HTHSCI 2HH3 - Cardiovascular System Infections

bacteremia

presence of bacteria in the bloodstream; may or may not be clinically significant

transient bacteremia

self-resolving in clients without underlying illness, immune deficiency or turbulent cardiac blood flow (ex. cutting your gums while brushing teeth, bacteria may get into small cuts)

primary bacteremia

direct inoculation of the bloodstream (ex. health care acquired infections, IV drug use)

secondary bacteremia

microorganisms causing infection at another site (ex. pneumonia) invade the bloodstream and disseminate via the circulation to other body areas (hematogenous spread) (ex. opportunistic infections)

sepsis

life-threatening organ dysfunction due to a dysregulated host response to infection (ex. the body’s response to an infection injuries its own tissues and organs)

sepsis is not bacteremia

What is sepsis characterized by?

infection (suspected or confirmed) AND acute, life-threatening organ dysfunction is measured using the Sepsis-related Organ Failure Assessment (SOFA) tool which measures respiratory, hepatic, cardiovascular, renal, central nervous system, and platelet dysfunction

septic shock

subset of sepsis in which underlying circulatory (critically hypotensive) and cellular/metabolic abnormalities (increased serum lactate) are profound enough to substantially increase mortality

endocardium

thin continuous lining inside chambers of the heart; extends to cover valves

myocardium

muscle tissue of the heart

pericardium

thin double-layered sac that encloses the heart

rheumatic fever

• complication of streptococcal pharyngitis (streptococcus pyogenes); usually develops 2-3 weeks after infection

• autoimmune disease lasting approximately 3 months

• form of molecular mimicry; microorganisms with epitopes similar to host self-antigens triggers autoimmune-mediated tissue damage even after infection is cleared

manifestations of rheumatic fever

• carditis (50-70% of patients)

  • acute valvulitis; valvular regurgitation, chronic valvulitis; valve stenosis

  • typically affects left-sided valves with greater affinity for the mitral valve

  • symptoms of heart failure develop with progressive heart valve damage

• polyarthritis; asymmetric, large joints, lasting approximately 2-3 weeks

• erythema marginatum; rarely observed in adults

• chorea; rarely observed in adults, observed in children

• no infection, not an infective process, won’t find bacteria as these sites are sterile

management of rheumatic fever

• symptomatic management, no specific treatment or cure

• anti-inflammatory drugs (high dose ASA) to relieve inflammation and bed rest

• pharmacological therapies used for HF (in symptomatic patients) (beta blockers, ACEi)

• treatment for GAS regardless of the presence/absence of pharyngitis at the time of diagnosis; to eradicate any residual GAS carriage

• valvuloplasty and valve replacement may be required for those with residual heart disease - percutaneous mitral balloon commissurotomy for mitral valve stenosis is the treatment of choice in those with a suitable valve

prevention of rheumatic fever

• prevention of future (subsequent) cases is key as they are at risk for serious cardiovascular diseases/infections if someone were to get it again

• prophylaxis with targeted antibiotics

  • no residual heart disease: Pen G (BPG) IM, every 4 weeks until age 21 or 10 years after last acute rheumatic fever (ARF)

  • residual heart disease: BPG IM, every 4 weeks until age 40 or 10 years after last ARF, lifetime prophylaxis may be needed

• azithromycin and erythromycin can be used in cases of serious, true penicillin allergy

residual heart disease

persistent valvular disease (documented by clinical or echocardiographic evidence) - sometimes referred to as rheumatic valve

rheumatic heart disease

• clients with a rheumatic heart valve are at an increased risk of complications associated with bacteremia

• increased risk associated with the turbulent blood flow at the site of the damaged valve and the resulting damage to the endocardium

• turbulent blood flow can roughen or erode endocardium

• minor fibrin and platelet deposition can occur on the low-pressure side of the damaged valve and can lead to non-bacterial thrombotic endocarditis (NBTE)

  • those with certain congenital heart defects and damaged/prosthetic valves can be similarly predisposed

• transient cases of bacteremia become problematic; microbe now has a place to adhere (due to roughening of endocardium), increasing the risk of infective endocarditis

vegetation

rough and bumpy growths indicate endocarditis, not structurally stable, can break off and travel elsewhere in the body, can be seen on echocardiography

infective endocarditis

infection and inflammation of the endocardium; commonly affects heart valves

subacute endocarditis

• symptoms develop slowly (weeks to months); mild fever, malaise/fatigue, weakness, myalgias, cough, headache, back and/or chest pain, weight loss

