CP Microbiology x8 lectures Flashcards
Define - Antibiotic
Chemical products of microbes that inhibit or kill other organisms
Define Antimicrobial agents
-Antibiotics
-Synthetic compounds with similar effect
-Semi-synthetic i.e. modified from antibiotics
Different antimicrobial activity/spectrum, pharmacological properties or toxicity
Define Bacteristatic
Inhibit bacterial growth
Protein synthesis inhibitors
Define Bactericidal
Kill bacteria
Cell wall-active agents
Define minimum inhibitory concentration (MIC)
Minimum concentration of antibiotic at which visible growth is inhibited
Define Synergism
Activity of two antimicrobials given together is greater than the sum of their activity if given separately
Define Antagonsim
One agent diminishes the activity of another
Define indifference
Activity unaffected by the addition of another agen
Define clinical relevance
Synergism
β-lactam/aminoglycoside combination therapy of streptococcal endocarditis
What are antibacterial mechanisms
Inhibition of critical process in bacterial cells
- Antibacterial targets
- Enzymes, molecules or structures
Selective toxicity
- Target not present in human host
- Target significantly different in human host
What are antibiotic targets
Cell wall Protein synthesis DNA synthesis RNA synthesis Plasma membrane
What is the major component of bacterial cell wall
Peptidoglycan
polymer of glucose-derivatives, N-acetly muramic acid NAM and N-acetly glucosamine NAG
Not present in animal cells therefore ideal for selective toxicity
What drugs are cell wall synthesis inhibitors
β-lactams
Glycopeptides
Explain β-lactams
- Benzylpenicillin
- All contain β-lactam ring
- Four-membered ring structure (C-C-C-N)
- Structural analogue of D-alanyl-D-alanine
- Interfere with function of “penicillin binding proteins”
- Transpeptidases enzymes involved in the peptideoglycan cross-linking
What areβ-lactam antibiotics
example drugs
Penicillins
Benzylpenicillin (PEN), amoxicillin, flucloxacillin
Relatively narrow spectrum
Cephalosporins
Cefuroxime (CXM), ceftazidime etc.
Broad spectrum
Carbapenems
Meropenem (MER), imipenem
Extremely broad spectrum
Monobactams
Aztreonam (AZT)
Gram-negative activity only
What are glycopeptides
- Vancomycin, teicoplanin
- Large molecules, bind directly to terminal D-Alanyl-D-Alanine on NAM pentapeptides
- Inhibit binding of transpeptidases and thus peptideoglycan cross-linking
- Gram-positive activity
- Unable to penetrate Gram-negative outer membrane porins
In bacteria where does protein synthesis occur
Ribosome
- ribonucleoprotein complexes
- Catalyze peptide bond formation and synthesize polypeptides
Stages: initiation, elongation, termination, and ribosome recycling
50S (large) and 30S (small) subunits combine to form 70S initiation complex
S=Svedberg units; relative sedimentation rate
What do aminoglycosides do
Protein synthesis inhibitors
Gentamicin, amikacin
Bind to 30S ribosomal subunit
Mechanism of action not fully understood
What are Macrolides, Lincosamides, stretogamins (MLS)
protein synthesis inhibitors Erythromycin, clarithromycin (macrolides) Clindamycin (lincosamide) Bind to 50S ribosomal subunit1 Blockage of exit tunnel Inhibit protein elongation
What does tetracycline do?
Protein synthesis inhibitor Tetracyclines (tetracycline, doxytetracycline) Bind to 30S ribosomal subunit Inhibit RNA translation Interfere with binding of tRNA to rRNA
actions of oxazolidines
Oxazolidinones Linezolid Inhibits initiation of protein synthesis Binds to 50S ribosomal subunit Inhibits assembly of initiation complex May also bind to 70S subunit
What are mupirocin and fusidic acid
protein synthesis inhibitors
Examples of DNA synthesis inhibitors
Trimethoprim and sulfonamides
Inhibit folate synthesis
Folic acid is a purine synthesis precursor
Trimethoprim
Dihydrofolate reductase
Sulfonamides
Dihydropteroate synthetase
Combined as co-trimoxazole (trimethoprim-sulfamethoxazole)
Quinolones1 and fluoroquinolones2
Inhibit one or more of two related enzymes
DNA gyrase and topoisomerase IV
Involved in remodelling of DNA during DNA replication
Supercoiling/strand separation
Examples
Nalidixic acid1, ciprofloxacin2, levofloxacin2
RNA synthesis inhibitors
Rifampicin
RNA polymerase inhibitor
Prevents synthesis of mRNA
Plasma membrane agents
Daptomycin
Cyclic lipopeptide
Inserts lipophilic tail into cell membrane resulting in depolarisation and ion loss
Effective in Gram-positives only
Adverse effects of all drugs
Nausea, vomiting, headache, skin rashes etc.
