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GCUH FRACP Writtens 2020 > Infectious Diseases > Flashcards

Infectious Diseases Flashcards

1
Q

Upon which co-receptor does Maraviroc act?

A

CCR5

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2
Q

What is the significance of the delta 32 frameshift mutation?

A

Stops HIV CCR5 integration (protective)

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3
Q

With regard to HIV, what defines an elite controller and what does this mean with respect to treatment?

A

Naturally maintains VL <50, do not require ART

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4
Q

Name 4 mechanisms of entry/cellular targets of HIV

A
  1. CD4+ T-cells (inc. rapid depletion of intestinal CD4+ after acute HIV infection)
  2. CCR5 co-receptor - effector sites (e.g. lamina propria of colonic mucosa)
  3. CXCR4 co-receptor
  4. Destruction of lymphoid tissue
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5
Q

Which HLA allele results in hypersensitivity to abacavir?

A

HLA-B*57:01

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6
Q

HLA alleles that are protective against HIV

A 
HLA-B*57
HLA-B*27
HLA-B*58:01
HLA-B*51
HLA-B*13
HLA-B*81:01
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7
Q

HLA alleles that accelerate the progression of HIV

A

HLAB*58:02

HLA-B*35Px

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8
Q

What infections are seen in HIV with a CD4 count between 200-500? (Name 4)

A

Herpes zoster
Pneumococcal pneumonia
Oral candidiasis
Tuberculosis

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9
Q

What pathologies are seen in HIV with a CD4 count between 50-200? (Name 6)

A 
PJP
CNS toxoplasmosis
Cryptococciosis
Kaposi's sarcoma
NHL
Primary CNS lymphoma
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10
Q

What infections are seen in HIV patients with a CD4 count <50? (Name 3)

A

Disseminated MAC
CMV retinitis
Cryptosporidiosis

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11
Q

What is the primary prophylaxis for MAC in HIV, and when do you give it?

A

Azithromycin 1g when CD4 <50

Stop when CD4 >100 for 3 months and completed 12 months Tx for MAC and asymptomatic

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12
Q

What is the primary prophylaxis for PJP and CNS toxoplasmosis in HIV, and when do you give it?

A

Bactrim, CD4 <200 for 3 months

Stop when CD4 >200 for 3 months, induction completed and asymptomatic

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13
Q

With HIV and TB, when do you start ART if CD4 <50?

A

Initiate ART at 2-4 weeks of TB treatment to minimise AIDS progression and death

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14
Q

With HIV and TB, when do you start ART if CD4 >50?

A

Start ART after 4-8 weeks of TB treatment to minimise risk of IRIS

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15
Q

What are common side effects relating to nucleoside analogues (such as Zidovudine, Lamivudine, Emtricitabine and Abacavir)? Name 2

A

Rash and increased CV risk

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16
Q

What are common side effects relating to nucleotide reverse transcriptase inhibitors (such as tenofovir)? Name 2

A

Renal impairment and osteopenia

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17
Q

What are common side effects relating to non-nucleoside reverse transcriptase inhibitor nevirapine? Name 2

A

Rash and hepatitis

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18
Q

What is a common type of side effect relating to non-nucleoside reverse transcriptase inhibitor efavirenz? Name 1

A

Neuropsychiatric adverse effects

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19
Q

What are common side effects relating to protease inhibitors? (e.g. atazanavir, darunavir, lopinavir/ritonavir). Name 5

A 
Bilirubin
Renal impairment
Hyperlipidaemia
Diarrhoea
Increased CV risk
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20
Q

Which PIs used in “baby” doses help to boost exposure to other PIs? Name 2

A

Ritonavir

Cobicistat

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21
Q

In terms of viral load, what defines incomplete virological response and virologic failure?

