Micro Exam 3 (real real)

FUCK ME IN MY ASS

Define empiric therapy and prophylaxis

Empiric Therapy: Starting antimicrobial treatment before the exact causative organism has been identified. Treatment is selected based on the most likely pathogen

Prophylaxis: Giving an antimicrobial to prevent an infection rather than to treat an existing infection

Antibiotic classes: cellular targets and mechanisms of action

β-lactams (penicillins, cephalosporins, carbapenems) (BC)

• Inhibit cell wall synthesis by preventing peptidoglycan cross-linking

Glycopeptides (vancomycin) (BC)

• Disrupt bacterial cell wall synthesis

Tetracyclines, Macrolides (BS)

• Inhibit protein synthesis by targeting ribosomal subunit

Aminoglycoslides (BC)

• Disrupt protein synthesis by targeting ribosomal subunit

Fluoroquinolones (BC)

• Inhibit DNA replication by targeting DNA gyrase/topoisomerase

Rifamycins (rifampin) (BC)

• Inhibit RNA synthesis by targeting RNA polymerase

Sulfonamides (BS)

• Inhibit folic acid synthesis

Polymyxins (BC)

• Disrupt bacterial cell membrane

Bactericidal vs. Bacteriostatic

• Bactericidal: Kills bacteria (BC)

• Bacteriostatic: Stops bacterial growth and reproduction (BS)

Four mechanisms of antibiotic resistance

Inactivation by enzymes

• Bacteria produce enzymes that destroy or chemically modify antibiotics

• Ex. β-lactamases breakdown β-lactam antibiotics

Blocked penetration of the drug

• Bacteria alter their outer membrane or pores (porins), preventing antibiotics from entering

• Ex. Pseudomonas aeruginosa decreases its OprD porin, contributing to carbapenem resistance

Efflux pumps

• Bacteria use pumps to remove antibiotics from inside the cell

• This decreases the concentration of the drug inside the bacterium

• Ex. Pseudomonas aeruginosa and azoe resistance in Candida species

Target modification

• Bacteria change the cellular structure that an antibiotic normally binds to

• The antibiotics can no longer effectively attach to its target

• Examples:

  • Altered penicillin-binding proteins (PBPs) ^→ β-lactam resistance

  • Altered peptidoglycan peptide chains → vancomycin resistance

Distinguish broad-spectrum and narrow-spectrum antimicrobials. Why might empiric therapy be broad-spectrum?

Broad-spectrum: Effective against a wide variety of bacterial organisms, including different Gram-positive and Gram-negative bacteria

Narrow-spectrum: Targets a smaller, more specific group of bacteria

Why use broad-spectrum empiric therapy?

• When the causative organism is unknown, broad-spectrum antibiotics provide coverage against multiple possible pathogens. This allows treatment to begin before laboratory results identify the specific organism

• Once the pathogen is identified, treatment can be adjusted to a narrower-spectrum antibiotics when appropriate

Describe the various strategies for immunization against RSV

RSV (respiratory syncytial virus) prevention uses different strategies for different age groups

• Older adults: RSV vaccination helps protect against severe respiratory illness

• Pregnant people: Maternal RSV vaccination allows protective antibodies to pass through the placenta to the fetus

• Newborns/infants: Monoclonal antibodies provide passive immunity by supplying antibiotics directly to the infant

Important distinction:

• Vaccination stimulates the person’s immune system to produce an immune response

• Monoclonal antibodies provide ready-made antibodies (passive immunity)

How are influenza A strains subtypes and named?

Influenza A viruses are classified according to two surface proteins:

• H = Hemagglutinin: Helps the virus attach to and enter host cells

• N = Neuraminidase: Helps newly produced viruses leave infected host cells

H1N1, H3N2

Compare and contrast SARS, MERS, and COVID-19

SARS

• Virus: SARS-CoV-1

• First outbreak: 2002

• First identified: Guangdong, China

• Virus type: Enveloped RNA coronavirus

• Fatality rate: ~9%

• 2002-2003 outbreak

MERS

• Virus: MERS-CoV

• 2012

• Middle East

• Enveloped RNA coronavirus

• Fatality rate: ~35%

• Ongoing outbreaks

COVID-19

• SARS-CoV-2

• 2019

• Wuhan, China

• Enveloped, single-stranded RNA coronavirus

• ~0.1%-0.3%

• Global pandemic

Identify the step in viral replication blocked by each medication

Nirsevimab

• Target: RSV

• Viral attachment/fusion and entry

Clesrovimab

• Target: RSV

• Viral fusion and entry

Ribavirin

• Multiple RNA viruses, including RSV

• Viral RNA synthesis

Oseltamivir (Tamiflu)

