Transcript Antibiotics - DENTISTRY 2012

Antibiotics
Hamzeh Elayan 2015
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Antibiotics
-chemical substances produced by microorganisms such as fungi, actinomycetes and
bacteria that suppress the growth of other
micro-organisms (Bacteriostatic) or destroy
them (Bactericidal)
-used to treat bacterial infections.
- Ideally, before beginning antibiotic therapy,
the causative organism should be identified
and sensitivity tests to antibiotics should be
determined.
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Selection of Antimicrobial Agent
Empiric therapy
- prior to identification of organism in critically ill patients
Prophylactic therapy
treatment with antibiotics to prevent an infection, as in
intra-abdominal surgery
Organism’s susceptibility to the antibiotic
Patient factors
-hypersensitivity, renal/hepatic function, age, pregnancy
Effect of site of infection on therapy
–blood brain barrier
Safety of the agent
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Cost of therapy
Chemotherapeutic Spectra
Narrow-spectrum Antibiotics:
Act on a single / limited group of micro-organisms; e.g.,
isoniazid given for mycobacterium
Extended-spectrum Antibiotics:
Effective against gram-positive organisms and a significant
number of gram-negative organisms; e.g., ampicillin
Broad-spectrum Antibiotics:
Effective against a wide variety of microbial species; e.g.,
tetracycline & chloramphenicol.
Used for infections of unknown origin
Can alter the nature of intestinal flora = super infection
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Combinations of Antimicrobial Drugs
Advantages
Synergism; the combination is more effective
than either drug used separately; betalactams and aminoglycosides
Disadvantages
Bacteriostatic (tetracycline) drugs may interfere
with bactericidal ( penicillin and cephalosporin)
drugs
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Complications of Antibiotic Therapy
Resistance –
inappropriate
use of
antibiotics
Hypersensitivity
– penicillin
Direct toxicity –
aminoglycosids
= ototoxicity
Super infections – broad spectrum antimicrobials
cause alteration of the normal flora; often difficult to treat.
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Drug Resistance
1. Alteration of the target site
methicillin resistance among
Staphylococcus aureus.
2. Enzyme inactivation
Some bacteria secrete beta- lactamase enzyme which
destroys the beta lactam ring, rendering beta-lactam
antibiotics ineffective (penicillins & cephalosporins).
Solution - add clavulanic acid - a beta- lactamase
inhibitor
3. Active transport of the antibiotic out of the bacterial
cell (efflux pumps) tetracyclines, macrolides, &
quinolones
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4. Decreased permeability
Alteration in the proteins that form channels in the
bacterial cell membrane
– Resistance of Pseudomonas aeruginosa to
penicillins & cephalosporins
Decreased Permeability of the Drug Prevents the
drug reaching the target penicillin binding
proteins (PBPs)
Presence of an Efflux pump also reduces the
amount of the intracellular drug
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Classification of antibiotics according to
mechanisms of action.
1. Inhibiton of bacterial cell wall.
Penicillin & cephalosporin (structurally similar).
Cycloserine, vancomycin
2. Agent affecting cell membrane permeability leading to
leakage of intercelluar compounde. Polymyxin,
3. Inhibition of protein synthesis. Chloramphenical,
Tetracycline, Erythromycin, Clindamycin,
Aminoglycosides.
5. Affecting bacterial nucleic acid metabolism. Rifampin
& the quinilones.
6 . Interfering with folate metabolisum.
trimethoprim& sulfonamide.
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Cell wall inhibitors
Interfere with synthesis of the
bacterial cell wall
(mammalians cells do not have it).
Cell wall inhibitors require actively proliferating
(multiplying) microorganism.
The cell wall inhibitors include :
Penicillins, Cephalosporins,, Monobactams,
Carbepenems, and Vancomycin.
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Penicillins
From mould penicilium notatum
Bactericidal
The safest & most commonly used.
Mechanism: Inhibiting cell wall synthesis.
Natural penicillin
Benzylpenicillin (Penicillin G)
Destroyed by stomach acid. Given IM or IV.
