Infectious Diseases Flashcards
Treatment for TB
Two Months Rifampicin (Inducer of CYP/Yellow secretions) Isoniazid Pyrazinamide Ethambutol
Six Months
Rifampicin
Isoniazid
Duration of treatment for meningeal TB
12 months
Streptomycin replaces Ethambutol
Isonazid adverse effects
Peripheral neuropathy
Hepatitis
Rash
Rifampicin adverse effects
Febrile reactions
Hepatitis
Rash
GIT disturbance
Pyrazinamide adverse effects
Hepatitis
GIT disturbance
Hyperuricaemia
Streptomycin adverse effects
8th cranial nerve damage
Rash
Ethambutol adverse effects
Retrobulbar neuritis (may present as colour vision loss) Arthralgia
TB Diagnosis
Two sputum samples (one early morning) for acid fast bacilli
Sputum culture = highest specificity
Chemoprophylaxis regimen for TB
Rifampicin + Isoniazid for 3 months
Isoniazid for 6 months
Offered to those who are positive for latent TB (TST/IGRA) or patients who are HIV infected and close contact with a smear positive individual.
Testing for latent TB
1) Turberculin skin test
- False +: BCG or infection with non-mycobacterium TB
- False -: immunosuppressed or overwhelming TB infection
2) IGRA
Testing for Syphilis
Non-Treponemal Tests: VDRL/RPR
(False positives from active infection with infectious mono, chickenpox and malaria as well as pregnancy)
(False negatives in secondary syphilis)
Treponemal Tests: Treponemal test remain positive even after treatment
Nb If Non-treponemal test + but treponema test - usually indicates a false positive finding.
If test positive in asymptomatic individual then needs to be repeated.
NB: Check treatment response at 3, 6 and 12 months with a nontreponemal test. Syphilis is considered cured if the nontreponemal titre falls by at least four-fold (two dilutions).
Brucellosis (Brucella) findings on culture and gram stain
Gram-negative coccobacilli
Nonencapsulated, nonmotile
Facultatively intracellular
Mechanism of action of neurominidase inhibitors
Neuraminidase inhibitors reduce viral shedding by interrupting the cleaving process of Neuraminidase.
Mechanism of action fo echinocandins
- Anidulafungin
- Caspofungin
- Micafungin
Inhibit 1,3-beta-D-glucan synthase
Effect
- Fungicidal against Candida
- Fungistatic against Aspergillus
Mechanism of action of azoles
Impair the synthesis of ergosterol
Adverse effects of azoles
General: rash, headache, dizziness, nausea, vomiting, abdominal pain, diarrhoea, elevated liver enzymes
Specific: Thrombocytopenia and blue-green visual aura with voriconazole
Mechanism of action of Flucytosine
Converted to fluorouracil inhibits fungal DNA synthesis and is also incorporated into fungal RNA, affecting protein synthesis.
Adverse effects of flucytosine
Blood dyscrasias
Diarrhoea, nausea, vomiting, elevated liver enzymes (dose-related), rash
Nb: oxicity is associated with prolonged concentrations >100 mg/L. Need to undertake TDM
Amphotericin B mechanism of action
Binds irreversibly to ergosterol in fungal cell membranes causing cell death by altering their permeability and allowing leakage of intracellular components.
Amphotericin B adverse effects
nephrotoxicity
LFT derranagements: increased serum bilirubin, increased ALP,
Metabolic changes: hyperglycaemia, hyponatraemia
Other: tachycardia,
Linezolid mechanism of action
Inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit
Used for treatment of gram + and some anaerobes
Adverse effects of Linezolid
Reversible myelosupression Serotonin syndrome (weak MAOI) Optic and peripheral neuropathy (interference with mitochondria activity) Lactic Acidosis (interference with mitochondria activity)
Mechanism of action of Guanine Analogue anti-virals
- Aciclovir
- Famciclovir
- Ganciclovir
- Valaciclovir
- Valganciclovir
Guanine analogues
phosphorylated by virally-encoded cellular enzymes –> acyclovir triphosphate, which competitively inhibits viral DNA polymerase
Treatment of Syphilis
Penicillin
If allergic and non-pregnant doxycycline
Mechanism of action of Tetracyclines
- Doxycycline
Bacteriostatic; inhibit bacterial protein synthesis by reversibly binding to 30S subunit of the ribosome
Adverse effects of tetracyclines
Photosensitivity
Photo-onycholysis and nail discolouration
Teratogenic post 18 weeks gestation (inhibit bone growth)
Glycopeptides mechanism of action
- Vancomycin
- Teicoplanin
Bactericidal; inhibit bacterial cell wall synthesis by preventing formation of peptidoglycan polymers.
