1. Nailya Bulatova MD, PhD,
Professor of Pharmacotherapy
The University of Jordan-School of
Pharmacy-Department of
Biopharmaceutics and Clinical
Pharmacy,
Amman, Jordan
Antibacterial agents
(dentistry students)
2. CARDINAL FEATURES OF
ANTIMICROBIALS
• Chemotherapeutic substances: agents possessing
selective toxicity against causative agents of
infectious & parasitic diseases – antibacterial,
antiviral, antifungal, antiprotozoal & antihelmintic
drugs.
A. selectivity of action against certain kinds of
microorganisms (specific spectrum of antimicrobial
action);
B. Low toxicity for humans.
3. SYSTEMIC VS. TOPICAL
• For systemic infections: orally & parenterally.
• May be applied topically (→ absorption is minimal
→↓risk of ADEs) to:
- mucous membranes
- skin
- orally for intestinal infections (agents that are not
absorbed from GIT).
4. CLASSES OF ANTIBACTERIAL
(AB) CHEMOTHERAPEUTIC
DRUGS - ANTIBIOTICS
Penicillins Cephalosporins
Other antibiotics
with β-lactam
ring:
carbapenems &
monobactams
Macrolides &
azalides
Tetracyclines
Chloramphenicol
group
Aminoglycosides
group
Cyclic
polypeptides
(polymyxins, etc)
Lincosamides Glycopeptides Fusidic acid Topical antibiotics
5. CLINICAL APPLICATION OF AB
CHEMOTHERAPEUTIC DRUGS
1. Identifying causative agent & its sensitivity to
chemotherapeutic agents.
• If known, drugs with narrow spectrum are used; if
unknown, drugs with the broadest spectrum of
activity should be used.
• Sometimes, 2 agents with combined spectrum of
activity targeting suspected microorganisms.
2. Treatment ASAP: microbs have extensive growth &
reproduction.
3. Doses must be sufficient to reach bacteriostatic or
bactericidal concentrations in biological fluids &
tissues. Use of loading dose in beginning.
6. CLINICAL APPLICATION OF
AB CHEMOTHERAPEUTIC
DRUGS (continued)
4. Optimal duration to avoid recurrence.
5. With some infections, a repeated course is needed.
6. Proper route of administration (e.g., degree of
absorption from GIT).
7. Sometimes, 2-3 antibacterial drugs are administered.
But: wrong combination may lead to antagonism or to
toxic effects.
7. ANTIBIOTICS1
• 1 Greek: anti - against, bios - life.
• Are chemical compounds of biological origin,
produced by actinomyces (ray fungi), mold & certain
kinds of bacteria.
• Synthetic analogues & derivatives of natural fungi
also belong here.
• There are antibiotics with antibacterial, antifungal &
anticancer action.
Mode of action:
• Bacteriostatic: (-) cell division
• Bactericidal: causing cell lysis
9. RESISTANCE OF
MICROORGANISMS TO
ANTIBACTERIAL DRUGS
• May develop during therapy.
• Rapid with use of streptomycin & rifampicin.
• Slow with use of fluoroquinolones, penicillins,
tetracyclines & chloramphenicol;
• Cross-resistance: affects other antibiotics having
similarities in chemical structure (e.g., all tetracyclines).
Ways to overcome resistance:
• Using doses, regimen of antibiotic therapy &
combinations correctly.
• If resistance to the 1st choice antibiotic happened, it
should be replaced by alternative1 one.
11. Superinfection
• Superinfection (dysbacteriosis) results from partial
suppression of saprophyte flora, e.g., of GI tract
• favors growth of m/o that are not sensitive to
particular antibiotic [yeast-like fungi, Clostridium
difficile, proteus, Pseudomonas aeruginosa (P.
pyocyanes), staphylococci].
• Most commonly superinfection develops after broad-
spectrum antibiotic therapy.
12. Penicillins
Commonly used penicillins
• bactericidal effect.
• Impair synthesis of cell
wall components blocking
peptide linkage formation
via transpeptidase enzyme
inhibition.