• consider if they have valve issues as symptoms are similar to flu

• new or changing heart murmur, peripheral manifestations

• associated with commensal (low virulence) microorganisms (ex. viridans group streptococci from oropharynx) and mostly seen in cases of pre-existing valve damage

acute endocarditis

• symptoms develop quickly (within days); high fever, chills, tachycardia

• new or changing heart murmur, peripheral manifestations

• associated with highly virulent bacteria (staphylococcus aureus)

peripheral manifestations of infective endocarditis

splinter hemorrhages, janeway lesions, osler’s nodes, roth spots

splinter hemorrhages

linear lesions in the long axis of the distal third of the nail, red in appearance, then brown/black in a few days; non-specific finding

janeway lesions

painless macular lesions, commonly on palmar surfaces of hands and feet (septic emboli - blood clots in periphery)

osler’s nodes

small painful nodular lesions, commonly on pads of fingers and toes, mainly seen in cases of subacute endocarditis due to constant bacteria being introduced into bloodstream stimulating immune system

roth spots

pale-centered retinal hemorrhages; fibrin and platelet aggregation with white center

risk factors for infective endocarditis

• bacteremia

• cardiac conditions

  • abnormal valves (ex. rheumatic valve, prosthetic valve, mitral valve prolapse, congenitally abnormal valve)

  • prior infective endocarditis

  • endovascular cardiac implantable electronic devices (CIEDs) (pacemakers, defibrillator leads)

• IV drug misuse, indwelling line for venous access - recreational drugs are not processed correctly, more jagged, scrapes endocardium, regulated IV drugs are made to travel smoothly in blood vessels and heart

• these all damage the endocardium

complications of infective endocarditis

• persistent bacteremia & risk of seeding distant site - risk of secondary infection and sepsis

• direct cardiovascular tissue damage - damage to heart valve, heart failure

• fragmentation of the vegetations - pulmonary embolism, MI, stroke, seizure, vascular insufficiency and necrosis

• stimulation of antibodies - combine with bacterial antigens and form circulating immune complexes that deposit in kidneys (glomerulonephritis) or skin (osler’s nodes) impairing perfusion of tissues

clinical criteria for infective endocarditis

• use Duke criteria for endocarditis

• definitive IE: 2 major or, 1 major and 3 minor or, 5 minor criteria must be met

• possible IE: 1 major and 1 minor or, 3 minor criteria

Duke Criteria for Endocarditis - Major Criteria

A. Microbiologic Major Criteria

Positive Blood Cultures

i. Microorganisms that commonly cause IE isolated from 2 or more separate blood culture sets or

ii. Microorganisms that occasionally or rarely cause IE isolated from 3 or more separate blood culture sets

Positive laboratory tests

Positive polymerase chain reaction (PCR) or detection of antibodies for bacteria that cause blood culture negative endocarditis

B. Imaging Major Criteria

Echocardiography and Cardiac CT Imaging

i. Showing vegetation, valvular/leaflet perforation, aneurysm, or abscess or

ii. Significant new valvular regurgitation on echocardiography compared to previous imaging or iii. New partial dehiscence of prosthetic valve compared to previous imaging

▪ Transesophageal echocardiogram (TEE) provides better detection and characterization of local abnormalities – especially in cases of cardiovascular implantable electronic devices and prosthetic valves, hence TEE is mandatory in cases of suspected IE

PET/CT Imaging

i. Showing abnormal metabolic activity involving a native or prosthetic valve, ascending aortic graft (with concomitant evidence of valve involvement), intracardiac device leads or other prosthetic material

C. Surgical Major Criteria

i. Evidence of IE documented by direct inspection during heart surgery in the absence of major criterion satisfied by cardiac imaging

Duke Criteria for Endocarditis - Minor Criteria

A. Predisposing condition e.g., history of IE, prosthetic valve, CIEDs, IV drug use

B. Fever >38C

C. Vascular phenomena e.g., arterial emboli, intracranial hemorrhage, cerebral abscess, Janeway lesions

D. Immunologicphenomenae.g.,positiverheumatoidfactor,Osler’snodes,Roth’sspots, immune complex-mediated glomerulonephritis

E. Microbiology e.g., Positive blood cultures not meeting major criteria or positive PCR for microbe consistent with IE from a sterile body site (e.g. cardiac tissue or prosthesis)

F. Imaging e.g., abnormal metabolic activity on PET/CT around site of implantation <3 months cardiac surgery

G. Physical examination e.g., new valvular regurgitation identified on auscultation (echo not available)

treatment for infective endocarditis

• targeted parenteral (IV), bactericidal antimicrobial therapy (long duration (4-6 weeks) depending on susceptibility and nature of valve (native vs prosthetic)