Active against: most gram-positive bacteria with the
exception of penicillinase-producing S. aureus
- most Neisseria species and some gram-negative
anaerobes
- Not active against most gram-negative aerobic organisms
Pinicillin G is inactivated by β-lactamase (Penicillinase).
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Penicillin G clinical uses
Streptococcal infections that include pneumonia,
otitis media, meningitis, and septic arthritis.
Also effective against:
Neisseria meningitidis
N. Gonorrhea
Clostridium tetani
diphtheria
syphilis
Listeria monocytogenes
(anaerobic causes food poisoning)
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Benzathine penicillin
Long acting, IM once every 3–4 weeks
A single IM injection of 1.2 million units, is effective
treatment for beta–hemolytic streptococcal
pharyngitis, it prevents re-infection.
Also prophylactic.
Prevents reoccurrence of rheumatic fever.
Benzathine penicillin G, 2.4 million units IM once a
week for 1–3 weeks, is effective in the treatment of
syphilis.
Also prophylactic.
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Phenoxymethylpenicillin (Penicillin V)
Acid stable, orally active.
less potent than penicillin G.
Penicillin V often employed in the treatment of oral
infection, effective against some anaerobic organism.
•Penicillin V is the most frequently prescribed antibiotic
for oral infections.
It is the first choice in the treatment of odontogenic
infections.
- post extraction infection
- pericoronitis and
- salivary gland infection
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Penicillinase -resistant Penicillins
Methcillin (Not available), Oxacillin, Cloxacillin,
Narrow spectrum, well-absorbed orally.
• Antibacterial spectrum is the same as for penicillin G,
but less potent.
•Their use is restricted to treatment of infections caused
by penicillins -resistant bacteria.
Many Staphylococci are now resistant to them.
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Extended Spectrum Penicillins
Ampicillin, fairly well absorbed orally.
Amoxicillin, prodrug to ampicillin very well absorbed.
Their antibacterial spectrum is the same as for penicillin
G plus some Gram-negative bacteria.
Most useful antibiotics for treating children suffering
from sensitive gram-negative aerobic bacteria,
enterococci, and β-lactamase-negative H. influenzae.
widely used in the treatment of respiratory infections.
Used orally to treat urinary tract infections, sinusitis,
otitis, and lower respiratory tract infections.
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Broad Spectrum Penicillins
Carbenicillin, Ticarcillin, and Piperacillin.
Very poorly absorbed from the gut.
They are susceptible to β- lactamases.
Antibacterial spectrum is the same as the extended
spectrum drugs plus pseudomonas.
Ticarcillin is more potent against pseudomonads ,
available with clavulanic acid.
P aeruginosa develops resistance during treatment, so a
penicillin is frequently used in combination with an
aminoglycoside or fluoroquinolone .
Used in the treatment of urinary tract, lung, and
bloodstream infections caused by ampicillin -resistant
enteric gram-negative pathogens (e.g. E. coli).
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Unwanted effects
-hypersensitivity reactions (main side-effects)
- Alter bacterial gut (GI disturbances, diarrhea).
(More with extended spectrum).
- All Penicillins, particularly Methicillin, have the
potential to cause acute nephritis, thus Methicillin is
no longer available.
- All oral penicillins are best given on an empty
stomach to avoid the absorption delay. Exception
amoxicillin.
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Cephalosporins
β- lactam antibiotics
isolated from a strain of Streptomyces.
large number (70) available for clinical
use, termed first- second- third- fourth generations.
First-generation are active against Gram(+) bacteria,
and successive generations have increased activity
against Gram(-) bacteria with reduced activity against
Gram-positive organisms.
Bactericidal and work in the same way as the penicillins by
interfering with the cell-wall.
Only a few cephalosporins are administered orally ,
e.g. cephalexin, most are administered IM or IV.
Their t½ are short & excreted in the urine.
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First Generation
Cephalexin
Cefazolin
effective orally
IV, IM
Effective against the same gram-positive organisms
affected by penicillin G plus some Gram (-) bacteria
(Proteus, E.coli and Klepsiella pneumonia).
