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Antibiotics
Antibiotics
Introduction
 Contents
1.
2.
3.
4.
5.
6.
7.
8.
Sulfonamides
Penicillin's
Cephalosporin's
Macrolides
Quinolones/Fluoroquinolones
Aminoglycosides
Tetracycline's
Miscellaneous Drugs
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 Antibiotics are drugs of pertaining ability to destroy or
interfere with the development of a living organism.
 Antibiotics can be classified into:
1. Bacteriostatic
2. Bactericidal
Sulfonamides
 Sulfonamides are chemically related group of antibiotics that
are all synthetic derivatives of sulfonamide.
 They were one of the first group of drugs used as antibiotics
and some of the more commonly prescribed agents.
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 These antibiotics achieve very high concentration in kidneys
through which they are eliminated. There fore they are
primarily used for the treatment of urinary tract infections
(UTI).
 Sulfonamides are also used in the treatment of rheumatoid
arthritis, in addition they may be combined with other
antibiotics to increase their antibiotic potency.
Drugs
 Sulfadiazine
 Sulfamethiazole
 Sulfamethoxazole
 Sulfisoxazole
 Sulfadimidine
 Sulfametopyrazine
Chemistry
Sulfapyridine
Mechanism of action
 Sulfonamides donot actually destroy bacteria but inhibit their
growth.
 They inhibit the growth of susceptible bacteria by preventing
the synthesis of folic acid.
 The enzyme dihydrofolic acid DHF, synthase converts paraamino benzoic acid PABA to DHF, which subsequently
converts into tetrahydrofolic acid THF.
Therapeutic Uses
 Sulfonamides are used for the treatment of:
Urinary tract infections caused by, enterobacter spp,
klebsiella spp, proteus vulgaris, & staphylococcus aureus.
2. Nocardiosis
3. Infected burns and leg ulcers (silver sulfadiazine)
4. Inflammatory bowel disease (sulfasalazine)
1.
Side-effects
 Headache
 Convulsion
 Aplastic anemia
 Nausea
 Vomiting
 Diarrhea
 Toxic nephrosis
Sulfamethoxazole
 Sulfamethoxazole is an intermediate acing sulfonamide
antibiotic.
 Because it is eliminated by means of kidneys and reaches very
high concentrations there, it is commonly used to treat
urinary tract infections caused by susceptible organisms.
 It is combined phenazopyridine (analgesic) that affects the
mucosa of UTI.
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 Sulfamethoxazole by it self comes as a 500mg/5ml oral
suspension and 500mg tablet.
 It is a pregnancy category C.
Co-trimaxazole
 Co-trimaxazole is a combination of Sulfamethoxazole and
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Trimethoprim.
The optimum synergistic in vitro effect against most
susceptible bacteria is achieved with 5: 1 ratio of
Sulfamethoxazole and trimethoprim.
Has an half life of 10 hour.
Used for UTI caused by susceptible bacteria, pneumocystis
carinii pneumonia.
Used for ear infection (otitis media)
Used for bronchitis
Used for STD including gonorrhea and syphilis.
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 Available 40mg/5ml oral suspension
 Available 80mg trimethoprim & 400mg Sulfamethoxazole=
480mg co-trimaxazole.
 Available 180mg trimethoprim & 800mg Sulfamethoxazole
= 980mg co-trimaxazole.
 Available 16mg/ml trimethoprim & 80mg/ml
Sulfamethoxazole= 96mg/ml injection.
Sulfisoxazole
 Sulfisoxazole is a short acting sulfonamide antibiotic that is
primarily used urinary tract infections.
 Used for ear infection (otitis media) in small children.
 It is a pregnancy category C agent.
 Available 500mg tablet & 500mg/5ml suspension.
Penicillin's
 The penicillin's are very large group of chemically related
antibiotics that are derived from a fungus or mold, often seen
on bread or fruit.
 The penicillin's may also be called beta-lactam, a term which
refers to their chemical structure.
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 The penicillin's was first introduced on the market in the
early 1940 and to this day they have remained very effective
and safe antibiotics.
