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SYSTEMIC
ANTIBIOTICS
IHAB YOUNIS,MD
ß-LACTAM ANTIBIOTICS
1-Penicillins
2-Cephalosporins
ß-lactam ring
PENICILLINS
History
• Penicillin was discovered by
Sir Alexander Fleming working
at St. Mary's Hospital in London
in 1928
• He observed that a plate
culture of Staphylococcus had been
contaminated by a blue-green mold &
that colonies of bacteria adjacent
to the mold were being dissolved
• Curious, Alexander Fleming grew the
mold in a pure culture and found that
it produced a substance that killed a
number of disease-causing bacteria
• Naming the substance penicillin, Dr.
Fleming in 1929 published the results
of his investigations, noting that his
discovery might have therapeutic
value if it could be produced in
quantity
• It was not until 1939 that Dr. Howard
Florey and three colleagues at Oxford
University began intensive research and
were able to demonstrate penicillin's ability
to kill infectious bacteria
• As the war with Germany continued to
drain industrial and government resources,
the British scientists could not produce the
quantities of penicillin needed for clinical
trials on humans and turned to the United
States for help
• They were quickly referred to the Peoria
Lab where scientists were already working
on fermentation methods to increase the
growth rate of fungal cultures
• Ironically, after a worldwide search, it was
a strain of penicillin from a moldy
cantaloupe in a Peoria market that was
found to produce the largest amount of
penicillin when grown in the suitable
conditions
• Penicillin production was quickly scaled up
and available in quantity to treat Allied
soldiers wounded on D-Day. As production
was increased, the price dropped from
nearly priceless in 1940, to $20 per dose
in July 1943, to $0.55 per dose by 1946
• As a result of their work, two members of
the British group and Dr. Andrew J. Moyer
from the Peoria Lab became Nobel
laureates
• Physicians and the industry seem to have
decided to discard penicillin. In
Switzerland, long-acting slow-release
penicillin preparations are not available
any longer. The oral penicillin V is also
being superseded more and more,
whether this is justified or not remains
open. Only the intravenous treatment (e.g.
of meningitis or other severe infections) is
still relatively indisputable
Variants in clinical use
1- Benzathine penicillin(Durapen,Penicid,Lastipen,1.2
megaunit/vial)
• It is slowly absorbed into the circulation, after
IM injection. It is the drug-of-choice when
prolonged low concentrations of penicillin are
required, allowing prolonged antibiotic action
over 2–4 weeks after a single IM dose e.g.
for syphilis
2- Benzylpenicillin(Penicillin G,Aqua-pen,1 megaunit/vial)
• Penicillin G is typically given by a parenteral
route of administration because it is unstable
to the hydrochloric acid of the stomach
• It is used when higher tissue concentrations
of penicillin e.g. in pneumonia
3- Phenoxymethylpenicillin(Ospen tab,1
megaunit;Cliacil tab,1.2megaunit)
• Commonly known as penicillin V
• It is the orally-active form of penicillin
• It is less active than benzylpenicillin, so it is
only appropriate in conditions where high
tissue concentrations are not required e.g. in
skin infections
• 4- Procaine penicillin(Penicillin procain
vial,100,000 IU+300,000 IU proc./vial)
• is a combination of benzylpenicillin with
the local anaesthetic agent procaine .This
combination is aimed at reducing the pain
and discomfort associated with a large IM
injection of penicillin
5-Ampicillin(Ampicillin,Epicocillin,Amphpen125*-250500 mg)
• It was approved by the FDA in 1963
• Ampicillin is one of the most widely
prescribed antibiotics
6- Amoxicillin(Hiconcil,Ibiamox,Amoxil,Emox, 125*-250500 mg)
• It is usually the drug of choice within the
class because it is better absorbed,
following oral administration, than other
ß-lactam antibiotics
7-Methicillin
• It is deactivated by gastric acid so ,it has
to be administered by injection
• Methicillin was previously used to treat
infections caused by penicillin resistant
bacteria ,e.g staph but it has now been
largely replaced by the oxacillin series
Mode of action:
• ß-lactam antibiotics work by inhibiting the
formation of peptidoglycan cross links in the