Infusion reactions
Allergic reactions
Generation of antibiotic resistance (see separate lecture)
Selection of resistant strains in patient
Preferential colonisation on exposure to resistant strains
Fungal infection
Superficial and invasive candidiasis
Clostridium difficile infection
Antibiotic specific adverse effects
- aminoglycosides
- B-Lactams
- Linezolid
Aminoglycosides
Reversible renal impairment on accumulation
Therapeutic drug monitoring indicated
B-lactams
Main problems are allergic reactions
Generalised rash 1-10%
Anaphylaxis approx. 0.01%
Linezolid
Bone marrow depression
B lactams and allergy
Intolerance Nausea, diarrhoea, headache etc. Minor allergic reactions Non-severe skin rash Severe allergic reactions Anaphylaxis, urticaria, angio-oedema, bronchospasm, severe skin reaction (Stevens-Johnson syndrome)
Safe to use cephalosporins and carbapenems in patients with non-severe penicillin allergy
Safe to use aztreonam in patients with any penicillin allergy
Antibiotics and C diff
Common precipitating antibiotics
Cephalosporins
Ciprofloxacin (esp. ribotype 027)
Clindamycin
Less common precipitating antibiotics Benzylpenicillin Aminoglycosides Glycopeptides Piperacillin-tazobactam
May be precipitated by any antibiotics
What are the following antibiotics used to treat
- Flucloxacillin
- Benzylpenicillin
- cephalosporins
- metronidazole
- vancomycin
- meropenem
Flucloxacillin - Staphylococcus aureus (not MRSA)
Benzylpenicillin – Streptococcus pyogenes
Cephalosporins (avoid in elderly) – Gram-negative bacilli
Metronidazole – anaerobes
Vancomycin – Gram-positives (MRSA)
Meropenem – most clinically-relevant bacteria
what are the pharmacokinetic considerations
Important determinant of in vivo efficacy is concentration at site of action
CSF β-lactams Good availability in presence of inflammation Aminoglycosides and vancomycin Poor availability
Urine Trimethoprim and β-lactams Good availability MLS antibiotics Poor availability
What are pharmacodynamic considerations
Concentration dependent
Main determinant of bacterial killing is the factor by which concentration exceeds MIC
Administered intermittently to achieve high peaks
Aminoglycosides
Time dependent
Main determinant of killing is the amount of time for which antibiotic concentration exceeds MIC
Administered frequently to maintain high level
Β-lactams
In vitro phenomena applied in vivo
What is combination therapy
To increase efficacy
Synergistic combination may improve outcome
β-lactam/aminoglycoside in streptococcal endocarditis
To provide adequately broad spectrum
Single agent may not cover all required organisms
Polymicrobial infection
Empiric treatment of sepsis
To reduce resistance
Organism would need to develop resistance to multiple agents simultaneously
Antituberculous chemotherapy
What are the antibiotic resistant organisms
- Meticillin-resistant Staphylococcus aureus (MRSA)
- Vancomycin/glycopeptide-resistant enterococci (VRE/GRE)
- Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL)
- NDM-1 producing Gram-negative bacilli
- Multi-drug resistant tuburculosis (MDR-TB)
- Extremely-drug resistant tuberculosis (XDR-TB)
Others
- Enterobacteriaceae resistant to amoxicillin, ciprofloxacin, gentamicin, carbapenems etc.
- Pseudomonas resistant to ceftazidime, carbapenems etc.