 They are bactericidal and can kill a wide variety of gram
positive bacteria
 Half life of penicillin's is 2h approximately.
Classification of drugs
 The penicillin's can be divided into:
Natural penicillin's
2. Penicillinase resistant penicillins
3. The amino-penicillins
4. The extended spectrum penicillin's
1.
Mechanism of action
 Penicillin's involves several steps that together result in the
inhibition of bacterial cell wall synthesis.
 They block penicillin binding proteins (PBP), by inhibiting
peptidoglycan in the cell wall bacteria.
Side-effects
 Anemia
 Lethargy
 Bone-marrow depression
 Hallucination
 Nausea
 Vomiting
 Sore throat
 Abdominal pain
Natural Penicillin's
 Natural penicillin's are:
1.
2.
3.
4.
5.
6.
Pen G
Pen V
Pen M
Pen N
Pen X
Pen F
Penicillin G
Penicillin V
Penicillin G
 Penicillin G consists of:
Benzathine
2. Potassium
3. Sodium
4. Procaine
1.
Penicillin G Benzathine
 Given IM injection
 Long acting drug
 Expected to work over the course for several days.
Penicillin G K+ & Na
 Commonly administered IV for the treatment of life
threatening illnesses such as:
1. Septicemia
2. Meningitis
3. Pericarditis
4. Severe pneumonia
Aminopenicillins
 There are three aminopenicillins:
Amoxicillin
2. Ampicillin
3. Bacampicillin
 Because of the presence of a free amino group on the
penicillin's nucleus, the aminopenicillins have enhanced
activity against gram negative bacteria.
1.
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 Amoxicillin is an analogue of ampicillin and becampicillin is a
prodrug of ampicillin.
 The aminopenicillins are contraindicated:
1. Hypersensitivity
 They are rated in a pregnancy category B drugs.
Amoxicillin
Ampicillin
Ampicillin
 Ampicillin is the prototypical amino penicillin, that has
amino group.
 It is available in three different forms:
1. Anhydrous
2. Trihydrate
3. Sodium
 Anhydrous and trihydrate Ampicillin are administered
orally.
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 Ampicillin sodium is given parenterally.
 Available 250mg, 500mg capsules, 250mg/5ml suspension,
125, 250, 500, 1000, 2000, 10,000mg vial for injection.
 Adult dosage is PO: 250mg- 500mg Qid, IM/IV: 250mg500mg Qid.
Penicillinase Resistant Penicillin's
 These congeners have side chains that protect the beta-lactam
ring from attack by staphylococcal penicillinase.
 However this also partially protects the bacteria from the
beta lactam ring. Their only indication is infectious caused by
penicillinase producing staphylococci, for which they are the
drugs of choice except in areas where methicillin resistant
staph aureus (MRSA) has become prevalent.
Methicillin
 It is highly penicillinase resistant but not acid resistant, must
injected. it is also an inducer of penicillinase production.
 The MRSA have altered PBPs which donot bind penicillins.
 The drug of choice for these organisms is
vancomycin/linezolid, but ciprofloxacin can also be used.
 Haematuria, albuminuria, and nephritis are the side effects of
methicillin.
Cloxacillin
 It has an isoxazolyl side chain and is highly penicillinase as
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well as acid resistant.
It is more active than methicillin against penicillinase
producing staph.
Cloxacillin is incompatibly but dependably absorbed from
oral route, especially if taken in empty stomach.
Plasma half life is about 1 hour.
Elimination occurs primarily by kidney, also partly by liver.
It is available 0.25g, 0.5g cap and injections.
PROCAINE PENICILLIN ALLERGIC REACTION
 ID/CC: A 21 year old male comes to the health clinic
because of the development of fever, marked itching all over
his body, generalized rash with joint swelling and difficulty
breathing.
 HPI: he just returned from a trip abroad, where he had
developed a purulent urethral discharge and went to a local
doctor who gave him two pills of procaine penicillin.
 PE: mild hypotension, mild cyanosis and difficulty breathing.
 Imaging: CXR is normal
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 Treatment: Subcutaneous epinephrine, oxygen,
hydrocortisone, antihistamines. Maintain airway and provide
assisted ventilation if necessary. Severe reactions may result
in laryngeal obstruction, hypotension and death.
