Microbiology Flashcards
What are the potential targets for antibiotics?
Inhibit cell wall synthesis
Inhibit protein synthesis
Inhibit DNA synthesis
Inhibit RNA synthesis
Cell membrane toxin
Inhibit folate metabolism
Which classes of antibiotics inhibit cell wall synthesis
Beta lactams
Glycopeptides
What are the different types of beta-lactam?
Penicillins e.g. benzylpenicillin
Cephalosporins: ceftriaxone
Carbapenems e.g. meropenem
What are the indications for beta-lactams?
Gram positive
[Gram negative- 3rd generation cephalosporin)
What are some examples of glycopeptides?
Vancomycin, Teicoplanin
What are the indications for glycopeptides?
MRSA, C. Diff
Which classes of antibiotics inhibit protein synthesis?
Aminoglycosides
Tetracyclines
Macrolides
Chloramphenicol
Oxazolidines
Give an example of an aminoglycoside
Gentamicin
Give an example of a tetracycline
Doxcycline
Give an example of a macrolide
Erythromycin
Give an example of a chloramphenicol
Eye drops
Give an example of an Oxazolidinone
Linezolid
What are the indications for aminoglycosides
Gram -ve sepsis
Gram -ve sepsis
Gentamicin
What are the indications for tetracyclines
Intracellular- chlamydia
Rx for chlamydia
Doxycycline
What are the indications for macrolides
Gram +ve in context of Pen Allergic
Rx Gram +ve in context of pen allergic
Erythromycin (macrolide)
What are the indications for chloramphenicol
Bacterial conjunctivitis
Rx bacterial conjunctivitis
Chloramphenicol
What are the indications for oxazolidinones
Gram +ve, MRSA + VRE
Rx for Gram +ve, MRSA + VRE
Linezolid
or
Daptomycin
What classes of antibiotics inhibit DNA synthesis
Fluoroquinolones
Nitroimidazoles
Given an example of a fluoroquinolone
Ciprofloxacin
Given an exmple of a nitroimidazole
Metronidazole
Indications for fluoroquinolones
Gram -ve
Indications for nitroimidazoles
Anaerobes and protozoa
What class of antibiotics inhibits RNA synthesis?
Rifamycin
Given an example of a rifamycin
Rifampicin
Indications for rifamycins
MTB
Rx for anaerobes and protozoa
Metronidazole
What classes of antibiotics act as cell membrane toxins
Polymyxin
Cyclic lipopeptide
Give an example of a polymyxin
Colistin
Give an example of a cyclic lipopeptide
Daptomycin
What are the indications for polymyxins?
Gram -ve
What are the indications for cyclic lipopeptide
Gram +ve, MRSA +VRE
What classes of antibiotics inhibit folate metabolism?
Sulfonamides
Diaminopyrimidines
Give an example of a sulfonamide
Sulphamethoxazole
What are the indications for sulfonamides?
PCP (with trimethoprim: co-timoxazole)
What are the indications for diaminoprimidines?
UTI e.g. Trimethoprim
What are some broad spectrum antibitoics?
Co-amoxiclav
Tazocin
Ciprofloxacin
Meropenem
What is tazocin?
Combination antibotic containing penicllin (piperacillin) and a beta-lactamasae inhibitor tazobactam
What is co-amoxiclav?
Combination antibiotic containing penicllin amoxillin and beta-lactamase inhibitor clavulanic acid
What are some narrow spectrum antibiotics?
Flucloxacillin, metronidazole, gentamicin
Features of beta-lactams
Activity?
Ineffective against?
- Inactivate the enzymes that are involved in the terminal stages of cell wall synthesis (transpeptidases also known as penicillin binding proteins) – β-lactam is a structural analogue of the enzyme substrate
- Bactericidal
- Active against rapidly-dividing bacteria
- Ineffective against bacteria that lack peptidoglycan cell walls (e.g. Mycoplasma or Chlamydia)
Penicllin uses
Broken down by?
Gram +ve organisms e.g. strep, clostridia
Broken down by beta-lactamase, prod by S. aureus
Amoxicillin uses
Broken down by?
Broad spectrum, extends coverage to enterococci and Gram -ve organisms
Beta-lactamase produced by S. aureus and many gram negative organisms
flucloxacillin uses
NB
Similar to penicllin although less active
Stable to beta-lactamase produced by S. aureus
Uses of piperacillin
Similar to amoxicillin, extends coverage to pseudomonas and other non-enteric gram negatives
Broken down by beta-lactamase producing organisms e.g. S. aureus and gram negatives
Clavulanic acid and tazobactam
Beta-lactamase inhibitors extend coverage of penicllins to include S.aureus, Gram negatives and anaerobes
What changes with the generations of cephalosporins?
Increasing activity against gram negative bacilli
What is a 1st generation cephalosporin?
Cephalexin
What is a What is a 2nd generation cephalosporin?
Cefuroxime
What is a 3rd generation cephalosporin?
Cefotaxime
Ceftriaxone
Ceftazidime
What are ESBL organisms resistant to?
All cephalosporins regardless of in vitro results
Use of cefuroxime
•Stable to many β-lactamases produced by Gram negatives. Similar cover to co-amoxiclav but less active against anaerobes
With what is ceftriaxone associated?
C diff
What is the use of ceftazidime?
anti-Pseudomonas
What are the uses of carbapenems?
What is an issue
Stable to ESBL enzymes
Carbapenemase enzymes becoming more widespread
There are multidrug resistant Acinetobacter and Klebsiella species
What are the key points for beta-lactams
- Relatively non-toxic
- Renally excreted (so ↓dose if renal impairment)
- Short half life
- Will not cross intact blood-brain barrier
- Cross-allergenic (penicillins approx 10% cross-reactivity with cephalosporins or carbapenems)
Why are glycopeptides effective against Gram +ve?
- Large molecules, unable to penetrate Gram –ve outer cell wall
- Active against Gram +ve organisms
Rx for MRSA administration
IV only
What is used to treat serious C diff?
Oral vancomycin
What is an issue with glycopeptides?
As a consequence?
Nephrotoxic
Need to monitor drug levels to prevent accumulation
Rx vs P. aeruginosa?
Gentamicin and tobramycin
Features of aminoglycosides
What is significant
- Bind to amino-acyl site of the 30S ribosomal subunit
- Rapid, concentration-dependent bactericidal action
- Require specific transport mechanisms to enter cells (accounts for some intrinsic R)
Ototoxic and nephrotoxic: monitor levels
Combination of beta-lactams and aminoglycosides?
Synergistic
What are the features of tetracyclines
What is significant
Side-effect?
- Broad-spectrum agents with activity against intracellular pathogens (e.g. chlamydiae, rickettsiae & mycoplasmas) as well as most conventional bacteria
- Bacteriostatic
- Widespread resistance limits usefulness to certain defined situations
Do not give to children or pregnant women
Light-sensitive rash
Features of macrolides
- Bacteriostatic
- Minimal activity against Gram –ve bacteria
- Useful agent for treating mild Staphylococcal or Streptococcal infections in penicillin-allergic patients
- Also active against Campylobacter sp and Legionella. Pneumophila
- Newer agents include clarithromycin & azithromycin with improved pharmacological properties
Rx for Campylobacter and L. pneumophila
Macrolide
MOA Macrolides
•Bind to the 50s subunit of the ribosome
1) Interfere with translocation 2)Stimulate dissociation of peptidyl-tRNA
MOA tetracyclines
- Reversibly bind to the ribosomal 30S subunit
- Prevent binding of aminoacyl-tRNA to the ribosomal acceptor site, so inhibiting protein synthesis.