Lippincott
13. PENICILLINS
(continued)
II. Semisynthetic penicillins
A. For both parenteral & oral use
(acid-stable)
1) Resistant to penicillinase
- Oxacillin - Nafcillin
2) Extended spectrum of action
- Ampicillin - Amoxicillin
B. For parenteral use (destroyed in
gastric acid)
* Extended spectrum of action
including Pseudomonas aeruginosa
- Carbenicillin - Ticarcillin - Azlocillin
C. For oral use (acid-stable)
- Carbenicillin - Carfecillin
I. Biosynthetic penicillins
A. For parenteral use (destroyed in
gastric acid)
1) Short-term action -
Benzylpenicillin
2) Long-term action
- Procaine-benzylpenicillin
- Benzylpenicillin-benzathine
(bicillinum 1)
- Benzicilline-5 (bicillinum 5)
B. For oral use (acid-stable)
- Phenoxymethylpenicillin
14. MAIN SPECTRA OF ACTION
OF SOME PENICILLINS &
CEPHALOSPORINS
cephalosporins.
15. BENZYLPENICILLIN
(Penicillin G)
• is obtained by
fermentation
procedures from
strains of Penicillium.
• monobasic acid
containing β-lactam
(L) & thiazolidine (T)
rings).
• cyclic dipeptide (L-
cystein & D-valin).
Chemical structure of 6-
aminopenicillanic acid. L - β-
lactam ring, T - thiazolidine ring.
PENICILLINS
(continued)
17. BENZYLPENICILLIN
(continued)
• All benzylpenicillin salts are destroyed by gastric acid.
• benzylpenicillin Na & K salts: IM & IV; short duration
(3-4 h).
• poorly soluble benzylpenicillin salts: IM only (are
absorbed slowly from site of injection).
- procaine benzylpenicillin: 2-3 TD,
- bicillin 1 – Q 7-14 d;
- bicillin 5 – Q mth) .
19. 1. Penicillinase-resistant
semisynthetic
(antistaphylococcal) penicillins
• oxacillin, dicloxacillin, nafcillin: active against penicillinase-
producing strains of staphylococci.
• oxacillin: stable in acid
• is given every 4-6 h PO, IM, IV.
• nafcillin: given both PO & parenterally.
• drugs of choice (DOC) for infections caused by penicillinase-
producing staphylococci that are resistant to benzylpenicillins.
• Penicillinase (β-lactamase)
• Produced by S. aureus, H. influenzae, N. gonorrhoeae, etc.
• 4 groups (A, B, C & D).
• β-lactamase inhibitor, clavulanic acid, (-) β-lactamase group A
effectively, group D not significantly & does not affect β-
lactamase groups B & C.
20. 2. Semisynthetic penicillins
with broad spectrum of
activity
I. Drugs that are not active against Pseudomonas
aeruginosa
◊ Aminopenicillins - Ampicillin - Amoxicillin
II. Drugs that are active against Pseudomonas
aeruginosa - Carbenicillin - Ticarcillin - Piperacillin
21. 2. Semisynthetic penicillins
with broad spectrum of
activity (continued)
• Ampicillin: widely used
• Affects both Gr+ & Gr- [Salmonellas, Schigellas, some
strains of Proteus, Escherichia coli, Klebsiella
pneumoniae, Hemophilus influenzae]
• Broken-down by penicillinase
• Resistant to acid –used PO, (IM & IV as sodium salt –
pentrexil)
• Given every 4-8 h
• Low toxicity
• Ampiox (ampicillin with oxacillin)
• Amoxicillin = ampicillin in activity & spectrum of action
• Absorbed from gut > completely
• Used only PO
22. 2. Semisynthetic penicillins
with broad spectrum of
activity (continued)
• Agents active against P. aeruginosa are destroyed
by penicillinase
• Carbenicillin (Pyopen) = ampicillin in antimicrobial
spectrum of activity + Proteus & P. aeruginosa
• Broken-down in stomach + poorly absorbed →used
IM & IV.