• Target: Influenza

• Viral release from infected cells

Baloxavir marboxil

• Influenza

• Viral mRNA transcription

Remdesivir

• SARS-CoV-2

• Viral RNA replication

For each viral disease, describe the causative agent, transmission, diagnosis, treatment, and vaccine

Common Cold

• Causative agent: Multiple viruses, especially rhinovirus

• Virus type: Rhinovirus are non-enveloped RNA viruses

• Transmission: Respiratory droplets, direct contact, and contaminated surfaces

• Signs and symptoms: Runny nose, congestion, sneezing, sore throat, and cough

• Diagnosis: Usually clinical presentation

• Treatment: Supportive care

• Vaccine: No general common-cold vaccine

RSV (Respiratory Syncytial Virus)

• Causative agent: Respiratory syncytial virus

• Virus type: Enveloped RNA virus (single stranded)

• Transmission: Respiratory droplets and direct contract

• Signs and symptoms: Cold-like symptoms; can cause bronchiolitis and pneumonia, especially in infants

• Diagnosis: NAAT

• Treatment: Supportive care

• Vaccine: Subunit (F protein)

Influenza

• Causative agent: Influenza A and B viruses

• Virus type: Enveloped RNA viruses (single stranded)

• Transmission: Respiratory droplets and aerosols

• Signs and symptoms: Fever, headache. muscle aches, fatigue, cough, and sore throat

• Diagnosis: NAAT

• Treatment: Oseltamivir and bayloxavir marboxil

• Vaccine: Whole inactivated/recombinant (injected), Live attenuated (nasal mist)

SARS

• Causative agent: SARS-CoV-1

• Virus type: Enveloped RNA coronavirus

• Transmission: Respiratory droplets and close contact

• Signs and symptoms: Fever and respiratory illness; can progress to severe pneumonia

• Diagnosis: NAAT

• Treatment: Supportive care

• Vaccine: No routinely available vaccine

MERS

• Causative agent: MERS-CoV

• Virus type: Enveloped RNA coronavirus

• Transmission: Animal-to-human transmission and human-to-human respiratory transmission

• Signs and symptoms: Fever, cough, and severe respiratory illness

• Diagnosis: NAAT

• Treatment: Supportive care

• Vaccine: No routinely available vaccine

COVID-19

• Causative agent: SARS-CoV-2

• Virus type: Enveloped, single stranded RNA virus

• Transmission: Respiratory droplets and aerosols

• Signs and symptoms: Can range from asymptomatic to flu-like symptoms to acute respiratory distress syndrome (ARDS)

• Treatment: Supportive care and remdesivir

• Vaccines: RNA vaccines and recombinant viral vector vaccines

Describe the parts of the upper and lower respiratory systems

Upper respiratory tract (URT): Includes the pharynx and epiglottis

Lower respiratory tract (LRT): Includes the lower airways and lungs, including the bronchi, bronchioles, and alveoli

Explain how superantigens function as virulence factors

Superantigens are exotoxins that cause nonspecific activation of T-helper cells

They bypass normal T-cell receptor/epitope specificity

They can activate approximately 1 in 5 T helper cells

This causes excessive immune system activation

The result is massive inflammation that can harm the host

Ex. Erythrogenic toxin

• Produced by some Streptococcus pyogenes strains

• Acts as a superantigen

• Causes inflammation and dilation of capillaries

• Produces the characteristics rash of scarlet fever

Define sequelae. How does it relate to treatment of GAS bacterial pharyngitis

Sequelae: A condition that occurs as a consequence of a previous disease or injury

GAS (Streptococcus pyogenes) pharyngitis can lead to complications including:

• Scarlet fever

• Rheumatic fever

• Rheumatic heart disease

• Acute glomerulonephritis (AGN)

Antibiotic treatment of GAS pharyngitis helps prevent complications associated with the infection

Describe the Lancefield classification system for Streptolococcus species

The Lancefield classification system categorizes certain Strep species based on their cell-wall carbohydrate antigens

Different groups are identified using letters

Examples:

• Streptococcus pyogenes (Group A) (GAS)

• Streptococcus algalactiae (Group B) (GBS)

