Micro Flashcards
Adverse effects of antimicrobials
GI upset Fever & Rash (SJS) Renal dysfunction Anaphylaxis (very rare)* Hepatitis (more common to have derranged LFTs than full blown hepatitis)
*don’t let the fact that someone has a mild allergy disuade you from using that abx if it is the best abx for that patient.
What determines what abx we should choose
CHAOS
Choice
Host factors
- E.g. Age (can’t use tetracyclines in kids cos they deposit in bone. Also kids, don’t give 6x/day) Pregnancy (can’t use folate antagonists e.g. trimethoprim), Immunocompromised, Renal failure, Liver failure, severity of disease, interactions with other drugs e.g. statins and fusidic acid -> liver failure, warfarin, SSRIs and lineozlid,.
Antimicrobrial susceptibilities
Trust policies
Organisms
E.g. pneumonia - pneumococcus, haemophilus, moraxella (g-ve) (Amoxicillin is broad and covers pneumo and haemophilus)
Site
Some sites are difficult to treat e.g. bone, CNS, some abx are difficult to get into the blood and wouldn’t be good for a septicaemia
ALWAYS LOOK AT LOCAL POLICIES.
How do we identify the infective organism?
Gram stain the joint aspirate, CSF or pus
PCR/immunoflorescence - rapid antigen detection
When do and don’t we change from IV to po abx?
We change from IV to PO asap i.e. 48 hours after pt is stabilised.
Exceptions: meningitis as PO doesn’t reach csf, endocarditis and osteomyelitis
Why is it important to measure the serum level of abx (less in clinical context and more in research context)
The level of the peak of the drug predicts how successful the drug will be (adjust dose if too high or lose)
The level of trough predicts elimination (concern if it isn’t being eliminated) (adjust interval if too high or low)
TYPE 1- This is important for aminoglycosides as they have a dose dependent effect. therefore they usually have a OD regimen where you try to maximise the peak.
TYPE 2 - For pencillins, the time above the MIC is important and therefore the regimens are usually 3-4tds.
TYPE 3 - Clinda, Vancomycin - its the area under the curve i.e. the total amount your body receives over time that determines efficacy.
What specific time recommendations exist for antimicrobials?
Generally, short as possible a part from:
N meningitides meningitis - 7d
Acute osteomyelitis in adults - 6 weeks
Bacterial endocarditis - 4-6 weeks
Gp A Strep (pharyngitis) - 10 d (rheum and glom)
Simple cystitis - 3d
Generalisations for abx indications for specific diseases
Skin/soft tissue - worried about strep/staph - fluclox (unless MRSA or worried about pen allergy)
Mild CAP - pneumococcus hib and moraxella - amoxicillin
Severe - clina + coamoxiclav (worried about resistance)
Pharyngitis - ben pen 10d
HAP - tend to be g-ve e.g. pseudomonas - cephalosporin, ciclosporin, tazobactam
Meningitis - Neisseria menigitids, S pneumoniae - Ceftriaxone (listeria if neoatae, lederly or pregnant - add amoxicillin)
UTI - Trimethoprim 3d
Hospital UTI - (trimeth resistance high) so cephalexin or co-amoxiclav
What is the eagle effect?
Effect that bacteria are only susceptible to abx when dividing so if they are in the stationary phase e.g. in group a strep there is a high burden and they stop replication (May be due to lack of nutrition) and increase the dose of abx won’t be effective
C dif colitis mx
Stop the offending abx (usually ceph)
If severe treat with oral metro
If that fails use vanco.
What do you do if there is no response in 48 hours?
Does the pt really have a bacterial infection
Is there a persistent focus/source present e.g. urinary catheter
Is there a deep seated collection that requires drainage e.g. abscess
Could the patient have bacterial endocarditis
Am i using the right dose?
Is there another infection present e.g. candida?