How does resistance affect the treatment of infection
Empiric therapy
-Risk of under-treatment
If “traditional” antibiotic is used
-Risk of excessively broad-spectrum treatment
-If risk of resistance is taken into account
Targeted therapy
Requires use of alternatives which may be:
-Expensive
E.g. linezolid, tigecycline, daptomycin vs. flucloxacillin for MRSA
-“Last line”
E.g. meropenem vs. ciprofloxacin for multi-resistant Enterobacteriaceae
Toxic
-E.g. colistin vs. meropenem for NDM-1 producers
Why is sensitivity testing important
- To enable transition from “empiric” to “targeted” antibiotic therapy
- To explain treatment failures
- To provide alternative antibiotics in case of
- Treatment failure
- Intolerance/adverse effects
- To provide alternative oral antibiotics when IV therapy no longer required
How does disk susceptability work
1) add organism
2) add antibiotics
3) incubate
4) read and interrupt result
- zone of inhibition
5) clinical interpretation
How does liquid medial (microtitre) susceptibility work
1) add antibiotic vary concentrations
2) add organism
3) incubate
4) read MIC
5) compare with breakpoint
6) interpret results
Range - more resistant –> more susceptible
Uses and Limitations of susceptibility testing
-The infection may not be caused by the organism that has been tested
-The correlation between antimicrobial sensitivity and clinical response is not absolute
-A patient with an infection caused by a specific micro-organism is more likely to respond if treated with an antibiotic to which the organism is “sensitive” than one to which it is “resistant”
-Certain organisms are “clinically resistant” to antimicrobial agents even where in vitro testing indicates susceptibility
Resistance genes may be expressed in vivo in response to antibiotic exposure
E.g. AmpC β-lactamase genes in Enterobacteriaceae
Hence the need for “clinical interpretation”
What are the mechanisms for antibiotic resistance
- No target – no effect
- Reduced permeability – drug can’t get in
- Altered target – no effect
- Over-expression of target – effect diluted
- Enzymatic degradation – drug destroyed
- Efflux pump – drug expelled
What are reasons for Absent target
Fungi/virus
infection is not bacterial
Reasons for reduced permeability
1)Vancomycin:Gram-negative bacilli
Gram-negatives have an outer membrane that is impermeable to vancomycin
2) Gentamicin:anaerobic organisms
Uptake of aminoglycosides requires an O2 dependent active transport mechanism
Reasons for target alteration
1)Flucloxacillin: MRSA
Altered penicillin-binding protein (PBP2’, encoded by MecA gene) does not bind β-lactams
2)Vancomycin: VRE
Altered peptide sequence in Gram-positive peptideoglycan (D-ala D-ala D-ala D-lac)
Reduces binding of vancomycin 1000-fold1
3)Trimethoprim: Gram-negative bacilli
Mutations in dhr (dihydrofolate reductase gene)
What drugs are effected by enzymatic degradation
1) Penicillins and cephalosporins: β-lactamases (including ESBLs and NDM-1)
2) Gentamicin: aminoglycoside modifying enzymes
3) Chloramphenicol: chloramphenicol acetyltransferase (CAT)
Drug efflux - causes?
Multiple antibiotics, specially in Gram-negative organisms1
Antifungal triazoles and Candida spp.
