Infectious Disease Flashcards
Treatment for MAC
Non-Tb Mycobacterium
- Azithromycin or Clarithromycin
- Rifampicin
- Ethambutol
IRIS
Immune reconstitution inflammatory syndrome
Parodoxical worsening of underlying infections at approx 1-2 months post-commencement of ART for HIV
Organisms not covered by Carbapenems
MRSA, enterococcus faecium, legionella, mycoplasma and chlamydia
Ertepenum does not cover Pseudomonas
CMV prophylaxis
Oral Valganciclovir
Required for all solid organ transplants;
D + / R - = 6 months
D - / R + = 3 months
D - / R - = no prophylaxis unless
Stem cell transplant if donor negative but host positive
CMV prophylaxis
Oral Valganciclovir
- Required for all solid organ transplants;
D + / R - = 6 months
D - / R + = 3 months
D - / R - = no prophylaxis unless
- Stem cell transplant if donor negative but host positive
- HIV with CD4 count < 50
Syphilis testing
Screening w trepenomal test;
- TP-EIA IgM and IgG serology
- TP-EIA will be confirmed in the lab against TPPA
Diagnosis w non-trepenomal tests
- RPR - Used to confirm diagnosis of new infection, old infection or re-infection
- VDRL - only used on CSF
Treatment of Syphilis
10 days of long-acting IM penicillin (Benzathine Penicillin)
Requires this longer acting penicillin to obtain continuous levels of penicillin to eliminate the treponemes which divide slowly.
Antigens involved in “Antigen Drift” in Influenza A
Glycoproteins
Glycoprotein H antigen - haemoagglutinin
Neuramindase N antigen
Live Vaccines
MMR
Polio
Yellow fever - uses eggs, can cause hypersensitivity reaction (along with Q fever vaccine)
Varicella Zoster
Mb BCG
Typhoid
Mechanism of MRSA
MecA gene - encodes additional penicillin binding proteins (PBP2) which cross-links the cell wall and leads to poor affinity of beta-lactams
Rx with Vancomycin if MIC < 2, or daptomycin if Vanc MIC > 2 (except for MRSA pneumonia where Daptomycin will be inhibited by surfactant -> use Linezolid)
Mechanism of VRE
Changes in cell wall components make it have low affinity for Vancomycin
Van A - Linezolid
Van B - Linezolid or Teicoplanin
Treatment of Tb Meningitis
12 month Rx with
- Izoniazid
- Rifampicin
- Pyrazinamide
- Moxifloxacin (better CNS penetration than ethambutol)
plus acute Dexamethasone use
Infectious causes of mesenteric adenitis
Yersinia from undercooked pork
Candida Krusei resistance
To Fluconazole
Active Tb treatment
2 months 4 drug regime;
Isoniazid
Rifampicin
Pyrazinamide
Ethambutol
followed by 4 months 2 drug regime;
Isoniazid
Rifampicin
Latent Tb Treatment
- Isoniazid for 9 months
or - Rifampicin for 4 months
or - Isoniazid + rifampicin for 3 months
MRSA treatment
Vancomycin if MIC < 2
If Vanc MIC > 2 for Daptomycin or Linezolid
Choose Linezolid for pneumonia as daptomycin is inactivated by surfactant
Epstein Barr Virus
HHV 4
Proliferates in B cells and generates a CD8 T cell response -> can lead to lymphproliferative disorders
Causes
- Mononucleosis
- Burkitts
- Hairy Cell leukoplakiain HIV
- Cold agglutinin AIHA
Investigation
- Monospot (serology), early IgM -> late IgG
- EBNA gene production, delayed > 4 weeks
Dengue tests
Before 5 days;
- PCR
- NS1 protein Ag
After 5 days
- Antibodies IgM or IgG if > 10 days
Conservative management
Vaccination only for seropositive patients -> can worsen first infection in seronegative patients
Infections post-splenectomy
Strep pneumonia
Haemophilis Influenzae
Neisseria Meningitidis
Capnocytophaga canimorsus (dog bite)
Salmonella
Gram negative infections (E.Coli, Pseudomonas)
Bactericidal antibiotics
Very Finely Proficient At Cell Murder
Vancomycin
Fluroquinolones
Penicillin
Aminoglycosides
Cephalosporin, Carbapenem
Metronidazole
Bacterostatic antibiotics
ECSTaTiC
Erythromycin
Clarithromcyin
Sulfonamides
Trimethoprim
Tetracyclines
Chloramphenicol
Mechanism of Antibiotics
Beta-lactams and Vancomycin - cell wall inhibitors
Fluroquinolones - DNA Gyrase
Aminoglycosides and Tetracyclines - 30s ribosome
Trimethoprim & sulfonamides - Folate synthesis
Rifampicin - RNA polymerase
All others 50s ribosomal subunit
HIV opportunistic infection
> 200 - Shingles, pneumococcal, candida, Tb
< 200 - PJP
< 100 - Cryptococcus, Toxoplasmosis
< 50 - Disseminated MAC, CMV
Syphilis stages
Primary - Painless chancre and lymphadenopathy
Secondary - condyloma lata, contagious genital ulcers, mouth ulcers, uveitis
Tertitary - Neurosyphilis, aortitis, gumma.
