advanced micro Flashcards
what 5 parts of a patients social history could be relevant to ascertain the causative organism of an infection?
- travel
- occupation
- hobbies
- animal contact
- sexual history
at what temperature is someone deemed to have a definite fever?
38 degrees (or above)
FBC blood test: what types of blood cells are raised in:
- bacterial infection?
- viral infection?
bacterial = neutrophils
viral = lymphocytes
what colour does:
- gram positive stain?
- gram negative stain?
gram positive = purple
gram negative = pink/red
“stuff that’s red is bad”
what is the difference between an antibiotic and an antibacterial agent?
antibiotic
- chemical PRODUCTS OF MICROBES that inhibit/kill bacteria
antibacterial agent
- ANY chemical that inhibits/kills bacteria (irregardless of source)
nb often used interchangably in practise
what does minimum inhibitory concentration (MIC) or minimum bactericidal/fungicidal concentration (MBC/MFC) mean?
what does it mean if there is a low MIC?
MIC = minimum conc of antimicrobial agent at which visible growth is inhibited
MBC/MFC = minimum conc of antimicrobial agent at which most organisms are killed
a low MIC (or MBC/MFC) means that the bacteria (or fungi) is killed by a very small amount of antimicrobials - ie it’s sensitive
what type of cell mechanics tend to be targetted in:
- bacteriostatic antibiotics?
- bacteriocidal antibiotics?
bacteriostatic
- eg protein synthesis inhibitors
bacteriocidal
- eg attack cell wall or membrane
nb in vivo little difference, mainly terms used in lab
in terms of antimicrobial interactions, define the following terms:
- synergism?
- antagonism?
- indifference?
synergism
- activity of 2 antimicrobials given together is greater than the sum of their activity if given seperately
antagonism
- one agent diminishes the activity of the other
indifference
- activity unaffected by the addition of another agent
what is the component of the fungal cell wall which a lot of anti-fungals target?
what is another component of the fungal cell wall?
beta-1,3-glucan
chitin - antifungals don’t currently target this
what classes of antimicrobials are cell wall synthesis inhibitors:
- in bacteria? 2
- in fungi? 1
antibacterial agents:
- B-lactams
- glycopeptides
antifungal agents:
- echinocandins
what is an anti-tuberculous agent which targets the cell wall of TB?
cycloserine
“need lots of cycles of treatment to treat drug-resistant TB”
in terms of drug delivery, what does parenterally mean?
injection or infusion
- eg IM, IV, subcutaneous
(ie NOT orally)
how do B-lactam antibiotics kill bacteria?
interfere with function of ‘penicilin binding proteins’
- these are transpeptidase enzymes involved in peptidoglycan cross-linking
what three types of drug name suffixes or prefixes indicate that an antibiotic is a B-lactam antibiotic?
why is this important to know in clinical practise?
what are the 2 main exceptions to this?
suffixes:
= -cillin (penicillins)
= -penem (carbapenems)
prefixes:
= cef- (cephalosporins)
people with ‘penicilin allergies’ are allergic to ALL B-lactam antibiotics
other B-lactams:
- aztreonam (a monobactam)
- co-amoxiclav (combination of an antibiotic and an acid)
name 4 different types of penicillins (with at least one example for each)
penicillins
- benzylpenicillin
- phenoxymethylpenicillin
broad spectrum penicillins
- amoxicillin
- pivemecillinam
penicillinase-resistant penicillin:
- flucloxacillin
beta lactam-betalactamase inhibitor combinations
- amoxicillin-clavulanic acid (aka co-amoxiclav
- piperacillin-tazobactam
name 3 different classes of B-lactam antibiotics (with at least one example for each) which AREN’T penicillins!
monobactam
- aztreonam
cephalosporins
- cephalexin
- cefuroxime
- cefotaxime
- ceftriaxone
- ceftazidime
carbapenems
- ertapenem
- imipenem
- meropenem
what enzymes do penicillin-resistant bacteria produce?
what is their mechanism of action?
