene): Used
as adjunct to antitoxin in gas gangrene. Although main
treatment is by neutralization of toxin using human
tetanus immunogloblin.
vii other infections: anthrax, listeria infections, lyme
disease, leptospirosis, actinomycosis, rat-bite fever, e.t.c
are effectively treated with penicillin G.
viii Anaerobic infections
ix Prophylactic use: rheumatic infection, bacterial
endocarditis.

41. 41
PENICILLINS
Semi-synthetic Penicillins

Acid resistant penicillin – phenoxymethyl penicillin (penicillin
V)

Penicillinase-resitant penicillins – methicillin, cloxacillin

Extended spectrum penicillins
a.
Aminopenicillins e.g. ampicillin, bacampicillin, mezlocillin
b.
Carboxypenicillins e.g. carbenicillin, ticarcillin
c.
Ureidopenicillins: Piperacillin, mezlocillin

β-lactamase inhibitors e.g clavulanic acid, sulbactam,
tazobactam

42. 42
PENICILLINS
Therapeutics uses of aminopenicillins
i. Upper respiratory tract infections; ampicillin and
amoxicillin are effective for pharyngitis, sinusitis, otitis
media, bronchitis caused by S. pyogenes, H. influenza
ii. Urinary tract infection; fluroquinolones is preferred
ampicillin can be used if organism is sensitive
iii. Meningitis; third generation cephalosporins along with
vancomycin are drugs of choice. Combinations of
ampicillin, vancomycin, and third generation
cephalosporins are used for empirical therapy of bacterial
meningitis

43. 43
PENICILLINS
iv bacillary dysentery; flouroquinolones are drug of choice.
Some cases may respond to ampicillin but many strains have
develop resistant to it.
v Cholecystitis (inflammation of the gall bladder): ampicillin
is a good drug because high concentrations are attained in
bile.
vi Sub-acute bacterial endocarditis; combinations of
ampicillin and gentamicin are advocated
vii Typhoid fever; rarely used due to emergence of resistance.
Less efficacious than ciprofloxacin in preventing carrier state.

44. 44
CEPHALOSPORINS
Cephalosporins are obtained from a fungus
‘Cephalosporium’ and are chemically related to penicillins.
Classification of Cephalosporins
They are classified into generations(more active against
gram positive);
a. First generation e.g. cephalothin, cefazolin, cephalexin,
cephradine, cefadroxil
b. Second generation(more on positive) e.g. cefuroxime,
cefoxitin, cefaclor, cefuroxime axetil, cefoxitin, cefotetan,
cefprozil

45. 45
CEPHALOSPORINS
c. Third generation(against both) e.g. cefotaxime,
ceftizoxime, cefixime, cefdinir, ceftibuten,
ceftazidime,cefoperazone, etc
d. Fourth generation e.g. Cefepime, Cefpirome
Cephalosporins are generally effective against both
gram positive, gram negative and anaerobic infections.
Although fourth generation are not effective against B.
fragilis.
Cefazolin is highly susceptible to β-lactamase enzyme

46. 46
CEPHALOSPORINS
Among the second generation cephalosporins
cefoxitin and cefuroxime are resistant to β-
lactamases. While most third and fourth
generation members are resistant to the
enzyme except cefoperazone
Pharmacokinetics
The major routes of administration of
Cephalosporin include both parental and oral

47. 47
CEPHALOSPORINS
 While all first generation agents do not cross the
blood-brain barrier, some second generation
cephalosporins such as cefuroxime do cross the
barrier.
 Among the third generation agents only cefotaxime
and ceftriaxone cross the BBB. However, all fourth
generation crosses and are as well found in CSF
 Some of these drugs like cefotaxime are metabolized
in the body by deacetylation before excretion.
Cefoperazone is mainly excreted through bile.

