W1P2 Flashcards
(145 cards)
1
Q
Antibiotics
A
Derivative produced by the metabolism of microorganisms that possesses antibacterial activity at low concentrations and is not toxic to the host. Also includes molecules obtained by semi-synthesis
2
Q
Antiseptics
A
Compounds used for the external treatment of wounds (19th century)
- Dakin’s solution (1915)
- Isopropyl alcohol
- Chlorhexidine
3
Q
What are the two factors involving in choosing an antibiotic
A
Route of administration
Oral (po), IV, IM, topical
Dosage
May depend on weight, age (sexual maturation), body surface area
Route and dosage DEPENDS on WHAT you are trying to treat and WHERE in the body.
- Pharmacodynamics and pharmacokinetics
POPULATION Age (Neonate, child, elderly) - Restrictions on use in various ages Pregnancy - Restrictions (harm to fetus) Renal or liver dysfunction - Routes of elimination
Site of Infection
4
Q
Empirical Treatment
A
Need to know which bacteria are usually involved in a particular clinical syndrome
- and you use an AB that you GUESS will work best
Need to know the prevalence of resistance to a particular antibiotic locally – hospital-level or community-level… changes over time
5
Q
What are the common potential pathogens in our Nose and Sinus
A
S.pneumoniae, GAS, S.aureus, H.influenzae
6
Q
What are the common potential pathogens in our Throat/Pharynx
A
GAS
7
Q
What are the common potential pathogens in our Lungs/Bronchi
A
S.pneumoniae, H.influenzae, S.aureus,
Klebsiella spp/other Enterobacteriaceae
8
Q
What are the common potential pathogens in our Middle Ear
A
S.pneumoniae
9
Q
What are the common potential pathogens in our Intestines
A
Salmonella, Shigella, E.coli O157:H7
10
Q
What are the common potential pathogens in our Urinary Tract
A
Enterobacteriaceae
Enterococcus
11
Q
What are the common potential pathogens in our CNS
A
N.meningitidis, H.influenzae, S.pneumoniae, Listeria
12
Q
What are the common potential pathogens in our Eye
A
Haemophilus, Moraxella, N.gonorrhoeae, S.aureus, S.pneumoniae
13
Q
What are the common potential pathogens in our Blood
A
anything. anYtHiNg
14
Q
What are the common potential pathogens in our Wouds
A
S.aureus, GAS
15
Q
What are the common potential pathogens in our Bone and Joints
A
S.aureus, GAS, Kingella kingae
16
Q
Pharmacokinetics
A
what the body does to the drug
17
Q
Pharmacodynamics
A
what the drug does to the body (therapeutic/toxic effects)
18
Q
What are the Important Drug Parameters
A
Absorption Distribution Half-life Protein binding Elimination
19
Q
***Which Antibiotics have such good bioavailability that po= IV availability?
- What is the rate limiting step here?***
A
Clindamycin po = IV Fluoroquinolones po = IV Septra po = IV Tetracyclines po = IV Metronidazole po = IV Linezolid po = IV
rate-limiting step:
- GI tolerance
- GI absorption (e.g. patient is nauseated etc)
20
Q
Pharmacokinetics: what are the two ways antibiotics work?
A
a. Time- dependent AB
- conc INdependent: really doesn’t matter HOW much you give***
b. Concentration- dependent AB
21
Q
Examples of Time- dependent antibiotics
A
Beta Lactams:
- Penicillins
- Cephalosporins
- Carbapenems
Just remember THESE^
Other: Vancomycin Macrolides Clindamycin Tetracyclines Linezolid Quinipristin/dalfopristin
22
Q
Concentration Dependent AB
A
Aminoglycosides
Fluoroquinolones
Metronidazole
23
Q
Pharmacokinetics: Time-Dependent Activity
A
Activity of the antibiotic is dependent on the AMOUNT of time that is spent above the minimum inhibitory concentration (MIC) of the organism for that specific antibiotic at that specific place/tissue/organ.
Classic type of antibiotic class that uses this: Beta-lactams
24
Q
***Pharmacokinetics
Concentration Dependent activity***
A
Activity of the antibiotic is dependent on the CONCENTRATION above the minimum inhibitory concentration (MIC) of the organism for that specific antibiotic at that specific place/tissue/organ.
Classic type of antibiotic class that uses this: aminoglycosides
25
What determines if the antimircrobial activity is Bacteriostatic vs Bactericidal?
```
Bacteriostatic vs. bactericidal:
Depends on activity of antimicrobial
Inhibition of cell wall synthesis or protein synthesis = cidal
Changes in bacterial physiology = static
Depends on drug concentration
```
26
What are the antimicrobial Classes
```
B- lactam AB [penicillins and their derivatives]
Cephalosporins
Carbapenems and
Monobactams
Glycopeptides
Macrolides and Ketolides
Aminoglycosides
Fluoroquinolones
Sulfonamides
Tetracyclines and Tigecycline
Lincosamides
Metronidazole
Rifamycins
```
27
Beta-Lactam Group
Penicillins
Cephalosporins
Carbepenems
Monobactam
28
* **Penicillins and their Derivatives are..**
- a part of which group?