B-lactamase enzymes
enzyme hydrolyses, thus inactivating, B-lactams
what does BLBLI stand for?
name 2
why are they used?
what problems can they cause? 2
B-lactam/B-lactamase inhibitor combinations
amocixillin-clavulanate
- aka augmentin
- aka co-amoxiclav
piperacillin-tazobactam
- aka tazocin
increases the spectrum of antibiotics by deactivating B-lactamases produced by the bacteria
- very broad spectrum (predispose to C. diff infection)
- names don’t have -illin/cef- so importance of penicillin allergy may be missed
what is another class of antibacterial agents (bar B-lactams) which targets bacterial cell walls?
give 2 examples.
when are they used?
glycopeptides
- vancomycin
- teicoplanin
- penicillin resistance
- penicillin allergy
name a class of antifungals which target fungal cell walls.
give at least one example (what is the suffix?)
what is the mode of action?
echinocandins
- anidulafungin
- caspofungin
- micafungin
-fungin suffix
inhibition of B-1,3-glucan synthase
nb very good as few side effects
name 5 classes of anti-bacterial agents which work by targetting protein synthesis
give at least one example for each
aminoglycosides
- gentamicin
- amikacin
Macrolides
- erythromycin
- clarithromycin (fewer side effects than erythromycin)
- azithromycin
lincosamide
- clindamycin
tetracyclines
- tetracycline
- doxycycline
- tigecycline (more broad, active against gram -ve)
oxazolidionones
- linezolid (used against MRSA + nasty infects but lots of side effects)
(nb also fusidic acid)
nb macrolides and aminoglycosides are ones used most in practise
name 2 antiobiotics which are DNA synthesis inhibitors
mehanism of action:
- both agents inhibit folate synthesis (act at different steps in pathway)
trimethoprim
sulfonamides
name a combination treatment of an anti-fungal and an anti-biotic which are normally given together as an antibacterial agent but is also effective a type of fungal pneumonia seen in immunosuppressed patients
co-trimoxazole
trimethoprim-sulfamethoazole
name a class of antibiotics which are DNA synthesis inhibitors - give 2 examples (suffix?)
mechanism of action:
- inhibit remodelling of DNA during DNA replication
quinolones
- nb most in clinical use are actually fluoroquinolones (incl egs below)
- ciprofloxacin
- levofloxacin
-oxacin suffix
name an anti-biotic which is a RNA synthesis inhibitor
what infection is it predominately used against?
rifampicin
cornerstone of anti-tuberulous chemotherapy
- ie used against TB
name a class of antibacterial agents which target bacterial cell MEMBRANES
give 2 examples
(gram -ve or +ve?)
cyclic lipopeptides
- colistin (gram -ve)
- daptomycin (gram +ve)
nb these are old but having to use them more + more due to anti-biotic resistance
name 1 class of antifungal agents which target fungal cell MEMBRANES - and 2 other different antifungals (that target cell membranes)
what specific component of fungal cell membranes do these drugs target?
azoles
- clotrimazole
- fluconazole
terbinafine
nyacin
target: ergosterol
nb ergosterol is only in fungal cell membranes, not human cell membranes!
metronidazole:
- how it targets bacteria?
- what other type of organism does it target?
targets DNA replication
protazoa
give 4 examples of groups of bacteria which have innate resistance to specific antibacterial agents
nb remember this is what DOESN’T work!
gram-negatives:
- glycopeptides (vancomycin, teicoplanin)
- daptomycin
gram-positives:
- aztreonam
- colistin
anaerobes:
- aminoglycosides (amikacin, gentamicin)
streptococci:
- aminoglycosides (amikacin, gentamicin)
name two methods by which bacteria can acquire genes, which encode an antibiotic resistance mechanism.
- new mutation
- horizontal transfer (genetic exchange between bacteria, via plasmids)
name the 5 possible types of resistance mechanisms (can be innate or acquired)
- absent target
- decreased permeability
- target modification
- enzymatic degradation
- drug efflux
what is the most common acquired resistance mechanism found in anti-fungal-resistant candida?
drug efflux
what mechanism is present in MRSA which results it being resistant to many antibiotics?
which antibiotics is it resistant to?
target modification
- altered penicillin-binding protein (encoded by MecA) does not bind B-lactams
resistant to ALL B-lactams!
what is the most common mechanism of resistance to B-lactams?
enzymatic degradation
- bacteria produce penicillinases (inactivate penicillin etc)
what does ESBL stand for? what are they?
extended-spectrum B-lactamases
enzymes produced by B-lactam resistant bacteria which inactivate penicillins AND cephalosporins
what does VRE stand for?
what method of resistance is found in these organisms?
vancomycin resistant enterococci
target modification
- mutation results in reduction of binding to vancomycin 1000-fold
what does minimum inhibitory concentration (MIC) mean?
the lowest concentration of an antimicrobial drug (antibiotics/antifungals/etc) that will inhibit the visible growth of a microorganism after overnight incubation
which types of viruses tend not to have lipid envelopes?
ones that replicate in the gut
eg:
- adenoviruses
- enteroviruses
what type of DNA/RNA to acute/chronic viruses tend to have?
give at least 4 examples of each
acute - RNA
- influenza
- measles
- mumps
- hep A
chronic - DNA
- latent with/without recurrences:
- herpes simplex
- varicella zoster
- cytomegalovirus
- persistent:
- HIV
- HTLV
- hep B
- hep C
rashes:
- difference between vesicular and non-vesicular rash?