How does resistance occur
Antibiotic-modifying enzymes Β-lactamases (including ESBL) Penicillins, cephalosporins Aminoglycoside-modiying enzymes Gentamicin
Altered antibiotic targets
Penicillin-binding protein 2’ (“PBP two prime”) in MRSA
Peptide sequence in VRE peptidoglycan
Resistance genes encoded in plasmids
Circular DNA sequences transmitted within species and (less commonly) between species
Mainly by conjugation
Horizontal transfer of resistance
Enabled by transposons and integrons
DNA sequences designed to be transferred from plasmid to plasmid and/or from plasmid to chromosome
Often contain “cassettes” with multiple resistance genes
Vertical transfer of resistance
Chromosomal or plasmid-borne resistance genes transferred to daughter cells on bacterial cell-division
Consequences of antibiotic exposure
1) Sensitive strains exposed to antibiotics at sub-lethal concentrations
2) Chance of survival will be enhanced by development of resistance
3) Resistant strain will out-compete sensitive strains
4) Resistance perpetuated by vertical transfer
How to avoid problems with antibiotics
Never use an antibiotic unless absolutely necessary
Always use the most “narrow-spectrum” agent available
Use combination therapy if indicated
Be willing to consult expert information sources
What was the estimated number of people living with HIV in 2012
2.3million (1.9-2.7 million)
Pathogenesis of viral infections
- acute
- chronic
Acute - flu, measles, mumps
Chronic
- latent (with/without recurrence) - Herpes simplex, cytomegalovirus
-Persistent - HIV, Hep B, Hep C
What do viruses consist of
Nucleic acid (DNA, RNA) Protein - structural coat, enzymes Lipid evelope Obligate intracellular parasite
How does viral replication occur
1) Virus attachment to cell (via receptor)
2) Cell Entry
3) Virus Uncoating
4) Early proteins produced – viral enzymes
5) Replication
6) Late transcription/translation – viral structural proteins
7) Virus assembly
8) Virus release
What are examples of polymerases
- DNA to DNA
- DNA to RNA
- RNA to RNA
- RNA to DNA
1) DNA to DNA -Eukaryotes, DNA viruses
2) DNA to RNA, Eukaryotes, DNA viruses
3) RNA to RNA- RNA viruses
4) RNA to DNA, Retroviruses (HIV), Hepatitis B virus
What is the structure of a nucleotide
Base, Ribose sugar, triphosphate
What is AZT - azidothymidine
Inhibits HIV replication
NRTI - nucleoside reverse transcriptase inhibitor
What are NRTIs
Examples x2
Nucleoside reverse transcriptase inhibitors
Pyrimidine analogues
-Thymidine analogues
-Zidovudine
Cytosine analogues
-Lamivudine
Purine analogues (Adenine and Guanidine)
- Abacavir
- Tenofovir
HBV - what is it
Hep B virus
contains reverse transcriptase enzyme,
Lamividine and tenofovir active against HBV
What are NNRTIs
examples x2
Non-nucleotide reverse transcription inhibitors
1) Efavirenz
2) Nevirapine
What are protease inhibitors
Atazanavir Darunavir Fospamprenavir Lopinavir Nelfinavir Ritonavir* Saquinavir
Newer HIV drugs
Fusion Inhibitor
Integrase inhibitor
Chemokine receptor antagonists
1) Fusion inhibitor
Enfuviritide (T20, given by IM injection)
2) Integrase Inhibitors
Raltegravir
3) Chemokine receptor
antagonsits (Co-receptor)
Maraviroc (CCR-5)
What is HAART
how does HAART work
Highly Active Antiretroviral Therapy 2 NRTIs + NNRTI 2 NRTIs + boosted PI Started when CD4 falls Aim to switch off virus replication Taken life long Suppression >10yrs achieved Now problems with toxicity
What HIV mutation is immune to Lamivudine
What will this mutation lead to
M184V
Strain with mutation will become dominant
Lamivudine will no longer be an effective treatment option
How is HIV “cured”
HIV suppressed on antivirals
Existing CD4 lymphocytes destroyed by conditioning
Stem cells reconstituted with HLA-matched but delta 32 homozygous allogeneic donor
Antiviral therapy stopped following transplantation
Remained HIV negative (by PCR)
HIV antibody titres have declined
How is Hep C virus treated
Interferons and ribavirin
(40-90% cure rate)
Increasing number of direct antivirals
How do antivirals work
block stage of viral replication,
act on virally encoded proteins
Types of pathogenic fungi
Yeast
Pneumocystis jiroveci
Dimorphic
filamentous fungi
what are the anti fungal targets
1) DNA synthesis
2) Mitosis
3) Cell membrane (Ergosterol)
4) Protein Synthesis
5) Cell wall - B-1,3-glucan
What is Ergosterol
- Found in fungal cell membrane
- Clusters in phospholipid bilayer
- regulates membrane permeability
- required for normal growth and function of fungal cell wall
What is the biosynthesis of Ergosterol
Squalene (Squalene epoxidase) Lansterol (Lansterol 14a demethylase) Ergosterol
What are B-1,3-glucans
- Large polymers of UDP-glucose
- 50 ‑ 60% of the dry weight of the fungal cell wall
- Form a fibrous network on the inner surface of the cell wall
- Synthesized by β-1,3-glucan synthase
What are the classes of anti fungal drugs
Polyenes Allylamines Azoles Echinocandins Others
Polyenes
- modes of action
- examples
Mode of action
Association with ergosterol
Formation of pore-like molecular aggregates
Aqueous vs. non-aqueous pores1
Loss of membrane integrity and leakage of K+
Cell death
Examples
Amphotericin B
Nystatin
What is Amphotericin B
Spectrum of activity
Most fungi of medical importance
Aspergillus spp., Candida spp., Cryptococcus spp.