• Streptococcus pneumoniae (No Lancefield grouping)

Describe the mechanisms for the rise in macrolide resistance in GAS

• GAS strains can acquire resistance genes through horizontal gene transfer

• mefA gene

• The mefA gene encodes a macrolide efflux pump

• This pump removes macrolide antibiotics from bacterial cells

Define antigen, antibody, antitoxin, and toxoid

Antigen: A substance recognized by the immune system that can trigger an immune response

Antibody: An immune protein produced by B cells/plasma cells that specifically binds an antigen

Antitoxin: An antibody that neutralizes a specific toxin

Toxoid: An inactivated toxin that cannot cause the toxin’s usual harmful effects but can stimulate an immune response

How is antitoxin produced, and how can it treat diphtheria?

Diphtheria antitoxin (DAT) is produced using horses

Horses are exposed to diphtheria toxin in a controlled process that stimulates antibody production

Antibodies are collected and purified, later administered to humans

They bind and neutralize diphtheria toxin

Important: Antitoxin neutralizes the toxin but does not directly kill the bacteria

Bacterial upper respiratory infections

Otitis media

• Causative organisms:

  • Streptococcus pneumoniae (GPC)

  • Haemophilus influenzae (GNCB)

  • Moraxella catarrhalis

• Transmission

  • Respiratory droplets and spread of organisms from the upper respiratory tract

• Disease features:

  • Middle ear infection, Ear pain, Fever, Can occur following a cold

• Diagnosis:

  • Clinical examination

• Treatment:

  • Antibiotics when indicated

• Vaccine:

  • Pneumococcal conjugate vaccine and Hib conjugate vaccine help prevent infections caused by certain organisms associated with otitis media

Bacterial pharyngitis

• Causative agent:

  • Streptococcus pyogenes (GAS)

• Morphology

  • Gram-positive cocci in chains (GPC)

• Transmission

  • Respiratory droplets

• Precautions:

  • Droplet precautions

• Disease features:

  • Throat inflammation and exudate

• Diagnosis:

  • Immunochromatographic assay (ICA); if negative. bacterial culture for GAS

• Treatment:

  • Antibiotics, typically penicillin. Macrolides may be used in penicillin-allergic patients

• Vaccine:

  • No vaccine listed

• Possible complications

  • Scarlet fever

  • Rheumatic fever

  • Rheumatic heart disease

Scarlet fever

• Causative agents:

  • Streptococcus pyogenes (GAS)

• Mechanism

  • Erythogenic toxin acts as a superantigen

• Transmission:

  • Respiratory droplets

• Disease features

  • Red, sandpaper-like rash

  • Strawberry tongue

  • Skin peeling after the rash resolves

• Treatment:

  • Antibiotics

Diphtheria

• Causative agent:

  • Corynebacterium diphtheriae

• Morphology:

  • Gram-positive bacillus (GPB)

• Transmission + Precautions:

  • Respliratory droplets

  • Droplet precautions

• Disease features:

  • Cold-like symptoms, Sore throat, Low-grade fever, Bull neck, Pseudomembrane in the upper airway, Respiratory distress

• Pathogenesis:

  • Bacteria produce diphtheria toxin, toxin inhibits host-cell protein synthesis, host cells die, dead mucosal epithelial cells contribute to pseudomembrane formation, can lead to airway obstruction

• Diagnosis:

  • Bacterial culture (may take 7-10 days)

• Treatment:

  • Antibiotics

  • Diphtheria antitoxin (DAT)

• Prevention:

  • DTaP vaccine

  • Contains diphtheria toxoid

Pertussis (Whooping cough)

• Causative agent:

  • Bordetella pertussis (GNB)

• Transmission:

  • Respiratory droplets and direct contact

  • Droplet precautions

• Diagnosis:

  • NAAT

• Treatment:

  • Antibiotics

• Vaccine:

  • DTaP, subunit vaccine

• Signs and symptoms:

  • Severe coughing attacks

  • Classic whooping sound when inhaling

  • Most dangerous in infants and toddlers

Describe and differentiate the types of specimens and laboratory tests used to diagnose LRTIs

Specimens:

• Sputum: Mucus coughed up from the lower respiratory tract

• Bronchoalveolar lavage (BAL): Fluid collected from the lower respiratory tract during bronchoscopy

• Blood: Used when bloodstream infection is suspected

• Pleural fluid: Fluid collected from around the lungs when infection is suspected in that area