- Mechanism of action
- Resistance
- what is their pharmacokinetics
Beta-Lactam group: All have a β-lactam ring in their molecular structure
Mechanism of action:
Inhibition of cell wall synthesis by binding to penicillin-binding proteins
Resistance:
Inactivation of antibiotic (penicillinase, or β-lactamase) (e.g. most MSSA)
Mutated penicillin-binding protein (e.g.. MRSA)
Decrease in penetration of antibiotics
SHEILD against resistance: β-lactamase inhibitors are added to penicillins to “mop-up” β-lactamase enzymes (irreversibly bind to them)
TIME-DEPENDENT KILLING
29
Penicillins
- What does it target
- resistance
While penicillin did/does well against gram-positive organisms including gram-positive anaerobes
Resistance:
S. aureus started to become resistant to it
- specifically those that developed Penicillinase (β-lactamase specific for penicillin)
Gram negative enterobacteriaceae started to become resistant
- β-lactamases
Emergence of new (and resistant) pathogens such as Pseudomonas spp became apparent
Obviously things needed to change... elevated AB were created to address resistant strains
30
What are new penicillins created for specific bacterial species?
S. aureus targeting designs
- Cloxacillin
- (Methicillin)
* Due to increased S. aureus activity = loss of anaerobic activity
* Aminopenicillines gives Expanded gram negative coverage (i.e. against E. coli)
- Ampicillin IV
- Amoxicillin (Amoxil) po
Expanded gram negative coverage (esp. Pseudomonas aeruginosa)
- Ticarcillin
- Piperacillin
31
Penicillins and B-lactamase inhibitors
This combination makes them resistant to β-lactamases
- side effect: Diarrhea, due to β-lactamase inhibitor
BROAD SPECTRUM
All combinations are active against:
- S. aureus
- Most gram-positive organisms including
- Enterococcus and Listeria spp
- Most gram-negative respiratory pathogens (Haemophilus and Moraxella spp)
- Most gram-negative enteric bacteria
- Most anaerobes (gram-positive and gram-negative)
Timentin and Pip/tazo
- Active against ALL above BUT ALSO Pseudomonas spp
32
General activity of Cephalosporins on gram positive vs gram negative
Cephalosporins effectiveness for gram +
Great in 1st gen, gets worse then 5th gen is good cause it acts against MRSA
They are inverse in their effectiveness against gram positive vs gram negative :
- Earlier gens: better at gram positive, nothing for gram negative
- Later gens: better at gram negative, worse for gram positives
* Generally are resistant to simple B lactamases
33
What are the Gram Negative EXCEPTIONS on the action of Cephalosporins
It has NO EFFECT on Campulobacter ssp
and
no effect on Pseudomonas EXCEPT Ceftazidime which works for pseudomonas in the 3rd and 4th generation ONLY
34
What are the Gram Positive EXCEPTIONS on the action of Cephalosporins
Cephalosporins don't work against these gram +ve: ENTEROCOCCUS and LISTERIA … therefore need to use another Antibiotic
35
Carbapenems
BROAD SPECTRUM
Like BROAD SPECTRUM β-lactams/β-lactamase inhibitor combinations
- Gram-positives (MSSA), gram-negative, anaerobes
- Usually resistant to β-lactamases
Recent emergence of carbapenemases in gram-negative enteric rods
- Emerging problem
36
Adverse reactions
All β-lactams
- Mild side effects
- Serious side effects
Mild side effects
- GI upset
- Diarrhea (β-lactamase inhibitors; cefixime/Suprax)
- Drug induced neutropenia
Serious side effects
- Seizures
ALL β-lactams lower seizure threshold**
Wide therapeutic window so pretty safe
Some lower the threshold more than others (e.g. imipenem)
- SO DON'T GIVE TO PEOPLE WITH MENINGITIS
- Anaphylaxis
If anaphylaxis with one penicillin, high risk of reacting to another penicillin – less risk with cephalosporins
3% cross-reactivity between penicillins and carbapenems
37
Pharmacological key points
β-lactams
| - Which cross the BBB
Which β-lactams cross the BBB appreciably?
```
Penicillin IV (high dose)
Ampicillin IV (high dose)
Third generation cephalosporins IV (high dose)
Cefepime
Carbapenems
```
38
Which β-lactams have activity against MSSA?
Cloxacillin po/IV (and methicillin)
β-lactam/β-lactamase combinations (po/IV)
1st and 2nd generation cephalosporins po/IV
- 3rd generation IV NOT that good – just OK
Cefepime
Carbapenems
39
Which β-lactams have activity against Pseudomonas spp?
```
Ticarcillin and Piperacillin (IV)
Timentin and Pip/tazo (IV)
Ceftazidime (IV)
Cefepime (IV)
Carbapenems (IV)
```
40
Which β-lactams have activity against anaerobes?
Penicillin (po/IV)
All β-lactam/β-lactamase combinations (po/IV)
Carbapenems (IV)
41
What are the 4 groups that beta lactams work against?