Adverse effects
Allergic reactions
Nephrotoxicity
Pores are formed in ergosterol-free membranes
Lipid Associated Amphotericin B
Several different formulations
- Liposomal AmB (L-AmB)
- AmB lipid complex (ABLC)
- AmB colloidal dispersion (ABCD)
Minimize delivery of AmB to kidney cells
Delivery targeted to fungal cells and/or reticulo-endothelial system
Reduce nephrotoxicity
Clinical Uses
Amphotericin B
Nystatin
Amphotericin B
- Not orally absorbed
- serious sytemic infections
Nystatin
- Not absorbed orally
- superficial infections
- too toxic for systemic use
Allylamines
- how do they work
- example
Inhibit ergosterol syntheisis
- squalene epoxidase
Terbinafine
- broad spectrum
- liver toxicity adverse effect
Clinical uses of Allylamines
Dermatophyte infections
- topical - athletes foot, tinea corporis, (ring worm)
- systemic (oral) use - scalp ringworm, onychomycosis
Azoles
- what are they
Synthetic compound containing 5 membered azole ring
- Imidazoles - 2 N atoms
- Triazoles - 3 N atoms
What is the mode of action of Azoles, and spectrum of activity
inhibit ergosterol synthesis
build up non-ergosterol 14a-sterols in cell membrane
Spectrum
- essentially broad
exception - Fluconazole to treat aspergillus spp.
Uses of Imdazole
uses of triazoles
give examples of drugs for BOTH
Imidazole - TOXIC - rarely used systemically = Clotrimazole - superficial infections - candidiasis, dermatophytes
Triazole - less toxic -systemic use common = Fluconazole = Itraconazole = Voriconazole - systemic infections, aspergillosis, candidiasis
Adverse effects and drug interactions of Azoles?
Hepatotoxicity
- mild liver enzyme abnormalities (7% fluconazole)
Drug interactions - inhabit cytochrome P-450 enzymes
- increase conc of all drugs metabolised by Cy-P450
What is the anti fungal spectrum of
- fluconazole
- Itraconazole/ voriconazole
- Isavuconazole/Posaconazole
1) Fluconazole - Yeasts
2) Itraconazole/voriconazole - yeast, aspergillus
3) Posaconazole, isavuconazole
- yeast, aspergillus, mucoraceous moulds
Echinocandins
- action
- example
- adverse effects
- clinical use
inhibtion of B-1,3-glucan synthase
Anidulafungin
Caspofungin
Micafungin
minimal - rash, nausea vomiting
clinical - systemic infections
parenteral formulation only
5- fluorocytosine
- what is it?