Excellent agents for skin and soft tissue infections
caused by S. aureus and S. pyogenes.
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Second generation
Cefaclor Cefoxitin Cefuroxime
Less effective against gram positive bacteria.
Effective against H influenza, Entreobacter
aerogenes and Nesseria sp.
Some agents (cefoxitin) also active against the
Bacteroides fragilis so can be used to treat mixed
anaerobic infections such as peritonitis.
Cefuroxime is used to treat community-acquired
pneumonia because it is active against beta-lactamaseproducing H influenzae or K pneumoniae and penicillinresistant pneumococci.
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Third Generation
Ceftazidime , Ceftriaxone, Cefotaxime
Cefoperazone
Relatively weak against gram-positive but more potent
against gram-negative bacteria including beta-lactamase producing Enterobacteriaceae.
•some agents (ceftazidime and cefoperazone ) also is
active against Pseudomonas aeruginosa.
The third-generation, with or without aminoglycosides, are
the drugs of choice for serious infections caused by
Klebsiella, Enterobacter, Proteus, Serratia, and
Haemophilus spp.
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Ceftriaxone and cefotaxime
-are the most active cephalosporins against
penicillin-resistant strains of pneumococci and are
recommended for empirical therapy of serious
infections that may be caused by these strains.
- Ceftriaxone is the therapy of choice for all forms
of gonorrhea and for severe forms of Lyme disease
(caused by Borrelia sp. transmitted via the bite of an
infected tick.
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Fourth generation
Cefepime
developed to fight against the resistant gramnegative bacteria.
Cefepime has an extended spectrum of activity
compared with the third generation.
indicated for the empirical treatment of nosocomial
infections
particularly useful when gram-positive bacteria,
Enterobacteriaceae, and Pseudomonas are potential
etiologies.
Cross blood-brain barrier and are effective in
meningitis.
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Adverse Effects
Hypersensitivity, cross resistance with penicillin.
GI system- Nausea, vomiting, diarrhea, anorexia,
abdominal pain and flatulence are common effects.
CNS – headache, dizziness, lethargy and paresthesias.
Drug-Drug interactions
Aminoglycosides, if given with cephalosporins may
increase the risk of kidney toxicity
Anti-coagulants- may experience increased bleeding
tendencies
ALCOHOL- many patients experience a disulfiram -like
reactions. This may occur even up to 72 hours of
cephalosporin discontinuance.
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Carbapenems
imipenem, and meropenem
Broad spectrum β-Lactam antibiotics
Highly resistant to most β-lactamases.
Imipenem has a wide spectrum against many gramnegative rods, including Pseudomonas aeruginosa,
gram-positive organisms, and anaerobes.
Carbapenems are one of the antibiotics of last
resort for many bacterial infections, such as E. coli
and klebsiella pneumoniae.
Recently, alarm has been raised over the spread of
drug resistance to carbapenem antibiotics due to
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production of carbapenemases
Imipenem is inactivated by dehydropeptidases in renal
tubules, so administered with cilastatin (inhibitor of
renal dehydropeptidase) for UTI.
A carbapenem is indicated for infections caused by
organisms that are resistant to other drugs, e.g.,
P aeruginosa, and for treatment of mixed aerobic and
anaerobic infections.
A carbapenem is the beta-lactam antibiotic of choice for
treatment of enterobacter infections because it is
resistant to destruction by the lactamase .
side-effects
Nausea and vomiting been the most frequently
At high doses neurotoxicity can occur.
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Vancomycin
A glycopeptide antibiotic, naturally occurring made
by the soil bacterium first isolated in 1953.
Bactericidal, acts by inhibiting cell wall synthesis.
Active only against gram-positive bacteria,
particularly staphylococci.
primarily used for of serious infections caused by
Gram-(+) bacteria resistant to other antibiotics.
Not absorbed, given by slow IV (over 60 min).
to avoid pain & thrombophlebitis
and to avoid an infusion reaction
known as the red man syndrome
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first-line treatment for complicated skin
infections, bloodstream infections, endocarditis,
bone and joint infections, and meningitis infections
caused by methicillin-resistant S. aureus.
