Bacterial Diseases - Med Path

What are gram-positive aerobic organisms

• Typically causes skin infections , but sometimes pneumonia, endocarditis, and osteomyelitis.

  • Commonly leads to abscess formation.

Staphylococci

_______ is among the most ubiquitous and dangerous human pathogens, for both its virulence and its ability to develop antibiotic resistance.

• Carried, usually transiently, in the anterior nares of about 30% of healthy adults and on the skin of about 20%.

• From these locations, staph can cause infection in the host and others.

• Carriage rates higher in hospital patients and personnel.

Staphylococcus Aureus

What does this refer to

• Neonates and breastfeeding mothers.

• Patients with influenza, chronic bronchopulmonary disorders (e.g., cystic fibrosis, emphysema), leukemia, tumors, chronic skin disorders, or diabetes mellitus.

• Patients with a transplant, an implanted prosthesis, other foreign bodies, or an indwelling intravascular plastic catheter.

• Patients receiving adrenal steroids, irradiation, immunosuppressants, or antitumor chemotherapy.

• Injection drug users.

• Patients who have chronic kidney disease and are being treated with dialysis.

• Patients with surgical incisions, open wounds, or burns.

People who are predisposed to staphylococcal infections

Predisposed patients may acquire _____________ from other patients, health care personnel, or inanimate objects in health care settings. Transmission via the hands of personnel is the most common means of spread, but airborne spread can also occur.

antibiotic-resistant staphylococci

What does this refer to

• Disease is caused by:

  • Direct tissue invasion (MC).

  • Exotoxin production.

• Direct tissue invasion includes:

  • Skin infections.

  • Pneumonia.

  • Endocarditis.

  • Osteomyelitis.

  • Infectious (septic) arthritis.

Staphylococcus Aureus

Multiple exotoxins are sometimes produced by __________.

• Some have local effects; others trigger cytokine release from certain T cells, causing serious systemic effects (e.g., skin lesions, shock, organ failure, death).

• Toxin-mediated diseases

  • Toxic shock syndrome.

  • Staph scalded skin syndrome.

  • Staph food poisoning.

staphylococci

In the 1940s, medical treatment for __________ infections became routine and successful with the discovery and introduction of antibiotic medicine, such as penicillin.

• From that point on, however, use of antibiotics—including misuse and overuse—has aided natural bacterial evolution by helping the microbes become resistant to drugs designed to help fight these infections.

In the late 1940s and throughout the 1950s, ________ developed resistance to penicillin.

• Methicillin, a form of penicillin, was introduced to counter the increasing problem of penicillin-resistant _______.

• Methicillin was one of most common types of antibiotics used to treat _______ infections; but, in 1961, British scientists identified the first strains of ______ bacteria that resisted methicillin.

• This was the so-called birth of MRSA.

The first reported human case of MRSA in the United States came in 1968.

• Subsequently, new strains of bacteria have developed that can now resist previously effective drugs, such as methicillin and most related antibiotics.

MRSA is actually resistant to an entire class of penicillin-like antibiotics called beta-lactams.

• This class of antibiotics includes penicillin, amoxicillin, oxacillin, methicillin, and others.

_______ is evolving even more and has begun to show resistance to additional antibiotics.

• In 2002, physicians in the United States documented the first S. aureus strains resistant to the antibiotic, vancomycin, which had been one of a handful of antibiotics of last resort for use against S. aureus.

• Though it is feared that this could quickly become a major issue in antibiotic resistance, thus far, vancomycin-resistant strains are still rare.

S. aureus

_______, a form of penicillin, was introduced to counter the increasing problem of penicillin-resistant S. aureus. (no longer works thats why we have MRSA)

Methicillin

Group A streptococcal (GAS aka Strep pyogenes) pharyngitis is the etiologic precursor of _________.

• Host and environmental factors are important.

• GAS M proteins share epitopes (antigenic-determinant sites that are recognized by antibodies) with proteins found in synovium, heart muscle, and heart valve, suggesting that molecular mimicry by GAS antigens from rheumatogenic strains contributes to the arthritis, carditis, and valvular damage.

acute rheumatic fever

What does this refer to

Risk factors: those that predispose patients to strep infections.

