KSMU

Department of clinical pharmacology

"Clinical pharmacology of antibacterial drugs»

Lecturer, associate Professor Yulia Luneva

 THE MAIN CHARACTERISTICS OF
ANTIBACTERIAL AGENTS (1)

1. Spectrum of action
• broad
• narrow (Gr+, Gr-)
• effects on aerobic
and / or anaerobic
flora
2. Origin of the drug
• natural
• semi-synthetic
• synthetic
 THE MAIN CHARACTERISTICS OF
ANTIBACTERIAL AGENTS (2)
3. The mode of the action.
bactericidal
bacteriostatic
 THE MAIN CHARACTERISTICS OF ANTIBACTERIAL
AGENTS (3)
These types of actions are
implemented using the
following mechanisms:
• Interferes with the cell
wall synthesis or
maintenance
• disturbance of function
of the cytoplasmic
membrane
• Interferes with protein
and nucleic acid
synthesis
• violation of the
synthesis of
intermediates
 THE MAIN CHARACTERISTICS OF
ANTIBACTERIAL AGENTS (4)
4. Acid resistance.
5. Features of pharmacokinetics
(duration of action, ability to accumulate
in any organ).
6. Resistance to adverse effects of
microorganisms on antibiotics (the
ability to maintain its therapeutic
activity).
Penicillins
 CLASSIFICATION OF PENICILLINS
Natural benzylpenicillin,
benzylpenicillin procainbenzatin,
benzylpenicillin phenoxymethylpenicillin
Isoxazolyl oxacillin,
penicillins cloxacillin,
dicloxacillin
Amino penicillins amoxicillin,
ampicillin
carbenicillin,
Carboxy penicillins ticarcillin

Ureido penicillins azlocillin,

piperacillin,
meslocillin
Penicillin activity spectrum
 Ceftaroline fosamil
• Active against Gram "+" cocci
(streptococcus, Staphylococcus aureus);
Klebsiella, Escherichia coli and
Haemophilus influenzae
• Microorganisms with natural
resistance: Chlamydophila spp.,
Legionella spp., Mycoplasma spp.,
Proteus spp., Pseudomonas aeruginosa.

Indications:
• Skin and soft tissue infections
• Community-acquired pneumonia
 Ceftolosan + Tazobactam
The drug is active against: Complicated intra-abdominal infections
1. Gram-negative microorganisms:
Enterobacter cloacae
Escherichia coli
Klebsiella oxytoca
Klebsiella pneumoniae
Proteus mirabilis
Pseudomonas aeruginosa
2. Gram-positive microorganisms:
Streptococcus anginosus
Streptococcus constellatus
Streptococcus salivarius
Complicated urinary tract infections, including pyelonephritis.
• Gram-negative organisms:
Escherichia coli
Klebsiella pneumoniae
Proteus mirabilis
Indications:
Complicated Intraabdominal Infections.
Complicated urinary tract infections, including pyelonephritis.
 CARBAPENEMS
• Imipenem (thienam = imipenem + cilastatin)
• Meropenem
• Ertapenem
• Doripenem
 CARBAPENEMS
Pharmacodynamics
Meropenem vs imipenem:
• more active against Gr - bacteria,
• less active against staphylococci and
streptococci,
• not inactivated in the kidneys,
• does not have pre-convulsive activity,
• less likely to cause gastrointestinal upsets.
 CARBAPENEMS
Ertapenem compared with imipenem and
meropenem:
•
less active against non-fermenting Gr “-” bacteria
(pseudomonas, akinetobacter),
• has priority in use in community-acquired
pneumonia,
• not inactivated in the kidneys,
• resistant to many types of beta-lactamases
(including extended spectrum)
 CARBAPENEMS
Pharmacodynamics Doripenem vs imipenem and
meropenem:
•
more active against Gr-bacteria, incl. 2-4 times more
pronounced effect on Pseudomonas aeruginosa,
• active against methicillin-sensitive staphylococci,
• not inactivated by the enzymes of most
microorganisms,
• does not inhibit the enzymes of the cytochrome P450
system,
• does not have pre-convulsive activity.
 MONOBACTS – aztreonam
• Features of the spectrum of action.
Aztreanam is active against aerobic Gr -
microorganisms, incl. producing β-
lactamases and resistant to penicillins and
cephalosporins.
• Does not affect anaerobes, MRSA, Gr +
cocci.
• Destroyed by β-lactamases of these
microorganisms.
Classification of macrolides according to the
carbon number of lactone ring
• 14 – 15 - 16 -membered ring macrolides
ANTI-MICROBIAL SPECTRUM ACTIONS OF
MACROLIDES

• gram-positive bacteria
• gram-negative bacteria other
than Enterobacteriaceae
• intracellular pathogens
• anaerobes
 TETRACYCLINES