bacterial cell wall
• The ß-lactam moiety of penicillin binds to the
enzyme)transpeptidase) that links the
peptidoglycan molecules in bacteria, and this
weakens the cell wall of the bacterium when it
multiplies
Adverse effects
• Allergic reactions to any β-lactam antibiotic
may occur in up to 10% of patients
receiving that agent
• Anaphylaxis will occur in approximately
0.01% of patients
• Common reactions include: diarrhoea,
nausea, urticaria, superinfection (including
candidiasis)
Resistance
• Resistance to penicillin is now common amongst
many hospital acquired bacteria due to the rise
of ß-lactamase producing bacteria which secrete
an enzyme that breaks down the ß-lactam ring
of penicillin, rendering it harmless to the
bacteria. These bacteria may remain sensitive to
other ß-lactam antibiotics
• Resistance also arises through modifications to
the bacterial cell wall; this resistance usually
extends to other ß-lactam antibiotics
Methicillin-resistant Staphylococcus
aureus(MRSA)
• It is a strain of the Staphylococcus aureus
that has developed antibiotic resistance ,first
to penicillin since 1947 and later to methicillin
and related anti-staphylococcal drugs and is
now widespread
• MRSA causes as many as 20% of
Staphylococcus aureus infections in
populations that use intravenous drugs
• As of early 2005, the number of deaths in the
UK attributed to MRSA has been estimated by
various sources to lie in the area of 800 to 955
per year
• While an MRSA colonisation in an otherwise
healthy individual is not usually a serious
matter, infection with the organism can be
life-threatening to patients with deep
wounds ,intravenous catheters or as a
secondary infection in patients with
compromised immune system
• The antibiotic of choice for an infected
inpatient is vancomycin given intravenously.
Oral clindamycin may be used in minor soft
tissue infections in outpatients
Drug Interactions
Penicillin should be used with caution if
the patient is taking the following drugs:
• Anti-inflammatories, as these may
compete for elimination and result in
penicillin toxicity
• Oral contraceptives, as penicillin
antibiotics occasionally reduce their
effectiveness
Cephalosporins
• Discovered in the 1940s by Giuseppe
Brotzu, a professor at the University of
Cagliari, Sardinia
• He isolated a fungus called
Cephalosporium acremonium
• One product of this fungus, cephalosporin
C, became the prototype of our current
cephalosporins
Mode of action
As with the penicillins, the cephalosporins
inhibit a series of enzymes, known as
penicillin-binding proteins, that catalyze
important steps in the formation of the
bacterial cell wall
Antimicrobial activity
• They have been grouped into
“generations” on the basis of their general
antimicrobial activity
I-First Generation Cephalosporins
-Cephalexin (Ceporex,Keflex,125*-250-500 mg tab)
-Cephradine (Velosef,Farcocef 125*-,250-500-1000 mg
tab)
-Cefadroxil (Duricef,Curisafe,Ibidroxil,125*-250-500-1000
mg tab)
• The most active of all the cephalosporins against
staph & nonenterococcal streptococci
• Methicillin-resistant S. aureus are usually
resistant to these agents
II-Second Generation Cephalosporins
– Cefprozil (Cefzil, 125*-250-500 mg tab)
– Cefuroxime )Zinnat,Cefumax 125*-250-500 mg tab)
– Cefaclor (Cefaclor,Ceclor,250-500 tab)
• Have increased gram-negative activity, but
decreased gram-positive activity
III-Third Generation Cephalosporins
– Cefotaxime (Claforan,Cefotax, 250-500-1000 mg / vial)
– Ceftriaxone )Rocephin,Cefotrix, 500-1000 mg / vial)
– Cefoperazone (Cefobid,Cefozone 500-1000 mg / vial)
• Demonstrate less activity against grampositive organisms and an increased
spectrum of gram-negative activity
because of greater ß-lactamase stability
IV-Fourth generation cephalosporins:
-Cefepime )Maxipime 500,1000 mg/vial)
-Cefpirome )Cefrom, 500,1000 mg/vial)
• They have a greater spectrum of activity
against gram-positive organisms than the third
generation cephalosporins
• They also have a greater resistance to ßlactamases than the third generation
cephalosporins
Pharmacokinetics
• 1st generation cephalosporins & cefaclor,
are best absorbed from an empty stomach
• First- and second-generation
cephalosporins are excreted primarily by
