Pneumonias Flashcards
Categories of material that the lung encounters in an average
- Small particulate matter
- Noxious gases
- Microorganisms
Major sources of material that the lung encounters
- Matter that is breathed in via the oral cavity-respiratory route
- Matter that is secreted along the upper GI tract and aspirated back into the respiratory route
- Matter that is dissemianted through the blood and arrives at the lungs and bronchi through circulation
Categories of defenses that the lung uses to protect itself
- Physical or anatomic barriers
- Antimicrobial peptides
- Innate immunity
- Adaptive immunity
Inhaled particles often accumulate at. . .
. . . subcarinae, or the points of division of the airways
Size of particles
>10 μm : Likely to settle in the nose
5 - 10 μm : Likely to settle in the trachea or conducting airways
0.5 - 5 μm : Likely to make it down to the level of the alveoli and distal lung parenchyma
Mechanical defense of the trachea and bronchi
- Cough (triggered by irritant receptors)
- Mucocilliary escalator
Cilium cross section
Layers of the mucous blanket
Proximal to the cells is the sol layer, made up of cilia and an aqueous solution full of antimicrobial peptides.
Above this layer is the gel layer, which is where the mucous produced by mucosal and submucosal goblet cells resides. It is beated forward towards the esophagus by the cilia down beneath in the sol layer.
Major anti-microbial molecules of the respiratory tract
- IgA
- Lysozyme
- Lactoferrin
- Defensins
- Collectins (aka surfactant A and D)
Lysozyme
Synthesized by respiratory epithelial cells, serous glandular cells, and macrophages
As the name implies, lysozyme causes bacterial cell death by inducing lysis. It is most active against gram-positive organisms.
Deficiency associated with presdisposition to acute bronchitis.
Lactoferrin
Present in airway fluid. Produced by serous cells and neutrophils.
Lactoferrin acts to agglutinate and kill bacteria, enhance neutrophil adherence, and prime neutrophil superoxide production. Also functions to block iron from supporting bacterial metabolism.
Defensins
The major defensins of the lung are α-defensins and β-defensins. α-Defensins are synthesized by resident neutrophils; β-defensins are made by respiratory epithelial cells.
Broad antimicrobial activity against both gram-positive and gram-negative organisms. They act by making the microbial cell wall permeable, thus causing release of microbial cell contents and destruction of the membrane potential.
Activity sensitive to salt concentrations, and as such they are inactive in cystic fibrosis.
Collectins
Produced by type II pneumocytes.
Antimicrobial function is a result of binding and aggregating microbes and facilitating interaction with phagocytic cells (opsonization). Also appear to be important in regulation of pulmonary macrophage activity and cytokine production.
Pulmonary alveolar macrophages
Bone marrow monocyte-derived. Adhere to and patrol alveolar epithelium. Have a major role in killing microorganisms that have reached the lower respiratory tract.
Aided by numerous opsonins in the alveolar space, including IgG, secretory IgA, complement, and fibronectin.
Interestingly, macrophages have a somewhat high barrier to proinflammatory cytokine secretion, presumably as a means of activating alveolitis only when it is truly necessary for immune defense.
Most of the IgA along the respiratory tract resides within. . .
The nasopharynx and upper airways
Requirements for effective coughing
- Ability to inspire deeply
- Ability to increase intrathoracic pressure against a closed glottis
- Ability to coordinate an expiratory blast during which the glottis opens
Dyskinetic cilia syndrome
Defect in ciliary structure and function leads to absent or impaired ciliary motility and hence to ineffective mucociliary clearance. Most commonly results form ineffective dynein.
