Question book 5 Flashcards
21 year old from Colombia, 21 weeks pregnant
Presents with morbilliform rash, conjunctivitis, fever
develops pneumonitis
Which therapy is advocated for this patient?
ribavirin aciclovir paliziumab measles specific IgG human normal immunoglobulin
human normal immunoglobulin
suggestive of measles - and may be unvaccinated
HNIG can attenuate disease if given early to immunocompromised, pregnant, or infants <9 months (who will be unvaccinated)
26 year old, 16 weeks pregnant, has fever nad URTI
Influenza A confirmed
Started on oseltamivir
What is mechanism of action of oseltamivir?
inhibits neuraminidase cleavage of budding virions
inhibits haemagglutinin binding to epithelial sialic acid
inhibits dissociation of viral ribonuclearproteins
inhibits neuraminidase preventing virion epithelial entry
inhibits epithelial endosome fusion with the viral membrane
inhibits neuraminidase cleavage of budding virions
influenza binds to sialic acid on host epithelial cells through haemagluttinin, and then gains access through endosome fusion.
Neuraminidase normally cleaves sialic acid, to allow new virions to bud from cell
which of the following is not used for treatment against the specified virus
lamividuine HIV lamivudine and HBV amantadine and influenza B ribavirin and RSV aciclovir and HSV
amantadine and influenza B
amantadine inhibits with M2 ion channel in influenza A, preventing uncoating.
influenza B has different structure of M2, so oseltamivir is ineffective
lamivudine inhibits reverse transcriptase - HBV/ HIV
aciclovir inhibits thymidine kinase thereby inhibiting DNA polymerase of herpes viruses
What is mechanism of action of fusidic acid
binding to ribosomes and dissociation of peptide-tRNA
inhibition of topoisomerase IV
inhibition of protein synthesis at 30S subunit
interference with pencillin binding protein activity
binding with elongation factor G and interference with protein synthesis
binding with elongation factor G and interference with protein synthesis
fusidic acid only effective on gram pos bacteria
fusidic acid is bacteriostatic
Discharging wound grows Staph aureus
Antibiogram shows resistance to penicillin, fusidic acid and gentamicin
What is the main mechanism whereby staphylococcal gains resistance to aminoglycoside therapy
ribosomal binding site alteration
aminoglycoside degrading enzyme production
loss of porin channels
up-escalation of efflux mechanisms
alteration of cell wall d-ala-d-ala cross linkage
aminoglycoside degrading enzyme production
3 types of aminoglycoside resistance:
- reduced uptake/ reduced cell permeability - common in Pseudomonas and other gram negatives
- alterations to ribosomal binding site - uncommon as ribosome has multiple binding sites, so needs multiple mutations
- production of aminoglycoside modifying enzymes (most common) - enzymes usually found on plasmids or transposons
What is mechanism of aminoglycoside post-dose effect
prevention of cross-linking of peptide chains
inhibition of cell wall synthesis
binding to protein G and inhibition of protein synthesis
inhibition of ribosomal function
inhibition of topoisomerase IV
inhibition of ribosomal function
aminoglycosides damage cell membrane, and bind to 30S subunit of ribsome
need once a day dosing, as there post-dose effect is to block ribosomes from functioning
Plan to use amoxicillin in pregnant patient who has LRTI/
Which pregnancy safety category is amoxicillin classed under
Category A Category B Category C Category D Category X
Category B
FDA guidelines
Cat A - randomised controlled trial shows it is safe
No RCT in pregnant women, but penicillin known to be safe
Patient with CNS TB
Which drug is best for crossing BBB
rifampicin isoniazid ethambutol streptomycin pyrazinamide
isoniazid
34 year old with drug-susceptible TB, commenced on quadruple therapy.
