Antimicrobial chemotherapy Flashcards
what is MIC
minimal inhibitory concentration
the minimum conc of antimicrobial needed to inhibit the growth of a given organism
What is MBC
minimal bacterial conc.
minimum conc. of antimicrobial needed to kill a given organism
sensitive
organism is sensitive if it is inhibited or killed by the antimicrobial available at the
site of infection
resistant
organism is resistant if it is not killed or inhibited by the antimicrobial available at the
site of infection
bacteriocidal
antimicrobial that
kills bacteria
(penicillins)
bacteriostatic
antimicrobial that inhibits growth
of bacteria
(erythromycin)
What are antibiotics only active against?
bacteria
which 3 areas of metabolic activity may antibiotics act on to inhibit or kill bacteria?
inhibition of cell wall synthesis (e.g penicillins and cephalosporins
also glycopeptide antibiotics)
inhibition of nucleic acid synthesis (e.g trimethoprim and ciprofloxacin)
inhibition of protein synthesis (e.g gentamicin and erthromycin)
Discuss polyene drugs (antifungal)
class of extremely toxic drugs with a wide range of side effects including, renal, hepatic and cardiac toxicity
they bind to ergosterol, which is present in the fungal cell wall and this results in an increase in the permeability of the cell wall
they also bind to other sterols e.g cholesterol in mammalian cell membranes and this is the reason why they are toxic in humans
Discuss azole (antifungal) drugs
class of drugs inhibit ergosterol synthesis so disrupt cell wall.
what do the anti-fungal drugs allylamines do?
also suppress ergosterol synthesis, but act at a different stage of the synthesis pathway from azoles
The only allyalmine in common use is terbinafine. This drug is used for fungal infection of skin and nails (ringworm, athlete’s foot etc)
what to the antifungal drugs called echinocandins do?
they inhibit the synthesis of glucan polysaccharide in several types of fungi- target cell wall
they are used for serious Candida and Aspergillus infections
Antiviral drug types
anti-herpes virus drugs
anti-HIV drugs
drugs for chronic Hep B and C
drugs for viral respiratory infections
anti-herpes virus drugs
aciclovir is a class of anti-herpes drugs
they are nucleoside analogues ie disrupt nucleic acid synthesis
IV form given to treat severe infections
specific for viral infected cells- as only works once activated by an enzyme coded for by virus genome
-has a very low toxicity for uninfected host cells
Antibiotics that inhibit cell wall synthesis
penicillins and cephalosporins- these groups contain Beta lactams (rings)
parenteral route of administration?
intra-venously (iv)
or intra-muscularly (im),
occasionally subcutaneously.
which test allows you to compare the MIC of one antibiotic against another organism?
E-test
examples of polyenes
anti-fungal
amphotericin B - serious fungal + yeast infections
Nystatin- topically or in oral suspension- skin and vaginal infections etc
examples of Azoles
Fluconazole is used to treat a yeast infection. Not all yeasts are sensitive to flucanazole
voricanazole, itraconazole - fight aspergillosis
examples of echinocandins
caspofungin- used in serious candida and aspergillus infection, safe, only given by IV
micafungin
anti-HIV drugs
zidorudine- first ever drug used for this- nucleoside analogue
slows replication but doesn’t kill it
nowadays combination therapy is common in HIV treatment
Viral respiratory infections: drugs to treat this
zanamivir and oseltamivir - treat influenza A or B within 48 hours of onset of symptoms
ribavirin
who is aciclovir restricted from
patients with renal impairment as without excreting it toxicity levels rise so we want to prevent neurological toxicity
what are 2 ways to combat Beta-lactamase (produced by bacteria to be resitant to antibiotics)?
- introduce 2nd component to the antibiotic (B-lactamase inhibitor) protecting the antibiotic from enzymatic degradation
- modify antibiotic side chain producing new antibiotic resistant to actions of B-lactamase (flucloxicillin)
inherent or intrinsic resistance
bacteria’s natural ability to resist antibiotics due to its inherent structural or functional characteristics
acquired resistance
via spontaneous mutation or spread of resistance by plasmid -genetic transfer or by transposons
what is the major current issue relating to bacterial resistance
widespread use of antibiotics causes selective pressure and encourages new resistant organisms to outgrow sensitive strains
bacteria are becoming more and more resistant to everyday antibiotics and soon we won’t be able to fight many diseases/infections that would normally be treatable
common antibiotics that inhibit cell wall synthesis
penicillins, cephalospoirins, vancomysin, teicoplanin
common antibiotics that inhibit protein synthesis
gentamicin, erythromicin
common antibiotics that inhibit DNA synthesis
trimethoprim, sulphamethoxazole, ciprofloxacin
How do drugs inhibit cell wall synthesis?
they inhibit kill the bacteria by disrupting peptidoglycan from cross-lining the carbohydrate chains. They do this by inhibiting the enzymes responsible for this.
peptidoglycan layer is important for cell wall structural integrity in bacteria however more so in gram positive as it is in the outer membrane.