MOA aminoglycosides
) Prevent elongation of the polypeptide chain
2) Cause misreading of the codons along the mRNA
What are the significant adverse effects of chloramphenicol
Aplastic anaemia
Grey baby syndrome in neonates: inability to metabolise drug
MOA chloramphenicol
•Chloramphenicol binds to the peptidyl transferase of the 50S ribosomal subunit and inhibits the formation of peptide bonds during translation
MOA Nitroimidazoles
- Include the antimicrobial agents metronidazole & tinidazole
- Under anaerobic conditions, an active intermediate is produced which causes DNA strand breakage
What are nitrofurans?
Compounds related to nitroimidazoles e.g. nitrofurantoin used for UTIs
Considerations when Rxing rifampicin
Monitor LFTs
beware interactions with other drugs that are metabolised by the liver
Orange secretions
Why should you never use rifampicin as a single agent?
- Except for short-term prophylaxis (vs. meningococcol infection) you should NEVER use as single agent because resistance develops rapidly
- Resistance is due to chromosomal mutation.
- This causes a single amino acid change in the ß subunit of RNA polymerase which then fails to bind Rifampicin.
Features of colistin
Colistin – a polymyxin antibiotic that is active against Gram negative organisms, including Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella. pneumoniae. It is not absorbed by mouth. It is nephrotoxic and should be reserved for use against multi-resistant organisms
Why is sulphonamide and diaminopyrimidine combined Rx useful?
- Act indirectly on DNA through interference with folic acid metabolism
- Synergistic action between the two drug classes because they act on sequential stages in the same pathway
- Sulphonamide resistance is common, but the combination of sulphamethoxazole+trimethoprim (Co-trimoxazole) is a valuable antimicrobial in certain situations (e.g. Treating Pneumocystis. jiroveci pneumonia)
- Trimethoprim is used for Rx community-acquired UTIs
What are the mechanisms of antibiotic resistance?
Inactivation
Altered target
Reduced Accumulation
Bypass
How does resistance to beta-lactams occur?
NB
Beta lactamases
Not the mechanism of resistance in penicllin resistant pneumoccoci and MRSA
How does beta-lactam resistance develop in MRSA?
Altered target: mecA encodes novel PBP (2a) which has a low affinity for binding beta lactams, substitutes for teh essential functions of high affinity PBPs at otherwise lethal concentrations othe antibiotic
How does Strep pneumonia resist Beta lactams?
Altered target: Penicllin is the result of the acquisition of stepwise mutations in PBP genes, lowe rlevel resistance can be overcome by increasing the dose
What are ESBLs?
What can they do?
NB?
Extended spectrum beta lactamases
Able to break down cephalosporins, becoming more common
Resistant to cephalosporins regardless of in vitro finding
What leads to macrolide resistance?
Altered targets:
- Adenine-N6 methyltransferase modifies 23S rRNA
- Modification reduces the binding of MLS antibiotics and results in resistance
- Encoded by erm (erythromycin ribosome methylation) genes.
IFV vaccines in use today
Triaelent or quadrivalent inactivated vaccine: split or subunit HA rich. Given to those at risk. Short term strain specifica immunity mediated by Ab to HA head.
Live attenuated vaccine also quadrivalent or trivalent: cold adapted virus limited to URT, given to children, broader more cross reactive immunity
Features of IFV
Orthomyxovrius
What are the three strains that tend to affect humans each year?
How is this combatted?
IFV: A (H1: peaks begnning of January)
IFV: A (H1N1: peaks end of December)
IFV B: Peaks march
Trivalent vaccine in targetted populations which consists of a purified fraction with HA + NA of inactivated virus
What is the natural resrvoiir of IFV A
Why is these limited human-human transmission
Ducks
Because the vrius doesn’t replicate in the colder URT
What is the structure of IFV
8 RNA segements of nucleocaspid protein very prone to mutation
Outline IFV viral entry
NA (sialidase): cleaves sialic acid residues exposing receptor son host cell disrupting mucin barrier
HA: binds sialic acid receptors-> virus entry. Endosomal-viral envelope fusion= release
How are IFVs named?
H1= HA1
N1= N1
What is antigenic drift?
Mutation of HA/NA to give new viral strains
What is antigenic shift?
Complete change of HA/NA
Reassortment of RNA segments between IFV strains
Can only occur in IFVA
What is the pathogenesis of IFV H5N1
Cleavage of HA by clara-tryptase in the lung leads to exteded tropism/grwoth for H5 + H7
What are the causes of severe outcome in flu?
Secondary bacterial pneumonia
Mutant virus
Co morbidity
Cytokine storm
What is amantadine
Indication
MOA
Issue
Antiviral for IFV
IFVA only
Targets M2 ion channel but single AA mutation in M2= resistance
Give some examples of neuraminidase inhibitors
Oseltamivir (tamiflu)
Zanamivir (relenza)
Sialic acid
Only effective if given <48hrs aftern infection
What are the various issues with the different ROA in vaccines?
Subcute: good, uptake, processing and presentation to Langherans cells
IM: OK
IV Ag: taken to spleen
Orally: good response and local response within GIT
Intranasal: OK but may get allergic response
What are some examples of APCs?
Macrophages
B-lymphocytes
Langerhans
DCs
What does clonal expansion of CD4 cells require?
Specific antigent in combination with a cytokine e.g. IL-2
What response does the TH1 subset mediate
What cytokines are involved?
Cell-mediated immune response
IL-2
IFN-G
TNF
What response does the TH2 mediate?
What cytokines are involved?
Humoral response
IL-4
IL-5
IL-6
Why is it called haemagglutinin?
Causes agglutination of RBCs/URT cells
What are the 2 subsets of memory cells?
Central memory T cells: CCR7+CD62Lhigh: migrate efficiently to peripheral LNs, produce IL-2 but no IFN or perforin
Effector memory T cells: found in other sites, produce high levels of IFN and perforin but no IL-2
What are the three phases of T cell immunological memory?
Expansion
Contraction
Memory
What does the choice of antibiotic depend on?
CHAOS
Choice
Host
Antimicrobial susceptibilites of the
Organism itself and also the
Site of the infection
Choice of drug best features
Narrow spectrum
Bactericidal
Based on local sensitivity
Patient characteristics
Cost
When is IV antibiotic use indicated
Serious infection or no PO absorption
If need to access deep site or CNS
What factors influence antibiotic dose?
Age
Renal/hepatic function
Drug monitoring
Allergy
Principles for empirical treatment with antibiotics:
Collect specimens
Use a broad-spectrum antibiotic
Empirical cover may then be changed to a more specific agent on the basis of culture results
What are thhe preliminary investiations for identification of a bacterial infection
Gram stain: CSF, joint aspirate, Pus
Rapid antigen detection: immunofluorescence, PCR
What are the important factors to consider about the site of the infection?
pH
Lipid-solubility
CNS penetration
Special considerations required for Rx of endocarditis or osteomyelitis
Administration of antibiotics route of choice
IV : serious or deep seated infection
PO: usually easy but differential absorption between different antibiotic classes
IM: not an option for long term use, avoid id bleeding tendency
Topical: limited application that may cause local sensitisation
Generally after a patient has been on IV antibiotc for 48hrs switch to oral if they have stabilised
What is a type 1 pattern of antibiotic activity?
What is the goal of therapy?
Which antibiotics?
