Infectious Diseases Flashcards
What is the MOA of sulfonamides?
SulFOnamides eg Sulfamethoxazole inhibit FOlic acid synthesis
What is the MOA of macrolide antibiotics?
Macrolides (eg Erythromycin, Azithromycin, Clarithromycin, Roxithromycin) block protein synthesis by binding to the 50S ribosomal subunit
What is the MOA of Aminoglycosides?
Aminoglycosides (Gentamycin, Streptomycin) block protein synthesis by binding the 30S ribosomal subunit
(A”MINI”-glycoside = block the mini/smaller subunit)
What is the MOA of Quinolones / Fluoroquinolones?
(“People who wear FLUORO like to GYRATE in discoes”)
Inhibition of DNA gyrase / DNA topoisomerases
Fluoroquinolones - Cipro, Norflox, Moxifloxacin
How does Cutaneous Anthrax present?
Anthrax is caused by a gram positive rod, Bacillus anthracis.
It results in:
Black eschar
NO PUS
Painless with widespread oedema
Usually contracted by direct contact of bacteria into an open wound, usually by touching an infected animal.
Mortality is low with antibiotics, which contrasts with pulmonary anthrax.
In a E.Coli O157:H7 outbreak of diarrhoea, what measures would be most effective in reducing the transmission of this organism?
E.Coli O157:H7 is most commonly found in contaminated meat (Cattle are a major source).
Ensuring that meat products are thoroughly cooked will reduce transmission in an outbreak.
Raw meat should be separated from ready-to-eat food.
Hand wash AFTER handling raw meat.
Antibiotics are not routinely indicated.
How do you differentiate between tuberculous, viral and bacterial meningitis on CSF?
BACTERIAL:
glucose - low; LESS THAN HALF of plasma glucose
Protein - high >1.0g/L
White cells - 10-5000 polymorphs/mm3
VIRAL:
glucose - normal, or only mildly low (Always more than half of serum BSL)
Protein - high or normal
white cells - 15-1000 lymphocytes/mm3
TUBERCULOUS (similar to bacterial meningitis except a predominance of lymphocytes)
Glucose - low; LESS THAN HALF of plasma glucose
Protein - HIGH >1.0
White cells - 10-1000 lymphocytes/mm3
Hypervirulent strain C.Diff.
What is the mechanism of this strain of C.Diff?
Hypervirulent C.Diff aka “NAP-1/027 strain”
= an increased production of TOXINS A AND B (20x normal)
due to a mutation in a binary toxin (MUTATED TCDC GENE), whose normal action is to downregulate these toxins.
(TCDC = “The C. Diff Crazy” gene)
(C.Diff is a gram positive rod that forms spores)
Usually results from exposure to FLUOROQUINOLONES (15x rel risk) but also exposure to other Abx such as Cephalos, Macrolides)
The stool culture/C.Diff assay does not discriminate between the normal and Hypervirulent strain.
What are the clinical signs of severity in an episode of Hypervirulent C.Diff?
NO further diarrhoea (due to Ileus) Shock High WCC Low Albumin renal impairment Megacolon / Perforation / Ileus
What are the salvage regimens for C.Diff treatment (ie after trying Metronidazole and Vancomycin, and pulsed Vancomycin over a few weeks)
RIFAXIMIN and po Vancomycin
- FIDAXOMICIN **
- efficacy is as good as Vanc!
- relapse rate is better than Vanc!
- very expensive
- works as a “macrocyclic antibiotic”, minimally absorbed
FAECAL TRANSPLANT
What are the common drug combinations used for treatment of HIV?
What are the side effects of these drugs?
Always Triple Therapy, including TWO Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
- “TEE” - Tenofovir (NRTI) + Ermtracitabine (NRTI) + Efavirenz (NNRTI)
- “TER” - Tenofovir (NRTI) + Ermtracitabine (NRTI) + Ripilvirine (NNRTI)
- “TEA” - Tenofovir (NRTI) + Ermtracitabine (NRTI) + Atazanivir (PI) but also add Ritonavir (PI) to boost the effect of Atazanivir by saturating Cyp3a4
Side effects of:
TENOFOVIR - renal impairment
ERMTRACITABINE - minimal s/e!!
Efavirenz (NNRTI) - Psych/mood disorders / CNS disturbance
Protease Inhibitors (“-navir” drugs) - ** Increases CV risk **
Nevirapine - SJS!! Liver toxicity, Rash (“NEVER use NEViparine”)
A patient with newly-diagnosed HIV is found to have active TB. What is the next step in management?
DELAY antiretroviral therapy. Treat TB first.
Do not start antiretroviral therapy until 4-8 weeks after TB treatment to minimise Immune Reconstitution/IRIS.
What is the diagnosis & treatment for Cryptococcal Meningitis in HIV?