Clinically associated with chronic sinusitis, chronic bronchitis, and bronchiectasis
Causes of impaired mucociliary clearance
- Dyskinetic (immotile) cilia syndrome
- Viral respiratory tract infection
- Cigarette smoking
- High concentrations of O2 for prolonged periods (90% to 100% inhaled for more than several hours)
- General anesthesia
Ventilator-associated pneumonia
Bacterial infection of respiratory tract due to endotracheal tubing
Common contributing factors for pneumonia in the immunocompetent host are:
- Viral upper respiratory tract infection
- Ethanol abuse
- Cigarette smoking
- Heart failure
- Chronic obstructive pulmonary disease
Overarching categories of pneumonias
- Viral
- Bacterial
- Mycoplasma
Bacterium most frequently associated with pneumonia
Streptococcus pneumoniae
Of note, it also produces much more severe pneumonias than many other etiologies
Gram-negative organisms that commonly cause pneumonia
- Haemophilus influenzae (increased risk with COPD)
- Klebsiella pneumoniae (increased risk with alcoholism)
- Pseudomonas aeruginosa (often nosocomial, primarily seen in patients who are hospitalized, debilitated, and have been previously treated with antibiotics)
Most common cause of anaerobic pneumonia
Aspiration of secretions from the oropharynx into the tracheobronial tree
Populations at increased risk for pneumonia caused by anaerobic or mixed mouth organisms
- Patients prone to aspirate:
- Patients with impaired consciousness (coma, lcohol or drug ingestion, or seizures)
- Patients with difficulty swallowing (as a result of stroke or diseases causing muscle weakness)
- Patients with poor dental hygiene or with gum disease
With prolonged hospitalization, the organisms populating the oropharynx may switch:
- Streptococci are displaced by:
- Staph aureus
- Aerobic gram-negative bacilli
Legionella pneumophila
Gram-negative bacillus that stains very poorly and is generally not seen by conventional staining methods
Cause of numerous epidemics and small sporadic cases of pneumonia
Chlamydophila pneumoniae
Recognized in epidemiologic studies as the cause of approximately 5% to 10% of cases of pneumonia. Obligate intracellular parasite related to gram-negative bacteria.
Diagnosis is rarely made clinically because of the lack of distinguishing clinical and radiographic features, and the organism is not readily cultured. As a result, serologic studies serve as the primary means of diagnosis, although they are infrequently obtained.
Mycoplasma
A class of organisms intermediate between viruses and bacteria
Unlike bacteria, they have no rigid cell wall. Unlike viruses, they do not require the intracellular machinery of a host cell to replicate and are capable of free-living growth.
Now recognized as a common cause of pneumonia, perhaps responsible for a minimum of 10% to 20% of all cases.
Lobar Pneumonia
A process not limited to segmental boundaries but rather tending to spread throughout an entire lobe of the lung.
Spread of the infection is believed to occur from alveolus to alveolus via pores of Kohn.
Streptococcus pneumoniae is a prime example.
Bronchopneumonia
Distal airway inflammation is prominent along with alveolar disease, and spread of the infection and the inflammatory process tends to occur through airways.
Patchy in distribution, depending on where spread by airways has occurred.
Ex, staphylococci and a variety of gram-negative bacilli
Interstitial Pneumonia
Interstitial pneumonias are characterized by an inflammatory process within the interstitial walls rather than alveolar spaces.
Viral pneumonias classically start as interstitial pneumonias, severe cases generally show extension of the inflammatory process to alveolar spaces as well.
Often following infection and clearance of S. pneumoniae, the lungs. . .
Often following infection and clearance of S. pneumoniae, the lungs heal with little to no scaring and are essentially normal.
Often following infection and clearance of staphylococcal and anaerobic pneumonias the lungs. . .
Often following infection and clearance of staphylococcal and anaerobic pneumonias the lungs are necrosed and may have diffuse cavities, resulting in scarring and permanent loss of some parenchyma.
Patients with pneumonia frequently have a PCO2 ____.
Patients with pneumonia frequently have a PCO2 less than 40 mm Hg
In other words, they are hyperventilating
The primary cause of hypoxemia in pneumonia is ___.
The primary cause of hypoxemia in pneumonia is V/Q mismatch.