the kidney. Dosage adjustment is required
for patients with renal insufficiency
• Because of their excellent staph & strept
coverage, the first-generation agents have
proved to be excellent choices for the
treatment of many skin and soft-tissue
infections
• Most comparative studies have not shown
major differences in clinical efficacy of
different cephalosporins in treating skin
infections
• The second-generation agents have been
effectively used to treat cellulitis when the
causative organisms are H. influenzae or
Enterobacteriaceae. They offer no
advantage for the treatment of grampositive aerobic organisms over the firstgeneration agents
• The third-generation agents have also
been used successfully to treat cellulitis,
soft-tissue abscesses, and diabetic foot
ulcers
Adverse effects
• The most frequent adverse reactions to cephalosporins are gastrointestinal
• Skin reaction: urticaria, maculopapular eruptions
and pruritus have been reported in frequencies
varying from 1% to 3%
• Approximately 5% to 10% of patients allergic to
penicillins also will be allergic to cephalosporins
ß-LACTAM ANTIBIOTIC/ßLACtaMASE INHIBITOR
COMBINATIONS
• In 1940, soon after the introduction of
penicillin, Abraham and Chain in Oxford
discovered an enzyme (penicillinase) capable
of inactivating penicillin & later other ß-lactam
antibiotics e.g. cephalosporins; therefore the
name was changed to ß-lactamase
• ß-lactamase inhibitors, when combined with
existing ß-lactam antibiotics, act synergistically
to inhibit ß-lactamases
Formulations available:
• Amoxicillin-clavulanate (Augmentin,
Megamox,Hibiotic,156*-375-625-1000-1200 tab & vial)
• Ampicillin-sulbactam (Unasyn, Unictam,250*-375-7501500 tab & vial)
Antibacterial activity
• In vitro activity is significant for Staph,
Haemophilus, Klebsiella, E. coli, and
Proteus
Pharmacokinetics
• Bioavailability of amoxicillin/clavulanic acid
are unaffected by food
• Serum concentrations are higher and halflives of the combinations are prolonged in
patients with renal impairment, thereby
necessitating dosage adjustments
Dermatologic indications
• Ideally suited for the treatment of serious
infections of the skin and soft tissue when
polymicrobial organisms are suspected
• Amoxicillin/clavulanic acid is the recommended
oral agent after animal or human bites in which
both aerobic and anaerobic organisms may be
pathogens
• These drugs often have no advantage for
infections caused by single pathogens
Adverse effects
• Gastrointestinal complaints are common, with
diarrhea occurring more frequently with use of
amoxicillin/clavulanic acid (10%)
• Sulbactam has been associated with pain at the
intramuscular injection site, usually lasting 5
minutes to 1 hour. To minimize this, the powder
may be diluted with lidocaine before injection
MACROLIDES
• Erythromycin(Erythrocin,Erythrocid,Erythrin, 200*-250-500 tab) ,
the prototype of the macrolide antibiotics, was
isolated in 1952 from the metabolic products of a
strain of Streptomyces erythreus obtained from the
soil samples in the Philippines
• The new macrolides are:
-Clarithromycin (Klacid,125*-250-500 tab)
- Azithromycin (Zithromax,Azrolid,Zisrocin ,200*-250-500 tab)
Mode of action
They penetrate the cell walls of
susceptible bacteria and reversibly bind to
the 50S subunit of the ribosome, inhibiting
RNA-dependent protein synthesis
•
•
•
•
Antibacterial activity
In vitro, clarithromycin is generally equivalent to
or 2-4 fold more potent than erythromycin
against gram +ve organisms such as Staph &
Strept
In contrast, the activity of azithromycin against
gram +ve organisms is 2-4 fold less active than
erythromycin
Clarithromycin and azithromycin possess
increased activity against several gram -ve
pathogens
Azithromycin is 4-8 times more potent than
erythromycin against Mycoplasma
Pharmacokinetics
• Erythromycin has an erratic oral
bioavailability.The major advantage offered
by the new macrolides is their consistent
oral bioavailability
• Clarithromycin is well absorbed, with or
without food.The absorption of
azithromycin is decreased with food and
should be taken 1 hour before or 2 hours
after a meal
• Clarithromycin is extensively metabolized
and cleared by the kidney. As renal
function declines, the half-life increases.