• Duration of action is 4-6 h
• Ticarcillin >active than carbenicillin, especially
against P. aeruginosa
• Antipseudomonal activity: piperacillin > ticarcillin >
carbenicillin
23. β-Lactamase inhibitors
(continued)
• Ampicillin: used mainly in conditions caused by Gr-
microorganisms or by mixed flora (urinary, biliary,
respiratory & GI tracts & in purulent surgical
infections)
• Indications for amoxicillin: same as ampicillin (PO).
• Carbenicillin, carphecillin, ticarcillin, azlocillin:
infections caused by P. aeruginosa, Proteus, E. coli (in
pyelonephritis, pneumonia, septicemia, peritonitis,
etc).
24. β-Lactamase inhibitors
• clavulanic acid, sulbactam, tazobactam
• Prevent destruction of β-lactam antibiotics.
• Are used in combination with β-lactam antibiotic
• Augmentin = amoxicillin + clavulanic acid
• Clavulanic acid (produced by Streptomyces
clavuligerus) is β-lactam derivative
• Has no antibacterial activity
• Does not affect β-lactamases produced by
some Enterobactericeae
25. β-Lactamase inhibitors
(continued)
• Augmentin: broad spectrum including β-lactamase-
producing
- Gr+ bacteria (staphylococci, most streptococci,
enterococci)
- Gr- (N. gonorrhoeae, N. meningitides, Gardenella
vaginalis, Bordetella pertussis, E. coli, K. pneumonia,
Pr. mirabilis, Salmonella),
- many strains of anaerobes producing β-lactamase
• Used PO & IV 2-3TD (BID-TID).
• Uses: respiratory & urinary tract infections, bacterial
lesions of skin, soft tissues, bones & joints.
26. Adverse & toxic effects
of penicillins
Toxicity: low
• The most common ADEs: allergic reactions, (1-10%
cases) (may start from minutes to weeks)
• No dose dependence
• Severity: from skin rashes, dermatitis & fever to
swelling of mucosa, arthritis, arthralgia, damage to
the kidneys, erythroderma
• The most severe: anaphylactic shock (↓ arterial
pressure, bronchial spasm, abdominal pain, brain
edema, unconsciousness, etc.)
• It develops within 20 min after penicillin injection
27. Adverse & toxic effects
of penicillins (cont’d)
Treatment of allergic
reactions:
• cessation of penicillin
preparations
• glucocorticoids
• antihistamines
• calcium chloride
• other drugs
• Treatment of
anaphylactic shock (IV):
• α- & β -
adrenomimetics (↑BP&
relieve bronchospasm),
epinephrine (DOC) or
ephedrine
• hydrocortisone
• diphenhydramine
• calcium chloride
28. Adverse & toxic effects
of penicillins (cont’d)
non-allergic ADEs.
• irritating effect:
- PO - glossitis & stomatitis, N,V,D
- IM: pain, infiltration & aseptic muscle necrosis
- IV: phlebitis or thrombophlebitis
• Neurotoxicity (arachnoiditis, encephalopathy):
especially endolumbar use or in renal failure
• Impairment of heart function
• Oxacillin occasionally inhibits hepatic enzymes
• Acid-resistant penicillins (e.g., ampicillin):
dysbacteriosis (most commonly - candidiasis)
29. CEPHALOSPORINS
• Are semisynthetic derivatives of cephalosporin C
isolated from fungus Cephalosporinum acremonium
• Chemical base is 7-aminocephalosporanic acid.
• are similar to penicillins: contain β-lactam ring (L)
• Bactericidal: inhibit cell wall synthesis by suppressing
activity of transpeptidase (like penicillins)
• Resistant to penicillinase of staphylococci
• Many are destroyed by β-lactamases produced by
certain Gr- microorganisms (e.g., P. aeruginosa,
Enterobacter aerogenes) (cephalosporinases)
30. CEPHALOSPORINS
(continued)
• 1st generation, e.g. cephalexin PO & cephazolin IV,
• Gr+cocci (pneumococci, streptococci, staphylococci)
• some Gr-ive bacteria (E. coli, Klebsiella pneumoniae,
Proteus mirabilis).
• 2nd generation: as 1st generation + Enterobacter &
indol-positive proteus + H. influenza & some Neisseria
species.
