immuno bac Flashcards
whats prontosil
the first example of a sulphonamide antibiotic
only effetcive with gp bacteria
charateritics
Bacteriostatic.- doesnt kill only stop repliccating
Synthetic
what is it sometimes used with
Trimethoprim called (co-trimoxazole). both have some function
treat
UTIs, RTIs, bacteraemia and prophylaxis for HIV+ individuals.
Bactericidal
kills bacteria.
Bacteriostatic
stops bacteria growing
Antimicrobial
hemical that selectively kills or inhibits microbes (bacteria, fungi, viruses).
Antiseptic
chemical that kills or inhibits microbes that is usually used topically to prevent infection.
what does ab resistance lead to
AB resistance leads to increased mortality, morbidity and cost
Increased time to effective therapy.
Requirement for additional approaches – e.g. surgery.
Use of expensive therapy (newer drugs).
Use of more toxic drugs e.g. vancomycin.
Use of less effective ‘second choice’ antibiotics.
where are Aminoglycosides
Bactericidal.
Target protein synthesis (30S ribosomaml subunit), RNA proofreading and cause damage to cell membrane.
Toxicity has limited use, but resistance to other antibiotics has led to increasing use.
can cause hearing loss
what is Rifampicin
Bactericidal.
Targets RpoB subunit of RNA polymerase.
Spontaneous resistance is frequent.
Makes secretions go orange/red – affects compliance taking long causes
what is Vancomycin
Bactericidal.
Targets Lipid II component of cell wall biosynthesis, as well as wall crosslinking via D-ala residues
Toxicity has limited use, but resistance to other antibiotics has led to increasing use e.g. against MRSA
given intravenously
what is Linezolid
Bacteriostatic.
Inhibits the initiation of protein synthesis by binding to the 50S rRNA subunit.
Gram-positive spectrum of activity.
doesn’t effect gn
Daptomycin
Bactericidal. Targets bacterial cell membrane. Gram-positive spectrum of activity. Toxicity limits dose. can't target lps on gn given intervenosly
Beta-lactams
Interfere with the synthesis of the peptidoglycan component of the bacterial cell wall.
Examples include Penicillin and methicillin.
Bind to penicillin-binding proteins.
PBPs catalyse a number of steps in the synthesis of peptidoglycan.
inhibite biosythesis of cell wall
Antibiotics target many different bacterial processes and are selectively toxic
they inhibit process in bacterial cell not in human cells
The large number of differences between mammals and bacteria result in multiple targets for antibiotic therapy – selective toxicity
What is unique to bcteira
peptidoglycan wall
lpa
Macrolides
treats gonococal
Gram-positive and some Gram-negative infections.
Targets 50S ribosomal subunit preventing amino-acyl transfer and thus truncation of polypeptides.
preventing growth
Quinolones
Synthetic, broad spectrum, bactericidal.
Target DNA gyrase in Gm-ve and topoisomerase IV in Gm+ve. dna damage and death of organism
against gonnocal and lung
Breakpoint
(clinically-achievable concentration)
if bacteria can grow at that point or higher than reistant, if less that suseptible
what does routine use of penicllin provide
Routine use of penicillin provided selective pressure for the acquisition and maintenance of resistance genes.
how does antiboitic resistance occur
Altered target site.
Inactivation of antibiotic.
Altered metabolism.
Decreased drug accumulation.
what is altered target site
Can arise via acquisition of alternative gene or a gene that encodes a target-modifying enzyme.
Methicillin-resistant Staphylococcus aureus (MRSA) encodes an alternative PBP (PBP2a) with low affinity for beta-lactams.
Streptococcus pneumoniae resistance to erythromycin occurs via the acquisition of the erm gene, which encodes an enzyme that methylates the AB target site in the 50S ribosomal subunit.
Inactivation of antibiotic
Enzymatic degradation or alteration, rendering antibiotic ineffective.
Altered metabolism
Increased production of enzyme substrate can out-compete antibiotic inhibitor (e.g. increased production of PABA confers resistance to sulfonamides).
Alternatively, bacteria switch to other metabolic pathways, reducing requirement for PABA.
Decreased drug accumulation
Reduced penetration of AB into bacterial cell (permeability) and/or increased efflux of AB out of the cell – drug does not reach concentration required to be effective.
Sources of antibiotic resistance genes
Plasmids – extra-chromosomal circular DNA, often multiple copy. Often carry mutliple AB res genes – selection for one maintains resistance to all.
Transposons. Integrate into chromosomal DNA. Allow transfer of genes from plasmid to chromosome and vice versa.
Naked DNA. DNA from dead bacteria released into environment.
what is transformation
allow bacteria to take up dna from their environment
plasmid or chromosomes
Transduction
phage-mediated DNA transfer)
Conjugation
pilus-mediated DNA transfer)
Biofilm
matrix encased community of bacteria that are highly drug tolerant
intracellular location
in human cells shielding them
Slow growth
if they not using lots of process to replicate then antiboitics can’t inhibit them
Spores
VERY RESISTANT TO HEAT SNTISEPTIC AND ANTIBOITIC
Persisters
dormant
not using any process that are inhibited by antibiotics
Non-genetic mechanisms of resistance/treatment failure
Biofilm Intracellular location Slow growth Spores Persisters
why may treatment fail
Inappropriate choice for organism
Poor penetration of AB into target site
Inappropriate dose (half life)
Inappropriate administration (oral vs IV)
Presence of AB resistance within commensal flora e.g. secretion of beta-lactamase
can Genes encoding resistance can be shared between bacteria via horizontal gene transfer
yep
why do hospitals provide strong selective pressure for AB resistance
Large numbers of infected people receiving high doses of antibiotics - strong selective pressure for emergence/maintenance of AB resistance
Risk-factors for HAI
High number of ill people! (immunosuppression)
Crowded wards
Presence of pathogens
Broken skin – surgical wound/IV catheter
Indwelling devices - intubation
AB therapy may suppress normal flora
Transmission by staff – contact with multiple patients
why is bacteria killing gut and microbiota dangerous
Pathogen has no competition - overgrowth
Addressing resistance
Prescribing strategies – tighter controls, temporary withdrawal of certain classes. Restriction of ABs for certain serious infections
Reduce use of broad-spectrum antibiotics- damage microbiota
Quicker identification of infections caused by resistant strains
Combination therapy 2 or more ab tohether
Knowledge of local strains/resistance patterns
Overcoming resistance
Modification of existing medications to e.g. Prevent cleavage (beta-lactams) or enhance efficacy. E.g. Methicillin.
Combinations of antibiotic + inhibitor of e.g. Beta-lactamase. E.g. Augmentin.
how to fungi eat
ukaryote organisms that digest their food outside of the cell by secreting hydrolytic enzymes which can break down biopolymers to be absorbed for nutrition
what do fungi cause
Allergy – allergic reactions to fungal products e.g. allergic bronchopulmonary aspergillosis (ABPA)
Mycotoxicoses – ingestion of fungi and their toxic products e. g. aflatoxin
Mycoses – superficial, subcutaneous or systemic colonisation, invasion and destruction of human tissue.
what are the targets for antifungal therapy
cell membrane
dna sythesis
cell wall
