Lung Drugs & Bugs Flashcards
What are some signs and symptoms of an infection of the lungs?
- Cough
- Chest pain
- Fever
- Fatigue
- Dyspnea
- Increased tactile fremitus
- Egophony
- Tubular breath sounds
- Wheezes
- Dullness
- Elevated WBC
- Abnormal chest imaging
Nosocomial pneumonia is defined as a pneumonia that begins _ hours after admission
Nosocomial pneumonia is defined as a pneumonia that begins 48 hours or more after admission
Ventilator-associated pneumonia is defined as a pneumonia that begins _ hours after intubation
Ventilator-associated pneumonia is defined as a pneumonia that begins 48 hours after intubation
Name the defense mechanisms in the airways/lungs that pneumonia must overcome
- Mechanical filtering (nose and upper airways)
- Mucociliary clearance and cough
- Antimicrobial substances (IgA, lactoferrin, lysozymes, defensins)
- Cellular immunity (macrophages, T cells, PMNs)
Infection of the lung can take one of three routes of entry:
Infection of the lung can take one of three routes of entry:
1. Aspiration (pathogens colonizing the oropharynx, GI)
2. Inhalation (droplets or particles in the air)
3. Hematogenous (ex: Staph that gets in via IV drug use)
Aspiration pneumonia is most common in _ population
Aspiration pneumonia is most common in individuals with altered mental status
* Aspiration pneumonia is the reason that we can’t eat before surgery
Explain microaspiration vs gross aspiration
Microaspiration is a minor aspiration event where individuals aspirate pathogens colonizing the oropharynx without even noticing
Gross aspiration involves contents of the mouth or GI tract
This is _ pneumonia
This is lobar pneumonia
This is _ pneumonia
This is bronchopneumonia
This is _ pneumonia
This is interstitial pneumonia
What type of pneumonia?
Bronchopneumonia
What type of pneumonia?
Lobar pneumonia
A pneumonia caused by _ may be confirmed with urine antigens
A pneumonia caused by Legionella may be confirmed with urine antigens
A pneumonia caused by mycoplasma may be confirmed by _
A pneumonia caused by mycoplasma may be confirmed by mycoplasma
_ is the most common cause of pneumonia in an immunocompromised host; however, _ are also possible
Streptococcus pneumoniae is the most common cause of pneumonia in an immunocompromised host; however, possible to have:
* Atypical mycobacterium
* M tuberculosis
* Pneumocystis jiroveci
* Crytococcus
* Histoplasma
The most common cause of community-acquired pneumonia is _
The most common cause of community-acquired pneumonia is streptococcus pneumoniae
* It is also a cause of childhood otitis media, sinusitis, conjunctivitis
* It colonizes the upper respiratory tract
* Spreads via respiratory droplets
Strep pneumoniae is _ hemolytic, has _ shape, is catalase _ and optochin _
Strep pneumoniae is alpha hemolytic, has diplococci shape, is catalase negative and optochin sensitive
“Rusty sputum” is usually pathoneumonic for
“Rusty sputum” is usually pathoneumonic for strep pneumo
Strep pneumo has 4 important virulence factors:
Strep pneumo has 4 important virulence factors:
1. Polysaccharide capsule to hide from phagocytosis
2. Adhesins to bind host cells
3. Pneumolysin a pore-forming toxin
4. IgA protease which cleaves mucosal IgA
We can take advantage of the _ structure of strep pneumo to vaccinate individuals < 2, > 65, and chronic medical conditions
We can take advantage of the polysaccharide capsule of strep pneumo to vaccinate individuals < 2, > 65, and chronic medical conditions
* We now recommend the conjugate vaccine Prevnar
What makes conjugate vaccines so effective against bacteria with polysaccharide capsules like strep pneumo?
In these vaccines, the polysaccharides are covalently conjugated to carrier proteins that will engage the help of T cells
What color will strep pneumo be when plated on blood agar plate?