• Cefoxitine, cefmetazol & cefotetan: also Bacteroides
fragilis (but not DOC) & certain strains of Serratia.
• 2nd is < potent than 1st group in activity against Gr+
cocci.
31. CEPHALOSPORINS
(continued)
• 3rd generation, e.g. ceftriaxone: broader spectrum,
especially against Gr- bacteria.
• Gr+ cocci < than 2nd generation.
• Acts against Enterobacter, Serratia & strains
of Hemophilus & Neisseria that produce β-lactamases
• Penetrate through BBB.
• Ceftazidime & cefoperazone: P. aeruginosa.
• Ceftizoxime & moxalactam: Bacteroides fragilis.
32. • 4th generation (e.g., cefipime): broader spectrum
than 3rd generation.
• > effective against Gr+ cocci (but not MRSA).
• Highly active against P. aeruginosa & other Gr-
bacteria, including β-lactamase producing strains.
• 5th generation: Ceftaroline (fosamil): IV.
• Spectrum: as ceftriaxone + MRSA + S. pneumonia
(but not P. aeruginosa, ESBL-producing
Enterocbacteriacea, Acinetobacter baumanii)
CEPHALOSPORINS
(continued)
33. CEPHALOSPORINS
(continued)
• Most cephalosporins are poorly absorbed from GIT.
• Some are given PO; BA is 50-90%.
• Bactericidal.
• 1st & 2nd generations do not pass via BBB.
• Most are renally excreted via filtration & secretion
but some are eliminated with bile (cefoperazone,
ceftriaxone).
• Sometimes cephalosporins are combined with β-
lactamase inhibitor sulbactam, e.g.,
sulperazone (cefoperazone + sulbactam).
34. CEPHALOSPORINS
(continued)
• Used for the treatment of diseases caused by Gr- (e.g.,
UTI) & Gr+ bacteria, if penicillins fail or are not
tolerated.
• Drugs of choice (DOC) for Klebsiella pneumoniae
infections.
• Ceftazidime & cefoperazone: P. aeruginosa infections.
• For gonorrhoea DOC is ceftriaxone.
• For meningitis caused by meningococci or
pneumococci, preparations that cross BBB, e.g.,
cefuroxime & 3rd generation agents (except
cefoperazone & cefixime).
• Cefoxitin & ceftizoxime: in infections caused by
bacteroides (B. fragilis).
36. OTHER β-LACTAMS
Carbapenems
• Imipenem: broad spectrum: against many aerobs &
anaerobs.
• Blocks cell wall synthesis; bactericidal effect.
• Resistant to β-lactamase, but is destroyed by
dehydropeptidase-1 in renal proximal tubules → low
concentrations in urine.
• is used in combination with cilastatin
(dehydropeptidase-1 inhibitor) = tienam (primaxin).
• used IV every 6 h.
• ADRs: N&V, cramps & allergic reactions.
37. OTHER β-LACTAMS
(continued)
• Meropenem (meronem): carbapenem.
• Resistance to dehydropeptidase-1 & majority of β-
lactamases.
• Carbapenems are used in severe infections: pneumonia,
peritonitis, meningitis, & sepsis.
• Also: exacerbation of chronic bacterial bronchitis,
uncomplicated UTI, infections of skin & its appendages.
• Given IM & IV Q 8-12 h.
• ADEs: allergic reactions, irritation at sites of injection, GI
distress, reversible leukopoiesis disorders, HA &
dysbacteriosis.
38. OTHER β-LACTAMS
(continued)
Monobactams: Aztreonam
• Resistant to β-lactamases produced by some Gr-
bacteria (Klebsiella, Pseudomonas & Serratia groups).
• Not effective against Gr+ bacteria & anaerobes.
• Inhibits cell wall synthesis: bactericidal.
• It is given parenterally.
• Used to treat infections of urinary tract, respiratory
system, skin, etc.
• SEs: GI upset, skin allergic reactions, HA;
superinfection; hepatotoxic effect is not common.
39. MACROLIDES
• Structure:
macrocyclic lacton
ring + different
sugar moieties.