- mode of action
- spectrum of activity
- adverse effects
- clinical use
synthetic analogue of cytosine
inhibits RNA/protein synthesis, and DNA synthesis but converting 5 flurouracil and 5 flurodeoxyurindine monophosphate
- yeast only, candida, cryptococcus
- bone marrow suppression
- crytococcal meningitis (comb with AmB)
Griseofluvin
- action
- spectrum
- adverse effects
- clinical use
- inhibition of fungal mitosis
- dermatophytes
- minimal adverse effects
- dermatophytes infections in kids
What antifungals need Therapeutic drug monitoring
Itraconazole
5-fluorocytosine
Voriconazole
Define parasite
The parasite derives all benefits from the association and the host may either be harmed or may suffer the consequences of this association
Define symbiosis
living together; close, long term interaction between two different species
Define Mutualism
an association in which both species benefit from the interaction
Define Commensalism
an association in which the parasite only is deriving benefit without causing injury to the host
What are the classes of host and define them
Definitive host
Either harbours the adult stage of the parasite or where the parasite utilizes the sexual method of reproduction
In the majority of human parasitic infections, man is the definitive host
Intermediate host
Harbours the larval or asexual stages of the parasite
Some parasites require two intermediate hosts in which to complete their life cycle
Paratenic host
Host where the parasite remains viable without further development
Classification of parasites
Protozoa - micro
Helminths - macro
Giadria lamblia
Entamoeba sp
P.Falciparum
are all examples of what
Protozoa
Cestode - Taenia sp
Trematode - schistosoma sp
Intestinal nematode - Ascaris Lumbeicoides
Tissue Nematode - Wuchereria bancrofti
are all examples of what
Helminths
Ascariasis Lumbricoides
- what type of parasite
- how is it acquired
- infection rate?
Lung Migrations
Intestinal phase
Treatment?
Control?
- Macro parasite , Intestinal Nematode
- Ingestion of eggs, poor hygiene
- 1 billion affected,
Lung
Loefflers syndrome - dry cough, dyspnea, wheeze, eosinophilic pneumonitis
Intestinal
Malnutrition, migration to hepatobilary tree, intestinal obstruction
Treatment - Albendazole
- prevents glucose absorption
Control - educated, community deworming
Schistosomiasis
- type
- caused by
- causes?
- Immediate host?
- clinical features
- Treatment
- control
Macro parasitite - helminth, fluke
aka - Bilharzia disease
S. haematobium
S. manson S. intercallatum
S. japonicum
S. mekongi
Immediate host - snap
causes - bladder cancer, liver cirrhosis
Swimmers itch, fever, haematuria, bladder fibrosis, portal hypertension, liver cirrhosis
Treatment - Praziquantel
Treat longterm complications
Control - kill snails, chemoprophylaxis, avoid snail infested water, education
Hydatid Disease
- type
- host
- caused by?
- clinical
- control
Macro parasite - tapeworm
Human accidental host, sheep
Echinococcus sp
Cysts - 70% liver 20% lungs
mass effect, bacterial infection
control - worm dogs, hand hygiene
Malaria
- type
- causes by
- vector?
- clinical
- control
Micro parasite - protozoa, sporozoan (plasmodium) P. falciparum P. vivax P. ovale P. malariae
Mosquitoes
Clinical - fever, rigors, cerebral malaria, renal failure, hypoglycaemia, pulmonary oedema, circulatory collapse, anaemia, bleeding, DIC
Control - insecticide, larvicidal spray of breeding pool, bed nets, chemoprophylaxis
Cryptosporidiosis
- cause
- causes
- how is it spread
- clinical
- treatment
- control
micro parasite - sporozoan Cryptosporidium parvum/ hominis - Diarrhoeal disease - faecal oral spread - 2-10day incubation - watery diarrhoea with mucus, bloating, cramp, fever, vomiting - usually self-limiting
Treatment - symptomatic - rehydration, nitazoxanide
Immunocompromised - Paromomycin, HAART
Control - Hand hygiene, boil water, pasteurise dairy products
Common anti protozoal treatments
Metronidazole Pentamidine Nitazoxanide Pyrimethamine Anti malarials - treatment - prophylaxis
Common anti Helminthic treatments
Albendazole
Mebendazole
Ivermectin
Praziquantel
When is IgM produced