Therefore, dosage modifications are
recommended in patients with severe
renal impairment
• Only 20% of azithromycin is excreted
unchanged in the urine, so dosage
adjustments in patients with renal
impairment are not necessary
Dermatologic indications
• Azithromycin was compared with
erythromycin in 82 patients with pyoderma,
abscess, infected wound, ulcer, or
erysipelas.S. aureus was the most common
pathogen
• The dose of azithromycin was 1 gm on day
1, followed by 250 mg every day for 4 days
compared with erythromycin 500 mg every 6
hours
• Clinical response rates were 86% for patients
receiving azithromycin and 82% for patients
receiving erythromycin
• In a randomized trial of 146 patients with mild to
moderate skin infections, clarithromycin 250 mg
taken twice daily was compared with oral
erythromycin 250 mg four times a day for 7 to 14
days.The most frequently isolated organisms were
S. aureus and S. pyogenes
• Clinical success was seen in 96% of the
clarithromycin-treated patients compared with 94%
in erythromycin-treated patients
Drug interactions
• Erythromycin & Clarithromycin inhibit the
hepatic cytochrome P- 450 enzyme system
leading to a decrease in the metabolic
clearance of several drugs e.g. theophylline,
phenytoin, digoxin, warfarin, nonsedating
antihistamines , and methylprednisolone
• Azithromycin does not affect the cytochrome
P- 450
Adverse effects
• Nausea, abdominal pain and diarrhea
•
• Azithromycin and clarithromycin
appear to be well tolerated. Both cause
fewer adverse gastrointestinal
reactions (approximately 3% of
patients) than erythromycin )5.8%)
FLUOROQUINOLONES
• The first quinolone, nalidixic acid, was
introduced in 1962
• It had numerous clinical limitations, such
as rapid emergence of resistance, narrow
spectrum of activity, and frequent side
effects
• However, the introduction of a fluorine
atom resulted in second-, third-, and
fourth-generation fluoroquinolones, which
have improved coverage of gram-positive
organisms
Quinolone generations
I-First generation:Nalidixic acid (Nalidram,500 tab)
II-Second generation:
Lomefloxacin (Lomex,Lomeflox,400 mg tab)
Norfloxacin (Noroxin,Epinor, 400 mg tab)
Ofloxacin (Tarivid,Ofloxacin, Kirol,200 mg tab)
Ciprofloxacin(Ciprobay,Ciprofloxacin,Mifoxin,Serviflox,R
ancif,Ciprofar,250-500-750 tab)10 generics
III-Third generation:
Levofloxacin (Tavanic,Leoxin,Unibiotic,150-500 mg tab)
Sparfloxacin (Sparcin,Spara,200 mg tab)
Gatifloxacin (Tequin,400 mg tab or vial)
Moxifloxacin (Avalox,400 mg tab)
IV-Fourth generation:
Trovafloxacin (Trovan tab & vial not available in Egypt)
Mode of action:
• Inhibition of bacterial DNA gyrase resulting
in the interference of DNA replication
Antimicrobial activity
•As a group, they have adequate activity
against methicillin-sensitive and methicillinresistant S. aureus, levofloxacin is the most
active
•Levofloxacin and is more active against
streptococcal species compared with the
other fluoroquinolones
• Ciprofloxacin, ofloxacin, and levofloxacin are
active against Mycobacterium spp., including M.