Green- alpha hemolytic
Pseudomonas aeruginosa has gram _ rods and is _ hemolytic and _ positive
Pseudomonas aeruginosa has gram negative rods and is beta- hemolytic and oxidase positive
“fruity odor”
Pseudomonas aeruginosa
Pseudomonas has a _ pigment when plated due to its _
Pseudomonas has a blue-green pigment when plated due to its pyocyanin
Pseudomonas can be found in _
Pseudomonas can be found in soil, water, human throat and stool
In healthy individuals, Pseudomonas can cause _ or _
In healthy individuals, Pseudomonas can cause hot tub folliculitis or otitis externa (swimmer’s ear)
We primarily worry about pseudomonas in immunocompromised patients like patients with _
We primarily worry about pseudomonas in immunocompromised patients like patients with burns, CF, AIDs, diabetes, neutropenia
* Often cause hospital acquired infections (VAP, CAUTIs)
Pseudomonas virulence factors include:
Pseudomonas virulence factors include:
* Alginate/biofilm formation- encapsulated
* ExoA- inhibits host cell protein synthesis
* ExoS- disrupts the host cytoskeleton
* Elastase- disrupts the ECM
Pseudomonas has two exotoxins;
ExoA _
ExoS _
Pseudomonas has two exotoxins;
ExoA ADP ribosylates EF2 and inhibits host cell protein synthesis
ExoS disrupts host cytoskeleton
Gram-negative coccobacilli, non-hemolytic, aerobic, twitching motility via pili
Gram-negative coccobacilli, non-hemolytic, aerobic, twitching motility via pili: Acinetobacter baumannii
Acinetobacter baumannii is found in _
Acinetobacter baumannii is found in in moist environments; colonizes human skin and RT
* It is an opportunistic pathogen that causes VAP
The smallest free-living organism that only infects humans is _
The smallest free-living organism that only infects humans is mycoplasma penumoniae
Bacteria that has a “fried egg” appearance when plated
Bacteria that has a “fried egg” appearance when plated: Mycoplasma pneumoniae
Mycoplasma pneumoniae cannot be gram stained because _
Mycoplasma pneumoniae cannot be gram stained because it lacks a cell wall
_ is the most common cause of community-acquired “atypical” pneumonia
Mycoplasma pneumoniae is the most common cause of community-acquired “atypical” pneumonia
Mycoplasma pneumoniae does not have any known toxins; instead it secretes _ to cause damage
Mycoplasma pneumoniae does not have any known toxins; instead it secretes H2O2 to cause damage
_ bacteria lives within amoebas in freshwater and often causes pneumonia in people who are exposed to contaiminated water in AC units and water towers
Legionella bacteria lives within amoebas in freshwater and often causes pneumonia in people who are exposed to contaiminated water in AC units and water towers
Legionnaires disease occurs when _
Legionnaires disease occurs when Legionella colonizes the lower RT and alveolar macrophages phagocytose the bacteria –> pneumonia
_ is a flu-like infection that is caused by legionella (not pneumonia)
Pontiac fever is a flu-like infection that is caused by legionella (not pneumonia)
Legionella must be stained using _ stain and it requires _ to grow
Legionella must be stained using silver stain and it requires charcoal yeast extract agar with iron and cysteine to grow
The groups most at risk of legionella include _
The groups most at risk of legionella include smokers, > 50 yo, COPD patients
_ is a common electrolyte abnormality associated with Legionella
Hyponatremia is a common electrolyte abnormality associated with Legionella
_ is Legionella virulence factor and it is able to replicate within _
T4SS (Dot/Icm) is Legionella virulence factor and it is able to replicate within macrophage vacuoles (the bacteria survive by inhibiting phagosome-lysosome fusion)
* It uses nutrients from the host cell and evades host immunity
* It causes damage via macrophage cytokine release and inflammation
Bordetella pertussis is an aerobic gram _ , _ (shape)
Bordetella pertussis is an aerobic gram-negative , coccobacilli
“100 day cough”
“100 day cough” : Bordetella pertussis
* It is highly transmittable via respiratory droplets
* Causes the whooping cough
The highest risk group of bordetella pertussis is _
The highest risk group of bordetella pertussis is unvaccinated infants
B pertussis has _ virulence factor which enables it to bind to ciliated respiratory epithelial cells
B pertussis has pili (Fim) virulence factor which enables it to bind to ciliated respiratory epithelial cells
Virulence factors _ and _ help B pertussis with adhesion
Virulence factors pertactin and filamentous hemagglutinin help B pertussis with adhesion
B pertussis has three toxins:
B pertussis has three toxins:
1. Tracheal cytotoxin
2. Adenylate cyclase toxin
3. Pertussis toxin
Tracheal cytotoxin causes _
Tracheal cytotoxin causes ciliary paralysis
