antimicrobial chemotherapy 2 - optional Flashcards
which antibiotics inhibit cell wall synthesis
cycloserine vancomycin bacitracin penicillins cephalosporins monobactams carbapenems
which abx act on folic acid metabolism
trimethoprim
sulfonamides
which abx act on the cytoplasmic membrane structure
polymyxins
daptomycin
which abx act on DNA gyrase
quinolones: nalidixic acid, ciprofloxacin,, novobiocin
which abx act on RNA elongation
actinomycin
which abx act on DNA directed RNA polymerase
rifampicin
streptovaricins
which abx are protein synthesis 50S inhibitors
erythromycin (macrolides)
chloramphenicol
clindamycin
lincomycin
which abx are protein synthesis 30S inhibitors
tetracyclines spectinomycin streptomycin gentamycin kanamycin amikacin nitrofurans
which abx act on protein synthesis (tRNA)
mupirocin
puromycin
6 examples of penicillin abx
benzylpenicillin penicillin V amoxicillin flucloxacillin co-amoxiclav piperacillin/tazobactam
activity of benzylpenicillin, penicillin V
streptococci
Neisseria
spirochetes
main uses of benzylpenicillin, penicillin V
soft tissue pneumococcal meningococcal gonorrhoea syphilis
benefits of benzylpenicillin, penicillin V
IV/IM usage
cheap
activity of amoxicillin
broad spectrum but resistance is common
main uses of amoxicillin
UTI
RTI
benefits of amoxicillin
cheap
activity of flucloxacillin
staphylococci
main uses of flucloxacillin and benefits
S. aureus
cheap
activity of co-amoxiclav
broad spectrum
incl. anaerobes
main uses of co-amoxiclav
UTI
RTI
soft tissue infections
surgical wound infections
disadvantages of co-amoxiclav
C. difficile infection
action of piperacillin/tazobactam
broad spectrum incl. pseudomonas and anaerobes
main uses of piperacillin/tazobactam
neutropenic sepsis
route of administration of piperacillin/tazobactam
IV only
5 examples of cephalosporin abx and their generation
1st - cefradine
2nd - cefuroxime
3rd - ceftriaxone/cefotaxime, ceftazidime
4th - ceftaroline/ceftobiprole - anti-MRSA
cefradine activity
broad spectrum
resistance +
main uses of cefradine
UTI
soft tissue infection
advantages of cefradine
oral
cheap
activity of cefuroxime
broad spectrum
main uses of cefuroxime
UTI
TRI
surgical prophylaxis
activity of ceftriaxone/cefotaxime
broad spectrum esp good against gram -ve bacilli
main uses of ceftriaxone/cefotaxime
hospital infections e.g. bacteraemia pneumonia, abdo sepsis
disadvantages of ceftriaxone/cefotaxime
risk factor for MRSA, C diff
IV/IM only
activity of ceftazidime
like ceftriaxone but also active against pseudomonas
main uses of ceftazidime
pseudomonal infections in hospital and in CF
disadvantages of ceftazidime
risk factor for MRSA, C diff
IV only
ceftaroline/ceftobiprole activity
broad spectrum
less gram -ve cover
MRSA
main uses of ceftaroline/ceftobiprole
skin and soft tissue infection
endocarditis resistant to other treatment
disadvantages of ceftaroline/ceftobiprole
risk factor for development of C diff
expensive
IV only
2 examples of aminoglycoside abx
gentamicin
amikacin
activity of gentamicin and
amikacin
gram -ve bacilli
main uses of gentamicin and
amikacin
serious gram -ve infections e.g. bacteraemia, endocarditis, neutropenic sepsis
disadvantages of gentamicin and amikacin
IV? and IM only
renal and ototoxicity
measuring levels is essential
3 examples of macrolide abx
clarithromycin
erythromycin
azithromycin
activity of clarithromycin
streptococci staphylococci mycoplasma chlamydia legionella
main uses of clarithromycin
resp infection
soft tissue infection (if penicillin allergic)
STD
activity of erythromycin
streptococci staphylococci mycoplasma chlamydia legionella
main uses of erythromycin
resp infection
soft tissue infection (if penicillin allergic)
STD
disadvantages of erythromycin
GI intolerance
advantages of clarithromycin
better tolerated
activity of azithromycin