• Macrolides:
erythromycin,
oleandomycin,
roxithromycin,
clarythromycin &
azithromycin.
Chemical structure of some
macrolides & azalides
1 A base of macrolide chemical structure of erythromycin group is a 14-membered ring with a
heteroatom of oxygen. Azalides (like azythromycin) comprise a 15-membered ring with a hetero-
atoms of nitrogen & oxygen. Josamycin (vylpraphen) contains a 16-membered lacton ring.
40. MACROLIDES
(continued)
• Erythromycin (erythran, erythrocin) is produced
by Streptomyces erythreus.
• Most sensitive bacteria: Gr+ cocci & pathogenic
spirochetes.
• Also: Gr- cocci, dyphtheria bacillus, anaerobes,
rickettsia, chlamydia, mycoplasma, causative agents
of amoebic dysentery.
• MoA: inhibition of protein synthesis in bacterial
ribosomes: suppression of peptide translocase
enzyme.
• bind irreversibly to 50S subunit of ribosome
• bacteriostatic.
41. MACROLIDES
(continued)
• Erythromycin: not resistant to gastric acid → has to
be given in acid-fast enteric-coated capsules or
tablets.
• Readily penetrates via placenta.
• Accumulates in phagocytes (as other macrolides).
• Duration: 4-6 h.
• Excreted with bile & partially with urine.
• Use is limited due to resistance→ 2nd choice
antibiotic
• Used orally (erythromycin base) & topically.
• Low toxicity: GI upset, allergic reactions;
superinfection.
42. MACROLIDES
(continued)
• Clarithromycin (clacid): 2-4 times > active against
staphylococci & streptococci than erythromycin.
• Used in infections caused by Micobacterium avium
intracellulare & Helicobacter pylori.
• Partially metabolized by liver → active metabolite →
renal excretion.
• t1/2 ~3 times longer compared to erythromycin.
• Roxythromycin (rulid): broad antibacterial spectrum.
• Well absorbed PO.
43. MACROLIDES
(continued)
• Azithromycin (sumamed): 2-4 times < active against
staphylococci & streptococci than erythromycin, but
> against H. influenzae & Gr- cocci.
• Poorly absorbed in gut, especially in presence of
food.
• Accumulates in high concentrations in cells (10-100
times > than in blood).
• Used orally & IV.
• ADRs: Nausea & diarrhea; auditory impairment is
rare.
44. MACROLIDES
(continued)
• Novel macrolide - josamycin (vylpraphen).
• Resistance rarely develops.
• Macrolides are effective against obligate intracellular
microorganisms that cause so-called «atypical»
pneumonias:
- Chlamydia,
- Mycoplasma,
- Legionella.
45. • MoA: same as erythromycin.
• used mainly in infections caused by Gr+ organisms,
including MRSA & streptococcus, & anaerobes.
• C. difficile is always resistant to clindamycin.
• Available both IV & orally.
• Low urinary elimination → not for UTI.
• Accumulates in severe renal impairment or hepatic
failure.
• ADRs: skin rash; pseudomembranous colitis due to C.
difficile.
• Treatment: metronidazole or vancomycin PO.
Clindamycin
(source: Lippincott)
Lippincott
49. Tetracyclines
(continued)
• MoA: 1. (-) protein synthesis by bacterial ribosomes:
• bind reversibly to 30S subunit → prevent binding of
tRNA to mRNA–ribosome complex
• 2. bind to metals (Mg2+, Ca2+) forming chelate
compounds & (-) enzyme systems.
• Bacteriostatic effect; especially active against
dividing bacteria.
• Form chelate compounds with ions of Ca, Fe & Al →
tetracycline absorption is impaired when taken with
food (e.g., milk) or drugs (e.g., antacids), which
contain these ions.
50. Tetracyclines
(continued)
• Doxycycline & minocycline do not significantly
chelate with Ca → are absorbed readily &
completely.
• Penetrate placenta.
• Small amounts of tetracycline are found in liver &
bones for long period after intake.
• Are indicated when m/o (microorganisms) become
resistant to penicillin & streptomycin, or in cases of
hypersensitivity to these antibiotics.
