10th lecture - gram positive antibiotics Flashcards
beta-lactam antibiotics include: (4)
Penicillins and cephalosporins.
also carbapenems and monobactams
(these latter two more important for human med)
They contain a beta-lactam ring and are chemically similar.
antibiotics with effects against gram+ bacteria include what classes of antibiotics? (3+)
beta-lactam antibiotics (Penicillins, cephalosporins, carbapenems and monobactams)
Macrolides
Lincosamides
Pleuromutilins,
glycopeptides,
streptogramins
How many penicillins exist?
Over 40 penicillins have been synthesised.
1 IU = how many µg of pure standardised benzylpenicillin (Pen G) sodium salt.
1 IU = 0.6 µg of pure standardised benzylpenicillin (Pen G) sodium salt.
Penicillins are freely soluble, form salts, are easily…?
hydrolysable. Hydrolysis is the main reason for inactivation.
This may occur in the syringe together with other medicinal products and in the acidic environment of the stomach.
The alkaline sodium salts of sulfonyl amides inactivate?
penicillin.
Penicillin is incompatible with (3)
heavy metal salts, oxidizing substances and alcohol.
(render it inactive)
What do many microorganisms produce that is an antagonist of penicillin and one of the reasons for resistance and ineffectiveness?
Many microorganisms produce beta-lactamase enzyme (penicillinase).
Classification of Penicillins (5)
Natural Penicillins
Acid-resistant penicillins
Penicillinase resistant penicillins
Synthetic broad (extended) spectrum penicillins
Antipseudomonal penicillins
Natural Penicillins include (2)
Benzylpenicillin or Penicillin G which is produced by fermentation.
When administered using the oral route, it is quickly broken down by gastric acid.
Acid-resistant penicillins include (1)
Phenoxymethylpenicillin, commonly known as penicillin V, can be administered using the oral route/ isnt destroyed by gastric acids.
Penicillinase resistant penicillins include (3)
Oxacillin, cloxacillin, nafcillin and others
Synthetic broad (extended) spectrum penicillins
include (3)
Aminobenzyl penicillins: ampicillin, amoxicillin
Amidopenicillins: mecillinam (only for human med).
Antipseudomonal penicillins include (2)
Carboxypenicillins: carbenicillin, ticarcillin
Ureidopenicillins: azlocillin, mezlocillin, piperacillin
These are only for human med.
Spectrum of activity of Natural penicillins/ are effective against?
Streptococci, non-penicillinase-producing staphylococci, some G+ and G- bacteria
e.g. Corynebacterium, Listeria monocytogenes, Pasteurella multocida, Haemophilus influenzae.
Anaerobes: Fusobacterium, Peptococcus, Peptostreptococcus, Bacteroides (some strains), Clostridium.
Spirochaetes: Leptospira, Borrelia.
Spectrum of activity of Aminopenicillins:
They are effective when there is resistance to natural penicillins.
Additionally, some enterobacteriaceae (E. coli, Proteus, Salmonella).
Spectrum of activity of Penicillinase resistant penicillins:
Staph. aureus b+, some G+ ja G- bacteria and spirochaetes.
They are generally of lower effectiveness than other penicillins.
Spectrum of activity of Extended spectrum penicillins:
enterobacteriaceae, Pseudomonas, Proteus, Salmonella, Klebsiella.
They are of a lower effectiveness against other bacteria compared to other penicillins.
Absorption of penicillins
they absorb quickly when administered into muscle or under the skin.
Larger doses are required when administering through the oral route.
Distribution of penicillins
diffuse from blood plasma to tissue with the concentration gradient.
Larger concentration in the kidneys and liver compared to other tissues.
poorly penetrate the blood–brain barrier and placental barrier. Short half-life.
Excretion of penicillins
mainly with urine
90% is eliminated unchanged.
Mechanism of action of penicillins
bacteriocidal:
inhibition of microbial cell wall synthesis
The basis of this effect is the inhibiting of the microbial cell wall synthesis on the transpeptidase enzyme level and the outcome is lysis of the cell.
penicillins are most effective during the growing phase of bacteria.