better for gram -ve e.g. haemophilus
chlamydia
main uses of azithromycin
chlamydia
2 examples of quinolones
ciprofloxacin
levofloxacin/moxifloxacin
activity of ciprofloxacin
gram -ve bacilli
pseudomonas
some activity against staphylococci and streptococci
main uses of ciprofloxacin
complicated UTI
complicated hospital acquired pneumonia
some GI infections
disadvantages of ciprofloxacin
C. diff
may affect growing cartilage
activity of levofloxacin/moxifloxacin
enhanced activity against staphylococci/streptococci less against pseudomonas active against pneumococcus mycoplasma chlamydia legionella
main uses of levofloxacin/moxifloxacin
2nd/3rd line agent for pneumonia
disadvantages of levofloxacin/moxifloxacin
C. diff
may affect growing cartilage
2 examples of glycopeptide abx
vancomycin
teicoplanin
activity of vancomycin and teicoplanin
gram +ve bacteria only (streptococci and staphylococci)
main uses of vancomycin and teicoplanin
MRSA
pts allergic to penicillin
C. difficile (oral vanc)
disadvantages of vancomycin and teicoplanin
IV/IM only (except for C. diff)
regular levels required
nephrotoxicity
activity of trimethoprim
gram -ve bacilli
some activity against streptococci and staphylococci
main uses of trimethoprim
UTI
resp infection
MRSA
advantages of trimethoprim
cheap
what 2 drugs make up co-trimoxazole
trimethoprim
sulphamethoxazole
uses of co-trimoxazole
broad spectrum
pnemocysititis jiroveci
main uses of co-trimoxazole
resp infection
PCP
disadvantages of co-trimoxazole
rashes
activity of clindamycin
streptococci
staphylococci
anaerobes
main uses of clindamycin
soft tissue infection
gangrene
disadvantages of clindamycin
associated w/ C. diff
activity of tetracycline and doxycycline
streptococci staphylococci chlamydia rickettsiae brucella
main uses of tetracycline and doxycycline
Q fever brucellosis chlamydia atypical pneumonia MRSA
disadvantages of tetracycline and doxycycline
CI in pregnancy and childhood (effects on teeth and bones)
activity of rifampicin
mycobacteria
meningococcus
staphylococci
main uses of rifampicin
TB
MRSA
meningococcal prophylaxis
complicated staphylococcal infections
disadvantages of rifampicin
drug interactions -enzyme inducer
activity of meropenem
broad spectrum incl. anaerobes
pseudomonas
main uses of meropenem
2nd or 3rd line for hospital infections
advantages of meropenem
good CNS penetration
but IV only
activity of metronidazole
anaerobes
protozoa e.g. giardia
main uses of metronidazole
surgical infections
giardiasis
amoebiasis
trichomonal infections
disadvantages of metronidazole
antabuse - reaction w/ alcohol
activity of linezolid
gram +ve bacteria only: streptococci, staphylococci, enterococci
main uses of linezolid
2nd line agent for MSSA, MRSA, VRE
route of administration for linezolid
oral and iV
disadvantages of linezolid
blood and optic neuropathy
S/Es
activity of daptomycin
gram +ve bacteria only (streptococci, staphylococci, enterococci)
main uses of daptomycin
2nd line agent for MSSA, MRSA, VRE
disadvantages of daptomycin
IV only
inactive in lung
myositis S/E
activity of tigecycline
very broad spectrum incl. MRSA, ESBL, anaerobes
main uses of tigecycline
3rd line intra-abdo sepsis
soft tissue infections
disadvantages of tigecycline
IV only
ineffective against pseudomonas
indications for antimicrobials
therapy
prophylaxis
what is empirical therapy
w/o microbiology results
what is directed therapy
based on microbiology results
what is 1y prophylaxis
anti-malarial, immunosuppressed pts
pre-operative surgical
post-exposure e.g. HIV, meningitis
what is 2y prophylaxis
prevent a 2nd episode e.g. PJP
how is a diagnosis of infection made
clinical
laboratory
none - no treatment
severity assessment of infection
? sepsis (qSOFA)
Septic shock
qSOFA criteria
syst BP <100
altered mental state
RR >22
patient characteristics to consider when prescribing