Symptoms- headache, fever, altered mental state.
Usually occurs when CD4 count is below 50.
DIAGNOSIS with CSF: Cryptococcal Ag positive, India Ink staining.
MANAGEMENT:
- AMPHOTERICIN-B and FLUCYTOSINE for 2/52
- followed by Fluconazole 8/52
- then maintenance Fluconazole for 1 year until CD4 count is above 100 and sustained for at least 3 months
WATCH FOR IRIS –> may need Steroids.
CD4 Countdown. What are the common AIDS-defining illnesses associated with these CD4 counts: 1. > 200 2. 100-200 3. 50-100 4. <50
CD4 counts:
- > 200
- Oesophageal Candidiasis
- TB (affects everyone- General population & HIV pts with high CD4 counts)
- Kaposi’s Sarcoma - 100-200
- Pneumocystic Jiroveci (fungal. Rx Bactrim) - 50-100
- Respiratory Candidiasis
- Toxoplasmosis Encephalitis (Rx ANTIFOLATE agents - Pyrimethamine-Sulfadiazine)
- MAC, atypical mycobacterias (Rx Rifamp, Ethambutol, Clarithromycin) - <50
- CMV Retinitis / Enteritis / Pneumonitis (Rx Valganciclovir)
- Cryptococcus Neoformans (fungal) meningitis
- LYMPHOMAS
- Progressive Multifocal Leukoencephalopathy
Features of Kaposi’s Sarcoma
Skin- purple nodules / Macules
Lymphoedema
Associated with Herpes Virus
What is Miraviroc?
CCR5 Receptor antagonist (Viral ENTRY Inhibitor)
Blocks signal 2 on CD4 T cells.
Which antiretroviral drugs have good CNS penetration?
NRTIs - Abacavir (but increases CV risk!)
Zidovudine (S/E anaemia, neutropaenia, neuropathy)
NNRTIs - Nevirapine (S/E liver toxicity, rash, SJS)
PIs - Fosamprenavir-Ritonavir OR Idinavir-Ritonavir
What happens to the GI lymphocytes in the first 2 weeks of HIV infection?
Early depletion of ALL LYMPHOCYTES / CD4 CELLS in the gut for the first 2 weeks of HIV infection
- -> Leadpiped bowel for 2/52
- -> Peyers patches and all lymphocytes lost
Patient has HIV and neurocognitive issues.
What are the factors that increase risk of HIV-Associated Neurocognitive disorders?
What is the management?
Increased risk in:
- Low CD4 count nadir
- Hep C Co-infection (associated with neuroinflammation)
Symptoms range from mild to dementia.
Only 2% severe.
TREATMENT:
ABACAVIR (as long as no CV risk factors)
Or any of the antiretroviral drugs that cross the BBB that can lower the viral load in patient’s CSF (see other flash card)
Define MDR TB and XDR TB.
MDR TB = resistance to Rifampicin and Isoniazid
XDR TB = resistance to Rifampicin, Isoniazid, FLUOROQUINOLONES AND AN INJECTABLE AGENT (Kanamycin / Amikacin (aminoglycoside) / Capreomycin)
What is the standard short-course therapy for Tuberculosis?
2 months of RIPE, followed by 4 months of Rifampicin and Isoniazid.
Either a daily regimen or an intermittent regimen (3xweekly with DOT) can be used.
What is the management for MDR TB?
Detect drug-resistance with “Rapid GeneXPert” tests for Rifampicin resistance.
Second-line drugs are necessary and the treatment duration is usually extended to 18-24 months.
DOT is recommended in all patients with drug-resistant TB to prevent further drug resistance.
Use RIPE \+ MOXIFLOXACIN for 18 MONTHS \+ INJECTABLE - AMIKACIN, KANAMYCIN (aminoglycosides)
What is the management of TB in Pregnant women?
Pregnant women should be started on the STANDARD short-course therapy (RIPE)
When born–> Infants should be treated with Isoniazid.
Breastfeeding can continue.
What is the management of TB in HIV patients?
Use STANDARD RIPE therapy (with DOT)
Plus Pyridoxine supplementation to decrease risk of peripheral neuropathy from Isoniazid.
** RIFAMPICIN IS ESSENTIAL (regimens without Rifampicin are less effective) but Rifampicin (Cyp inducer) interferes with antiretroviral agents!!! **
AVOID Saquinovir/RItonavir (PI) (contraindicated)
NEVer use NEVirapine (NNRTI) especially due to bad side effects - hepatotoxic, SJS.
Can continue to use TEE and TEA regimens.
TEN-ERM-Efavirenz (TEE) is best combination.
NEED TO DELAY ARV TREATMENT by 2 weeks if CD4 50 delay ARV by 4 weeks.
Watch for IRIS / paradoxical inflammatory response to TB treatment.