Penicillins primarily act against
gram+ microbes
The biological inactivation of penicillin is relatively
unclear. The inactivation occurs in the stomach partially as a result of hydrochloric acid and bacterial enzymes.
Penicillin in the blood is mostly in plasma and 10% also in
the erythrocytes.
A portion of penicillin metabolises using an unknown mechanism. 90% is eliminated unchanged.
describe Penicillin Toxicity/side effects (3)
They have the lowest level of toxicity among antibiotics.
The most frequent side effect is allergic reactions that range from mild skin conditions to lethal anaphylactic shock.
Also possible: hives, hypersalivation, vomiting, cramps. In isolated cases, pregnant animals may abort (sows).
Cephalosporins are
Semisynthetic antibiotics that are chemically similar to penicillins.
First-generation cephalosporins have the highest activity against gram-positive organisms and the lowest against gram-negative.
Based on spectrum of activity and pharmacokinetic differences, cephalosporins are divided into
five generations, with the addition of some active substances that are not classified intothe generations.
1st and 2nd gen. used in veterinary med
First-generation cephalosporins spectrum of activity?
Give drug examples.
are of a narrow spectrum of activity, mainly acting against G+ microbes.
Cephalothin,
cephalexin,
cephaloridine,
cefacetrile.
Second, third and fourth generation cephalosporin spectrum of activity?
a wide spectrum of activity and act against G+ cocci and most G- microbes.
Examples of Second generation cephalosporins: (3)
cefuroxime, cefamandole and cefoxitin.
Examples of Third generation: cephalosporins (4)
ceftriaxone, cefotaxime, ceftiofur, ceftazidime.
Fourth generation cephalosporin example:
cefquinome
(Fifth generation: ceftobiprole, ceftaroline (not used in veterinary medicines))
Cephalosporins administration route
oral route, some can be administered parenterally.
First and second generation cephalosporins do not penetrate where? whilst 3rd gen. do
the central nervous system.
Third generation substances penetrate the blood–brain barrier and may be used in case of brain infections.
Paradoxically The fourth generation cephalosporins are indicated for use in the treatment of mastitis however?
legislation dictates they should not be utilized in vet med.
Cephalosporins Toxicity
They are of low toxicity but hypersensitivity reactions can occur.
Cephalosporin side effects
Allergy and pain at the site of the injection may be experienced.
Cross-reacting allergy can occur meaning if someone is hypersensitive or resistant to penicillins, the same will apply to the cephalosporins due to chemical similarity.
Spectrum of activity of 1st generation cephalosporins
Streptococci, Staphylococci, E. coli, Proteus mirabilis, Klebsiella.
do not use which gen.s of cephalosporins in vet med?
do not use third to fifth generation cephalosporins in veterinary medicine (the fifth generation is not used in veterinary medicine anyway).
amoxicillin and clavulanic acid synergistic mechanism
Amoxicillin on its own is vulnerable to destruction by beta-lactamases produced by some bacteria. However, clavulanic acid destroys the beta-lactamases allowing amoxicillin to remain active.
Name some beta lactamase inhibitors
Clavulanic acid
Sulbactam
Tazobactam
They are of low antibacterial activity, but inactivate bacterial beta-lactamase,.
They are used in combination with beta-lactam antibiotics (e.g. amoxicillin + clavulanic acid).
Carbapenems use in vet med is
limited!
Can be used in dogs and cats but use should not be frequent.
Examples of carbapenems (3)
Imipenem, meropenem, biapenem.
carbapenems are Active against
almost all clinically important aerobic and anaerobic gram-positive and gram-negative cocci or rods.
describe Monobactams
belong to the class beta-lactams.
Used in human medicine in a wide variety of infections involving gram-negative bacteria.
Rarely used in veterinary medicine.
describe Macrolides
a class of AB that (are not beta-lactams!)
They have a complex chemical structure, acting agasint many G+ microbes and some Listeria strains.
Examples of common macrolides
erythromycin,
tylosin,
spiramycin,
tilmicosin,
tulathromycin,
gamithromycin and
tylvalosin.
Macrolides are frequently used when
the microbe is resistant to beta-lactam antibiotics.