A

Incomplete virological response - inability to achieve virological suppression after 24 weeks therapy (VL >200 on 2 consecutive plasma samples)

Virologic failure - inability to maintain suppression of viral replication (to an HIV RNA level <200)

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22
Q

In what patients groups would you expect to see a Mantoux induration of >5mm? Name 4

A

HIV-infected
Immunosuppressed
Close contacts of infectious TB
Old TB on CXR

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23
Q

In what patient groups would you expect to see a Mantoux induration of >10mm? Name 5

A 
Patients with medical risk factors (CRF, CA etc)
Foreign-born in endemic TB areas
Healthcare workers
Nursing home residents
Prisoners
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24
Q

What treatment is provided for latent TB, and who should receive it? (Name 4 groups)

A

9m isoniazid = 4m rifampicin = 3m rifampicin/isoniazid (daily) = 90% efficacy

HIV infected
Other immunosuppressed groups
Children <5 years old
Recent contacts

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25
Q

What is the treatment for tuberculous meningitis?

A

HRZMox (moxiflox has better CSF penetration than ethambutol), 9-12 months total treatment

Dex reduces mortality (2 weeks with 6-8 weeks tapering)

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26
Q

What is the standard short course of tuberculosis treatment?

A

Initial - 2 months of HRZE

Continuation - 4 months of HR (daily, or 3-5x per week)

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27
Q

Isoniazid resistance is common in TB. What is the recommended treatment for isoniazid-resistant TB?

A

Rifampicin, pyrazinamide, ethambutol and moxifloxacin for 6 months

OR

Rifampicin, ethambutol +/- pyrazinamide for 9 months

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28
Q

What is the treatment for pyrazinamide-resistant TB?

A

Isoniazid and rifampicin for 9 months

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29
Q

What defines XDR-TB? Name 4 aspects

A 
Resistance to:
Rifampicin
\+ Isoniazid
\+ Quinolones
\+ one of amikacin, kanamycin or capreomycin
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30
Q

What region is tested via genotypic testing for rifampicin resistance?

A

rpoB

Rifampicin resistance is highly predictive of MDR-TB

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31
Q

What is the gold standard for assessing MDR-TB?

A

Liquid media based drug sensitivity testing (DST)

However, this is slow (approx 2 months) and provides an opportunity to transmission prior to the recognition of drug resistance.

32
Q

Modified Duke’s criteria for IE involves 2 major criteria, 1 major and 3 minor criteria or 5 minor criteria. What are the major criteria? Name 5

A

Major:

Typical microorganisms consistent with IE from 2 separate BCs

Persistently positive BCs

Single positive BC for Q-fever or IgG titre >1:800

Echo positive for IE

New valvular regurg

33
Q

How does clavulanic acid work?

A

Inhibits beta-lactamase enzyme capable of hydrolysing penicillin

34
Q

How does MRSA resistance work, and which gene is involved for coding?

A

mecA gene encodes for PBP2a, which is a modified penicillin-binding protein (altered target site of beta-lactam)

Confers resistance to all penicillins, cephalosporins and carbapenems, and cannot be overcome by beta-lactamase inhibitor as non-enzymatic (e.g. augmentin)

35
Q

Which gene is associated with community-associated MRSA (and to a lesser extent, hospital-associated)?

A

PVL

36
Q

What is the definition of multi-resistant MRSA?

A

Resistance to beta-lactams plus…

Either two of more of the non-beta-lactate antibiotics (e.g. erythro/clinda/co-trim/genta/rif/fusidic/mupirocin/tetracycline/chloramphenicol)

Or ciprofloxacin

37
Q

What is the treatment for severe MRSA?

A

SOURCE CONTROL, source control, source control

Glycopeptides e.g. vancomycin, teicoplanin IV

Higher vanc MICs has increased treatment failure

38
Q

Which antibiotic is inactivated by pulmonary surfactant and therefore ineffective for respiratory tract infections?

A

Daptomycin

39
Q

Which antibiotic undergoes biliary clearance therefore has limited utility in UTIs?

A

Tigecycline

40
Q

How does vancomycin resistance work?

A

Vancomycin binds to D-Ala D-Ala terminus of peptapentide side-chain, preventing cross linking

This terminus is changed to D-Ala D-Lac, preventing vancomycin from bonding

41
Q

What are the main gene clusters that give rise to vancomycin resistance, and what is the significance of each?