age renal function liver function immunocompromised pregnancy known allergies
things to consider when making antimicrobial selection
guideline or individualised therapy likely organism empirical therapy or result based bactericidal vs bacteriostatic drug single agent or combination potential adverse effects
30% rule of prescribing abx
30% of all hospitalised inpatients at any given time recieve abx
>30% of abx are prescribed inappropiately in the community
up to 30% of all surgical prophylaxis is inappropriate
10-30% of pharmacy costs can be saved by antimicrobial stewardship programmes
how does abx resistance occur
natural phenomenon
bacteria adapt to survive
bacteria rapidly multiply and can generate resistance very quickly
4 main mechanisms of resistance
enzymatic inactivation of drug
modified targets for drugs
reduced permeability to drug
efflux of drug
genetics of resistance
chromosomally mediated
plasmid mediated
chromosomally mediated resistance
mutation in gene coding for drug target or membrane transport system
frequency of spontaneous mutations 10^-7 to 10^-9
much lower than frequency of acquisition to plasmids
less of a problem clinically
basis for multi drug therapy e.g. TB
what is binary fission
DNA replicates
cell elongates
divides in 2
2 identical bacteria
plasmid mediated resistance
plasmid = extra-chromosomal strand of DNA
replicate independent of cell chromosome
carry genes for enzymes which degrade abx and modify membrane transport systems
may carry 1 or more resistance gene
how is plasmid mediated resistance passed on
bacteria have ability to conjugate
can transfer resistance genes to other species of bacteria
certain bacteria can take up plasmids by transformation
5 medically important resistant organisms
MRSA VRE ESBL CPE Clostridium difficile
methicillin
methicillin is a penicillinase resistant penicillin (e.g. similar to flucloxacillin)
used in lab to determine whether organisms are sensitive to flucloxacillin
MRSA
methicillin resistant staphylococcus aureus
MRSA has an altered binding protein compared w/ MSSA
resistant to flucloxacillin
clinical effects of MRSA
most often colonisation w/o infection
can cause severe invasive infections e.g. osteomyelitis, endocarditis
mortality in pts w/ MRSA bacteraemia = 2x that of MSSA bacteraemia
carriage of MRSA is promoted by use of abx
VRE
vancomycin resistant enterococci
enterococci are intrinsically only sensitive to a limited number of abx
VRE are only sensitive to 1 or 2 abx
VRE colonise GI tract in pts exposed to multiple abx
can cause invasive disease (e.g. endocarditis) esp in pts w/ prosthetic devices
ESBL producing enterobacteraciae
extended spectrum beta lactamase
confer a range of resistance mechanisms, enzymatic degradation of antibiotic, reduced porins, increased efflux
resistant to beta-lactam abx, often cephalosporins
may be associated w/ further resistance mechanisms such as resistance to aminoglycosides and carbapenems
CPE
carbapenem producing enterobacteriacae multiple resistant bacteria typically only sensitive to a few abx of last resort can colonise gut of healthy individuals associated w/ high mortality can colonise healthcare environment
factors influencing abx resistance
widespread abx use encouraging selective pressure
abx use by medical professions, veterinary practices, farming
pts surviving longer w/ more medical conditions and hospital contact
more invasive procedures and prosthetic devices
increased bed pressure in UK encourages spread of resistant organisms
quinolones - example and resistance
ciprofloxacin
levofloxacin
associated w/ C diff
overuse associated w/ increased MRSA rates
macrolides - example and resistance
clarithromycin
erythromycin
limited spectrum of activity not for severe infections
licosamides - example and resistance
clindamycin only gram +ve and anaerobic activity
