Pathophysiology of Bacterial Infections: Pneumonia, UTI, and IE Flashcards
What are the most common infection sites?
Respiratory tract
Urinary tract
What is virulence?
The strength of a microorganism’s pathogenicity
Virulence factors: adhesins, protective capsules
What is inoculum?
The quantity of microorganisms
“How many microorganisms cause ___?”
ex. COVID, the inoculum is higher in an enclosed space rather than outside
The chain of transmission of an infection
Infectious agent
Reservoir
Portal of exit
Mode of transmission
Portal of entry
Susceptible victim
What is a nosocomial infection?
An infection acquired during the course of a stay in a hospital, nursing home, or other healthcare facilities
What are the stages of infection? Describe each one
Incubation: between exposure and symptoms
Prodrome: non-specific symptoms
Illness: overt s/sx of infection
Recovery: return toward homeostasis
Chronic Carrier State: is possible in some infections
What is community-acquired pneumonia (CAP)?
Acquired outside of hospitals or extended-care facilites
What is hospital-acquired pneumonia (HAP)?
Acquired in the hospital
> 48 hours after admission
Increased risk for MDR (multi-drug resistant) bacteria
What is ventilator-associated (VAP)?
Diagnosis made 48-72 hours after endotracheal intubation
What is healthcare-associated (HCAP)?
Diagnosis made while in the community or < 48 hours after hospital admission
Usually following ICU admission
What is the most common pathogen in all types of locations?
Streptococcus pneumonia
What are some risk factors for pneumonia?
Young and old people
Smoker
Lung disease
Dysphagia
Immobility and/or depressed cough reflex
IVDU
What is pneumonitis?
Pneumonia caused by a chemical source
Inhalation of liquid, gases, or small particles
What is atypical pneumonia? How is it presented?
Pneumonia with different symptoms than typical pneumonia
Appear different on x-ray
Respond to different antibiotics
Extrapulmonary s/sx: confusion/change in mental status, GI symptoms, ear pain, sore throat
DOES not mean it is uncommon
What is walking pneumonia?
Patient will look fine and healthy but have pneumonia
no s/sx
Name the normal respiratory tract defense mechanisms
Cilia
Mucus
Mucociliary Escalator
Cough Reflex/ Swallowing
Alveolar Macrophages
What virulence factors does S. pneumoniae have?
- Able to avoid phagocytosis
- Secretes a protein that permits it to adhere to the mucosa
- Secretes a protein that lyses and destroys ciliated cells
- Secretes a protease that inhibits the function of IgA
- Secretes hydrogen peroxide –> damage to host cells
- Activates inflammatory cascade
- Induces vascular permeability
- May become invasive –> move into blood or BBB
How does S. pneumoniae avoid phagocytosis?
Its external polysaccharide capsule prevents opsonization by complement
** Most important virulence factor
What does IgA do? How does S. pneumoniae affect it?
IgA normally binds bacteria to mucus to facilitate clearance from the respiratory tract
S. pneumoniae secretes a protease that inhibits function of secretory IgA
How does bacteria make its way to the lungs?
Inhalation (nose)
Aspiration (mouth)
Hematogenous (bloodstream)
Which patients are we going to be most concerned about, regarding their risk for aspiration?
Patients with dysphagia (ex stroke patients)
What are neutrophil extracellular traps (NETS? What do they do?
A meshwork containing antimicrobial proteins that trap and kill bacteria
Extruded by neutrophils
Can also cause damage
What happens when alveolar air spaces fill with exudative fluid and debris?
Decreased gas exchange
What causes the clinical manifestations of pneumonia?
The inflammatory response rather than the proliferation of the bacteria
S/Sx of Pneumonia
Fever
Chills
Dyspnea
Productive cough
Pleuritic chest pain
Tachycardia
Diminished breath sounds
Inspiratory crackles
Definition of a UTI
Significant bacteria anywhere along the urinary tract, from the kidneys to the urethra
UTIs are more frequent in people born with ____ urethras
Shorter urethras
Lower UTI vs Upper UTI
Lower UTI:
- Cystitis
- Infection confined to the bladder and/or urethra
Upper UTI:
- Pyelonephritis
- Infection is above the bladder (i.e., kidneys, ureters, peri-renal tissue)
What is vesicoureteral reflux? What can it result in?
