Infectious Diseases Flashcards
Mechanism of C diff colitis
C difficile produces an exotoxin that induces necrosis of the superficial mucosa.
Management of CDI Colitis
Mild-mod - Metronidazole
Severe or recurrent - PO Vancomycin
Multiple recurrences - faecal transplant
Polyenes (amphotericin B)
MOA: Bind to membrane egosterol causing pore formation, potassium efflux and cell death.
A/E: Renal toxicity, infusion reactions, hypoK, hypoMag, hepatotoxicity.
Few drug interactions.
Pyrimidine Analogues (5-fluorocytosine)
MOA: Binds to cytosine permease, imported into cell, converted to fluorouracil by cytosine deaminase, inhibits nucleic acid synthesis
Indication:
Pathogenic YEASTS (cryptococcus)
A/E:
Bone marrow suppression, hepatotoxicity.
Azole Antifungals
Imidazoles: Clotrimizole, ketoconazole, miconazole.
Triazoles: fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole
MOA: Inhibit the enzyme C13-Alpha-Sterol demethylase, which causes build up of sterol precursors and inhibits ergosterol synthesis (integral for cell wall?)
Indications: Varies for each azole.
- Candidiasis - fluconazole, itraconazole, voriconazole, posaconazole
- Cryptococcosis - fluconazole, itraconazole
- Invasive Aspergillosis (voriconazole, isavuconazole)
- Mucormycosis - isavuconazole
A/E:
- Hepatoxocity, QT prolongation, CYP450 inhibition
Voriconazole causes photosensitivity, reversible photpsia, and bone marrow toxicity
Echinocandins (caspofungin, micafungin, anidulafungi
MOA: Inhibit fungal cell wall polysaccharide B-1,3 glucan synthesis –> fungicidal. For aspergillus spp inhibits this at the hyphae tip which is fungistatic.
Indications:
- Invasive fungal infections (especially candida)
Well tolerated, minimal drug interactions.
Chlamydia trachomatis
Screen women <25year annually, and older women with risk factors.
Treat:
- Doxycycline 100mg BD for 7 days
OR
- Azithromycin 1g PO STAT (preferred in pregnancy)
Treat for LONGER if ANORECTAL INFECTION
Retest in 3 months after treatment.
Contact trace for 6 months
COVID-19
RNA virus
PCR Nasal swab has 70% sensitivity
Dengue Virus
Most common arthopod borne human disease, most common cause of febrile illness in travellers from Asia and South America.
Genus: Flavivirus
4 different serotypes.
Transmission: Aedes mosquito
Incubation: 3-14 days (usually 4-7). If fever starts >14 days after travel Dengue is very unlikely.
Symptoms: Fever, headache, back and extremity pain (breakbone fever)
Usually self-limiting disease.
If infected for a second time by a different serotype, at risk of “dengue hemorrhagic fever” with an untreated mortality rate of 50%
Dengue Hemorrhagic Fever
50% untreated mortality, 5% with supportive management.
Severe inflammatory response leads to leaky capillaries and extravasation of fluid.
Diagnosis:
Management:
- Fluid management to maintain organ perfusion
- Management of coagulopathy if significant bleeding - NO role for prophylactic transfusion.
- NO role for high dose steroids.
Phases of Dengue Infection:
Febrile phase
- lasts for 3-7 days with high fevers, headache, pain.
- Bloods often show thrombocytopenia, leukopenia, LFT derangement.
Critical Phase (more likely to occur with SECONDARY INFECTION, with a different serotype)
- around the time of defervescence (days 4-7), a small number of people develop a systemic vascular leak phase.
- increasing haematocrit, hypoproteinaemia, 3rd spacing of fluid (ascites pleural effusions).
- haemorrhage may occur in this phase, labs may show thrombocytopenia, prolonged PT and APTT, low fibrinogen. But it is not DIC.
Recovery Phase:
- Critical phase usually resolves over 48-72 hours.
Dengue Diagnosis:
PCR
ELISA for NS1 antigen
High titre IgM
Management of Human bite wounds:
- Do not close, allow to heal by secondary intention.