Oral vancomycin is is used for intestinal infection
with Clostridium difficile, a common side effect of
treatment with broad-spectrum antibiotics.
Unwanted effects:
fever, rashes and local phlebitis.
Ototoxicity and nephrotoxicity can occur
Hypersensitivity reactions are occasionally
encountered.
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Monobactams
Aztreonam
β- lactam antibiotic, activity is limited to aerobic
gram-(-) rods (including pseudomonas).
No activity against gram (+) bacteria or anaerobes.
Resistant to most β -lactamases.
•Penicillin-allergic patients tolerate aztreonam
used to treat serious infections such as pneumonia,
meningitis, and sepsis caused by gram-(-) bacteria.
Side-effects: similar to other β -lactam antibiotics.
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Protein Synthesis Inhibitors
All protein synthesis inhibitors
are bacteriostatic, except aminoglycosides
Chloramphenicol is bacteriostatic
but bactericidal against certain organisms.
Because of overuse,
resistance is common.
Mechanism:
Combine with the bacterial
ribosomes & interferes with
m-RNA ribosome
combination
which ultimately prevents
protein synthesis.
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TETRACYCLINES
Doxycycline, Minocycline, Tetracycline
Mechanism of action
Bind to both mRNA & the ribosomal
30S subunit where they prevent the
binding of aminoacyl-tRNA.
By this mechanism, bacterial protein
synthesis is inhibited
•Bacteriostatic not bacteriocidal.
Spectrum of activity is very wide and includes Gram-(+)
and Gram-(-) bacteria, some spirochaetes & some
protozoa (amoebae).
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Resistance is common and is mainly due to a plasmidmediated efflux pump.
Mutations in the tetracycline
target site are also found.
Administered orally but can
be given parenterally.
Absorption from the gut is
irregular and better in the
absence of food.
Tetracyclines chelate di - and
tri- valent metal ions, forming insoluble complexes, so
absorption is decreased in the presence of milk,
certain antacids & iron preparations.
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Tetracyclines, con.
Tetracyclines are the drugs of choice for:
-Cholera
-Chlamydia infection
-Rocky mountain spotted fever caused by Rickettsia
-Lyme disease caused by Borrella.
-Mycoplasma pneumoniae which causes community
acquired pneumonia
-A tetracycline in combination with aminoglycoside is
indicated for brucellosis
-used in combination regimens to treat gastric and
duodenal ulcer disease caused by Helicobacter p
-Treatment of Acne
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Tetracyclines, con.
-Tetracycline is occasionally used in Dentistry to
treat bacterial infections.
-It concentrates in the gingival fluids around the
teeth so it is often used to treat gingivitis and gum
disease.
-it is one of the first choices for the
treatment of ANUG (Acute necrotizing
ulcerative gingivitis )
Which appears with stress.
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Tetracyclines, con.
Doxycycline and Minocycline
Prescribed for up to two weeks for different types of
periodontal (gum) diseases, including juvenile
periodontitis.
Doxycycline even in very low doses can inhibit
collagenase enzyme which breaks down collagen, and
patients taking doxycycline can have fewer infections
in skin and gum.
Doxycycline , prescribed in a low dosage for up to nine
months as an adjunctive therapy to dental scaling to
shrink periodontal pockets and to arrest bone loss in
adults with periodontal disease.
The typical dose is 20 milligrams twice each day.
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Tetracyclines, con.
Side Effects:
Most Common: GI disturbances (irritation) &
modification of gut flora, causing Suprinfection
& Candida infections (common)
Deposited in growing bones & teeth, causing staining
& sometimes dental hypoplasia & bone deformities.
Phototoxicity: to sun or ultra-violet rays.
Not given to children, pregnant women or nursing
mothers. (may causes hepatotoxicity in pregnant
women).
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Chloramphenicol
Broad-spectrum antibiotic.
Active not only against bacteria, but also against other
microorganisms, such as Rickettsia.
Bactericidal or (more commonly) bacteriostatic,
depending on the organism.