• Undernutrition.

• Overcrowding.

• Lower socioeconomic status.

Rheumatic Fever (Acute Rheumatic Fever)

Although GAS infections of both the pharynx and of other areas of the body (skin and soft-tissue structures, bones or joints, lungs, and bloodstream) may cause poststreptococcal glomerulonephritis, nonpharyngitis GAS infections do not lead to ______.

• The reason for this distinct difference in complications resulting from infection by the same organism is not well understood.

The joints, heart, skin, and CNS are most often affected.

• Pathology varies by site.

Acute Rheumatic Fever

What does this refer to

Manifests as carditis.

• Typically affects the heart from the inside out.

  • Valves and endocardium.

  • Then myocardium.

  • Finally, pericardium.

Sometimes followed years to decades later by chronic rheumatic heart disease.

• Valvular stenosis.

• Regurgitation.

• Arrhythmias.

• Ventricular dysfunction.

Rheumatic valvular disease most commonly involves the mitral and aortic valves.

• Tricuspid and pulmonic valves are seldom, if ever, affected in isolation.

Acute Rheumatic Fever: Heart

What does this refer to

• Aschoff bodies often develop in the myocardium and other parts of the heart.

• Fibrinous nonspecific pericarditis, sometimes with effusion, occurs only in patients with endocardial inflammation and usually subsides without permanent damage.

• Characteristic and potentially dangerous valve changes may occur.

• Acute interstitial valvulitis may cause valvular edema.

Acute rheumatic fever

What does this refer to

• Valve thickening, fusion, and retraction or other destruction of leaflets and cusps may occur.

  • Leads to stenosis or insufficiency.

• Chordae tendineae can shorten, thicken, or fuse.

  • Worsens regurgitation of damaged valves.

  • Causes regurgitation of an otherwise unaffected valve.

• Dilation of valve rings may also cause regurgitation.

Chronic rheumatic fever

What does this refer to

• Manifests as nonspecific synovial inflammation.

  • Bx —> small foci resembling Aschoff bodies.

    • Granulomatous collections of leukocytes, monocytes, and interstitial collagen.

• Unlike the cardiac findings of ARF, the joint abnormalities are not chronic.

  • Do not leave scarring.

  • Do not leave residual abnormalities.

  • “ARF licks the joints, but bites the heart.”

Acute rheumatic fever (joints)

What does this refer to

• Subcutaneous nodules appear indistinguishable from those of juvenile idiopathic arthritis (JIA), but biopsy shows features resembling Aschoff bodies.

• Erythema marginatum differs histologically from other skin lesions with similar macroscopic appearance, e.g., the rash of systemic JIA, Henoch-Schönlein purpura, erythema chronicum migrans, and erythema multiforme.

• Perivascular neutrophilic and mononuclear infiltrates of the dermis occur.

Acute rheumatic fever (skin)

What does this refer to

Sydenham chorea, the form of chorea that occurs with ARF, manifests in the CNS as hyperperfusion and increased metabolism in the basal ganglia.

• Increased levels of antineuronal antibodies have also been shown.

Acute rheumatic fever: CNS

What does this refer to

• Anaerobic gram-positive rod.

  • Survives in soil and marine sediment by forming spores.

  • Under anaerobic conditions that permit germination, it synthesizes and releases a potent exotoxin.

  • Microbiologically, the organism stains gram-positive in cultures less than 18 hours old. The organism may stain gram-negative after 18 hours of incubation, potentially complicating attempts at diagnosis.

• Pathophysiology of disease:

  • Toxin-mediated blockade of neuromuscular transmission in cholinergic nerve fibers.

    • Inhibiting acetylcholine release at the presynaptic clefts of the myoneural junctions OR

    • Binding acetylcholine itself

  • Toxins are absorbed from the stomach and small intestine, where they are not denatured by digestive enzymes.

    • Hematogenously disseminated and block neuromuscular transmission in cholinergic nerve fibers.