• Routinely taken PO.
• Parenterally (IV, IM, into cavities).
52. Tetracyclines
(continued)
ADRs:
• Allergic reactions (skin lesions, mild fever, etc.): <
common than to penicillins or cephalosporins.
• Irritant effect (especially oxytetracycline).
• PO: GI upset (N&V, D), glossitis, stomatitis.
• IM: painful; IV infusion: thrombophlebitis.
• Hepatotoxicity (mainly oxytetracycline).
• In young children & women in late pregnancy:
deposited in bone tissue, including teeth, & form
chelate complex with calcium salts → suppression of
bone growth; pigmentation & impairment of teeth.
53. Tetracyclines
(continued)
• Photosensitivity 1 (especially demeclocycline) →
dermatitis.
• (-) protein synthesis (antianabolic action), ↑
elimination of Na, H2O, amino acids, certain vitamins
etc.
• Minocycline: vestibular disorders.
• Superinfection is common [(-) normal flora of GIT &
promote candidiasis, staphylococci, proteus & P.
aeruginosa infections].
• Vitamins B-group deficiency
1 Greek: phos (photos) - light, Latin: sensibilis - sensitive.
54. Tetracyclines
(continued)
• Need addition of antifungal nystatin & vitamin B
complex.
• Pseudomembranous colitis (Clostridium
difficile infection): should be treated by vancomycin.
• Glycilcyclins: Tygecyclin: derivative of tetracycline.
• Broad-spectrum, including MRSA, VRE, ESBL-
producing Gr-, A. baumanii (but not P. aeruginosa &
proteus).
• Administered when other antimicrobial are
ineffective due to microbial resistance.
1 Greek: phos (photos) - light, Latin: sensibilis - sensitive.
57. CHLORAMPHENICOL
GROUP
• Clinical uses:
- Typhoid fever,
- Food poisoning (salmonellosis)
- Rickettsia infections.
- Sometimes: diseases caused by H. influenzae (e.g.,
meningitis, UTI);
- Brucellosis etc.
• Routinely used PO, topically to skin1 & parenterally
(SC, IM & IV).
• 1 Synthomycinum, synthetic racemate of
chloramphenicol, is also applied topically.
Chloramphenicol is a left-rotating isomer.
58. CHLORAMPHENICOL
GROUP
ADRs:
1. Significant bone marrow (-) → in severe cases,
aplastic anemia (fatal)
• → requires regular blood count monitoring.
• Chloramphenicol course should be short-term &
repeated courses are not advisable.
2. Allergic reactions: skin rashes, fever, etc.
3. Mucous membranes irritation (nausea, diarrhea),
including anorectal syndrome.
59. CHLORAMPHENICOL
GROUP
ADRs (continued):
4. Skin rashes & dermatitis.
5. Psychomotor disorders.
6. Myocardial depression.
7. “Grey Baby Syndrome”: severe intoxication
accompanied by cardiovascular collapse in neonates &
infants <1 month old - results from slow excretion of
the drug by kidneys & liver enzyme insufficiency at this
age.
8. Superinfection (e.g., candidiasis, infections caused by
Staphylococci or Proteus).
60. AMINOGLYCOSIDES
GROUP
• Streptomycin, neomycin, kanamycin, gentamicin,
amikacin, tobramycin, sisomicin, monomycin, etc.
• Mechanism : direct influence on protein synthesis in
ribosomes.
• Bactericidal.
Streptomycin: broad spectrum.
- M. tuberculosis,
- Causative agents of tularemia & plague,
- Pathogenic cocci,
- Certain strains of proteus,
- P. aeruginosa,
- Brucella,
- Other Gr- & Gr+ bacteria.
61. AMINOGLYCOSIDES
GROUP (continued)
Streptomycin (continued):
• Resistance develops quickly
• Poorly absorbed from GIT.
clinical use:
1. Most commonly: treatment of TB (in combination),
2. Tularemia,
3. Plague,
4. Brucellosis,
5. Infections of urinary & respiratory systems, etc.
• administered mainly parenterally IM (1-2 times daily)
or into body cavities.
