Infections (Chronic and Acute) Flashcards
Type of parasite that causes malaria
Plasmodium
5 types of malaria
P. Falciparum, P vivax, P knowlesi, P. Malariae and P. Ovale
Most resistance malarial organism
Falciparum
Diagnosis of malaria
Thick and thin films- however if antimalarials have been taken then this can mask the result.
Uncomplicated vs complicated malaria features
Positive parasitology screen with Giemasa stain and thick and thin films. Severe malaria is defined as any of the following: parasite count higher than 2 % or 100, 000 per microlitre. Impaired consciousness Jaundice oliguria Resp distress Severe anaemia Hypoglycaemia Vomiting clinical acidosis AKI
In short- any end organ damage or signs of systemic illness.
Treatment of uncomplicated malaria
Artemether + lumefantrine 10/120mg first line
atovaquone + proguanil 250/100 mg second line
Quinine + doxy 600/100 mg third line
Which agent should be added in northern australia where human to host transmission is aiming to be limited
primaquine is given as a one off
Can not give to G6PD def. patients - severe haemolysis
Which malarial parasites can lie dormant in the liver
Ovale and vivax: Hypnozoites are not eliminated by the uncomplicated malaria regimen. Primaquine or tafenoquine should be given.
Treatment of severe malaria
Artesunate IV or if unavailable then IV quinine
Additional therapy in severe malaria
Addition of ceftriaxone and paracetamol is recommended- especially if hypotensive.
HIV treatments regimen
Typically made up of a nucleoside reverse transciptase inhibitor, Non-neucleoside transscriptase inhibitor and an integrase inhibitor
NRTI, NNRTI, Integrase inhib. Alternatively can have two NRTIs and an integrase
Entry inhibitors
maraviroc (binds to CCR5, preventing an interaction with gp41), enfuvirtide (binds to gp41, also known as a ‘fusion inhibitor’)
prevent HIV-1 from entering and infecting immune cells
Nucleoside analogue reverse transcriptase inhibitors (NRTI)
examples: zidovudine (AZT), abacavir, emtricitabine, didanosine, lamivudine, stavudine, zalcitabine, tenofovir
general NRTI side-effects: peripheral neuropathy
tenofovir: used in two recommended regime NRTI. Adverse effects include renal impairment and ostesoporosis
zidovudine: anaemia, myopathy, black nails
didanosine: pancreatitis
Non-nucleoside reverse transcriptase inhibitors (NNRTI)
examples: nevirapine, efavirenz
side-effects: P450 enzyme interaction (nevirapine induces), rashes
Protease inhibitors (PI)
examples: indinavir, nelfinavir, ritonavir, saquinavir
side-effects: diabetes, hyperlipidaemia, buffalo hump, central obesity, P450 enzyme inhibition
indinavir: renal stones, asymptomatic hyperbilirubinaemia
ritonavir: a potent inhibitor of the P450 system
It acts by inhibiting aspartyl protease enzymes, preventing viral maturation and prevents functional virion formation.
Integrase inhibitors
block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell
examples: raltegravir, elvitegravir, dolutegravir
MOA azoles
Inhibits 14 alpha demethylase which produces ergosterol (adverse) = P450 inhibition and liver toxicity
Amphotericin B and nystatin MOA
Binds with ergosterol forming a transmembrane channel that leads to monovalent ion leak. Nephrotoxic
Terbinafine MOA
Inhibits squalene epoxidase
Griseofulvin MOA
Interacts with microtubules to disrupt mitotic spindle
Flucytosine MOA
Converted to 5-Flurouracil, inhibitis thymidylate synthase and disrupts protein synthesis
Caspofungin MOA
Inhibits synthesis of beta-glucan and major cell wall component
Name gram positive rods
Actinomyces Bacillus anthracis (anthrax) Clostridium Diphtheria: Corynebacterium diphtheriae Listeria monocytogenes
Gram positive cocci
Staph, Strep and enterococci
Gram negative coci
Neisseria and moraxella
Trimethoprim MOA
transient rise in creatinine: trimethoprim competitively inhibits the tubular secretion of creatinine resulting in a temporary increase which reverses upon stopping the drug
trimethoprim blocks the ENaC channel in the distal nephron, causing a hyperkalaemic distal RTA (type 4). It also inhibits creatinine secretion, often leading to an increase in creatinine by around 40 points (but not necessarily causing AKI)
Treponema pallidum diagnosis
Two main devisions: cardiolipin tests, trepnomal-specific anti-body tests.