Remains smear positive at 2 months
Therapeutic drug monitoring showed low levels of some of anti-mycobacterials
Genetic testing showed that he was a fast acetylator
Which drug is affected by this genetic mechanism
isoniazid rifampicin pyrazinamide ethambutol moxifloxacin
isoniazid
N-acetyletransferase is an enzyme involved in isoniazid clearance, and genetic variation (fast acetylators) can lead to fast clearance of isoniazid
What is mechanism whereby Streptococcus pneumoniae can display phenotypic resistance to both erythromycin and clindamicin
efflux pump enzymatic degradation porin loss target alteration impermeability
target alteration
macrolide erythromycin and lincosamides clindamicin insert into 23S subunit of 50S ribosome - blocking protein assembly
This is bactericidal for S.pneumoniae
mutation in ermB gene encodes resistance to both drugs - and alters target site at ribosome
At which site do the fluoroquinolone class of antimicrobials act
cell wall synthesis DNA-dependent RNA polymerase RNA-dependent DNA polymerase Topoisomerase IV ribosomal protein synthesis
Topoisomerase IV
Quinolones act on:
DNA gyrase of gram negative bacteria
topoisomerase for gram pos bacteria
What is the mechanism of action of rifampicin
cell wall inhibitor DNA gyrase inhibitor DNA-dependent RNA polymerase inhibitor DNA-dependent DNA polymerase inhibitor Folate inhibition
DNA-dependent RNA polymerase inhibitor
resistance caused by alteration of rpoB gene which encodes part of ribosome subunit
What is main side effect of rifampicin therapy
eighth nerve toxicity optic neuritis hepatitis dental discolouration pulmonary fibrosis
hepatitis
optic neuropathy caused by ethambutol or linezolid
peripheral neuropathy caused by isoniazid or linezolid
eighth nerve toxicity caused by aminoglycosides
dental discolouration caused by tetracyclines
pulmonary fibrosis caused by nitrofurantoin
23 year old with enteritis and Campylobacter jejuni detected in stools by PCR
what is suitable antimicrobial therapy
amoxicillin ciprofloxacin tetracycline azithromycin ceftriaxone
azithromycin
most cases do not require antibiotics
if severe infection - e.g fever/ hypotension or immunosuppressed, then may require treatment
22% rate of fluoroquinolone resistance UK. Even higher if campylobacter imported by traveller
C. jejuni causes 90% UK infections
C. coli causes other 10%
65 year old diagnosed with paucibacilliary leprosy
What is an essential component of the treatment regime?
isoniazid moxifloxacin dapsone clarithromycin clofazimine
dapsone
Paucibacilliary - ( lepromatous) one or more hypopigmented macules
Treatment is dapsone + rifampicin for 6 months
Multibacilliary (tuberculoid) - symmetrical skin nodules with thickened dermis
Treatment is dapsone + rifampicin + clofazimine for 24 months
65 year old with paucibacilliary leprosy - commenced on dapsone and rifampicin. Develops rash and eosinophilia
What is most likely diagnosis
agranulocytosis allergic dermatitis stevens-johnson syndrome toxic epidermal necrolysis dapsone syndrome
dapsone syndrome
On spectrum of DRESS (Drug relation eosinophilia with systemic symptoms)
presents with rash, fever, eosinophilia
Patient commenced on linezolid
What monitoring should be undertaken
therapeutic drug levels FBC colour vision LFTs clotting
FBC
use over 14 days can lead to myelosuppression
use over 28 days can also lead to optic neuropathy
Patient commenced on linezolid. Which medication significantly interacts with linezolid
venlafaxine propranolol salbutamol nifedipine sodium valproate
venlafaxine
linezolid is weak inhibitor of monoamine oxidase A and B
Avoid SSRI - citalopram, fluoxetine, venlafaxine, sertraline
6 day old has meningitis
What is most frequent adverse event from chloramphenicol usage
optic neuritis isolated thrombocytopenia agranulocytosis gray baby syndrome apalstic anaemia
gray baby syndrome
chloramphenicol binds to 50S ribosomal subunit, preventing peptide elongation
side effects include bone marrow suppression - requires FBC monitoring
in neonates, immature liver means chloramphenicol not metabolised fully. Un-metabolised chloramphenicol can cause hypotension and cyanosis
6 day old has meningitis.
Mother has anaphylaxis to pencillin.
What is empiric therapy for neonate
ceftriaxone benzylpenicillin chloramphenicol amoxicillin vancomycin
benzylpenicillin
maternal history of allergy has no predictive value in neonatal allergy
6 day old has meningitis.