    • The nervous, gastrointestinal, endocrine, and metabolic systems are predominantly affected.

Botulism

What does this refer to

Infant.

• Ingestion of spores.

• Germinate in the intestines.

• Produce toxins.

• Typically come from bee honey or the environment.

Foodborne.

• Improperly canned or home-prepared foods.

Wound.

• Contamination of a wound with toxin-producing C. botulinum.

Botulism

What does this refer to

• Following traumatic injury that involved soil contamination.

• Among injection drug users (particularly those who use black-tar heroin).

• After cesarean delivery.

• The ______ may appear deceptively benign.

• Traumatized and devitalized tissue provides an anaerobic medium for the spores to germinate into vegetative organisms and to produce neurotoxin, which then disseminates hematogenously.

• The nervous, endocrine, and metabolic systems are predominantly affected.

• Symptoms develop after an incubation period of 4-14 days, with a mean of 10 days

Wound Botulism

What does this refer to “Gram positive obligate anaerobic toxin-forming bacillus”

Clostridium tetani

What does this refer to

__________ tetanospasmin interferes with neurotransmission at spinal synapses of inhibitory neurons.

• Minor stimuli result in uncontrolled spasms.

• Reflexes are exaggerated.

Neurotoxin

What does this refer to

• Spores of the organism are ubiquitous in soil and may germinate when introduced into a wound.

• Incubation period = 5 days – 15 weeks (average 8-12 days).

• Most cases occur in unvaccinated individuals.

• Persons at risk:

  • Older adults.

  • Migrant workers.

  • Newborns.

  • Injection drug users.

• Puncture wounds are particularly prone to infection.

  • Any wound, including bites or decubiti, may become colonized/infected.

Tetanus

What is a Gram positive, club-shaped bacteria.

Diphtheria (Corynebacterium diptheriae)

What does this refer to

• Green club shaped.

• Metachromatic granules: dark blue spots made of phosphate at the bacterial poles.

• When they cluster together, they look like Chinese letters.

Albert’s stain (Diphtheria (Corynebacterium diptheriae))

What does this refer to

Subspecies can be toxigenic or not, depending on if they produce the ________ toxin (DT).

• Cytotoxic protein that damages host cells.

• All subspecies start out non-toxigenic, but become toxigenic once they are infected by a beta-bacteriophage.

Diphtheria (Corynebacterium diptheriae)

What part of diptheria does this refer to

• Virus that attaches to bacteria and merges its genome with the bacteria’s.

• Contains tox-genes that code for DT production.

• Now the diphtheria bacteria can cause diphtheria.

Beta-bacteriophage

________ has two subunits, A and B, connected by a disulfide bond.

• Subunit B attaches to host cell membrane.

• Whole _____ complex is engulfed, forming a sac inside the cell (endosome).

• Medium inside the endosome becomes acidic, breaking the disulfide bond.

• Subunit A leaves the endosome and goes to the host cell ribosomes.

• Interferes with cell protein synthesis.

• Leads to cell death.

Diptheria

What is this referring to

• Unvaccinated or immunocompromised people.

• Transmitted mainly be respiratory droplets (coughing, sneezing).

• Pharyngeal type.

• Bacteria attaches to pharyngeal epithelial cells and releases DT toxin.

• Leads to necrosis of the tissue.

• Necrotic tissue builds up over the pharynx/larynx, forming a gray film.

  • Gray, adherent, leathery membrane (pseudomembrane).

• May partially detach, get lodged in the trachea/bronchi, block airways.

  • Death by asphyxiation.

• Bacteria gradually invade deeper into the pharyngeal wall, into the bloodstream and to other locations in the body.

  • Myocarditis.

  • Acute tubular necrosis.

  • Nerve demyelination, polyneuropathy.

  • Oculomotor nerve —> palsy —> impaired ocular movements.

  • Phrenic nerve —> affects diaphragm —> trouble breathing.

• Transmitted through open skin lesions.

  • Cutaneous type.

