ID Flashcards
Presentation Dengue fever
- Initial acute phase: Fever, severe headache (retro-orbital pain), malaise, severe joint and muscle pain, N&V
Rash several days after fever onset - Secondary severe phase (3-7 days after sx onset; ~ when fever starts to subside): haemmhoragic shock
- > skin: petechiae, purpura, bruising
- > bleeding from gums, nose, eyes
- > intestinal and other internal bleeding
- > thrombocytopaenia
- > late eosinophilia
Pertussis
‘whooping cough’
bacteria - bordatella pertussis
After 1 to 2 weeks and as the disease progresses, the traditional symptoms of pertussis may appear and include: Paroxysms (fits) of many, rapid coughs followed by a high-pitched “whoop” sound. Vomiting (throwing up) during or after coughing fits. Exhaustion (very tired) after coughing fits
- often whooping cough occurs in 6mo-5 year olds. may be absent in older or younger people
- may be dehydrated with conjunctival or facial petechiae from intense coughing
Live vaccines
Rotavirus
MMR
Varicella
IN influenza
BCG
Travel - yellow fever
Immunology of vaccination
mimic response to infection without severe disease
Vaccine injection -> attracts dendritic cells, monocytes, neutrophils -> activation of those cells following Ag presentation -> migration of those cells to draining lymph node -> in LN you have activation of T and B cells
How do toxin-mediated vaccines work
High yield strain of C tetani is cultured to produce commercial toxoid which is harvested, purified and detoxified -> IgG levels correlate with protection
ex: tetanus
Conjugate vaccines - Mechanism
Benefits
Ex
- A conjugate vaccine is a type of subunit vaccine which combines a weak antigen with a strong antigen as a carrier so that the immune system has a stronger response to the weak antigen.
- Usefully for vaccines against bacteria which are protected by polysaccharide capsule
- (The three most common causes of bacterial meningitis –
- Neisseria meningitidis (the meningococcus A,C,W,Y)
- Streptococcus pneumoniae
- Haemophilus influenzae type b (Hib)
Benefits
- T cell dependent
- high serum levels IgG
- produces long-lasting immune memory
- Decreases carriage which produces broader herd immunity
Generation of B cell memory responses
Generated in response to T-dependent Ag in the germinal centres (spleen/lymph nodes) in parallel to plasma cells.
At their exit, they differentiate into memory B cells that transiently migrate through blood towards extrafollicular areas of spelln and nodes
Persist there as resting cells until re-exposed to their specific Ag
On secondary exposure, memory B cells readily proliferate and differentiate into plasma cells
-> secrete large amt of high affinity Ab that can be detected in serum a few days after boosting
Vaccine side-effects
inactivated vs activated
Inactivated
- SE within 72 hours
- Fever, local reaction
Live attenuated
- Delated side effect
- MMR: 5-14d (peak d10), fever, febrile convulsion (incr risk), rash
- Varicella, rotavirus - fever, vomiting
- Rotavirus -> intussusception (up to 7 days following first vaccine)
Anaphylaxis very rare (1 case per million vaccinated)
Immune compromised individuals - how does this affect the vaccination schedule?
Live vaccines are generally CI as they can cause vaccine-related disease due to replication of the vaccine virus/bacteria
Includes BCG, oral typhoid, yellow fever, MMR, VZV
Rotavirus can be given except in case of intussusception
Household contacts should be vaccinated, incl with live vaccines (MMR, rotavirus)
Tetanus Vaccination schedule
Vaccination
o Immunisations at 2,4,6 months then boosters at 18 months, 4 years and 10-15years
o Need 2x boosters to provide lasting immunity until middle age
o 10 year boosters no longer given but provides indication of how long immunity last (eg if treating someone > 10 years post booster, repeat booster)
o DTPa = childhood vaccine, increased doses of diphtheria and pertussis, dTpa = adult vaccine
Passive vs active immunisation
- Passive immunisation = acquisition of PRE-FORMED antibodies
- Natural: Ab transfer from mo to baby across placenta
- Artificial: for example give HSV, hep B or varicella Ig to a pt after tehy are exposed to try to stop them developing the disease
- Active immunisation = administration of an antigen to stimulate the body’s OWN immune response
- via Infection
- or via immunisation
Types of vaccines
- examples
Effect on immunity
Whole organism vaccines
i. Attenuated (live)
ii. Inactivated (killed) - old pertussis
Subunit
(acellular pertussis, 13vPCV, HiB, HepB)
Recombinant protein (IPV, Hep A+B, Influenza)
Polysaccharide (pneum23V, men polysaccharide)
Conjugated
- Rubella
- HIB
- pneumococcal 13
- Men C
Toxoids (Diptheria, tetanus)
Viral vector (covid-19)
Live vaccines/replicative
- self replicating
- relatively long lasting immunity, mimics natural infx
Inactive/Nonreplicative
- preformed Ag mass
- relatively short lasting immunity, may require boosters
Vaccine adjuvant . what is it?
