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Antibiotics
ATB according to chemical structure
Antibiotics
• β-lactams
• penams
• cephems
• monobactams
• carbapenems
• amphenikols
• tetracyklines
• aminoglykosides
• makrolides
• azalids
• ketolids
• streptogramins
• oxazolidinones
• lincosamines
• glycopeptides
Chemoterapeutics
• sulphonamides
• pyrimidines
• chinolons
• (nitro)imidazoles
• nitrofuranes
• others
Specifics of ATB therapy
§ Selective toxicity
§ ATB spectrum
§ MIC, MBC, MAC
§ Postantibiotic effect
§ Resistance
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BETA-LACTAMS
I. PENICILLINES (Penams)
II. CEPHALOSPORINES +
CEPHAMYCINES (Cephems)
III. MONOBACTAMS
IV. CARBAPENEMS
V. COMBINATIONS WITH βLACTAMASE
INHIBITORS
BETA-LACTAMS
MoA:
l administration
AE:
Penicillin binding proteinPenicillin binding protein
Penicillines
l from Penicillium chrysogeum
l Basic structure: 6-aminopenicillanic acid
l semisyntetic – substitution in R position
Classes: basic
beta-lactamase resistant (against Staphylococcus)
wide-spectrum
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Basic penicillines
§ PNC G =
§ PNC V =
§ penamecillin (acetoxymetylester PNC G)
l acidostable
§ depot preparations:
§ Respiratory infections and others caused by G+
and G- cocci:
- streptococci, pneumococci, gonococci, meningococci,
aktinomykosis, anaerobic infections (gangrena
emhysematosa), lues, borreliosis, gonnorrhoea…
Beta-lactamase
resistant
§ Beta-lactamase = penicillinase
§ Infections by S. aureus
Wide-spectrum penicillines
§ Aminopenicillines
§ Carboxypenicillines
§ Ureidopenicillines
§ extended spectrum against G– (enterobac.) → E.coli, Salmonela spp.,
Shigella spp., pseudomonády, Haemophilus spp., Enterococcus spp.,
Proteus
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PNC combined with betalactamase
inhibitors
§ extended spectrum against G– (sulbaktam)
§ E. coli, Proteus, Salmonella, Haemophilus, M.
catarrhalis, Klebsiella, Neisseria, Enterobacter,
Bactoroides
§ 1st choice in otitis media and sinusitis
c.a. + amoxicillin(Augmentin)
+ tikarcillin
s. + ampicillin (Unasyn)
+ cephoperazon
t. + piperacillin
CEPHALOSPORINES
l Derived from 7-aminocephalosporanic acid
l Better resistance against beta-lactamase
l classification: 1. – 4. generation
AE:
I. generation
l G+ cocci (stafylococci, streptococci), E.coli, Proteus,
Klebsiela, Neisserie
l G- mostly resistant
Use:
l infections S. aureus, prophylaxis in surgery
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II. generation
l G+ and Gl
H. influ, enterobakterie, Neisseria, Proteus,
E. coli, Klebsiella, M. catarrhalis, anaerobs
and B. fragilis.
l Less effective against S. aureus than I.
generation
III. and IV. generation
III:
enterobacteria, partially pseudomonades
l more stable, higher activity (best against G-)
l penetration into CNS
IV:
l The widest spectrum
l G+ and G- bacteria (not anaerobes)
l high stability, longer half-life
MONOBACTAMS
Narrow antibacterial spectrum
l aerobic G- bacilli
l H. influenzae, E. coli, Klebsiella, Proteus, Pseudomonas aerug.
l antipseudomonase activity ↑ than ureidoPNC
I: sepsis, infections in abdominal cavity
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CARBAPENEMS
http://www.youtube.com/watch?v=Zy6XOwY3iJQ&feature=related
ATB except β-lactames
1) Amphenicols
2) Tetracyklines
3) Macrolides
4) Lincosamines
5) Aminoglycosides
6) Glycopeptides
1) AMPHENICOLS
MoA:
l Wide-spectrum including anaerobes
l Perfect tissue penetration, plasma leves after p.o and i.v.
are identical
l mtb. by glucuronidation in liver
l important AE
I: bacteral meningitis, typhus and paratyphus, severe pneumonias, anaerobic,
mixed, abdominal or sever hemophillus infections
It is not 1st choice in any indication!
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2) TETRACYCLINES
MoA:
I: infections of airways and urinary tract, mycoplasma infections,
chlamydia infections, borelliosis, leptospirosis, acne
(minocyclin), gonorrhea, syphilis
l good penetration into tissues (placenta!!!, HEB 10%)
l absorption is significantly reduced by antacides, milk and food rich with
Ca2+, Mg2+, Al3+ -) CHELÁTY!!!
AE:
2) TETRACYCLINES
l Glycylcyclines
l Basic
l Modified
l New (II.generation)
3) MACROLIDES
MoA:
l bacteriostatic
l Wide spectrum
l G+ G- bakteria (mycoplasma, chlamydia, spirocheta (Borelia burgdorferi),
neisseria, leptospira, campylobacter, legionella, Toxoplasma gondii,
Helicobacter pylori
l Increase in resistance in last years (4-46%)
l Streptococcus pyogenes (15 %) !!!, Streptococcus pneumoniae,
Staphylococcus aureus
l AE:
.
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3) MACROLIDES
- better tolerance, higher activity, lower toxicity
- better pharmacokinetics (interval of administration 12, resp. 24 h)
ATB related to macrolides
Azalids
Streptogramines
Ketolids
Oxazolidindiones
4) LINCOSAMINES
MoA:
Spectrum:
l G+ bakteria, anaerobes
l S. aureus, Str. pyogenes, pneumoniae
I: alternative therapy in patient not tolerating β-
lactams
AE:
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4) LINCOSAMINES
AE: GIT problems, allergies, hematotox.
interactions: macrolides, chloramphenicol
I: anaerobic and staphylococcus infections
- osteomyelitis
- infections in pelvic and abdominal area
- bacterial vaginal infections
- endokarditis prophylaxis
- acne
5) AMINOGLYCOSIDES
MoA:
l rapid bactericidal effects against almost all Gl
No effects on anaerobes, limited against streptococci
l parenteral application
l postantibiotic effect –1x day
I:
AE:
5) AMINOGLYCOSIDES
l classic l modern
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6) GLYCOPEPTIDES
MoA:
l bactericidal
l G+ flora – stafylococci, streptococci, enterococci
I: back-up ATB for severe and resistant G+
infections, locally (p.o.) intestine infections therapy
AE:
.
Other ATBs
Rifampicin
Fusidic acid
Polymyxin B, kolistin (polymyxin E; natrium kolistimethate)
.