• if clinically stable may switch to oral therapy

• 50% require valve surgery; cases of heart failure, uncontrolled infection or to prevent embolism

• risk of repeat endocarditis

prevention of infective endocarditis

patients at high risk of IE who undergo procedures that are associated with transient bacteremia should receive antibiotic prophylaxis (ex. dental work)

infectious myocarditis

• most often associated with viral infection of the myocardium and infiltration of cardiac muscle by T-lymphocytes

  • enteroviruses; coxsackie B, adenovirus, HSV, influenza virus, SARS-CoV-2, HIV

  • Non-infectious causes should be considered (e.g., autoimmune reactions to vaccines, medications, autoimmune disorders e.g. SLE)

• risk factor - history of recent (within 1-2 weeks) viral infection (upper respiratory or gastrointestinal)

signs, symptoms & diagnosis of infectious myocarditis

fatigue, weakness, SOB, edema, palpitations, similar to mild heart failure, pain reported in those with concomitant pericarditis or myocardial ischemia (acute coronary syndrome)

diagnosis based on clinical presentation, lab tests, ECG, and imaging studies (echocardiography, MRI)

infectious myocarditis in children

• acute (sudden or severe onset) symptoms - cardiogenic shock and acute heart failure, sudden death

• CAR (coxsackie-adenoviral Rc) acts as portal of entry which is expressed in myocytes, children have a higher concentration of myocytes (younger vs older heart) than adults which explains increased risk of infection

• should suspect in young individuals with sudden onset HF, persistent arrhythmia, or with clinical features of MI with normal results of coronary angiography

infectious myocarditis in adults

symptoms progress more slowly, progressive HF & dilated cardiomyopathy

treatment for infectious myocarditis

• similar to that of heart failure (ACEi, beta blockers)

• avoid NSAIDs as they increase the risk of mortality from HF; NSAIDs induce fluid retention (due to vasoconstriction of blood vessels in the kidney and the resulting retention of sodium and potassium)

• immunosuppressive therapy (steroids), antimicrobials (ex. acyclovir in cases of HSV)

complications of infectious myocarditis

• early resolution of symptoms ( < 2 weeks) leads to complete recovery

• prolonged symptoms ( > 2 weeks to months) - dilated cardiomyopathy, heart attack & stroke, worsening heart failure, death (or cardiac transplantation)

infectious pericarditis

• inflammation of the pericardium; commonly co-occurs with myocarditis

• infectious causes are viruses (similar to myocarditis), appears 2-3 weeks post URI or GI infection

• non-infectious causes should be considered; post-MI pericarditis, autoimmune disease, cancer, trauma, medications, cancers

infectious pericarditis symptoms

sharp, stabbing chest pain caused by rubbing of two layers of the pericardium, dry cough, dyspnea, pain worsens when laying down, with deep breaths, swallowing and coughing, pain improves with sitting upright or forward

infectious pericarditis diagnosis

abnormal heart sounds (pericardial rub), abnormal ECG, CT and echocardiogram (TEE) - pericardial effusion (new-onset or worsening)

infectious pericarditis treatment

NSAIDs, colchicine, glucocorticoids (assess for concomitant myocarditis), maybe antimicrobials

infectious pericarditis complications

• cardiac tamponade (tachycardia, SOB, increased RR & prominent neck veins) - pericardiocentesis (withdraw fluid to relieve)

• constricitive pericarditis (progressive weakness, chest pain, palpitations, systemic venous congestion, hypotension, low pulse pressures) - pericardiectomy (pericardium removal)

• pericardium is hard and rigged, “leather-like”

lyme disease

most common vector-borne infectious disease in the temperate northern hemisphere; affecting hundreds of thousands of people annually in NA, caused by Borrelia burgdorferi

Borrelia burgdorferi

gram-negative, spirochete-shaped bacteria with internal periplasmic flagella, motile, transmitted to humans by infected deer ticks or black legged ticks (Ixodes scapularius and pacificus)

lyme disease transmission and infection

• tick bite (portal of entry); spirochetes spread locally in the dermis at a rate of 4um/s

• tick saliva induces local inflammation at the site of the bite, ring of inflammation follows the migrating bacteria (accounting for distinctive rash present in 80% of cases)

• bacteria move from the site of infection into blood and lymph, causing systemic symptoms

• local and disseminated phases of infection; symptoms can be similar to other diseases (people can be unaware they have it)

• no evidence of person to person transmission

deer tick life cycle

• 3 developmental stages; larva, nymph, adult; all stages can feed on humans

• larvae become infected with first blood meal (small mammals & birds); bacteria replicate in their digestive system during winter