Causes of acute meningitis
Causes: Neisseria meningitidis (A, B & C serotypes) (GRAM NEGATIVE- ATTRACTS NEUTROPHILS) Streptococcus pneumoniae (GRAM POSTIVE, DIP) Haemophilus influenzae (GRAM NEGATIVE, COCOBACILI, oxidase and catalase positive)
Streptococcus pneumoniae meningitis has a bimodal distribution (mainly in children/young people and elderly patients)
Other causes:
Listeria monocytogenes (key cause of meningoencephalitis) (GRAME POSITIVE, RODS)
Group B Streptococcus (can cause neonatal meningitis)
Escherichia coli (biphasic - old people and neonates)
Rare causes:
TB (ZN IS BLUE BACKGROUND RED CHAINS)
S. aureus, T. pallidum,
Cryptococcus neoformans (fungal) (HIGH OPENING PRESSURE, ORBIT STRUCTURE - circles with mass in the middle, india ink stain which is red) (HIV is RF)
Neisseria meningitidis- Enters the body through the nasopharyngeal mucosa in a susceptible individual. Causes infection in < 10 days
Chronic Meningitis
This is TB Meningitis
Similar presentation to acute meningitis (fever, headache, neck stiffness)
• More common in immunosuppressed patients
• Takes weeks to present
Involves the meninges and basal cisterns of the brain and spinal cord
Cx: Tuberculous granulomas, asbcesses and cerebritis
Also, there is leptomeningeal enhancement
Chronic meningitis needs to be managed by specialists
Aseptic Meningitis
MOST COMMON infection of the CNS
Presentation: headache, stiff neck, photophobia
A non-specific rash may accompany these symptoms MOST COMMON Organisms
• Coxsackie group B
• Echoviruses
o Usually occurs in children < 1 year
o Self-limiting disease that resolves in 1-2 weeks
Risk factors for bacterial meningitis
Complement deficiency, hyposplenism (susceptibleto encapsulated organisms), hypogammaglobulinaemia
S.pneumoniae specifically: Immunodeficiency (alcoholic), infection (pneumonia), entry #, previous head trauma w/ CSF leak
Encephalitis causes
Viral: Coxsackie, M & M, VZ, EBV, CMV
IMPORTANT: West Nile Virus is becoming a leading cause of encephalitis worldwide
Bacterial - Listeria Amoebic Encephalitis (Naegleria fowleri) Parasitic Encephalitis (Toxoplasma gonadaii)
Most likely route of infection of brain abscess and causative organism
Tend to occur due to direct extension (e.g. otitis media, mastoiditis, paranasal sinuses)
Can occasionally spread haematogenously (e.g. endocarditis). Common ENT pathogens are staph and strep.
Most likely route of infection of spinal infection and causative organism
Pyogenic vertebral osteomyelitis is a common form of vertebral infection (e.g. staph and strep)
It can spread via direct open spinal trauma from infections in adjacent structures or it can spread haematogeously
If untreated, it can lead to:, Permanent neurological deficits, Significant spinal deformity and Death
Risk Factors
• Age
• IV drug use
• Long-term systemic steroids
• Diabetes mellitus
• Organ transplantation
Meningitis Mx
Ceftriaxone 2g IV BD is good at killing meningococcus, pneumococcus, haemophilus and E. coli
However, Ceftriaxone does NOT cover Listeria monocytogenes- This requires amoxicillin. Therefore add amoxi if immunocompromised or >50 (2g IV 4 hourly)
Meningoecephalitis Mx
Aciclovir 10mg/kg IV TDS
Ceftriaxone 2g IV BD
Staph Aureus
Gram positive coccus, catalase positive, coagulase positive, bunch of grapes
Preformed toxin -> rapid onset of symptoms
Prominent vomiting, watery, NON BLOODY diarrhoea
Self limiting
B cereus
Heat labile diarroheal toxin, heat stabile emetic toxin, gram positive, rod-spores,
Watery non bloody diarrhoea
self limiting
rare cx cerebral abscess
C diff
- Pseudomonas colitis (abx induced diarrhoea*) (can be any abx - apart from aminoglycoside - that caused it but usually the 4Cs cipro cef clina coamox)
Stop abx. Metro is first line for mild, oral vanco is second line. Infection control.
f-o transmission via spores
*abrupt, with explosive, water, foul-smelling diarrhoea
Rf
o Administration of antibiotics
o 65+ years
o Duration of hospital stay
o Severe underlying diseases
Anaerobic organisms
C diff species
Actinomyces species
Lactobacillus species
Listeria
Listeria monocytogenes - GRAM POSITIVE, RODS
V or L shaped, ß haemolytic, aesculin +ve, tumbling mobility
GI watery diarrhoea, cramps, headache, fever, little vomiting.