Mechanisms of resistance of enterococcus species to vancomycin
Alteration of the peptidoglycan synthesis pathway
Daptomycin Mechanism of Action
Gram-positive bacterial cytoplasmic membranes in the presence of calcium, causing depolarisation, potassium efflux (impairing potassium-dependent DNA, RNA and protein synthesis) and cell death.
Treatment of systemic and life-threatening infections caused by Gram-positive organisms
Interaction between HIV and CD4 cells
Attachment occurs by interaction of GP120 on the surface of the virus and the CD4 antigen receptor on the surface of the host cell
Binding then occurs via a co-receptor
- CCR5 on Macrophages
- CXCR4 on CD4 cells
Red man syndrome
Occur from infusion of glycopeptide (note vancomycin > teicoplanin)
Related to rate of infusion
Note an allergic reaction although histamine release involved
Treat with antihistamine (promethazine)
Mechanism of action of carbapenems
- Meropenem
- Etrapenem
- Imipenem
Inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins. Usually bactericidal
Febrile neutropenia
Gram negative or Gram positive
Anaerobes
Treatment for New Delhi metallo-beta-lactamase 1 (NDM-1)
Colistin or tigecycline
Colisitin mechanism of action
Bactericidal; interacts with lipopolysaccharides in the outer bacterial membrane changing its permeability.
Tigecycline mechanism of action
Binds to 30S ribosomal subunit preventing incorporation of amino acids into bacterial peptides; bacteriostatic.
Treatment regimen in HIV
2NRTI
+
NNRTI/PI/Integrase Inhibitor
When using a protease inhibitor why is ritonvair also used in the treatment of HIV
Ritonavir (a protease inhibitor in itself) interacts with both P-glycoprotein (reducing efflux) and inhibitors CYP3A leading to increased concentration and elimination half lives of other PIs.
Which form of malaria can result in the severest haemolysis
P Falciparum (invades red cells of all ages)
Criteria for severe P Falciparum malaria infection
Parasite count > 2%
Complication of malaria
Treatment for severe Falciparum malaria
IV Artesunate
or
IV Quinine
If >10% circulating erythrocytes consider exchange transfusion
Empiric treatment for suspected bacterial meningitis
1) 3rd generation cephalosporin - Ceftriaxone/Cefotaxime
2) Dexamethasone
3) Ben pen - if alcoholic, older than 50, immunocompromised, pregnant or debilitated (to cover for Listeria)
4) Vancomycin - if concern for Strep pneumoniae (Gram-positive diplococci)
Main risk factors for HIV associated lipoatrophy/dystrophy
Stavudine but also zidovudine (NRTIs)
Older age
Low baseline triceps skin fold values
Prevention of hepatitis B when contaminated by source +HBV
Not vaccinated: Immunoglobulin + Hepatitis B vaccine
Non responder to vaccine: Check source HBsAg is positive or if it cannot be obtained, the HCP should receive two doses of hepatitis B immunoglobulin (HBIG). The second dose of HBIG should be given one month after the first dose.
