Antibiotics.txt

covers only G+ve agents

covers G+ve and G-ve

• G+ve
• G-ve
• anaerobes

• kills organism
• eg penicillin

• stop replication
• but organism still there, alive and dormant
• then phagocytes comes to kill organism

• 1. neutropenic patients
• 2. site of infection where neutrophils cant get to

• minimum amount of antibiotic (mg/l) available in the bloodstream
• after a therapeutic dose
• that will inhibit an organism

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

minimum bacterial concentration: lowest concentration needed to kill the bacteria

MIC

spectrum: MRSA? pseudomonas? anti anaerobic?

• chlamydia
• Mycoplasma Tb
• salmonella typhi (typhoid)

• 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• acquired: acq genetic info that changes the organism so drug no longer active eg G+ve: B-lactamase (staphylococci), PBP (penicillin binding protein), G-ve: porins permeability, efflux.

stephens johnsons syndrome

narrow spectrum: G+ve ONLY mainly streptococcal except also neisseria meningitis (not gonoccocal) which is G-ve

• penicillin V oral
• Penicillin G iv (aka ben pen)
• procaine penicllin im

penicillin V: oral - use for strep sore throat, prophylaxis in splenectomy pt.

• qds
• poor absorption in stomach
• poor tissue distribution
• (but reaches in adequate concentration in hyperaemic tonsil

• remember if give high dose remember its got Na/K salt.
• infective endocarditis against strep viridans,
• cellulitis against GAS,
• GBS in children,
• meningococal meningitis,
• pneumonia

allergy

inhibit cell wall synthesis

penetrates most tissue including inflamed meninges

• safe in children, pregnancy
• not many kidney, liver or BM problems
• cheap

cleaved by beta lactamase

• procaine penicillin im
• use: treponema palladium (syphilis)

flucloxacillin

narrow: staph (some strep, but MIC to GAS is much higher than pen)

• iv: staph endocarditis, toxic shock, osteomyelitis, septic arthritis
• oral: simple staph in community - abscess, folliculitis

• 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

• glycopeptides
• vancomycin or teicoplanin

narrow spectrum as only for problem G+ve agents

• iv only
• penetration limited
• vancomycin nephrotoxic so have to measure levels
• expensive
• resistance - VRE

iv only

• poor
• none to CSF as large molecule

need to measure levels as nephrotox

C Diff (bowel)

• oxazolidinones eg linezolid (only G+ve, oral and iv, excellent penetration skin and brain.
• daptomycin ( lipopeptides)

• vancomycin
• gentamicin
• as nephrotoxic

only G+ve

oral and iv

• v gd skin, soft tissue
• CSF

• suppression of BM: aplastic anaemia, thombocytopenia
• peripheral neuropathy inc optic neuritis
• cannot be given with MAOi

acts on ribosome

• 1st line for VRE
• 2nd line for MRSA

exponential gram -ve cover

amoxicillin

• UTI eg E coli
• > 50% resistant to amoxicillin as have learnt to make beta lactamse (enterobetalactamase)

dihydrofolate reductase inhibitor

trimpethoprim

amoxillin high dose

• UTI in pregnancy
• not B lactamase stable (so cant use with staph)
• don't use for sore throat empirically as EBV rash

• some G-ve activity
• tds
• better absorbed from stomach
• oral

• use amoxicillin
• not penicillin G as poor absorption and penetration and need it qds

• enterococcal: but NOT e.faecium as its resis to amox!
• listeria

resistance

augmentin

• beta lactamase stable
• because the clavulanate binds to the beta lactamase produced by organism
• releasing the amoxicillin

• 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

• G+ve
• G-ve
• anti-anaerobic

you are going to wipe out anaerobes so all the normal flora

• metronidazole
• co-amoxiclav
• piptazobactam
• carbapenems

• aspiration pneumonia: mouth flora - streps and anaerobes
• chronic osteomyelitis in diabetics
• involve GI: diveriticulitis, appendicitis, tooth abscess,
• severe sinusitis

CAP secondary to chronic exacerbation of COPD where you need to cover strep and HAEMOPHILUS which is potent producer of beta lactamase

• sepsis without cause
• need to cover broad spectrum

• piptazobactam = piperacillin & tazobactam
• tazobactam: beta lactamase inhibitor
• route: only iv
• spectrum: staph, strep, anaerobic, G-ve, pseudomonas

• pseudomonas
• klebsiella
• enterobacter
• proteus
• serratia
• acinetobacter
• as multi drug resistance and ESBL

extended spectrum beta lactamase?

• cephalosporin
• beta lactam inhibitor combination may fail!

carbapenems eg meropenem and ertapenem

very broad: G+ve, G-ve, anaerobic and pseudomonas

problem causing G+ve (4 eg MRSA) so need glycopeptides for them

iv not oral

no anti pseudomonal activity

if ESBL producing organism

hospital acquired not community

• some G+ve
• minimal G-ve

cephalexin

10-12% so use with caution

yes even though MIC is much higher than flucloxacillin

• UTI in pregnancy where you cant give amoxicillin because its resistance or pt is allergic
• they concentrate in urine well

oral

cefuroxime

• iv
• (oral has no better properties than 1st gen)

broad spectrum so G+ve and G-ve

• serious UTI - cystitis, pyeloneph
• strep pneumo pneumonia
• COPD pt as want to cover haemophilus aswell which is G-ve

anaerobics

• depends on hospital
• hospital acquired infection - C-diff with cephalosporin treatment