Due to its toxicity, its use is
restricted to life-threatening
infections for which no
alternatives exist.
Mechanism of action
Binds to the bacterial 50S ribosomal subunit and
inhibits bacterial ribosomal and, to a lesser extent,
mammalian mitochondrial protein synthesis.
Pharmacokinetics
IV or orally. widely distributed ,enters CSF.
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Chloramphenicol, cont..
Chloramphenicol is indicated for:
-Ampicillin-resistant H. influenzae infections.
-Patients allergic to penicillin with pneumococcal,
meningococcal or H. influenzae meningitis
-treatment of brain abscess and other severe
anaerobic infections (excluding endocarditis) due to
Bacteroides fragilis
Resistance
-reduced permeability, mutation of the 50S ribosomal
subunit, the presence of an R factor that codes for an
acetyl coenzyme A transferase. This enzyme
inactivates chloramphenicol.
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Adverse Effects
Chloramphenicol, cont..
Clinical use limited to life threatening infections
because of serious side effects
GI upsets,
Overgrowth of Candida albicans
Anaemias – hemolytic anemia
Aplastic anemia, rare and usually fatal. Aplastic
anemia is independent of dose and may occur after
therapy has ceased.
Gray baby syndrome – poor feeding, depressed
breathing, cardiovascular collapse, cyanosis &
Bone Marrow depression
Interactions – blocks the metabolism of warfarin,
phenytoin, tolbutamide & chlopropamide = increased
effects of the drugs
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MACROLIDES
A group of antibiotics with a
macrocyclic lactone structure
to which one or more deoxy sugars are attached.
Erythromycin was the first of these drugs, as an
alternative to penicillin in individuals allergic to β lactam antibiotics.
The newer members of this family
clarithromycin, azithromycin & Telithromycin
All are well absorbed orally.
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macrolides cont.
Mechanism of action
macrolides bind irreversibly
to a site on the 50S subunit
of the bacterial ribosome,
thus inhibiting the
translocation steps
of protein synthesis.
Bacteriostatic, they may be bactericidal at higher doses.
Antibacterial spectrum
Erythromycin:
Effective against the same organisms as penicillin G ,
therefore, it may be used in patients who are allergic to
the penicillins.
Orally as enteric-coated tablets or esterified form.
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macrolides cont.
Clarithromycin:
spectrum of antibacterial
similar to erythromycin, but it is also effective
against Haemophilus influenzae.
Its activity against intracellular pathogens,
such as Chlamydia, Legionella, Moraxella, and
Ureaplasma species and Helicobacter pylori, is
higher than that of erythromycin.
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macrolides cont.
Azithromycin:
less active against streptococci & staphylococci than
erythromycin.
azithromycin is far more active against respiratory
infections due to H. influenza and Moraxella
catarrhalis.
Azithromycin is now the preferred therapy for
urethritis caused by Chlamydia.
Also used for:
Respiratory track infection.
Urinary track infection & Otitis media
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macrolides cont.
Telithromycin
Antibacterial spectrum similar to that
of azithromycin.
The structural modification neutralizes
the most common resistance
mechanisms (methylase -mediated
and efflux-mediated) that make
macrolide ineffective.
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macrolides cont.
Resistance
most strains of staphylococci are resistant
Several mechanisms have been identified:
1) Efflux pump limit the amount of intracellular drug.
2) Decreased affinity of the 50S ribosomal subunit
due to methylation of an adenine in ribosomal RNA.
3) The presence of a plasmid-associated
erythromycin esterase.
Both clarithromycin and azithromycin show crossresistance with erythromycin, but telithromycin
can be effective against macrolide-resistant
organisms.
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macrolides cont.
Adverse effects
1. Epigastric distress: common
Clarithromycin and azithromycin better tolerated
but GI problems are their most common side
effects.
2. Cholestatic jaundice: Erythromycin estolate is
associated with reversible hepatotoxicity in pregnant
women
3. Ototoxicity: Transient deafness with erythromycin,
especially at high dosages.
4. Contraindications: Patients with hepatic
dysfunction because these drugs accumulate in the
liver.