Perinatal infection, immunocompromised patients Outbreaks of febrile gastroenteritis
Refrigerated food (unpasteurised dairy, vegetables)
Mx: 1st Ampicillin. Ceftriaxone, Cotrimoxazole
Enterobacteriaceae
Enterobacteriaceae includes, along with many harmless symbionts, many of the more familiar pathogens, such as Salmonella, Escherichia coli, Klebsiella, and Shigella. Other disease-causing bacteria in this family include Enterobacter and Citrobacter.
Members of the Enterobacteriaceae can be trivially referred to as enterobacteria or “enteric bacteria”, as several members live in the intestines of animals.
In fact, the etymology of the family is enterobacterium with the suffix to designate a family (aceae)—not after the genus Enterobacter (which would be Enterobacteraceae)—and the type genus is Escherichia.
E coli
Facultative anaerobes, oxidase negative
- ETEC - the main type
Toxigenic, Travellers diarrhoea (fo)
Heat labile LToxin stimulates adenyl cyclase and cAMP
Heat stable SToxin stimulates guanylate cyclase.
Acts on the jejeunum, ileum not on colon.
2. EIEC - invasive Invasive dysentery (bloody diarrhoea)
- EPIC - paeds
Infantile diarrhoea
4.EHIC - haemorrhagic
Caused by verotoxin
4b. 0157: H7 subtype Anaemia, thrombocytopenia, renal failure
Mx: Self limiting - can treat with ciprofloxacin (avoid Abx)
Salmonella
Antigens: O, H, Vi Ag’s
H2S producers (black colonies), TSI agar, XLD agar
Motile
3 main species we are worried about: typhi (paraptyphi), enteriditus, cholerasuis
- Typhi/Paratyphi
Only transmitted by humans
Multiplies in Peyers patches,
Slow onset fever + CONSTIPATION, relative bradycardia Splenomegaly and rose spots, anaemia and leukopaenia
Spreads via ERS -> bacteraemia will occur, 3% will become carriers (in gallbladder)
SCD pts are particularly at risk, as our any pts with bone grafts
Ceftraixone or ciprofloxacin - Enteritides
Poultry, eggs and meat, invasion of small and large bowel Bacteraemia is infrequent. Stool is positive.
Invasion of epithelial and subepithelial tissue
Enterocolitis i.e. loose stool Self limiting non-bloody diarrhoea
Management usually not needed
Rose spots
Recurrent infections are associated with salmonella being carried by reptillian pet
Shigella
Non-lactose fermenters, non H2S, non motile
Mainly affects the distal ileum + colon -> mucosal inflammation, fever, pain, BLOODY diarrhoea.
Shiga enterotoxin
Most effective enteropathogen (low ID 50)
No animal reservoir or carreir state
Also has cell wall O antigens and polysaccharide (groups A-D)
Avoid abx (Cipro if required)
Vibrios
Late lactose fermenters Oxidase +ve, COMMA SHAPED, ‘beautiful’ lol
Two groups O1 - most lie in here, associated with epidemics. The non O1 group: sporadic, non pathogens.
- Vibrio cholerae
Rice water stool. T: Human faeces (e.g. water borne foods in shellfish)
Path: ↑cAMP opens Cl channel at apical membrane of enterocytes -> efflux of Cl to lumen (loss of H2O and
electrolytes).
Massive diarrhoea without inflammation
Mx: Electrolye replacement, fluid resus - Vibrio parahaemolytics
Raw/uncooked fish
Self limiting (lasts 3 days)
Difficult to pick up, have to use salty agar - Vibrio vulnificus
Cellulitis in shell fish handlers/divers cut by coral can cause shock and be fatal, thorough hx needed
Doxy
Campylobacter
Campylobacter- (curved, comma or S shaped)
Microaerophilic, Oxidase +ve, motile, sensitive to nalidixic acid (first quinolone).