• C-difficile
• enterococcal infections as they are resistant to cephalic
• rise in ESBL producing organisms

macrolide eg erythromicin or clarythromycin

metronidazole (gut anaerobes)

• ceftazidime
• problem G-ve as long as not ESBL producers
• prob G-ve: klebsiella, enterobacter, proteus etc

• ceftriaxone
• ceftazidime
• cefotaxime

• G-ve: meningococcus, haemophilus
• G+ve: pneumococcus
• these covered are most likely cause of acute meningitis thats why treat empirically with ceftriaxone

iv

• ceftriaxone: slugging of bile in neonate and raised LFTs so use cefotaxime
• cefotaxime: tds (ceftriaxone is od)

hospital acquired eg ventilator associated pneumonia

history: if anaphylactic avoid all beta lactam

macrolides

ribosome 50S

• erythromycin
• clarythromycin
• azithromycin

• narrow spectrum
• G+ve

static

• alternative to penicillins
• staph and strep
• where you can give it orally - out in community (not iv)

thrombophlebitis

no penetration to CSF

• atypical pneumonias eg
• myocplasma pneumonia
• chlamydia pneumonia
• legionella pneumonia

• because it doesn't have a cell wall and penicillons act by inhibiting cell wall!
• need macrocodes which cause

beta lactam eg penicillin & macrolides (atypicals)

• they are intracellular organisms
• macrocodes penetrate intracellularly very well

clary: iv and oral, better tolerated iv, marginally better spectrum as also covers haemophilus

clarythromycin: alternative for penicillin, good for atypicals, got some haemophilus activity.

• gum clinic: STI eg chlamydia
• typhoid as intracellular

• very long half life
• huge intracellular concentration

lincosamide

• staph and strep ie G+ve
• anaerobic
• (but no G-ve cover)

• acts on ribosome switch off toxin making material in cell
• so good for toxic infections: TSS, necrotising fasciitis

• orthopaedic infection
• penetrates bone and joint v well

fusidic acid

• 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

oral and iv

assoc with C-diff diarrhoea

quinolone - ciprofloxacin

• flucloxacillin
• fusidic acid

quinolones

ciprofloxacin

• broad
• staph but NOT STREP
• all G-ve including pseudomonas
• not anti-anaerobic so if treating gut infection add metronidazole

ciprofloxacin (quinolone)

• v gd penetration intracell
• adequate brain penetration

• widespread resistance
• C-diff recently

not liscenced in pregnancy and not yet in children

• cystic fibrosis
• so use cipro off licence - document risk v benefit

ciprofloxacin - salmonella

• food poisening
• epididymitis
• orchitis
• prostatitis
• cystitis
• concentrates very well into that tissue

• strep infection
• skin, soft tissue
• pneumonia
• sore thraoat

• its the only oral anti-pseudomonal
• only one for pen allergic

• levofloxacin
• moxifloxacin
• have activity against PNEUMOCOCCAL

• DNA gyrase- not cell wall acting
• so single agent to treat pneumonia

not anti-pseudomonal

• broad spectrum
• G+ve: staph NOT strep
• G-ve: potent, including pseudomonas

only iv

• nephrotoxicty oto
• measure levels

• 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

if suspect septicaemia - rigors

• IE: anti-microbial synergy against strep and staph
• beta lactam creates leaky cell wall and gentamicin enters and acts on ribosome

• innate
• acquired

• 1. genetic modification: mutation/acquire DNA or plasmid/loss of DNA
• 2. selection pressure
• 3. add antibiotic - selective advantage

• 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

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

PBP2a: unable to bind B-lactam abx

• 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

infection control

• vancomycin
• teicoplanin
• gentamicin
• chloramphenicol

• rifampicin
• tetracycline eg doxycycline
• fusidic acid
• trimethorpim

• 1. linezolid: iv and oral
• 2. daptomycin: iv only
• 3. tigecycline

MRSA pneumonia as it is inactivated by surfactant

• irreversible: neuropathy, inc optic neuropathy
• reversible: BM suppression

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.

• they are big molecules
• so don't penetrate tissue well
• stay in blood (so good to Rx MRSA bacteraemia)

need to measure levels - which is useful for MRSA bacteraemia as want to know how much is getting to the organism

very hepatotoxic

• combination
• vanco/teic + oral drug eg rifampicin (as oral has better absorption)

mild MRSA infection eg cellulitis

rifampicin as penetrates biofilms well

c diff diarrhoea (2nd line after metronidazole) as it stays in gut where we want it to act

• need to decolonize. treat at home
• 5 days MUPIROCIN up nose
• chlorhexidine shampoo
• mouthwash
• side room
• adjust surgical prophylaxis to cover MRSA

extended spectrum beta lactamases

if it is able to hydrolyse 3rd generation cephalosporins and penicillins

enterobacteriacaea eg E Coli, Klebsiella

• 1. carbapenems
• 2. amikacin (aminoglycoside) - sometimes
• 3. colistin
• 4. tigecycline (tetracycline)

• fits
• renal failure

• 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

• nitrofurantoin
• fosfomycin

fosfomycin

1st gen ceph

cipro

• aminoglycosides
• tetracycline

• macrolides
• chloramphenicol
• clindamycin - lincosamides