9th lecture - antibiotics Flashcards
Antibiotics are substances produced by
microbes, fungi, animal-based and plant-based organisms that have a powerful antibacterial, antimycotic, partially also antiviral and anti-tumour activity.
Chemotherapy is the systematic administration of
substances with an antimicrobial effect and/or cytotoxic effect.
MIC means
minimum inhibitory concentration
which is the lowest concentration of antibiotics that inhibits the growth of microorganisms.
It is measured in micrograms per ml.
Explain Hospital-acquired infection
An infection caused by the microbes existing in the hospital environment.
The parallel in veterinary medicine – stable infection.
hospital aquired infections are also known as nosocomial.
Explain Infection recurrence
Relapse is the recurrence of a past medical condition with the same microbial strain.
Reinfection is infection following recovery from a previous infection with new agents or of another serotype of the same agent.
explain superinfection
a second infection superimposed on an earlier one especially by a different microbial agent of exogenous or endogenous origin that is resistant to the treatment used against the first infection.
Mechanism of action of antibiotics can be (2)
bactericidal
bacteriostatic
Substances that inhibit cell wall synthesis are
bactericidal.
Beta-lactam antibiotics such as (penicillins, cephalosporins), aztreonam, imipenem, vancomycin, bacitracin.
Beta-lactam antibiotics act how
bactericidal.
inhibit bacterial cell wall synthesis
2 examples of Beta-lactam antibiotics
penicillins, cephalosporins
Substances that inhibit the functions of the bacterial cell membrane are
bactericidal.
Polymyxins, colistin, aminoglycosides, nitrofurans.
Substances that inhibit microbial protein synthesis are
bacteriostatic.
Chloramphenicol, tetracyclines, macrolides, clindamycin, lincomycin, etc.
Substances that impact the microbial nucleic acid metabolism are
bacteriostatic.
Rifampicin, quinolones.
Antimicrobial resistance is
The adaptation of microbes to the substances that are harmful to them.
It is caused as a result of selection or adaptation.
The resistant population of microbes will remain after each antibiotic treatment.
Resistance is capable of passing from one generation of bacteria to the next and from one type of bacteria to another.
Main reasons for failures in antimicrobial treatment
Infection is caused by resistant strain – antibiotics are not effective.
Transfer of resistant gene from one bacteria to another (including normal microflora!), from one bacterial generation to another.
Treatment without specific bacterial diagnosis, disease can be caused by virus or there is no infection at all.
Lot of gram-negative microbes are resistant to ?
How?
beta lactams.
Some microbes evolve to have too few binding points for the AB molecule to bind to and thus it cannot enter the bacterial cell.
Some microbes produce betalactamases which break down the AB.
PBPs are
Penicillin-binding proteins (PBPs) are membrane-associated proteins involved in the biosynthesis of peptidoglycan (PG), the main component of bacterial cell walls.
These proteins were discovered and named for their affinity to bind the β-lactam antibiotic penicillin.
When bactria begin to grow resistant to beta lactams - one mechanism of this resistance is they evolve to have less AB binding points.
Streptococci are not susceptible to what type of AB?
aminoglycosides
Some microbes have natural barriers to AB such as streptococci to aminoglycosides.
Aquired resistance examples (2)
Mutations in bacterial chromosome.
Plasmids – genetic material, exists concurrently with the bacterial chromosomal DNA, carries resistance information.
E.g. plasmids mediate information that induces production of betalactamases in Staphylococcus aureus and some intestinal bacteria. Resistant bacteria survive after exposure to AB and are then spread.
Bacterial cross‐resistance can be defined as
resistance to multiple distinct antimicrobial agents conferred by a single molecular mechanism.
Or
resistance to all the antibiotics belonging to the same class due to a single mechanism.
Name 3 Structures responsible for transmissioon of resistance
Plasmids (small circular DNA molecule found in bacteria)
Transposons (class of genetic elements that can “jump” to different locations within a genome)
Integrons
(are genetic elements that contain a site-specific recombination system able to integrate, express and exchange specific DNA elements)
Describe Plasmids
Extrachromosomal self-replicating small, circular genetic elements.
Not necessary for the survival of the bacteria, but they carry genes that support some selective advantages to the host bacterium, e.g. antimicrobial resistance genes.
Can be transferred both vertically and horizontally between commensal and pathogenic bacteria and can lead to massive establishment of resistant pathogens in an individual animal within days.
Describe transposons
„jumping genes“ - specific DNA fragments, genetic elements.
They can not replicate themselves, but can move from one location to another in the chromosome.
Resistance genes can also move within the genome of a bacterial cell.
They can hop from the chromosome to a plasmid, between different plasmids and back to the chromosome, allowing development of different resistance gene combinations.
Describe integrons
They are usually part of composite transposons (jumping genetic elements).
They are not able to move themselves but encode mechanisms that can capture new resistance genes and to excise them, thereby increasing the horizontal mobility of resistance genes.
list mechanisms for Transmission of Resistant Genes (3+3)
Transformation, transduction, conjugation.
Plasmids
Transposons
Integrons
MECHANISM OF ACTION of
β-Lactam antibiotics
are bactericidal agents that interrupt bacterial cell-wall formation as a result of covalent binding to essential penicillin-binding proteins (PBPs), enzymes that are involved in the terminal steps of peptidoglycan cross-linking in both Gram-negative and Gram-positive bacteria.
