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what is a narrow spectrum antibiotic?
covers only G+ve agents
what is a broad spectrum antibiotic?
covers G+ve and G-ve
what do the broadest spectrum antibiotics cover?
what is a bactericidal agent?
- kills organism
- eg penicillin
what is a bacteriostatic agent?
- stop replication
- but organism still there, alive and dormant
- then phagocytes comes to kill organism
who should bacteriostatic agents NOT be used in?
- 1. neutropenic patients
- 2. site of infection where neutrophils cant get to
what is MIC?
- minimum amount of antibiotic (mg/l) available in the bloodstream
- after a therapeutic dose
- that will inhibit an organism
why is MIC important?
cant have an MIC that is unsafe - as even though it would kill the organism, it would also kill the patient. so need to know the MIC
what is MBC?
minimum bacterial concentration: lowest concentration needed to kill the bacteria
what is generally higher, MIC or MBC?
SE to kidney, liver, bone marrow?, children?, pregnancy?
spectrum: MRSA? pseudomonas? anti anaerobic?
name 3 intracellular organisms
- Mycoplasma Tb
- salmonella typhi (typhoid)
what are 2 forms of resistance?
- innate: eg if G+ve agent only, wont act on G-ve structures
- acquired: acq genetic info that changes the organism so drug no longer active eg G+ve: B-lactamase (staphylococci), PBP (penicillin binding protein), G-ve: porins permeability, efflux.
what SE assoc with sulphonamide?
stephens johnsons syndrome
what is the spectrum of penicillin V (oral)
narrow spectrum: G+ve ONLY mainly streptococcal except also neisseria meningitis (not gonoccocal) which is G-ve
what are the routes of penicillin?
- penicillin V oral
- Penicillin G iv (aka ben pen)
- procaine penicllin im
what are uses of penicillin V?
penicillin V: oral - use for strep sore throat, prophylaxis in splenectomy pt.
why is penicillin V use limited?
- poor absorption in stomach
- poor tissue distribution
- (but reaches in adequate concentration in hyperaemic tonsil
what are uses of iv ben pen? and what do you need to remember with it?
- remember if give high dose remember its got Na/K salt.
- infective endocarditis against strep viridans,
- cellulitis against GAS,
- GBS in children,
- meningococal meningitis,
what are SE of B lactam?
what is MOA of penicillin?
inhibit cell wall synthesis
what is penetration of penicillin?
penetrates most tissue including inflamed meninges
what are advantages of penicilins?
- safe in children, pregnancy
- not many kidney, liver or BM problems
what is major problem of penicillin?
cleaved by beta lactamase
is there an im version of penicillin? what is it called and use?
- procaine penicillin im
- use: treponema palladium (syphilis)
which penicillin is B lactamase stable therefore can be used for staph?
what is the spectrum of fluclox?
narrow: staph (some strep, but MIC to GAS is much higher than pen)
what is route of fluclox?
- iv: staph endocarditis, toxic shock, osteomyelitis, septic arthritis
- oral: simple staph in community - abscess, folliculitis
what are the 4 problem G+ve agents?
- MRSA: res to flucloxacillin
- Enterococci in general: e. faecium is resistant to amoxicillin
- VRE: res to vancomycin
- CNS: (in prosthesis and lines) most resistant to flucloxacilin
which group of abx used for problem G+ve organism?
- vancomycin or teicoplanin
what is the spectrum of glyocpeptides?
narrow spectrum as only for problem G+ve agents
what is the problem with glycopeptide?
- iv only
- penetration limited
- vancomycin nephrotoxic so have to measure levels
- resistance - VRE
what is route of glycopeptide?
what is penetration of glycopeptide?
- none to CSF as large molecule
why is vanc expensive?
need to measure levels as nephrotox
when use oral vancomycin?
C Diff (bowel)
what is used to treat VRE?
- oxazolidinones eg linezolid (only G+ve, oral and iv, excellent penetration skin and brain.
- daptomycin ( lipopeptides)
which 2 abx do u have to measure levels for?
- as nephrotoxic
what is spectrum of linezolid?
what is route of linezolid?
oral and iv
what is penetration of linezolid?
- v gd skin, soft tissue
what are the 3 important SE of linezolid?
- suppression of BM: aplastic anaemia, thombocytopenia
- peripheral neuropathy inc optic neuritis
- cannot be given with MAOi
what is the MOA of linezolid?
acts on ribosome
what are 2 uses of linezolid?
- 1st line for VRE
- 2nd line for MRSA
what are broad spectrum penicillins good for?
exponential gram -ve cover
what was 1st broad spec pen?
what is simplest, commonest G-ve infection you see in community?