Traditionally based on whole bacteria (CFA) or bacterial cell walls (IFA)
- Gives danger signal to immune system – stimulates TLR and PRR that turn on the immune response
- Amplifies immune response
What extra vaccines do these patients groups need to obtain?
- Indigenous
- Umnderlying medical conditions
Indigenous - Hep A (12mo), Tb and influenza >6mo
Underling medical conditions - pneumococcal (13v at 6mo, 23v at 4yo), influenza >6mo
Preterm- pneumococcal (13v at 6mo, 23v at 4yo), influenza >6mo, Hep B at 12 mo
*Note- give vaccines at chronological age (without correcting for prematurity)
Largest R out of vaccinatable infectious diseases?
Measles R12-18
Pertussis R12-17
Note
- Covid
–> alpha R 2.5
–> delta 5-7
–> omicron ?10
HPV
- disease
- vaccine
- vaccine schedule
Disease - risk of cervical cancer (high risk is 16, 18)
- most cleared within 12-24 mo but 10% persist
Vaccine is recombinant (virus-like particles) . Does NOT contain viral DNA and cannot cause infection.
3x doses at age 12-13yrs
- ok if immunonocompromgsed
- not if pregnant
Which vaccine is CI in HIV pts regardless of CD4+ count?
BCG vaccine
Typhoid + polio oral live attenuated (use inactivated instead)
Varicella post exposure options
Active immunisation (Varicella vaccine) - for healthy hosts within 3-5 days of exposure if haven’t received the full (2) -dose series.
Passive immunisation (Varicella-specific Ab) - in immunocompromised if haven't received the full dose series OR if bone marrow transplant within 24 months or if requiring immunosuppression or having chronic GVHD
Effect of bone marrow transplant on immunity
- Lose immunity to pathogens which they were previously immunised
- Require immunisation against pneumococcus, HiB, tetanus etc
- Avoid live vaccines for 24mo following HSCT (use inactive vaccines or passive immunisation when possible)
- Live vaccines can be given >24mo following HSCT if there is no immunosuppression or GVHD
Indication for hep A vaccination
Travel to endemic areas in children >1yo
Almost universal seroconversion within 4 weeks of vaccination (repeat testing for seroconversion not indicated)
Single dose provides immunity for at least 1 year
Second dose recommended to prolong duration of protection
Least effective vaccine at providing long-lasting immunity
pertussis
Considerations for vaccination of patients with congenital heart disease
- May have asplenia or functional hyposplenia
- May have associated T cell deficiency
- May have increased risk of deterioration/ collapse following immunisation
Considerations for vaccination of oncology patients for those who have NOT completed primary vaccination vs those who HAVE COMPLETED primary vaccination
NOT completed primary vaccination
o Live vaccines contraindicated
- Those receiving immunosuppressive therapy
- Poorly controlled disease
o Administer to seronegative person 3 months after completion of chemotherapy if in remission
- Defer if recent IVIG
o Inactivated vaccines can be given however immune response suboptimal
COMPLETED primary vaccination
o Given a booster course following completion of treatment
How does the rotavirus vaccine work?
Live attenuated
Rotarix - 2,4 mo (Live attenuated human rotavirus vaccine)
-> Monovalent human G1P1A strain – protects against non-G1 serotypes on the basis of other shared epitopes
vs Rotatec 2,4,6 mo (Live attenuated pentavalent human–bovine reassortant rotavirus vaccine)
Prevents rotavirus gastroenteritis of any severity in 70% of those vaccinated + prevents SEVERE gastro req hospitalisation in 85-100% of those vaccinated
CI if previous history of intussusception or a congenital abnormality that may predispose to intussusception (ie mocker’s diverticulum)
BCG vaccine
- efficacy
- neonatal vaccination indications
Efficacy
a. 80% protection in the first 15 years of life; reduces subsequently
b. Greatest benefit in preventing miliary tuberculosis and tuberculosis meningitis in children, and pulmonary TB in adults
c. Best efficacy in newborns and infants not previously exposed
Neonatal vaccine indications
a. Living in a house or family with a person with either current or past history of TB
b. Household members who within the last 5 years have lived 6 months or longer in countries with high TB rates
c. For first 5 years will be spending >3 months in high-incidence country
Vaccines recommended in pregnancy and why?