A

VanA gene cluster - vancomycin (high MIC) and teicoplanin resistance; transferable from plasmids and chromosome (transposon)

VanB gene cluster - vanc resistant (low MIC) but teicoplanin sensitive; transferable from transposon

VanC gene cluster - low level vanc resistance but teicoplanin sensitive (D-Ala D-Ser); not transferable

42
Q

What are treatment options available to VRE? Name 5 categories.

A

Penicillin/amoxicillin/ampicillin - may be isolated against vancomycin resistance

Teicoplanin for VanB/VanC

Linezolid

Tigecycline

Other - nitrofurantoin, fosfomycin

43
Q

Which mutation is associated with high level penicillin resistance?

A

PBP 2x

44
Q

How does macrolide resistance occur with S pneumonia?

A

Occurs via either mefA gene (efflux pump, low level resistance)

Or

ermB gene (alteration of binding site, high level resistance)

Macrolide resistance, unlike penicillin resistance, cannot be overcome by high doses

45
Q

Name 4 mechanisms of beta lactam resistance.

A

Altered porin - keep it out

Beta lactamases - destroy the ring

Prevention of binding - altered PBPs

Efflux pumps - pump it out

46
Q

In which bacteria are AmpC beta-lactamase genes found?

A

“ESCHAPPPM” (first three are most important)

Enterobacter

Serratia marcescens

Citrobacter freundii

Hafnium alvei

Acinetobacter and aeromonas

Proteus vulgaris

Providencia

Pseudomonas

Morganella morganii

47
Q

What antibiotics should be used for AmpC beta lactam resistant organisms? Name 2.

A

Carbapenems - empiric antibiotics of choice

Cefepime

Pip/taz - may work but unreliable

48
Q

What are ESBLs?

A

Extended-spectrum beta lactamases

ESBLs are a group of enzymes that hydrolyse all penicillins, cephalosporins (including cefepime) and aztreonem

49
Q

What are risk factors for acquiring ESBL infections?

A

Prior hospitalisation

Antibiotic therapy (particularly cephalosporins)

Community-acquired ESBL (increasingly common)

Travel to India/Asia

50
Q

Which 2 organisms are most likely to harbour ESBLs?

A

E Coli

Klebsiella

51
Q

How do you treat ESBL infections?

A

Carbapenems (impenem, meropenem, ertapenem)

ESBL enzymes do not hydrolyse the cephamycin antibiotics (cefoxitin and cefotetan), but these drugs are not recommended as first-line due to frequent co-occurrence of additional resistance mechanisms

ESBLs can additionally be inhibited by beta-lactamase inhibitors such as clavulanate, sulbactam and tazobactam

52
Q

Name 5 carbapenem-resistant enterobacteriae harbouring carbapenemase-enzymes.

A

Klebsiella pneumoniae carbapenemase (KPC) - USA

New Delhi metallo-beta-lactamase proteinase (NDM)

Oxacillin-type beta-lactamase-48 (OXA-48) - Mediterranean

Verona-integron-encoded metallo-beta-lactamase (VIM)

Imipenem hydrolysing metallo-beta-lactamase (IMP) - QLD

Top 3 are the important ones

53
Q

How are CRE infections treated? Name 4 options.

A

Combination of 2 or 3 of the following:

Colistin (Polymixin E) or Polymixin B

High-dose tigecycline - but not very useful for bacteraemia

Aminoglycosides e.g. gentamicin, tobramycin, amikacin

Carbapenems - high dose to achieve MIC; consider double-dose so that one carbapenem saturates enzyme, allowing other carbapenem to treat

54
Q

What is avibactam and how does it work?

A

Second generation beta-lactamase inhibitor

Most beta-lactamase inhibitors act as “suicide molecules”, get hydrolysed and allow other antibiotics to take action

Avibactam binds to the beta-lactamase enzyme and inactivates it, but through a process of reverse cyclisation, it is released/regenerated to continue to inhibit other molecules

55
Q

Which enzymes/organisms does avibactam have activity against?

A

Can inhibit class A enzymes (ESBL, KPCs), class C (AmpC producers) and class D (OXA-48)

No activity against the metallo-beta-lactamases (NDM, VIM, IMP)

56
Q

Name 5 indications for empirical vancomycin use in the neutropenic patient.