- UTI eg E coli
- > 50% resistant to amoxicillin as have learnt to make beta lactamse (enterobetalactamase)
what is MOA of trimethroprim?
dihydrofolate reductase inhibitor
what is Rx of UTI?
what is Rx of UTI in pregnancy?
amoxillin high dose
what is use of amoxicillin?
- UTI in pregnancy
- not B lactamase stable (so cant use with staph)
- don't use for sore throat empirically as EBV rash
what is advantage of amoxicillin?
- some G-ve activity
- better absorbed from stomach
if want to switch from iv ben pen to oral form, what use?? and why
- use amoxicillin
- not penicillin G as poor absorption and penetration and need it qds
which 2 organisms is amoxicillin the DRUG OF CHOICE for?
- enterococcal: but NOT e.faecium as its resis to amox!
what is the main limitation of amoxicillin
what is trade name for co-amoxiclav?
what is advantage of co-amoxiclav?
- beta lactamase stable
- because the clavulanate binds to the beta lactamase produced by organism
- releasing the amoxicillin
could you use co-amoxiclav to treat a pure staph infection?
- you could as beta lactamse inhibitor
- but wouldn't because it is too broad a spectrum when you can hit the staph with a narrow spec eg fluclox
what is spectrum of co-amoxiclav?
why is it bad to treat staph infection with co-amox?
you are going to wipe out anaerobes so all the normal flora
what are the main anaerobic antibiotics?
when are you likely to get multiple org eg staph, anaerobes and G-ve infection?
- aspiration pneumonia: mouth flora - streps and anaerobes
- chronic osteomyelitis in diabetics
- involve GI: diveriticulitis, appendicitis, tooth abscess,
- severe sinusitis
when in community are you likely to use co-amoxiclav?
CAP secondary to chronic exacerbation of COPD where you need to cover strep and HAEMOPHILUS which is potent producer of beta lactamase
what is scenario of use of co-amox?
- sepsis without cause
- need to cover broad spectrum
which penicilins cover pseudomonas? route and spectrum?
- piptazobactam = piperacillin & tazobactam
- tazobactam: beta lactamase inhibitor
- route: only iv
- spectrum: staph, strep, anaerobic, G-ve, pseudomonas
what are the problem G-ve organisms? why?
- as multi drug resistance and ESBL
what are ESBLs?
extended spectrum beta lactamase?
what can you NOT use for ESBL?
- beta lactam inhibitor combination may fail!
what do you treat for ESBL producing organisms?
carbapenems eg meropenem and ertapenem
what is spectrum for carbapenems?
very broad: G+ve, G-ve, anaerobic and pseudomonas
what do carbapenems not do?
problem causing G+ve (4 eg MRSA) so need glycopeptides for them
what is route of carbapenems
iv not oral
what is problem with ertapenem?
no anti pseudomonal activity
why would u use ertapenem?
if ESBL producing organism
where do you normally get pseudomonas from?
hospital acquired not community
what is the spectrum for 1st gen cephalosporin?
give an example of 1st generation cephalosporins
what % of pen allergic are also cephalosporin allergic?
10-12% so use with caution
can you use cephalosporins for staph aureus?
yes even though MIC is much higher than flucloxacillin
what is the main use of 1st gen cephalosporin? why?
- UTI in pregnancy where you cant give amoxicillin because its resistance or pt is allergic
- they concentrate in urine well
what is route of 1st gen cep?
what is name of a 2nd gen cep?
what is route of cefuroxime
- (oral has no better properties than 1st gen)
what is spectrum of 2nd gen cep?
broad spectrum so G+ve and G-ve
what is use for iv cefuroxime?
- serious UTI - cystitis, pyeloneph
- strep pneumo pneumonia
- COPD pt as want to cover haemophilus aswell which is G-ve
what does cefuroxime NOT cover?
how do you know when to use co-amoxiclav or 'cefuroxime and metronidazole'?
- depends on hospital
- hospital acquired infection - C-diff with cephalosporin treatment
what have cephalosporins been assoc with?
- enterococcal infections as they are resistant to cephalic
- rise in ESBL producing organisms
if you are treating infection above the diaphragm what do you want to add to cefuroxime?
macrolide eg erythromicin or clarythromycin
if you are treating infection below the diaphragm what do you want to add to cefuroxime?
metronidazole (gut anaerobes)
which cephalosporin is anti-pseudomonal?
- problem G-ve as long as not ESBL producers
- prob G-ve: klebsiella, enterobacter, proteus etc
name 3 3rd gen cephs?
what is the spectrum of ceftriaxone?