Concentration-dependant killing and prolonged persistent effects
Maximise concentrations
Aminglycosides, daptomycin, fluoroquinolines, ketolides
What is a type 2 pattern of antibiotic activity?
Goal of therapy
Antibiotics?
Time-dependant killing and minimal persistent effects
Maximise duration of exposure
Carabapenems, cephalosporins, erythromycin, linezolid, penicllins
What is a type 3 pattern of antibiotic activity?
Goal of therapy
Antibiotics
Time-dependent killing and moderate-to prolonged persistent effects
Maximise amount of drug
Azithromycin, clindamycin, oxazolidinones, tetracyclines, vancomycin
Recommended Rx course for N. meningitides meningitis?
7d
Recommended Rx course for acute adult osteomyelitis?
6w
Recommended Rx course for bacterial endocarditis
4-6w
Recommended Rx course for GpA streoptococcal pharyngitis
10d
Recommended Rx course for simple cystitis
3d
Skin infections common types
Common organism
Rx?
Impetigo, cellulitis, wound infection
S.aureusm, beta-haemolytic streptoccoci
Fluclox unless penallergic or MRSA
Invasive group A strep treatment
Aggressive and early debridement
Antibiotics: adjunctive use of protein synthesis inhibitors esp. clindamycin
Use of IVIG
What is the Eagle effect?
Proposed mechanism?
- Named after Harry Eagle who first described it, originally referred to the paradoxically reduced antibacterial effect of penicillin at high doses, though recent usage generally refers to the relative lack of efficacy of beta-lactam antibacterial drugs on infections having large numbers of bacteria.
- Penicillin is a bactericidal antibiotic that works by inhibiting cell wall synthesis but this synthesis only occurs when bacteria are actively replicating (or in the log phase of growth).
- In cases of extremely high bacterial burden (such as with Group A Strep), bacteria may be in the stationary phase of growth.
- In this instance since no bacteria are actively replicating (presumably due to nutrient restriction) penicillin has no activity.
Rx in pharyngitis?
Benzyl-pen 10d
CAP Rx (mild)
Amoxicllin
CAP Rx (severe)
Co-amoxiclav and clarithromycin
HAI
Rx
Second most common cause of HAI
Associated with highest mortality
Greatest risk associated with tracheal intubation and mechanical ventilation
Cephalosporin, ciprofloxacin, tazocin, if MRSA colonised ris consider addition of vancomycin
What are the main pathogens in bacterial meningitis?
Rx?
N meningitidis
S pneumonia
+/- Listeria in very young/elderly/immunocompromised
Ceftriaxone +/- amoxycilllin if Listeria likely
Meningitis in neonate Rx
Cefotaxime + amoxicillin
Why is cefotaxime used in neonates?
Used insteead of ceftriaxone as it displaces bilirubin from albumin and can cause biliary sludging
N menigitidis treatment
Benzylpen or ceftriaxone/cefotaxime
Rx simple cystitis in community
Trimethoprim
HA-UTI Rx
Infected urinary catheter?
Cephalexin or Augmentin
Change under gentamicin cover
Rx for C diff
Stop offending antibiotic: usually a cephalosporin
If severe, RX with PO metronidazole
If fails use PO vancomycin
Def: bacturia
Def: cystitis
Presence of bacteria in urine
Inflammation of the bladder, often caused by infection
Classification of UTIs?
Uncomplicated: infection in a structureally and neurologically normal urinary tract
Complicated: with functional or structural abnormalities including catheters/calculi
Which patients are generally affected by complicated UTIs?
Men
Pregnant Women
Children
Patients who are hospitalised or in healthcare settings
Prevalence of bacturia in young non-pregnant women?
Incidence of symptomatic UTIs in women?
1-3%
40-50%
What causes 95% of UTIs?
E. coli
•Urinary tract infections are caused by many species of microorganisms, however, only a few serogroups of E. coli, O1, O2, O4, O6, O7, O8, O75, O150, and O18ab, cause a high proportion of infections
What other orangisms cause UTIs?
- Proteus mirabilis
- Klebsiella aerogenes
- Enterococcus faecalis
- Staphylococcus saprophyticus
- Staphylococcus epidermis
What is significant in recurrent UTIs, especially those with structural abnormalities?
The relative frequency of infections caused by atypical organisms (i.e. not E. Coli) increases greatly
What are the antibacterial host defences in the urinary tract?
Urine: osmolality, pH, organic acids
Urine flow and micturition
Urinary tract mucosa: bactericidal activity, cytokines
Causes of renal obstruction
Mecahnical:
Extrarenal: valves, stenosis or bands, cacluli, extrinsic ureteral compression and BPH
Intrarenal: nephrocalcinosis, uric acid nephropathy, analgesic nephropathy, PKD, hypokaelmic nephropathy and the renal lesions of sickle cell trait/disease
Neurogenic:
Polio
Tabes dorsalis
Diabetic neuropathy
SC injuries
What dose vesicoureteral reflux lead to?
Perpetuation of infection by maintaining a residual pool of infected urine in the bladder after voiding
What is significant about infection in the kidney?
Frequently a site of abscesses in patients with S aureus bacteremia or both
Infection by gram negative bacilli rarely occurs by the haematogenous
Symptoms of UTI in neonates/children <2y/o?
>2y/o?
Failure to thrive, Vomiting, Fever
Frequency, dysuria, abdo or flank pain
Lower UTI symptoms?
- The lower tract symptoms result from bacteria producing irritation of urethral and vesical mucosa, causing frequent and painful urination of small amounts of turbid urine.
- Patients sometimes complain of suprapubic heaviness or pain.
- Occasionally, the urine is grossly bloody or shows a bloody tinge at the end of micturition.
- Fever tends to be absent in infection limited to the lower tract.
Upper UTI symptoms
- fever (sometimes with rigors)
- flank pain
- and frequently lower tract symptoms (e.g., frequency, urgency, and dysuria)
- at times, the lower tract symptoms antedate the appearance of fever and upper tract symptoms by 1 or 2 days
- the symptoms described, although classic, may vary greatly
Symptoms of UTI in older patients
- The vast majority of older adult patients with urinary infection are asymptomatic
- Symptoms, when present, are often not diagnostic, because noninfected older adults often experience frequency, dysuria, hesitancy, and incontinence
- Symptoms of upper tract infection are often atypical e.g., abdominal pain, change in mental status
Ix of UTI (uncomplicated):
Urine Dip
MSU for MCS
Bloods: FBC, UE, CRP
Ix of complicated UTI
Renal US
IV urography
What indicates contamination of a urine sample on microscopy?
Squamous epithelial cells
Causes of sterile pyruia?
(pus in urine)
Prior treatment with antibiotics
Calculi
Catheterisation
Bladder neoplasm
TB
STI
What are the differentiating culture forming units/mL in urine sample
10^5 cf/mL in infection
Patients without infection: <10^4 cfu/mL
What is the most common cause of candida infection in UT?
Occurs with indwelling catheters
Can be cured by removal of catheter
Rx of fungal UTI
There is no demonstrated benefit in treatment of asymptomatic infection
Exceptions made for renal transplant patients and patients who are to undergo elective urinary tract Sx
Features of pyelonephritis
Commonly associated with sepsis and septicaemia
Requires more aggressive Rx
Broad spectrum bios
Co-amoxiclav +/- gent
Imaging: calculi, structural cause
Rx of pyelonephritis?
Co-amoxiclav +/- gent
Cefuorxime +/- gent
Cxs of pyelonephritis?