48. 48
CEPHALOSPORINS
Cephalosporins are excreted through the kidney
by glomerular filtration or active tubular
secretion which is blocked by Probenecid.
Adverse Effects
Hypersensitivity reactions such as skin rashes,
urticaria and anaphylaxis
Gastrointestinal disturbance mainly diarrhoea,
vomiting, anorexia

49. 49
CEPHALOSPORINS
Pain at injection site with use of cephalothin and
generally they cause thromboplebitis after
intravenous injection.
Nephrotoxicity is seen with the use of
cephaloridine (currently withdrawn). Also
combination of cephalothin and gentamicin
increases the risk of nephrotoxicity
Cefotetan and cefoperazone causes intolerance
to alcohol

50. 50
CEPHALOSPORINS
Severe bleeding due to hypoprothombinemia
or thrombocytopenia and platelet dysfuction
can occur

51. 51
Uses
• Combined with amimoglycoside for treatment of
septisemia caused by gram –ve organism
• Surgical prophylaxis, e.g artificial heart valves ,
artificial joint
• Meningitis, optimal therapy of biogenic meningitis e,g
ceptazidime and gentamycin are the most effective
therapy for pseudomonas meningitis
• Gonorhea caused by penicilogen producing organism
using ceftriaxone and ceprotacin. Also use for
canchroid

52. 52
Uses contd
• Intravenous ceftriaxone and cefoperazone are effective
in enteric fever caued by salmonela typhi
• For mix aerobic and anaerobic infection in cancer
patient
• In colorectal surgery or obstetrics complication
• Nosocomial infection and resistance to commonly used
antibiotic using cefotaxine and ceftizoxime
• Prophylaxis of treatment of infection in nitropenic
patient such as hiv e.g Ceftaxidime, alone of in
combination with a third generation compound

53. 53
Uses
• Alternative to penicilin G particularly in
allergic patient
• Use for respiratory, urinary and soft tissue
infection cause by gram negative organism
• Treatment of penicillin producing
staphilococcal infection such as beta
lactamases, cephalosporin will be an
alternative

54. 54
AMINOGLYCOSIDES
Aminoglycosides are polybasic amino groups
linked to two or more amino sugar (streptidine,
2-deoxystreptamine, garosamine) residues.
Aminoglycosides are deliberately produced to
treat infections due to gram negative
organisms.
Examples of aminoglycosides are streptomycin,
gentamicin, tobramycin, amikacin, netilmicin,
paromomycin

55. 55
AMINOGLYCOSIDES
Properties of Aminoglycosides
Contain two or more amino sugars attached to hexose
ring by glycosidic linkage
They are highly ionized (polar) at all pH hence are
poorly absorbed from the GIT
Administered by parenteral route and distributed in
extracellular fluid not CSF because of their polar nature
Aminoglycosides are not metabolized and are excreted
intact in urine

56. 56
AMINOGLYCOSIDES
Exert bactericidal effect against gram negative
aerobic bacteria and are more active in alkaline pH
Major side effects are ototoxicity and nephrotoxicity
Molecular oxygen is required to transport
aminoglycosides into bacterial cell which implies that
anaerobic organisms are resistant to aminoglycosides
Cross-resistance among aminoglycosides is partial

57. 57
AMINOGLYCOSIDES
Mechanism of Action
In the presence of oxygen aminoglycosides are
transported into the cell, they bind to 30s
ribosomal subunits, block the initiation of
protein synthesis by causing misreading of
mRNA which results in premature termination
of protein synthesis or incorporation of
incorrect amino acid

58. 58
AMINOGLYCOSIDES
into the growing peptide chains.
Hence defective or non-functional proteins are
incorporated into bacterial cell membrane.
Finally, there is an altered permeability and
disruption of the cell membrane – a bactericidal
effect.
Mechanism of Bacterial Resistance
1. The bacteria acquires an inactivating enzyme that
has an ability to phosphorylate, acetylate or

59. 59
AMINOGLYCOSIDES
adenylate the drug. The conjugated molecule is
incapable of binding to the 30s ribosome, hence
protein synthesis is unaffected.
2. Genetic alteration in the ribosomal subunit through
mutation can decrease its affinity for aminoglycosides.
Examples include development of streptomycin
resistance by single step mutation in E. coli.
3. The transporting mechanism of the
aminoglycosides is interfered by decreasing the pore

60. 60
AMINOGLYCOSIDES
space of the outer coat or decreasing the efficiency of the
active transport mechanism.
Aminoglycoside Toxicity
There are toxic effects which are common to all
aminoglycosides. These are;
1. Nephrotoxicity: Concentration of aminoglycosides in
the renal cortex results in nephrotoxicity which
manifests as tubular damage, low G.F.R., reduced
concentrating power of the kidneys, nitrogen
retention, casts

61. 61
AMINOGLYCOSIDES
and albuminuria.
Therapeutics Uses
1. Streptomycin is one of the first line drugs used in
tuberculosis in addition to other drugs.
2. It is also used in tularemia, plague and
brucellosis.
3. Neomycin is used topically for infections of skins
and mucous membranes e.g. ulcers, wounds and
burns.