tuberculosis
• Ofloxacin is also active against Chlamydia
trachomatis and U. urealyticum
• The fluoroquinolones show no appreciable
activity against anaerobic bacteria
Pharmacokinetics
• The fluoroquinolones are mainly excreted
renally. Therefore, in patients with
impaired renal function dosage
adjustments are necessary
Dermatologic indications
• Fluoroquinolones achieve appropriate
concentrations in the skin and its
appendages, making them ideal agents for
the treatment of severe skin infections
caused by multiresistant gram-negative
bacteria such as abscesses, cellulitis,
ulcers and wound infections
Drug interactions
• All fluoroquinolones show a significant decrease
in absorption , when they are administered
together with aluminum-, magnesium-, and
calcium-containing antacids and iron- and zinccontaining products . These drugs should be
taken at least 2 hours after the administration of
the fluoroquinolone
• May increase caffeine, cyclosporine,
theophylline and warfarin level
• May prolong QT if used concomitantly
with antiarrhythmics
• May increase risk of CNS stimulation and
convulsions if used concomitantly with
nonsteroidal anti-inflammatory drugs
• May lead to hypoglycemia and/or
hyperglycemia if used with antidiabetics
Adverse effects
• In animals, fluoroquinolones impair cartilage
formation; therefore the routine use of these
agents is not recommended for children or for
pregnant or nursing mothers
• The most common adverse reactions are
nausea, abdominal discomfort, vomiting,
diarrhea, mild headache, dizziness, agitation,
and sleep disturbances
Dosing
• The recommended total daily doses:
norfloxacin, 800 mg; ciprofloxacin, 500 to
1500 mg; ofloxacin, 400 to 800 mg;
lomefloxacin, 400 mg; and levofloxacin,
500 mg
RIFAMYCINS
• The rifamycins were first isolated in 1957
from a soil isolate, Nocardia mediterranei
• The substance was nicknamed Riffi after the
title of a then popular French movie, “LeRiffi.”
•
• Mode of action
• Rifamycins inhibit bacterial RNA synthesis by
interacting directly with RNA polymerase.
Mammalian RNA polymerases are not
affected
Types of Rifamycins
• Rifampin or rifampicin (Rimactan,
Rifadin,Rifactin2%*-150-300 mg cap)
• Rifabutin (Ansamycin,Not available in Egypt) is used
to treat M. avium in AIDS
Antimicrobial activity
• Rifampin is active against
staphylococci (both coagulasenegative[comensals] and
coagulase-positive) strains
• It is not particularly active against aerobic gramnegative bacilli E.coli
•
•
•
•
Pharmacokinetics
Absorption is impaired if the drug is taken
during or right after a meal. Food with a high
fat content can interfere with absorption
Rifampin has good penetration into
abscesses and can enter living phagocytes
and kill intracellular bacteria
Rifampin is metabolized by the liver. Its halflife is prolonged in patients with hepatic
disease. The dosage does not need to be
adjusted for renal insufficiency
Rifampin crosses the placenta readily and is
not approved for use in pregnant women
Dermatologic indications
• Cutaneous tuberculosis remains the primary
indication for rifampin therapy
• Rifampin is the only bactericidal drug to M.