Condition in which the ureterovesical junction (UVJ) fails to function as a one-way valve, allowing urine and bacteria to reflux back to the kidney
Causes urine and bacteria to reflux back into the kidney
Chronic infection can cause scarring in the kidney
Complicated vs. Uncomplicated UTI
Complicated:
- associated with an underlying condition that increases the risk of therapy failure (ex. DM, pregnancy, renal failure, presence of a catheter)
Uncomplicated:
- Healthy, nonpregnant adults with no risk factors for treatment failures
Name the normal defenses mechanisms of the urinary tract
Urination – flushes out bacteria before it adheres
Low bladder pH
Proteins secreted by kidneys prevent bacterial adherence
Vaginal lactobacilli kill uropathogens
Prostatic secretions are also bactericidal
Secretory IgA
The mucopolysaccharide lining of the urethra/bladder makes it difficult for bacteria to penetrate and adhere
Cell apoptosis –> exfoliate/desquamate –> bacteria are carried away in urine
Inflammatory response by neutrophils and cytokine signaling
Why is E. coli such a common cause of UTI?
- Present in large amounts in the lower gut (close to the vagina and urethra)
- Its flagella permit motility
- Virulence factors (adhesins, fimbriae, capsule, inflammation, hemolysin, toxins, iron transport system)
What are E. coli’s virulence factors? Describe each one
Adhesins allow binding and attach to the urethra and bladder
Fimbriae permit adherence to uroepithelial cells and also block phagocytosis
Polysaccharide capsule prevents phagocytosis and complement attachment
Induces inflammation and exfoliation –> tissue damage –> easier for bacteria to invade
Hemolysin production: induces the formation of pores –> cell lysis
Iron transport system –> uptake iron even in iron-poor environments
Produce toxins
How does E. coli avoid phagocytosis?
Its fimbriae permit adherence to the uroepithelial cells and block phagocytosis
Its polysaccharide capsule prevents phagocytosis
How does a lower UTI occur? Describe the steps
- Bacteria ascend the urethra
- Attach to the bladder epithelium
- Invade the epithelium
- Replicate (produce a biofilm)
- Bacterial toxins and proteases cause exfoliation of cells
- Inflammatory response to the invasion, the possibility of bacterial persistence in the epithelium
Can continue to ascent to the ureter to the kidneys (pathway to pyelonephritis)
How does a lower UTI progress to pyelonephritis (upper UTI)? What can this then lead to?
Bacteria continue their ascension up the urethra and into the kidney(s)
Can lead to acute kidney injury (AKI)
Lower UTI s/sx
- Dysuria
- Urgency
- Frequency
- Nocturia
- Suprapubic heaviness or pain
- Gross hematuria (see blood in urine)
What would you see in the labs of a person with a lower UTI?
Bacteriuria
Pyuria (WBC)
Nitrite
Leukocyte esterase
How do the presence/absence of nitrites and leukocyte esterase affect a UTI diagnosis?
The absence of nitrites or leukocyte esterase does not necessarily rule out a UTI
Their presence provides enough evidence that a UTI is likely occurring
Upper UTI s/sx
- Fever, chills
- Flank pain
- Nausea/vomiting
- Malaise
Can be with or without lower UTI s/sx
Upper UTI CVA PE:
Costovertebral tenderness present
What would you expect to see in the labs of a person with an upper UTI?
Bacteriuria
Pyuria (WBC in urine)
Increased serum WBCs
Nitrite
Leukocyte esterase
How are UTIs clinically presented in pediatric patients?
Infants and children under 2 y.o. may present with FEVER as the sole manifestation of UTI
Children above 2 y.o. will often have the same sx as an adult, but will complain of abdominal pain and bladder incontinence
How are pneumonia and UTI clinically presented in geriatric patients?
They may not present with any of the classic symptoms. They may not even be febrile
A common cluster of s/sx of both pneumonia and UTI in a geriatric patient is a “change in mental status”:
- Confusion
- Delirium
- Lethargy
- Sudden incontinence in a previously continent patient
Delirium vs. Dementia
Delirium:
- Sudden onset
- Dramatic changes in cognition in behavior (morning vs. night)
- Can vary/have periods
- Reversible
- Can be brought on by infection, pain, other illness, disorientation of the hospital setting
Dementia:
- Develop over the years
- Progressive changes in cognition and behavior
- Will not vary in the course of a single day
- Not reversible
What is asymptomatic bacteriuria? What does this mean for our geriatric patients? What problems can arise?