Adenylate cyclase toxin causes _
Adenylate cyclase toxin causes increased cAMP –> inhibition of PMN function
Pertussis toxin causes _
Pertussis toxin causes AB toxin that ADP-ribosylates G proteins –> causes the systemic pertussis symptoms of fever and increased WBC count
The _ vaccine protects against B pertussis
The DTaP and Tdap booster protects against B pertussis
_ and _ are two gram-positive branching, filamentous beaded rods that can cause pneumonia
Nocardia and Acinomyces are two gram-positive branching, filamentous beaded rods that can cause pneumonia
* They almost look like fungus-like hyphae
(Nocardia/ Actinomyces) can be distinguished from its counterpart by being weakly acid-fast
Nocardia can be distinguished from its counterpart by being weakly acid-fast
* It is an aerobe, while Actinomyces is anaerobic
Actinomyces can be found in _ so is often associated with _
Actinomyces can be found in normal oral flora so is often associated with cervicofacial abscesses
_ forms “molar tooth” colonies on plates
Actinomyces forms “molar tooth” colonies on plates
Actinomyces has low virulence but is known to form the characteristic _
Actinomyces has low virulence but is known to form the characteristic yellow sulfur granules
* Composed of bacteria, immune cells, calcium phosphate, and pus that drains through the sinus tracts
Nocardia is found in the _
Nocardia is found in the soil
Nocardia causes pneumonia that is characterized by _
Nocardia causes pneumonia that is characterized by abscess formation and cavity formation –> can spread to cause brain abscesses
Nocardia: forms dry, chalky, wrinkled colonies on plates & fluffy, “cotton balls” under dissecting scope
Nocardia virulence factors
- Cord factor: inhibits phagosome-lysosome fusion
- SOD: detoxifies oxygen radicals
- Catalase: detoxifies oxygen radicals
Name some of the common causes of community acquired pneumonia
Streptococcus pneumoniae G+
Hemophilus influenzae G-
Moraxella catarrhalis G-
Mycoplasma pneumoniae Atypical
Staphylococcus aureus G+
Legionella pneumophila Atypical
Initial empiric treatment for CAP must cover G+ G- and Atypical bacteria
Patients with CAP and no other risk factors who are treated outpatient may receive _ , _ , or _
Patients with CAP and no other risk factors who are treated outpatient may receive:
Amoxicillin
Macrolide (Azithromycin)
Doxycycline
Note that amoxicillin does not cover atypical bacteria
Amoxicillin MOA:
Amoxicillin inhibits bacterial cell wall synthesis by binding one or more of the penicillin binding proteins (PBPs)
Macrolide MOA:
Macrolides like azithromycin bind the bacterial 50S ribosomal subunit causing the cessation of bacterial protein synthesis
Doxycycline MOA
Doxycycline is a tetracycline so it binds to the 30S ribosomal subunit
For mild inpatient cases, where the local macrolide resistance is high we may give a combination of _ or _
For mild inpatient cases, where the local macrolide resistance is high we may give a combination of
Amoxicillin + Macrolide
Amoxicillin + Doxycycline
For patients with severe inpatient pneumonia we might give a combination of _ or _
For patients with severe inpatient pneumonia we might give a combination of
Amoxicillin/ Clavulanic acid + macrolide
Amoxicillin/ Clavulanic acid + doxycycline
If patient has had recent amoxicillin use or cannot have amoxicillin, we might give _ drug on its own to treat mild or severe inpatient pneumonia
If patient has had recent amoxicillin use or cannot have amoxicillin, we might give fluoroquinolone on its own to treat mild or severe inpatient pneumonia
* Alternatively we can combine 3rd generation cephalosporin with a macrolide or with doxy
Fluoroquinolone MOA
Fluoroquinolone impairs DNA replication by targeting DNA gyrase and topoisomerase IV
Cephalosporin MOA
Cephalosporin work by binding to penicillin binding proteins and interfere with cell wall enzymes
Fluoroquinolone treatment for CAP must be a respiratory pneumonia like _
Fluoroquinolone treatment for CAP must be a respiratory pneumonia like levofloxacin, moxifloxacin, gemifloxacin
* Note that ciprofloxacin is not a respiratory fluoroquinolone because it is not effective against Strep pneumo
Antibiotics for hospital acquired pneumonia need to cover _ and _ specifically
Antibiotics for hospital acquired pneumonia need to cover Pseudomonas aeruginosa and Staph aureus specifically
In simple cases of HAP against drug sensitive strains we can give _ antibiotics
In simple cases of HAP against drug sensitive strains we can give:
* Piperacillin-Tazobactam
* Cefepime
* Levofloxacin
If we are worried about MRSA, we must treat HAP with:
- Piperacillin-Tazobactam
- Cefepime
- Levofloxacin
PLUS
- Vancomycin or
- Linezolid
If we are worried about MRSA and drug resistant pseudomona aeruginosa then we must give a combination of three drugs:
- Piperacillin-Tazobactam
- Cefepime
- Levofloxacin
PLUS
- Vancomycin or
- Linezolid
PLUS
- Ciprofloxacin or
- Amikacin
Amikacin MOA
Amikacin is an aminoglycoside so it works by binding the 30S ribosomal subunit
* Recall that the aminoglycosides (-mycin) and the tetracyclines (-cyclin) target 30S
* Macrolides (-ithromycin) target 50S
Linezolid works by targeting _
Linezolid works by targeting 50S ribosomal subunit
Recall that vancomycin is a common drug used against MRSA, it works by _
Recall that vancomycin is a common drug used against MRSA, it works by binding the D-ala-D-ala terminus and inhibiting cell wall synthesis
Name an example of each
Ro represents _
Ro represents the number of people that a single infected person can be expected to transmit that disease to
* Dependent on transmission efficiency, how long a person is infectious, number of susceptible people exposed
_ is a member of the orthomyxovirus family and is enveloped and has a helical capsid
Influenza is a member of the orthomyxovirus family and is enveloped and has a helical capsid
Influenza has _ type genome and replicates in the _
Influenza has a negative sense ssRNA segmented genome and replicates in the nucleus
Most other negative sense ssRNA viruses replicate in the _
Most other negative sense ssRNA viruses replicate in the cytosol
* Influenza is an exception because it carries its own RNA-dependent RNA polymerase
_ is a influenza’s glycoprotein that binds to the host sialic acid for attachment
Hemagglutinin (HA) is a influenza’s glycoprotein that binds to the host sialic acid for attachment
_ is influenza’s enzyme that cleaves sialic acid for release
Neuraminidase (NA) is influenza’s enzyme that cleaves sialic acid for release
M2 channel is a proton ion channel that _
M2 channel is a proton ion channel that maintains proper pH for membrane fusion to endosomal membrane and virus uncoating
_ is the accumulation of point mutations that change the HA/NA sequence each year and requires us to get yearly flu vaccinations
Antigenic drift is the accumulation of point mutations that change the HA/NA sequence each year and requires us to get yearly flu vaccinations
_ is the reassortment or swapping of genome segments in type A viruses that causes pandemics every 10-40 years
Antigenic shift is the reassortment or swapping of genome segments in type A viruses that causes pandemics every 10-40 years
Respiratory syncytial virus is a member of _ family
Respiratory syncytial virus is a member of paramyxovirus family
Describe the features of RSV
RSV:
* Enveloped
* Helical capsid
* Negative sense RNA genome
* Carries its own RNA-dep-RNA polymerase
RSV is the most common cause of _ in infants
RSV is the most common cause of bronchiolitis in infants
RSV has a G protein (glycoprotein) that _ and fusion protein (F) that _
RSV has a G protein (glycoprotein) that binds cilitated cells (RT) and fusion protein (F) that mediates membrane fusion for viral entry
_ is a member of the coronavirus family that is enveloped, +ssRNA, with a helical capsid
SARS-CoV-2 is a member of the coronavirus family that is enveloped, +ssRNA, with a helical capsid
SARS has _ proteins that allow it to bind to the host receptor _
SARS has spike proteins that allow it to bind to the host receptor ACE2
* ACE2 is expressed on epithelial cells of the oral cavity, nose, lung, intestines, kidney, blood vessels
* Airway inflammation is driven by pro-inflammatory cytokines
_ is a nucelotide analog drug that can be used to treat RSV; howevever, it is not commonly used due to its _
Ribavirin is a nucelotide analog drug that can be used to treat RSV; howevever, it is not commonly used due to its narrow therapeutic window
Ribavirin works as a _ to disrupt the action of _
Ribavirin works as a nucleotide analog to disrupt the action of viral RNA polymerase in a number of ways
Ribavirin blocks host _ and therefore is a pregnancy x drug; it is also known to cause _
Ribavirin blocks host DNA replication and therefore is a pregnancy x drug; it is also known to cause hemolytic anemia
* It is stored in RBCs and has a very long half life of 40 days
Amantadine is a flu drug that inhibits _
Amantadine is a flu drug that inhibits M2; it blocks virus uncoating
Oseltamivir, zanamivir, and peramivir are all release inhibitors; they inhibit the action of _
Oseltamivir, zanamivir, and peramivir are all release inhibitors; they inhibit the action of neuraminidase
Nirmatrelvir is a _ that can be used to treat SARS; it is often paired with _ in order to slow the metabolism
Nirmatrelvir is a protease inhibitor that can be used to treat SARS; it is often paired with ritonavir in order to slow the metabolism
Ritonavir is a CYP3A4 _
Ritonavir is a CYP3A4 inhibitor
