Infectious Disease Flashcards
(142 cards)
1
Q
Mechanism of action of Maraviroc and Enfuvirtide
A
Maraviroc - CCR5 inhibitor. Prevents viral entry. However tropism assay is essential prior to therapy to confirm that HIV is R5 strain.
Enfuvirtide - inhibits gp41 and prevents fusion of virus and the cell. Must be injected.
2
Q
What is the approximate sensitivity and specificity of IGRA testing?
Caveats to IGRA testing?
A
Specificity 98-100% for low TB population with no risk factors
Sensitivity 80-85% in patients with active TB
Therefore IGRA cannot be used as an test to exclude active TB.
Also cannot be used to differentiate between active/latent TB.
IGRA may stay positive after successful TB treatment therefore cannot be used to assess outcome of treatment.
Cross reactivity with other mycobacterium spp occurs, but not with BCG vaccination.
3
Q
Action and side effects of linezolid
A
Entirely synthetic protein synthesis inhibitor therefore no known pre-existing resistance.
Good tissue penetration and bioavailability.
SE: GI, cytopenias, neuropathy, MAO inhibition (therefore avoid SSRI, tramadol, pethidine)
4
Q
Name the diseases common with following CD4 counts:
CD4 cell count 200-500
50-200
<50
A
200-500 - herpes zoster, pneumococcal pneumonia, TB, oral candida
50-200 - PJP, CNS toxo, cryptococcosis, cancers (kaposis sarcoma, CNS lymphoma, NHL)
<50 - MAC, CMV retinitis, cryptosporidiasis
5
Q
Treatment of choice for uncomplicated falciparum infection?
What about in severe malaria? (eg, jaundice, decreased LOC, oliguria, severe anaemia, hypoglycaemia)
A
- Artemether + lumefantrine
- Atovaquone + proguanil
- Quinine + doxycycline (or clindamycin)
IV artesunate or IV quinine
6
Q
Mechanism of daptomycin?
A
A cyclic lipopeptide which binds to bacterial cell membrane and causes rapid depolarisation of membrane potential in both growing and stationary phase cells. This loss of membrane potential causes inhibition of DNA, RNA and proteins, resulting in bacterial cell death with negligible cell lysis.
Cannot be used in pneumonia due to inactivation by surfactant.
7
Q
Mechanism of action of foscarnet?
Activity against?
Side effects?
A
Pyrophosphate analogue which does not require phosphorylation unlike aciclovir/ganciclovir.
Directly inhibits pyrophosphate binding site of DNA polymerase.
Active against CMV, HSV1/2, VZV, Hep B and HIV.
Renal dysfunction, metabolic disturbances.
8
Q
Define the following HIV outcomes:
Incomplete virological response
Virological rebound
A
Incomplete virological response - HIV RNA >200 copies/mL after 24 weeks on ARV
Virological rebound - repeated detection of HIV RNA >200copies/mL after viral suppression
9
Q
4 Indications for moxifloxacin in TB?
A
- MDR-TB
- Ethambutol required but contraindicated (eg due to eye disease)
- IV therapy required or hepatotoxicity
- CNS TB disease
10
Q
Why are there different cut off points for different population groups in Mantoux test?
A
To maximize sensitivity in high risk groups, and to maximize specificity in low risk groups.
High risk groups = >5mm (HIV, immunosuppressed, close contact with infectious TB person, old TB scar on CXR)
Low risk groups = BCG vaccinated, all other persons
11
Q
Treatment options in VRE infection and colonization?
A
If infected, Linezolid, Daptomycin, Tigecycline.
If colonized, avoid anti-anaerobic antibiotics (which can increase VRE burden in the colon), contact isolation if diarrhoea etc which may spread VRE around
12
Q
What is caused by aflatoxins and mycotoxins produced by aspergillus fungi?
A
Associated with development of HCC and may be associated with high rates of p53 mutation
13
Q
What must be excluded before primaquine use?
A
G6PD deficiency - can cause haemolysis
14
Q
Compare and contrast CJD vs vCJD
A
CJD - spontaneous, iatrogenic or familial causes. Rapidly progressive dementia associated with myoclonus and extrapyramidal signs in 2/3.
EEG shows periodic synchronous sharp wave complexes. MRI showing involvement of putamen and head of caudate.
Elevated levels of 14-3-3 proteins found in CSF.
vCJD - almost certainly due to bovine to human transmission of BSE. Affects younger patients and less rapid progression. More sensory/psychiatric features.
14-3-3 and EEG much less useful. PrPsc found in tonsilar tissues.
15
Q
What does MDR TB mean?
A
Resistance to Isoniazid, Rifampicin +/- others.
Around 5% of TB infections worldwide.
16
Q
What should you use for recurrent genital herpes cause by HSV? Valaciclovir or aciclovir?
A
You can use both… no significant benefit of valaciclovir over aciclovir but compliance is the main issue (valaciclovir only needs to be taken twice a day, aciclovir 5 times a day)
17
Q
Pathogenesis of HIV associated lipoatrophy.
Cause?