Perinephric abscess
Chronic pyelonephritis- scarring, chronic renal impairment
Septic shock
Acute papillary necrosis
What are the most common causes of UTI
E Coli
Proteus
Klebsiella
Staph saprophyticus
What is the dipstick finding in UTI?
Nitrites + leucocytes +ve
Rx of UTI?
Timeothprim or nitrofurantoin
What is tabes dorsalis?
abes dorsalis, also known assyphilitic myelopathy, is a slow degeneration (specifically,demyelination) of the nerves primarily in the dorsal columns(posterior columns) of the spinal cord (the portion closest to the back of the body). These nerves normally help maintain a person’s sense of position (proprioception), vibration, anddiscriminative touch.
What are the routes of entry for meningitis?
Haematogenous spread
Direct implantation (e.g. surgery, LP)
Local extension (secondary to established infection)
And PNS into CNS (viruses)
Meningitis def:
Infection of the meninges and CSF
Dura mater
Pia mater
Arachnoid mater
Symptoms of meningitis
Headache
Stiff neck
Soome disturbance of brain function
Organsisms causing meningitis
N meningitidis
Pneumococcus
H influenzae
L monocytogenes
GBS
E Coli
Staph aures
Treponema pallidum
TB
Virus
Cryptococcus neoformans
Candida
Grows on chocolate agar, gram negative cocci=
N meningitidies
Transmission of N meningitidis
Person-person from asymptomatic carriers
Pathogenic strain found in only 1% of carriers
Through nasopharyngeal mucosa in susceptible individuals
Causes infection in less than 10 days
Outcome of N meningtiides infection
Septicaemia in 7-10%
Meningitis in 50%
Both in 40%
NB re LP in septicaemia?
Coagulopathy…
Neuropathology of N. meningitis
Direct bacterial toxicity, indirect inflammatory process and cytokine release and oedema
Shock seizures and cerebral hypoperfusion
10% mortality with 5% of survivors having neurological sequelae (predominantly sensorineural deafness)
Clinical spectrum of septicaemia?
Produced by four processes
Capillary leak: albumin, and other plasma proteins leading to hypovolaemia
Coagulopathy: leads to bleeding and thrombosis
Metabolic derangement: acidosis
Myocardial failure and multi-organ failure
Acute meningitis
Usually bacterial
Chronic meningitis
Headaches for months
TB or cryptococcus or spirochetes
More common in immunosuppressed
Involves the meninges and basal cisterns of the brain and SC
Can result in tuberculous granulomas, abscesses or cerebritis
Aspetic meningitis
Usually acute biral, most common CNS infection
Presents with headache, fever, neck stiffness, photophobia
Non-specific rash
Most frequent in children younger than 1y
Self-limiting course that resolves in 1-2w
Most commo organisms causing aseptic meningitis
80-90% caused by coxsackie virus group B and echoviruses
Most common causes of bacterial meningitis in enonates
GI flora: GBS, L monocytogenes, E Coli
Most common cause of bacterial meningitis in elderly
GBS
Listeria
MTB (subacute)
What is another important cause of aseptic meningitis
HSV
Remember to ask re symptoms of HsV infection
Def: encephalitis
Symptoms
Infection of the brain parenchyma
(Meningoencephalitis- inflammation of the meninges and brain parenchyma)
Disturbances of brain function
Organisms causing encephalitis?
Rabies
Arboviruses
Trapanasome brucei gambiense
TB
Prions
Amoeba
West Nile
Features of Brain abscesss
SOL on imaging: looks like cancer, needs histopathology to say which
Spreads from otitis media, mastoiditis, paranasal sinuses, endocarditis, haematogenously
Organisms likely to cause brain abscesses
Streptococci
Staph
Gram negative (particulalry in neonates)
MTB
Fungi
Parasites
Actinomyces
Nocardia specias
Def: myelitis
Infection of the spinal cord
What is a common form vertebral infection?
Spread?
Px?
Pyogenic vertebral osteomyelitis
Direct pen trauma, infections in adjacent structures, from haematogenous spread
If left untreated can lead to permanent neurological deficit, significant spinal deformity or death
Symptoms of myelitis
Significant organism?
Disturbance of nerve transmission
Polio
What are the factors for myelitis
Advanced age
IVDU
LT-systemic steroids
DM
Organ transplantation
Malnutrition
Cancer
Neurotoxin causing rigid paralysis?
Tetanus from C tetani
Neurotoxin causing flaccid paralysis?
Botulism
C botulinum
Risk factors for N meningitis?
Complement deficiency
Hyposplenism
Hypogammaglobulinameia
Risk factors for Strep meningitis?
Complement deficiency
Hyposplenism
Immune defect (ETOH)
Infection (pneumonia)
Entry #
Previous head trauma with CSF leak
Gram -ve cause of meningitis?
Neisseria
Gram +ve cause of meningitis?
Strep pneumoniae
MRI in meningitis
Better than CT in detecting parenchymal abnormalities such as abscesses and infarctions
Meningitis Ix
Clinical and blood cultures
Throat swabs (neisseria)
Serum-Ag
EDTA-PCR
CSF: WCC, protein, glucose
Different types of CSF study
Colour/clarity
WCC/differentaition
Protein, glucsoe
Culture: blood agar, chocolate agar, sabourand’s agar
Limitations of the Ix in meningitis?
MRI oedema pattern and moderate mass effect cannot be differentiated from tumour or stroke or vasculitis
Abx given before culture samples
Amount of CSF
PCR
Methods to detect amoebic infections
CSF:
Clear
0-5 leukocytes
Negative gram stain or Ag test
Protein 0.15-0.4
Glucose 2.2-3.3
Normal
CSF normal WCC
0-5
Protein CSF normal?
0.15-0.4
CSF glucose?
2.2-3.3 (>50% serum)
CSF:
Turbid
100-200 polymorphs
Positive gram stain
0.5-3 on protein (raised)
Reduced glucose
Bacterial menintisi
?Meningococcus
?pneumococcus
?Listeria
CSF: clear or slightly turbid
15-500 lymphocytes
Negative gram stain
0.5-1 protein
Normal glucose
Aseptic meningitis
CSF:
Clear or slighlty turbid
300-500 mixed lymphocytes and polymorphs
Negative gram satin
Raised protein
Reduced glucose
MTB or cryptococcal meningitis
CSF:
Glucose normal
WCC high with polymorphs
Think partiall treated bacterial infection
What CNS infections may show a normal CSF?
Cerebral abscesses (Streptococci)
Viral encephalitis
Mx of bacterial meninigits
ABC
Corticosteroids before Abx
Ceftriaxone (2g IV BD) for pneumo and meningococcus
If elderly/immunocompromsied add amoxicillin or ampicillin to cover for Listeria)
Mx of Meningoencephalitis
Aciclovir
Ceftriaxone
If >50y or immunocompromised add amoxicillin for Listeria cover 2g IV 4 hourly
Mx of aseptic meningitis
Give ceftriaxone until you know it is herpes, no aciclovir
Doses of ceftriaxone?
2g IV BD
Dose of acicvlovir?
10mg/kg IV TDS
Dose of amoxicillin
2g IV 4 hourly
What are the features of the Glasog Meningococcal Septicaemia prognostic score?
Systolic BP
Skin-Rectal T difference
Modified coma scale
Deterioration
Neck stiffness
Extent of purpura
Base deficit
Used as a tool to identify those who may need transfer to a tertiary centre with a PICU
Kwashiorkor?