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Aminoglycosides
Amikacin, Gentamicin,
Tobramycin, & Neomycin.
Gentamicin
Were the mainstays for treatment of serious infections
due to aerobic gram-negative bacilli.
serious toxicities, replaced to some extent by safer
antibiotics, such as the third- and fourth-generation
cephalosporins, the fluoroquinolones, and the
carbapenems.
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aminoglycosides cont.
Bactericidal
protein synthesis
inhibitor
Bind to the ribosomal 30S
Subunit, inhibit initiation
of peptide synthesis and
cause miss-reading of
the genetic code.
Effective against many aerobic Gram-negative
and some Gram-positive bacteria,
Their greatest use against Gram-negative enteric
organisms & in sepsis.
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aminoglycosides cont.
Antibacterial spectrum
Effective in combination for the empirical treatment of
infections suspected of being due to aerobic gramnegative bacilli, including Pseudomonas aeruginosa.
synergistic effect when combined with vancomycin, or a
drug active against anaerobic bacteria.
The aminoglycosides are effective only against aerobic
organisms because strict anaerobes lack the oxygenrequiring drug transport system.
Aminoglycosides may only be used as monotherapy for
urinary tract infections (UTIs).
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aminoglycosides cont.
Resistance
Resistance caused by
1) decreased uptake of drug
2) plasmid-associated synthesis
of enzymes that inactivate
aminoglycoside antibiotics.
Amikacin is less affected by these enzymes
Pharmacokinetics
Not absorbed. Not metabolized, all aminoglycosides (except
neomycin) must be given parenterally
Because of severe nephrotoxicity associated with neomycin its
current use is limited to topical application for skin
infections or orally to prepare the bowel prior to surgery.
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aminoglycosides cont.
The bactericidal effect of aminoglycosides is concentration
and time dependent, the greater the concentration of drug,
the greater the rate at which the organisms die.
Also have a post antibiotic effect. One dose/day adequate.
Distribution: Concentrations in CSF are inadequate.
Except for neomycin, the aminoglycosides
may be administered intrathecally or
intraventricularly.
All aminoglycosides cross the placental barrier and may
accumulate in fetal plasma and amniotic fluid.
Fate: Not metabolized. All are rapidly excreted into the urine.
Accumulation occurs in patients with renal failure
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aminoglycosides cont.
Clinical uses
1) Gram – ve bacillary infection – septicemia, pelvic
& abdominal sepsis
2) Bacterial endocarditis – enterococcal,
streptococcal or staphylococcal.
3) Pneumonias, Tuberculosis
4) Brucellosis
5) Neomycin is used to sterilize the bowel of
patients who receive immunosuppressive therapy,
before surgery.
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aminoglycosides cont.
Gentamycin is the First choice due to low cost,
reliable activity and long experience of use.
Used in infected burns, otitis externals, acute
pyelonephritis
Tobramycin is the most active against Pseudomonas
infections
Amikacin
is the Broadest antibacterial spectrum.
Preferred in serious nosocomial G –ve bacillary
infection in hospitals where Tobramycin &
Gentamycin have developed resistance
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aminoglycosides cont.
Adverse effects
1. Ototoxicity:.
Deafness may be irreversible and affect fetuses in
uterus. Vertigo and loss of balance
2. Nephrotoxicity: mild, reversible renal impairment to
severe, acute tubular necrosis, which can be
irreversible
3. Neuromuscular paralysis: after large IP or
intrapleural doses. Patients with myasthenia gravis
are particularly at risk.
4. Allergic reactions: Contact dermatitis to topically
applied neomycin
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Clindamycin
Antibiotic of of the lincosamide class
Binds to the 50S ribosomal subunit and inhibit the
correct attachment of the amino acid end of
aminoacyl-tRNA.
-treat infections with anaerobic bacteria, but can
also treat protozoal disease, such as malaria.
-tropical treatment of acne
-useful against some methicillin -resistant S.
aureus.
main clinical use in infections caused by
bacteroides and staphylococcal infections of
bones and joints.
.
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Clindamycin is a highly effective when used to fight
dental infections.