A
Due to inhibition of mitochondrial DNA polymerase gamma resulting in ‘mitochondrial toxicity’
NRTI exposure is the major risk factor - stavudine and zidovudine in particular
18
Q
Factors which reduce HIV acquisition?
A
- Circumcision - decreased HIV acquisition in heterosexual men but efficacy in MSM conflicting. (circumcized penis is more keratinized and resistant to acquisition. Also foreskin has lots of dendritic cells which circumcision removes)
- CCR5 D32 homozygotes resistant to HIV infection
1% Caucasians are homozygous for this. Rare in Africans and Asians.
20% Caucasians are heterozygous for CCR5D32 allele - 2 fold reduction in time to progression to AIDS in adults.
19
Q
Presenting symptoms of typhoid fever?
Complications at 3-4 weeks?
Treatment?
Consequence of chronic carrier state?
A
Fevers, abdominal pain, CONSTIPATION, rose spots
Complications:
- Intestinal perforation
- Endocarditis
- Splenic/liver abscess
- Endovascular infection in grafts, aneurysms and atherosclerotic plaques especially >50 age
Treat with ciprofloxacin, ceftriaxone
Increased risk of gallbladder Ca if chronic carrier state.
Higher frequency of chronic carrier state if concurrent schistosoma infection or biliary abnormalities.
20
Q
Mechanism of action of protease inhibitors
A
Inhibits cleavage of Gag-Pol polyprotein which is necessary for maturation of viral particles.
21
Q
Which drugs are implicated in TB therapy induced hepatitis?
Describe your management to this situation.
A
Pyrazinamide > Isoniazid > Rifampicin.
If 2-5x ULN and asymptomatic, monitor closely.
If >5x ULN or >3x with symptoms, cease medications or add liver safe medications (moxifloxacin, ethambutol, amikacin)
Once ALT <2x ULN, restart Isoniazid, then rifampicin. If tolerated, then do not start pyrazinamide as this was likely the implicating cause and just extend the treatment to 9 months with HRE.
22
Q
Typical treatment regimen for TB?
Describe the three compartment model
A
2 months of HRZE followed by 4 months of HR
Isoniazid kills the rapidly multiplying TB
Pyrazinamide targets the slowly multiplying TB in the acidic environment (eg inside caseous necrosis, macrophages etc)
Rifampicin targets the sporadically multiplying TB.
23
Q
What is the transmission risk of HCV with needle stick?
A
Between 2-3%, highest risk with PCR positive source.
PCR detects virus 10 days-6 weeks after infection.
24
Q
Mechanism of action for cidofovir?
A
NucleoTIDE analogue of dCMP.
Also does not require phosphorylation by TK/UL97
Active against resistant viruses and wider range of viruses including HHV6/8, adenovirus, polyomavirus, HPV.
Causes renal dysfunction.
Brincidofovir is the prodrug of cidofovir.
25
4 causes of QTc prolongation in antibiotics
1. Voriconazole
2. Macrolides
3. Moxifloxacin
4. Pentamidine
26
Describe TB paradoxical reaction
Clinical/radiological deterioration of preexisting lesions whilst on therapy, occurring 20-150 days into treatment.
Does not mean treatment failure - usually if resistant TB, patients do NOT get better.
Therefore manage with continuation of existing TB treatment, corticosteroids, aspiration of pus, excision etc.
Seen in 2-23% of HIV negative TB patients.
27
3 Contraindications to use of mefloquine?
1. Neuropsychiatric disorders
2. Epilepsy
3. Cardiac conduction defects
28
1 major benefit of abacavir and 2 major side effects to be aware of?
Major benefit in once a day dosing.
3-5% have allergic reaction with GIT symptoms, myalgia, rash, cough, leucopenia.
Strongly associated with HLAB5701. Most commonly occurs in firest 6 weeks. Dont rechallenge - switch to another drug
Also 2x AMI risk therefore avoid in CVD.
29
Pathogenesis in botulism?
Toxins A, B and E binds to pre-synaptic nerves and prevents release of ACh. Affects cranial nerves then symmetrical descent. No sympathetic or sensory involvement.
30
3 causes of peripheral neuropathy in antibiotic use
1. Linezolid
2. Metronidazole
3. Isoniazid
31
What is involved in ART drug resistance testing?
Genotype testing - can test for mutations in the reverse transcriptase gene (resistance to NRTI/NNRTI), protease gene (resistance to PIs) and integrase gene (resistance to INSTIs) from individuals viral isolates.
Usually need HIV VL >1000 copies/mL for the test.
32
How do you make the diagnosis of HIV?
HIV ELISA +/- confirmatory western blot. Can be negative in acute setting (<2 weeks after acquisition)
HIV viral load testing is important in high risk groups with negative or indeterminate western blots, but false positives can occur in 4-26% therefore cannot be used as a screening tool.
33
Risk factors for vertical transmission of HIV from mother to infant
1. High viral load
2. Low maternal CD4 count
3. Breast feeding doubles risk
ART reduces risk from 10% to <1%
Risk is also reduced with LSCS however ?usefulness after ART
34
Classical MRI pattern seen in TB meningitis?