62. 62
AMINOGLYCOSIDES
• Neomycin is also used in combination with
bacitracin or polymyxin B in infections of the eye
and external ear.
• Neomycin administered orally is used for
treatment of hepatic encephalopathy. It reduces
blood ammonia
• Gentamicin is the most widely used
aminoglycoside used for
i. Severe aerobic gram-negative bacillary infection

63. 63
AMINOGLYCOSIDES
e.g. UTI, Pneumonia, Meningitis
ii Bacterial endocarditis
iii Tuberculosis
iv Other gram negative infections e.g. plague,
brucellosis, tularaemia.

64. 64
QUINOLONES
Nalidixic acid
•Nalidixic acid is the first quinolone and it is a urinary
antiseptic. Nalidixic acid is effective against gram negative
bacteria such as E. coli, Proteus, Klebsiella, Enterobacta,
Salmonella Shigella, but not Pseudomonas.
•Nalidixic acid act by inhibition of DNA gyrase enzyme
thereby interfering with the replication of bacterial DNA. It
is useful in the treatment of uncomplicated UTI due to gram
negative bacteria and diarrhoea due to Shigella and
Salmonella

65. 65
QUINOLONES
• Adverse effects are related to GI tract, central
nervous system CNS and skin.
Fluoroquinolones
• They are synthetic fluorinated analogues of
nalidixic acid. The important fluroquinolones
are; norfloxacin, ciprofloxacin, perfloxacin,
ofloxacin, levofloxacin, gemifloxacin and
moxifloxacin

66. 66
QUINOLONES
Mechanism of Action
• Fluoroquinolones inhibit DNA gyrase in gram
negative bacteria which results in inhibition of
nicking, formation of negative supercoils and resealing
of strands of DNA. Thus, synthesis of bacterial DNA is
blocked. In gram-positive bacteria topoisomerase IV is
inhibited.
Pharmacokinetics
• Ciprofloxacin is administered by oral, i.v. or topical
routes

67. 67
QUINOLONES
• It is well absorbed from the gut but food delays its
absorption. Ciprofloxacin is widely distributed in the body
and reaches high concentration in kidney, lungs, prostatic
tissue, bile, macrophages, e.t.c. and excreted mainly in urine.
Adverse Effects
• Nausea, vomiting, discomfort,
• headache, dizziness, insomnia, confusion, hallucinations and
convulsions
• Skin rashes, urticaria, itching, eosinophilia and
photosensitivity

68. 68
QUINOLONES
• Tenosynovitis and tendon rupture can occur in
athletes
• Moxifloxacin can cause prolongation of QT interval
• Fluoroquinolones are contraindicated in pregnancy
and are avoided in young children
Therapeutic Uses
1. Urinary tract infections: fluoroquinolones are
effective against gram-negative bacteria such as E.
coli, Proteus, Enterobacta. They are superior over
cotrimoxazole for the treatment of urinary tract
infection.

69. 69
QUINOLONES
They are effective for treatment of prostatitis since
concentrations in prostatic fluid is high.
2. Bacterial infections: effective for a variety of GI infections
caused by E. coli and Salmonella and also travellers diarrhea
which can also be treated with cotrimoxazole.
3. Typhoid fever: ciprofloxacin is the preferred drug for the
treatment of typhoid fever. Levofloxacin and ofloxacin are
used in eliminating the carrier state of Salmonella typhi.
Multi-drug resistant cases are treated with ceftriaxone or
azithromycin.