Diptheria

What does this refer to

Contagious infection due to vibrio cholera.

• Gastroenteritis, watery diarrhea-”rice water diarrhea”

• Rapid dehydration, which can be fatal.

Cholera

What does this refer to

Gram negative, curved bacteria.

• Flagellum.

Cholera

What does this refer to

Transmission

• Fecal to oral route.

• Consuming untreated sewage water.

• Raw or undercooked fish/shellfish.

• Improper hygiene (not washing hands after BM).

More common in developing countries

• Africa, South America

Cholera

What does this refer to

Once in the intestines…

• Moves toward intestinal wall.

• Propels through the mucous layer.

• Attaches to villi on the surface of epithelial cells.

• Multiplies, producing toxins.

• V. cholera does not enter the cells, but the toxins do.

Toxins produced depend on the strain of bacteria.

• Some toxins produce little or no symptoms.

• Cholera enterotoxin (choleragen) —> significant symptoms.

  • Disrupts the osmotic balance between the intestines and the surrounding tissues.

  • Water, bicarbonate, and potassium rush into the lumen of the intestines.

  • Leads to voluminous amounts of watery diarrhea (rice water).

Cholera

What does this refer to

• A comma-shaped bacteria.

  • Gram negative.

  • Has a flagellum; motile.

• One of the most common causes of gastroenteritis worldwide.

Campylobacter jejuni

What does this refer to

Transmission:

• Animals to humans.

• Fecal-oral route (ingestion of stool particles containing bacteria).

• GIT of birds (undercooked poultry).

• Cows (unpasteurized milk).

• Infected pets (puppies with infected stool).

• May contaminate fresh water supplies.

Campylobacter jejuni

What does this refer to

• Gram negative curved bacillus found in poultry and frequent etiology of food poisoning worldwide

• 1-7 day incubation period.

• Once in the body…

  • Attach to mucosa of small intestine and colon.

  • Uses spiral shape and flagella to drill into the mucosa.

  • Release toxins (cytolethal distending toxins-CDT).

  • Damage nearby epithelial cells, causing inflammation.

  • Colon can dilate, causing toxic megacolon.

  • Bacteria may keep drilling until they reach the blood stream (bacteremia).

  • Immune system may react by producing anti-ganglioside antibodies.

    • Attack peripheral nerves.

    • Cause Guillain-Barre syndrome.

  • May prompt an autoimmune reaction, attacking the joints.

    • Reactive arthritis.

Campylobacter jejuni

What does this refer to

Gram-negative.

• Cannot retain the crystal violet stain used during gram staining.

• Unlike other GN bacteria, chlamydia has no layer of murein (peptidoglycan).

• Cannot retain the pink safranin dye used in gram staining.

• Best stained with giemsa stain, which colors them pinkish blue.

Chlamydia (C. Trachomatis)

Chlamydia (C. Trachomatis) has 15 serotypes

• A-C —> ____________

conjunctivitis in adults (trachoma).

Chlamydia (C. Trachomatis) has 15 serotypes

• D-K —> ____________

genital infection (chlamydia)

Chlamydia (C. Trachomatis) has 15 serotypes

• L1, L2, L3 —> ____________

infect lymph nodes (lymphogranuloma venereum)

What does this refer to

• Untreated, can progress to keratoconjunctivitis.

• Infection of both the cornea and conjunctiva.

• May lead to total blindness.

Chlamydia conjunctivitis

What does this refer to

• Most common STD in men and women.

• Men:

  • Urethritis, prostatitis.

• Women:

  • Urethritis, vulvovaginitis, cervicitis, pelvic inflammatory disease, Fitz-Hugh-Curtis syndrome (once inflammation spreads to peritoneum).

Chlamydia

What does this refer to

• Can be passed to baby during vaginal delivery.

• Late onset neonatal conjunctivitis.

• Neonatal pneumonia if travel down respiratory tract.

Chlamydia during pregnancy.

What “Most commonly affects the inguinal lymph nodes.”

Lymphogranuloma venereum (chlamydia)

What does this refer to

A purulent infection of the mucous membranes caused by Neisseria gonorrhoeae.

