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ANTIBIOTICS

Satarkulova A.M.

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ANTIBIOTIC
a substance produced by a
microorganism that, at low
concentrations, inhibits or kills other
microorganisms.
All antibiotics are antimicrobials, but
not all antimicrobials are antibiotics.

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ANTIBIOTICS
Medications used to treat bacterial
infections
Ideally, before beginning antibiotic
therapy, the suspected areas of
infection should be cultured to
identify the causative organism and
potential antibiotic susceptibilities.

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TYPES OF BACTERIA
Aerobic bacteria needs O2 to
survive
Anaerobic bacteria

survives in the absence of O2

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BACTERIA SHAPES

(a) Round cocci


(b) Rod-like bacilli
(c) Spiral-shaped spirochetes

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GRAMS STAIN RESULTS AND
RELATED DISEASES
Shape Grams Bacteria Related
Stain Disease

rods gram-positive Corynebacteria endocarditis

gram-negative E. Coli UTI


GRAMS STAIN RESULTS AND
RELATED DISEASES
Shape Grams Stain Bacteria Related
Disease

cocci gram-positive Staphylococcus toxic shock


syndrome

gram-negative Neisseria gonorrhea


GRAMS STAIN RESULTS AND
RELATED DISEASES
Shape Grams Stain Bacteria Related
Disease

curved or gram-negative Campylobacter septicemia


spiral rods

spirochetes gram-negative Treponema syphilis


palladium
CELL WALL SYNTHESIS
INHIBITORS
BetaLactams:
Penicillins
Cephalosporins
Carbapenems
Monobactams
Vancomycin

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BETA LACTAMS
B-lactams inhibit
transpeptidase.
Only effective
against rapidly
growing
organisms that
synthesize
peptidoglycan.
(Ineffective
against
mycobacteria.)
PENICILLINS
Natural penicillins: penicillin G,
penicillin V.
Penicillinase-resistant penicillins:
methicillin, nafcillin, oxacillin.
Aminopenicillins: amoxicillin,
ampicillin.
Extended-spectrum penicillins:
piperacillin, ticarcillin, carbenicillin.
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S
H2 N CH3
CH3
T
L

N O
O C
OH

Nucleus of penicillin molecule


L beta-lactame ring, T thiazoline ring
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PENICILLINS
Bacteria produce enzymes beta-
lactamases capable of destroying
penicillins.
Inhibitorof beta-lactamases :
Clavulanic acid
Tazobactam
Sulbactam
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Unasyn (ampicillin/sulbactam)
RESISTANCE MECHANISMS
B-lactamase hydrolyze the B-
lactam ring.
Alteration of penicillin-binding
protein (PBP) affinity. (Strep.
Pneumo., MRSA).
Change in porins.

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PENICILLINS:
THERAPEUTIC USES
Prevention and treatment of
infections caused by susceptible
bacteria, such as:
gram-positive bacteria:
Streptococcus,
Enterococcus,
Staphylococcus species.

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PENICILLINS: ADVERSE EFFECTS
Allergicreactions: urticaria,
pruritus, angioedema
Nausea, vomiting,
Diarrhea, abdominal pain
Cation toxicity
Nephritis

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CEPHALOSPORINS
FirstGeneration: cefazolin
Good gram-positive coverage
Poor gram-negative coverage
Second Generation: cefaclor, cefuroxime

Good gram-positive coverage


Better gram-negative coverage than first
generation
Third Generation: cefotaxime, ceftriaxone

Most potent group against gram-negative


Less active against gram-positive
Fourth Generation: cefepime: broad spectrum.
S
H2N

L D

N CH2 O CO CH3
O
O
C
OH

Structure of cephalosporins
L beta-lactame ring, D dihydrothiazine ring

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CEPHALOSPORINS:
THERAPEUTIC USES
First Generation:
used for surgical prophylaxis.
Second Generation:
Otitis media in children
Third Generation:
Usefulfor meningitis and sepsis.
Respiratory infections

UTIs (gonorrhea)

Fourth Generation:

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COMPLICATIONS, CAUSED BY
CEPHALOSPORINS

Irritation of mucous membrane of


GIT,
infiltrates after IM ,
phlebitis after IV
Disbacteriosis, superinfection
Allergic reactions, including cross
allergy with penicillins
Nephrotoxicity
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TETRACYCLINES
Demeclocycline
Oxytetracycline
Tetracycline
Doxycycline
Minocycline