leprae. In 15 to 30 days no bacteria can be
found
• Rifampin is bactericidal to gram-ve cocci and
is an excellent agent in treating pyodermas
• Rapid emergence of resistance has been observed
when monotherapy is employed. Therefore rifampin
should only be used in conjunction with another
gram-positive agent
• In a study, patients with recurrent furunculosis in
whom at least three courses of conventional
systemic antistaphylococcal therapy had failed
were given rifampin and cloxacillin for 7 to 10 days;
31 of 32 patients were cured
• Cutaneous leishmaniasis and rhinoscleroma also
respond well to rifampin because it easily
penetrates the cell membrane and attacks
intracellular pathogens
• The usefulness of rifampin in psoriasis
remains controversial
• Rifampin is used in treatment of pruritus in
patients with primary biliary cirrhosis. The
mechanism may be enhanced hepatic
microsomal function that perhaps
accelerates metabolism of pruritogenic
metabolite of bile acids
• Rifampin leads to reduced absorption of
several compounds. Some notable
problems include:
- Decreased efficacy of oral contraceptives
- Decreased prothrombin time in patients
receiving warfarin
- Addisonian crisis in patients taking
glucocorticoids
Adverse effects
• The most obvious inconvenience is orange-red
discoloration of urine and permanent staining of
soft contact lenses
• Rifampin passes into the breast milk. However,
no problems were reported in nursing babies
• Gastrointestinal complaints
• Increased liver function tests
• Hypersensitivity reactions characterized by a flulike syndrome
Dosage
• The recommended daily dosage is usually 10 to
20 mg/kg (600 mg maximum) in a single daily
administration
• The dosage recommended for elimination of
staphylococcal carriage is higher
• For prophylaxis for exposure to Neisseria
meningococcus, the recommended dosage is
600 mg every 12 hours for 2 days
TETRACYCLINES
• Types of Tetracyclines
I-The short-acting agents:
-Oxytetracycline (Oxytetracid,Oxytetrine,250 mg cap)
-Tetracycline (Hostacycline,Tetracid,500 mg cap)
II-The intermediate-acting compound is
demeclocycline(not available in Egypt)
III-The long-acting compounds:
-Doxycyline (Vibramycin,Farcodoxin,Tolexin,Doxy,100 mg cap)
-Minocycline (minocine,50-10 mg tab)
Mode of action:
Inhibition of protein synthesis by binding
to the 30S ribosomal subunit
Pharmacokinetics
• The tetracyclines are better absorbed in the
fasting state except for doxycycline and
minocycline
• Absorption of tetracyclines is impaired by the
concurrent ingestion of dairy products, aluminum
hydroxide gels, calcium, magnesium, iron or zinc
salts
• Both doxycycline and minocycline are lipid
soluble, allowing superior tissue penetration
• The tetracyclines, except doxycycline, should
not be used in patients with renal failure as
renal failure prolongs the half-life of most
tetracyclines except doxycycline
• These drugs should be used cautiously in
patients with hepatic failure because of
potential hepatotoxicity
Dermatologic indications
• The major use of tetracycline has been for the
treatment of acne. These drugs inhibit P. acne
• Tetracycline is also used in the treatment of acne
rosacea and perioral dermatitis
• Less conventional uses for the tetracyclines
include the combination of tetracycline and
nicotinamide for treatment of bullous
pemphigoid, dermatitis herpetiformis and linear
IgA bullous dermatosis
Nondermatologic indications
• Chlamydia nonspecific urethritis,
lymphogranuloma venereum and as an
alternate therapy for primary syphilis
Drug interactions
• Tetracyclines potentiate the effects of oral
anticoagulants
• Barbiturates, phenytoin, and
carbamazepine decrease the serum halflife and serum concentration of
doxycycline
Adverse effects
• In children brown discoloration of the teeth
and depression of bone growth may occur
so tetracyclines are contraindicated during
pregnancy and in children younger than 9
years of age
• The most commonly described are
epigastric burning, nausea, and vomiting
• The drugs are hepatotoxic, particularly in