70. 70
QUINOLONES
4.Sexually transmitted diseases: This includes;
gonococcal infections; treatment of cervicitis and urethritis
caused by N. gonorrhea but its use has declined due to high
rates of resistance
chanchroid; ciprofloxacin is effective
chlamydial cervicitis and urethritis; treated with levofloxacin
and ofloxacin
5. Skin, soft tissue and bone infection due to S. aureus and
gram-negative bacilli requires prolonged use of
fluoroquinolones in combination with an agent effective against
anaerobes

71. 71
QUINOLONES
6. Mycobacterial infections; fluoroquinolones in
combination with other antimicrobial agents are used
in treatment of multidrug-resistant tuberculosis,
atypical micobacterial infections and leprosy
7. Prophylaxis and treatment of infections in
neutropenic patients
8. Ciprofloxacin, levofloxacin, moxifloxacin and
ofloxacin are used topically for conjunctivitis due to
susceptible organisms

72. 72
QUINOLONES
9. Respiratory infections: levofloxacin and
moxifloxacin are highly effective for
community-acquired pneumonia and chronic
bronchitis
10. Anthrax: ciprofloxacin is used for treatment
and prophylaxis of anthrax.

73. 73
TETRACYCLINES
Tetracycline is a broad spectrum antibiotic that has a cyclic
ring structure
Types of tetracyclines include;
i. chlortetracycline - oral, i.v., topical
ii. oxytetracycline - oral, i.v., topical
iii. tetracycline - oral, i.v., topical
iv. demeclocycline - oral
v. methacycline - oral
vi. doxycycline - oral, i.v.
vii. minocycline - oral, i.v.

74. 74
TETRACYCLINES
Mechanism of action
 Tetracycline actively taken up by susceptible
organisms binds reversibly to 30s ribosomal
subunit and prevents the addition of aminoacyl
tRNA to mRNA-ribosome complex. Consequently,
binding of amino acid to growing peptide chain is
prevented thereby producing bacteriostatic effect.
Resistance to tetracyclines
 Bacterial resistance to tetracyclines is due to;

75. 75
TETRACYCLINES
1. decreased influx or increased efflux of
tetracyclines
2. inactivation of the drug by enzymes
3. synthesis of a plasmid-mediated protection
protein which protects the ribosomal binding
site from tetracycline
 Nearly complete cross resistance among
different members of tetracyclines occur

76. 76
TETRACYCLINES
Pharmacokinetics
 Older tetracyclines are incompletely absorbed after oral
administration, however absorption is better when taken on
empty stomach
 Doxycycline and minocycline are completely absorbed
irrespective of food
 Tetracyclines have chelating properties and forms insoluble
and unabsorbable complexes with calcium, magnesium and
other metals. Absorption is therefore reduced by
simultaneous administration with diary products, antacids,
iron

77. 77
TETRACYCLINES
sucralfate and zinc salts.
 Tetracyclines are widely distributed in the body
including liver, spleen, bone, dentine, enamel of
unerupted teeth but concentration in CSF is
relatively low.
 They cross placental barrier and are metabolized in
liver and excreted in urine. Doxycycline is excreted
mainly in faeces via bile. Hence, doxycycline is safe
for use in patients with renal insufficiency.

78. 78
TETRACYCLINES
Adverse Effects
 Gastrointestinal (GI irritation i.e. nausea, vomiting, epigastric
distress, abdominal discomfort)
 Phototoxicity: seen with doxycycline and demeclocycline.
They produce sun-burn like reaction in the skin on exposure
to sunlight. May also produce pigmentation of the skin.
 Hepatotoxicity: More likely to occur in pregnant women, it
causes acute hepatic necrosis in patients taking high doses (>
2 g/day) i.v.
 Renal toxicity: Demeclocycline may produce nephrogenic
diabetes insipidus by blocking the action

79. 79
TETRACYCLINES
of ADH on collecting ducts. This effect of demeclocycline has been
used in patients with syndrome of inappropriate ADH secretion
(SIADH)
 Superinfection: due to their incomplete absorption from the gut
they cause alterations of the gut flora. Superinfections occur with
organisms like Candida, Proteus, Pseudomonas, C. difficile, etc.
 Effects on bone and teeth: Use of tetracyclines in children and
during pregnancy can cause permanent brownish discoloration of
deciduous teeth.
 Hypersensitvity reactions: skin rashes, fever, urticaria, exfoliative
dermatitis

80. 80
TETRACYCLINES
Therapeutic Uses
 Rickettsial infection; oral doxycycline
 Mycoplasma pneumonia infections; doxycycline or
macrolides
 Chlamydial infections; doxycycline or macrolide for
lymphogranuloma venereum
 Cholera; single dose of tetracycline or doxycycline
reduces stool volume
 Brucellosis; combinations of doxycycline with
rifampicin/gentamicin/streptomycin