- X-ray to assess for fracture, foreign body or air in joint.
- Do not need to swab, is usually polymicrobial with aerobic and anaerobic bacteria
- Give prophylactic antibiotics with Amox/Clav
Flu Vaccine
- becomes effective 10-14 days after administration.
- 50% effectiveness against Flu A, 70% with flu B
- High dose trivalent vaccine recommended for >65 years.
Influenza in pregnancy:
- Can be vaccinated in any trimester
- Recommend treatment with neurominidase inhibitors with infected
Listeria Monocytogenes
Small, gram positive, facultative intracellular bacteria.
Ubiquitous in nature, and therefore acquired from contaminated food products (unpasteurised dairy, meats, vegetables)
Vertical transmission across the placenta or during delivery can occur.
Clinical disease:
- menigoencphalitis
- sepsis
- gastroenteritis
Patients affected are older, immunocompromised, diabetics, pregnant or new borns.
Infection in pregnancy can lead to premature birth or foetal death.
Intrinsically resistant to cephalosporins
Treatment is with penicillin.
Species of Plasmodium causing Malaria in humans
Plasmodium falciparum - risk of severe disease
Plasmodium vivax - usually milder disease, can cause recurrent disease.
Plasmodium malariae
Plasmodium ovale
Plasmodium wallikeri
Plasmodium knowlesi - can cause severe disease.
Malaria epidemiology
Transmission: Anopheles mosquito
Most common species:
- Africa (Falciparum)
- Asia/Oceana (Falciparum and Vivax)
- Americas (Vivax > Falciparum)
Malaria lifecycle
- Sporozoites are inoculated by the bite of a ANOPHELES mosquito
- Pre-erythrocytic phase is the liver which lasts for 1-2 weeks
- Erythrocytic phase with serial cycles of asexual reproduction causes increasing levels of paracitaemia.
- A subset of intra-erythrocytic paracites switch to sexual reproduction which produce male and female gametocytes which are transmitted back to the mosquito via a blood meal.
In Vivax and Ovale a some of the sporozoites lay dormant in the liver as hypnozoites and may cause relapse months or years later.
Pathogenesis of Malaria:
Symptoms occur once the paracitaemia passes a certain threshold (100 paracites per microL)
Incubation periods:
- Falciparum or knowlesi 10-14 days
- Vivax or Ovale 2-3 weeks
- Malariae >3 weeks
- But note some species of vivax can have incubation period up to 3-6 months.
Pathogenesis of Malaria:
Symptoms occur once the paracitaemia passes a certain threshold (100 paracites per microL)
Incubation periods:
- Falciparum or knowlesi 10-14 days
- Vivax or Ovale 2-3 weeks
- Malariae >3 weeks
- But note some species of vivax can have incubation period up to 3-6 months.
Falciparum is special. Erythrocytes with mature paracites sequester in small and medial blood vessels which causes endothelial dysfunction and obstruction:
- Brain - coma
- Lungs - respiratory disease
- pregnant women - placenta - foetal death
Anaemia caused by extravascular and intravascular haemolysis.
Clinical presentation of Malaria
Split into 2 disease presenations - uncomplicated or severe.
Uncomplicated:
- Non-specific symptoms - fever, headache, malaise, cough etc
Complicated - end organ dysfunction:
- Confusion, seizures
- Respiratory distress
- Bleeding
- jaundice
- Oliguria
- Shock
Lab criteria for complicated:
- Hb < 70, haemoglobinuria
- Hypoglycaemia
- Lactic acidosis
- AKI
- Asexual paracitaemia > 2%
Diagnosis of Malaria
Thick film - provide sensitivity
Thin film - provides quantification and speciation.
Rapid Diagnostic Tests (RDT) - detect antigen
NAAT - highly sensitive
Management of Severe Malaria
Severe malaria
- IV Artesunate ASAP
- Monitor paracitaemia 6-12 hourly
- Supportive care
- Give for at least 24 hours, and then can change to PO ACT once able to eat and drink
Adjunctive therapy:
- Bacteraemia is common, give IV Ceftriaxone until blood cultures negative
- Paracetamol
2nd line is quinine loading.