- *DTP** in third trimester
- more effective in reducing the risk of infant pertussis than maternal vaccination post partum
- *Influenza** anytime during pregnancy
- protects the mother, as pregnancy increases her risk of severe influenza, and also protects her newborn baby in the first few months after birth
Live vaccine deferred until after delivery - contraindicated
When can you vaccinate following blood products?
Live vaccines (MMR/VZV) specifically
• 5 months after PRBC
• 9-11months after IVIG
This is because low levels of antibodies may be present in the blood product that may impair the immune response to the live vaccine.
- How do penicillins work?
- Which penicillin would you use for gram positive cover alone (oral and IV options) without staph cover?
- Which penicillin would you use for MSSA cover?
- Which would you use for pseudomonas cover?
- Which would you use for broad GP and GN cover including pseudomonas?
- MRSA cover
- Inhibit cell wall synthesis by inhibiting binding of penicillin binding proteins (irreversibly bind the binding site)
- Oral – phenoxymethylpenicillin/penicillin V -> amoxicillin, ampicillin; IV benpen/pen G
- Fluclox or diclox
- Ticarcillin, piperacillin
- Amox/clav (augmentin), ticarc/clav (timentin), pip/taz (tazocin)
- IV Vancomycin; PO clindamycin, bactrim, doxycycline, linezolid
Why do we avoid ceftriaxone in neonates?
Risk of biliary sludging
Which generation cefalosporins can cross BBB (give examples x3)
Third (ceftriaxone, ceftazidime, cefotaxime)
How do cephalosporins work?
Inhibit cell wall synthesis (target penicillin binding proteins and disrupt cross-linking of peptidoglycan to prevent formation of bacterial cell wall)
IE - same as penicillins, but are less susceptible to beta lactamase activity
Which cefalosporins cover pseudomonas?
Ceftazidime (third gen) and cefepime (4th gen)
How is HIV transmitted to children?
Vertical transmission (transmission from mother to baby intero 5-10% chance, during labour/delivery 10-15% chance or via breastfeeding 5-20% chance)
What is the highest risk period for vertical transmission of HIV from mother to child?
During labour and delivery 10-15% risk (due to +++ secretions and blood)
How do you prevent transmission of HIV from mother to child?
- Mother should be on antiretroviral therapy -> suppression of viral load
-
Post-exposure prophylaxis for the infant within 4 hours of birth.
- > if very low risk setting, AZT monotherapy for 2 weeks
- > if low risk: AZT mono therapy for 4 weeks
- > if high risk (high viral load or you don’t know anything about mother’s treatment): combination therapy (AZT+3TC+NVP) - Avoid BF (note this is not a complete CI, excl BF > mixed feeding)
Risk stratification for mother and baby for HIV transmission
V low risk - LOW/suppressed viral load (<50copies/ml) & on cART >10weeks (from 28 weeks GA)
Low risk - low viral load >= 36 weeks gestation.
High risk - uncertainty about adherence or viral load or whether mother is on cART
When to commence cART for HIV pos mothers who are pregnant?
By 28 weeks gestation latest (at least 10 weeks prior to delivery)
Mode of delivery for HIV positive mothers
If viral low LOW (<50copies/ml): NVD
If >400 copies/ml: C/S
If 50-400 copies/ml: could do either. take other factors into consideration.
Diagnosis of HIV in children and teens
HIV serology (Ag and Ab)
Diagnosis of HIV in infants
- HIV DNA PCR
-> at birth 50% sensitivity -> 100% by 3 months
-> 99.8% specificity at birth and 100% by 1 mo
Ideally you do serial testing x3 tests, last at 3months (if neg then, considered neg for HIV)
HIV presentation
Initial non specific pres:
- FTT
- Dev delay
- Encephalopatjy
- B/L parotiditis
- Fever
- Lymphadenopathy
- Hepatosplenomegaly
- Oral candiasis
Pregression of immunosuppression and progressive CD4 count
- opportunistic infections (PJP, HSV, Tb, CMV, molluscum contagiosum)
Opportunistic infections
- PJP
- Molluscum contagiosum
- HSV
- Tb
- NTM (Non Tb mycobacterium)
- Disseminated CMV
- Oesophageal candiasis
- HIV encephalopathy
- Toxoplasmosis of brain
- Recurrent bacterial pneumonia
Natural history of perinatal HIV
2 patterns
- Rapid disease progression
- Slower disease progression over 5-10 years (80-85% of patients in developed regions vs 55% in developing regions)
Pathophys of HIV infection of host
Enters via CD4 receptor -> reverse transcription RNA into HIV DNA -> uses cell’s molecular mechanisms to transcribe HIV DNA into own cells’ DNA (via ‘integrase’) -> then it is transcripts into HIV RNA which then leaves cells to infect over cells
Treatment of paediatric HIV
2 nuclear reverse transcriptase inhibitors (NRTIs) + another agent (ie protease inhibitor, integrate inhibitor etc)
Usually coformulated 2-3 drugs in one tablet, taken once a day = ‘fixed dose combination pills’
Monitoring of HIV
- aims in treatment
CD4 count (aim >500 cells)
Viral load (aim undetectable <5o copies/ml)
What group has highest risk of drug resistance w HIV medications
Perinatally acquired HIV have much higher rates of resistance due to length of exposure and time
Morbidities assoc w long-term HIV
Metabolic (dislipidaemia, CV cx)
Poor bone health
Lower neurocognitive outcomes (school performance)
Infectious diseases w largest burden of morbidity and mortality
- Influenza
- HPV
- Pneumococcal disease
- Meningococcal disease
- Shingles
MOA for Pfizer vaccine.