patients receiving larger doses
• Tetracycline derivatives can produce mild
to severe phototoxic reactions
• Hypersensitivity reactions have been
described ranging from mild exanthem to
Stevens-Johnson syndrome
TRIMETHOPRIMSULFAMETHOXAZOLE
• In the mid-1970s a combination of
trimethoprim and sulfamethoxazole
became available. It is a fixed dose ratio of
one part trimethoprim (TMP) to five parts
sulfamethoxazole (SMX)
Mode of action
• The two components of this drug provide
sequential inhibition of enzymes involved
in the bacterial (but not human) synthesis
of tetrahydrofolic acid and thereby disrupts
nucleic acid synthesis
Antimicrobial activity
Many gram-positive aerobic cocci are
inhibited by TMP-SMX in vivo. This
includes many S. aureus, S. pyogenes,
and S. viridans
Dermatologic indications
• An alternate choice for treatment of
pyodermas, chancroid, and
lymphogranuloma venereum
• TMP-SMX has been used to treat acne
vulgaris in tetracycline- and erythromycinresistant patients
Drug interactions
• TMP-SMX should be used with caution in
patients taking methotrexate because it
can interfere with folic acid availability
Adverse effects
• Common adverse effects of TMP-SMX are
gastrointestinal and hypersensitivity
reactions
CLINDAMYCIN
• Clindamycin (Dalacin C, Clindacin,150 mg cap) is a
derivative of lincomycin that has an
increased antibacterial potency and is
better absorbed than its parent
Mode of action
• Clindamycin binds to the 50S portion of
the ribosome and inhibits protein synthesis
by blocking transpeptidation
Antimicrobial activity
• Clindamycin is active against most anaerobic
organisms (including most Propionibacterium),
most gram-positive cocci and certain protozoa
• The spectrum of activity includes many S.
aureus, S. pneumoniae, S. pyogenes (although
increased resistance of this organism has been
increasingly reported)
Pharmacokinetics
• Clindamycin is mainly metabolized in the
liver. Dose adjustment is needed for
patients with severe liver failure
Dermatologic indications
• Clindamycin has been successfully used
to treat many skin and soft-tissue
infections, such as cellulitis, folliculitis,
furunculosis, carbuncles, impetigo,
ecthyma and hidradenitis suppurativa
• Clindamycin is effective at low dose in
preventing recurrent staphylococcal skin
infections
• Clindamycin is used in topical preparations
for the treatment of acne. The risk of
pseudomembranous colitis has limited oral
usage in this condition
Drug interactions
• Clindamycin has been shown to have
neuromuscular blocking properties that may
enhance the action of other neuromuscular
agents (e.g., ether, tubocurarine, pancuronium)
• Antagonism has been observed between
erythromycin and clindamycin in vitro
Adverse effects
• The most serious adverse effect is
pseudomembranous colitis due to Clostridium
difficile toxin. The reported incidence ranges from
0.1% to 10%. Ampicillin and cephalosporins have
been associated with a similar risk
• The most frequently reported adverse effect to
clindamycin is a generalized morbilliform eruption
• Other gastrointestinal side effects include anorexia,
nausea, vomiting, diarrhea, and elevated
hepatocellular enzymes
Dosage
• The usual adult oral dosage of clindamycin
is 150 to 450 mg every 6 hours
• Acne vulgaris has been treated with 150
mg every 12 hours
NEW ANTIBIOTICS
1-LINEZOLID
• Linezolid (Zyvox) has been approved by
the FDA in April 2000
• Linezolid is a synthetic antibiotic belonging
to a new class of antimicrobials called the
oxazolidinones
Mode of Action
• Linezolid disrupts bacterial growth by binding to
50 S ribosomal subunit inhibiting the initiation
process in protein synthesis
• Linezolid is bacteriostatic against enterococci
and staphylococci, and bactericidal for the
majority of streptococci
Pharmacokinetics
• Linezolid is highly absorbed when
administered orally & not affected by food
• This allows conversion from intravenous to
oral therapy as soon as the patient is
clinically stable; thus, it provides an
advantage over comparative therapy that can
be delivered only parenterally e.g.