What does IgG give
What are the materanal antibodies
- acute infection
- Long term immunity
- IgG and IgA (breast milk)
Measles
- Virus
- transmission
- infectivity
- incubation
- clinical features
- complications
- Treatment
- Prevention
- Paramyxovirus (single strand RNA virus)
- Person to person, Droplet
- 1st day of symptoms –> 4 days after rash gone
- 7-18days incubation
Clinical Features
- Rash - erythematous, maculopapular
- Fever
- Koplik’s spots
- Prodrome - fever, malais, 3 C’s
Complications
- otitis media
- pneumonia
- diarrhoea
- acute encephalitis 1/2000
- Subacute sclerosing pan encephalitis 1/25000
- Death
Treatment - Supportive, antibiotic for superinfection
Prevention - MMR live vaccine
Human normal immunoglobulin
What are the 3 c’s
Conjunctivitis, coryza, cough
Chicken Pox
- virus
- transmission
- incubation
- infectivity
- clinical features
- complications
- treatment
- prevention
- Viral Zoster Virus - herpes virus
- Respiratory spread, 15min face to face
- 14 days incubation
- 2 days before rash –> after dried up
Clinical features
Fever, malaise, anorexia
Rash - centripetal, vesicular
Complications
- Pneumonitis
- CNS involvement
- Foetal varicella syndrome
- Zoster
- Death
Treatment
- Acyclovir - oral
- Chlorpheniramine - for itch
- supportive
Prevention
- Vaccine - 2 live doses
- VZ immunoglobulin
Rubella
- Virus
- Transmission
- Incubation
- Infectivity
- clinical features
- complications
- Togavirus (RNA virus)
- Droplet spread/ airborne
- 14-21 days incubatoin
- 1 week pre rash 4 days post
Clinical Features
Prodrome
Lymphadenopathy
Rash - nonspecific
Complications
thrombocytopenia
post infection encephalitis
arthritis
Rubella in pregnancy
- what is congenital rubella syndrome
- treatment
- Foetal Damage
cataracts, deafness, cardiac abnormalities, microcephaly, small birth wieght, inflammatory lesions - brain, liver, lungs, bone marrow.
Foetal damage rare post 16/40
deafness reported 20/40
Treatment - non available
- immunoglobulin to pregnant woman
- vaccine - MMR
Parvovirus B19 (slapped cheek)
- Virus
- transmission
- incubation
- foetal disease
- clinical
- treatment
- control
B19 - DNA virus
- Respiratory secretions
- 4-14 days incubation
- anaemia, hydrops in foetus, risk of miscarriage
clinical minor respiratory illness slapped cheek arthralgia aplastic anaemia anaemia in immunosuppressed
Treatment
none - self limiting
blood transfusion
control
- hard as infectous before rash
Enteroviral infections
90% asymptomatic
hand foot and mouth
fever/rash syndromes
meningitis - PCR of CSF
Treatment - supportive, good hygiene to prevent infection
Respiratory Syncytial Virus (RSV)
- virus
- Bronchiolitis
- Diagnosis
- Treatment
Pneumovirus
Bronchiolitis - under 1yo, life threatening, reinfection common
Dx - PCR nasopharyngeal secretions
Rx - O2, manage fever, fluid intake
Immunoglobulin, monoclonal abs, Palivizumab
manage at home
Metapneumovirus
- what is it
- causes
- Diagnosis
- Treatment
Paramyxovirus
Respiratory illness similar to RSV
Dx - PCR
Rx - supportive only
Adenovirus
- Clinical
- Dx
- Rx
10% childhood Resp infections C- mild URTI, conjunctivitis, diarrhoea Dx- respiratory panel PCR, eye swap PCR Rx - none cidofovir if immunocompromised
Parainfluenza
- virus
- transmission
- clinical
- Dx
- Rx
Paramyxovirus Person to person inhalational C - croup, bronchiolitis, URTI Dx - multiplexed PCR Rx - none
Rhinovirus
- Virus
- Clincal
Picornaviridae
C - URTI, runny nose,
Rotavirus
- Virus
- Transmission
- Incubation
- Clinical
- Dx
- Rx
- Prevention
Reovirus (RNA) Faecal oral route 1-2 days incubation C- Diarrhoea, vommiting, risk mortality Dx - PCR Rx - rehydration Prevetion - oral live vaccine
Norovirus
- transmission
- course
- Dx
- Rx
Person to person, food borne
12-60hour course
Dx - PCR
Rx - rehydration
Mumps - virus - transmission - infecitivty - incubation - Preventions - clinical - complications Treatment
Paramyxoviridae family Droplet, direct contact, fomites pre parotid swelling and post 2-4 weeks incubations Prevention - MMR C - prodrome, earache, tenderness over ipsilateral parotid, pyrexia 40 degrees swelling decreases after 1 weeks