Basal meningitis - can cause strokes affecting perforating vessels supplying the base of the brain
35
3 Major mechanisms of antibiotic resistance
1. Inactivation - beta lactamases, erm methylation genes in pneumococcus for macrolides
2. Alteration of binding target - pneumococcus and alteration of PBP, staph aureus and methicillin like antibiotics
3. Decreased uptake - reduced penetration eg with porins for pseudomonas and carbapenems, and antibiotic efflux - eg with pneumococcus with mef gene for macrolides.
36
Mechanism of action of Raltegravir
'tegra' - integrase strand transfer inhibitor INSTI.
Blocks integration stage of HIV replication.
Another example is Elvitegravir.
37
5 functions of antibody
1. B cell activation
2. Neutralization of toxins eg tetanus
3. Complement activation (complement binds to Fc portion of IgG or IgM)
4. Opsonization for phagocytosis
5. Ab dependent cell mediated cytotoxicity - cytotoxic cells with Fc receptors for Igs can bind lyse target cells.
Also direct leukocyte into areas of damage - eg NK cells guide neutrophils
38
Treatment of choice for meningicoccal prophylaxis?
Single dose IM ceftriaxone (97%). More effective than oral rifampicin for 2 days (75-81%)
Everyone should be vaccinated if exposed, and within 4 weeks of onset of disease in the case.
39
Describe the mechanism behind Mantoux test
Tests type 4 hypersensitivity reaction with T cells.
Tuberculin once injected into the skin is taken up by APC and presented to T cell, which then secretes INF gamma, TNF alpha, IL-8 over 72 hours, causing induration.
40
Compare R5 and X4 strains.
R5 strains infect macrophages and T cells. Usually in early infection and less aggressive and uses CCR5 to gain entry into CD4 cells. More frequently transmitted.
X4 strains infect only T cells and T cell lines. Gains entry via CXCR4 co receptors. More aggressive with high viral titres. More rapid decline in CD4 and increased rate of progression to AIDS.
41
Antibiotic regimen for:
Mild CAP
Moderate CAP
Severe CAP
Mild CAP - amoxycillin/doxycycline
Moderate CAP - penicillin plus doxycycline
Severe CAP - ceftriaxone plus azithromycin
42
Treatment of choice for vivax/malariae/ovale?
Chloroquine followed by 14 day course of primaquine for vivax/ovale
43
Describe HIV viral entry
All HIV strains recognize CD4 and binds to it via gp120 on the viral surface. Co receptor affinity varies depending on the gp120 structure.
Co receptors include CCR5, CXCR4.
Binding results in conformational change to gp41 resulting in membrane fusion and entry of viral particles into the cytoplasm. RNA reverse transcriptase transcribes the RNA to dsDNA which is then incorporated into the cell nucleus and transcribed.
Notes: dendritic cells are the first cells to become infected. They later transfer the virus to lymphocytes at the LN. DCs also express CD4, CCR5 but not CXCR4.
44
What is the treatment of choice for herpes zoster (shingles)?
Valaciclovir.
More effective than aciclovir in reducing zoster associated pain (acute pain and PHN), also PHN was less likely with VACV over ACV
45
Manifestation of cryptosporidiasis
Usually gastrointestinal manifestations - profuse watery diarrhoea, loss of weight, abdo pain.
Diagnose via stool culture, bowel biopsy.
Eradication is rare, and hard to cure.
46
What is hVISA?
Where is it seen?
What do you treat it with?
Heterogeneous combination of majority MRSA and minotrity of VISA. Hard to detect and is associated with thickened cell wall thereby more targets of D-Ala-D-Ala for vancomycin to bind onto.
Seen in dialysis patients or infected foreign bodies
Vancomycin failure is common, therefore need to use linezolid, tigecycline, ceftaroline, rafampicin/fusidate
47
What is the role of antibiotic 'locks' in long term CVC?
Locks such as heparin+vancomycin or vancomycin+ciprofloxacin did reduce rates of catheter related blood stream infection and longer time until CR-BSI, however there are concerns regarding VRE - therefore currently NOT routinely recommended.
48
What anti-TB meds can be used in pregnancy?
All 1st line drugs can be used in pregnancy. (ie, HRZE)
49
# Define culture negative infective endocarditis.
Name 5 causes of culture negative IE.
IE with 3x negative PBC after 7 days
Causes: Q fever, Bartonella, mycoplasma hominis, clamydophila, fungi
50
When would you consider adding metronidazole in aspiration pneumonitis/pneumonia?
1. Terrible gum disease/foul smelling sputum
2. Severe alcohol abuse
3. Lung abscess with fluid level
4. Empyema/complete white out
51
3 factors causing false positive tests in Mantoux testing?
1. BCG vaccinations
2. Repeat Mantoux testing causing boosting
3. Non-tuberculous mycobacteria infection
52
What is the malaria prophylaxis of choice for a traveller travelling to chloroquine/mefloquine resistant area?
Atovaquone + proguanil or doxycycline.
53
How does post transplant lymphoproliferative disease manifest?
Management?