Blood culture grows E.coli
What is best empiric therapy for neonate
Ceftriaxone Cefotaxime Amoxicillin Meropenem Benzylpenicillin
Cefotaxime
Avoid ceftriaxone in neonates because it competes with bilirubin in binding to serum albumin, which can cause hyperbilirubinaemia
No concerns with cefotaxime
Amoxicillin used in listeria
Benzylpenicillin initial empirical therapy, particularly for GBS
54 year old with methicillin susceptible Staph aureus batceraemia
What is the treatment regime
Flucloxacillin Flucloxacillin and rifampicin Flucloxacillin and gentamicin Vancomycin Vancomycin and rifampicin
Flucloxacillin
bacteraemia with no focus can have monotherapy
54 year old with methicillin susceptible Staph aureus prosthetic valve endocarditis
What is the treatment regime
Flucloxacillin Flucloxacillin and rifampicin Flucloxacillin, rifampicin and gentamicin Vancomycin and rifampicin Vancomycin, rifampicin and gentamicin
Flucloxacillin, rifampicin and gentamicin
Because it is a prosthetic valve. Gent has synergistic effect with flucloxacillin. Rifampicin reduces biofilms on valve
flucloxacillin monotherapy suitable for native valve endocarditis
Which drug is most likely to significantly interact with rifampicin
penicillin ibuprofen lansoprazole furosemide warfarin
warfarin
significant interactions with rifampicin: warfarin oral contraceptive statins tacrolimus azole antifungals, ARVs
75 year old with urosepsis prescribed an aminoglycoside therapy
What is mode of action of aminoglycoside
disruption of cytoplasmic membrane function
inhibition of cell wall synthesis
inhibition of DNA gyrase
inhibition of tRNA binding at ribosomal active site
interference with bacterial folic acid metabolism
disruption of cytoplasmic membrane function
aminoglycosides have two mechanisms of action:
- bind to 30S ribosome subunit - provides post-dose effect
- cell membrane dysfunction
tetracyclines - inhibition of tRNA binding at ribosomal active site
Note gentamicin ends in “micin” as developed from a bacteria. Neomycin/ streptomycin developed from Streptomycin species, so keep “mycin” suffix
What is most frequent adverse event from aminoglycoside therapy
low frequency hearing loss high frequency hearing loss interstitial tubular nephritis focal segmental glomerulonephritis nephrotic syndrome
high frequency hearing loss
patient commenced on daptomycin therapy
What monitoring must be undetaken
creatinine clearance creatine phosphokinase platelet count ALT ALP
creatine phosphokinase - check baseline, then weekly monitoring
not to be used for gram pos pneumonia as it is inactivated by lung surfactant
14 year old with cerebral palsy diagnosed with sepsis secondary to ESBL E.coli in urinary tract
meropenem commenced
Which medication might this antimicrobial significantly interact with
levetiracetam baclofen valproate phenytoin gabapentin
valproate
beta-lactams, carbapenems, and particularly quinolones reduce the seizure threshold
meropenem directly reduces levels of sodium valproate
45 year old has sputum which grows Pseudomonas
Phenotypically resistant to ceftazidime, tazocin, meropenem
which drug is most likely to be effective as treatment for this patient
ceftobiprole ceftraroline ceftolozane-tazobactam ceftazidime-avibactam cefotaxime
ceftolozane-tazobactam
loss of ceftazidime susceptibility is due to combination of upregulation of AmpC betalactamase production and increased efflux
Pseudomonas usually remains susceptible to ceftolozane-tazobactam combination
ceftaroline is 5th generation cephalosporin - primarily for gram pos eg MRSA
Which agent must rifampicin not be co-prescribed with
fusidic acid flucloxacillin voriconazole acivlovir ciprofloxacin
voriconazole
rifampicin is potent enzyme inducer, and greatly affects metabolism of azoles
Which antifungal requires therapeutic drug monitoring
amphotericine B micafungin flucytosine caspofungin anidulofungin
flucytosine
anti-fungal drugs requiring monitoring: flucytosine itraconazole posaconazole voriconazole
15 year old diagnosed with tinea capitis and Microsporum spp grown
Which antifungal treatment is appropriate for fungal infection of hair shaft
topical terbinafine topical ketoconazole oral ketoconaozle oral voriconazole oral griseofulvin
oral griseofulvin
invade hair shaft - so topical treatment is ineffective
37 year old neutropenic patient is on ward, and there is building work on oging in next ward.
Which antifungal is not indicated for prophylaxis
liposomal amphotericin B amphotericin B deoxycholate posaconazole voriconazole fluconazole
fluconazole
building work suggests risk of aspergillus.
Fluconazole is only drug here that does not have activity against aspergillus
Which antifungal is not effective against PCP
caspofungin voriconazole pentamidine dapsone co-trimoxazole
voriconazole
Treatments for PCP: co-trimoxazole primaquine + clindamicin pentamidine dapsone + trimethoprim atovaquone caspofungin - rarely used, but some effect on PCP
Small company designing alternative to traditional antibiotics which work to increase the expression of anti-inflammatory chemokines and cytokines and reduce expression of pro-inflamamtory cytokines in which class of anti-infective would this agent be described
antimicrobial peptide innate defence peptide engineered bacteriophage probiotic metal chelation
innate defence peptide
What drug must fusidic acid not be co-prescribed with
fusidic acid and statins have risk of myotoxicity
What is mechanism of action of dapsone?
inhibits synthesis of dihydrofolic acid
What are indications for dapsone?
leprosy - essential treatment
PCP
toxoplasmosis
also used for anti-inflammatory effects such as acne, and other skin conditions
What are indications for dapsone?
leprosy - essential treatment
PCP
toxoplasmosis
also used for anti-inflammatory effects such as acne, and other skin conditions
75 year old with CAP and pencillin allergy prescribed doxycycline
What is mode of action of tetracyclines
disruption of cytoplasmic membrane function
inhibition of cell wall synthesis
inhibition of DNA gyrase
inhibition of tRNA binding at ribosomal active site
interference with bacterial folic acid metabolism
inhibition of tRNA binding at ribosomal active site