Examples of Cardiolipin tests are VDRL and RPR - these should become negative post treatment
Treponemal specific antibody tests e.g. TPHA (Treponema pallidum haemagglutination tests) remains positive after treatment
False positive cardiolipin tests in pregnancy, SLE, TB, leprosy, Malaria, HIV
Tetanus
Exotocin from clostridium tetani (Gram +ve rod). Prevents relesae of GABA via tetanospasmin
Supportive therapy is first line including benzodiazepines as a muscle relaxant.
IM tentaus immunoglobulin can be administered in high risk individuals. Can give metronidazole
MOA Vancomycin
inhibits cell wall formation by binding to D-Ala-D-Ala moieties, preventing polymerization of peptidoglycans
Mechanism of resistance
alteration to the terminal amino acid residues of the NAM/NAG-peptide subunits (normally D-alanyl-D-alanine) to which the antibiotic binds
PCP pneumonia
PCP is the most common opportunistic infection in AIDS
all patients with a CD4 count < 200/mm³ should receive PCP prophylaxis
Features dyspnoea dry cough fever very few chest signs
Management
co-trimoxazole
IV pentamidine in severe cases
aerosolized pentamidine is an alternative treatment for Pneumocystis jiroveci pneumonia but is less effective with a risk of pneumothorax
steroids if hypoxic (if pO2 < 9.3kPa then steroids reduce risk of respiratory failure by 50% and death by a third)
Differentiate Legionella from mycoplasma pneumonia
Legionella: lymphopenia, hyponatraemia, dianosis on urinary antigen
Mycoplasma: Haemolytic anaemia or ITP Erythema multiforme GBS Myocarditic Seroligcal diagnosis
Both cause flu like illness, dry cough, and are treated with a macrolide
Jarisch-Herxheimer reaction
fever, rash, tachycardia after the first dose of antibiotic
in contrast to anaphylaxis, there is no wheeze or hypotension
it is thought to be due to the release of endotoxins following bacterial death and typically occurs within a few hours of treatment
No treatment is needed other than antipyretics if required
Visceral leishmaniasis
By sand flys transmitting protozoa called leishman donovani - disease is AKA kala-azar
Fevers, sweats, splenomegaly, weight loss, grey skin, pancytopenia
Bone marrow or splenic aspirate
Hepatitis C
RNA flavivirus
Vertical tranmission rate 6%
No vaccine
30% of patients will develop features: fatigue, arthralgia, fatigue
HCV RNA is the investigation of choice for diagnosis
Chronic hepatitis C: rheumatological problems (sjogren’s syndrome), icrrhosis, HCC, cryoglobulinaemia (typically type II), membranoproliferative GN
Interferon alpha and ribavirin: ribavirin is teratogenic
Syphilis
G.Negative bacterium - obligate parasite - Spirochete
Primary chancre is painless with a sloughy base and rolled boarder
3 stages: primary syphilis, secondary (6-12 weeks) - occurs with spirochetemia - non-itchy manulopapular rash - usually resolves in weeks to months, stage 3 is latent i.e. dormant, asymptomatic.
Early phase within a year of infection
Late phase after 1 year - which triggers tertiary syphilis: type 4 hypersens. reaction driven by T cells.
Can cause aortitis from inflammation of vasa vasorum
Neurosyphilis: Tabes dorsalis (wasting of dorsal column), can also get anterior spinal cord inflammation too
ARGYLL ROBERTSON PUPIL: accommodates to a nearby object by loses light reflex
Diagnosis: non-treponemal tests: RPR or VDRL and anti-cardiolipin antibody tests
Trepenemal tests TPRA or FTA-ABS are specific to T pallidum
Live Vaccines
ROME I'm Your Big Travel Pest Rubella, OPV, measles, epidemic typhus Influenza Mumps Yellow fever BCG Plague Typhoid (active)
Malignancies associated with EBV
Burkitt’s lymphoma
Hodgkin’s
Nasopharyngeal
HIV associated CNS
Caspofungin MOA and family
Echinocandins, inhibits 1-3 B-D glucan synthesis . disrupts integrity of cell wall
Azoles MOA
inhibit ergosterol synthesis
Polyenes MOA
Bind ergosterol (Amphotericin and nystatin)
Bugs fight back: Drugs affected by decreased permeability
Permiability barrier: trimethoprim, sulphonamide, vancomycin
Porin channels - beta lactams, aminoglycosides, chloramphenicol
Bugs fight back: Inactivated enzymes
Beta lactamase, aminoglycoside modifying enzymes, esterases and acetyltransferase: Predominantly these organises are staph aureus, escappm organisms, E. COli, H. Influenza, N.Gonorrhoea, K pneumonia
Bugs fight back: Alteration of target site binding:
Penicilin binding proteins made by MRSE, coag negative staph and strep pneumo.