What is the main SE and limitation for use in resource limited places?
mRNA based vaccine: encodes SARS-CoV2 spike protein, wrapped in lipid nanoparticles
-> incr expression and stimulation of neutralising Ab
Needs storage at -60 to -80C
Main SE - pericarditis esp in males after 2nd dose
Currently all children >=12yo eligible
R0 reproduction rate - what does this represent?
Mean number of infections generated during the infectious period of a single infected person
What is sepsis?
main causes in chidren
systemic inflammatory response to a suspected infection
Causes
- s aureus
- N meningititis
- GAS
- e coli
Toxic shock syndrome
Definition
Causes
Presentation (what is the MAIN feature?)
Causes by super Ag from either
- staph (Staph enterotoxin)
- or group A strep (strep exotoxins A and B) - 60% culture +
Features
- HYPOTENSION is main feature!
- fever
- renal impairment
- coagulpathy
- maclar rash
- soft tissue necrosis (GAS)
Pathophys of super Ags
- Super Ag overcomes binding between T cell MHCII and Ag presenting cell of -> rapid non-specific activation of inflammatory response
Method of resistance and tx of MSSA
Beta lactase production
- need fluclox or diclox or cefazolin (1st gen cephalosporin)
MRSA - method of resistance to methicillins
Carry a penicillin-binding protein, PBP 2a (encoded by genes mecA and mec C), that has a low affinity for all beta-lactam drugs other than those specifically designed to target it
VRSA mechanism of resistance to vancomycin
VanA gene resulting in change in peptidoglycan target and thus vancomycin resistance
N meningititis
- what sort of bacteria is it?
- methods of pathogenicity
- treatment
- who needs treatment
- Gram neg diplococcus
- Encapsulated - polysaccharide capsule for survival in blood.
- Produces endotoxin which produces sepsis like picture
Contains factor H binding protein - inhibit C’ cascade and alternative pathway (critical for encapsulated organisms)
Pili - enables adherence to and crossing BBB
Treatment of meningitis - IV ceftriaxone
Contact Prophylaxis
- cipro (rifampicin in young children)
- ceftriaxone in pregnancy
Who needs prophylaxis?
- all household contacts or day care contacts exposed within 10 days of index case illness onset
- all healthcare contacts giving mouth to mouth or inadequate PPE within 10 days
Causes of encephalitis
Viral
- HSV
- Varicella (adolescents)
- Enterovirus
- Paraechovirus
- Flu
- Covid
Bacterial - Mycoplasma pneumonia, Tb
Fungal - Cryptococcal species
Parasitic - Malaria, toxoplasma gondii
Immune mediated
Note 64% cases no pathogen identified
Presentation of encephalitis
- General
- Seizures is classic of what cause?
- Drooling is classic of what cause?
- Flaccid paralysis is classic of what cause?
- Preceding pneumonia in what causes?