high risk of C diff
resistance reasonably common in staph and strep
co-trimoxazole
limited IV supply
good spectrum of coverage
less active against strep pneumoniae
caution in renal dysfunction, marrow toxicity
aminoglycosides
gentamicin
potent antimicrobial use limited by renal and ototoxicity
not used as single agent in gram +ve infection
glycopeptides
vancomycin teicoplanin need monitoring to achieve therapeutic agents less active against staph aureus no gram -ve cover
daptomycin
only gram +ve activity
toxicities include eosinophilic pneumonia and myositis
can’t be used in pneumonia
tetracycline
doxycycline
GI intolerance common
not used in bacteraemic infection
tigecycline
broad spectrum of coverage
not used in bacteraemic illness
oxazolidinones
restricted antibiotic
marrow toxicities
types of hypersensitivity reactions
type I anaphylaxis type II type III type IV
type I hypersensitivity reactions
IgE mediated
stimulates pro-inflammatory release
uritcaria, laryngeal oedema, bronchospasm, circulatory collapse
anaphylaxis and penicillin
occurs in 4-15/100 000 penicillin treatment courses
type II hypersensitivity reactions
beta lactam specific IgG or IgM antibodies
bind to circulating blood cell
haematological reactions or interstitial nephritis
type III hypersensitivity reactions
circulating beta lactam specific IgG or IgM
bind to beta lactam antigens fixing compliment
lodge in tissues
serum sickness and drug related fever
type IV hypersensitivity reactions
not antibody mediated
T cell recognises antigen leading to localised inflammation e.g. contact dermatitis
management of a pt w/ beta lactam allergy
5-20% of pts give hx of beta lactam allergy
less that 1% of those will have type 1 penicillin allergy
difficult to confirm - lack of available testing
good hx is important
define resistance
inability of antibiotic to kill bacteria
can be detected in the lab by measuring MIC levels - minimum inhibitory conc
clinical failure may occur despite lab reports of sensitivity
reasons for failure of therapy
inadequate dose of antibiotic
inappropriate route
non-compliance
bacteria walled off in abscess cavity
foreign bodies e.g. surgical implants, prosthesis
poor penetration of drug to site of action
name 3 abx w/ good biofilm availability
rifampicin
daptomycin
ceftobiprole
what is antibiotic stewardship
using the right antibiotic for the right indication for the right duration of time
how to achieve antibiotic stewardship
use an antibiotic only if suspected or proven bacterial infection
use abx as per guidelines and review w/ results of microbiology
review antibiotic prescriptions regularly and stop ASAP
limit use of broad spectrum blind antibiotic therapy to seriously ill patients
when to consider switching patients from IV to oral abx
after 48hrs provided that: pt is improving clinically and is able to tolerate an oral formulation i.e. all of the following: able to swallow and tolerate fluids temp 36-38C for at least 48hrs HR <100bpm for prev 12hrs WCC between 4 and 12x10^9L
when would you not switch to oral abx
yes to any of the following: oral route compromised - vomiting, nil by mouth, steatorrhoea, swallowing disorder, unconscious continuing sepsis special indication febrile neutropenia hypotension/shock
special indications for not switching to oral abx
endocarditis meningitis staph. aureus bacteraemia immunosuppression bone/joint infection deep abscess CF prosthetic infection
alert microbials
restricted use only under the authorisation of a microbiologist or infectious disease specialist
and/or
according to approved indications within local guidelines/policies
how to help prevent antibiotic resistance
use abx only when prescribe
prescribe abx only when neccesary and appropriate
complete the full course
never share abx or use leftover prescriptions