Macrolides mechanism of action
inhibit bacterial protein synthesis.
They are bacteriostatic and in large concentrations bactericidal.
Macrolides pharmacokinetics, absorption
They absorb well in case of all routes of administration and are evenly distributed in the organism.
They poorly penetrate the blood–brain barrier and penetrate well the placental barrier.
The half-life may shorten in in sick organisms.
Macrolides pharmacokinetics, excretion
Metabolism is mostly in the liver, they are excreted in the bile to a large extent, thus they are suitable for treatment of bile duct infections.
(e.g.erythromycin and tylosin)
Macrolides Toxicity/side effects
possible side effects from PO route: vomiting, diarrhoea (mainly in cats), increased salivation.
Swelling and irritation may occur at the site of administration.
The most serious side effects are experienced by horses.
Advanced generation macrolides include what products:
Roxithromycin,
dirithromycin,
clarithromycin,
azithromycin.
What are Advanced generation macrolides exactly?
They are newer macrolides that are
acid stable,
produce fewer gastrointestinal side effects,
have higher bioavailability following oral administration,
longer half-lives,
higher tissue concentrations.
Still limited experience in veterinary medicine (used in dogs, cats, foals).
Newer macrolides may have advantages in the treatment of
intracellular infections in monogastrics; e.g. Bartonella, Chlamydophilia psittaci, atypical mycobacterial infections.
Ketolides are
Semisynthetic new macrolides such as telithromycin, cethromycin.
Developed for oral use.
Spectrum of activity similar to newer macrolides.
Used in human medicine (generally).
Lincosamides are
chemically similar to macrolides. They are not beta lactams.
Representatives are lincomycin, clindamycin and pirlimycin.
Lincosamides act against
many G+ microbes, anaerobes and mycoplasmas.
They are bacteriostatic. They inhibit microbial cell protein synthesis.
Lincosamides Pharmacokinetics, absorption
They are absorbed and distributed well following administration through the oral route and in muscle.
e.g. clindamycin
Lincosamides Pharmacokinetics, excretion
They are metabolised in the liver and excreted to a large extent in the bile, 20% is excreted unchanged in urine.
Lincosamides Antimicrobial activity
Gram-positive aerobes: Bacillus spp., staphylococci, streptococci (not enterococci).
Gram-negative: Campylobacter jejuni, many anaerobes including Actinomyces spp., Bacteroides spp.
Clindamycin has activity against some protozoa: toxoplasma gondii, plasmodium falciparum.
Clindamycin belongs to which class?
It has activity against some protozoa such as?
class lincosamides
toxoplasma gondii, plasmodium falciparum.
Lincosamides side effects/toxicity
As a side effect, they may cause diarrhoea, especially in humans, horses and rabbits.
Cattle may experience lack of appetite, diarrhoea, ketosis and a reduction in milk production.
Horses may experience hemorrhagic colitis and fatal diarrhea.
Lincosamides are particularly toxic to?
They are particularly toxic to sheep, rabbits, guinea pigs and hamsters.
They are of a relatively low toxicity to dogs and cats.
Pleuromutilins mainly act against
anaerobes and mycoplasmas.
Pleuromutilins are not beta lacrams, Representatives are tiamulin (pigs & poultry) and valnemulin.
Side effects are mainly allergic reactions.
Not to be used in horses.
describe Streptogramins
are not beta lactams.
They inhibit bacterial protein synthesis.
Natural: virginiamycin, pristinamycin.
Semisynthetic: quinupristin, dalfopristin.
Virginiamycin can be used in swine to control dysentery, but results have sometimes been poor – the drug does not eradicate infection, treatment period is several weeks.
Describe Glycopeptides
are not beta lactams.
Are active against gram-positive bacteria, particularly gram-positive cocci.
examples are:
Vancomycin.
Dalbavancin.
Oritavancin.
Teicoplanin.
Telavancin.
name a Glycopeptide AB serious human health concern
Vancomycin which belongs to the group called glycopeptides, has resistance against it in the Enterococcus spp (VRE-vancomycin resistant enterococci).
Cephalosporins Mechanism of action
Bactericidal, inhibit of the microbial cell wall synthesis.