RIbosoms sites can alter streptomycin, erythromycin and tetracycline activity. DNA gyrase alteration for fluroquinolones
RNA polymerase and DHFR - tetracyclines
Bugs fight back: Active efflux pump
Linezoild pumped out
Bad prognsotic signs in Malaria Faciparum infection
Schizonts on blood film, impaired consciousness, acidosis, Parasitaemia >10% or P.Knowlesi >0.5%
Bugs that commonly cause endocarditis
Staph aureus, viridans strep, coagulase negative staph, enterococci, strep bovis and HACEK group of G negative bacilli
Haemophilus, aggregatibacter, cardiobacterium hominus, eikenella corrodens, kingella
First line therapy for native valve endocarditis.
Benzylpenicillin 1.8 g IV Q4H + Flucloxacillin 2 g Q4 H plus Gentamycin IV over 3-5 minutes (7mg/kg if otherwise well prior but needing ICU, 5mg/kg if not requiring ICU
If MRSA is suspected e.g. people who inject drugs or higher risk groups then use vancomycin IV 30 mg/Kg IV loading
If Penicillin allergic
Cefazolin
Therapy for infective endocarditis of foreign material e..g cardiac pacing wires, valves etc.
Flucloxacillin + Vancomycin + gentamycin
Duration of Staph endocarditis therapy
4-6 weeks: if non-complicated 4 weeks, if complex like abscess or septic metastatic complications then 6 weeks
Duration of therapy for tricuspid valve endocarditis
R sided MSSA endocarditis can have 2 weeks of fluclox IF
No prostehetic, no metastatic infection e.g. OM, no cardiac complications, vege smaller than 20mm, clinical and micro response within 72-96 hours of therapy. Immunocompetent
If MRSA or prosthetic valve - 6 weeks
Strep endocarditis regimen
Ben pen and gent for 2 weeks if uncomplicated
Single ben pen for 4 weeks can also be used
Ceftriaxone for 2 weeks if allergic
HACEK group endocarditis
Ceftriaxone 2 g 4-6 weeks
Causes of errythema Nodosum
NO cause found in 60% Drugs (Sulfas) Oral contraceptices Sarcoid and lofgrens syndrome Ulcerative colitis, Crohns and Bechet's Micro: Tb, Viral, Bacterial, Fungal
Mantoux test: Cellular response
T cell response (delayed hypersensitivity)
Interferon gamma release assay
I.e. Quantiferon Gold
Still may be negative in active disease. Doesn’t tell you latent or active
Doesn’t tell you predictive value i.e. who will go one
Detecting exposure to TB
4 tubes: CD4, CD8 as well as mitogen control and negative control looking at Interfron gamma background activity
NAATs (Nucleic acid amplification test) For TB
Highly specific, relatively good 85% sensitivity)
Culture is the gold standard
What is most important to do to increase dx yield on LP for TB meningitis ?
Get lots of fluid
In TB meningitis: Clinical suspicion and amount of fluid are important
Treatment options for latent TB
9 months of Isoniazid: Hepatotoxic, 15% now resistant or 4 Months of Rifampicin or 3 months of rif and iso
Standard short course TB treatment
2 Months of RICE and 4 months of Rif and Iso
Hierachy of hepatitis in TB treatment
P > I > R
If 2-5 x ULN and asymptomatic then monitor
If >5 or >3 with symptoms then stop
Can give amikacin, ethambutol and moxifloxacin as liver sparing
Bedaquiline MOA
First novel agent - targets DNA synthase
Delamanid MOA
Nitromidazole class that inhibits mycolic acid synthesis
Treatment of MDR-TB
-Floxacin (Moxi or levo) + Bedaquiline + Linezolid
+ 2 second line drugs Clofazimine and Cycloserine
How to treat TB in patients with HIV
CD4 <50 EARLY ART (before 2 weeks) - will increase IRIS risk but improve mortality
>50 then ART by week 8 after starting TB therapy
HIV meds to use in TB
Truvada (TDF + FTC (Emtracitabine)) + Raltegravir or dolutegravir
TB risk as per immunotherapy risk
Adalimumab > infliximab >etanercept
