CP Microbiology x8 lectures Flashcards
(137 cards)
1
Q
Define - Antibiotic
A
Chemical products of microbes that inhibit or kill other organisms
2
Q
Define Antimicrobial agents
A
-Antibiotics
-Synthetic compounds with similar effect
-Semi-synthetic i.e. modified from antibiotics
Different antimicrobial activity/spectrum, pharmacological properties or toxicity
3
Q
Define Bacteristatic
A
Inhibit bacterial growth
Protein synthesis inhibitors
4
Q
Define Bactericidal
A
Kill bacteria
Cell wall-active agents
5
Q
Define minimum inhibitory concentration (MIC)
A
Minimum concentration of antibiotic at which visible growth is inhibited
6
Q
Define Synergism
A
Activity of two antimicrobials given together is greater than the sum of their activity if given separately
7
Q
Define Antagonsim
A
One agent diminishes the activity of another
8
Q
Define indifference
A
Activity unaffected by the addition of another agen
9
Q
Define clinical relevance
A
Synergism
β-lactam/aminoglycoside combination therapy of streptococcal endocarditis
10
Q
What are antibacterial mechanisms
A
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
11
Q
What are antibiotic targets
A
Cell wall Protein synthesis DNA synthesis RNA synthesis Plasma membrane
12
Q
What is the major component of bacterial cell wall
A
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
13
Q
What drugs are cell wall synthesis inhibitors
A
β-lactams
Glycopeptides
14
Q
Explain β-lactams
A
- 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
15
Q
What areβ-lactam antibiotics
example drugs
A
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
16
Q
What are glycopeptides
A
- 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
17
Q
In bacteria where does protein synthesis occur
A
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
18
Q
What do aminoglycosides do
A
Protein synthesis inhibitors
Gentamicin, amikacin
Bind to 30S ribosomal subunit
Mechanism of action not fully understood
19
Q
What are Macrolides, Lincosamides, stretogamins (MLS)
A
protein synthesis inhibitors Erythromycin, clarithromycin (macrolides) Clindamycin (lincosamide) Bind to 50S ribosomal subunit1 Blockage of exit tunnel Inhibit protein elongation
20
Q
What does tetracycline do?
A
Protein synthesis inhibitor Tetracyclines (tetracycline, doxytetracycline) Bind to 30S ribosomal subunit Inhibit RNA translation Interfere with binding of tRNA to rRNA
21
Q
actions of oxazolidines
A
Oxazolidinones Linezolid Inhibits initiation of protein synthesis Binds to 50S ribosomal subunit Inhibits assembly of initiation complex May also bind to 70S subunit
22
Q
What are mupirocin and fusidic acid
A
protein synthesis inhibitors
23
Q
Examples of DNA synthesis inhibitors
A
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
24
Q
RNA synthesis inhibitors
A
Rifampicin
RNA polymerase inhibitor
Prevents synthesis of mRNA
25
Plasma membrane agents
Daptomycin
Cyclic lipopeptide
Inserts lipophilic tail into cell membrane resulting in depolarisation and ion loss
Effective in Gram-positives only
26
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
27
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
28
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
29
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
30
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
31
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
```
32
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
33
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
34
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.
35
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
36
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
37
How does disk susceptability work
1) add organism
2) add antibiotics
3) incubate
4) read and interrupt result
- zone of inhibition
5) clinical interpretation
38
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
39
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”
40
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
41
What are reasons for Absent target
Fungi/virus
| infection is not bacterial
42
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
43
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)
44
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)
45
Drug efflux - causes?
Multiple antibiotics, specially in Gram-negative organisms1
| Antifungal triazoles and Candida spp.
46
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
47
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
48
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
49
What was the estimated number of people living with HIV in 2012
2.3million (1.9-2.7 million)
50
Pathogenesis of viral infections
- acute
- chronic
Acute - flu, measles, mumps
Chronic
- latent (with/without recurrence) - Herpes simplex, cytomegalovirus
-Persistent - HIV, Hep B, Hep C
51
What do viruses consist of
```
Nucleic acid (DNA, RNA)
Protein - structural coat, enzymes
Lipid evelope
Obligate intracellular parasite
```
52
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
53
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
54
What is the structure of a nucleotide
Base, Ribose sugar, triphosphate
55
What is AZT - azidothymidine
Inhibits HIV replication
| NRTI - nucleoside reverse transcriptase inhibitor
56
What are NRTIs
| Examples x2
Nucleoside reverse transcriptase inhibitors
Pyrimidine analogues
-Thymidine analogues
-Zidovudine
Cytosine analogues
-Lamivudine
Purine analogues (Adenine and Guanidine)
- Abacavir
- Tenofovir
57
HBV - what is it
Hep B virus
contains reverse transcriptase enzyme,
Lamividine and tenofovir active against HBV
58
What are NNRTIs
| examples x2
Non-nucleotide reverse transcription inhibitors
1) Efavirenz
2) Nevirapine
59
What are protease inhibitors
```
Atazanavir
Darunavir
Fospamprenavir
Lopinavir
Nelfinavir
Ritonavir*
Saquinavir
```
60
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)
61
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
```
62
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
63
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
64
How is Hep C virus treated
Interferons and ribavirin
(40-90% cure rate)
Increasing number of direct antivirals
65
How do antivirals work
block stage of viral replication,
| act on virally encoded proteins
66
Types of pathogenic fungi
Yeast
Pneumocystis jiroveci
Dimorphic
filamentous fungi
67
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
68
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
69
What is the biosynthesis of Ergosterol
```
Squalene
(Squalene epoxidase)
Lansterol
(Lansterol 14a demethylase)
Ergosterol
```
70
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
71
What are the classes of anti fungal drugs
```
Polyenes
Allylamines
Azoles
Echinocandins
Others
```
72
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
73
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
74
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
75
Clinical Uses
Amphotericin B
Nystatin
Amphotericin B
- Not orally absorbed
- serious sytemic infections
Nystatin
- Not absorbed orally
- superficial infections
- too toxic for systemic use
76
Allylamines
- how do they work
- example
Inhibit ergosterol syntheisis
- squalene epoxidase
Terbinafine
- broad spectrum
- liver toxicity adverse effect
77
Clinical uses of Allylamines
Dermatophyte infections
- topical - athletes foot, tinea corporis, (ring worm)
- systemic (oral) use - scalp ringworm, onychomycosis
78
Azoles
| - what are they
Synthetic compound containing 5 membered azole ring
- Imidazoles - 2 N atoms
- Triazoles - 3 N atoms
79
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.