1 NATURAL TETRACYCLINES
• tetracycline
• oxytetracycline
• chlortetracycline
-
2 SEMI-SYNTHETIC TETRACYCLINES
• doxycycline
• rolytetracycline
• morphocycline
• metacyclin
• minocycline
 Pharmacokinetics of doxycycline.
• Doxycycline is more lipophilic and creates a
higher concentration in tissues than
tetracycline,
• the bioavailability of doxycycline is
independent of food intake,
• the drug is excreted through the kidneys
and gastrointestinal tract.
• Doxycycline is characterized by slightly
higher antistaphylococcal activity.
 Classification of Aminoglycosides

I II III IV V
generation generation generation generation generation

Streptomycin Gentamicin
Neomycin Tobramycin
Amikacin Isepamycin Plazomycin
Kanamycin Netilmicin
Monomycin Sizomycin
 SPECTRUM OF ACTION
• Dose-dependent bactericidal activity against
the Enterobacteriaceae family (E. coli,
Proteus spp., Klebsiella spp. And others),
non-fermenting gram-negative bacilli (P.
aeruginosa, Acinetobacter spp.).
• Aminoglycosides are active against
staphylococci (except MRSA).
• Aminoglycosides are inactive against S.
pneumoniae, anaerobes (Bacteroides spp.,
Clostridium spp., Etc.).
 Plazomycin
• It has a wide spectrum of bactericidal activity against
multiresistant gram-negative microorganisms of the
Enterobacteriaceae family, including strains resistant to
carbapenems.
• Active against bacteria that are resistant to other
aminoglycosides because it is not exposed to
aminoglycoside inactivating enzymes.
• Approved for use in the treatment of complicated UTI
(including pyelonephritis) caused by Escherichia coli,
Klebsiella pneumoniae, Proteus mirabilis, or Enterobacter
cloacae in adult patients with limited treatment options or
in the absence of alternative treatment options.
 Pharmacodynamics
Compared to gentamicin: netilmicin is
• active against gentamicin-resistant microorganisms,
• less nephro-and ototoxic.

Amikacin
• acts on gentamicin- and non-tilmicin-resistant
microorganisms,
• is active against Mycobacterium tuberculosis
and some atypical bacteria, and is less toxic.
Quinolones
 Quinolones CLASSIFICATION

Non-fluorinated
Fluorinated
Standard (old) Anti-pneumococcal
(new)
oxolinic acid norfloxacin Levofloxacin
nalidixic acid ofloxacin sparfloxacin
pipemidic acid pefloxacin moxifloxacin
ciprofloxacin hemifloxacin
lomefloxacin
 Glycopeptides
• vancomycin
• teicoplanin

Features of the spectrum of action.

Drugs inhibit aerobic and anaerobic
Gr + microorganisms (including
MRSA)
 Pharmacokinetics
• The drugs are not absorbed in the digestive tract
(administered parenterally),
• are not metabolized,
• excreted through the kidneys unchanged.
Pharmacodynamics
• Vancomycin is the drug of choice for infections
caused by MRSA, penicillin and aminoglycoside-
resistant enterococci.
• Teicoplanin compared with vancomycin is more
active against MRSA and enterococci, including
vancomycin resistant strains.
 OXAZOLIDINONES
- linezolid

Features of the spectrum of action.

Linezolid has a bactericidal effect on aerobic
and anaerobic Gr + microorganisms (including
MRSA, vancomycin-resistant enterococcus
strains), including strains resistant to penicillin,
ceftriaxone, clindomycin, tetracycline,
chlorampheniol.
 Cyclic lipopeptides
Daptomycin
The drug is characterized by bactericidal action
against:
• a wide range of Gram (+) pathogens, including
MRSA,
• S.aureus with intermediate sensitivity to
vancomycin,
• vancomycin-resistant S.aureus
• and vancomycin-resistant enterococci.
 Glycylcyclines.
The active substance in Tygacil, tigecycline,
belongs to a group of antibiotics called
‘glycylcyclines’.
• A wide spectrum of action against aerobic and
anaerobic gram-positive and gram-negative
microorganisms, multiresistant microorganisms
(MRSA, enterobacteria producing extended-
spectrum beta-lactamases, most species of
Acinetobacter spp.), Intracellular bacteria.
• Tigecycline is not active against Pseudomonas
aeruginosa.
 NITROIMIDAZOLE DERIVATIVES
- metronidazole (I generation)
- tinidazole (II generation)
- ornidazole (II generation)

Spectrum of action.
• Active against Gr + and Gr-anaerobes
(bacteroids, cocci, fusobacteria, clostridia),
some protozoa (Trichomonas, Giardia,
amoeba, balantidia), Helicobacter pylori,
• Inactive against aerobic bacteria
(staphylococcus, enterobacteria).