Amoebic Liver Abscess Treatment
Metronidazole 8-hourly for 7 days or Tinidazole 2 g orally, daily for 5 days and Paromycin 500 mg orally, 8-hourly for 7 day to eradicate cysts in the gut and prevent recurrence
Use of bactrim prophylaxis
PJP
Toxoplasmosis
HIV prophylaxis for patients with CD4 count
<200
<50
<200: PJP prophylaxis with Bactrim (if allergic give damson. atovaquone or aerosolised pentamidine)
<50: MAC prophylaxis with Azithromycin (unless on ART)
Cause of bullous impetigo
Staphylococcus aureus
Antibiotics for Streptococcal or Enterococcal Infective Endocarditis
Gentamicin and Benzylpenicillin
Antibiotics for Staphyloccocal Endocarditis
MSSA: Flucloxacillin 2g 4 hourly for 4-6 weeks
MRSA: Vancomycin for 6weeks
Antibiotics for HACEK endocarditis with Beta Lactamase
Ceftriaxone 2g daily for 4-6 weeks
Important parameter for effectiveness of beta lactam antibiotics
Time over minimum inhibitory concentration (time dependent)
Important parameter for effectiveness of amino glycoside antibiotics
Concentration max/MIC (concentration dependent)
Important parameter for effectiveness of vancomycin
AUC/MIC is most important.
Treatment for severe tropical pneumonia (north of Tenant Creek) in patients considered at risk (diabetes, hazardous alcohol consumption, CKD, COPD or Immunosuppressive therapy) or Gram Negative Bacilli identified on culture
Meropenem + IV azithromycin
How does HIV gain entry to the CD4 cell?
Glycoprotein 120 and 41 attach to CD4 molecules changing their shape and the attaches to CCR5 or CXCR4
Virus is then allowed to enter the cell
Abacovir delayed hypersensitivity
HLAB*57.01
Window period in which HIV cannot be identified by ELISA antigen antibody testing
2-3 weeks (15 days)
Tenofovir mechanism of action
Reverse Transcriptase Inhibitor
Preferred treatment regimens for HIV
Integrase Inhibitor
2 Nucelotide reverse transcriptase inhibitors
Mechanism of action of Nucleoside Reverse Transcriptase Inhibitors
Bind to viral reverse transcriptase at deoxynucleotide binding site and block DNA synthesis
Mechanism of non-nucleoside RTIs
Bind viral reverse transcriptase but not at deoxynucleotide binding site and alter the confirmation of enzyme blocking DNA synthesis
Protease Inhibitor mechanism of action
Block viral protease preventing maturation of the virus during and after budding
Ritonavir/Lopinavir/Atazanavir/Darunavir
Use of ritonavir for HIV
Inhibits CYP3A4 which boosts other protease inhibitors
Integrase inhibitors
Block viral integrate preventing integration of viral DNA into host DNA
Rategravir
Elvitegravir
Dolutegravir
Bictregravir
When to commence PEP for HIV
Within 72hrs (best within 24hr)
Who to give post-exposure prophylaxis
Non-occupational: If HIV load is unknown or detectable
- 3 drug regimen
Occupational:
- HIV load unknown or detectable: 3 drug regimen
- HIV load known to be undetectable: 2 drug regimen
Prep regimen
Tenofovir + Emtricitabine
PEP regimen
- 2 Drug regimen: 28 days of Tenofovir + Emtricitabine or Lamivudine
- 3 Drug regimen: 28 days Dolutegravir/Raltegravir/Rilpivirine
Monitoring while on Prep
6monthly: eGFR and ACR
12monthly: Hepatitis C
CD4 count and opportunistic infections
<250: PJP
<150: Cryptococcal/Toxoplasma
<50: MAC/Cytomegalovirus
Clinical presentation of PJP
Fever
Non productive cough
Marked exertion dyspnoea (well when sitting but drop sats on walking)
CXR: Diffuse bilateral infiltrates (Basal and apical sparing)
CT: Widespread ground glass changes
Diagnosis of PJP
CXR: Bilateral infiltrates with basal and apical sparing
CT: Ground glass
PCR of sputum
BAL (>90% diagnostic yield)
Treatment of PJP
Cotrimoxazole 15-20mg/kg/day
Allergy: IV Pentamidine, Dapsone or Atovaquone, Clindamycin + Primaquine