It is 90% absorbed & penetrates deeply into the soft
tissues of the body, as well as bone, where dental
infections reside.
used in combination with an aminoglycoside or
cephalosporin to treat penetrating wounds of the
abdomen and the gut;
-Treat infections in the female genital tract, e.g., septic
abortion and aspiration pneumonia.
Side-effects :
GI upsets but its most severe common
adverse effect is Clostridium difficile
associated diarrhea, the most frequent
cause of pseudomembranous colitis.
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FLUOROQUINOLONES
Naladixic acid is the predecessor to all
fluoroquinolones
Mechanism of action
quinolone binds to both
the DNA gyrase enzyme &
the DNA.
This inhibits the resealing step, and cause cell death.
Cross-resistance with other antimicrobial drugs is rare.
Broad spectrum antibiotic active against both Gramnegative and Gram-positive bacteria.
more active against Gram-negative species.
First oral antibiotics effective against gram-negative bacteria.
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Ciprofloxacin is the most commonly used
fluoroquinolone.
Ciprofloxacin most active agent against
gram-negatives, Pseudomonas aeruginosa
in particular
Levofloxacin, and moxifloxacin
improved activity against gram-positive
organisms, particularly S. pneumoniae and
some staphylococci.
used increasingly for treatment of upper and
lower respiratory tract infections.
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Their main uses are:
- complicated urinary tract infections
- respiratory infections
- Infections of soft tissues, bones, and joints and
in intra-abdominal
- bacterial prostatitis and cervicitis
-Also used in bacterial diarrhoea caused by
shigella, salmonella, E. coli.
Side-effects:
mild. GI disorders (nausea, vomiting, and
diarrhea) and skin rashes.
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Sulfonamides
Mechanism of action
sulfonamides are synthetic analogs
of PABA.They inhibit the synthesis
of dihydrofolic acid and the
formation of its essential cofactor
forms.
The sulfa drugs are bacteriostatic.
Antibacterial spectrum
active against Enterobacteria in the urinary tract.
Resistance may be due to
1)an altered dihydropteroate synthetase,
2) decreased cellular permeability to sulfa drugs, or
enhanced production of PABA.
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Sulphonamides are available as:
(1) Oral Absorbable Agents:
Sulfisoxazole and sulfamethoxazole.
almost exclusively to treat urinary tract infections.
(2) Oral Nonabsorbable Agents
Sulfasalazine is widely used in ulcerative colitis,
enteritis, and other inflammatory bowel disease
(3) Topical Agents
Silver sulfadiazine is used for prevention of
infection of burn wounds.
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Side effects:
mild to moderate side-effects including,
nausea, vomiting, headaches, and depression.
More serious side-effects include
hepatitis, hypersensitivity reactions, bone
marrow depression, and aplastic anemia.
Sulfonamides may provoke hemolytic
reactions in patients with glucose-6phosphate dehydrogenase deficiency.
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TRIMETHOPRIM
Antibacterial spectrum similar to sulfonamides.
Trimethoprim compounded with sulfamethoxazole,
producing the combination called cotrimoxazole.
A. Mechanism of action
inhibitor dihydrofolate reductase leading to a
decreased availability of the tetrahydrofolate
coenzymes required for purine, pyrimidine, synthesis.
Antibacterial spectrum
Similar to that of sulfamethoxazole. However, it is
20- to 50-fold more potent than the sulfonamide.
Trimethoprim may be used alone in the treatment of
acute UTIs and in the treatment of bacterial
prostatitis and vaginitis.
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COTRIMOXAZOLE
Combination of trimethoprim with sulfamethoxazole
Greater activity than either drug used alone
Mechanism of action
The synergistic activity results from its inhibition of two
sequential steps in the synthesis of tetrahydrofolic
acid: sulfamethoxazole inhibits folic acid production,
and trimethoprim prevents reduction of dihydrofolate to
tetrahydrofolate.
Effective in UTIs, prostatitis and respiratory tract
infections as well as in ampicillin- or chloramphenicolresistant systemic salmonella infections.
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