Acute form of childhood protein-energy malnutrition: oedema, anorexia, ulcerating dermatoses and heaptomegaly
Insufficient protein consumption but with sufficient calorie intake
Marasmus
Severe malnutrition, charactersied by energy deficiency. Emaciated
What are the Helminth diseases?
Schistosomiasis
Hookworm
Threadworm
Filiarisis
What are the protozoal dieases?
Leishmaniasis
Typanosomoiasis
Amoebiasis
Def: Sanitation
The state of being clean and conductive to health
The hygienic separation of human waste form contact. Safe containment, transporation, treatment and disposal of human excreta
Primary barrier to disease transmission
Fluids, fields, flies, fingers and food
Features of Hep A
Acute hepatitis, ofetn subclinical, short period 2-6w
Transmission of Hep A
Faecal-oral spread
Outbreaks associated with occupational risk e.g. sewage workers.
Soft fruit, sewage works, shellfish
anti-HAV IgM
Recent infection disappears after a few months or vaccine
anti-HAV IgG
Previous infection, lifelong or vaccine
Which of the hepatitis vrisuses are RNA?
A
C
D
E
What type of virus is Hep B?
dsDNA virus
What is a good screening test for Hep V and why?
Vrisu makes an excess of surface antigen
Therefore it is a good screening ttest
What is the timefrime for Hep B infection?
Acute <6m
Chronic
Latent virus can reactivate in immunocompromised
Transmission of Hep B
Sexual, vertical, horizontal
Blood products
Clinical picutre for Hep B
Causes and acute or chronic heaptitis
Pathophysiology in Hep B
Over decades leads to scarring and cirrhosis, eventually resulting in HCC. This is accelerated in males and drinkers
Mx of Hep A
Supportive
Mx of Hep B
Pegylated IFn alpha 2a
Lamivudine
Tenofovir
When is Hep B treatment initiated?
When liver damage occurs
Dx of Hep B?
ALT and AST
HbsAg
HBeAg (infectivity, changes form +ve to negative)
HBcAb (acute- IgM, chronic IgG)
Timeframe in Hep C infection
Acute,
80% progress to chronic
Transmission of Hep C
Blood products
How does the Hep C genotype inform treatment?
Genotpyes 1 and 4= 48w
2&3= 24w
Dx of Hep C
ALT
Anti-HCV
Mx of Hep C
Cure 54% treated with peg IFN alpha-2b and ribavirin combination therapy.
Considerations around Peginterferon alpha 2-b
Attacks bone marrow: low WCC, low platelets
Can lead to depression
Care in treating cirrhotic patients as will kill infected hepatocytes
Kidney trransplant is contraindication for IFN
Wariness about treating genotypes 1 and 4 and in elderly patients as there is less chance of a response and treatment is expensive
Hep D features
Only infect Hep B patients.
Transmitted through contaminated blood
Features of Hep B and D infection
Superinfection and likely to have a very acute hepatitis and develop cirrhosis in 2-3y
Treat with prolonged course of IFN
Hep E features
Faeco-oral spread
Mainly seen in tropical areas
Causes GI symptoms e.g. cramps, pain.
High mortality rate, esp in pregnant.
Usually just acute but can cause chronic if untreated
What are the different types of diarrhoea?
Secretory
Inflammatory
Enteric fever
What is the mechanism of secretory diarrhoea
Toxin production affecting the lumen
No fever or a low grade fever
No white cells on stool sample
What is the mechanism for inflammatory diarrhoea
Invasion of bacteria into the lamina propria causing exudative into the lumen or intiaiing an innate immune response mainly through LPS acting on TLR4,5
Fever, WBCs in stool samples, neutrophils +/- blood
What are two common causes of secretory diarrhoea?
Cholera toxin
Superantigens from E COli
What bacteria can cause an inflammatory diarrhoea?
C jejuni
Shigella
Atypical salmonella species
What is the mechanism for enteric fever?
Invasion, Peyer’s patches, interstitial inflamamtion, monocytes, innate immune response
Fever, WBC in stool, can be blood
Causes of enteric fever?
Typphoidal, salmoneall subtypes, enteropathic Yersinia spp. Brucella spp.
What differentiates between inflammatory diarrhoea and enteric fever
Depends on immune status of patient
Both have bacteraemia
If immunocompetenet there is interstitial inflammation aned enteric fever
If they are immunocompromised there is exudative inflamamtion and exudative diarrhoea. This leads to neutrophilia and spetic shock
What are the anaerobic causes of Gi infection
Clostriida:
botulinum
perfringens
difficile
What differentiates between GBS and botulism?
Botulism is a descending paralysis
Treatment of botulism
Antitoxin
C botulinum infeciton
Canned/vacuum packed foods: honey, beans
(ingestion of preformed toxin which would usually be inactivated by cooking0
Blocks Ach from peripheral nerves leading to paralysis
Features of C perfringens
Reheated meats, superantigen enterotoxin leads to massive cytokine production by CD4 leading to systemic toxicitiy
Acts on small bowel
Watery diarrhoe and cramps lasting 24hrs
What bacteria causes gas gangrene?
C perfringens
Features of C difficile
2 endotoxins (A and B)
Causes pseudomembranous colitis
Caused by Abx use, usually cephalosporins and fluorguinoloines
Mx of C diff
PO metronidazole
2nd line Vanco
Which antibiotics are associated with C diff infection
Cephalosporins/fluoroquinolones
What are the aerobic bacteria causing GI infection?
Bacillus cereus
S. aureus
Featuers of B cereus GI infection
Reheated rice, spores gerimnate. Sudden vomiting
Superantigen
Watery, non bloody diarrhoea
Mx of B cereus infection
Self-limiting
Features of S. aureus GI infection
Prominent vomiting and watery non bloody diarrhoea
Main virulence fctor i protein A.
Catalase, coagulase +ve
Appears in tetrads
Clusters on gram stain
Beta haemolytic on blood agar
S aureus
Mx of S. auerus GI infection
Don’t treat, self limited
Lactose fermenting cause of GI infection?
Gram -ve enterobacteriacae (faculative anaerobes, oxidase negative)
E. COli
What are the strains of E Coli causing GI infection?
ETEC
EIEC
EHEC
HUS
EPEC
ETEC
Toxigenic E coli, travellers diarrhoea.
Food/water contaminated with human faecaes
Enterotoxins: Heat labile: stimulates adenyl cyclase and cAMP
Heat stable: stimulates guanylate cyclase
EIEC
Invasive dysentry
EHEC
Haemorrhagic E Coli: caused by verotoxin
HUS
E Coli 01571:H7 toxin
Anaemia, thrombocytopenia, renal failure
EPEC
Infantile diarrhoea
Mx of E Coli
Self-limiting but can treat with ciprofloxacin if needed
Non lactose fermenters causing GI infection
Salmonella
Shigella
Yersinia
O, H, Vi Ag’s
H2S produces
TSI agar
XLD agar
Selenite F broth
Salmonella
What are the three species of Salmonella
Typhi (and paratyphi)
Enteritidis
Cholearsuis
Features of Salmonella Enteritidis
Transmitted from poultry, eggs, meat
Invades small and large bowel
Bacteraemia is infrequent
Self-limiting
Blood
Mx of S. enteritides
Ceftriaxone or ciprofloxacin (if required)
Features of S. Typhi
Human trtansmission
Multiplies in Peyer’s patches
Bactaeremia, 3% become carriers (gallbladder)
Slow onset fever + constipation
Splenomegaly and rose spots
Aneamia and leukopaenia
Haemorrrhage and perforation
Slow onset fever + constipation
Splenomegaly and rose spots
Aneamia and leukopaenia
Haemorrrhage and perforation
S. Typhi
Rose spots
Enteric (Typhoid) fever
Non-lactose fermenters, non H2S producers, non-motile
Shigella
Mx of Salmonella typhi
Ceftriaxone or ciprofloxacin
Features of Shigella
Mainly affects the distal ileum and colon.