If hypoxic consider adding steroids
Prophylaxis for PJP
CD <200
Cotrimoxazole daily or thrice weekly
Pentamadine three weekly nebulised
Cryptococcal Infection in HIV
Commonly meningitis (sub acute headache and fever) Pulmonary Cryptococcus
Cryptococcal infection in HIV diagnosis
LP: Raised opening pressure, Low glucose and raised WCC and protein
India ink and CRAG positive
Treatment of cryptococcal meningitis in HIV
LP/VP shunt
Amphotericin and flucytosine for 1-2 weeks followed by 8 weeks of high dose fluconazole
Ensure secondary prophylaxis until the CD 4 count rises
Treatment for IRIS
Steroids
Primary Prophylaxis in HIV (ETG)
CD4 <200: PJP –> Cotrimoxazole (Bactrim) either once daily or thrice weekly options
CD4 <100: Toxoplasma –> Cotrimoxazole (Bactrim) either daily or thrice weekly
CD4 <50: MAC –> Azithromycin 1.2gram once weekly or Clarithromycin 500mg BD
Live Vaccines contraindications
Should not be given to patients on anti-TNF or Rituximab
Need to give 4 weeks prior to commencement of same
Flu vaccine in immunosuppressed host
Twice in the first season and then twice thereafter
Caution with giving when patient on checkpoint inhibitor due to cytokine storm thereafter
Screening prior to Anti-TNF/DMARDS
Interferon Gamma assay
Treatment for latent TB infection on a patient pre anti-TNF or DMARD
9 month of isoniazid
Treatment/prophylaxis for patients pre commencement of rituximab with evidence of previous Hep B infection
HbSag+/- with Anti-Hbcore positive: Prophylaxis with Entecavir/tenofovir for 12 months after cessation go B cell depletion
When to commence PJP prophylaxis with cotrimoxazole?
- High dose corticosteroids >16-25mg/day or >4mg dexamethasone for >4weeks
- TNF alpha inhibition
- HIV with CD4<200
- Chemotherapy or monoclonal antibodies which cause prolonged lymphopenia
The ESCAPPM organisms
E: Enterobacter S: Serratia C: Citrobacter A: Acinetobacter P: Pseudomonas P: Porteus Valgaris M: Morganella Morganii
Mechanism of ESCAPPM antibiotic resistance
Inducible beta-lactamases (AmpC-cephalosporinases) which lead to resistance to third generation cephalosporins
I.e When you give someone with enterobacter ceftriaxone it will induce the beta lactamase and then become resistant
Mechanism of ESBL antibiotic resistance
Plasmid mediated inactivation of all cephalosporins
Treatment for ESBL infections
Meropenem or Cotrimoxazole
Mechanism of Vancomycin action
Binds to peptidoglycan terminus D-ala-D-ala in cell walls sequestering the substrate from transpeptidase and inhibiting cell wall cross linking
Mechanism of Vancomycin Resistant Enterobaciae
D-ala-D-ala is changed to D-ala-D-lac si tgar vancomycin cannot bind.
Treatment for VRE
Ampicillin (If sensitive)
Daptomycin
Linezolid
Mechanism of Beta-Lactams
Bind to PBP and inhibit cell wall synthesis/repair
Bacteriocidal
Aminoglycosides mechanism of action
Inhibit protein synthesis by binding to the 30S ribosomal subunit
Gentamicin, Tobramycin, Amikacin
Macrolides mechanism of action
Inhibit protein synthesis by preventing peptidyltransferase from adding the growing peptide attached to tRNA to the next amino acid
Erythromycin, clarithromycin, roxithromycin, azithromycin
Tetracycline mechanism of action
Inhibit protein synthesis by binding to the 30s ribosomal subunit
Doxyxycline, minocycline, tigecycline and tetracycline
Trimethoprim mechanism of action
Binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid to tetrahydropholic acid
Sulfamethoxazole mechanism of action
Inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA)
Fluoroquinolones mechanism of action
Interfere with DNA synthesis by inhibiting topoisomerase thereby preventing bacterial DNA from unwinding and duplicating.