A patient with a significant bacterial count in the urine, but the patient has no dysuria, increased frequency, fever, etc.
IDSA 2019 guidelines do not recommend screening and treating older adults with delirium / asymptomatic bacteriuria to avoid ADE such as C. diff infections.
It creates a fine line to balance the risk of infection –> sepsis with the risk of inappropriate drug treatment –> ADE
We don’t not want to treat an infection bc it can lead to sepsis but we also do not want to cause ADE/resistance.
Are there any exceptions to the “do not screen rule”?
Yes
Pregnant people due to a high risk of progression of symptomatic upper/lower UTI
Patients who undergo a urological procedure in which mucosal trauma is expected
What is the endocardium? What does it do?
thin, smooth layer that lines the chambers of the heart and also covers the valves
Its surface normally inhibits platelets, RBCs, and transient bacteria from attaching
What is ineffective endocarditis (IE)?
An infection of the endocardium, usually of the endocardium covering valves
What is a cardinal feature of IE?
Growth of “vegetation” on infected surfaces
Vegetations: dense aggregate of platelets, fibrin, pro-inflammatory, WBCs, bacteria, and other substances such as collagen
Tends to shield bacteria from the normal innate immune process
What are some causative microbes of IE?
S. aureus (most common)
Streptococci
Enterococci
Fungal (rare, but difficult to treat)
What contributes to vegetation finding a place to attach and grow in IE?
Structural heart disease –> surface that promotes attachment
Certain Gram+ bacteria, such as S. aureus, are able to release substances that allow them to attach even to smooth endocardium
What causes damage to the endocardium in IE?
IVDU practices thought to cause endocardial surface damage
Injection of cocaine –> vasospasm –> tissue damage
Damage to endocardium –> platelet-fibrin thrombus complex deposited on the surface –> thrombus grows larger along with vegetation making it difficult for antibiotics to kill bacteria
Bacteria also induce an inflammatory response –> more tissue damage
Vegetations may disseminate –> break off and enter circulation –> leading to stroke or MI
Clinical presentation of IE:
Non specific fever
Pneumonia, pleural effusion, empyemia (pus collection in pleural space)
May present with stroke, kidney failure or infarct of other organ systems
May already be in sepsis
Heart mummurs in non-IVDU
What must be present to diagnose IE?
Blood cultures x 3 showing microorganisms consistent with IE
Echocardiogram showing vegetation, abscess, or new partial dehiscence of prosthetic valve
Have a high index of clinical suspicion for anyone who has risk factors for IE and presents acutely ill
What are some sequelae of IE? What causes them?
Destruction of affected cardiac valve(s) and other tissue –> acute heart failure
Bits of vegetation may break off and embolize
- Stroke
- MI
- Pulmonary embolism
- Kidney failure
- Infarct necrosis of extremities
What is bacteremia? How does it occur?
Bacteria in the bloodstream
Results from translocation of bacteria from tissue or introduction by a break in skin/mucosal defenses
Potential sequelae of infection
What is sepsis?
Life-threatening organ dysfunction caused by the dysregulated host response to infection
Inappropriate, widespread inflammation is usually the culprit
S/Sx of Sepsis
Hypotension
Shivering, feeling cold
Fever
Extreme pain or discomfort
Diaphoresis or clammy skin
Confusion or disorientation
SOB, tachycardia, hypotension, low O2 stat
Organ failure
What is septic shock?
Defined as sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone
What are the two markers of septic shock?
- Persistent hypotension that requires vasopressors to maintain MAP > 65 mm Hg
- Serum lactate level > 2 mmol/L despite adequate volume resuscitation
May result in circulatory failure
What does the initial, rapid treatment of sepsis include?
Labs: measurement of serum lactate, blood cultures before Abx are started
Measures to increase MAP (fluids, vasopressors)
Early, broad-spectrum Abx until a culprit pathogen is identified –> de-escalate or change antimicrobial
What are some lingering effects of sepsis?
Muscle weakness
Fatigue
Difficulty swallowing, concentrating, sleeping
Anxiety, sadness, poor memory
What are the top two infections that lead to sepsis?
Pneumonia and UTI