Infalmmation, fever, pain, bloody diarrhoea
Dysentry
Mx of shigella
Avoid Abx, ciprofloxacin if required
Non-lactose fermenting preferring cold temperatures cause of GI infection
Yersinia enteroclitis
Features of Yersinia enterocolitis infection
Enterocolitis, mesenteric adenitis with necrotising granulomas
Associated reactive arthritis and erythema nodosum
Reye’s syndrome
Transmitted via food contaminated with domestic animal excreta
What are the different species of Vibrios
Cholear
Parahaemolyticus
Vulnificus
Curved, comma shaped, late lactose fermenters, oxidase positive
Vibrios
Features of Vibrio cholera
Rice water stool, human faecas
Increased cAMP causes massive diarrhoea without inflammation
O1 group: epidemic
Mx of cholera
Supportive
Features of vibrio parahaemolyticus
Ingestion of raw or undercooked seafoood
Major cause of diarrhoea in Japan or in the carribean
Self-limiting
Features of Vibrio Vulnificus
Cellulitis in shellfish handlers
Fatal septicaemia with D+V in HIV
Mx of vulnificus and parahaemolyticus
Doxy
Features of C jejuni
Drinking unpasteurised milk, food, egg
Prodrome of headache and fever with abdominal cramps
Bloody (foul smelling diarrhoea)
Associated with GBS, reactive arthritis
Mx of C jejnuni
Erythromycin or cipro if first 4-5/7
Curved, S sjaped, microaeriphilic, oxidase positive, motile, sensitive to nalidixic acid
Campylobacter
V or L shaped, beta haemolytic
Aesculin positive with tumbling motility
L monocytogenes
Features of Listeria GI infection
GI watery diarrhoea, cramps, headache, fever, little vomiting
Perinatal infection, immunocompromised patients
Refrigerated foods: unpasteurised dairy, vegetables
Mx of Listeria
Ampicillin
Ceftraixone
Cotrimoxazole
What are the protozoa causing GI infection
Entamoeba histolytica
Giardia lamlia
Cryptosporidium parvum
Protozoa
MSM, food, water, soil
Entamoeba histolytica
Protozoa
Travellers, hikers, MSM, mental hospitals
Giardia
Motile trophozoite in diarrhoea
Non-motle cyst in non-diarrhoeal illness
4 nuclei
Entamoeba histolytica
Flask shaped ulcer on histology
Entamoeaba
Features of Entamoeba infection
Dysentry
Wind
Tenesmus
Chronic weigtht loss and RUQ pain due to liver abscess
Stool microscopy
Mx of entamoeba histolytica
Metronidazole and paramomycin (if luminal disease)
Pear shaped 2 trophozoite with 2 nuclei and trophozoites and cysts in stooll
Giardia
Foul smelling, non-bloody diarrhoea
Giardia
Mx of Giardia
Metronidazole
Features of cryptosporidium
Infects jejunym
Severe diarrhoea in immunocompromised
Oocysts seen in stool by modified Kinyoun acid-fast stain
Mx cryptosporidum
Paromomycin
Nitazoxanide
What are the viruses causeing secretory diarrohea
Rotavirus
Adenovirus
Norovirus
Poliovirus
Enteroviruses (coxsackie, ECHO)
Hepatitis A
Features of rotavirus infection
Secretory diarrhoea with no inflammation
Watery diarrhoea through stimulation of the enteric nervous system
Very common in children <6.
Which types of adenovirus cause non bloody diarrhoea?
Which age group are affected?
Types 40, 41
<2y/o
Gram +ve
Aerobic
Acid alcohol fast
Thick waxy cell wall
Mycobacteria
Mycolic actids
Mycobacteria
Cough +/- haemoptysis
Fever with night sweats
Weight loss
Malaise
Ethnicity
Mycobacteria
Post primary TB occurs in?
Young adults
Features of post-primary TB
?Re-activation/re-infection
Upper lobes- may progress rapidly to cavitation
Caseating granuloma
Miliary spread rare
Healing by fibrosis and calcification
1st line treatment for TB
RIPE
Rifampicin and isoiazid for 6/12
Pyrazinamide and ethambutol for 2/12
Treatment of TB meningitis
Increase isoniazid and rifampicin to 8-10/12
Treatment of latent TB
6/12 isoniazid
Side effects of Rifampicin
Drug interactions (raised transaminases, cytochrome p450 induction)
Orange secretions
Hepatotoxicity
Drug interactions (raised transaminases, cytochrome p450 induction)
Orange secretions
Hepatotoxicity
Rifampicin
Side effects of isoniazid
Peripheral neuropathy (give B6/pyridoxine
Hepatotoxcityi
Peripheral neuropathy (give B6/pyridoxine
Hepatotoxcityi
Isoniazid
Side effects of pyrazinamide
Hyperuricaemia
Hepatotoxicity
Hyperuricaemia
Hepatotoxicity
Pyrazinamide
Side effects of ethambutol
Optic neuritis
Visual disturbance
Optic neuritis
Visual disturbance
Ethambutol
Additional considerations in treating TB
DOTS
Vit D therapy
Why is Vit D therapy important in treatment of TB
Accelerates clinical recovery
Mono resistant TB=
Resistance to one drug only
Prophylaxis of TB
Isoniazid
MDRTB=
Resistance to rifampicin and isoniazid
XDRTB=
Resistance to rifampicin, isoniazid and injectables (kanmycin/amikacin)/ quinolones
Injectables used as 2nd line in TB
Capreomycin
Kanamycin
Amikacin
What are the second line TB treatments
Injectables
Quinolones
Cycloserine
Ethionamide
PAS
Linelozid
Clofazamine
Subacute presentation
Weight loss, fever, neck stiffness
Personality change
Reduced GCS
Focal neurological signs
TB meningitis
Dx if TB meningitis
CT- tubercolmata
LP- lymphocytic
Lymphadenitis
Pericarditis
Peritonitis/ileitis
Genito-urinary, renal testicular
Skin liver etc
(maybe +HIV positive)
Extrapulmonary TB
What is a Ghon focus
A Ghon focus is a primary lesion usually subpleural, often in the mid to lower zones, caused by mycobacterium bacilli (tuberculosis) developed in the lung of a nonimmune host (usually a child).
Ghon focus
Primary TB
Which patient group gets primary TB?
Nonimmunocompetent=
Elderly
Children
HIV
What is progressive primary TB?
Focus or node ulcerates into bronchus-> pneumonia
Cavity formation, bronchiectasis, consolidation, collapse
What is primary complex TB
TB taken by macrophase to LN, generalised lympho-haematogenous spread
Rich foci seen in?
Miliary TB
Miliary TB
Ix in TB
Imaging: CXR (upper lobe cavitation), CT
Culutre: Sputum x3, BAL, urine (EMU), Lowenstein Jensen medium (gold standard)
Sputum microscopy- ZN, auramine staingin: gram +ve, acid fast, aerobic intracellular rods
Tuberculin skin test
IGRA
NAAT
Liquid culture mediums
gram +ve, acid fast, aerobic intracellular rods
TB
Risk factors for contracting TB
Recent migrant
HIV+
Homeless
Drug user
Prison
Close contacts
Young adults/elderly
Risk factors for reactivation of latent TB?