A

Clinically suspected serious catheter-related infections

Known colonisation with penicillin and cephalosporin-resistant pneumococci or MRSA

Positive results of blood culture for Gram +ve and institution high rates of MRSA

Hypotension or other evidence of cardiovascular impairment

H/O ciprofloxacin or trimethoprim-sulfamethoxazole

57
Q

Describe the method of action of echocandins and name 3 examples.

A

Echocandins (fungins) inhibit the enzymes that synthesis beta-glucans (the penicillin of antifungals)

Caspofungin

Anidulafungin

Micafungin

58
Q

Describe the method of action of polyenes and name an example.

A

Bind ergosterol, weaken the membrane, cause pore formation, leakage of K+ and Na+ resulting in fungal cell death (and mammalian toxicity)

Amphotericin

59
Q

Describe the method of action of a azole, and name 3 examples.

A

Inhibits the enzyme that synthesises ergosterol

Fluconazole

Posaconazole

60
Q

Which patients have a high risk (>10%) of having an invasive fungal infection? Name 3 groups.

A

AML (especially induction)

Allogenic HSCT

Severe GVHD

61
Q

Which fungi does the (1-3) B D glucan test detect? Name 3.

A

Candida

Aspergillus

Fusarium

60-90% sensitive. Does not pick up crypto/zygomycetes

62
Q

Name 2 fungi that a galactomannan assay picks up.

A

Aspergillus

Penicillium

63
Q

How is invasive aspergillosis managed?

A

Voriconazole

Liposomal amphotericin

Caspofungin third line

64
Q

Which agent is used as prophylaxis for high risk moulds?

A

Posaconazole

65
Q

When is only 1 week of therapy indicated in a patient with neutropenic fevers? Name 4 considerations.

A

Afebrile by day 3

Neutrophils >(0.5)

Cultures negative

Low risk patient, uncomplicated course

66
Q

When is more than 1 week of antibiotic therapy indicated if a patient has neutropenic fevers? Name 1 consideration.

A

If temperatures take more than 3 days to settle

Continue for 4-5 days after neutrophil recovery (>0.5)

67
Q

When is a minimum of 2 weeks antibiotic therapy indicated in patients with neutropenic fevers? Name 2considerations

A

Bacteraemia

Deep tissue infection

After 2 weeks, if remains neutropenic, but afebrile, no disease focus, mucous membranes, skin intact, no catheter site infection, no invasive procedures or ablative therapy planned - cease Abx and observe

68
Q

How would a nocardia rash appear under biopsy with an immunocompromised patient? And how would it be treated?

A

Red, string-like appearance = pathognomonic

Nocardia can cause pneumonia - branching acid-fast bacilli

Treat with Bactrim

69
Q

Name 10 criteria that help to classify malaria as severe.

A

Loss of consciousness

Jaundice

Oliguria

Respiratory distress

Severe anaemia

Hypoglycaemia

Parasite count >2%

Vomiting

Metabolic acidosis

Acute kidney injury

70
Q

How is non-severe malaria treated?

A

Oral therapy

Malarone (atovaquone/proguanil)

Or artemisinin

Do not give Malarone if it was used as prophylaxis; consider Riamet (artemether + lumefantrine)

71
Q

How is severe malaria treated?

A

IV artensunate - then change to oral as per non-severe malaria

72
Q

What medication should be given at the end of initial malaria therapy, for what reason, and what precaution needs to be taken?

A

Primaquine to eradicate liver hypnozoites (particularly in vivax or ovale infection)

Need to test G6PD status first

73
Q

What are the classic symptoms of measles, and what is the incubation time? Name 5 symptoms.

A

Non-productive cough

Coryza

Conjunctival suffusion

Temperature of 40 degrees

Few days later - macular rash starting on face and spreading to the rest of the body

Incubation typically 10 to 14 days (max 21)

74
Q

When returning from a Zika endemic area, for how long should pregnancy be avoided?

A

Female - 8 weeks

Male - 3-6 months (3 months as per CDC 2018)

75
Q

Which infections require airborne precaution negative pressure rooms? Name 3 conditions.

A

Tuberculosis

Measles

Varicella

GCUH FRACP Writtens 2020 (14 decks)

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