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 Discussion: Penicillin’s are antimicrobial drugs that block
cell wall synthesis by inhibiting peptidoglycan cross linking;
they are bactericidal for gram positive cocci and rods, gram
negative cocci. Most adverse reactions to penicillin are
allergic reactions that result when one of it is metabolites
acts as hapten. Anaphlytic reaction involves antigen reacting
with IgE on presensitized mast cells and basophils, it is
usually severe and immediate.
METHICILLIN RESISTANCE STAPHYLOCOCCUS AUREUS (MRSA)
 ID/CC: A 25 year old male presents with spiking fevers, malaise,
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left sided chest pain and cough.
HPI: His symptoms started two weeks ago and have progressively
worsened despite a full course of oral antibiotics. He also reports a
history of prior IV drug abuse.
PE:VS: Fever (39 centigrade), tachycardia (HR 105), tachypnea.
PE: amphoric, breath sounds heard over left lower lobe; S1 & S2
normally heard without murmurs, gallops or rubs.
Labs: induced sputum cultures grew methicillin resistant
staphylococcus aureu.
Imaging: XR, chest: 2 by 3cm cavity in left lower lobe of lung
with air fluid level. CT, chest: confirmed a left lower lobe lung
abscess.
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 Treatment: Intravenous Vancomycin therapy, add
aminoglycoside for synergistic bactericidal effect.
 Discussion: Antibiotic resistant is continuing to increase in
both the hospital and the community. Major resistant
nosocomial organisms include s.aureus, klebsiella, and
pseudomonas. MRSA is becoming widespread in a number of
communities and is more commonly seen in IV drug abusers,
patients with recent hospitalizations.
Cephalosporin's
 The cephalosporin's are semi-synthetic antibiotic derivatives
of cephaloporin C.
 These chemically altered derivatives of this fungus are
broadly referred to as cephalosporin's and they are
structurally and pharmacologically related to the penicillin's.
 Cephalosporin's have a broad spectrum of bacteria.
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 The safety profiles, contraindications and pregnancy ratings
of cephalosporin's are very similar to those of penicillin's.
 Because of cephalosporin's are chemically very similar to
penicillin's, a person who has had an allergic reaction to
penicillin's have also allergic reaction in cephalosporin's, this
is referred to as cross sensitivity.
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 Cephalosporin's of all generations are very safe agents that
are categorized as pregnancy category B agents.
 They are contraindicated:
1. Hypersensitivity
2. Younger than 1 month old
Classification of Drugs
 Cephalosporin's can be classified into:
First generation
2. Second generation
3. Third generation
4. Fourth generation
1.
First Generation
 Drugs
1.
2.
3.
4.
5.
Cefazolin sodium
Cephalothin
Cephalexin
Cephradine
Cephapirin
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 First generation are usually active against gram positive
bacteria and have limited activity against gram negative
bacteria.
 They are available both parenteral and oral.
Cefazolin sodium
 First generation of cephalosporin
 Excellent coverage against gram positive and poor coverage
of gram negative.
 Only available in parenteral formulation that comes 5001000mg vials for IM or IV injection.
 Adult dosage is IM/IV: 250mg-1g q8h-q12h.
Second Generation
 Drugs
1.
2.
3.
4.
5.
6.
7.
8.
Cefamandole
Cefoxitin
Cefuroxime
Cefonicid
Ceforanide
Cefmetazole
Cefaclor
Cefprozil
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 The second generation cephalosporin's have similar coverage
against gram positive organisms but enhanced gram negative
bacteria.
 They include both parenteral and oral formulations.
 The second generation cephalosporin's are also excellent
prophylactic antibiotics.
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 The qualities that make them excellent prophylactic agents
are:
1. Safety profile
2. Broad range of organisms they can kill
3. Relatively low cost
Cefoxitin
 It is a parenteral second generation cephalosporin.
 Cefoxitin has been used extensively as a prophylactic
antibiotic in patients undergoing such surgical procedures
especially in abdominal and colorectal operations.