Staph aureus
E. coli
Pseudomonas
Anaerobes
42
Glycopeptides
| - examples
Vancomycin
| Teicoplanin
43
Vancomycin Action
TWO STEPS
- Chain linking and
- Cross bridging
"Inhibition of cell wall synthesis
Inhibit the the chain formation and the cross-linking of peptidoglycan"
44
Vancomycin's antibacterial spectrum
Possesses ONLY Gram positive activity including anaerobic gram-positive
very good activity against clostridium difficile (oral treatment)
* Vanco is the most effective against gram positive HOWEVER it works SLOWER. so in emerg/severe cases, you want to pair it with say a beta-lactam* for faster action.
45
Vancomycin biological absorption
BBB penetration, mainly with inflammation
Need higher levels to penetrate BBB, bone and cartilage, heart tissue
Need higher levels when dealing with MRSA
measure peak levels of AB to make sure it is enough to cross barriers.
46
Adverse Reactions of Vancomycin
Nephrotoxicity
Usually with accumulation (high trough levels)
when co-administered with other nephrotoxic drugs
Therapeutic drug monitoring to prevent this
When administered over short period (1 hr) [given too fast]
- Histamine release (Red-(wo)man syndrome) :
Flushing
Hives
Even hypotension
47
What are examples of Macrolides?
```
Macrolides
Erythromycin (IV/po)
- Erythromycin estolate (po)
Clarithromycin (po)
- Biaxin
Azithromycin (IV/po)
- Zithromax
```
48
Macrolide spectrum of resistance
Essentially
Gram-positives:
S. pneumoniae (if S)
Group A Streptococcus (if S)
Gram-negatives:
Campylobacter spp
Bordetella pertussis
Atypical bacteria:
Mycoplasma spp, Chlamydia spp, Clamydophila spp
Non-tuberculous mycobacteria:
Clarithromycin, azithromycin
49
Do Macrolides cross BBB?
NO
| so you can't use them to treat meningitis
50
Biology of Viruses
Obligate intracellular parasites
Use host cell machinery to replicate
Contain nucleic acid core surrounded by a protein capsid (some with envelopes)
Attach to host cells by binding to receptors on host cell surface
Enter cell by endocytosis of membrane
Assemble new particles within host cell that are released during cell lysis or by budding
51
Latent Virus
i.e. Chicken pox when you are young can remain unproblematic
| until you're older and it re-activates, manifests as Shingles
52
What is Vertical Transmission
| - Examples
In utero- from mother to baby
Fetus becomes infected in-utero in two different ways:
Maternal viremia and infection of placenta (e.g.: rubella, CMV, Parvovirus)
OR
Exposure to virus in birth canal (e.g.: HSV, HIV)
53
In arthropod borne diseases, what are examples of arthropods
ticks
| mosquitos
54
What is the difference between aerosol vs droplet transmission
Aerosal: a suspension of fine solid particles or liquid droplets in air or another gas
Droplet Transmission: occurs when bacteria or viruses travel on relatively large respiratory droplets that people sneeze, cough, or exhale
55
Gastrointestinal Route of Viruses
| - examples of GI viruses
Viruses shed in stool contaminate food or water subsequently ingested by a susceptible host (Fecal-oral spread)
```
Viruses must withstand GI tract (stomach acid, bile salts, proteolytic enzymes)
Enteroviruses
Hepatitis A
Norovirus
Rota virus
```
56
Examples of Transcutaneous Virus routes
Direct inoculation from insect bites, animal bites or from mechanical devices (needles)
Arboviruses (e.g.: dengue, West Nile)
CMV, Hepatitis B, HIV
Rabies
57
Arbovirus
Refers to VECTOR borne viruses, i.e. Mosquito viruses
58
Transmucosal Viral Route examples
i. e. sexual, genital or oral transmission
| - CMV, Hepatitis B, HSV, HIV
59
What are methods of Diagnosis
Tissue Culture
Cell lines, embryonated eggs, suckling mice
Antigen detection
ELISA, Immunofluorescence
Nucleic acid detection
In-situ hybridization, PCR
Serology
IgM +, 4-fold rise in acute and convalescent sera
60
RSV- Respiratory Syncytial Virus
SS RNA
G protein (attachment)*
F (fusion) protein*
Yearly epidemics
*what are ABs attack
Syncytial: the cells are clumped up
61
RSV epi and presentation in newborns
```
75% of infants seropositive by 1 yr
**Bronchiolitis**
Coughing, wheezing, dyspnea
More severe in newborns, prematures, infants with congenital heart diseases and chronic lung disease
Transmitted by respiratory droplets
```
62
Rhinovirus
- type
- transmitted by
- Incubation period
```
SS RNA
Many serotypes
“common cold”
Average person has one rhinovirus/yr
Transmitted by respiratory DROPLETS, contact
Incubation period 1-4 days
Most viral shedding in first 1-3 days
```
63
Rhinovirus
| - Secondary complications
Secondary complications: sinusitis, otitis media, asthma
Following infection , neutralizing antibody develops to that serotype
No vaccine exists
64
Adenovirus
- type
- structure
- Transmission
- What can it cause
47 human immunotypes
DS DNA, non-enveloped (helps** survive the stomach acid), not affected by pH, bile or proteolytic pancreatic enzymes, very stable
GI route^
Fecal-oral and aerosol transmission
URI, LRTI, GE, keratoconjunctivitis, hemorrhagic cystitis (blood in the urine)
65
Adenovirus
- epi
- clinical timeline
- use in therapy
75% of infections before 14 yrs. of age
Most respiratory or gastrointestinal
Latency with recurrent/prolonged shedding
Modified adenoviruses suitable candidates for recombinant vaccines,
(Covid) or as vectors for gene delivery
66
Coronavirus
- type
- epi
- serogroup
Enveloped SS RNA
30% of common colds (before covid, previous strains)
Serogroup 1: HCV 229E
Serogroup 2: HCV OC43
Sporadic, URI, pneumonia
67
SARS
- type
- year
- isolation level
Enveloped SS RNA
SARS CoV
recombinant mammalian and avian coronavirus?