Drinking unpasteurised milk, food eg: poultry
Prodrome of headache and fever, debilitating abdo cramps, bloody (foul-smelling) diarrhoea
Assoc with Guillain-Barre, reactive arthritis (Reiter’s)
Mx: Erythromycin or Cipro if first 4-5/7 but mostly get better by the time you diagnose
Yersinia enterocolitis
Enterocolitis, mesenteric adenitis w/ necrotising granulomas, assoc reactive arthritis & eythema nodosum.
Transmitted via food contaminated with domestic animals excreta. Prefers 4oC “cold enrichment”
What have we forgotten?
TB - IT CAN ALWAYS BE TB
Non0bacterial causes of diarrhoea
Viruses: Secretory Diarrhoea • Rotavirus - <6yrs • Adenovirus – Types 40,41 cause non bloody diarrhoea (<2yrs) • Norovirus – Adult outbreaks, vomiting. • Poliovirus • Enteroviruses (coxsackie, ECHO) • Hepatitis A
Protozoa
Entamoeba Hystolytica
Motile trophozoite in diarrhoea
Non-motile cyst in non-diarrhoeal illness
4 nuclei and no animal reservoir. Colonize colon
Makes a flask-shaped ulcer on histology
Symptoms: dysentery, wind, TENESMUS. Chronic weight loss + RUQ pain due to liver abscess !
Stool microscopy
Rf camping and didn’t boil water
Metro + paromycocin if luminal disease
Giardia
Pear shaped trophozoite 2 nuclei Trophozoites/cysts found in stool
rf: travellers, hikers, day care,MSM, mental health hospital
Get it by ingesting cysts from faecally contaminated H2O
Malabsorption of protein + fat - FOUL SMELLING non- bloody diarrhoea
Metronidazole
Dx = ELISA string test
Mx = Metro
Cryptocsporidium Parvum
DONT GO SWIMMING POOL IF YOU’VE HAD D&V BECUASE OF THIS BAD BOI
Infects the jejunum. Severe diarrhoea in immunocompromised.
Oocysts seen in stool by modified Kinyoun acid fast stain
Lecturer said self-limitng, meded says Paromomycin, Nitazoxanide in kids
HIV epidemiology
- The vast majority of cases occur in Sub-Saharan Africa
- 1 in 10 people living with HIV are children
- HIV is a massive contributor to under-5 mortality rates across the world
- HIV accounts for 35% of deaths in children < 5 years old in Sub-Saharan Africa
- There is an increasing proportion of cases appearing in teenagers with undiagnosed perinatally-acquired HIV
- Over 90% are due to mother-to-child transmission
- However, child sexual abuse is also a major risk factor for vulnerable children
HIV Manifestations
• Chronic swelling of the parotids is an early indication of HIV infection
• Molluscum contagiosum is also associated with HIV (if it is recurrent or chronic)
• Lymphadenopathy is an important and common presenting feature
• Dental caries, gingivitis and upper respiratory infection are also very common
• Lymphoid interstitial pneumonitis is a lung condition associated with HIV that is characterised by lymphoproliferation due to immune activation
o NOTE: if the lymphoid tissue contracts, you will end up with bronchiectasis and chronic suppurative lung disease
• Shingles is usually uncommon in children, however, seeing shingles in more than one dermatome raises suspicion of immunodeficiency
• HIV Encephalopathy
o Basal ganglia calcification
o White matter changes
o Atrophy
o Vasculopathy/stroke
• Severe failure to thrive is another key feature of HIV in childhood
• CMV coinfection (which is transmitted perinatally) usually causes no consequences but can cause sight-threatening retinitis
• Kaposi sarcoma is associated with co-infection with HHV8
Risk factors for vertical transmission of HIV
- Vaginal birth
- the first twin
- something that can damage the placenta and impair its barrier (e.g. malaria,toxoplasmosis)
- PROM
Should HIV mothers breast feed?
o NOTE: however, the difference in mortality was not that big because formula-fed babies were more likely to develop diarrhoea
o Therefore, the decision to avoid breastfeeding is dependent on the context of the society - if infant mortality is high, then it would be better to exclusively breastfeed
o I.e. consider whether formula feeding is accessible, affordable and safe
o WHO recommends that if infant mortality rate > 40/1000 live births, recommend:
• Exclusive breastfeeding
• ARVs for mother and baby
Barriers to treating HIV in africa
o Malnutrition
o Multiple co-infections (especially TB)
o Risk of immune reconstitution inflammatory syndromes (IRIS)
• Revamping the immune system can lead to a severe inflammatory response which leads to deterioration in clinical state
o Family disruption (Children as caretakers)
o Stigma in school
o Depression
o Poverty
Arrow trial showed what?