Bacterial meningitis treatment
Emperic - Ceftriaxone + Benpen + Dex
Strep - Benpen or Ceftriaxone, add Vancomycin if Cef MIC > 1
Meningicoccus - Ceftriaxone
Listeria - Benpen
Dex only has benefit in Strep & H.Influenzae
Culture negative Endocarditis
Coxiella (Q fever)
Bortenella (Cat scratch)
Legionella
Chlamydia
Fever in returned traveller
- Malaria - cyclical fevers without rash, myalgia, GI upset
- Dengue - saddleback fevers and back pain, with macular rash
- Zika Virus - mild illness with teratogenicity
- Yellow Fever - acute hepatitis
- Chikungunya - Severe joint pain
- Typhoid/Paratyphoid - enteric fever- stepwise fevers with relative bradycardia and abdominal pain, rose spots
- Enterotoxigenic E.Coli - acute diarrhoea illness
- Giardia - delayed diarrhoea illness
- Bacillus cereus bacteria - reheated rice within 6 hours (very early!)
HACEK group
Haemophilis, Aggregatibacter, Cardiobacterium, Eikenella, Kingella
Small gram negative bacteria that cause IE
Major Dukes Criteria
- Microbiology - ‘typical’ bugs in 2 separate blood cultures OR persistently positive culture of unusual organism
- Echocardiogram - oscillating mass, abscess, new partial dehiscence of prosthetic valve OR new valvular regurgitation
- Serology - for Coxiella (Q fever)
Minor Dukes Criteria
- Predisposition - IVDU or heart condition
- Fever 38°C
- Vascular phenomena - arterial embolism, septic pulmonary infarct, Janeway lesion, mycotic aneurysm, intracranial haemorrhage
- Immunological phenomena - glomerulonephritis, Oslers nodes, Roth spots
- Suggestive microbiology
HIV Drugs
Nucleotide reverse transcriptase inhibitors - stop RNA to DNA transcriptase via binding at deoxynucleotide binding site
Non-nucleotide reverse transcriptase inhibitors - stop RNA to DNA transcriptase by binding at an alternative site to the deoxynucleotide
Integrase inhibitors - stop viral replicated DNA being integrated with host DNA
Protease inhihbitors - stop budding and maturation of virus from host cells, main role is to inhibit CYP3A4 to increase efficiency of other HIV drugs
Linezolid side effects
Bone Marrow suppression with thrombocytopenia
Neuropathy
Serotonin syndrome
Strongyloides
GI symptoms, dry cough, hyper infection decades after infection due to immunosuppression, larvae rash & organ failure due to infiltration or overlying bacterial infection
Worse with co-infection human T-lymphocytic virus 1 (HTLV1)
Ix - Serology or Rhabditiform larvae in stool
Rx Ivermectin
Types of non-live vaccination
Conjugated (Ag bound to protein) - will induce a T cell response and long-term immunity
- 13PCV pneumococcal - single dose to be given before non-conjugated
- monovalent Menigicoccal - Against serotype C
- Quadravalant Meningicoccal - Against serotypes A, C, W, Y
- Meningococcal B
Unconjucated (Ag not bound to protein)- will only induce a B cell response, and no long term immunity
- 23PPV pneumococcal - for 2 further doses to make up total 3 doses over 5 years
- Haemophilus
Antibiotic post-splenectomy
Amoxicillin for 3 years if otherwise healthy
Lifelong if Hx opportunistic infection
Maleria treatment
Mild - 3 day course chloroquine followed by 14 day course Primaquine OR Artemether + lumefantrine
Latent - 14 days primaquine
Severe - IV Artesunate - resistance due to KELCH 13 gene in SE Asia
Kelch 13
Mutation in malaria strains of SE asia which cause IV artesunate resistance
Side effect Primaquine
If G6PD deficient, will cause haemolysis
Mosquito’s which transmit disease
Anopheles - Malaria
Aedes - Flavivirus
Antigen test for Dengue
NS1
Zika virus complications
Teratogenic
Gullian Barre
Dx PCR < 7 days, serology > 7 days
Typhoid
1-3 weeks incubation
Enteric fever due to Salmonella.
- Stepwise fevers
- diarrhoea or constipation w abdominal pain,
- Relative bradycardia
- Salmon coloured papule on skin (rose spots)
- Rx with Ceftriaxone.