81. 81
TETRACYCLINE
 Plague; doxycycline highly effective
 Anthrax and leptospirosis; doxycycline for
treatment and prevention
 Lyme disease; treated with doxycycline
 Granuloma ingunale; treated with doxycycline
 Acne; low doses of tetracyclines are used
 Malaria; doxycycline in combination with
other antimalarial agents for treatment of

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TETRACYCLINES
Chloroquine-resistant P. falciparum (they are
slow-acting blood schizonticides against all
species of plasmodia in man). Also used alone
for malaria chemoprophylaxis
 Demeclocycline used for treatment of
SIADH(syndrone of inapproriate secretion of
antidiuraric homorne) secretion to promote
diuresis

83. 83
TETRACYCLINES
 Amoebiasis
Advantages of doxycycline
 It can be administered orally as well as
intravenously
 It is highly potent
 Completely absorbed after oral administration
 Food does not interfere with its absorption
 It has a longer duration of action (t ½ - 24 h)

84. 84
TETRACYCLINES
 Incidence of diarrhea is rare and does not
affect intestinal flora
 Can be given safely to patients with renal
failure as it is excreted in bile

85. 85
CHLORAMPHENICOL
An antibacterial agent isolated from Streptomyces
venezuela in 1947, chloramphenicol is a broad
spectrum antibacterial agent that has dangerous
effect on bone marrow. Hence, its use is restricted.
The drug is now synthesized in a commercial
quantity.
The antibacterial activity of chloramphenicol and
its better taste is attributed to the nitrobenzene
substitution on the hexose ring

86. 86
CHLORAMPHENICOL
Chloramphenicol binds to 50s ribosomal
subunit and interferes with the transfer of the
elongating peptide chain to the newly amino
acyl tRNA on the mRNA-ribosome-complex.
Thus, it stops peptide formation.
The mitochondrial mammalian synthesis is
inhibited (acts on 70s ribosomes) at high doses
of chloramphenicol. This effect mostly is seen
in the bone marrow.

87. 87
CHLORAMPHENICOL
Development of resistance to chloramphenicol
Production of R plasmid encoded glucoronyl
transferase enzyme by H. influenza, S. typhi,
and S. aureus which inactivates the drug.
Decreased permeability of the drug which
enters passively into cell and reduced affinity
of the drug to the 50s ribosomal subunit.
Cross resistance between chloramphenicol and

88. 88
CHLORAMPHENICOL
tetracyclines, erythromycin and clindamycin occur.
Pharmacokinetics
Absorption of chloramphenicol is complete and
rapid from the intestine
The drug is activated in the intestine by pancreatic
lipase
It is also administered via oral and topical routes
Chloramphenicol is 50-60% bound to plasma
proteins and is widely distributed in the body

89. 89
CHLORAMPHENICOL
The volume of distribution is 1 L/kg
It freely penetrates the serous cavities and blood-
brain barrier
Concentration of chloramphenicol in the CSF
equals the concentration of the free drug in the
plasma
It crosses the placenta and is found in breast milk
Chloramphenicol is metabolized by glucoronide

90. 90
CHLORAMPHENICOL
conjugation in the liver. The dose is reduced in
those with liver cirrhosis and neonates due to
reduced conjugation capacity.
The metabolite of chloramphenicol is excreted
mainly in urine
The half-life of the drug in adults is 3-5 hours.
Though it increases marginally in renal failure.

91. 91
CHLORAMPHENICOL
Adverse Effects
The adverse effects of chloramphenicol are
related to its inhibition of mitochondrial protein
synthesis. These effects include;
1. Bone marrow suppression (dose-dependent
effect) characterized by aplastic anemia,
pancytopenia, leukopenia, and
thrombocytopenia.
a. Idiosyncratic non-dose related irreversible

92. 92
CHLORAMPHENICOL
aplastic anemia, which is often fatal.
b. Myelosuppression that is related to dose and
duration of therapy; a direct predictable toxic effect
due to inhibition of mitochondrial enzyme
synthesis. It is reversible with no long term effect
and often occur during liver and kidney disease.
2. Gray baby syndrome: this condition occur in
premature babies due to deficiency in glucoronyl
transferase that results in inability to

93. 93
CHLORAMPHENICOL
inactivate chloramphenicol. The condition is
manifested by nausea, vomiting, abdominal
distension, cyanosis, refusal to suck, irritability
and circulatory collapse.
The skin appears ‘ashen gray’ hence the name
gray baby syndrome.
The above symptoms occur when approximately
100 mg/kg dose is given prophylactically to
neonates.