Emerged in Guangdong province of China late 2002-early 2003
Worldwide spread
- 8098 infected, 774 deaths
Isolation of virus:
- Level 4 Facility needed
68
MERS-CoV
- place of origin, year
- transmission
Middle East beginning in 2012
Direct or indirect contact with infected camel
Limited, non-sustained human to human transmission
Nov 2019: 2494 cases, 858 deaths (34.4% case fatality)
83% from Saudi Arabia
69
COVID-19, SARS-Cov2
- date of origin
- variants of concern
- transmission
- TREATMENTS
WHO declares Pandemic
March 11, 202
SARS-CoV-2 is a beta coronavirus (same group as SARS virus and MERS virus )
Variants of concern: Delta, Omicron
Transmission: respiratory droplet/aerosol
Vaccination
Treatment: Remdesivir, steroids , monoclonal antibodies, thromboprophylaxis
70
Influenza Virus
- type
- 2 sig glycoproteins
- Antigen shift
- Antigenic Drift
SS RNA
Influenza A, B, C
2 glycoproteins:
HA (hemagglutinin) (H1, H2, H3)
NA (neuraminidase) (N1 N2)
```
Antigenic Shift (big changes in BOTH protein type )
(H1N1--> H2N2)
- heralds a pandemic because it has changed enough for people to not have immunity to it
```
Antigenic Drift (the 2 or 1 of the glycoproteins stay the same but other components of virus changes
71
Influenza
- Symptoms
- Transmission route
- Secondary complications
Fever, myalgias, HA, cough
Transmitted by droplets
There are a lot of secondary complications, especially bacterial pneumonia
72
Reassortment
The mechanism used by influenza to evade our immune system
1. Can affect, birds pigs humans
2. it can mix and mutate and hybridize [re-assort] in a bird or pig then come back to humans
73
Influenze Treatment
| - just know the main two
Interference with M2 (Amantadine):
Interferes with viral protein required for uncoating after endocytosis
Only for influenza A
Many side effects
```
Neuraminidase inhibitors (oseltamivir, (TamifluR) zanamivir):
Useful treatment and prophylaxis
```
74
Influenza Prevention
- types
- Mechanism
Vaccination
- Inactivated vaccines
- Live, attenuated, cold-adapted vaccines (cause your nose is coldest part of your body)
Need yearly vaccination
Each vaccine has 4 circulating viruses
Mechanism:
Injected into the nose where it multiplies, when it invades further down the throat = it will die cause too hot
We get local immunity in the nose since influenza gets in through there
Influenza and vaccine only stays in nose!
75
What are all the respiratory viruses cover (5)
RSV: respiratory syncital virus (infants)
rhinovirus (common cold)
```
Influenza
Covid, MERS, SARS
Adenovirus
Rhinovirus
RSV
```
76
Herpes Viruses (HSV)
- Type
- examples of some
- clinical timeline
DNA viruses
Herpes Simplex Virus 1, 2 (cold sores periodically is a reactivation of the herpes virus)
Varicella zoster virus
Epstein Barr virus
Cytomegalovirus
Establish latent infections, with reactivation
ubiquitous
77
HSV
- Transmission
- Target site
- Mechanism
Infection by direct inoculation of mucous membranes (mouth, eye, genital tract etc.)
Virus accesses nerve cell endings in epidermis
transported to the nerve cell bodies in peripheral ganglia to become latent
Reactivated virus travels down axonal processes
78
HSV Manifestations
| - sites of infection
```
Ocular infection
Oral infection
Genital herpes
Neonatal herpes [if mother has it and baby passes through vagina = can be deadly to baby]
Encephalitis
Disseminated herpes
```
79
Antiviral treatments for Herpes Infections
Nucleoside analogs (acyclovir)
- Analog of guanosine
- Can be phosphorylated by herpes virus enzymes, and then incorporated into viral DNA as a chain-terminating nucleotide.