vancomycin
• Linezolid is metabolized via hepatic
oxidation
• Presently, no dosage adjustment is
recommended for patients with renal
insufficiency; however, linezolid is
removed by hemodialysis and should be
administered following dialysis
Antimicrobial activity
• Gram-positive infections in adult patients
• Other pathogens include penicillin-resistant S.
pneumoniae, vancomycin-sensitive E. faecalis,
vancomycin-resistant E. faecalis, methicillinsusceptible Staphylococcus epidermidis and
methicillin-resistant S. epidermidis,
Corynebacterium
• It is recommended that coverage for gramnegative organisms be added when indicated
• The safety,efficacy& dosage have not been
established in children younger than 18 years
Adverse Effects
• Two % of patients have the following: rash,
headache, diarrhea, nausea, vomiting, insomnia,
constipation and fever
• FDA has recently reported cases of
myelosuppression
• Price Zyvox (linezolid) 600mg
20 tablets
$1,168.77
Comparitive studies
Linezolid X Clarithromycin
Cure rate
91%
93%
Linezolid X Vancomycin
Cure rate
73.2%
73.1%
• Dosing
• The dosage regimen for linezolid is 400 mg
or 600 mg every 12 hours for a duration of to
28 days, with an intravenous or oral route of
administration, based on the indication
• The 400-mg dose is approved for
uncomplicated skin infections; however,
because many other antibiotic therapies are
available, the use of linezolid for this
indication should be discouraged in order to
reduce the potential for developing bacterial
resistance
2-QUINUPRISTIN-DALFOPRISTIN
(SYNERCID)
• It was approved by the FDA in September
1999
• Quinupristin-dalfopristin is a streptogramin
antibiotic produced by Streptomyces
pristinaepiralis
• It is available in an IV form only
Mode of action
• The combination of quinupristin and
dalfopristin is synergistic, and is generally
bactericidal
• The main target is the bacterial 50S
ribosome, with the formulation acting to
inhibit protein synthesis
Pharmacokinetics
• It is eliminated mainly by the liver
• Quinupristin-dalfopristin demonstrates a
prolonged postantibiotic effect, which is the
phenomenon of continued suppression of
bacterial growth after serum levels have fallen
below the minimum inhibitory concentration.The
duration of this effect may be up to 10 hours
Drug Interactions
• The plasma levels of some drugs will be
raised e.g. cyclosporin, methylprenisolone
& diazepam
Adverse Reactions
• Pain and inflammation at the infusion site are
common but require discontinuation of treatment
in fewer than 10 percent of patients
• The most common side effects of quinupristindalfopristin have been arthralgias (9 %) and
myalgias (6 %)
• A 500-mg vial of quinupristin-dalfopristin
costs approximately $107
Antimicrobial activity
Results obtained in treating
complicated skin in fections:
• Quinupristin and dalfopristin:68%
• Vancomycin:71%
• Cephazolin:71%
Dosage:
• The recommended infusion volume and
duration is 250 mL given over 60 minutes
3-DAPTOMYCIN
Cubicin
• It was Approved by the FDA in September
2003
• It is derived from the fermentation of
Streptomyces roseosporus
Mode of action
• Rapid depolarization of bacterial cell
membrane due to K efflux and that this
associated with a disruption of DNA, RNA
and protein synthesis resulting in death
Antibacterial activity
• Gram positive organisms even if they
MRSA or VRSA
• It is NOT active against Gram negative
organisms
Pharmacokinetics
• IV administration only
• 78% excreted via kidney
• Reduce dose for patients with creatinine
clearance <30 ml/min
• significant post antibiotic effect
Dermatological indications
• Complicated skin and soft tissue infections
due to susceptible organisms
Adverse effects
• GI effects are the most commonly reported
adverse reactions occurring in 3% to 6%
• Elevations in serum (CPK) were reported
in 3% with no symptoms of myopathy.
Monitor CPK weekly
Dosage
• 4 mg/kg of daptomycin should be
administered over a 30-minute period by
IV infusion once every 24 hours for seven
to 14 days