• the following spring, ticks molt into nymphs and feed a second time, infecting new hosts with Borrelia

• nymphs develop into adults; feed a final time (infecting their host), then mate, lay eggs and die

• live for 2 years

lyme disease transmission

• infected ticks must be attached to host for more than 24 hours to transmit sufficient spirochetes to establish Borrelia infection

• nymphs (poppy seed) most responsible for human infection as adults (sesame seed) are easier to see and remove

• ticks can’t fly or jump, they wait for a host on grasses and shrubs “questing”

• blacklegged tick attaches to host and sucks blood slowly for several days

• removing a tick quickly (within 24 hours of bite) can greatly reduce risk of lyme disease, the longer the tick is attached the greater the risk

lyme disease prevention

• tick removal - don’t crush, squeeze or damage tick; could facilitate infection

• remove with tweezers, grasp tick close to skin surface, pull upward, clean bite area after, if alive, secure in container and contact public health, submit photo for identification

• avoid tick bites - cover up (light clothing), walk in centre of trail, insect repellent (w/ DEET or icaridin), tick checks on people and pets, shower, put clothes in dryer to kill ticks on clothing

localized lyme disease symptoms

• erythema migrans - skin rash at bite site appears within 3-30 days, initially a red spot (macula) that slowly expands, circular or oval, “bull’s eye”, may be warm, not itchy or painful, may go unnoticed, some never develop rash (70% do)

• fever, chills, headache, stiff neck, fatigue, decreased appetite, muscle and joint aches, swollen lymph nodes, symptoms are non-specific (hard to tell without rash)

• if untreated can spread to joints, heart and nervous system (disseminated infection)

localized lyme disease diagnosis

challenging as symptoms vary from person to person, based on symptoms, travel history, exposure to blacklegged ticks, blood test (serology) may be required

localized lyme disease treatment

most individuals treated with antibiotics in early localized phase of lyme disease and recover rapidly and quickly, early diagnosis and proper treatment can prevent disseminated infection

antibiotics - doxycycline, amoxicillin, cefuroxime preferred, azithromycin or clarithromycin used in cases of allergy or tolerance

disseminated lyme disease symptoms

manifestations 1-4 months after initial infection, skin rashes distal to portal of entry or original rash, arthritis (pain, redness, swelling in large joints), intermittent pain (shooting), weakness, or numbness (tingling) in limbs (peripheral neuropathy), facial palsy, headaches, neck stiffness, poor memory and reduced ability to concentrate (meningitis, encephalitis), conjunctivitis and/or damage to deep eye tissues, lyme carditis (palpitations, arrhythmias, myocarditis, pericarditis), episodes of dizziness or SOB

disseminated lyme disease diagnosis

past exposure and signs and symptoms, serologic testing for presence of antibodies (IgG or IgG/IgM testing), Borrelia burgdorferi antigens differ from region to region; travel history is important and due to antibody persistence, single positive serologic test results cannot distinguish between active and past infection

disseminated lyme disease treatment

supportive therapy (ex. anti-inflammatory drugs), antibiotics determined by systems affected (ex. neurologic lyme disease, lyme carditis, lyme arthritis; referral to infectious disease or another specialist)

lyme disease prophylaxis (post-exposure)

• risk of developing lyme disease from an infected tick is 1-3% in ontario, normally take “wait and see” approach

• post-exposure prophylaxis can be considered if 4 criteria are met:

  • tick was attached > 24 hours

  • tick was removed within past 72 hours

  • tick bite occurred in area where prevalence of ticks infected is > 20%

  • doxycycline is not contraindicated

• prophylaxis treatment is 1 dose PO doxycycline

late-persistent lyme disease syndrome (PTLDS)

• some individuals (10-20%) will experience symptoms of pain, fatigue, insomnia, difficulty thinking that last < 6 months post treatment

• why some experience PTLDS is unclear - associated with tissue damage that occurred before infection was eliminated

• Borrelia burgdorferi may trigger an autoimmune response causing symptoms that persist well after the infection is eradicated; autoimmune responses occur following other bacterial infections

  • Campylobacter jejuni (Guillain-Barré syndrome), Chlamydia trachomatis (reactive arthritis), and streptococcal pharyngitis (rheumatic heart disease)

• not a chronic infection

• osteoarthritis, rheumatoid arthritis, multiple sclerosis, demyelinating disease, ALS, neuropathies, dementia, depression, have all been misdiagnosed as “Chronic Lyme”

  • No credible research to demonstrate that Lyme disease is a chronic infection