 It is rated pregnancy category B.
 Available only in parenteral formulations 1,2, 10g vials for
injection
Third Generation
 Drugs
1.
2.
3.
4.
5.
6.
Cefoperazone
Cefotaxime
Ceftizoxime
Ceftriaxone
Ceftazidime
Cefixime
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 Third generation cephalosporin's are the most potent in
fighting gram negative bacteria.
Ceftriaxone
 Ceftriaxone is a parenterally administered third generation
cephalosporin that differs from the other agents in that it has
a very long half life that allows it to be given once a day.
 It can be given both intravenously and intramuscularly.
 It can easily pass meningitis and BBB, making it an excellent
agent for the treatment of CNS infection.
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 Available 250, 500mg, 1, 2, 10 gram vials.
 Adult dosage is: IM/IV 1-4 g/day as a single dose or divided
doses.
Tetracycline's
 The tetracycline's are small chemically related group of five
antibiotics, three of which are naturally occurring and two of
which are semi-synthetic.
 They are derivatives of streptomyces organisms.
 Tetracycline's can only inhibit the growth of bacteria, they
cannot kill bacteria, therefore they are considered
bacteriostatic.
Chemistry of Tetracycline
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 The three naturally occurring tetracycline's are:
1.
2.
3.
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1.
2.
Tetracycline
Demeclocycline
Oxytetracycline
The two semi-synthetic tetracycline's are:
Doxycycline
Minocycline
Mechanism of action
 Tetracycline's work by inhibiting protein synthesis 30S in
susceptible bacteria.
Therapeutic uses
 Chlamydia
 Syphilis
 Lyme
 Rickettisiae
 Protozoa
 Acne
 Cholera
 Shigellosis
 Mycoplasma pneumonia
Side-effects
 Discoloration of teeth
 Tooth enamel hypoplasia
 Retard fetal skeletal development
 Photosensitivity
 Alteration of the intestinal flora
 Diarrhea
 Gastric upset
 Reduced bacterial vitamin K synthesis
Doxycycline
 Doxycycline is a semi synthetic tetracycline antibiotic.
 Doxycycline comes in the following three different salt
forms:
1. Calcium
2. Hyclate
3. Monohydrate
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 It is useful in the treatment of rickettsial infections,
gonorrhea and many gram negative infections.
 It comes orally as a 25 and 50mg/5ml oral suspension, 50,
100mg capsules and 100, 200mg per ml injections.
 It is rated in a pregnancy category D drug.
TETRACYCLINE RASH
 ID/CC: A 19 year old red haired female visits her
dermatologist at a local clinic because of a rash that appeared
after she spent the sunny weekend hiking without sun block
protection.
 HPI: Two months ago, her dermatologist put her on the low
dose tetracycline to prevent acne.
 PE: Normal
 Labs: Mild proteinuria
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 Treatment: Sun protection, both mechanical and
pharmacological, while taking tetracycline.
 Discussion: Tetracycline’s are bacteriostatic antibiotics that
bind to 30s ribosomal subunit, blocking synthesis of protein.
If they are taken with alkaline foods such as milk and
antacids, GI absorption is decreased. Tetracyclines are used
therapeutically and prophylactically for chylamdial infections,
lyme disease, acne and cholera.
Aminogylcosides
 Aminoglycosides are group of natural and semi-synthetic
antibiotics that destroy bacteria, rather than inhibit their
growth, so they are bactericidal.
 They are derived from streptomyces organisms.
 They are not given orally because of their poor oral
absorption.
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 They can kill both gram positive and gram negative bacteria
but are customarily used to kill gram negative such as,
pseudomonas, E. coli and klebsiella.
 The aminogylcosides work in a way that is similar to that of
tetracycline's in that they also bind to ribosomes and thereby
prevent protein synthesis in bacteria.
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 The aminogylcosides have been shown to cross the placenta
and cause fetal harm when administered to pregnant women.