94. 94
Therapeutic Uses of Chloramphenicol
• Use for Salmonella typhi and for enteric fever
• Pyogenic meningitis
• Anaerobic infection
• Intra occular infection such as conjunctivitis
• Also for second
• UTI infection
• Topical for conjunctivitis

95. 95
MACROLIDE ANTIBIOTICS
• Macrolides are antibiotics having a macrocytic
lactone ring with attached sugars.
• Erythromycin was discovered in 1952 by
McGuire and coworkers in the metabolic
products of a strain of Streptomyces erythreus
• Clarithromycin is a semisynthetic derivative of
erythromycin.
• Ketolides (telithromycin) are semisynthetic
derivative of erythromycin with activity

96. 96
MACROLIDE ANTIBIOTICS
-against some macrolide -resistant strains.
• Roxithromycin and azithromycin are other agents.
• Erythromycin have been used as an alternative to
penicillins.
Mechanism of Action
• At low concentration erythromycin is bacteriostatic
and at high concentration bacteriocidal.
• Erythromycin act by binding to 50s ribosomal

97. 97
MACROLIDE ANTIBIOTICS
-subunit to inhibit protein synthesis. It more active
at alkaline pH.
Pharmacokinetics
• Erythromycin is absorbed adequately from the
gastrointestinal tract, but it is acid labile.
• To protect against gastric acid, ethromycin must
be administered as an enteric-coated tablet.
• Food can delay the asorption of erythromycin

98. 98
MACROLIDE ANTIBIOTICS
• It is widely distributed and reaches high
concentration in prostatic fluid but does not
cross the blood-brain-barrier.
• Part of erythromycin is metabolized in liver
and excreted in bile.
Preparations
• Include erythromycin base, erythromycin
estolate, erythromycin stearate

99. 99
MACROLIDE ANTIBIOTICS
Adverse Effects
1. Gastrointestinal tract (enteral toxicity):
Nausea, vomiting, epigastric pain, diarrhea,
increase in mortility of GIT by stimulating
motilin in gut, cholestatic jaundice,
hepatotoxicity in pregnant women.
2. Hypersensitivity reactions such as skin rashes,
urticarial, drug fever, eosinophilia, hepatitis.

100. 100
MACROLIDE ANTIBIOTICS
Drug Interaction
• Clarithromycin and erythromycin are enzyme
inhibitors which cause accumulation of
theophylline, carbamazepine, valproate,
warfarin, digoxin, cyclosporine etc and
potentiate their effects
Drawbacks of Erythromycin
1. Narrow spectrum of activity

101. 101
MACROLIDE ANTIBIOTICS
2. Oral bioavailability is low
3. Short duration of action
4. Poor patient compliance due to gastrointestinal side
effects
• Hence semisynthetic macrolides are developed
Clarithromycin
• Mechanism of action is similar to that of erythromycin
• It is orally administered and achieve high
concentration in prostate

102. 102
MACROLIDE ANTIBIOTICS
• Also it is used for treatment of M. Avium,
leprosy and H. pylori
Azithromycin
• Administered orally and intravenously
• Ingestion should be done 1 hour before or 2
hours after meal.
• Azithromycin is not distributed to the brain
and more effective against H. influenza than

103. 103
MACROLIDE ANTIBIOTICS
-clarithromycin and erythromycin.
• Distributed widely in tissues and achieve high
concentration intravenously.
Therapeutic Uses
1. M. pneumonia – azithromycin,
clarithromycin, erythromycin are for
treatment of hospital arquired pneumonia
2. Legionnare’s pneumonia - azithromycin

104. 104
MACROLIDE ANTIBIOTICS
3. Chlamydia infection – affects children and
pregnant women and treated with erythromycin
4. Diptheria – use of erythromycin for carrier
state
5. Pertusis – erythromycin is most effective
6. Erythromycin is an alternative in penicillin
allergy in tetanus, streptococcal infections,
prophylaxis.