1. Mononucleosis-like syndrome - tonsilar and LN involvement
2. Diffuse polymorphous B cell infiltration involving many viscera, presents with hepatitis
3. Localized extranodal tumours in GIT, neck, thorax and CNS.
Highest risk in seronegative recipient, prolonged anti-T cell immunosuppressive therapy eg: OKT-3
Aciclovir is of no proven efficacy. Only way to manage is with reduce immunosuppression.
54
What is the risk of functional asplenia/hyposplenism?
Increased life time risk of serious infection at 5%
Pathogens - strep pneumoniae, neisseria meningitidis, H influenzae, capnocytophaga canimorsus
Manage with immunisations and sometimes antibiotic prophylaxis with amoxycillin/phenoxymethylpenicillin
55
What is the difference between valaciclovir/famciclovir and aciclovir?
They are prodrug of a 'prodrug' which is aciclovir.
| Greater bioavailability.
56
Mechanism of action for ganciclovir?
Analogue of nucleoside guanosine.
Preferentially phosphorylated by CMV viral kinase UL97
Usually administered IV.
Causes chain termination. Effective against CMV.
57
How do bacterias acquire new DNAs for antibiotic resistance?
1. Conjugation between gram negatives to transfer plasmid mediated DNA materia via pilus
2. Transformation with transfer of DNA between bacteria
3. Transduction with transfer of DNA between bacteria via bacteriophages
58
Which drug is most commonly involved in TB drug resistance?
Isoniazid in 13%.
Use 6RZE or 9R(Z)E.
59
Mechanism of action for azoles
Inhibits CYP450 required for cell membrane ergosterol synthesis by the fungi.
Eg: fluconazole (candida), itraconazole (aspergillus), voriconazole (candida), posaconazole (zygomycetes)
60
Post exposure prophylaxis in HIV for:
1. Low risk (mucosal exposure, intact skin exposure, low viral load)
2. Higher risk (percutaneous needle injury, deep injury, high viral load)
1. Lamivudine and zidovudine for 4 weeks
2. Above plus third drug eg: lopinavir+ritonavir for 4 weeks
Low dose ritonavir is added to boost lopinavir bioavailability
61
What organisms have inducible beta-lactamases?
Class C AmpC type beta lactamases present in ESCAPPM organisms with inducible chromosomal beta lactamases:
```
Enterobacter cloacae/aerogenes
Serratia
Citrobacter
Acinetobacter
Proteus
Providencia spp
Morganella morganii
```
62
2 ways in which MAC infections often present?
How would you treat MAC infection?
1. Old ladies with RML involvement, often multiple genotypes and smear negative. Low bacterial load.
2. Male smokers/drinkers infected with single genotype and heavy growth/high bacterial load.
Standard therapy is 3 agents 3x/week for at least 12 months:
Clarithromycin/azithromycin, rifampicin, ethambutol.
Can add streptomycin or amikacin for first 2 months if cavitating disease.
Need to use all 3 drugs or guaranteed to fail.
63
Mechanism of action for echinocandins?
Inhibits glucan synthase which is required for production of beta 1,3 glucan in the fungal cell wall.
Eg: caspofungin (candida)
64
How do you treat concurrent HIV and Hep B infection?
Use tenofovir based therapy which is a nucleotide inhibitor (together with nucleoside inhibitors such as FTC or 3TC)
If Hep B negative, vaccinate!
65
Notable characteristics of class B beta-lactamases
Metallo-proteinases - zinc dependent.
Found especially in pseudomonas and acinetobacter
Usually plasmid mediated
Hydrolyzes all beta lactams and carbapenems except aztreonam
NDM-1 is an example of metallo-proteinase.
Has a cost to the bacteria - over time, if NDM-1 is not necessary, it is selected out secondary to competition from non-resistant bacteria. Takes 6 months.
66
Mechanism of action for amphotericin B
Side effects?
Inserts into fungal cytoplasmic membrane with increased membrane permeability, closely bound to sterols. Increases K+ channel activity, with loss of intracellular K.
SE: nephrotoxicity via decrease in GFR, direct vasoconstriction of afferent arterioles, K/Mg/HCO3 wasting
Also infusional reaction - mainly myalgia.
67
What does XDR-TB mean?
What is the consequence of XDR-TB infection?
Resistance to Isoniazid, Rifampicin, Quinolones AND injectables (such as amikacin, kanamycin or capreomycin).
10% of MDR is XDR.
Essentially successful outcomes are halved:
1/2 sputum smear conversion, 1/2 treatment success, 2x mortality rate (20%)
Takes 4x longer to treat with 100x the cost!!!
68
Mechanism of fosfomycin?
Inhibits MurA enzyme thereby inhibits bacterial cell wall biogenesis. Bactericidal.
Mainly for resistant UTIs as the antibiotic becomes highly concentrated in the urine.
69
Name 4 nucleoside analogues and 1 nucleotide analogue
Zidovudine, Lamivudine, Emtricitabine, Abacavir
Tenofovir
70
Which cell does JC Virus predominantly affect?
Polyomavirus which attacks myelin-producing oligodendroglia of the brain
71
How does botulinum toxin work?
Blocks release of acetylcholine from peripheral nerve synapses
72
What does NORSA stand for and its significance?
Non multiply resistant oxacillin resistant staph aureus.