 The pregnancies categories of the various aminogylcosides
are as follows:
1. Gentamycin, neomycin: pregnancy category C
2. Tobramycin,Amikicin,kanamycin:pregnancy D
3. Streptomycin: pregnancy category B
Drugs
 Gentamycin
 Tobramycin
 Amikacin
 Kanamycin
 Neomycin
 Streptomycin
Mechanism of action
 Aminoglycosides kill bacteria by binding and disrupting
protein synthesis in bacteria specifically they do this by
binding to both 30s and 50s ribosomal subunit.
Side-effects
 Renal failure
 Hearing loss (Ototoxicity)
 Nausea
 Vomiting
 Proteinuria
 Increase serum creatinine level
Gentamycin
 Gentamycin is a naturally occurring aminoglycoside that is
obtained from cultures of micromonospora purpurae.
 It is one of the Aminoglycosides most commonly used in
clinical practice today.
 It is classified pregnancy category C.
 Available 10, 40mg/ml injection IM/IV, 10, 60, 80 mg per
ml intravenous infusion.
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 Available 3% solution or ointment for ophthalmic.
 Comes also 0.1% ointment for topical application on:
Superficial skin infection
2. Burns
3. Skin ulcers
1.
GENTAMICIN SIDE EFFECTS
 ID/CC: A 34 year old women presents with her family
practitioner complaining of hearing loss, vertigo and inability
to walk properly due to lack of balance.
 HPI: she took IV Gentamicin for 10 days
 PE: Well hydrated, oriented and cooperative
 Imaging: normal
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 Treatment: Discontinuation of the drug, supportive
therapy.
 Discussion: Gentamicin is an aminoglycoside and thus
shares the Ototoxicity and Nephrotoxicty of streptomycin,
kanamycin, Amikacin, and tobramycin. Ototoxicity is mainly
cochlear and marked by ataxia and vertigo. Nephrotoxicity is
minimized if care is taken to hydrate the patient and keep
serum levels therapeutic.
Quinolones
 The quinoline antibiotics are very potent broad spectrum
antibiotics.
 They are bactericidal
 The first of these agents to come available were:
1. Cinoxacin
2. Nalidixic acid
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 The newer quinoline antibiotics include:
1.
2.
3.
4.
5.
6.
Norfloxacin
Ciprofloxacin
Enoxacin
Ofloxacin
Lomefloxacin
Perfloxacin
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 A fluorine atom was added on to the basic quinolone
structure to create these newer agents and increased their
anti-bacterial activity.
 Because of chemical, these agents are sometimes called
fluoroquinolones.
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 The fluoroquinolones are active against a wide variety of
gram negative and selected gram positive bacteria.
 Fluoroquinolones are primarily excreted by the kidneys,
which contain a high percentage of unchanged drug, this
makes them good for treating of UTI.
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 Their use in children is not currently recommended because
they have been shown to suppress growth in laboratory
animals.
Mechanism of action
 Quinolone antibiotics destroy bacteria by altering DNA and
they accomplish this by interfering with DNA gyrase,
enzyme necessary for the synthesis of bacterial DNA, if
bacteria cannot produce DNA they die.
Side-effects
 Dizziness
 Insomnia
 Fatigue
 Nausea
 Rash
 Fever
 Blurred vision
Ciprofloxacin
 Ciprofloxacin was one of the first potent fluoroquinolones to
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come available.
First marketed in an oral form and advantage of convenience
of oral preparation plus excellent bioavailability.
Effective against to kill gram negative bacteria.
Orally comes 250, 500, 750mg tablet, parenterally comes
200, 400mg.
The common dosage is 250mg-750mg Tid, Bid.
FLUOROQUINOLONE SIDE EFFECTS
 ID/CC: A 21 year old college baseball player restarted his
training 3 days ago, running 1600 meters a day in preparation
for the upcoming state tournament, yesterday he hit a home
run and started off to first base when he suddenly fell to the
ground and couldn’t work due to acute pain.
 HPI: He had spent 4 weeks in the hospital recovering from
perforated appendicitis where he received IV ciprofloxacin
for 2 weeks due to surgical wound infection with
pseudomonas aeruoginosa that was resistant to all other
antibiotics.