Inflammation of the brain (vs meningitis- of the meninges)
- Cognitive dysfunction
- Behavioural changes
- Seizures - classic of immune mediated
- Drooling - classic of rabies
- Flaccid paralysis - classic of enterovirus
- Preceding pneumonia - in influenza or mycoplasma
CSF interpretation
Normal
Viral
bacterial
Tb
Fungal
Normal values:
- Neuts 0
- Lymph <22
- Protein <1
- Glucose >2
Bacterial
- High pressure
- Turbid colour
- High protein
- Low glucose
- low glucose CSF:serum ratio
- Positive gram stain
- High WCC (>500)
- >90% polymorphs
Viral
- Pressure normal or mildly incr
- Clear
- Low protein
- Normal glucose (high glucose CSF:serum ratio)
- Normal gram stain
- High WCC (<1000)
- monocytes
- can also have very high polymorphs
Fungal
- Fibrin web appearance
- Normal protein
- mildly low glucose
- low glucose CSF:serum ratio
- WCC moderately elevated (100-500)
- monocytes
Classic presentation of tetanus
- Trismus (spasm of the jaw muscles, causing the mouth to remain tightly closed)
- Opisthotonos (spasm of the muscles causing backward arching of the head, neck, and spine)
- Spasms
- Seizures
- Autonomic instability
What bacteria causes tetanus (and type of bacteria)
Pathophys of infection
Clostridium tetani - spore forming GP anaerobic bacillus
From stool and soil
Produces an exotoxin which is transported though peripheral nerves and INHIBITS ACH release from motor nerve end plates
- binds at the NMJ, enters motor nerve, travels peripheral to spinal cord -> acts on inhibitory neurons by preventing release of GABA and glycine -> leads to contraction and rigidity
Tetanus treatment
Local tetanus Ig and excision of site of infection
AND
Systemic tetanus Ig
and Metronidazole
With ICU, benzos, Mg
Indications for tetanus prophylaxis w wounds
For minor clean wounds:
- Don’t need tetanus Ig.
- For Tetanus vaccine if not fully immunised or if due for routine booster anyway (booster needs to be within 10 yrs)
For unclean and/or major wounds:
- Need tetanus Ig
- Also need vaccine If >5 years since last booster
What kind or virus is RSV
How does pavilizumab work?
How does it spread?
Enveloped single stranded RNA virus
- G protein required for attachment
- F protein required for host cell fusion (blocked by palivizumab thus blocking cell fusion)
Droplet and contact spread
Risk factors for severe RSV
- Cyanotic heart disease
- PPHN
- Prematurity
- Bronchopulmonary dysplasia (CLD)
- Immunosuppression (BMT, lymphopaenia, HIV etc)
How does influenza bind/attach to epithelial cells?
How does it escape from cells?
INfluenza contains 2 glycoproteins:
- Haemagglutinin (HA) facilitates binding to respiratory epithelium, entering cells
- Neuraminidase enables the virus to be released from/exit the host cell (target of influenza tx - inhibitors)
Highest risk for severe influenza
- <5
- CF
- Haem malignancy
- Neurodevelopmental disability
Complications of influenza
- Secondary pneumonia (bacterial - s aureus)
- Myositis
- Reye syndrome (acute noninflammatory encephalopathy with fatty liver failure assoc w influenza, varicella and NSAID use)
- Guillan barre syndrome (progressive bilateral ascending symmetric weakness starting at feet and hands)
- Seizures
- Necrotising encephalitis
Antiviral treatment for influenza - how does it work and indications for use
Neuraminidase inhibitors (zanamivir, oseltamivir, peramivir) trap influenza in host cells
Reduce duration of sx by 1 day in healthy adults
Antiviral tx should be offered as early as possible to those:
- For severe, complicated or progressive ilness
- Children at HIGH risk of cx
- Household contacts of those at high risk
S pneumonia - what type of bacteria is it?
Gram positive Diplococci
Aerobic
ENCAPSULATED! Capsule is pathogenic
Asymptomiac carriage in 20-60% of children but can cause invasive disease
S pneumonia - vaccination schedule
2, 4, 6 and 12 mo (prevenar 13 = conjugate vaccine, includes 13 of the most invasive serotypes)
indigenous and high risk children recieve the 23v vaccine at 4 years of age (booster 5 years later)
RF for invasive pneumococcal disease
Immunodeficiency
- Primary immunodeficiency
- Prematurity
- Transplant
- HIV
- Malignancy
Other
- Chronic disease (lung/kidneys/liver/lungs etc)
- Sickle cell
MIC targets for s pneumonia susceptibility (CSF vs non-CSF)
- what abx to use for sensitive, intermediate or resistant strains?
MIC
- Non-CSF isolates <= 2
- CSF isolates <0.1
are susceptible to penicillins
-> note for intermediate susceptibility: still use penicillin but at higher dose
Resistant: Ceftiraxone or vanc
Pertussis
What type of bacteria is it?
Pathophys of infection
Presentation
Treatment
Gram negative aerobic bacilli
Secretes toxin
-> incr bradykinin production and increases 1/2 life of bradykinin -> stimulates cough receptors (‘100 day cough’)
Note long incubation period (up to 3 weeks!)