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CARBAPENEMS
Imipenem
Broadest spectrum B-lactam:
Staph, Strep, Neisseria,
Haemophilus, Proteus,
Pseudomonas, Klebsiella,
Bacteroides, anaerobes.
Toxicities:
PCN allergy cross reactivity.
Seizures noted in Imipenem studies.
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MONOBACTAMS
Aztreonam
B-lactamase resistant.
Very little cross-allergenicity
May be a safe alternative for pcn allergic
patients.
Narrow antibacterial spectrum: Aerobic
G (-) rods: H. flu, N. gonorrhea , E. coli,
Klebsiella, Proteus, Pseudomonas).
Adverse reactions;
Gram positive superinfection (20-30%)
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VANCOMYCIN
Tricyclic glucopeptide
Inhibits synthesis of cell wall
phospholipids.
Active against G (+) bacteria, Strep.
pneumo, Clostridia, Enterococcus, Staph.
epi and MRSA.
Used in treatment of MRSA
Adverse effects.
Fever, chills, phlebitis and red man
syndrome.
Slow injection and prophylactic
antihistamines. Uploaded by: http://mbbshelp.com
PROTEIN SYNTHESIS INHIBITORS
Target the bacterial ribosome.
Bacterial 70S (50S/30S)
Mammalian 80S (60S/40S)

High levels may interact with mammalian ribosomes.


50S binders - Macrolides, Clindamycin,
Chloramphenicol, Streptogramins.
30S binders - Aminoglycosides, Tetracyclines

Mupirocin

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TETRACYCLINES
Natural and semi-synthetic
Bacteriostaticinhibit bacterial
growth
Inhibit protein synthesis
Bind to Ca2+ and Mg2+ and Al3+ ions
to
form insoluble complexes
Thus, dairy products, antacids, and
iron salts reduce absorption of
tetracyclines
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TETRACYCLINES: THERAPEUTIC
USES
Wide spectrum:
gram-negative, gram-positive,
protozoa, Mycoplasma,
Rickettsia, Chlamydia, syphilis,
Lyme disease
Chronic bronchitis
Lyme disease
Mycoplasma pneumoniae infection
Rickettsia infection
Some venereal diseases, such as Chlamydia infection
Travelers diarrhea
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TETRACYCLINES: SIDE EFFECTS
Discoloration of permanent teeth and tooth
enamel in fetuses and children
May retard fetal skeletal development if taken
during pregnancy
Superinfection (overgrowth of nonsusceptible organisms
such as Candida)
Diarrhea

Pseudomembranous colitis

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AMINOGLYCOSIDES

Gentamicin
Kanamycin
Neomycin
Streptomycin

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AMINOGLYCOSIDES
Natural and semi-synthetic
Poor oral absorption; only IM or IV

Bactericidal

Used to kill gram-negative bacteria such as


Pseudomonas spp., E. coli, Proteus spp.,
Klebsiella spp., Serratia spp.
Binds the 30S subunit.
Only active against anaerobes because an oxygen
dependent system is required to transport the
molecules into the cell.
Synergism with cell wall inhibitors is seen because
they increase the permeability of the cell.
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AMINOGLYCOSIDES: SIDE EFFECTS
Neuromuscular blockade
Vertigo

Superinfections

Skin rash
Ototoxicity

Nephrotoxicity

Resistance decreased uptake, decreased binding


affinity, enzymes (plasmids).

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MACROLIDES

Erythromycin
Azithromycin
Clarithromycin
Telithromycin
Irreversibly bind the 50S subunit.

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MACROLIDES:
THERAPEUTIC USES
Streptococcus pyogenes,
Haemophilus influenzae,

Syphilis and Lyme disease,

Gonorrhea,

Chlamydia,

Mycoplasma

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MACROLIDES: SIDE EFFECTS
GIT: nausea, vomiting, diarrhea,

Hepatotoxicity, jaundice,

Ototoxic (high doses)

Drug interactions
Inhibits P-450 other substrates and increases their
serum concentrations.
Theophylline, warfarin, astemizole, carbemazepine,
cyclosporine, digoxin, terfenadine.

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MACROLIDES RESISTANCE
Efflux mechanism.
Ribosomal alteration.

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CLINDAMYCIN
Lincosamide

Irreversibly binds the 50S subunit


Used for deep neck space infections,
chronic tonsillo-pharyngitis, odontogenic
abscesses, and surgical prophylaxis in
contaminated wounds.
Resistance: MLSB ribosomal alteration.

Antibiotic spectrum:
Strep species, Staph (some MRSA), B. fragilis,
anaerobes

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CLINDAMYCIN
CLINDAMYCIN:
ADVERSE EFFECTS
Pseudomembranous colitis
Abdominal pain, fever, leukocytosis,
Diarrhea commonly develops on days 4-9 of treatment.
Life threatening cases can be treated with oral
Vancomycin.