- G-ve: meningococcus, haemophilus
- G+ve: pneumococcus
- these covered are most likely cause of acute meningitis thats why treat empirically with ceftriaxone
what is route of ceftriaxone?
what is difference between cefotaxime and ceftriaxone?
- ceftriaxone: slugging of bile in neonate and raised LFTs so use cefotaxime
- cefotaxime: tds (ceftriaxone is od)
what is cause of getting pseudomonas infection?
hospital acquired eg ventilator associated pneumonia
how to diagnose pen allergy?
history: if anaphylactic avoid all beta lactam
what is alternative to beta lactam?
where do macrolides act?
name 3 types of macrolides
what is spectrum of macrolides?
are macrocodes bacteriostatic or cidal?
what is erythromycin good for?
- alternative to penicillins
- staph and strep
- where you can give it orally - out in community (not iv)
why should erythromycin not be used iv?
what is penetration of erythromycin like?
no penetration to CSF
what are macrocodes especially good for treating? give eg
- atypical pneumonias eg
- myocplasma pneumonia
- chlamydia pneumonia
- legionella pneumonia
why cant you use penicillin to treat mycoplasma pneumonia?
- because it doesn't have a cell wall and penicillons act by inhibiting cell wall!
- need macrocodes which cause
what is empirical Rx of pneumonia?
beta lactam eg penicillin & macrolides (atypicals)
what is advantage of macrolide for mycoplasma pneumonia and chlamydia pneumonia specifically and why?
- they are intracellular organisms
- macrocodes penetrate intracellularly very well
what is the difference between erythromycin and clarythromycin?
clary: iv and oral, better tolerated iv, marginally better spectrum as also covers haemophilus
in community, which macrolide is better?
clarythromycin: alternative for penicillin, good for atypicals, got some haemophilus activity.
what is azithromycin used for?
- gum clinic: STI eg chlamydia
- typhoid as intracellular
what is adv of azithromycin?
- very long half life
- huge intracellular concentration
what type of organism is clindamycin?
what is spectrum of clindamycin?
- staph and strep ie G+ve
- (but no G-ve cover)
what is advantage of clindamycin and therefore its use?
- acts on ribosome switch off toxin making material in cell
- so good for toxic infections: TSS, necrotising fasciitis
what is clindamycin the alternative to fluclox for?
- orthopaedic infection
- penetrates bone and joint v well
what do you combine fluclox for orthopaedic infections?
what are uses of clindamycin?
- 1. aspiration pneumonia: as has strep and anaerobic cover
- 2. toxin assoc conditions eg TSS, necrotising fasciitis
- 3. penetration into bone and joint
- 4. abscesses
route of clindamycin?
oral and iv
disadvantage of clindamycin?
assoc with C-diff diarrhoea
what give if patient had pseudomonal or pyelonephritis if allergic to penicillin?
quinolone - ciprofloxacin
for bone and joint infections what is first line? (remember combo)
- fusidic acid
if pen allergic what give for pseudomonas?
what is eg of quinolone?
what is spectrum of quinolone?
- staph but NOT STREP
- all G-ve including pseudomonas
- not anti-anaerobic so if treating gut infection add metronidazole
what is the only non-beta lactam anti-pseudomonal?
what is the penetration of cipro?
- v gd penetration intracell
- adequate brain penetration
what are 2 main problems with cipro?
- widespread resistance
- C-diff recently
is cipro liscenced for everyone?
not liscenced in pregnancy and not yet in children
which group of children get lots of pseudomonal lung infections?
- cystic fibrosis
- so use cipro off licence - document risk v benefit
what is drug of choice for food poisoning?
ciprofloxacin - salmonella
what is ciprofloxacin very good for and why?
- food poisening
- concentrates very well into that tissue
when should you NOT give cipro?
- strep infection
- skin, soft tissue
- sore thraoat
what is special about cipro and its anti-pseudomonal activity?
- its the only oral anti-pseudomonal
- only one for pen allergic
what are the newer quinolones called? and advantage?
- have activity against PNEUMOCOCCAL
what is site of action of quinolones?
- DNA gyrase- not cell wall acting
- so single agent to treat pneumonia
what is disadv of newer quinolones?
what is spectrum of aminoglycosides?
- broad spectrum
- G+ve: staph NOT strep
- G-ve: potent, including pseudomonas
route of gentamicin?
SE of gentamicin?
- nephrotoxicty oto
- measure levels
where in body will gent act best?