62. AMINOGLYCOSIDES
GROUP (continued)
ADEs of streptomycin:
1. Ototoxicity (damage of sensory cells in cochlea &
vestibular apparatus of the ear) → vestibular
dysfunction > auditory disturbances.
2. Nephrotoxicity.
3. Inhibits neuromuscular synapses →respiratory
depression
4. Irritant → injections are painful.
5. Allergic reactions (fever, skin lesions, eosinophilia;
anaphylactic shock).
6. Superinfection.
63. AMINOGLYCOSIDES
GROUP (continued)
• Neomycin: produced by Actinomyces fradiae.
• Broad spectrum: Gr+ & Gr- m/o
• Poorly absorbed when given PO → action is confined to
GIT.
• Used for treatment of enteritis caused by susceptible
m/o.
• may be useful as a preoperative medication before GI
operation (partial "sterilization" of gut).
• High activity against colonic bacilli, certain strains of
proteus & Pseudomonas aeruginosa.
• SEs: GI distress, allergic reactions & candidiasis
64. AMINOGLYCOSIDES
GROUP (continued)
• Topical use of neomycin: infected wounds, skin
infections (pyodermia, other), eye diseases (e.g.,
conjunctivitis), etc.
• Absorption from undamaged skin & mucous
membrane is poor;
• For external use: with glucocorticoids (e.g.,
fluocinolone acetonide or flumetasone), ointments
«Locacorten-N» or «Synalar-N» (N means the
presence of neomycin);
• Contraindicated (c/i) in renal disorders & diseases of
auditory nerve.
65. AMINOGLYCOSIDES
GROUP (continued)
• Gentamicin sulphate (garamicin):
• Broad spectrum of action: Gr+ & Gr-: P.
aeruginosa, proteus, E. coli, staph resistant to penicillin.
• Incomplete GI absorption→used IM & IV Q 8-12 h;
topically
• Used in diseases caused by Gr- bacteria: UTI
(pyelonephritis, cystitis), sepsis, wound infections &
burns.
• < toxic than neomycin.
• typical ADEs for aminoglycosides:
Ototoxicity (vestibulotoxicity > hearing impairment),
Nephrotoxicity,
Curare-like properties.
66. AMINOGLYCOSIDES
GROUP (continued)
• Tobramycin (brulamycin): highly active against P.
aeruginosa.
• Nephro- & ototoxicity < than with gentamicin.
• Sisomicin: >active than gentamicin against different
types of proteus, P. aeruginosa, klebsiella &
enterobacter.
• Amikacin (amikin): broadest spectrum of
antimicrobial action among the group: aerobic Gr-
(including P. aeruginosa, proteus, Klebsiella, E.
coli, etc) & M. tuberculosis.
67. Polymyxin M
• Used orally (poorly absorbed from GIT) & topically.
• Uses: enterocolitis caused by P. aeruginosa, E. coli &
schigella; for intestinal clearance before surgery.
• Topically: suppurative processes caused by mostly Gr-
microorganisms, including P. aeruginosa).
• SEs: rare - orally, GI distress, sometimes superinfection.
• Contraindicated in patients with renal disorders.
• Monitoring of renal function is obligatory.
• In a number of countries > commonly used drugs
are polymyxin B & polymyxin E(colistin).
68. GLYCOPEPTIDES
• Vancomycin: complex glycopeptide produced by
actinomyces of Streptomyces orientalis.
• Impairs bacterial cell wall synthesis
• Bactericidal effect
• Highly effective against Gr+ cocci, including MRSA &
strains producing β-lactamases, clostridia,
including Clostridium difficile, corinebacteria.
• Poorly absorbed from GIT.
• Used IV (PO only topically) for:
infections caused by Gr+ cocci resistant to penicillin
(e.g., MRSA).
pseudomembranous enterocolitis.
69. GLYCOPEPTIDES
(continued)
Vancomycin ADEs:
Ototoxic.
Nephrotoxic.
Phlebitis.
Allergic reactions,
Neutropenia & thrombocytopenia.
• Teicoplanin: analogous to vancomycin but has long-
term action.
