Final - Biomedical Sciences (No Westburg)

Antibiotic Susceptibility Testing (AST)

when drugs are tested in vitro against a specific organism to determine a minimal inhibitory concentration

MIC (Minimal Inhibitory Concentration)

the lowest concentration of a drug that inhibits bacterial growth

MIC50

the drug concentration that inhibits 50% of the bacterial population

Susceptibility Breakpoint

the threshold of MIC or zine diameter used to categorize bacteria as susceptible, intermediate, or resistant to an antibiotic

How is culture and susceptibility testing conducted?

step 1 and 2:

- culture patient site and incubate sample until it turns positive

- gram stain and identification (takes up to 24-48 hours)

step 3:

- tak bacteria grown form the sample and inoculate/conduct susceptibility testing

- incubate 24-48 hours

advantages and disadvantages: broth microdilution

advantage: gold standard, automated testing, can test multiple strains

disadvantage: manual processes can be confusing; small volume.

advantages and disadvantages: agar dilution

advantage: quantitative, can test multiple strains

disadvantage: time-consuming, manually prepared, mainly for research

advantages and disadvantages: gradient diffusion strips

advantage: quantitative, faster than agar dilution

disadvantage: expensive, subjective reading, no clinical guideline recommendations

advantages and disadvantages: disk diffusion (Kirby-Bauer)

advantage: simple, inexpensive

disadvantage: qualitative only (no MIC values), limited by plate/bug/drug specifications

Susceptible

effective treatment likely at standard doses

Susceptible-dose-dependent (SDD)

effective only with higher or adjusted doses

Intermediate

moderate likelihood of treatment efficacy

Resistant

likely ineffective at normal doses

How is antibiotic therapy optimized based on AST results?

- after obtaining C&S results, determine the best antibiotic

- adjust dosing based on MIC proximity to breakpoints

- consider SDD drugs for higher dosing regimens or frequent administration

What is the role of breakpoints in antibiotic selection?

they are established based on clinical data and pharmacokinetics

How is pharmacodynamics helpful in antibiotic selection?

it helps define the concentration needed for effective therapy

High MIC values may indicate the need for __________ doses and ____________________ infusions.

higher/extended

Epidemiological Cutoff Values (ECV)

- represents the highest MIC in the wild-type (non-resistant) microbial population)

help assess microbial populations and resistance

Rapid Diagnostic Testing (RDT)

speed up diagnosis an susceptibility testing from days to hours

advantages and disadvantages of RDTs

advantages: timely antimicrobial optimization, improved patient outcomes, and reduced hospital costs

disadvantages: expensive, not widely used yet, and require significant teamwork and clinical intervention

What are bacterial pathogens that cause respiratory tract infections?

Haemophilus influenzae

Bordetella pertussis (whooping cough)

Moraxella catarrhalis

Streptococcus pneumoniae (Pneumococcus)

Pseudomonas aeruginosa

Legionella pneumophila

Klebsiella pneumoniae

Mycoplasma pneumoniae

Chlamydophila pneumoniae

Acinetobacter

Burkholderia

Stenotrophomonas

What are pathogens the cause community-acquired pneumonia (CAP)?

Streptococcus pneumoniae

Haemophilus influenzae

Mycoplasma pneumoniae

Chlamydophila pneumoniae

Legionella pneumophila

Moraxella catarrhalis

What are important bacterial pathogens that cause otitis media?