Coughing paroxysms, mostly without fever. often to point of vomiting.
Tx w Oral macrolides (azithromycin. erythromycin avoided as it has been shown to incr rates of pyloric stenosis)
HIB
what type of bacteria is it?
Treatment
Gram negative coccobacillus
Serotype B is the strain responsible for the majority of severe disease
-> cause of meningitis, sepsis, SA, epiglottis, empyema (many fewer cases now w vaccination)
Treatment with 3rd generation cephalosporins (ceftriaxone- meningitis cover)
Rotavirus infection
what type of virus
Pathophys of infection
vaccination schedule
treatment
Non enveloped dsDNA virus
- damage to gut epithelium -> mixed osmotic, secretory, exudative diarrhoea
- Release of 5HT -> vomiting and delayed gastric emptying
- PE2, IL6 -> fever
Vaccination: live vaccine at 2, 4 months
- reduces hospitalisation and disease severity
Mx - rehydration and monitoring of electrolytes. can supplement zinc
what is most common cause of SA in children <4yo
<3mo: Staph, E coli, GBS
>3mo <5yo: Kingella kingsae
- presents w unusual joints for SA
- classically lower ESR and CRP than s aureus infections
- often culture negative (need to order DNA PCR instead)
- rare cause of endocarditis in children w heart disease
Measles - what sort of pathogen?
What presentation ?
Cx?
Diagnosis?
RNA virus
4 Cs: Cough, coryza, conjunctivitis, koplick spots
Fever, confluent rash (onset 3-5 days after symptoms begin), miserable
Complications - encephalitis, myocarditis
diagnosis: Measles IgM or PCR from throat or nasopharynx
Complications of varicella infection
Treatment of varicella
Bacterial superinfection - group A strep
Cerebellar ataxia
Aseptic menigitis
Incr stroke risk
transverse stroke risk
IV or oral acyvlovir, valaciclovir
Antiviral spectrum of activity
Treatment of neonatal/infant varicella exposure
Main causes sepsis in newborns (EOS)
What is empiric treatment for this?
EOS
- Group B strep
- E coli
- Listeria
- HSV
Mx
- Benpen and gent
- Benpen and cefotaxime
Main causes meningitis in toddlers
What is empiric treatment
Bacterial
- Strep pneumoniae
- N meningitidis
- Haemophilis influenza
Viruses: enterovirus, HSV
Treat with cefotaxime and acyclovir as empiric cover
What is the single most important factor in blood culture collection?
Blood volume
-> minimum 1 ml but should be ~ child’s age in ml
Main causes of sepsis (not meningitic) in children >3mo (not immunocompromised)
- S aureus
- Strep pneumoniae
- GAS
- N meningitis (particularly in adolescents)
Empiric treatment: ceftriaxone and flucloxacillin
Main causes of sepsis in immunocompromised patients eg oncology patients
What is empiric treatment
Pseudomonas
Candiasis
Line site infections - Staph
Amikacin and tazocin (piperacillin tazobactam) +/- vancomycin if high risk/very unwell
Neuraltamivit, peramivir, osteltamavir, zanamivir how do they work, what is their spectrum?
Neuraminidase inhibitors specific for influenza
interferes with host cell release of complete viral particles
Valaciclovir and Aciclovir
MOA
Spectrum of action
Antiviral is converted by viral thymidine kinase to ACV MP then by host cell kinases to active product which inhibits and inactivates HSV DNA polymerases
Active against:
- HSV
- VSV
NOT active against CMV
- CMV viral thymidine kinase doesn’t convert acyclovir to ACVMP very well
Ganciclovir and Valganciclovir
MOA and spectrum of action
CMV as well as HSV, VZV
Valganciclovir (PO form) an oral prodrug that is rapidly converted to ganciclovir (IV form)
Ganciclovir MOA: inhibits viral DNA polymerases and disrupts DNA chain elongation
Foscarnet and Cidofovir
Spectrum of action and MOA
MOA: pyrophosphate analog. Selectively inhibits the pyrophosphate binding site on viral DNA polymerases.
BROAD spectrum
Foscarnet:
- HSV
- VZV
- CMV
- HHV6 and 7
- (NOT influenza)
Cidofovir - all of the above PLUS:
- Adenovirus
- BK/JC
MOA azoles
Inhibits formation of fungal cell membrane via
- inhibition of fungal enzyme (14alpha demethylase) that converts lanosterol to ergosterol (component of fungal cell membrane)
‘fungins’
Echinocandins
MOA
Stop synthesis of gluten in cell wall via non competitive inhibition of the enzyme 1,3 beta gluten synthase
Polyenes (amphotericin, nystatin) MOA
Binds ergosterol in fungal membrane causing cell membrane to become leaky
what types of bacteria have a peptidoglycan cell wall?