- examples of 5 viruses which cause non-vesicular rashes?
- examples of 3 viruses which cause vesicular rashes?
vesicular just means vesicles are present
non-vesicular rashes:
- measles
- rubella
- parvovirus
- adenovirus
- HHV6 (human herpes virus 6)
vesicular rashes:
- chicken pox (HHV3)
- herpes simplex (HHV1/2)
- enteroviruses
name 6 viruses which can cause respiratory infections
- influenza A/B
- respiratory syncitial virus
- parainfluenza virus
- human metapneumovirus
- rhinovirus
- coronavirus (incl SARS)
name 5 viruses which can cause gastroenteritis
- rotavirus
- norovirus
- astrovirus
- sapovirus
- adenovirus (group F)
name 5 viruses which can cause encephalitis/meningitis
- HSV (reactivation)
- enteroviruses
- rabies
- japanese encephalitis virus
- nipah virus
when would you use antivirals for acute infections in general population? 4
- primary HSV + herpes simplex encephalitis
- chickenpox in adolescents + adults
- shingles in eye
- elderly (shingles, influenza)
nb 99% of people with viral infections won’t need antivirals
nb many viruses don’t actually damage the host cell, it’s the immune response to the virus which causes the damage
what is AZT (azidothymidine)?
what’s it used for?
a nucleoside reverse transcriptase inhibitor (NRTI)
- inhibits reverse transcriptase (used by retroviruses to transform RNA -> DNA)
used against the reterovirus HIV
- inhibits its replication
what are the two types of NRTIs used to treat HIV?
give 2 examples of each
NRTI = nucleoside reverse transcriptase inhibitor
pyrimidine analogues:
- zidovudine (thymidine analogue)
- lamivudine (cytosine analogue)
purine analogues:
- abacavir
- tenofovir
which NRTIs are effective against hep B?
- lamividine
- tenofovir
name 2 herpes virus polymerase inhibitors.
give 2 strains of herpes virus which each is effective against
aciclovir
- herpes simplex
- varicella zoster
ganciclovir
- cytomegalovirus
- HHV6 (human herpes virus 6)
(- as well as HSV + VZV)
nb MUST KNOW THESE!
name an antiviral used to treat hep C
how does it work?
sofosbuvir
hep C RNA polymerase nucleotide inhibitor
“people with hep C tend to be sat on their SOFAS taking drugs”
apart from NRTIs, what is another type of anti-viral drug used to treat HIV?
give 2 examples
non-nucleotide reverse transcriptase inhibitors (NNRTIs)
(work the same as NRTIs but structure is not based on nucleotides)
- efavirenz
- nevirapine
what is another type of antiviral which is used to treat both HIV and hep C?
give some examples
protease inhibitors (PI)
HIV
- atazanavir
- darunavir
- ritonavir
Hep C
- paritaprevir
- grazoprevir
what does HAART stand for?
what’s it used to treat?
what does it consist of?
highly active antiretroviral therapy
HIV
- started when CD4 count falls
- aims to switch off virus replication
- taken lifelong
- 2 NRTIs + NNRTI
- 2 NRTIs + boosted PI
nb now problems with toxicity
what are exogenous interferons used to treat? 6
- some leukaemias
- AIDS related Kaposi’s sarcoma
- chronic hep B
- chronic hep C
- MS
- genital warts (caused by HPV)
what are two anti-virals used in the treatment of influenza?
what is the mechanism?
osteltamivir
- “TAMI flu”
zanamavir
- both are neuramididase inhibitors
what is the antiviral used for the treatment of RSV, hep C and hep E?
ribavirin
when would you deliberately use bacteriocidial antibacterial agents (as opposed to bacteriostatic)?
if the patient had a compromised immune system
- as bacteriostatic drugs require endogenous immmune system to ‘finish off the job’
what is the difference between:
- sepsis?
- severe sepsis?