Common in prisoners, IVDU, MSM, indigenous population.
Has Panton-Valentine Leucocidin associated with virulence.
Causes Necrotising fasciitis, rapidly progressive septicaemia, OM, endocarditis.
73
2 major NRTI backbones available?
1. TDF/FTC combination
FTC = emtricitabine
2. Abacavir/3TC
3TC - lamivudine
74
What is the effect of PIs and NNRTIs on CYP3A4?
Most PIs and NNRTIs are INDUCERS of CYP3A4.
Except Ritonavir which is a INHIBITOR.
Ritonavir is therefore given together with other PIs to prevent metabolism and to increase blood level and hence improve pharmacokinetic profile.
75
Mechanism of colistin?
Binds to lipopolysaccharides and phospholipids in outer cell membrane, leading to disruption of cell membrane, leakage and cell death.
Main SE being renal and neurotoxicity.
Mainly against gram negatives including pseudomonas, acinetobacter, klebsiella, salmonella.
Used in infections resistant to meropenem.
76
How does tetanus toxin cause disease?
Transported from peripheral to the CNS by retrograde axonal transport. It interferes with the exocytosis of inhibitory neurotransmitters. Sustained excitatory discharge ensues, causing the characteristic muscle spasm of tetanus.
77
Mechanism of action of nucleoside/nucleotide RTIs in HIV treatment
Interferes with RNA dependent DNA reverse transcriptase - inhibits HIV replication via causing premature chain termination.
All the Nucleoside analogues ends with 'ine', eg stavudine, emtricitabine... except Abacavir.
Nucleotide analogues - tenofovir.
78
What medications are absolutely contraindicated with ritonavir/cobicistat?
Ritonavir and cobicistat are used to boost PIs.
Potent inhibitors of P450 3A4 enzymes.
Absolute contraindications in:
1. Statins - rhabdomyolysis
2. Cisapride - QTc prolongation leading to TdP
3. Midazolam/triazolam prolonged sedation therefore use propofol.
79
Mechanism of action of NNRTIs
Disrupts RT catalytic sites by binding to RT and denatures it.
Examples: nevirapine, efavirenz.
80
Which cell is involved in latent EBV Infection?
B lymphocytes
81
Name 2 NNRTIs and their associated side effects
Efavirenz - 40% CNS side effects - vivid dreams, sleep change, headache, teratogenic.
Nevirapine - rash in 5-10%, especially higher in women, hepatotoxicity
82
What is the interaction between nevirapine and methadone?
Nevirapine induces P450 3A4.
Concurrent use of nevirapine and methadone may result in methadone withdrawal.
Cessation of nevirapine may result in overdose.
83
Which malaria species are associated with relapses?
P ovale/vivax, therefore requires treatment with primaquine.
vivax especially associated with dormant liver stages
84
Describe the effect of mutation of CCR5 to form CCR5delta32
Results in CCR5 not being expressed on cell surface therefore HIV cannot use CCR5 co-receptor to gain entry.
85
3 Risk factors for immune reconstitution inflammatory syndrome in HIV/TB coinfection?
When and how does IRIS present?
1. Early commencement of ART
2. Low CD4 count
3. High viral load.
Usually presents ~ 1 month after initiation of ART.
Can present with unmasking of subclinical TB infection, or paradoxical worsening of clinical manifestations of active TB infection whilst on TB treatment after commencing ART.
86
What is the treatment of choice for TB meningitis?
HRZ + moxifloxacin for 12 months.
Moxifloxacin has a better CNS penetration than ethambutol.
Also add dexamethasone - reduces mortality but not morbidity.
87
What was the result of the VICTOR study?
It showed that valganciclovir orally was non inferior to IV ganciclovir in treatment of CMV infection. However the trial excluded severe life threatening infections (such as pneumonitis, GI involvement, heavily immunosuppressed patients with CMV infection) and patients only had modest CMV viral load only.
88
How does P falciparum causes end organ damage?
Alters the surface of RBC causing adhesion to endothelial cells in capillary beds and results in organ sequestration especially kidney and cerebrum.
89
Mechanism of aciclovir?
Efficacy against which viruses?
Requires initial activation by viral thymidine kinase.
Analogue of deoxyguanosine.
Gets incoorporated into the viral DNA and causes chain termination.
Effective against HSV/VZV
Active against some CMV but CMV have generally higher MIC to aciclovir therefore ganciclovir is more effective.
90
Describe mechanism of Q-gold assay
Whole blood is exposed to TB antigen in which sensitised lymphocytes release measurable cytokines in response. Also need to test response to mitogens and to nothing.
If mitogen response is negative - indeterminate test.
Potential false +ves from Mycobacterium marinum/kansasii infection
91
3 Side effects of TDF (tenofovir)
1. Fanconi Syndrome - RTA with loss of HCO3, phosphate, glucose, aminoacids
2. Decline in eGFR without Fanconi's syndrome
3. Decreased BMD
92
Role of HSV-2 in HIV transmission
HSV coninfection elads to increased excretion and transmission of HIV.
Valacyclovir decreased genital and plasma HIV-1 RNA, but RCT of acyclovir did not decrease HIV transmission.