Almost every pneumonia presents as . . .
- Fever
- Cough (Non-productive in viral and mycoplasmal, productive in bacterial)
- Shortness of breath
Physical exam findings of pneumonia
- Tachycardia, tachypnea, fever
- Crackles or rales overlying region of pneumonia
- Bronchial breath sounds around pneumonia
- Increased fremitus
- Egophony
- Dullness to percussion
- Leukocytosis (often with bandocytosis in bacterial)
Course of pneumococcal pneumonia
- Abrupt onset of syptoms
- Fever and chills
- Productive cough, yellow/green and sometimes blood-tinged
- Often with history of upper respiratory tract infection just prior
Course of mycoplasmal pneumonia
- Slow, insidious onset
- Prominent, nonproductive cough
- Low fever, usually without chills
- Most often affects young adults
Course of staphylococcal pneumonia
- Often very ill
- Often with impaired defense mechanisms or previous antibiotics
- Often occurs secondary to influenza infection just prior, or resulting from staphylococcal hematogenous dissemination
Course of gram-negative bacillary pneumonia
- Often very ill
- Often with impaired defense mechanisms or previous antibiotics
Course of anaerobic bacterial pneumonia
- Generally occurs in patients with impaired consciousness or difficulty swallowing (aspiration risk)
- Often poor dentition
- Gradual onset
- Productive cough with foul smelling sputum
- Necrosis and abscess formation are common sequellae
Course of Legionella pneumonia
- aka Legionnaires’ disease
- Often part of a cluster of cases
- Patients often extremely ill, with respiratory compromise or failure and with GI, CNS, hepatic, and renal disease accompanying the pneumonia
Pleural fluid commonly accompanies pneumonia of ___ origin.
Pleural fluid commonly accompanies pneumonia of bacterial origin.
What is the likely diagnosis?
Lobar pneumonia of the right middle lobe, likely Streptococcus pneumoniae
Routine stains and cultures of sputum are not useful for three of the important causes of pneumonia:
- Mycoplasma
- Legionella
- Chlamydophila
These often require serology
In the case of pneumococcal pneumonia, ___ traditionally has been the most appropriate agent
In the case of pneumococcal pneumonia, penicillin traditionally has been the most appropriate agent
When high-level resistance of pneumococcus to penicillin is found,
quinolones or vancomycin are usually used
____ is the antibiotic of choice for pneumonias caused by either Legionella or Mycoplasma.
A macrolide or a quinolone is the antibiotic of choice for pneumonias caused by either Legionella or Mycoplasma.
Penicillinaseresistant derivative of penicillin
Often required to treat staphylococcal pneumonia.
Major ones are oxacillin or nafcillin.
If these don’t work, vancomycin is the next best bet.
Pneumonia caused by anaerobes is treated most commonly with either ___ or ___.
Pneumonia caused by anaerobes is treated most commonly with either penicillin or clindamycin.
Treating viral pneumonias
No definitive forms of therapy are available for most viral pneumonias
Treating influenza virus pneumonia
Prevention: Vaccines!!!!
Treatment: Antiviral agents (amantadine or rimantadine for influenza A, a neuraminidase inhibitor such as zanamivir or oseltamivir for influenza A or B) may reduce the duration or severity of the illness if given soon after onset of clinical symptoms.
Community acquired pneumonia guide
Natural history of nosocomial pneumonia
- Onset at least 48 hours after admission to hospital
- Especially prevalent in patients coming out of ICU
- Colonization of nasopharynx with organisms that are not normally there
- Usually enteric gram-negative bacilli or Staphylococcus aureus
Treating a lung abscess
- Drainage, usually through tracheobronchal tree, surgical if necessary
- Followup antibiotics
Treating empyema
Empyema may result if pus leaks into pleural space, and is particularly concerning if it evolves to fibrosis.