o Showed no difference in outcome when clinical monitoring is compared to laboratory monitoring
Prion diseases
- Prion stands for protein-only infectious agent
- Rare transmissible spongiform encephalopathies in humans and animals
- They do contain DNA but they are only made of protein
- When they enter the brain they can trigger a cascade where existing prion proteins become rapidly affected and develop the abnormal isoform of the prion protein
- This leads to the development of spongiform vacuolisation of the brain
- Results in rapid neurodegeneration
- Currently UNTREATABLE
Prion Pathogenesis
All of us have a normal prion gene found on chromosome 20. It encodes a prion protein. The normal function of prion protein is poorly understood but it is thought to have some role in copper metabolism. The normal protein does NOT cause any issues - it is only when we get the abnormal isoform that it causes neurodegeneration. On Codon 129 there are THREE polymorphisms that we can find: MM - this predisposes to prion disease (methionine).
Problems occur when the normal prion protein transforms into the abnormal version (PrPSc)
This has a beta-pleated sheet configuration and is RESISTANT to proteases and radiation so it is difficult to get rid of (e.g. surgical instruments contaminated with diseased prions are impossible to clean)
Once you get a seed of the abnormal prion protein (PrPSc) it seems to act as a template which promotes conversion of PrP into insoluble PrPSc
This is what results in rapid neurodegeneration
The trigger for this process is unclear in sporadic cases
Sporadic CJD
Rapid dementia with: Myoclonus, Cortical blindness, Akinetic mutism, LMN signs Mean age: 65 years (range 45-75 years) Incidence : 1/million/year Death within 6 months Cause is uncertain o Could be due to somatic PRNP mutation o Spontaneous conversion of PrP to PrPSc o Environmental exposure to prions
Diagnosis
EEG (2/3 pts will have abnormal one)
MRI (Increased intensity in basal ganglia)
CSF (Raised 14-3-3 protein and S100 (these are markers of rapid neurodegeneration)
Brain biopsy - definitive, done at autopsy
Histology -spongiform vacuolisation
vCJD
Younger age of onset (median = 26 years)
Median survival time = 14 months
Psychiatric onset (Dysphoria, Anxiety, Paranoia, Hallucinations)
Followed by neurological symptoms (Peripheral sensory symptoms, Ataxia, Myoclonus, Chorea, Dementia)
MRI - shows pulvinar sign (high intensity in the putamen)
EEG - non-specific slow waves
CSF - 14-3-3- and S100 are NOT useful
Tonsillar biopsy is 100% specific and sensitive
Iatrogenic CJD
o Human cadaveric growth hormone
o Corneal transplants
o Neurosurgical procedures (e.g. corneal grafts)
o Blood transfusions
o Other surgical procedures (e.g. appendicectomy, tonsillectomy)
(NB there is no blood test)
o Starts with a progressive ataxia
o Dementia and myoclonus occurs at a later stage
o Speed of progression depends on route of inoculation (CNS inoculation is the fastest)
Familial Prion Disease
Autosomal Dominant mutations
1. GSS (Onset age 30-70 years, Survival 2-10 years, PRNP P102L (MOST COMMON mutation))
- Fatal familial insomnia
o PRNP D178N
CJD treatment
o Clonazepam for the myoclonus
o Quinacrine, tetracycline, pentosan for delaying prion conversion
PCP presentation and treatment
• Widespread, bilateral ground glass shadowing with reduced exercise tolerance and low saturations is suggestive of Pneumocystis jirovecii pnuemonia
Ix • This is visualised using a silver stain (Grocott-Gomori stain)
• This is treated with co-trimoxazzole
Actinomyces
o Gram-positive rod that branches
o Causes lung abscesses in immunocompromised patients (alcoholics and chronic illness such as DM)
o Closely associated with Nocardia (g+ rod)
o These infections tend to be indolent and go on for a long time
o They are slow-growing and very difficult to treat
o As it is slow-growing, it is hard to grow in the labs so you should notify the histopathologist and microbiologist that you are worried about actinomyces
Histological features of actinomyces
• Basophilic sulphur granules
• Gram-positive rods that form branches as they grow
Rifampicin
- One of the TB drugs
- Part of the rifamycin group under inhibit DNA synthesis class but actually inhibits RNA synthesis
- Good at disrupting biofilms and has good penetrance
Osteomyelitis management approach
o Antimicrobial therapy alone is NOT curative in most cases of osteomyelitis
o Continuous drug over a long period of time will lessen the amount of discharge, but it will not cure the disease because it cannot sterilise dead bone or cavities with necrotic content and rigid walls
o Removal of devitalised tissues and the prevention of extension of infection by providing adequate drainage is extremely important (debridement)
oThis is because immune system forms fibrous capsules can form around bacteria which makes it impenetrable to antibiotics and it becomes a chronic source of infection
Always always always be aware of an external source of infection e.g. prosthesis, implant, picc line, catheter. Their removal an adequate debridement is second to none.