Cannot eliminate latency
Long term treatment for suppression
80
Varicella
| - Complications
Varicella Zoster Virus
generalized vesicular rash, fever (aka chicken pox)
```
Complications:
bacteria superinfection (esp. Group A Strep)
thrombocytopenia
cerebellar ataxia
encephalitis
```
81
In which populations is Varicella MORE SEVERE
More severe disease in adolescents, adults and newborns
severe disease in immunocompromised
Reyes Syndrome
Fetal infection with embryopathy
82
Varicella Mechanism of action
| - Where does it establish latency
1. Aerosols enter respiratory tract (90% transmission rate*)
2. Replication of virus in regional lymph nodes, primary viremia, replication in liver and spleen
3. Secondary viremia, virus transmitted to the epithelial cells of the skin and mucosa
[so starts from core and spreads outwards]
Characteristic lesions
Establishes latency in dorsal root ganglia, reactivates as zoster (shingles)
83
Shingles
VZV—Zoster
Spread of virus to dorsal root ganglia
Zoster developing in later years along dermatome of the nerve from which the VZV was reactivated
There is a shingles vaccine for people around 50-60
84
CMV
- type
- timelines of protein production
This is a type of herpes virus
DS DNA, enveloped
Viral transcription follows CMV infection of cell
Appearance of IMMEDIATE EARLY PROTEINS (1 hr)
EARLY PROTEINS appear after 6-8 hr
LATE PROTEINS produced after initiation of replication
85
CMV
- infection rate/epi
- transmission routes
Ubiquitous: present, appearing, or found everywhere.
50-95% adults infected
Enter host through epithelium with persistence in hematopoietic and epithelial cells
Acquired early in life: perinatal, breast milk
Sexual acquisition
Congenital infection
86
CMV
- clinical presentations
- most at risk group
Most infections asymptomatic
Could be mono-like syndrome
Latent virus with periodic reactivation in saliva, urine, blood
Immunocompromised have more significant infection
87
EBV: Ebstein barr virus
- type
- route of transmission
- targets which cells?
aka kissing disease
Large enveloped DS DNA virus
Exposure of mucosal surfaces to virus
Infects B lymphocytes and epithelial cells
Latent infection with persistence of viral genome in memory B cells
88
EBV
- Infection rate
- age
- group most at risk
- Oncological potential
Infection rates 50-90% by adulthood
“infectious mononucleosis” infection in adolescence
Most at risk = In immunocompromised -can have B-cell immortalization and transformation
and Post-trasplant lymphoproliferative disease
Oncologic potential?
Hodgkin's Disease,
Links to Burkitt’s lymphoma,
nasopharyngeal carcinoma
89
What are the Herpes Viruses
Varicella
Varicella Zoster Virus
CMV
EBV
90
What are the viruses associated with Gastroenteritis
- Transmission
- Treatment
```
Rotavirus
Enteric adenoviruses
Norovirus
Astrovirus
Calicivirus
```
Clinically all have similar presentations
Transmission by fecal-oral route
Supportive treatment only
91
Rotavirus
- Type
- How many groups
- Peak age of infection
- season of increased risk
DS RNA, no envelope (acid-stabile, aka GI route, out through feceal matter) 70nm
A: most common, Re-infections with same serotype may occur
Peak age of infection : 6 months to 2 years
Most immune by age 4
Seasonal distribution peaking in winter
92
Rotavirus
- clinical features
- physiological consequences
- Detected by
Large number of rotaviruses in stool of infected child
Fever, vomiting, watery diarrhea, dehydration
Shortening and atrophy of small intestine villi
- Carbohydrate malabsorption
Detection
Don’t grow in tissue culture
Detect antigen by ELISA testing of stool
EM
93
Norovirus
- type
- named after?
- nature of outbreaks
- most frequent in which age group
- type of transmission
27 nm. Round, non enveloped calicivirus
Group of morphologically similar small round viruses (Norwalk, Hawaii, Snow Mountain)
Explosive outbreaks, incubation 1-2 days
Highly stabile in the environment
Most frequent in adult and school age children in outbreak setting
Perhaps second to rotavirus in causing diarrhea in children
Fecal-oral and aerosol transmission (vomiting)
shedding can last weeks after recovery
Short term immunity, but re-infection can occur
? Protection if blood Group B
94
Norovirus
- Symptoms
- Treatment
Usually mild and self-limiting illness
Vomiting, nausea, abdominal cramps, watery diarrhea. Usually no fever
Symptomatic treatment
95
Enterovirus
- List 3 main types
- Type
- how does this virus spread
- associated types of infection
1. Coxsackie A (23), Coxsackie B (6)
2. Echovirus (32)
3. Poliovirus 1, 2, 3,
```
type: Non enveloped = feceal-oral spread
Small picoRNAvirus
SS RNA, no lipid envelope, acid stable
Fecal-oral spread
Replicate in GI tract
```
Spread of virus through blood to target organs
Aseptic meningitis, herpangina, hand foot and mouth, myocarditis, hemorrhagic conjunctivitis
96
Echo Enterovirus, what does the name stand for?