- 100% water soluble - so not lipid soluble so wont cross BBB, no penetration into cells or tissue
- if remove O2 it will not work
- so only a bacteraemia agent - blood
- not lung consolidation as no oxygen
- not for cellulitis!
- but can be used as an adjunct
when would you add gentamicin?
if suspect septicaemia - rigors
what is gent an adjunct for?
- IE: anti-microbial synergy against strep and staph
- beta lactam creates leaky cell wall and gentamicin enters and acts on ribosome
what are the 2 types of resistance?
what are the 3 steps required for resistance?
- 1. genetic modification: mutation/acquire DNA or plasmid/loss of DNA
- 2. selection pressure
- 3. add antibiotic - selective advantage
name 4 methods of resistance?
- 1. B lactamase production
- 2. efflux pumps
- 3. target site alteration eg PBP or ribosomal binding site
- 4. impermeability: porins loss in G-ve
- 5. bypass ie even though the antibiotic blocks one enzyme, the organism will make another enzyme
why are porins only related to G-ve organisms?
G-ve have thick outer membrane: LPS which is hydrophilic so they evolved to get porins for things to get through and also antibiotics could get through! but when loss them the antibiotics cant get through
what mechanism of resistance does MRSA use?
PBP2a: unable to bind B-lactam abx
name 5 ways to reduce resistance?
- 1. narrow spectrum antibiotic to reduce the potential selection pressure on other organisms
- 2. culture before use broad spectrum antibiotics then target the antibiotic to the organism once know the organism = DE-ESCALATION
- 3. multiple drugs of different MOA = COMBINATION THERAPY
- 4. reserve new abx
- 5. prescribe when necessary
- 6. stop antibiotic early when you know its not the right organism as the longer the bacteria is exposed to a selection pressure, more resistance!
- 7. dose: short sharp dose. cipro acquires resistance in stepwise mutations
how do you stop infection spreading?
name 4 iv Rx for MRSA
name 4 oral Rx for MRSA
- tetracycline eg doxycycline
- fusidic acid
what are the 3 last ditch Rx for MRSA? and routes
- 1. linezolid: iv and oral
- 2. daptomycin: iv only
- 3. tigecycline
which type of MRSA infection can you not use daptomycin and why?
MRSA pneumonia as it is inactivated by surfactant
what are the SE of linezolid?
- irreversible: neuropathy, inc optic neuropathy
- reversible: BM suppression
what is MOA of glycopeptides?
inhibit cell wall synthesis by steric hindrance ie as they are bulky they can physically stop the molecules coming together to make the cell wall.
what is the disadvantage of glycopeptides?
- they are big molecules
- so don't penetrate tissue well
- stay in blood (so good to Rx MRSA bacteraemia)
what is the disadvantage of vancomycin?
need to measure levels - which is useful for MRSA bacteraemia as want to know how much is getting to the organism
what is the major SE of fusidic acid?
if there is a deep seated pneumonia or osteomyelitis MRSA, what is Rx?
- vanco/teic + oral drug eg rifampicin (as oral has better absorption)
when is the most likely scenario to use doxycycline in MRSA infection?
mild MRSA infection eg cellulitis
which agent is used for prosthesis infected by MRSA?
rifampicin as penetrates biofilms well
when is the only use vancomycin orally?
c diff diarrhoea (2nd line after metronidazole) as it stays in gut where we want it to act
what is Rx for a man due for operation but has MRSA in nose?
- need to decolonize. treat at home
- 5 days MUPIROCIN up nose
- chlorhexidine shampoo
- side room
- adjust surgical prophylaxis to cover MRSA
what does ESBL stand for?
extended spectrum beta lactamases
what makes an organism ESBL?
if it is able to hydrolyse 3rd generation cephalosporins and penicillins
which organisms commonly have ESBL?
enterobacteriacaea eg E Coli, Klebsiella
what is Rx for systemic ESBL infection?
- 1. carbapenems
- 2. amikacin (aminoglycoside) - sometimes
- 3. colistin
- 4. tigecycline (tetracycline)
which carbapenem would you use for ESBL, why?
- ertapenem as it does not have pseudomonal activity
- don't want to use meropenem as you increase the selection pressure and get resistance of mero to pseudomonas as it is everywhere in environment
how Rx local ESBL infection? eg UTI
which abx use for ESBL UTI in pregnancy?
if a pregnancy patient is pen allergic and has a simple UTI, what is Rx?
1st gen ceph
if a pregnant woman is pen allergic and has a complex UTI, what is Rx?
which 2 classes of abx act on 30s ribosome?
which 3 class of abx act on 50s?
- clindamycin - lincosamides