Immunosuppression
Malnutrition
Ageing
Chronic alcohol excess
Fever, sweats, weight loss, back pain
?Spinal TB
Ix of spinal TB
MRI/CT +/- biopsy/aspirate
Treatment of spinal TB
12/12 anti-TB
Pathophysiology of spinal TB
Haematogenous spread
Initial discitis
Vertebral destruciton and collapse +/- anterior extension causing iliopsoas abscess
Potts Disease
Pott disease or Pott’s disease is a form of tuberculosis that occurs outside the lungs whereby disease is seen in the vertebrae. Tuberculosis can affect several tissues outside of the lungs including the spine, a kind of tuberculous arthritis of the intervertebral joints.
Potts Disease
What is the BCG vaccination?
Attenuated strain of M. Bovis
Efficacy of BCG
0-80%
Use of BCG
Bad for pulmonary TB
Good for leprosy, TB meningitis, disseminated TB
Inidications for BCG
Babies born in or with parents/grand parents from areas with incidence ?40/100000
Previously unvaccinated new immigrants from high prevalence countries for TB
HIV and TB
HIV-ve latent TB -> active TB 5-10% lifetime risk
HIV+ve, yearly risk is 5-10%
Hansen’s disease
Leprosy
What are the organisms causing Hansen’s disease
M. Leprae
M. Lepromatosis
Skin: depigmentation, macules, plaques, nodules, trophic ulcers
Nerves: thickened nerves, sensory neuropathy
Keratitis, iridocyclitis
Periostitis aseptic necrosis
Leprosy
Rx in leprosy
Rifampicin, dapsone, clofazimine (if multibacillary)
What is the immunological spectrum of leprosy
Tuberculoid
BT
Borderline
Lepromatous
Tuberculoid leprosy
Paucibacillary
TH1 mediated
Depigmented lesions
BT leprosy
Nerve damageq
BB leprosy
Multiple plaques
Lepromatous leprosy
Multibacillary
Th2 mediated
Neuropathic ulcers
What are the indicators that an infection is being caused by NT Mycobacteria?
Environmental
No person-person transmission
Associated with impaired immunity, poor response to standard anti-TB regime
What is MAIC?
M. avium intracellulare complex
Presentation of MAC in children
Pharyngeal/cervical addenitis
Pulmonary MAC
Underlying lung disease, resembles TB
Disseminated MAC seen in?
Cytotoxics, lymphoma
Features of MAC infection in AIDS?
Disseminated multibacillary infection
Mycobacteraemia
Consider in HIV patients with longstanding diarrhoea
What is fish tank granuloma caused by?
M. Marinarum
Single or clusters of papules/plaques in swimming pool/aquarium owners?
M. Marinarum
What causes Buruli ulcer
M. Ulcerans
Transmission of M. uclerans
By insects, tropics/australia
Treatment of M. Ulcerans
Rifampicin
Streptomycin
Sx
Painless early nodule
Slowly progressive leading to ulceration, scarring and contractures
Seldom fatal but with hideous deformity
Buruli ulcer
Buruli Ulcer
M. Ulcerans
Def: pneumonia
Inflammation of lung alveoli
Can be lobar or bronchopneumonia
Def: bronchitis
Inflammation of medium sized airways, mainly in smokers.
Cough with sputum most days for 3m or 2 or more consecutive years
Organisms in bronchitis
Viruses
S. pneumoniae
H. influenzae
M. catarrhalis
CXR in bronchitis
Often normal
Rx in bronchitis
Bronchodilation, PT +/- Abx
CURB 65
Confusion of new onset (defined as an AMTS of 8 or less)
Blood Urea nitrogen greater than 7 mmol/l (19 mg/dL)
Respiratory rate of 30 breaths per minute or greater
Blood pressure less than 90 mmHg systolic or diastolic blood pressure 60 mmHg or less
Age 65 or older
CURB 0-1
Treat as an outpatient
CURB 2
Consider hospital
CURB 3-5
Hospitalise
?ITU
What are te classical causes of pneumonia
S. Pneumoniae
H. influenzae
M. catarrhalis
S. aureus
K. pneumonia
Pneumonia with:
Rust coloured sputum
Lobar on CXR
S. pneumonia
Pneumonia with:
Smoking/COPD
H. influenza
Pneumonia with:
Smoking
M. catarrhalis
Pneumonia with:
Recent viral infection (post-influenza) and cavitaiton on CXR
Staph aureus
Pneumonia with:
Alcoholic
Elderly
Haemoptysis
Klebsiella
Pneumonia with:
+ve diplococci
Strep pneumoniae
Pneumonia with:
-ve cocci-bacilli
H. infleunza
Pneumonia with:
-ve cocci
M. catarrhalis
Pneumonia with:
+ve cocci in grape bunch clusters
S. aureus
Pneumonia with:
-ve rod, enterobacter
Klebsiella
Atypical pneumonia clinically
No signs or chest XR or signs not in keeping with CXR
May be extrapulmonary signs e.g. hepatitis, hyponatraemia
Causes of atypical pneumonia
Legionella
Mycoplasma
Chalmydia pneumonia
Chlamydia psittaci
Other causes of pneumonia
Bordatella pertussis
TB
Pneumonia with:
Travel, air conditioning, water towers
HEPATITIS
HYPONATRAEMIA
Legionella
Pneumonia with:
Systmic symptoms
Joint pain
Cold agglutination test
Erythema multifrome
RIsk of SJS, AIHA
Mycoplasma
Pneumonia with:
TWAR agent
Chlamydia pneumonia
Pneumonia with:
Birds in hx
Chlamydia psittaci
Pneumonia with:
Whooping cough in unvaccinated
Bordatella pertussis
Pneumonia with:
Poor response to Abx
TB
Causes of pneumonia in patient with:
HIV
PCP
TB
Cryptococcans
Causes of pneumonia in patient with:
Neutropenia
Fungi- aspergillus
Causes of pneumonia in patient with:
BMT
Aspergillus
CMV
Causes of pneumonia in patient with:
Spleenctomy
Encapsulated organisms: H. influenzae, S. pneumonia, N. meningitides
Causes of pneumonia in patient with:
CF
Pseudomonas aeruginosa
Burkholderia cepacia (v. high mortality)
Lobar pneumonia
Strep
Cavitating pneumonia
Staph aureus
Ix in pneumonia
Non microbiological: FBC, U&E, CRP, ABG, CXR
Microbiology: sputum MC+S, blood cultures, effusion aspiration/BAL
Test in severe CAP for S. pneumoniae and Legionella?
Urine antigen tests
What is the use of antibody tests in pneumonia
Paired serum samples at presentation and 10-14/7
Rise in Ab level over time
Useful for difficult to culture (chalmydia, legionella)
Silver stain, boat shaped oragnisms
PCP
Def: HAP
>48 hours into hospital stay without previous infection
What is BAL used for?