Enteric Cytopathic Human Orphan Virus
enteric: came from stool
cytopathic: affects tissues
Human: came from human
Orphan: not associated with disease (from a child that was HEALTHY) HOWEVER we know know they ARE associated with illnesses, it IS. pathogenic one
97
Poli
- What type of Virus is it?
- two types of vaccines developed
Type:
Enterovirus
3 antigenic types
Invasion of brain and spinal cord, destroying anterior horn cells- become dependent on "iron lungs"
last major epidemic in Canada in 1959
1. inactivated vaccine (Salk) introduced in 1955 (IPV)
2. Trivalent oral live vaccine (Sabin) introduced in 1962 (OPV)
98
Polio Vaccine- IPV
Inactivated* Polio Vaccine
enhanced formulation with higher potency and more immunogenic than original
primary series will protect >99% of recipients
few adverse effects
99
Polio Vaccines- OPV
Oral Polio Vaccine
Live attenuated strains of Polio 1,2,3
immune response similar to natural infection with mucosal IgA immunity
vaccine virus shed in stool 1-2 weeks
Cheap, easy to administer, effective***
associated with VAPP: Vaccine Associated paralytic Polio (1 case/2.4 million doses)
so back to giving intramuscular
100
Rabbies
- Which virus
- Type of virus
- Where is it seen
- Which animals contribute and to what percent?
Lyssavirus: rod/bullet-shaped; RNA genome
Seen worldwide
- except Antarctica, and a few island nations
Worldwide animal rabies
Dogs 54%
Terrestrial wildlife (42%)
Bats (4%)
101
Rabies
| - How is it transmitted
Transmucosal transmission;
Salivary contact:
- Bite, mucous membranes, existing wound
- Respiratory tract
Bat caves
Incubation:
Days to years***
75% become ill in the first 90 days
- distance of bit from CNS (faster symptoms if bitten on the face)
102
Rabies
| - clinical presentation
Initial prodrome (lasts 4 – 10 days):
- Subtle neurological changes
- Tingling at bite site
- Headache, myalgia, non-specific flu-like illness
They get serious symptoms only once it progresses to:
CNS infection (encephalitis)
1. Confusion, agitation, hydrophobia, aerophobia
2. Progressive flaccid paralysis
103
Treatment of Rabbies
Used to be considered a lost cause once pt got meningitis
Milwaukee Protocol
- 2004, survival of Wisconsin teenager bitten by bat
- Drug-induced coma, Antivirals
Used since with limited success
Extremely high mortality rate
must focus on PREVENTION
104
Rabbies Prevention
Pre-exposure prophylaxis:
- Human diploid cell vaccine (given to Vets, needs to be re-administered often)
Post-exposure prophylaxis:
First: IMMEDIATE WOUND CARE
- May cut risk by 90%
- Povidone-iodine
Second: Rabies Immune Globulin (40 IU/kg) into all the wounds
Third step: Human diploid cell vaccine (up to 5 doses)
Local reactions are common but systemic reactions (Guillain-Barré) are VERY rare
105
Hemorrhagic Fever Viruses
- What does it look like
- Main examples
long, rod shaped, easily distinct
Ebola Virus
Dengue
106
Ebola Virus
- how serious is it
- reservoir
- Transmission route
Severe, often fatal disease in humans, primates
Natural reservoir unknown
Transmission from direct blood/secretions contact, contaminated needles
Person to person spread through direct contact with body fluids
Direct contact through broken skin or mucous membranes with virus-infected body fluid
[Named for Ebola River in Democratic Republic of Congo
First recognized 1976]
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Ebola Clinical Features
- incubation
- symptoms
```
Filovirus (filamentous shaped?)
Incubation 2-21 days
Fever, Headache,
joint pains
diarrhea, vomiting
Rash, red eyes
hemorrhage [end stage]
```
108
Dengue
- Genus
- Route of transmission
Type of Hemorragic Fever Virus
Genus: flavivirus
transmitted by MOSQUITO
- this vector has increased in population due to global warming it also found in central America. it has expanded it's distribution
Symptoms:
- Fever,
- Rash
- Muscle and joint pains
109
Dengue
- how many strains
- Distribution
- Epidemic vs Hyperendemic
4 strains.
Distribution: S. Asia, Africa, Caribbean, Southern US, Central America, South America, Pacific islands, Southern Europe
Epidemic (single virus strain)and hyperendemic (continuous circulation of multiple strains)
110
Dengue
- Type of virus
- What are the THREE clinical scenarios
Dengue Virus
RNA flavivirus
1. Dengue Fever:
Headache, myalgia, arthralgia, rash (may or may not have a rash)
2. Dengue Hemorrhagic Fever:
fever, bleeding, thrombocytopenia, plasma leakage
3. Dengue Shock Syndrome:
circulatory failure
no rapid test, hard to do serology. so HARD TO DIAGNOSE right away. no treatment anyway
111
Visibly what features of Tick tell you that they can cause Lyme disease?
only BLACK LEGGED Ticks cause lyme disease
112
What is the bacteria in Ticks that cause infections?