- septic shock?
sepsis
= presence (probably/definite) of infection with systemic manifestations of infection
severe sepsis
= sepsis-induced tissue hypoperfusion or organ dysfunction
septic shock
= sepsis-induced hypotension, persisting despite adequate fluid resuscitation
what does SIRS stand for?
what can it be due to?
what are the most common/obvious acute clinical signs? 3
systemic inflammatory response syndrome
- may be due to an infection but can also be autoimmune etc
- low BP
- high RR
- altered mental state
what is seen as a more specific biochemical marker for systemic bacterial infection than CRP?
procalcitonin
- doesn’t react to viral/fungal malignancy
nb CRP has a 24hr time lag
what happens to platelet levels in infection?
- platelets can go UP in chronic inflammation
- but can go down in severe acute infection (DIC)
what is the ‘sepsis 6’?
BUFALO
B - take Blood cultures U - measure Urine output F - give IV Fluid A - give broad-spectrum Antibiotics L - measure serum Lactabe + Hb O - give high-flow Oxygen
take 3 things:
- blood cultures
- lactate/Hb
- urine
give 3 things:
- fluid
- antibiotic
- oxygen
nb start antibiotics within ONE hour of severe sepsis/septic shock
why are nitrites present on urine dipstick test if infection is present?
nitrAtes are excreted by kidney normally, some bacteria will reduce them to nitrItes -> nitrites in urine
- so useful test, but not: not all bacteria do this!!
what are the 3 main groups of bacterial flora in the gut?
what is the likelihood of each causing a UTI?
what is a group of bacteria of skin flora which can, rarely, cause UTIs?
gram negative bacilli
- almost always (mainly e coli)
anaerobes
- very rarely
- if see, suspect something like fistula
enterococci
- can see, but uncommon
from skin flora
= staphylococci
what type of staphylococcus if commonly the cause cystitis in younger women?
staph saprophyticus
what is urine likely to look like macroscopically if there is a UTI?
cloudy
nb ‘smelly’ urine does not necessarily mean an infection, more to do with what you’ve eaten
which 3 antibiotics are most likely to result in C. diff infection?
- ciprofloxacin (a fluoroquinolone)
- cefuroxime (a cephalosporin)
- co-amoxiclav
what is the treatment time for an uncomplicated UTI?
3 days of Abx
what factors should influence your choice of antibiotics:
- related to Abx? 6
- related to the patient? 6
Abx related:
- spectrum
- bacteriostatic/cidal
- tissue penetration
- does it need to be monitored?
- side-effects
- route of administration
patient related:
- severity of illness
- site of infection
- immunosuppresed?
- co-morbidities
- co-medications
- allergies
what sort of empirical Abx should be given in:
- local infection?
- sepsis?
local infection
- ‘educated guess’, treat for most likely pathogen
sepsis
- give broad spectrum antibiotics
what broad types of cocci are:
- gram positive? 3
- gram negative? 2
gram positive:
- staphylocci
- streptococci
- enterococci
gram negative:
- meningococci
- gonococci (cause of gonorrhoea)
how are streptococci classified?
alpha haemolytic strep
- eg pneumococci
beta haemolytic streptococcus
- further categorised into group A, B, C or… etc strep
what type of organisms are seen as part of normal skin flora?
staphylococci
- coagulase negative staph (v unlikely to cause infection, only in immunosuppressed patients or something like central lines)
- staph aureus
streptococci
- alpha haemolytic
- beta haemolytic
what type of organisms commonly cause skin + soft tissue infections (SSTIs)?
staph aureus
- MSSA (methicilling sensitive…)
- MRSA
beta haemolytic strep
- group A strep
- strep pyogenes
what sort of normal colonising flora are seen in the:
- mouth/URT? 2
- nasopharynx? 5
mouth/URT:
- streptococci
- anaerobes
(also: gram -ve cocci, candida, staphylococci)
nasopharynx:
- strep pneumoniae
- haemophilus influenzae (gram -ve cocci)
- moraxella catarrhalis (gram -ve cocci)
- other gram negative cocci
- staph aureus
nb majority of URTI are caused by viruses
common causes of sore throat/tonsillitis:
- viral? 2
- bacterial? 2
viral:
- epstein barr virus
- rhinovirus
( and others)
bacteria:
- group A strep
- anaerobes
common causes of sinusitis:
- acute? 2
- chronic? 1
acute sinusitis:
- strep pneumoniae
- haemophilus influenzae
chronic:
- anaerobes
what are the common causes of pneumonia:
- bacterial CAP? 3
- bacterial HAP? 2
- atypical bacteria? 3
- viral? 2
bacterial CAP:
- STREP PNEUMO
- haemophillus influenzae (GNC)
- moraxella catarrhalis (GNC)
bacterial HAP:
- gram -ve bacilli
- staph aureus
(+ ones that cause CAP)
atypical bacteria:
- mycoplasma
- chlamydia
- legionella
viruses:
- influenza
- respiratory syncitial virus
nb virus can causes pneumonia by themselves but commonly just damage the mucosa -> secondary bacterial infection
what is a common cause of ventilator-associated pneumonia?