- Thoracentesis to collect fluid sample
- Drainage, usually requiring thorascopic surgery
- If fibrosis develops, continuous instillation of streptokinase into pleural space can releave tension on lungs
Bacillus anthracis
Gram-positive spore-forming rod. Infects via inhalation of aerosolized spores.
- Prominent edema
- Inhibition of neutrophil function
- Altered cytokine production
- Germination of spores in mediastinal lymph nodes can lead to hemorrhagic lymphadenitis and mediastinitis
- Often presents as flu-like illness at first, then several days later escalates to fever, dyspnea, cyanosis, septic shock, and meningitis
Treat with ciprofloxacin or doxycycline
Yersinia pestis (aka, plague)
Greatest epidemic killer of humans (~200 million). Gram-negative rod transmitted from fleas, to rodents, to humans.
Disseminates through skin to regional lymph nodes (bubonic plague). Can also disseminate to lungs (pneumonic plague). The lung form of disease is highly contagious.
- Acute illness
- High fever, chills, malaise, dyspnea, cyanosis
- Widespread bronchopneumonia resembling ARDS
Treat with streptomycin and doxycycline
Infectious diseases that have killed the most humans
Francisella tularensis (aka Tularemia)
Gram-negative coccobacillary organism. Infects small mammals, transferred via ticks to humans, or via aerosolization and inhalation.
- Patchy inflammation and consolidation of the lung parenchyma
- Enlargement of hilar lymph nodes
- Pleural effusion
- Fever, chills, malaise, and headache
Treat with streptomycin
What would be an appropriate empiric antibiotic regimen for a 62-year-old diabetic with community-acquired pneumonia being treated as an outpatient?
A quinolone
For healthy individuals being treated for community-acquired pneumonia as an outpatient, the most recent guidelines recommend treating with amoxicillin (a beta-lactam), doxycycline, or a macrolide (note that unless there is very high suspicion for an atypical pathogen (can be hard to determine clinically), macrolides should generally be avoided given the high rates of macrolide-resistant Strep pneumoniae in the US).
This patient is a diabetic and therefore warrants more aggressive therapy. She should be treated with a quinolone alone or a beta-lactam plus either a macrolide or doxycycline (these regimens, in addition to covering “atypical” organisms (Mycoplasma pneumoniae, Legionella pneumophila, Chlamydophila pneumoniae), add additional coverage for macrolide-resistant Strep pneumoniae).
Treatment plan for a healthy outpatient with community-acquired pneumonia
Amoxicillin (a beta-lactam) or doxycycline
Marolide use in outpatients with community acquired pneumonia
Unless there is suspicion of an atypical pathogen, macrolides should generally be avoided given the high rates of macrolide-resistant Strep pneumoniae in the US
Therapy plan for an unhealthy outpatient with community acquired pneumonia
Requires aggressive therapy plan
Quinolone alone or a beta-lactam plus either a macrolide or doxycycline
The most appropriate diagnostic test to identify the microbiologic cause of community acquired pneumonia in an outpatient is:
None necessary - empiric treatment should be adequate
Quinolones
Non-competitive inhibitors of gyrases and topoisomerases.
They prevent the enzymes from repairing the break in the DNA. This leads to death (bactericidal) of the bacterium, however the mechanism by which cell death occurs is not well understood
Tetracyclines
Antibiotics. Protein synthesis inhibitors.
Bind the 30S subunit of the ribosome and block the A-site.
Macrolides
Antibiotics. Inhibitors of protein synthesis via the 50S bacterial ribosome. Include erythromycin and azithromycin.
Bind in the exit tunnel of the 50S ribosomal subunit, blocking elongation of the nascent polypeptide.
If you suspect viral pneumonia, __ may help diagnosis.
If you suspect viral pneumonia, nasophaygngeal swave pcr may help diagnosis.
If you suspect mycoplasma pneumonia, __ may help diagnosis.
If you suspect mycoplasma pneumonia, nasophaygngeal swave pcr may help diagnosis.