Boreillia Burgdorferi
113
Lyme Disease
- Caused by
- How is it spread
- Where does it originate
Bacteria: Borrelia Burgdorferi
Spread to humans by deer ticks (BLACK LEGGED TICKS)
originates in rodents
Tick bites infected rodent, then bites human -> human contracts Lyme disease
stains gram NEGative
114
Diagnosing Lyme Disease
do test at least 4-6 weeks after bite
Theres a screening test but you don't tell patient that screening is positive until the confirmatory test comes back which will come in 5 days
it's a two step process
if you get a neg, you stop. if you get a positive you send for second check. if it is positive THEN
you check for IgM
if IgM positive: RECENT infection
IgM negative: past infection
115
Lyme Management
- Oral vs
- IV regimens
Oral regimens
Amoxicillin
Doxycycline – ONLY DRUG USED FOR PROPHYLAXIS AND TREATMENT
Cefuroxime axetil
Azithromycin for severely allergic patients (to beta-lactams)
IV regimens
Ceftriaxone
Cefotaxime
Treatment regimens are anywhere from 14 days to 28 (rarely 56) days depending on disease stage.
116
Doxycycline and Lyme Disease
Doxycycline is not contraindicated any more in both prophylaxis and treatment of Lyme disease in children < 8 years of age
- No increased risk of teeth staining
Prophylaxis with doxycycline for children now is an option. Reserved for:
- Tick bite in an endemic area of
Quebec (or outside Quebec) just give right away to reduce ris kby 90%
- Tick attached for >24 hours
- GIVE WITHIN 72 hours after removal of tick bite
- NO SIGNS of Lyme disease
- No contraindications for giving doxycycline
117
Testing ticks to identify Borrelia B presence
It is not recommended to regularly test any ticks for identification and if Ixodes scapularis to test them for Borrelia burdorferi PCR.
- What will it change?
- Testing is done for surveillance purposes only and will not affect your clinical approach
Basically you will give prophylaxis if NO SIGNS of Lyme disease in a recently bitten patient in an endemic area.
Prophylaxis is not recommended in all tick bite cases. In that case, watchful waiting by the parents/patients is recommended and seek medical advice if symptoms arise
118
In which tick bites cases would you AVOID giving prophylaxis
a. Tick bite LESS than 24 hours ( not enough time for transmission)
b. if its already been 3 days since the bite. would already be in the incubation period. giving AB now would reduce symptoms but it will likely return later.
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What are the visible EARLY signs of Lyme Disease
```
Early Localized (3-30 days)
Erythema Chronicum Migrans
greater than 5 cm
NON itchy
NON painful
```
VS
```
Early Disseminated (3-30days)
MULTIPLE Erythema Chronicum migrans at sites AWAY from initial bite +/- asthenia and fever
```
AND sometimes
Bell's palsy: an unexplained episode of facial muscle weakness or paralysis
120
What are the LATE signs of Lyme Disease
These are symptoms that arise LATER, like 1-2 MONTHS later
a. Cardiac disease Carditis, 1st-3rd blocks
b. Bell’s Palsy and Meningitis
c. Monoarticular arthritis (usually large joint (knee))
121
Chronic Lyme Disease
This is FAKE NEWS
There is no medical evidence that persistent vague symptoms (fatigue, “brain fog”, nightmares, depression) are due to ACTIVE Borrelia bacteria once Lyme Disease is properly DIAGNOSED and TREATED.
Lyme Disease is not cancer and is treatable at ANY stage of diagnosis
...?Persistent inflammation (knee pain for example or headaches that eventually go away) versus psychosomatic disturbances versus NO Lyme Disease diagnosis
122
IF you see someone with a tick hanging on them, what should you do?
you DO want to remove it ASAP, as if you can get it off within 24 hours reduces infection
HOWEVER, it needs to be done properly with tweezers, you have to make sure the HEAD of the tick is OUT
123
***Antibacterial spectrum of MACROLIDES
Essentially:
Gram-positives
S. pneumoniae (if S)
Group A Streptococcus (if S)
Gram-negatives
Campylobacter spp
Bordetella pertussis
Atypical bacteria
Mycoplasma spp, Chlamydia spp, Clamydophila spp
Non-tuberculous mycobacteria
Clarithromycin, azithromycin
124
Antibacterial Spectrum of Aminoglycosides
- including...
- excluding...