Streptococcus pneumoniae

Haemophilus influenzae

Moraxella catarrhalis

Klebsiella pneumoniae (in some cases)

Mycoplasmas

- unusual, self-replicating intracellular bacteria

- strict dependence on host for nutrients and refuge

- lacks a cell wall

Corynebacterium diphtheriae

- causes diphtheria

- symptoms of exudative pharyngitis with thick pseudomembrane on tonsils

- transmitted by inhalation or skin contact

- may cause obstructed breathing/suffocation, leading to mucosal cell death

Corynebacterium diphtheriae Pathogenesis

diphtheria toxin kills epithelial cells in the pharynx causing the pseudomembrane

- the important toxic effect are on the heart leading to heart failure

Atypical Pneumonia Charcateristics

- subacute onset

- nonproductive cough

- often less severe

- chest X-ray findings are often worse than the physical symptoms

What causes atypical pneumonia?

caused by Mycoplasma pneumoniae, Chlamydophila pneumoniae, and respiratory viruses

Typical Pneumonia Characteristics

- rapid onset

- productive cough

- more severe physical findings

What causes typical pneumonia?

caused by Streptococcus pneumoniae, Haemophilus influenzae, etc.

Describe how pneumonia pathogenesis occurs.

- pathogens are aspirated or inhales into the respiratory tract

- bacterial invasion leads to edema, infiltration of PMNs, RBCs, and macrophages

******Streptococcus pneumoniae causes no permanent tissue destruction, while S. aureus, enterobacteriaceae, and anaerobes cause permanent damage.

Transmitted via respiratory droplets

Haemophilus influenzae, Bordetella pertussis (Whooping Cough), Moraxella catarrhalis, Streptococcus pneumoniae (Pneumococcus), Mycoplasma pneumoniae, Chlamydophila pneumoniae

Klebsiella pneumoniae (from coughing or sneezing

Transmitted through contact with contaminated surfaces or medical equipment

Acinetobacter, Klebsiella pneumoniae, Pseudomonas aeruginosa, Burkholderia, Stenotrophomonas

Transmitted through aerosolized water droplets

Legionella pneumophila

found in environmental sources (e.g. soil and water)

Burkholderia species

found in aquatic environments

stenotrophomonas

skin and respiratory tract colonizer

Acinetobacter

Nosocomial (Hospital Acquired) Pathogens **Opportunistic

Acinetobacter, Klebsiella pneumoniae, Pseudomonas aeruginosa, Burkholderia, Stenotrophomonas

Which bacterial respiratory diseases are vaccine-preventable?

1. Streptococcus pneumoniae:

- vaccines cover 23 of the most common serotypes (adult vaccine) and 13 (childhood vaccine)

2. Haemophilus influenzae:

- Hib vaccine

- prevents meningitis, epiglottitis, and other infections

3. Bordetella pertussis:

- DTP vaccine prevents whooping cough

4. Corynebacterium diphtheriae:

- diphtheria vaccine

What are key aspects of bacterial pathogenesis in respiratory infections?

1. adherence

2. invasion

3. toxins

4. evasion of immune response

Adherence

bacteria attach to respiratory epithelial cells

Invasion

bacterial invasion of the alveoli causes inflammation, edema, and infiltration

Toxins

bacteria produce endotoxins or exotoxins that damage tissues and interfere with normal function

Evasion of Immune Response

bacteria use antiphagocytic capsules to evade immune system

Haemophilus influenzae Pathogenesis

- colonizes the upper respiratory tract and spreads via respiratory droplets

- produces endotoxins and antiphagocytic polysaccharide capsules, helping the pathogen evade immune defenses

Haemophilus influenzae causes

otitis media, sinusitis, bronchitis, pneumonia, meningitis, and epiglottitis

Bordetella pertussis Pathogenesis

- attaches to ciliated epithelial cells in the upper respiratory tract

- pertussis toxin interferes with cell signaling, leading to inflammation and cilial cell death

- causes persistent paroxysmal coughing, often leading to secondary complications like asthma exacerbations

________ treatment is most effective for treating Bordetella pertussis

early

Moraxella catarrhalis Pathogenesis

- transmitted via respiratory droplets and often causes otitis media in children

- can lead to bronchitis and pneumonia, particularly in older adults and immunocompromised individuals