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 PE: Surgical wound completely healed with no evidence of
infection or postincisional hernia; penrose drain orifice
within normal limits; inability to plantarflex left foot;
Achilles tendon completely severed.
 Labs: CBC: no leukocytosis; no anemia. SMA-7 normal. UA:
normal.
 Imaging: CXR/KUB: within normal limits.
 Micro Pathology: Achilles tendon shows inflammatory
neutrophilic infiltrate with areas of heamorrhage and
necrosis.
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 Treatment: Surgical repair.
 Discussion: Fluoroquinolones such as ciprofloxacin and
Norfloxacin are bactericidal antibiotics that are active against
gram negative rods, including pseudomonas; they are also
active against Neisseria and some gram positive organisms.
They act by binding DNA gyrase. Side-effects include damage
to cartilage, tendonitis, and tendon rupture; they also
produce gastric upset and nausea and may cause super
infection.
Macrolides
 The Macrolides are a large group of antibiotics that first came
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available in the early 1950s with the introduction of
erythromycin.
Macrolides have a macrocyclic lactone.
Macrolides are considered bacteriostatic but in high
concentration may be bactericidal in some susceptible
bacteria.
Macrolides are POM drugs.
Macrolides are rated pregnancy category C.
Drugs
 Azithromycin
 Clarithromycin
 Erythromycin
 Troleandomycin
 Roxithromycin
Erythromycin
Clarithromycin
Azithromycin
Mechanism of action
 They bind 50s ribosomal subunit inside the cells of bacteria
and by doing so prevent the production of the bacterial
protein needed for bacteria to grow, with the result that
bacteria eventually will die.
Antibacterial spectrum
 It is narrow, includes mostly gram positive and a few gram
negative bacteria.
 It is highly active in the following bacteria's:
1. str. pyogenes
2. Str. Pneumoniae
3. N. gonorrhoeae
4. Clostridia
5. C. dipthteriae
Uses
As an alternative to penicillin: streptococcal pharyngitis,
tonsillitis, community acquired respiratory infections
caused by pneumococci and H. influenzae, however many
bacteria resistant to penicillin are also resistant to
erythromycin.
2. Diphtheria: erythromycin 250mg Qid, acute stage as well
as for carriers 7 day treatment, antitoxin is the primary
treatment.
1.
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3. Tetanus: erythromycin 500mg is given Qid for 10 days to
eradicate clostridium tetani.
4. Syphilis and gonorrhea
5. Atypical pneumonia caused by mycoplasma pneumoniae
6. Whooping cough: 1 to 2 week course of erythromycin is the
most effective treatment for eradicating Pertussis from upper
respiratory tract.
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7. Chlamydia trachomatis infection of urogenital tract:
erythromycin 500mg QID for 7.
8. Penicillin resistant staphylococcal infections
9. Helicobacter pylori infection: Clarithromycin 500mg in
combination in Omeprazole 20mg, and amoxicillin 1g each
administered twice a day for 10 to 14 days, is effective for the
treatment of peptic ulcer disease.
10. Mycobacterial infection: Azithromycin or Clarithromycin
are recommended for the first line of prophylaxis and
treatment of pulmonary disease. E.g AIDS.
Side-effects
 Headache
 Dizziness
 Palpitation
 Heart burn
 Nausea
 Anorexia
 Vomiting
 Rash
 Hearing loss
Drug-Drug Interactions
 Clarithromycin and erythromycin inhibit CYP3A4.
erythromycin potentiates the effects of Carbamazepine,
corticosteroids, digoxin, Theophylline, Warfarin.
Erythromycin
 Most frequently prescribed macrolide antibiotic.
 It comes in several different salt and dosage forms that were
developed to circumvent some of the drawbacks it has
chemically.
 The absorption of oral erythromycin is enhanced if it is taken
on an empty stomach, but because of the high incidence of
stomach irritation, many of the agents are taken after meal or
snack.
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 Dosage range is:
children: 30-100mg/kg/day divided dose
2. Adult: 500mg as single dose or Bid
1.
Miscellaneous Drugs
 Vancomycin
 Clindamycin
 Metronidazole
 Chloramphenicol
Vancomycin
 It is a natural bactericidal antibiotic structurally unrelated to
any other commercially available antibiotics.
