Infectious Diseases Flashcards
Upon which co-receptor does Maraviroc act?
CCR5
What is the significance of the delta 32 frameshift mutation?
Stops HIV CCR5 integration (protective)
With regard to HIV, what defines an elite controller and what does this mean with respect to treatment?
Naturally maintains VL <50, do not require ART
Name 4 mechanisms of entry/cellular targets of HIV
- CD4+ T-cells (inc. rapid depletion of intestinal CD4+ after acute HIV infection)
- CCR5 co-receptor - effector sites (e.g. lamina propria of colonic mucosa)
- CXCR4 co-receptor
- Destruction of lymphoid tissue
Which HLA allele results in hypersensitivity to abacavir?
HLA-B*57:01
HLA alleles that are protective against HIV
HLA-B*57 HLA-B*27 HLA-B*58:01 HLA-B*51 HLA-B*13 HLA-B*81:01
HLA alleles that accelerate the progression of HIV
HLAB*58:02
HLA-B*35Px
What infections are seen in HIV with a CD4 count between 200-500? (Name 4)
Herpes zoster
Pneumococcal pneumonia
Oral candidiasis
Tuberculosis
What pathologies are seen in HIV with a CD4 count between 50-200? (Name 6)
PJP CNS toxoplasmosis Cryptococciosis Kaposi's sarcoma NHL Primary CNS lymphoma
What infections are seen in HIV patients with a CD4 count <50? (Name 3)
Disseminated MAC
CMV retinitis
Cryptosporidiosis
What is the primary prophylaxis for MAC in HIV, and when do you give it?
Azithromycin 1g when CD4 <50
Stop when CD4 >100 for 3 months and completed 12 months Tx for MAC and asymptomatic
What is the primary prophylaxis for PJP and CNS toxoplasmosis in HIV, and when do you give it?
Bactrim, CD4 <200 for 3 months
Stop when CD4 >200 for 3 months, induction completed and asymptomatic
With HIV and TB, when do you start ART if CD4 <50?
Initiate ART at 2-4 weeks of TB treatment to minimise AIDS progression and death
With HIV and TB, when do you start ART if CD4 >50?
Start ART after 4-8 weeks of TB treatment to minimise risk of IRIS
What are common side effects relating to nucleoside analogues (such as Zidovudine, Lamivudine, Emtricitabine and Abacavir)? Name 2
Rash and increased CV risk
What are common side effects relating to nucleotide reverse transcriptase inhibitors (such as tenofovir)? Name 2
Renal impairment and osteopenia
What are common side effects relating to non-nucleoside reverse transcriptase inhibitor nevirapine? Name 2
Rash and hepatitis
What is a common type of side effect relating to non-nucleoside reverse transcriptase inhibitor efavirenz? Name 1
Neuropsychiatric adverse effects
What are common side effects relating to protease inhibitors? (e.g. atazanavir, darunavir, lopinavir/ritonavir). Name 5
Bilirubin Renal impairment Hyperlipidaemia Diarrhoea Increased CV risk
Which PIs used in “baby” doses help to boost exposure to other PIs? Name 2
Ritonavir
Cobicistat
In terms of viral load, what defines incomplete virological response and virologic failure?
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)
In what patients groups would you expect to see a Mantoux induration of >5mm? Name 4
HIV-infected
Immunosuppressed
Close contacts of infectious TB
Old TB on CXR
In what patient groups would you expect to see a Mantoux induration of >10mm? Name 5
Patients with medical risk factors (CRF, CA etc) Foreign-born in endemic TB areas Healthcare workers Nursing home residents Prisoners
What treatment is provided for latent TB, and who should receive it? (Name 4 groups)
9m isoniazid = 4m rifampicin = 3m rifampicin/isoniazid (daily) = 90% efficacy
HIV infected
Other immunosuppressed groups
Children <5 years old
Recent contacts
What is the treatment for tuberculous meningitis?
HRZMox (moxiflox has better CSF penetration than ethambutol), 9-12 months total treatment
Dex reduces mortality (2 weeks with 6-8 weeks tapering)
What is the standard short course of tuberculosis treatment?
Initial - 2 months of HRZE
Continuation - 4 months of HR (daily, or 3-5x per week)
Isoniazid resistance is common in TB. What is the recommended treatment for isoniazid-resistant TB?
Rifampicin, pyrazinamide, ethambutol and moxifloxacin for 6 months
OR
Rifampicin, ethambutol +/- pyrazinamide for 9 months
What is the treatment for pyrazinamide-resistant TB?
Isoniazid and rifampicin for 9 months
What defines XDR-TB? Name 4 aspects
Resistance to: Rifampicin \+ Isoniazid \+ Quinolones \+ one of amikacin, kanamycin or capreomycin
What region is tested via genotypic testing for rifampicin resistance?
rpoB
Rifampicin resistance is highly predictive of MDR-TB
What is the gold standard for assessing MDR-TB?
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.
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
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
How does clavulanic acid work?
Inhibits beta-lactamase enzyme capable of hydrolysing penicillin
How does MRSA resistance work, and which gene is involved for coding?
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)
Which gene is associated with community-associated MRSA (and to a lesser extent, hospital-associated)?
PVL
What is the definition of multi-resistant MRSA?
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
What is the treatment for severe MRSA?