Complications submandibular/sublingual sialadenitis oophoritis meningitis encephalitis renal function abnormality Pancreatitis epididymo-orchitis
Rx - Supportive/symptomatic
why immunise
prevent disease
halt carriage and transmission
eliminate > eradicate disease
when does a primary immune response occur
IgM antibody
weeks following 1st exposure to antigen
When does secondary immune response occur
IgG - immunological memory
faster and more powerful
2nd exposure to antigen
Active immunity vaccination concepts
- live
- inactivated organisms
- components of organisms
- inactivated toxins
Live: MMR, BCG, Yellow fever, Varicella
Act like the natural infection
Inactivated organisms: pertussis, typhoid, IPV
Components of organisms: influenza, pneumococcal
Inactivated toxins: diphtheria, tetanus
Passive immunity vaccination concepts
- vertical transmission
- injected human immunoglobulin
Vertical transmission of auto-antibodies from mother to foetus & breastfeeding
Injection of human immunoglobulin
HNIG – pooled plasma
Specific – tetanus, botulism, hep B, rabies, varicella
Live vaccination
- advantages
- disadvantages
Advantages
Single dose often sufficient to induce long-lasting immunity
Strong immune response evoked
Local and systemic immunity produced
Disadvantages
Potential to revert to virulence
Contraindicated in immunosuppressed patients
Interference by viruses or vaccines and passive antibody
Poor stability
Potential for contamination
Inactivated vaccines
- advantages
- disadvantages
Advantages
Stable
Constituents clearly defined
Unable to cause the infection
Disadvantages Need several doses Local reactions common Adjuvant needed keeps vaccine at injection site activates antigen presenting cells Shorter lasting immunity
NHS vaccination programe
2mnths - 70 years
2 mth: DTaP/IPV/Hib + pneumo + rota 3 mth: DTaP/IPV/Hib + Men C + rota 4 mth: DTaP/IPV/Hib + pneumo 12 mth: Hib/Men C + MMR + pneumo 24 - 48 mth: annual flu 40 mth: dTaP/IPV + MMR 12 years: HPV for girls 14 years: Td/IPV + Men C 65 years: pneumo + annual flu 70 years: shingles
How are pathogenic organisms eliminated
- Environmental
- Equipment decontamination
- Antisepsis
- Antibiotic Prophylaxis
Environmental cleaning and decontamination
- H2O2 room decontamination
- Spillage management
- Laundry
Equipment decontamination
- Sterilisation
- Disinfection
Antisepsis
- Surgical skin prep
- MRSA decolonisation
Antibiotic prophylaxis
Perioperative
Post-exposure
What is an example of removing source/ reservoir
hand hygiene
environmental cleaning and decontamination
How is transmission minimised
- Hand Hygiene
- Personal protective equipment
- Equipment decontamination
- source and protective isolation
- disposable equipement
How is eliminated entry/exit acheived
Antisepsis
-Surgical skin prep
Asepsis
-Insertion and management of invasive devices
Air handling
- Air filtration and laminar flow
- Positive pressure ventilated lobby (PPVL) rooms
Sharps management
Patient management
-Minimise use and duration of invasive devices
How can susceptibility to infection be reduced
Antibiotic stewardship
- lower C.diff
immunisation
What is Sterilization
- methods
complete killing or removal of all types of microorganisms
Methods
- Heath - moist/dry
- Chemical - gas/liquid
- Filtration
- Ionising Radiation
How does sterilisation by heat work
- moist heat
- dry heat
Moist
- Autoclave - steam under high-pressure
Dry
- Oven - controlled temp cycles 160 2hrs or 170 1hr
What is disinfection
- what needs to be considered
Removal or destruction of sufficient numbers of potentially harmful micro-organisms to make an item safe to use
Chemical disinfectant - effect on micro-organisms, chemical properties, physical effects, harmful effects
What is antisepsis
applied to damaged skin or living tissues
Requires a disinfectant with minimal toxicity
How are surgical instruments reprocessed
Sterilization
Moist heat decontamination
How is a flexible endoscope reprocessed
High level disinfection
chemical disinfection
How is syringe needle processed
Sterilization
irradiation pre use
disposal after use