pseudomonas (a gram negative bacillus)
what are the two commonest causes of encephalitis?
herpes simplex viruses
enteroviruses
nb encephalitis almost always viral
common bacterial causes of meningitis:
- in all ages? 3
- neonates? 3
- immunosuppressed? 2
- post-neuro op? 1
in all ages:
- neisseria meningitis
- strep pneumoniae
- haemophilus influenzae
neonates:
- group B strep
- gram neg bacilli
- listeria
immunosuppressed:
- gram neg bacilli
- listeria
post neuro op
- + skin organisms (eg staph)
what type of bacteria tend to cause cerebral abscesses? why?
normally occur secondary to a local infection so tend to be caused by resp tract flora
what are the three main types of blood stream infections?
what are they often caused by?
- infective endocarditis (native/prosthetic)
- intracardiac device infections
- graft infections
- staphylococci
- streptococci
what are the four antibiotics/types of antibiotics which are most likely to result in c diff infections?
- clindamycin
- co-amoxiclav
- cephalosporins
- fluoroquinolones (-floxacin)
Penicillin G + V
- their other names?
- routes of administration?
- act well against? 1
- act okay against? 2
- not great against? 1
- destroyed by B-lactamases?
Penicillin G
- benzylpenicillin - “ben pen”
- IV/IM
penicillin V
- phenoxymethylpenicillin
- oral
good for:
- streptococci
okay for:
- many anaerobes
- some GNC
bad for:
- staphylocci (as often produced b-lactamases)
yes, destroyed by b-lactamases
flucloxacillin:
- route?
- act well against? 2
- act okay against? 2
- don’t work for? 1
- destroyed by b-lactamases?
oral/IV
good for:
- streptococci
- staphylcocci
okay for:
- many anaerobes
- some GNC
don’t work for:
- MRSA
NOT destroyed by b-lactamases
amoxicillin:
- route?
- act well against? 3
- not great against? 1
- destroyed by b-lactamases?
oral/IV
good for:
- streptococci
- enterococci
- some GNB
not good for:
- staphylococci
yes, destroyed by b-lactamases
co-amoxiclav:
- constituents?
- act well against? 5
- don’t work for? 2
- amoxicillin
- clavulanic acid (inhibits b-lactamases)
good for:
- streptococci
- staphylococci
- most enterococci
- many GNB
- many anaerobes
don’t work for:
- extended spectrum b-lactamase (EBSL) producers
- MRSA
tazocin:
- constituents?
- act well against? 7
- don’t work for? 2
- problem with it? 1
- piperacillin
- tazobactam (inhibits b-lactamases)
good for:
- staphylococci
- most streptococci
- most enterococci
- anaerobes
- PSEUDOMONAS
- GNC
- GNB
doesn’t work for:
- ESBL producers
- MRSA
doesn’t cross blood brain barrier!
nb not much stuff is active against pseudomonas!
macrolides:
- examples? 3
- effective against? 3
- not great against? 1
- erythromycin (lots of GI side effects)
- clarithromycin (fewer GI side effects)
- azithromycin (broader, also covers gram -ve stuff)
good for:
- atypical organisms (chlamydia, gonorrhoea, mycoplasma, legionella)
- staphylococci
- streptococci
not good for:
- gram negatives
glycopeptides:
- examples? 2
- route?
- good for? 3
- don’t work for? 1
- vancomycin
- teicoplanin
IV
- except oral vancomycin, not absorbed but works in gut, used for c diff
good for: - staphylococci - streptococci - enterococci basically gram positive stuff
don’t work for:
- gram negative (intrinsic resistance)
clindamycin:
- route?
- good for? 3
- problems with? 2
- good things about it? 2
oral/IV
good for: - staphylococci - streptococci - some anaerobes basically gram positive
problems:
- variable acquired resistance (do sensitivity test)
- associated with c diff
good things:
- anti-toxin action
- good tissue penetration (good for SSTIs)
ciprofloxacin:
- class?
- route?
- good for? 4
- poor for? 2
- problem? 1
- good things? 2
fluoroquinolones
oral/IV
good for:
- gram negatives
- pseudomonas
- staphylococci
- atypicals
poor for:
- streptococci
- anaerobes
problem:
- associated with c diff
good things:
- good absorption/tissue penetration
- intracellular activity
nb aka early fluoroquinolones