80
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
```
81
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
82
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
83
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
84
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)
85
Griseofluvin
- action
- spectrum
- adverse effects
- clinical use
- inhibition of fungal mitosis
- dermatophytes
- minimal adverse effects
- dermatophytes infections in kids
86
What antifungals need Therapeutic drug monitoring
Itraconazole
5-fluorocytosine
Voriconazole
87
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
88
Define symbiosis
living together; close, long term interaction between two different species
89
Define Mutualism
an association in which both species benefit from the interaction
90
Define Commensalism
an association in which the parasite only is deriving benefit without causing injury to the host
91
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
92
Classification of parasites
Protozoa - micro
| Helminths - macro
93
Giadria lamblia
Entamoeba sp
P.Falciparum
are all examples of what
Protozoa
94
Cestode - Taenia sp
Trematode - schistosoma sp
Intestinal nematode - Ascaris Lumbeicoides
Tissue Nematode - Wuchereria bancrofti
are all examples of what
Helminths
95
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
96
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
97
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
98
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
99
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
100
Common anti protozoal treatments
```
Metronidazole
Pentamidine
Nitazoxanide
Pyrimethamine
Anti malarials
- treatment
- prophylaxis
```
101
Common anti Helminthic treatments
Albendazole
Mebendazole
Ivermectin
Praziquantel
102
When is IgM produced
What does IgG give
What are the materanal antibodies
- acute infection
- Long term immunity
- IgG and IgA (breast milk)
103
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
104
What are the 3 c's
Conjunctivitis, coryza, cough
105
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
106
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
107
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
108
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
109
Enteroviral infections
90% asymptomatic
hand foot and mouth
fever/rash syndromes
meningitis - PCR of CSF
Treatment - supportive, good hygiene to prevent infection
110
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
111
Metapneumovirus
- what is it
- causes
- Diagnosis
- Treatment
Paramyxovirus
Respiratory illness similar to RSV
Dx - PCR
Rx - supportive only
112
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
```
113
Parainfluenza
- virus
- transmission
- clinical
- Dx
- Rx
```
Paramyxovirus
Person to person inhalational
C - croup, bronchiolitis, URTI
Dx - multiplexed PCR
Rx - none
```
114
Rhinovirus
- Virus
- Clincal
Picornaviridae
| C - URTI, runny nose,
115
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
```
116
Norovirus
- transmission
- course
- Dx
- Rx
Person to person, food borne
12-60hour course
Dx - PCR
Rx - rehydration
117
```
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
118
why immunise
prevent disease
halt carriage and transmission
eliminate > eradicate disease
119
when does a primary immune response occur
IgM antibody
| weeks following 1st exposure to antigen
120
When does secondary immune response occur
IgG - immunological memory
faster and more powerful
2nd exposure to antigen
121
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
122
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
123
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
124
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
```
125
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
```
126
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
127
What is an example of removing source/ reservoir
hand hygiene
| environmental cleaning and decontamination
128
How is transmission minimised
- Hand Hygiene
- Personal protective equipment
- Equipment decontamination
- source and protective isolation
- disposable equipement
129
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
130
How can susceptibility to infection be reduced
Antibiotic stewardship
- lower C.diff
immunisation
131
What is Sterilization
| - methods
complete killing or removal of all types of microorganisms
Methods
- Heath - moist/dry
- Chemical - gas/liquid
- Filtration
- Ionising Radiation
132
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
133
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
134
What is antisepsis
applied to damaged skin or living tissues
| Requires a disinfectant with minimal toxicity
135
How are surgical instruments reprocessed
Sterilization
| Moist heat decontamination
136
How is a flexible endoscope reprocessed
High level disinfection
| chemical disinfection
137
How is syringe needle processed
Sterilization
irradiation pre use
disposal after use