Gram positive bacteria
What is MIC
Lowest concentration of abx that stops bugs from growing
Time above MIC - what abx
Antibiotics
- Beta lactams (beta lactams, carbopenems, cephalosporins)
- Macrolides (erythromycin, roxithromycin, azithromycin and clarithromycin)
Method
- Used as continuous infusion, give more often as bigger doses
- Goal is to maximise duration of exposure
Peak MIC
what abx work via this?
Aminoglycosides (gentamicin, tobramycin etc)
Goal is to maximise concentrations
- has long post-abs effect even after abx is withdrawn or level not
AUC/MIC (Area under curve over the MIC)
What abx work according to this?
Fluoroquinolones (cipro)
Vancomycin
Azithromycin
goal is to maximise amount of drug
What defines an ESBL?
what do you treat them with?
=extended-spectrum beta lactamases
Resistant to 3rd gen cephalosporins (ceftriazone, ceftaz, cefotax etc) and broad spectrum penicillins
Need aminoglycocide (gent; don’t cross BBB) or carbapenem/meropenem (CNS cover)
What does ciprofloxacin NOT cover?
what does it cover?
Gram positives (Enterococcus MRSA, MSSA, CONS) and anaerobes
(Good Gram Neg cover - pseudomonas, enterobacter and atypicals)
What subclasses fall under beta-lactams
what bug is resistant to all of these?
penicillins
cephalosporins
carbapenems
MRSA is resistant to ALL of these - req vanc which is a glycopeptide
What bugs don’t penicillins cover?
C diff
MRSA
Pseudomonas (except for tazocin )
Atypicals
What bugs don’t cephalosporins cover?
Enterococcus!!!
MRSA (except ceftaRoline)
C diff
Atypical
What bugs don’t carbapenems cover?
C diff
MRSA
Enterococcus
Atypical
Pseudomonas is covered (except with erbapenem)
Bioavailability of vancomycin
Zero oral availability IV only (except given oral in c diff BECAUSE it is not absorbed)
Major toxicity with vancomycin
AKI
How do you treat red man syndrome
SLOW vancomycin infusion (is NOT an allergic reaction)
Major toxicity w daptomycin
Rhabdomyolysis - needs weekly CK check whilst using
Linezolid major toxicity
peripheral neuropathy and bone marrow suppression w extended use (peripheral neuropathy is irreversible - particularly optic nerve)
Glycopeptides (vancomycin, daptomycin, teicoplanin and linezolid)
what do they cover?
Treats GP bugs including MRSA
NO coverage of gram negatives, atypicals or anaerobes (except vanc for c diff)
Fluoroquinolones (cipro, levofloxacin, moxifloxacin)
GN (Enterobacteracae and psueudomonas) + atypicals
Moxiflox also covers GP and anaerobes
Tetracyclines
give example
what is it used for?
doxycycline . good oral bioavailability
MRSA -> used often for MRSA skin infections in community.
Not reliable for GN coverage
Memorise (p falciparum and P vivax)
Malaria stages in blood film
Pakistan refugee with
progressive erythematous papule to nodule to ulcerating lesion, enlarging over time
Painless
what is the diagnosis?
Cutaneous leishmaniasis
confirmed on biopsy
Phillipines
playing Barefoot in sand/dirt
Itchy snakelike/serpigenous rash
systemically well
what’s the diagnosis?
treatment?
Caused by contact w dog/cat faeces
= CLD (cutaneous larva migrans)
treatment w oral albendazole or ivermectin
Parvovirus B19
When is it most contagious?
What is the classic presentation?
Ix (and limitation) and tx
Most contagious in the few days preceding rash - this is when the viraemia peaks.
Affects SCHOOL AGED children (5-14 days)
Non-specific viral prodrome (fever, headache, myalgia) followed by ‘erythema infectiosum’ rash about 1 week later (cheeks and papular-pruritic glove and sock syndrome to hands/feet)
diagnosis w serology (note IgM stays positive for up to 3 mo)
Mx- supportive
Presentation of rubella and when does viral shedding occur relative to this?
Presentation:
Prodrome eye pain, conjunctivitis, headache, fever, malaise and tender lymphadenopathy
Forchheimer sign - petechiae on softpalate (20%) - see photo
50% asymptomatic
Rash on face, trunk, hands and feet (viral shedding 5 days pre to 4 days post rash)
Koplick spots - are a sign of what?
Measles.