 It is a glycopeptide antibiotic discovered in 1956.
 It destroys bacteria by binding to the bacterial cell wall
producing immediate inhibition of cell wall synthesis and
death.
 It is the antibiotic of choice for the treatment of MRSA.
Vancomycin
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 The parenteral form is indicated for the treatment of bone
and joint infections and bacterial blood stream infections
caused by staphylococcus spp.
 Classified pregnancy category B.
 Caution use:
1. Renal dysfunction
2. Hearing loss
3. Elderly patients
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 Contraindicated for hypersensitivity
 Available 125, 250mg capsules and 500mg, 1g for
intravenous infusions.
 Adult dosage is 0.5-2g per day in Tid for 7-10 days.
Mechanism of action
 Vancomycin inhibits the cell wall synthesis by binding with
high affinity, D-alanyl D-alanine.
 Vancomycin is a bactericidal.
Toxicity
 Systemic toxicity of Vancomycin is high. It can cause plasma
concentration dependant nerve deafness which may be
permanent.
 Kidney damage is also dose related.
 Skin allergy and fall of blood pressure during IV injection.
 Rapid IV injection has caused chills, fever and intense
flushing-Red man syndrome (an adverse anaphlytical reaction
to Vancomycin therapy causing pruritis, flushing of the head
and the upper part of the body, the condition is caused by the
release of histamine).
Uses
 MRSA
 Bacterial meningitis combination therapy with Ceftriaxone
or Cefotaxime.
 Used for dialysis patients
 Those undergoing chemotherapy for cancer patients.
 Penicillin allergic patients
Chloramphenicol
 Chloramphenicol was initially obtained from streptomyces
venezuelae in 1947.
 It was soon synthesized chemically and the commercial
product now is all synthetic.
 It has a nitrobenzene substitution, which is probably
responsible for the antibacterial activity and it is intensely
bitter taste.
Chloramphenicol
Mechanism of action
 Chloramphenicol inhibits bacterial protein synthesis by
interfering with transfer of the elongating peptide.
 It specifically attaches 50S ribosome.
Pharmacokinetics
 Chloramphenicol is rapidly and completely absorbed after
oral ingestion.
 Chloramphenicol is primarily conjugated with glucuronic
acid in the liver and little is excreted unchanged in urine.
 Plasma half life of chloramphenicol is 3-5 hours in adults.
 It is increased only marginally in renal failure.
Therapeutic Uses
 Enteric fever- Typhoid
 Pyogenic meningitis: Chloramphenicol 50-75mg/kg per day
may be used after the third generation of cephalosporin's.
 Anaerobic infections: Wound infections, pelvic and brain
infections.
 Intraocular infections: Chloramphenicol is given systemically.
Adverse Effects
 Bone marrow depression
 Hypersensitivity reactions like, fever, rashes, glossitis,
 Nausea
 Vomiting
 Diarrhea
 Pain on injection
 Gray baby syndrome: the baby stop feeding, vomited,
hypothermic, abdomen distended, respiration become
irregular and gray cyanosis occur.
CHLORAMPHENICOL SIDE EFFECTS
 ID/CC: A 31 year old truck driver visits a health clinic in
Buroa Togdheer region, complaining of recurrent infections,
excessive bleeding, weakness and anemia.
 HPI: He travels the border of Ethiopia daily and eats and
sleeps there. He has had a typhoid fever three times over the
past five years, for which he has been treated with high dose
of chloramphenicol.
 PE: Normal
 Labs: Anemia
Continue
 Treatment: Blood transfusions, cyclosporin for bone
marrow transplantation.
 Discussion: Chloramphenicol is a bacteriostatic antibiotic
that acts by inhibiting peptidyl transferase in the 50s
ribosomal unit. It is active against anaerobes and riclettsiae as
well as against typhoid fever and meningococcal. In infants
they produce gray baby syndrome. Owing to its potentially
fatal side-effect of Aplastic anemia, chloramphenicol is used
primarily for serious infections or acute salmonella typhi
infection.