93
Manifestation of cryptococcal disease in HIV
Typically CD4 count below <100
Commonly as meningitis, lung infection, prostatitis skin but can affect any organ.
Meningism and photophobia are unusual.
Screen with serum cryptococcal antigen which is very sensitive - if positive, proceed with CSF for cryptococcal antigen/india ink staining
94
What is the impact of HIV on HCV infection?
1. Higher likelihood of chronic infection
2. Higher HCV viral load
3. Accelerated rates of fibrosis and cirrhosis
4. Increased morbidity and mortality in ESLD.
95
How does staph aureus exotoxin cause disease?
Superantigen - activate large numbers of T cells resulting in massive cytokine production. Bypasses processing by APCs but instead interact directly with the invariant region of the MHC2 molecule. MHC2-superantigen complex then interacts with the T cell receptor at the variable part of the beta chain. Thus all T cells with a recognized V beta region are stimulated.
96
2 major side effects of enfuvirtide
1. Teratogenic - contraindicated in pregnancy
| 2. Increased incidence of bacterial pneumonia
97
Gentamycin ototoxicity
Exact mechanism of ototoxicity remains unknown.
Latency of clearance from the inner ear fluids mean that the ototoxicity can occur upto 6 months after last dose.
Risk factors:
1. Larger dose
2. Higher blood level
3. Longer duration of therapy
4. Older patients
5. Renal insufficiency
6. Other ototoxic meds such as loop diuretics
98
Characteristics of NAP-1 strain of C difficile
1. Produces binary toxin, an additional toxin which is not present in other strains
2. Produces larger quantities of toxin A/B compared to other strains
3. Partial deletion of tcdC, that is responsible for toxin production downregulation
4. Resistance to fluoroquinolones.
99
Features of infectious mononucleosis
1. Fever
2. Adenopathy
3. Pharyngitis
4. Splenomegaly
5. Fatigue
6. Atypical lymphocytosis
7. Maculopapular rash following ampicillin/amoxicillin
100
Monospot test
Checks for heterophile antibodies which react to horse red blood cells which then causes agglutination.
Highly specific for EBV infection - if monospot test is positive, no further investigations are required.
However not as sensitive, and false negative rates are highest during the initial phase of symptoms. If clinical suspicion is high, need to test for EBV specific IgG/IgM antibodies.
101
Mechanism of action of linezolid
Protein synthesis inhibitors - Although its mechanism of action is not fully understood, linezolid appears to work on the first step of protein synthesis, initiation, unlike most other protein synthesis inhibitors, which inhibit elongation.
It does so by preventing the formation of the initiation complex, composed of the 30S and 50S subunits of the ribosome, tRNA, and mRNA.
Due to this unique mechanism of action, cross-resistance between linezolid and other protein synthesis inhibitors is highly infrequent or nonexistent
102
2 most common organisms in ventilator associated pneumonia
1. MRSA/MSSA
| 2. Pseudomonas aeruginosa
103
5 vaccines contraindicated in immunocompromised
1. MMR
2. VZV
3. Yellow fever
4. Oral typhoid
5. BCG
Rabies, meningococcal, hep A/B, INJECTED typhoid vaccines, pneumococcal and influenza vaccines are ok.
104
NDM-1 mutation
Treatment options for NDM-1 gram negative infections
Carbapenemase and additional resistance to multiple classes including fluoroquinolones and aminoglycosides
Colistin or tigecycline
105
Ebola virus
Type of viral haemorrhagic fever
Ebola virus host are the fruit bats
Transmitted via direct contact with blood, secretions or other bodily fluids of infected people
Incubation period of 2-21 days
Illness starts with fever, headache, myalgia, followed by D&V, abdominal pain, and in some cases bleeding complications.
Case fatality of 25-90%
Treatment is supportive only.
106
Zika virus
Transmitted by Aedes mosquitos
Belongs to flavivirus family
Incubation period of 3-12 days
Fevers, rash, conjunctivitis, arthralgias, myalgias, headaches and malaise. Clinical course is usually mild.
Diagnosed via RNA in serum and urine.
Serum IgM develops days 4-7 and detectable upto 12 weeks.
Complications include microcephaly in fetus, Gullaine Barre syndrome.
107
Compare and contrast vancomycin resistant enterococci (faecalis and faecium)
E faecalis - often sensitive to amoxicillin and high level gentamicin and linezolid.
E faecium - often resistant to amoxicillin and high level gentamicin (upto 50%)
They are both sensitive to linezolid.
Important to know if it is vanA or vanB:
vanB confers sensitivity to teicoplanin, while vanA confers resistance to teicoplanin.
108
M protein in GAS
An important virulence determinant of GAS, M protein, is a filamentous protein anchored to the cell membrane. M protein has antiphagocytic properties. Many M types of GAS have been associated with necrotizing fasciitis; types 1 and 3 are most common [10,11]. These strains can produce one or more of the pyrogenic exotoxins A, B, or C [12,13]. Necrotizing fasciitis caused by these strains is associated with streptococcal toxic shock syndrome in about 50 percent of cases
109
2 forms of bacterial necrotising fasciitis
Type I necrotizing fasciitis is a mixed infection caused by aerobic and anaerobic bacteria. Risk factors include diabetes, peripheral vascular disease (PVD), immune compromise, and recent surgery, including minor procedures such as circumcision in newborn infants. Patients with diabetes and/or PVD frequently have lower extremity involvement. Neonates usually have abdominal or perineal involvement.