When stool samples are sent what are they tested for?
All faecal samples will be tested for:
o Salmonella
o Shigella
o Escherichia coli O157
Clostridium difficile testing is performed automatically in anyone > 65 years
C Diff colitis management
o Isolate in a single room
o Assess severity
o Stop offending antibiotics if possible
o Wash hands with soap and water before and after each patient contact and use gloves and aprons
• NOTE: alcohol gel isn’t effective against the spores
Commence C. difficile care pathway, fluid balance chart and Bristol stool chart
Non-Severe Disease - Metronidazole 400 mg PO TDS 14 days. If no response in 72 hrs -> classed as severe
Severe: vancomycin 125 mg PO QDS 10-14 days ±metro
What counts as severe c diff
>38.5 HR>90 WCC>15 Rising creatinine Signs of colitis Failure to respond in 72 hrs C. difficile Ribotype 027
C. difficile Ribotype 027
o Associated with a severe outbreak in 2005 o Associated with increased severity of disease o Identified by PCR ribotyping o Produces: • 16 x more toxin A • 23 x more toxin B • Compared to control strains assoc with high mortality
Path of C diff
C. difficile is a Gram-positive spore-forming anaerobe
• The organism produces two toxins:
o One toxin damages the epithelial cells (cytotoxin)
o The other disrupts the tight junctions
• This leads to a lot of inflammation with neutrophil infiltration of the tissues
• The disruption of tight junctions leads to lots of fluid loss into the bowels
• It is called pseudomembranous colitis because you are left with plaques of fibrous and damages material which looks like membranes
• NOTE: high WCC + low CRP is common in C. difficile infection
Hep C
Enveloped FLAVIVIRUS, positive sense ssRNA genome
1. Acute and chronic disease
2. Mainly blood product spread (apart from MSM) rf are blood transfusions, egyptian, 60-80% chronicity (worse for men)
Complications: Cirrhosis, Cryoglobulin Ax disease* +
glomerulonephritis.
- Genotypes 1 (40-50% of HCV UK burden), Treatment less successful
- Genotypes 2 and 3 – (40-50% of HCV UK burden) Treatment more successful
*Within the past decade, it has been recognised that a majority of patients with essential mixed cryoglobulinemia (MC) are chronically infected with hepatitis C virus (HCV). Although the underlying mechanisms have not been fully elucidated, cryoglobulin formation is clearly linked to the attempt of the host to clear the significant quantities of virions generated daily by the chronic infection.