Mechanism of anti-fungals
Azoles - inhibit D-14 alpha demethylase at CP450 to stop ergosterol synthesis at cell walls
Echinocandins - inhibit beta 1,3 D glucan to inhibit cell wall synthesis
Amphotericin (polyenes) - binds ergosterol to stop membrane function and create pores
How does HIV enter cells?
Via Glycoprotein 120 and glycoprotein 41 with co-receptors CCR5 (mild disease) and CXCR4 (late infection, more aggressive)
A lack of CCR5 causes a slower progression of disease
HIV co-receptors on CD4 T cells
CCR5 - early
CXCR4 - late
Lack of CCR5 in populations causes slower and milder disease
HIV co-receptors
CCR5 - early
CXCR4 - late
Lack of CCR5 in populations causes slower and milder disease
HLAB57.01 and CCR5 mutation
Patients with HLAB57.01 MHC type receptors on CD4 cells bind strongly to T killer cells and & are more likely to be able to control viral load/slower progression of disease. These patients cannot be treated with Abacavir.
CCR5 co-receptor mutations - less ability of HIV to bind co-receptors causing slower progression of disease
Time period and regime of HIV PEP
within 72 hours (best within 24 hours)
- High risk - 2 x NRTI + integrase inhibitor (Known HIV not on treatment with detectable viral load or high risk exposure to unknown patient)
- Low risk - 2 x NRTI (unknown HIV or on treatment with undetectable viral load)
Starting ART after Tb Rx
CD4 count > 50 - wait 8 weeks
CD4 count < 50 - wait 2 weeks
Antibiotics inhibiting 30S
Aminoglycosides (Gentamicin)
Tetracyclines (doxycycline)
MOA Quinolones
I.e. Ciprofloxacin
Bind DNA gyrase
MOA Rifampicin
Block RNA polymerase
MOA Sulphonamides and Trimethoprim
Block folate synthesis
MRSA resistance
Via mecA (mobile genetic element), which encodes for extra penicillin binding protein (PBP2a) that cross-links PBP and gives beta-lactams a lesser affinity
ESCAPPM
Inducible beta-lactamase via AmpC
Enterobacter
Serratia
Citrobacter
Acinetobacter
Proteus Vulgaris (but not mirabilis)
Providencia
Morganella Morgani
Enterobacter with Carbapenem resistance
New Delhi Metallo Beta Lactamase (NDM1) transferred by plasmids making enterobacter resistant to carbepenams
Genes for antibiotic resistance
MRSA - genetic mobile unit MecA
VRE - plasmid Van A, B, C
ESBL - plasmid CTX-M
ESCAPPM - inducible betalactamase AmpC
CRE - plasmid New Delhi Metallo (NDM1) beta lactamase
Empirical Rx for Nec Fasc
Meropenum, Vancomycin and Clindamycin (for toxins)
Side effects of Rifampicin
CYP inducer (particularly important in HIV meds)
Hepatotoxicity
Orange sercretions
Side effects of Isoniazid
Hepatotoxicity, Peripheral neuropathy
Side effect of Ethambutol
Optic neuropathy - require baseline eye tests
Side effects of Pyrazinamide
Gout, Hepatotoxicity
Major side effects of Tb Medications
Rifampicin - CYP inducers, orange secretions
Isoniazid - Peripheral Neuropathy (give w B6 Pyridoxine)
Ethambutol - Optic neuropathy
Pyrazinamide - Gout, Worst risk of hepatitis!
Which cohorts to treat latent Tb
Healthcare workers
< 35 years old
Immunosuppressed
Recent infection
CMV
- Mononucleosis- type illness with Fever and Lymphadenopathy “CMV-effect”
- Can affect many end organs “CMV disease” ( Pneumonia, hepatitis, GBS, Meningoencephalitis, myocarditis, thrombocytopenia, haemolytic anaemia)
- Owl eyes on blood film
- Risk of maternal -> fatal transmission 40%
Risk of CMV in transplant
Solid organ - Donar +, recipient -
Haematological - Donar -, recipient +
Commonest organism to cause IE
Staph Aereus
Or
Staph Epi if within 2 months of prosthetic heart valve
MRO resistance mechanisms
MRSA - MecA gene causing change in penicillin binding protein 2
VRE - Van A or B causing change in cell wall to reduce affinity for Vancomycin
ESBL - Plasma mediated genes which code for enzyme that hydrolyses bea-lactam, most commonly CTX-M gene. Causes resistance to penicillins & 3rd generation cephalosporins (Ceftr, Ceftaz)
ESCAPPM - ESBL with inducible beta-lactamase on Chromosomal AmpC (not plasmid)
CRE - Carbapenem resistant beta-lactamase - New Delhi Metallo-beta-lactamase-1 (NDM1) on plasmids
Types of Candida & Rx
Candida albicans - fluconazole (most common)
Candida glabrata - Echinocandin
Candida Krusei - Voriconazole (fluconazole resistance)
Candida Auris - Echnocandin (known multi-drug resistance)