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NEW ANTIBIOTICS FOR MRSA
Linezolid

Quinupristin-dalfopristin

Daptomycin

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LINEZOLID
Oxazolidinone inhibits the
initiation complex of bacterial protein
synthesis.
Antibiotic spectrum gram positives.
Oral = IV
May be superior to vancomycin for
MRSA pneumonia.
Adverse effects: Myelosuppresion,
thrombocytopenia.
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QUINUPRISTIN-DALFOPRISTIN
Quinupristin streptogramin A
Dalfopristin streptogramin B
Binds 50S ribosome.
High activity against MRSA and
VRSA.
Synergy with B-lactams.
Additive with vancomycin.
Adverse effects:
Arthralgias, myalgias
HyperbilirubinemiaUploaded by: http://mbbshelp.com
DAPTOMYCIN
Cyclic lipopeptide
Disrupts cell membrane function.
Only approved for complicated skin
and soft tissue infections.
Not used for pneumonia due to low
respiratory tract concentrations
Adverse effects reversible
myopathy.

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FOLATE ANTAGONISTS
Bacteria must synthesize folate in order to
form cofactors for purine, pyrimidine and
amino acid synthesis.
p-aminobenzoic acid (PABA) agonists.
Substrates for dihydropteroate synthetase.
Sulfonamides
Sulfamethoxazole (SMP)
Sulfasoxazole

Dihydrofolate Reductase Inhibitors.


Inhibits activation of folate to its active form,
tetrahydrofolate.
Trimethoprim (TMP)

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CLINICAL APPLICATIONS.
Antibacterial spectrum.
H. flu, Strep. pneumo, Neisseria species, S.
aureus, and Pneumocystis carinii
Pediazole (erythromycin + sulfasoxazole)
Alternative to amoxicillin for first line
treatment of acute otitis media.
Co-trimoxazole
(trimethoprim +
sulfamethoxazole; IV $8.71/day; Oral
$0.15/day)
MRSA, UTIs, PCP prophylaxis.
97% of UTMB outpt Staph. aureus isolates are
susceptible to Bactrim.
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ADVERSE REACTIONS
Dermatologic: Rashes are
common, ranging from
photodermatitis to Stevens-
Johnsons syndrome.
Hematologic: Hemolytic
anemia (G6PDH deficient
pts.), neutropenia and
thrombocytopenia (up to 80%
of HIV pts)
Drug interactions: Warfarin,
phenytoin, methotrexate.
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SULFONAMIDES
One of the first groups of
antibterial agents
sulfadiazine
sulfamethizole
sulfamethoxazole
sulfisoxazole

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SULFONAMIDES: MECHANISM OF
ACTION
Bacteriostatic action
Prevent synthesis of folic acid
required for synthesis of purines
and nucleic acid
Does not affect human cells or
certain bacteriathey can use
preformed folic acid

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STRUCTURE OF SULFONAMIDES
para-Aminobenzoic acid sulfonamide

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CLASSIFICATION OF
SULFONAMIDES

Short action: sulfadimezine,


norsulfazole, urosulfan, sulfizoxazole,
Intermediat action: sulfamethoxazole
Longlasting action: sulfadimethoxyn,
sulfapirydazin, sulfamonomethoxyn
Super longlasting action: sulfalen,
sulfadoxyn

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SULFAMETHOXAZOLE
THERAPEUTIC USES:
Totreat urinary tract infections
(UTIs)
Combined with trimethoprim:
Used to treat UTIs,
Pneumocystis carinii pneumonia,
ear infections,
bronchitis,
gonorrhea, etc.
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CO-TRIMOXAZOLE = BACTRIM
(TRIMETHOPRIM + SULFAMETHOXAZOLE)
SULFONAMIDES: SIDE EFFECTS
Blood: Hemolytic and aplastic
anemia, thrombocytopenia.
Photosensitivity,
Stevens-Johnson syndrome,
Epidermal necrolysis,
GIT: Nausea, vomiting,
diarrhea,pancreatitis,
Crystalluria,toxic nephrosis (fluid
intake).
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ANTIBIOTICS: QUINOLONES

Ciprofloxacin
Levofloxacin
Norfloxacin
Ofloxacin
Moxifloxacin

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QUINOLONES
Excellent oral absorption
Bactericidal

Effective against gram-negative organisms and some


gram-positive organisms
Alter DNA of bacteria, causing death

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QUINOLONES:
THERAPEUTIC USES
Lower respiratory tract infections
Bone and joint infections

Infectious diarrhea

Urinary tract infections

Skin infections

Sexually transmitted diseases

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QUINOLONES: SIDE EFFECTS
CNS: headache, dizziness, fatigue, depression,
restlessness.
GIT: nausea, vomiting, constipation,

Rash, pruritus, urticaria,

Photosensitivity

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