- known for exacerbating chronic obstructive pulmonary disease (COPD) in adults

Acinetobacter causes

pneumonia, sepsis, and UTIs

- often in immunocompromised patients

Streptococcus pneumoniae (Pneumococcus) Pathogenesis

- colonizes the nasopharynx and can spread to the lungs, causing pneumonia

-produces a capsule that inhibits phagocytosis, a major virulence factor

Streptococcus pneumoniae (Pneumococcus) causes

otitis media, sinusitis, meningitis, and pneumococcal pneumonia

Streptococcus pneumoniae (Pneumococcus) i worsend by

pre-existing conditions like influenza or smoking

____________ is the key virulence factor and vaccine target the most common serotypes.

capsule

Which pathogen is resistant to beta-lactam antibiotics?

mycoplasma pneumoniae

Mycoplasma pneumoniae Pathogenesis

adheres to respiratory epithelial cells causing cilial dysfunction and necrosis

causes walking pneumonia

Mycoplasma pneumoniae

Legionella pneumophila Pathogenesis

- intracellular pathogen that infects macrophages and monocytes in the lungs

- endotoxins from bacterium cause inflammation and systemic responses

- leads to severe pneumonia

Legionella pneumophila causes

Legionnaire's disease

- high mortality in the immunocompromised and smokers

Klebsiella pneumoniae Pathogenesis

- capsule provides protection against phagocytosis

- bacterium can cause sepsis and bacteremia

**often antibiotic resistant

Pseudomonas aeruginosa Pathogenesis

- aerobe that infects CF patients and hospitalized patients on ventilators

- strong biofilm formation helps persist in the lungs and resist antibiotic treatment

What percentage of all acute morbidity in the US is due to respiratory disease, and how many of these are viral infections?

- respiratory disease accounts for 80% of all acute morbidity in the US

- 80% are viral

What are the two parts of the respiratory system?

Upper Respiratory Tract:

- conditions air and brings it into the lungs

Lower Respiratory Tract:

- where gas exchange occurs, including the respiratory bronchioles, alveolar ducts, and alveoli

What are terminal bronchioles, respiratory bronchioles, alveolar ducts, and alveoli?

Terminal bronchioles (TB) branch into respiratory bronchioles (RB), which branch further into alveolar ducts (AD) and individual alveoli (A).

Where does gas exchange between air and blood occur in the respiratory system?

occurs at the membranous barrier between each alveolus and the surrounding capillaries

What types of infections are common in the upper respiratory tract?

infections caused by viruses like influenza, parainfluenza, and rhinoviruses.

Which pathogens are common causes of infections in the lower respiratory tract?

What are the causes of CAP? (virus focused)

SARS-CoV-2 Overview

- coronavirus

- ssRNA

- transmitted via respiratory droplets

- causes COVID-19 with potential for ARDS, cytokine storm, and viral sepsis

What is the general structure and mutation rate of coronaviruses?

Coronaviruses are single-stranded (+)-RNA viruses that mutate and recombine frequently.

They can exchange genes if they infect the same cell.

What respiratory conditions are caused by coronaviruses?

Most coronaviruses cause common cold symptoms. Some cause severe respiratory diseases like SARS, MERS, and COVID-19.

SARS - CoV1, highest death rates, very infectious, WIPED OUT

MERS - high likelihood of death if infected but difficult to transmit

How is SARS-CoV-2 transmitted?

via respiratory droplets

Where did SARS-CoV-2 originate?

from an animal source, specifically from viruses found in pangolins and bats

What is the general lifecycle of SARS-CoV-2?

infects cells through the ACE-2 receptor, replicates, and spreads throughout the body

Which cells does SARS-CoV-2 infect?

tissue in the nose, lung, and ileum

**predominantly infects the nose

**the ileum is where the virus replicates

What are the common signs and symptoms of COVID-19?

Fever, cough, difficulty breathing, loss of taste or smell, fatigue, muscle aches.