If you suspect Legionella pneumonia, __ may be helpful for diagnosis.
If you suspect Legionella pneumonia, urine analysis may be helpful for diagnosis.
Pseudonyms for Streptococcus pneumoniae
Pneumococci, diplococci, “gram + cocci in pairs)
Standard regimen for a nosocomial pneumonia with a stable patient
Beta-lactam + macrolide
OR
Respiratory fluoroquinolone
Standard regimen for a nosocomial pneumonia with an unstable patient
beta-lactam + macrolide
OR
beta-lactam + fluoroquinolone
Risk factors for streptococcus pneumoniae
- Asplenia
- Alcohol abuse
- Smoking
- Asthma
- HIV
Why does influenza predispose to bacterial pneumonia?
- Influenza destroys the pseudostratified columnar epithelium, impairing the mucocilliary escalator
- Some immunosuppressive effects
- Buildup of fluid within the lungs that is an excellent growth medium for bacteria
On CXR, influenza progresses as. . .
Very early phases: interstitial (usually we don’t see this, this is before people present to the hospital)
Mid-late phase: Patchy areas of consolidation
Much like influenza, COVID-19 predisposes to ___.
Much like influenza, COVID-19 predisposes to bacterial superinfection.
Treating a community pneumonia with presentation of purulent phlegm, pleuritic chest pain, positive egophony sign, high fever, tachypnea, tachycardia. Patient is young and appears stable.
Likely streptococcus pneumoniae.
Treat w/ amoxicillin and doxycycline. This also covers mycoplasma just in case.
___ is an excellent antiboitoc for treating streptococcus pneumoniae.
Amoxicillin is an excellent antiboitoc for treating streptococcus pneumoniae.
Common causes of non-lobar pneumonia
- Mycoplasma
- Viral
- Chlamydophila pneumoniae
Common causes of lobar pneumonia
- Streptococcus pneumoniae
- Haemophilus influenzae
- Staphylococcus aureus
- Legionella
- Moraxella
When you see pneumonia + pleural effusion, you should think. . .
Parapneumonic effusion, which is likely empyema.
This requires diagnostic thoracentesis. If it is indeed empyema, it will need transthoracic or surgical drainage, as there is poor penetration of antibiotics into the pleural space.
MIC
Minimum inhibitory concentration
Most people who acquire pneumonia but are well enough to remain as an outpatient tend to have ___ or ___. These are organisms that rarely cause pneumonia so severe that it requires hospitalization.
Most people who acquire pneumonia but are well enough to remain as an outpatient tend to have mycoplasma or chlamydophila. These are organisms that rarely cause pneumonia so severe that it requires hospitalization.
Streptococcus pneumoniae is most common everywhere on the spectrum.
“Big 4” Respiratory viruses
- Influenzavirus
- RSV
- Adenovirus
- Parainfluenza virus
72-year-old woman with type 2 diabetes presents with 1 day of fevers; chills; muscle aches; and a hacking, non-productive cough. On exam, she has a temperature of 101.3 Fahrenheit, heart rate of 120 beats/minute, blood pressure of 100/60, respiratory rate of 30 breaths/minute, and oxygen saturation of 86% on room air. She appears ill.
On pulmonary auscultation, there are scattered crackles and wheezes. Her heart is tachycardic but regular with a normal S1 and S2. Her CXR is attached.
What are the next steps?
Likely influenza, possibly mycoplasma or other respiratory virus.
- Put on supplemental oxygen
- Nasopharyngeal swave for PCR to identify potential respiratory virus
- Wait until this is back until giving antibiotics (1-2 hours)
- If there are no hits on the viral screen, start antibiotics empirically
Patterns of inflammation in viral vs bacterial pneumonia
Viral: Lymphocytes in interstitial space
Bacterial: Lymphocytes in alveolar space
Lobar superinfection following influenza in a hospital setting. What is the likely cause?
Staphylococcus aureus