SOURCE CONTROL, source control, source control
Glycopeptides e.g. vancomycin, teicoplanin IV
Higher vanc MICs has increased treatment failure
Which antibiotic is inactivated by pulmonary surfactant and therefore ineffective for respiratory tract infections?
Daptomycin
Which antibiotic undergoes biliary clearance therefore has limited utility in UTIs?
Tigecycline
How does vancomycin resistance work?
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
What are the main gene clusters that give rise to vancomycin resistance, and what is the significance of each?
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
What are treatment options available to VRE? Name 5 categories.
Penicillin/amoxicillin/ampicillin - may be isolated against vancomycin resistance
Teicoplanin for VanB/VanC
Linezolid
Tigecycline
Other - nitrofurantoin, fosfomycin
Which mutation is associated with high level penicillin resistance?
PBP 2x
How does macrolide resistance occur with S pneumonia?
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
Name 4 mechanisms of beta lactam resistance.
Altered porin - keep it out
Beta lactamases - destroy the ring
Prevention of binding - altered PBPs
Efflux pumps - pump it out
In which bacteria are AmpC beta-lactamase genes found?
“ESCHAPPPM” (first three are most important)
Enterobacter
Serratia marcescens
Citrobacter freundii
Hafnium alvei
Acinetobacter and aeromonas
Proteus vulgaris
Providencia
Pseudomonas
Morganella morganii
What antibiotics should be used for AmpC beta lactam resistant organisms? Name 2.
Carbapenems - empiric antibiotics of choice
Cefepime
Pip/taz - may work but unreliable
What are ESBLs?
Extended-spectrum beta lactamases
ESBLs are a group of enzymes that hydrolyse all penicillins, cephalosporins (including cefepime) and aztreonem
What are risk factors for acquiring ESBL infections?
Prior hospitalisation
Antibiotic therapy (particularly cephalosporins)
Community-acquired ESBL (increasingly common)
Travel to India/Asia
Which 2 organisms are most likely to harbour ESBLs?
E Coli
Klebsiella
How do you treat ESBL infections?
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
Name 5 carbapenem-resistant enterobacteriae harbouring carbapenemase-enzymes.
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
How are CRE infections treated? Name 4 options.
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
What is avibactam and how does it work?
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
Which enzymes/organisms does avibactam have activity against?
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)
Name 5 indications for empirical vancomycin use in the neutropenic patient.
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
Describe the method of action of echocandins and name 3 examples.
Echocandins (fungins) inhibit the enzymes that synthesis beta-glucans (the penicillin of antifungals)
Caspofungin
Anidulafungin
Micafungin
Describe the method of action of polyenes and name an example.
Bind ergosterol, weaken the membrane, cause pore formation, leakage of K+ and Na+ resulting in fungal cell death (and mammalian toxicity)
Amphotericin
Describe the method of action of a azole, and name 3 examples.
Inhibits the enzyme that synthesises ergosterol
Fluconazole
Posaconazole
Which patients have a high risk (>10%) of having an invasive fungal infection? Name 3 groups.
AML (especially induction)
Allogenic HSCT
Severe GVHD
Which fungi does the (1-3) B D glucan test detect? Name 3.
Candida
Aspergillus
Fusarium
60-90% sensitive. Does not pick up crypto/zygomycetes
Name 2 fungi that a galactomannan assay picks up.
Aspergillus
Penicillium
How is invasive aspergillosis managed?
Voriconazole
Liposomal amphotericin
Caspofungin third line
Which agent is used as prophylaxis for high risk moulds?
Posaconazole
When is only 1 week of therapy indicated in a patient with neutropenic fevers? Name 4 considerations.
Afebrile by day 3
Neutrophils >(0.5)
Cultures negative
Low risk patient, uncomplicated course
When is more than 1 week of antibiotic therapy indicated if a patient has neutropenic fevers? Name 1 consideration.
If temperatures take more than 3 days to settle
Continue for 4-5 days after neutrophil recovery (>0.5)
When is a minimum of 2 weeks antibiotic therapy indicated in patients with neutropenic fevers? Name 2considerations
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
How would a nocardia rash appear under biopsy with an immunocompromised patient? And how would it be treated?
Red, string-like appearance = pathognomonic
Nocardia can cause pneumonia - branching acid-fast bacilli
Treat with Bactrim
Name 10 criteria that help to classify malaria as severe.
Loss of consciousness
Jaundice
Oliguria
Respiratory distress
Severe anaemia
Hypoglycaemia
Parasite count >2%
Vomiting
Metabolic acidosis
Acute kidney injury
How is non-severe malaria treated?
Oral therapy
Malarone (atovaquone/proguanil)
Or artemisinin
Do not give Malarone if it was used as prophylaxis; consider Riamet (artemether + lumefantrine)
How is severe malaria treated?
IV artensunate - then change to oral as per non-severe malaria
What medication should be given at the end of initial malaria therapy, for what reason, and what precaution needs to be taken?
Primaquine to eradicate liver hypnozoites (particularly in vivax or ovale infection)
Need to test G6PD status first
What are the classic symptoms of measles, and what is the incubation time? Name 5 symptoms.
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)
When returning from a Zika endemic area, for how long should pregnancy be avoided?
Female - 8 weeks
Male - 3-6 months (3 months as per CDC 2018)
Which infections require airborne precaution negative pressure rooms? Name 3 conditions.
Tuberculosis
Measles
Varicella