THINK:
- Gram-negative, gram-negative, gram-negative
Including Pseudomonas spp
-Except Salmonella spp, Neisseria spp
Some have activity against TB and non-TB mycobacteria
Paromomycin has anti-parasitic activity
- Giardia lamblia
125
Adverse reactions of Aminoglycosides
```
Renal toxicity:
Associated with high accumulated levels
- High trough levels
Increased if co-administered with other nephrotoxic drugs
Reversible
```
Vestibular and cochlear toxicity:
Associated usually with prolonged use
Tinnitus is the first problem sign
Irreversible hearing loss
for these two mentioned^ THERAPEUTIC DRUG LEVEL MONITORING REQUIRED
Muscular blockade:
Should be avoided in people with neuromuscular diseases
- Botulism, Duschenne muscular dystrophy, myasthenia gravis etc
126
Fluoroquinolones
| Which one do you have to remember***
Ciprofloxacin po/IV (Cipro)
Levofloxacin po/IV (Levaquin)
“The respiratory quinolone”
Moxifloxacin po (Avelox)
[Mechanism: Inhibition of bacterial DNA synthesis
DNA gyrase & topoisomerase II/IV]
127
Effectiveness of Fluroquinolones from 2nd to 4th gen on
a. s. pneumoniae
b. MSSA
c. Enteric Gram neg rods
d. Pseudomonas spp
e. Atypicals
WHICH COLOUR STAIN for each?
a. s. pneumoniae: starts fair and increases
BLUE STAIN
b. MSSA: starts poor, but increases
BLUE STAIN
c. Enteric Gram neg rods: all gens are EQUALLY effective
RED STAIN
d. Pseudomonas spp: starts well, decreases in effectiveness
RED STAIN
e. Atypicals: all gens are EQUALLY effective. this one
DOES NOT STAIN because no membrane
128
Fluoroquinolone bioavailbaility
oral = IV availability*
but you CAN'T take it with MILK
129
Antibacterial Spectrum for Sulfonamides
| - no activity against
```
It is broad spectrum
Great against gut gram negatives
- you can treat UTIs
- good against chlamydia too (atypical)
Good gram positive activity EXCEPT No activity against Group A Streptococcus, and Enterococcus spp
```
130
Bioavailability of Sulfonamides
PO = IV availability
131
Antibacterial Spectrum of Cyclines
Tetracyclines
Gram negative enteric rods
Anaerobes
Atypical bacteria
Tigecycline [more broad spectrum]
Gram negative enteric rods
- Even those resistant to tetracyclines
- Multiresistant Enterobacteriaceae
Gram positive
- MRSA, VRE, Penicillin-resistant S. pneumoniae
Anaerobes
Atypical bacteria
132
Availability of Cyclines
ORAL = IV availability
133
*****Mechanisms of Action and Resistance for Clindamycin
THIS IS A TYPE OD LINCOSAMIDE
Inhibition of protein synthesis
Resistance:
- Similar to macrolides
Bacteriostatic time-dependent activity
134
AB spectrum for Clindamycin
Think GRAM POSITIVE
and ANAEROBES
noooo gram neg coverage
135
Clindamycin, Bioavailability
oral = IV/IM availability
136
Adverse reactions of Clindamycin
Usually well tolerated
May cause moderate diarrhea
Associated with C.difficile colitis
like many other antimicrobials
137
Flagyl
This is a type of METRONIDAZOLE
spectrum: remember ANAEROBES (gram positive AND gram negative)
- good against clostridium difficle
ALSO THINK: Antiparasitic activity (Giardia lamblia, Entamoeba histolytica)
138
Which is the only AB you should avoid taking alcohol with?
Metronidazole/Flagyl
139
Bioavailability for Metronidazole
PO = IV
140
AB activity of Rifamycins
On their own, rifamycins induce RAPID resistance
- NEVER used alone to treat infections
Always with other antibiotics to buffer resistance
Can be used alone as prophylaxis
- Against developing meningitis from N.meningitides, and H. influenzae
141
AB spectrum for Rifamycins
- What are the MAJOR drug interactions
THINK:
Treatment:
- TB
- non-TB mycobacteria
Post-exposure prophylaxis:
- N. meningitides (meningitis and/or meningococcemia)
- H. influenzae (meningitis)
MAJOR drug interactions
- are metabolized in the liver and induce CYP-450 enzymes
142
Adverse reactions to Rifamycins
Mainly GI
Nausea
Increase in liver enzymes
Skin rashes
Rifampin:
Orange-red colouration of body fluids (urine, tears)
May stain contact lenses
Rifabutin:
Bronze discolouration of skin
Violet-red colouration of urine
143
* **Nitrofurantoin
| - USE
Only used for non-complicated cystitis treatment and UTI prophylaxis
**Therapeutic concentrations achieved ONLY in urine
THINK: treamtment of uncomplicated UTI/cystitis
144
ABs specifically produced for multiresistant gram-positive bacteria
AGAINST MRSA AND/OR VRE
Oxazolidinones
- Linezolid
Streptogramins
- Quinipristin/Dalfopristin
Daptomycin
Ceftaroline (5th generation cephalosporin)
– only for MRSA (not VRE)
they all inhibit protein synthesis
145
* ***Linezolid
- availability
- ADVERSE reactions
PO = IV
Risk of thrombocytopenia
(esp. if prolonged treatment > 2 weeks)
reversible
```
Inhibitor of monoamine oxydase
Serotonin syndrome
- Avoid SSRI
- Avoid or limit tyramine-containing foods
A. Cheeses
B. Smoked and processed meats
```