Type II necrotizing fasciitis due to group A Streptococcus (GAS) or other beta-hemolytic streptococci, either alone or in combination with other species, most commonly S. aureus. It can occur among healthy individuals with no past medical history, in any age group [6]. Predisposing factors include a history of skin injury, such as laceration or burn, blunt trauma, recent surgery, childbirth, injection drug use, and varicella infection (chickenpox)
110
4 cardinal features of dengue haemorrhagic fever
What about dengue shock syndrome?
1. Increased vascular permeability (plasma leakage syndrome) evidenced by hemoconcentration (20 percent or greater rise in hematocrit above baseline value), pleural effusion, or ascites [17]
2. Marked thrombocytopenia (100,000 cells/mm3 or lower)
3. Fever lasting two to seven days
4. A hemorrhagic tendency (as demonstrated by a positive tourniquet test) or spontaneous bleeding
Dengue shock syndrome is above plus evidence of shock.
111
Compare and contrast Chancre and Chancroid
```
Chancre:
Syphilis infection (treponema pallidum).
Painless
Typically single
Bilateral LN enlargement
Exudes serum
Hard indurated base with sloping edges
Heals spontaneously
```
```
Chancroid:
Haemophilus ducreyi.
Painful
Multiple
Regional unilateral LN enlragement
Grey/yellow purulent exudate
Soft base with undermined edges
```
112
Mechanism of action of sofosbuvir
Sofosbuvir, a direct-acting antiviral agent against the hepatitis C virus, is a prodrug converted to its pharmacologically active form (GS-461203) via intracellular metabolism. It inhibits HCV NS5B RNA-dependent RNA polymerase, essential for viral replication, and acts as a chain terminator.
113
Mechanism of action of tigecycline
Tigecycline is broad-spectrum antibiotic that acts as a protein synthesis inhibitor. It exhibits bacteriostatic activity by binding to the 30S ribosomal subunit of bacteria and thereby blocking the interaction of aminoacyl-tRNA with the A site of the ribosome
114
Mechanism of action of streptogramin.
Derived from bacterium Streptomyces pristinaespiralis
Oral formulation is called pristinamycin, IV formulation is quinupristin/dalfopristin, which are derivatives of the pristinamycin.
Pristinamycin is a mixture of two components that have a synergistic antibacterial action. Pristinamycin IA is a macrolide, and results in pristinamycin's having a similar spectrum of action to erythromycin. Pristinamycin IIA (streptogramin A) is a depsipeptide.[1] PI and PII are coproduced by S. pristinaespiralis in a ratio of 30:70. Each compound binds to the bacterial 50 S ribosomal subunit and inhibits the elongation process of the protein synthesis, thereby exhibiting only a moderate bacteriostatic activity. However, the combination of both substances acts synergistically and leads to a potent bactericidal activity that can reach up to 100 times that of the separate components.
Used for staph and VRE infections.
115
Second line agent for PJP after cotrimoxazole
PO clindamycin and primaquine
116
CNS infections caused by HSV
HSV1 - encephalitis
| HSV2 - causes aseptic meningitis, females affected more than males
117
Clinical manifestations of strongyloides infection
Itchy rash, classical running larvae skin appearance
Diarrhoea, anorexia, N&V
Dyspnoea, wheeze, dry cough
Treatment is with ivermectin
118
Which drugs should be avoided in HIV patients with increased CVD risk?
Abacavir and PIs such as darunavir, lopinavir, ritonavir, as they are associated with increased risk of MI.
Use Tenofovir based combinations instead with NNRTIs.
Also PIs such as ritonavir and cobicistat interacts with statins therefore should be avoided.
119
Give 4 examples of antibiotic resistance via alteration of antibiotic target
1. Pneumococcus and penicillin via alteration of PBP
2. Staph aureus and methicillin like antibiotics
3. Fluoroquinolones and alteration of DNA gyrase target by gram negatives
4. Rifampicin and lateration of RNA polymerase
120
Give 2 examples of antibiotic resistance due to decreased uptake
Reduced penetration of antibiotics due to alteration in porins - eg pseudomonas and their resistance to trimethoprim and some fluoroquinolones
Antibiotic efflux - as seen in pneumococcus and macrolides, pseudomonas and multiple agents.
121
Mechanism of action of teicoplanin
It is a semisynthetic glycopeptide antibiotic with a spectrum of activity similar to vancomycin. Its mechanism of action is to inhibit bacterial cell wall synthesis.
Given that it is a bigger molecule, less effective than vancomycin.
122
3 antibiotic choice for ESBL
Carbapenems, colistin, amikacin.
Fosfomycin if simple UTI.