Gram negative have peptidoglycan in it’s 3rd membrane in so is less sensitive to this kind of inhibition
Why are humans not affected by antibiotics that inhibit C.W synthesis?
eukayrotic cells do not have a cell wall
How do bacteria grow resistance to penicillin/ cephalosporins?
bacteria can synthesise a Beta-lactamase, an enzyme that attacks the beta lactam ring- which is essential in the effectiveness of the antbiotic
vancomycin and teicoplanin?
only able to penetrate the gram +ve cell wall due to being hydrophilic
they are not absorbed by the GI tract and so are only given parenterally (IV etc)
they act on a different stage of C.W synthesis than Beta lactamase
they inhibit the assembly of peptidoglycan precursor
what does inhibition of protein synthesis entail?
interruption of translation of messenger mRNA at the ribosome
gentamicin antibiotic
an aminoglycoside (class)
it’s toxic
targets mRNA by disrupting the way a specific codon of mRNA is read by RNA polymerase
insert a different amino acid into the sequence so the protein doesn’t work
useful for gram -ve treatment
why are humans not affected by gentamicin?
it only attacks bacterial ribosomes as they are different to human ones
erythromicin antibiotic
part of macrolides class inhibits protein synthesis by preventing the peptide bond from being created along amino acids useful alternative for patients who are allergic to penicillin
what does inhibition of nucleic acid synthesis entail?
wide range of antibiotics inhibit DNA synthesis either directly, or indirectly by interrupting the supply of precursors for DNA synthesis
or inhibition of different steps in purine synthesis A+G bases
Trimethoprim and sulphamethoxazole antibiotics
used in combined form in the drug ‘co-trimoxazole’
trimethoprim inhibits purine synthesis ie A+G bases on DNA won’t be in DNA so they’re no longer there in translation of RNA so not in the protein as a result- DNA structure no longer has correct amount of purine needed (need the same A-T and G-C)
bacteria will die as they can no longer replicate
ciprofloxacin antibiotic
fluoroquinolones class inhibit DNA synthesis more directly as it interrupts/inhibits function of DNA gryase (an enzyme that can wrap/unwrap DNA) so by inhibiting it and keeping DNA wrapped up there is no access to the DNA molecule for DNA replication to occur CAN'T BE USED IN CHILDREN
which common infections do penicillins treat?
chest infections
skin infections
UTI’s
which common infections does gentamicin treat?
staph. aureus
endocarditis
UTI’s
pneumonia
which common infections does erythromicin treat?
it treats respiratory tract infections ie bronchitis, whooping cough,
what does trimethoprim treat on its own? and what does it treat combined with sulfamethoxazole?
on it’s own: UTI’s
combined: chest infections
which common infections does cephalosporins treat?
septicaemia
pneumonia
meningitis
UTI’s
antibacterial resistance can be 2 things?
inherent or intrinsic
acquired
inherent or intrinsic resistance- explain
bacteria’s natural ability to resist antibiotics due to it’s inherent structural or functional characteristics
STREPTOCOCCI are always resistant to aminoglycosides
gram -ve always resistant to vancomycin as it is unable to pass through lipopolysaccharide outer membrane so can’t kill it effectively/exert its action
acquired resistance
via spontaneous mutation or spread of resistance by plasmid- genetic transfer or by transposons
which common bacteria is resistant to penicillin and why?
staph. aureus as it can produce Beta lactamase which inactivates penicillin by hydrolysing the beta lactam ring
what are two ways to combat Beta lactamase
introduce a second component to the antibiotic (Beta lactamase inhibitor) protectinng the antibiotic from enzymatic degradation
or
modify antibiotic side chain producing new antibiotic resistance to actions of Beta lactamase
can an infection be caused by a patients own microbiological flora?
yes for example in a UTI, E.coli from the gut causes infection
what types of diseases are TB, leprosy and syphilis?
granulomatous diseases
what are 2 common resistant mechanisms of staph aureus
Producing Beta lactamase
MRSA- has a gene that codes for Penicillin binding protein (PBP)- changes the active site of the antibiotic- not inhibited by beta lactam
which drug is the drug of choice treating MRSA?
Vancomycin (very toxic- careful with administration)- acts on CW synthesis at stage prior to beta lactamase
or paptomycin
What does MRSA stand for?
(meticillin)-resistant S. aureus (MRSA)
once you detect MRSA infection in a patient what happens?
isolate patient
treat with antibiotics
attempt treatment in different way- different combinations/ modify side chain
Which antibiotic is not inactivated by beta lactamase and should be used to treat infections caused by penicillin-resistant staphylococci?
flucloxacillin
drugs for chronic Hep B and C
Interferon alpha
lamivudine
what is nitrofurantoin?
an antibiotic used to treat bladder infections and UTIs
benzylpenicillin treatment for what?
pneumococcus or meningococcus bacteria- once you find this without meningitis use this antibiotic via IV
in culture what visual changes help determine between streptococci species?
haemolysis
if alpha haemolytic = partial haemolysis (green colour)
beta haemolytic- full haemolysis
non haemolytic = no difference
alpha haemolytic examples
strep viridans
strep pneumoniae
beta haemolytic examples
strep pyogenes
strep agalactiae
non-haemolytic bacteria example
enterococcus
how are vancomycin and teicoplanin administered
only given parenterally ie IV or intramuscular
Ototoxicity
toxicity to ear
hearing impairment
what are macrolides like erythromicin and clarithromicin useful in treating
gram negative bacteria that can’t be treated by penicillins
Linezolid what is it
new class of protein synthesis inhibitors in common use.
It has good activity against MRSA and can be
given orally- usually held in reserve for serious infection
co-trimoxazole used to treat what now and why?
chest infection since it Is less likely than other broad spectrum agents to cause Clostridium difficile infections.
VRE
vancomycin resistant enterococci
the peptidoglycan precursor to which vancomycin
normally binds has an altered structure
Nalidixic acid used to treat which one infection
UTI
Clostridium difficile infection (CDI)
is an important side effect of antibiotic therapy- causes diarrhea
piperacillin
has an extended spectrum and is active against
Pseudomonas species