Hep C treatment
- Vaccine: Recombinant vaccine, purified HbSAg
- Initially interferon therapy (Peg INF ⍺ 2b/2a)
- NS3/4 protease inhibitors (-previrs, block translation): telaprevir, boceprevir, simeprevir, asunaprevir (learn one or two)
- NS5A inhibitors (-asvirs, block release): ledipasvir, daclatasvir
- Direct polymerase inhibitors (- buvirs, block replication): Sofosbuvir, dasabuvir
Hep D
Deltavirus, enveloped virus, negative sense, single-stranded circular RNA
Always coinfection with HBV
Transmission: Sexual, parental, perinatal (only possible in combination with HBV)
Peginterferon-⍺
Hep E
Unenveloped positive sense ssRNA genome
1. Acute hepatitis – India
2. Faeco-oral transmission
Rare complications: CNS disease – Bell’s palsy, Guillain Barre, other neuropathy; Chronic infection
Largely supportive care
Vaccine - Effective in trials- recombinant HEVg1
Hep A
Unenveloped, picornavirus, positive sense ssRNA genome*
Acute hepatitis – 2-6 weeks incubation, severe in elderly Faeco-oral transmission
Incubation 2-6 weeks
Dx: Acute - Anti-HAV IgM (IgM persists up to 14w)
Supportive Tx, Vaccine
Live attenuated and inactivated preparations
* Positive-sense ssRNA viruses have genetic material that can function both as a genome and as messenger RNA; it can be directly translated into protein in the host cell by host ribosomes
Hep B
Enveloped, hepadnavirus genome is mixture of DNA and RNA
Incubation 2-6 months
90% of those >5y clear the virus, only 10% of neonates do
t: vertically, sexually and blood(ily)
In immunocompromised there is a risk of re@ e.g. rituximab usage
Ix: ALT and AST raised
HBsAg - infection and vaccination
HBeAg - infectivity
HBcAb (acute IgM)
Mx:
- Inf a
- Lamivudine
- Entecavir
- Telbivudine
- Tenofovir
Treatment goal – Prevent progression to cirrhosis + HCC. Maintain serum HBV DNA level as low as possible & attain histology improvement, ALT normalization. Loss of HBVeAg and seroconversion to HBVeAb Pegylated Interferon (INF) Alpha 2a (subcut) – Direct antiviral effect + upregulates expression of MHC on cell surfaces
epidemiology of surgical site infections
15.7% of HAI were SSIs
S Aureus E coli Pseudomonas Aeruginosa
How much bacteria is needed to cause an infection?
> 10^5 microorganisms/ gram of tissue increases the SSI risk. But, the threshold is reduced if there is metal work.
Septic Arthritis (aet/causative organism, PC, Ix, Mx)
Remember this is a JOINT infection
Aet: Abnormal joint (eg RA) or Immunosuppression & bacteraemia (eg diabetes, IVDU)
Bugs: Staph aureus(46%), Streptococci (22%)
Bug adheres to synovial membranes and proliferates in fluid.
• Px: Unwell febrile patient with red hot swollen joint (50%: knee, 90% monoarticular, unable to weightbear). Host inflammatory response damages joint.
• Dx: Blood culture before Abx, joint aspirate (>50,000cells/mm3), inflammatory markers. Imaging shows effusion
• Rx: IV antibiotics (cephalosporin or flucloxacillin) MRSA - Vanc. Drain joint.
Osteomyelitis
Remember this is an infection of BONE or B/MARROW
• Ax: Local or haematogenous spread!! (doesn’t originate within the bone and this is a relatively isolated site) Brodie abscess (subacute) > frank osteomyelitis
• Bugs: Staphylococcus aureus
• Px: Pain, fever, local swelling
• Dx: MRI best imaging, bone biopsy for culture/histology
• Rx: Antibiotics treat most cases. Second-line = Debridement. Remove sequestra and infected bone
Prosthetic Joint infection
• Ax: Local (wound infection);
Systemic bacteraemia (eg UTI)
• Bugs: Staphylococcus, Gram negatives eg Enterobacteriaceae
• Px: Pain, failure of joint, sinus, patient complains joint was ‘never right’
• Dx: Radiology – ‘loosening’, Joint aspirate – done with caution as risk of introducing
infection if joint is not infected.
• Rx: Remove metalwork and revise joint replacement: single or two stage revision. Use
Abx-impregnated cement.
types of osteomyelitis
Acute
Chronic (brodie abscess, sinus tract, pain)
Vertebral (older population) -most likely lumbar region, MRI, back pain and fever, 1/3 have neuro impairment
Metaphyseal (kids)
Septic arthritis bugs
Staph (recognises host factors such as fibronectin)
Strep pyogenes, agalactiae, pneumoniae), less commonly various gram -ve organisms e.g. E-Coli, Hib, nesssiera g, salmonella
Others: • Kingella kingae , Lyme, brucellosis,
SSI Prevention
Pre op - Stop DMARDs 4 weeks before and taper off steroids and radiotherapy, ensure DM is well controlled, treat all remote infections, proph abx
During op - skin prep, normothermia
Brucella granuloma Mx
Rifampicin, cirpofloxacin and doxy
What is Brodie’s abscess
Brodie’s abscess is a rare form of osteomyelitis. It involves a subacute or chronic infection of the bone with development of a localized abscess, usually within the metaphysis of long bones. The tibia is the most common bone involved and staphylococcus aureus is the most common organism identified.