123
Antibiotic spectrum for the following:
```
Vancomycin
Carbapenem
Fluoroquinolones
-Older
-Newer
Ceftriaxones
Aminoglycosides
Macrolides
Cotrimoxazole
```
Vancomycin - G+
Carbapenem - G+, G- and anaerobes
Fluoroquinolones
-Older - most aerobic G- including pseudomonas
-Newer - most G+, G-, anaerobes, TBs and atypicals except pseudonoas
Ceftriaxone - G+/G- but weak anaerobic cover
Aminoglycosides - G-, some G+, no anaerobic over
Macrolides - Atypicals, G+ and G- coccis, non enteric G- bacilli, some mycobacteria, H pylori
Cotrimoxazole - aerobic G- bacilli, NORSA, nocardia, listeria, melioidosis.
124
Mechanism of actions for following fungal agents
1. Azoles
2. Polyenes (amphotericin B)
3. Echinocandin
4. Flucytosine
1. Azoles - prevents lanosterol to ergosterol synthesis
2. Polyenes - causes intracellular K efflux
3. Echinocandins - inhibits glucan synthase and disrupts cell wall synthesis
4. Flucytosine - deaminated to 5FU and inhibits thymidylate synthetase which is required in DNA synthesis.
125
Difference between conventional amphotericin B and lipid formulations of amphotericin B
Lipids in the lipid formulations works as a liposome by binding preferentially to the fungal cell wall and releasing amphotericin B to bind to ergosterols in the cell membranes.
They preferentially accumulate in the CSF and RES, therefore generally have lower serum level compared to CAB, however more effective for fungal meningitis and are less nephrotoxic.
126
2 Indications for amphotericin B
1. Treatment of zygomycosis and fusariosis
2. Cryptococcal meningitis
3. Empiric therapy
Can be used as a second line therapy for proven/probable IA/IC/candidaemia
127
3 Indications for fluconazole
For candida and Cryptococcus.
1. Prophylaxis in HSCT patients
2. Treatment of fluconazole sensitive candidaemia in non-neutropenic patients who are HD stable
3. Consolidation therapy for cryptococcal meningitis after IV amphotericin B (together with 5FC)
Not useful for aspergillus
128
3 Indications for voriconazole
1. First line therapy for invasive/CNS IA
2. Treatment of IC/candidaemia in setting of fluconazole resistance
3. Alternative agent for use as empiric therapy (less toxic than amphotericin B)
129
Fungal empiric therapy options
1. Lipid formulation amphotericin B
2. Voriconazole
3. Caspofungin (although narrower spectrum compared to above, as it is only sensitive to aspergillus and candida, not to Cryptococcus, Fusarium, zygomyces)
130
5 Indications for caspofungin
1. Salvage treatment of IA (after voriconazole)
2. Combination therapy for IA
3. Treatment of IC if neutropenic and C glabrata infection
4. Alternative treatment for oesophageal candidiasis in HIV infected patients (if fluconazole resistance and intolerant to CAB)
5. Empiric therapy
131
Treatment of invasive aspergillosis
1. Voriconazole
2. LAB
3. Caspofungin if refractory to above
132
Treatment of invasive candidiasis
1. Fluconazole if non-neutropenic and susceptible
2. Voriconazole if fluconazole resistance
3. Can also use caspofungin if neutropenic patient with C glabrata infection
133
Which cephalosporins have anaerobic cover?
Second generation - cefoxitin.
Cefuroxime does not have anaerobic cover.
134
What is the difference between cefotaxime/ceftriaxone and ceftazidime?
Compared to cefotaxime/ceftriaxone, Ceftazidime have pseudomonas coverage, however they lose their activity against gram positives.
135
When do you treat infectious gastroenteritis?
For salmonella, campylobacter, shigella, and Yersinia, reasonable to treat if severe symptoms, at risk occupation for transmission, or immunocompromised.
Doxycycline, norfloxacin, cotrimoxazoles are reasonable choice to treat above.
Giardia - treat if symptomatic to contain spread. Treat with ornidazole or metronidazole.
136
Antibiotic choice for CNS toxoplasmosis
Sulfadiazine and pyrimethamine with folic acid
| Second line is clindamycin and pyrimethamine.
137
When should you start ART in setting of TB/HIV infection?
Depends on the CD4 cell count.
If <50 - initiate ART at 2-4 weeks of TB treatment to minimize AIDS progression and death
If >50 - initiate TB treatment first, then wait 4-8 weeks of TB treatment (to avoid IRIS)
138
When should you start ART in setting of acute opportunistic infection?
commence ART 2-4 weeks later - to prevent overlap of toxicity.
139
Infection risks associated with prolonged steroids
PJP
TB
Legionella
140
Infection risks associated with T cell depletion
Mainly viral reactivation especially herpes virus
141
Highest risk groups for invasive fungal infections
1. Prolonged neutropenia
2. GVHD
3. High dose ara-C
4. Fludarabine
5. Prolonged steroid use
142
What is the association between TNF alpha blockade and invasive fungal infection?
Risk of fungal infection is especially high with infliximab, if concurrent use of another immunosuppressant such as corticosteroids.
Risks are lower with adalimumab and etanercept.
Most common IF - histoplasmosis, candidiasis, aspergillosis. Fatal in 1/3 of patients.
