LECTURE HANDOUTS
ANTIBIOTICS
IHAB YOUNIS , MD
ANTIBIOTICS
ß-LACTAM ANTIBIOTICS
I-Penicillins
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II-Cephalosporins
1-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 slowrelease 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superseded more and more, whether this is justified or not remains open.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®,Amphpen®125*-250-500 mg)
 It was approved by the FDA in 1963
 Ampicillin is one of the most widely prescribed antibiotics
6-Amoxicillin(Hiconcil,Ibiamox®,Amoxi®l,Emox®, 125*-250-500 mg)
 It is usually the drug of choice within the class because it is better absorbed, following oral
administration, than other ß-lactam antibiotics
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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 of ß-lactam antibiotics
 They inhibit 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
 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 ßlactamase 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
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2-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
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
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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 gram-positive 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 ß- lactamases 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 gram-positive
aerobic organisms over the first-generation 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 cephalo-sporins 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/ß-Lactamase 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*-375-750-1500 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 half-lives 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
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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
3-MACROLIDES
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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
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Azithromycin and clarithromycin appear to be well tolerated. Both cause fewer adverse gastrointestinal
reactions (approximately 3% of patients) than erythromycin )5.8%)
4-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®,400mg tab)
-Norfloxacin (Noroxin®,Epinor®, 400 mg tab)
-Ofloxacin (Tarivid®,Ofloxacin®, Kirol®,200 mg tab)
-Ciprofloxacin(Ciprobay®,Ciprofloxacin®,Mifoxin®,Serviflox®,Rancif®,Ciprofar®,250-500-750 tab)
 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
 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 zinc-containing 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 antiinflammatory 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
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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
5-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®,Rifactin®2%*-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 coagulase-negative[comensals] and coagulase-positive)
strains
 It is not particularly active against aerobic gram-negative 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 half-life 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
Drug interactions
 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 flu-like syndrome
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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
6-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 half-life 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
7-TRIMETHOPRIM-SULFAMETHOXAZOLE
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)
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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 erythromycin-resistant 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
8-CLINDAMYCIN
 Clindamycin (Dalacin
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
C ®,
Clindacin®,150
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9-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, methicillin-susceptible Staphylococcus epidermidis and methicillinresistant S. epidermidis, Corynebacterium
 It is recommended that coverage for gram-negative 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
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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 quinupristin-dalfopristin 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
 mg/kg of daptomycin should be administered over a 30-minute period by IV infusion once every 24
hours for seven to 14 days
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