What antibiotics breakdown beta lactamase? ESBL?
- Fluclox
- Cephalosporins
- Merpenems (ONLY ONE THAT DOES ESBL)
- Coamoxiclav / Piptazobactam
What are the abx in spectrum of narrow to broad?
Ben pen
Flucloxacillin*
Amoxicillin
Co amoxiclav* (amoxi + the beta lactamase i clavulonic acid)
Piptaz/ tazocin (piperacillin + tazobactam)
Carbapenem
It’s impossible to put cephalosporins as a whole in there because each once is different and each generation has different breadths
Categories of abx
- Protein Synthesis i
- DNA synthesis i
- Cell wall synthesis i
- Others
- MALT
- Fluoroquinoloes, Nitroimadazoles, Rifampicyin
- Beta lactams and glycopeptides
- Cell membrane toxins, Anti folates
Protein Synthesis inhibitors
ALL of these inhibit the step when ribosomes come together and translate
GOOD FOR ATYPICALS
MALT
Macrolides - good for G+ve, atypicals
- Clari, Azithro, Erythro
- Clari - safe in pregnant
Aminoglycosides
- Gentamicin - very negative - knackers you kidneys, deafness but also good for gram negatives e.g. pseudomonas
- Not good for anaerobes
Linezolids
- Good for G+ve and MRSA/ other R strains
Tetracyclines- good atypical
-Doxcycline - atypical pneumonia, do’t give to pregnant women or children
DNA synthesis inhibitors
Fluoroquinoloines - good for g-ve, shit against anerobes Floxacins Ciprofloxacin Works against pseudomonas Not that good against anaerobes
Nitroimadzoles (2s)
1. Metro
2. Nitrofurantoin - not a nitro but similar
Only forms active inhibitory complex under anaerobic conditions -> used to treat gut and UTI
Rifamycins
Rifampicin (TB drug) (RNA synthesis)
Cell wall synthesis inhibitors
Originally good for gram positive but the later generations are good at both!
- Beta lactams (cephalosporins and carbopenems)
- Glycopeptides
- Ben pen - very narrow, group A strep for pharyngitis
- Flucloaxcilin - can break down beta lactamase
- Amoxicillin - relatively broad, good against some g+ (listeria) and G- but can be broken down by beta lactamase
- Piperacillin - same as amoxicilin but can work for pseudomonas
- Co- amoxiclav - Amoxi combined with clavulanic acid, now can’t be broken down by beta lactamase
- Piptaz/tazocin - Piperacillin combied with tazobactam - can’t be broken down be beta lactamase
- Carbapenems - can only be broken down by carbapenamses
Glycopeptides
- Glycopeptides -> Vanco
GOOD FOR G+VE that are resistant (never use for g-ve)
NOT ORALLY ABSORBED exception is c dif colitis (needs to stay in gut)
Antifolates
Antifolates (mostly UTIs)
Sulfonamide
Diaminopyrimidines - Trimethoprim used in UTI, PCP 2 classes of anti-folate e.g. co-trimoxazole (combo 1 from each class)
Cell membrane toxins
Cell Membrane Toxins:
Daptomycin - G+ve
Colistin - G-ve e.g. acinetobacter
Very toxic, last resort
“HAIL MARYS”
Psuedo monas tx
Fluoroquinolones - g-ve (puts pesudomonaz)
Gentamicn - g-ve
Ceftaz
Meropenem
What is post primary TB?
This is reactivation or exogenous re-infection o Happens > 5 years after initial infection o 5-10% lifetime risk Risk Factors for Reactivation • Immunosuppression • Chronic alcohol excess • Malnutrition • Ageing
Clinical Presentation can be Pulmonary or extra-pulmonary