• Used QD IM or IV.
70. FUSIDIC ACID
• Used as sodium salt mainly against Gr+ bacteria.
• Inhibits bacterial protein synthesis.
• Bacteriostatic.
• Readily absorbed orally.
• Accumulates in large amounts in bone.
• Metabolised in liver → excreted with bile.
• Treats infections caused by staphylococci resistant to
penicillin.
• Especially active in osteomyelitis.
• ADRs: dyspeptic disorders, rashes & jaundice.
71. TOPICAL ANTIBIOTICS
• Mupyrocin (bactroban).
• Produced by Pseudomonas fluorescens.
• Inhibits protein synthesis.
• Low concentrations: bacteriostatic effect, high
concentrations bactericidal.
• Used topically or intranasally for treatment of
infections of skin & mucous membrane of nasal
meatus by staphylococci (including MRSA) & β-
hemolytic streptococci.
74. Spectrum of SA activity:
broad
- Pathogenic cocci (Gr+ & Gr-), e.g., pneumococci,
meningococci, gonococci, hemolytic streptococci,
- Escherichia coli,
- Causative agents of bacilary dysentery (schigella),
- Vibrio cholerae,
- Causative agents of gas gangrene, anthrax, diphtheria,
- Haemophilus influenzae;
- Chlamydias - causative agents of trachoma, ornitosis,
lymphogranulema venereum;
- Actinomyces;
- Protozoa - causative agents of toxoplasmosis, plasmodium
malaria.
75. MoA of SA: competitive
antagonism with para-
aminobenzoic acid (PABA)
• Dihydrofolic acid is synthetized
from PABA by microbes but not
in humans (utilize preformed
dihydrofolic acid → selectivity
of SAs.
• SAs prevent PABA inclusion into
dihydrofolic acid + inhibit
dihydropteroate synthase
• →↓ conversion of dihydrofolic
acid into tetrahydrofolic acid,
(essential for synthesis of
purine & pyrimidine bases)
76. SAs USED FOR SYSTEMIC
ACTION (continued)
ADRs many:
• GI (N&V),
• HA, weakness, CNS disorders,
• Blood (hemolytic anemia, thrombocytopenia,
methemoglobinemia),
• crystalluria - may be ↓ by giving plenty of fluids,
especially alkaline ones.
• allergic reactions - from skin rashes to fever;
hepatitis, agranulocytosis; aplastic anemia.
• history of any allergic reactions to SAs is
contraindication for repeated use.
78. SAs & TMP
FORMULATIONS
(continued)
• Prolonged use of co-
trimoxazole needs
peripheral blood
monitoring.
• C/I: marked hepatic,
renal & hematopoiesis
impairment; children <
6 years of age &
pregnant women.
• Similar to co-
trimoxazole:
Some ADRs of TMP-SMX
79. QUINOLONE
DERIVATIVES
• Fluoroquinolones (contain fluorine atoms):
ciprofloxacin (ciprobay), norfloxacin, perfloxacin,
lomefloxacin, ofloxacin (tarivid), etc.
• Broad spectrum of action.
• Bactericidal effect against Gr(-)
(gonococci, E.coli, Schigella, Salmonella, K.
pneumoniae, Enterobacter, H.
influenzae, mycoplasma, chlamydia, etc.).
• Ciprofloxacin: P. aeruginosa.
• < effective against infections caused by Gr+.
80. MoA of synthetic
antimicrobial preparations
Quinolones MoA: inhibition of topoisomerases II (DNA-gyrase) & IV →
impair DNA replication & → RNA formation →↓bacterial growth &
division.
82. SYNTHETIC ANTIBACTERIALS
OF VARIOUS CHEMICAL
STRUCTURES (continued)
OXAZOLADINONES
• Linezolid (zivox): broad spectrum - aerobic Gr+,
certain Gr- & some anaerobes.
• Treats infections caused by bacteria resistant to other
antimicrobials.
• MoA: inhibition of early stages of protein synthesis.
• Bactericidal in vivo.
• Used both orally & parenterally.
• Used mainly for severe infections caused by Gr+.