To differentiate URT and LRT microbes
CAP
Classical
Mild-moderate
Amoxicillin or macrolide 5-7d
CAP
Classical
Moderate-Severe
Clarithromycin + co-amoxiclav/cefuroxime (2-3w)
CAP
Atypical
(Chlamydia, Mycoplasma)
Macrolide/tetracycline
Clarithromycin
What is consideration re durg interaction of clarithromycin
Increases anticoagulant effect of Warfarin
HAP 1st line
Ciprofloxacin +/- vancomycin
HAP second line/ITU
Piptazobactam + vancomycin
Abx in aspiration pneumonia
Cefuroxime
Metronidazole
Legionella abx
Macrolide + rifampicin
Staph aureus Abx
Fluclox
Pseudomonas Abx
Piperacillin + tazobactam (tazocin) or ciprofloxacin +/- gentamicin
Causative organism in HAP
Coliforms and pseudomonas more likely the longer the stay
Coliform bacteria
Escheria
Klebsiella
Citrobacter
Enterobacter
Causes of ventilator associated pneumonia
P. aeruginosa, acinetobacter, stenotrophomonas maltophilia
Alcoholic, acute SOB, fever, dirty brown sputum, pleuritic
chest pain, malaise, N&V
o Examiniation: tachypnoea, tachycardia, dullness to
percussion, crackles
Pneumococcal pneumonia
Army cadet, 2 week hx, headache, malaise, non-productive cough, examination unremarkable,
normal inflammatory markers
Mycoplasma pneumoniae
Confusion, fever, headache, myalgia, abdominal pain and diarrhoea.
o Low sodium and deranged LFTs
Legionella
MOA aciclovir
Guanosine analogue, blocks viral DNA extension through activation by thymidine kinase present in HSV
NB CMV doesn’t have this enzyme
Indication aciclovir
HSV
Indication ganciclovir
CMB, EBV, HHV-6
MOA ganciclovir
Nucleoside analgoue
SE of ganciclovir
BM suppression
RCHEP
CMV conseuqnecs
Retinitis
Colitis
Hepatitis
Encephalitis
Pneumonitis
Owl eye inclusions=
CMV infected cells
CMV infection
Owl eye inclusions
What is used as an alternative to ganciclovir if resistant/severe side effects
Foscarnet
MOA foscarnet
pyrophosphate analgoue. Inhiits nucleic acid synthesis without requring activation
Foscarnet indication
Used when CMV resistant to ganciclovir
Also used as prophylaxis post organ transplant
MOA Cidofovir
Nuceloside phosphonate
Indications Cidofovir
CMV retinitis
Often used in treatment of non-herpes viral infections in opportunistive post-transplant setting e.g. BK virus for BK nephropathy/BK cystitis/adenovirus/PML (JC virus)
What is a consideration re Foscarnet and cidofovir
Nephrotoxic
Maintain hydration and co=administer probenecid
HSV infection
Act Very Fast
Acyclovir
Valaciclovir
Famciclovir
Foscarnet/cidofovir in herpes infection
If it s resistant
When to treat VZV?
Immunocompromised
Pregnants
Adults with pneumonitis
Treatment of CMV in BMT
Pre-emptive therapy: monitor CMV viral load during high rrisk period
Acute therapy: reduce immunosuppression
1st line: ganciclovir (BM toxicity)
2nd line: foscarnet (+GCV) (nephrotoxic)
3rd line: cidofovir (nephrotoxic)
What determines when to treat HBV
Serum HBV DNA levels (>2000IU)
Serum transaminitis (above normal limit)
Liver biopsy histological grade and stage: moderate-severe active necroinflammation and or fibrosis
Treatment goals in HBV Rx?
Prevent progression to cirrhosis and HCC
Maintain serum HBV DNA as low as possible
Attain histological improvement
ALT normalisation
Loss of HBVeAg and seroconversion to HBVeAb
What are the drugs used in HBV Rx?
Pegylated INF alpha 2a
Nucelos(t)ide analogues
What is the MOA of INFa2a
Direct antiviral effect and upregulates expression of MHC on cell surfaces
(HBV) MOA:
Lamivudine
Inhibitor of viral polymerase
(HBV) MOA:
Adefovir dipivoxil
Inhibitor of viral polymerase
(HBV) MOA:
Entecavir
Inhibitor of viral polymerase (no resistance)
(HBV) MOA:
Telbivudine
Inhibitor of viral polymerase
(HBV) MOA:
Tenofovir
Inhibitor of reverse transcriptase
What is the preferred first line treatment in HBV infection?
Entecavir
PegINF a2a
Tenofovir
What is the treatment goal in HCV?
Sustained virologic response: persistent absence of HCV RNA in serum >6/12 after completing antiviral treatment
Prevent progression to cirrhosis, HCC or decompensated liver disease requiring treatment
MOA Ribavirin
RNA nucleoside analgoue
Major SE of ribavirin
Haemolytic anaemia
Treatment of HCV
PegINF a2a
Ribavirin
Which HCV genotypes have a worse treatment prognosis?
1,4,5,6
Which HCV genotypes have a better treatment outcome
2 and 3
What is the MOA and indication of:
Zanamivir (INH)
IFVA
NA inhibitor
What is the MOA and indication of:
Oseltamavir
IFVA
NA inhibitor
M” cWhat is the MOA and indication of:
Amantidine
M2 Channel
IFVA
What is the MOA and indication of:
Ribavirin
RSV/ parainfluenza
Guanosine analgoue
Live atttenuated vaccines=
MMR
Yellow fever
BCG
OPV
Varicella
Typhoid
Flu
Inactivated vaccines=
Rabies, pertussis, IPV, Hep A, typhoid
Recombinant protein vaccine=
HBV
Subunit vaccines=
Hib
Men C
PCV
Toxoid vaccines=
Tetanus
Diptheria
What causes SSPE?
Subacute sclerosing pancencephalitis
Measles
Special risk groups for vaccines
Pts on CTx, pts <6/12 after BMT, children on high dose steroids +/- cytotoxics
Can HIV patients be given MMR?
Yes if susceptible
What does DTP cause (side effect)
Anaphylaxis
Protracted crying
What does OPV/IPV vaccine cause (side effect)
Poliomyelitis (OPV)
What does measles vaccine cause (side effect)
Thrombocytopenia
What does rubella vaccine cause (side effect)
Acute arthritis
Should HIV patients be given BCG and yellow fever vaccines?
No
Sx: SOB, green sputum, fever. Hypoxic, heavy smoker.
o X ray: shadowing, ground glass changes and hypoxia exacerbated by exercise.
o Immunosuppression – HIV
PCP
Widespread lung fibrosis with ground glass shadowing on histology with a cough
PCP
India ink with halo=
Encapsulated yeast i.e. cryptococcus
Mx of CPC
Co-trimoxazole and oral prednisolone
2nd line= clindamycin and primiquine. IV methylprednisolone
Aerobic gram positive rod with branches
Seen in relatively immunocompromised patients, produces copious amounts of pus in abscess
Commo in alcohlics
Associated with lung abscess or pelvic asbscess
Slow growing and hard to treat
Actinomyces
How does rifampicin help in septic arthritis?
Affects biofilm formation
What are the STIs causing discharge?
Gonorrhoea
Chlamydia
Trichomonas
Candida
BV
What are the STIs causing ulceration?
Syphillis
HSV
LGV
Chancroid
Donovanosis
What are the STIs causing rashes/lumps/growths
Genital warts- HPV
Molluscum contagiosum
Scabies
Pubic lice
Painful genital ulcers=
Herpes
Chancroid
Painless genital ulcers=
Syphillis
Lymphogranuloma venereum
Granuloma inguinale
Obligate intracellular Gram -ve diploccocus causing STI
N. gonorrhoea
LGV
Chancre
Syphillis
Chancroid
Haemophilus ducreyi
Donovanosis
Herpes
Herpetic whitlow
Acrodermatitis chronic atrophicans
Lym disease
Late persistent
Tinea versicolour