What are the 4 ‘Cs’ of measles presentation
how does this relate to the viraemia?
Cough
Coryza
Conjunctivitis
‘Koplik’ spots (white spots in oral mucosa) - these are associated with viraemia
Rash develops days 4-7 of illness, starting on FACE
Serology will be positive 4-14 days after rash
If investigating before this, do PCR on throat or nose swab
Hand foot and mouth disease
What is the presentation
what age group does it affect
what virus causes this
Children <5yo
Spread via F/O route
Sore throat, fever and papulovesiscular lesions to palms, soles and oral mucosa. can also be on buttocks and genitals.
Caused by coxsackie viruses (also echoviruses and enteroviruses)
Cx: aseptic meningitis, encephalitis ?neurodevelopmental changes
What congenital infection is this rash associated with?
Congenital rubella syndrome (blueberry muffin rash)
due to extra medullary haematopoesis
Also CMV
Congenital rubella syndrome
Ears: SNHL
Eyes: Cataracts
Heart: Congenital heart disease (pulm stenosis or PDA)
Skin: Blueberry muffin rash (petechial/purpuric rash)
Bones: radiolucent bone lesions at metaphyses
Tx of rheumatic fever
National recommendations for secondary prophylaxis in ARF are IM benzathine penicillin every 28 days for 10 years or until 21 years old (whichever is longer).
For ARF with moderate rheumatic heart diseases is is for 19 years or until 35 years old (whichever is longer).
With severe rheumatic heart disease or post surgery it is up to 40 years or lifelong.
Sx of acute rheumatic fever
Major critera = ‘JONES’
- Joint inflammation (migratory poly arthritis)
- Heart damage (new murmurs)
- Nodules (elbows, knees, forearms)
- Erythema marginatum (rash)
- Sydenham’s chorea (rapid involuntary movement of face and hands)
Minor
- raised ESR, CRP
- fever
- arthralgia
- prolongued PR interval
- h/o rheumatic fever/rh heart disease
What antibiotics should a person with G6PD avoid?
Nitrofurantoin
Cotrimoxazole (Bactrim/septra)
Antimalarials (quinine, chloroquine, primaquine)
Due to risk of haemolysis (blood film ft target cells, bit cells, spherocytes and some fragmented cells)
what is the most common cause of viral hepatitis?
transmission/incubation/clinical illness and serology
Hep A Virus
- Transmission - faecal oral route
- Incubation - 2 weeks
- Malaise Prodrome (2 wks; HAV in stool) - flu-like illness (malaise, N&V, diarrhoea, headaches); N bili but AST elevated and urine bilirubin and urobilinogen incr
-
Jaundice (2-4wks; anti-HAVIgM pos) - cholestatic jaundice (elevated AST, ALP, bilirubin), pruritis, mild hepatosplenomegaly
- Rare cx: fulminant hepatic failure, myocarditis, arthritis, renal failure
-
Recovery phase: ALT normal, IgM decr and IgG increases
- self-limiting; supportive only
- No carrier state
Serology: Serum ALT is first to rise with viraemia
Molluscum contagiosum
Returned from India (or anywhere in tropics) with sudden onset fevers, myalgias, headahce and this eye sign (see photo) .
Had been fresh water swimming.
Whats the diagnosis?
Cx of such infection?
leptospirosis (urine/faeces of infected rats, cattle -> water; transmitted to humans mostly via fresh water swimming)
Sx: abrupt onset of fever, rigors, myalgias, and headache in 75 to 100 percent of patients.
-> Conjunctival suffusion (pic) in a patient with a nonspecific febrile illness should raise suspicion for the diagnosis of leptospirosis
- complicated by renal failure (non-oliguric w hypoK, hypoNa)
- uveitis
- hemorrhage
- ARDS with pulmonary hemorrhage
- myocarditis
- rhabdomyolysis. (See ‘Clinical features’ above.)
Spot diagnosis?
Diptheria
Formation of characteristic grey pseudomembrane
Returned traveller rfom hiking in north america p/w this rash (localised), fever, chills and malaise.
Diagnosis?
-
Lyme disease = bacterial infection Boriella Burgdorferi
- From tick bite
- early signs/sx (3-30d after tick bite)
- Erythema migrans rash (bulls eye at site of tick bite
- constitutional/flu like sx
- disseminated disease (days to months after exposure)
- meningitis
- cranial neuropathy
- carditis -heart block, myopericarditis
- arthritis
- Ix: elevated CRP, ALT, AST, CK
- diagnosis via enzyme specific immunoassay or IgM and/or IgG western blot
- tx: doxycycline