Rifamycin mechanism of action
Inhibit bacterial DNA-dependent RNA polymerase
Nitromidazole mechanism of action
Reduction of the nitro group on the antibiotic by nitroreductases produced by susceptible bacteria.
(Metronidazole/Tinidazole)
Lincosamide mechanism of action
Bind to the 50S subunit of bacterial ribosomes
Clindamycin
Mechanism of action of Linezolid
Binds to 50s subunit prevention of the formation of 70s subunit
Daptomycin mechanism of action
Binds to bacterial membranes and causes a rapid depolarisation which leads to cell death
Side effect of Daptomycin
Elevated CK and myalgias
Control of TB replication is dependent on which factors?
TNF alpha
Interferon Gamma
T cells
What affects the specitity to Mantoux
previous BCG
exposure to other non-TB mycobacteria
Advantage of interferon gamma release assay over Mantoux test
No cross reactivity with BCG or other Non-TB Mycobacterium
What does IGRA test
Previous exposure to TB
Gold standard for TB diagnosis
Culture
TB Meningitis CSF findings
High WCC (lymphocytic)
Elevated protein
Low glucose
Can IGRA determine between antibodies and latent infection?
No - therefore need to treat as if they are latent if IGRA positive
Risk factors for progression to active TB
- HIV (therefore test all patient with TB for HIV)
- Transplant
- Silicosis
- Chronic renal failure
- Biologic therapy (esp TNF alpha antagonist)
- Prednisone <15mg/day
- Diabetes
Treatment for latent TB
- 9 months Isoniazid or - 4 months Rifampicin or - 3 month Rifampicin and Isoniazid
Side effects of Isoniazid
Hepatotoxicity in 2% (increase with age)
Standard short course TB treatment
2 months RIPE –> 4 months RI
Adverse reactions from TB drugs
R: drug interactions, hepatitis, hypersensitivity
I: Hepatisis, peripheral neuropathy (give with pyridoxine)
E: Optic neuropathy
P: Hepatitis, skin, polyarthralgia and gout
Nb Hepatitis P>I>R
Hepatitis in TB
> 2 ULN/Assymptomatic: Monitor
5 ULN or >3ULN with symptoms - stop
If unable to stop TB treatment adopt in amikacin, moxifloaxcin
Most significant TB monoresistance
Isoniazid.
Treatment for Isoniazid resistant TB: 6 months RPE+Levofloxacin
What is MDR-TB
TB resistant to Isoniazid and Rifampicin
Treatment for MDR TB
10% can have short course treatment
Levo/Moxi Bedaquiline Linezolid \+ Clofazimine/Cycloserine
New treatment for TV
Bedaquiline: Oral diarylquinoloe
Delamanid: Nitromidazole, inhibits mycolic acid synthesis
HIV and TB dependent on CD4 count
CD4>200: Typical reactivation of TB
CD4<200: Atypical manifestations including diffuse lung infection (cavitation uncommon) and extra pulmonary TB
HIV and TB dependent on CD4 count
CD4>200: Typical reactivation of TB
CD4<200: Atypical manifestations including diffuse lung infection (cavitation uncommon) and extra pulmonary TB
Early ART treatment for patients with TB outcome
Improves mortality
If
CD4 0-50: Early ART (within two weeks)
CD4>50: ART 8 weeks after starting TB treatment
HIV, TB and IRIS
10-40% of patient with TB/HIV starting ART experience IRIS
Can consider prophylactic prednisone in those with CD4<100
Interaction between TB treatment and HIV
Rifampicin (TB) will increase the metabolism of protease inhibitors and therefore a high dose of a protease inhibitor may need to be used
Specific change to TB treatment for TB meningitis
Substitute moxifloxacin for ethambutol due to high CSF penetration
Give dexamethasone at commencement of treatment
Treat for 9-12 months
TB and Biologics
Higher rates of disseminated disease
Can have rebound disease when biologic removed
Adalimumab>Infliximab>Etanercept
