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.
Management of uncomplicated malaria
Artemisinin based combination therapy (ACT) is first line (except in 1st trimester pregnancy)
- Artemisin rapidly reduces paracitaemia
- Combination drug gradually removes residual paracites.
Artemether-lumefantrine is used in Aus.
2nd line is atovaquone + proguanil
Locations with artemisinin resistance is increasing:
- Vietnam
- Cambodia,
- Thailand
- Laos
- Myanmar
Vivax and Ovale must be treated concurrently with Primaquine for 14 days to eliminate hypnozoites (exclude G6PD prior to giving primaquine)
Management of malaria in pregnancy
In 1st trimester give quinine and clindamycin.
After 12 weeks treatment with ACT as per usual guidelines.
Malaria prophylaxis
Strongly recommended for children, pregnant women, people staying for >8 weeks, high risk areas, patients with hyposplenism.
Vector avoidance
Medications:
1 - Atovaquone + proguanil
- start 1-2 days prior, continue for 7 days on return
2 - Doxycycline
- Start 1-2 days before going, continue for 4 weeks on return
- Not recommended for < 8 years old
3 - Mefloquine (once weekly dose)
- start 2-3 weeks prior, continue for 4 weeks on return
- high resistance in Greater Mekong Subregion.
Why continue for so long on return?
Doxy and Mefloquine are not effective against pre-erythrocytic phase in liver.
Complication of malaria
Delayed anaemia
hyper-reactive splenomegaly
Neurological sequale
Meloidosis
Caused by bacteria Burkholderia pseudomallei
- aerobic, gram negative bacilli
Endemic in Northern Australia
Increased cases during Wet Season, transmission from direct contact with soil.
More common in immunosuppressed
Usually presents as pneumonia
But any organ can be affected - basically causes a bacterial infection +/- abscess formation of any organ.
Diagnosis:
Culture - will grow on normal media, send cultures from everywhere.
Treatment:
Intensive phase: IV Ceftazadime or Meropenem for 14 days
Eradication phase: PO Bactrim for 3months
Methenamine hippurate
In the presense of acidiic urine < pH 5.5, hiprex is hydrolysed to form fomaldehyde and ammonia. Formaldehyde is bacteriocidal to almost all pathogens.
It is not effective with:
- urinary catheters, as urine is drained immediately
- Urea splitting bacteria such a proteus
Some evidence that it reduces recurrence rate of UTI
Best given with something to acidify the urine - ascorbic acid, cranberry juice
also avoid in renal and hepatic failure
Splenectomy Guidelines - Vaccination
Patients with asplenia or hyposplenia are at high risk of fulminant sepsis:
- Streptococcus pneumoniae (most common)
Immunisation with pneumococcal, meningococcal, Hib, and influenza vaccine recommended.
If surgical splenectomy - vaccinated at least 2 weeks pre. If emergency, vaccinate at least 1 week after.
Splenectomy Guidelines - Antibiotic prophylaxis:
Who gets antibiotic prophylaxis:
- children less than 5
- Patients who have had a splenectomy - start prophylaxis post op and continue for at least 3 years.
Consider prophylaxis in other people who have asplenia/hyposplenia with additional risk factors:
- Incomplete vaccination
- immunodeficiency
- malignancy
- immunosuppressive therapy
- previous invasive pneumococcal disease
Amoxicillin 250mg daily
Duration:
- Until age of 5
- 3 years post splenectomy
- Ongoing if previous overwhelming post-splenectomy infection or if significantly immunosuppressed.
Other management of aslpenia
Sick day management:
- If develops fever take 2g amoxicillin and then 1 gram 8 hourly while awaiting urgent medial assessment.
Fpr children use Amox+Clavulanic acid
Definition of asplenia / hyposplenia
Asplenia:
- Anatomic asplenia due to splenectomy
- Functional asplenia due to Sickle cell disease
Hyposplenia:
- Considered significant (and therefore warrants antibiotic prophylaxis and vaccination) if sickle cell disease, recurrent infection with encapsulated organisms, or evidence of hyposplenia on bloods - Howell Jolly bodies.
Encapsulated organisms are usually cleared by the spleen:
- Pneumococcus
- Hib
- Neiserria meningitidis
5 Categories of Fungi:
YEASTS (unicellular, white, asexual reproduction = budding, smooth round colonies)
- Candida
- Crytptococcus
MOULDS (Multicellular, organised into hyphae, variety of colours, reproduce by spore formation (asexual or sexual), Colonies appear fuzzy)
- Aspergillus
- Mucorales
DIMORPHIC FUNGI
- Can act as yeast or mould
- Mould in soils, form spores and can be inhaled, form capulated lesions in lungs
- Hystoplasma, Blastomyes, Coccidiodes, Sporothrix
DERMATOPHYTES:
- Collection of fungi that share the ability to metabolize and live on keratin from skin
- names after body part involved.
PNEUMOCYTIS
- originally thought to be parasite, now recognised to be fungi
Fungal Cell Wall
Phospholipid bilayer
Ergosterol
Chitin
B 1-3 Glucan
Glucans
Glycoprotein
Polyene Antifungal Spectrum
Amphotericin
MOA: binds to ergosterol and forms pores in fungal cell wall
Extremely broad spectrum against basically all species of fungi including yeast (most candida and crptoccus), mould (most aspergillus spp and mucorales, and the dimorphic fungi
Fluconazole Spectrum
Effective against candida albicans, but not other candida species.
1dt line for cryptococcus
Effective against dimorphic fungi
NOT effective:
- non albicans candida species
- Moulds - aspergillus or mucorales
Itraconazole
Not recommended for systemic infections.
Used for ABPA against aspergillus
1st line for mild mod disease with dimorphic fungi
Voriconazole
1st line against invasive aspergillus disease
Posazonazole
Mould active with activity against both aspergillus and mucorales.