ARDS

adult (acute) respiratory distress syndrome

How does SARS-CoV-2 cause ARDS?

infection induces inflammation and cell death in the alveoli, causing edema and reduced oxygen exchange across the blood-gas barrier, leading to ARDS

What happens during a cytokine storm in SARS-CoV-2 infections?

the body thinks every tissue is being attacked which leads to an overactive immune response, causing widespread tissue damage and organ dysfunction, contributing to viral sepsis

How do COVID-19 tests work?

measure protein levels in nasal secretions using monoclonal antibodies that detect SARS-CoV-2 antigens

Influenza Overview

- segmented ssRNA

- transmitted by respiratory droplets

- causes URIs and LRIs

- can lead to secondary bacterial infections

What are the key properties of the influenza virus?

- orthomyxovirus with a segmented ssRNA genome

- has hemagglutinin (H) and neuraminidase (N) spikes on its surface

- infects many animal species

How is the influenza virus transmitted?

via respiratory droplets

Antigenic Drift

small, gradual changes in the virus's surface proteins (associated with seasonal flu epidemics)

Antigenic Shift

major genetic reassortment, often resulting in new, more dangerous strains (associated with pandemics)

What are the symptoms and complications associated with influenza infection?

Symptoms include:

- chills, fever, muscle aches, drowsiness

Complications include:

- pneumonia, bacterial superinfection, viral pneumonia with asphyxia

How does the influenza virus infect the respiratory tract?

- hemagglutinin binds to receptors on respiratory cells

- neuraminidase helps the virus release

- virus invades epithelium of URI and LRI

- leads to necrosis of ciliated and mucus-producing respiratory epithelial cells

- leads to secondary infections with viruses and bacteria

- can cause viral sepsis

Why are bacterial co-infections important in respiratory virus infections like influenza?

Influenza-induced damage to the respiratory epithelium increases susceptibility to bacterial colonization, making secondary bacterial infections more likely.

How does influenza cause local and systemic damage?

It causes local damage to lung tissue through cell necrosis and inflammation. Systemically, viral sepsis occurs due to the massive release of cytokines.

True or False: Both the SARS-CoV-2 and Influenza viruses can mutate leading to new strains.

True

What are the major genera of Gram-positive facultative cocci?

Staphylococcus, Streptococcus, and Enterococcus

What types of infections are caused by S. aureus?

- skin: boils, impetigo, cellulitis, mastitis

- bone and joint: osteomyelitis, septic arthritis

- necrotizing pneumonia, abscesses, sepsis

- toxinoses: gastroenteritis, food poisoning, toxic shock syndrome, scalded skin syndrome

What is a typical lesion caused by S. aureus?

Abscess (pus-forming) lesion

- can form externally or internally and is characterized by necrosis at the center

How does S. aureus cause damage at the cellular level?

It binds to epithelial cells using a binding protein expressed on the surface of the bacterial cell. It then releases a pore-forming toxin that damages the cells and attracts neutrophils to the infection site.

What is a furuncle and what causes it?

A furuncle (boil) is an infection of the hair follicle caused by S. aureus.

How does Methicillin-resistant Staphylococcus aureus (MRSA) resist antibiotics?

MRSA possesses genes that alter the target protein's (PBP) binding site. This prevents beta-lactam antibiotics from binding and inactivating the penicillin-binding protein (PBP).

What is the purpose of the sebaceous gland of a hair follicle?

It produces sebum which covers the skin and hair.

What is impetigo and how is it caused?

Impetigo is a superficial skin infection caused by either Streptococcus or S. aureus, characterized by weeping skin erosions and occasional bullous lesions.

How does S. aureus cause mastitis?

Mastitis often begins from cracks in the skin during nursing, leading to deep tissue infections and abscess formation.

What is osteomyelitis and how is it caused?

Osteomyelitis is an infection of the bone caused by S. aureus, typically leading to inflammation and pus accumulation in the bone.