• Gram-negative, intracellular, aerobic diplococcus.

An important public health problem.

• Major source of M/M worldwide

Gonococcal Infections

What is spread by

• Sexual contact.

• Transmission during childbirth (opthalmia neonatorum and systemic neonatal infection).

  • Neonatal prophylaxis is standard in the developed world.

Gonococcal Infections

How does gonococcal infections present in woman

• Endocervicitis.

• Urethritis.

• PID.

How does gonococcal infections present in men

Anterior urethritis.

What does this refer to

• Can also spread through the body to cause localized and disseminated disease.

• Refers to urethritis and/or cervicitis in a sexually active person

Gonococcal Infections

The presence of ________ in the blood stream.

• Can lead to disseminated gonococcal infection (DGI).

• Occurs in about 0.5-3% of patients with gonorrhea.

Gonoccocemia (N. gonorrhea)

Organisms spread from a primary site, such as the endocervix, the urethra, the pharynx, or the rectum, and disseminate to the blood to infect other end organs.

• Usually, multiple sites, such as the skin and the joints, are infected.

• Neisserial organisms disseminate to the blood due to a variety of predisposing factors, such as host physiologic changes, virulence factors of the organism itself, and failures of the host's immune defenses.

  • Changes in the vaginal pH during menses, pregnancy, puerperium make the environment more suitable for growth.

  • Defects in the host’s immune defenses make certain patients more likely to develop this.

  • Certain strains are more virulent and are associated with DGI.

Gonoccocemia

What does this refer to

Sexually Transmitted Infection

• Usually follows mucosal inoculation during vaginal, anal, or oral sexual contact.

  • It also may be caused by inoculation of mucosa by contaminated fingers or other objects.

• The risk of transmission of ________ from an infected woman to the urethra of her male partner is approximately 20% per episode of vaginal intercourse and rises to 60-80% after 4 or more exposures.

  • In contrast, the risk of male-to-female transmission approximates 50-70% per contact, with little evidence of increased risk with more sexual exposures.

N gonorrhoeae

What does this refer to

Importance in pediatric population is 3-fold.

• Common, preventable STD in sexually active teens.

• Perinatal infection at childbirth.

• Forensic aid in investigating sexual abuse.

Gonococcal Infections

What population of gonoccocal does this refer to

• May follow conjunctival infection during passage through the birth canal.

• Direct infection may occur through the scalp at the sites of fetal monitoring electrodes.

Neonatal

What does this refer to

• May occur from sexual abuse by an infected individual.

• May occur through nonsexual contact in the household or in institutional settings.

Gonococcal Infections: Pediatrics

What can occur when a person touches an infected site (genital organ) and contacts skin or mucosa?

Autoinoculation

What does this refer to

• Sexual exposure to an infected partner without barrier protection (e.g., failure to use a condom or condom failure).

• Multiple sex partners.

• Male homosexuality.

• Low socioeconomic status.

• Minority status - Blacks, Hispanics, and Native Americans have the highest rates in the United States.

• History of concurrent or past STDs.

• Exchange of sex for drugs or money.

• Use of crack cocaine.

• Early age of onset of sexual activity.

• Pelvic inflammatory disease (PID).

• Use of an intrauterine device (IUD).

Risk factors of gonococcal infection

What does this refer to

• Intracellular pleomorphic coccobacillus

• Causes Rocky Mountain Spotted Fever

• Tick-borne disease

  • The organism is endemic in parts of North, Central, and South America, especially in the southeastern and south-central United States.

  • Transmitted to humans by the bite of a tick.

    • Several hours of contact between the tick and the human host are required for transmission.

• Native Americans are at high risk for infection.

Rickettsia ricketsii

What is a life-threatening organ dysfunction caused by a dysregulated host response to infection?

Sepsis

What pathophysiology is the following

Inflammatory cascade → vasodilation, capillary leakage, coagulation abnormalities.

Sepsis

What has a high mortality if untreated; early recognition saves lives.

Sepsis

What contains common causes of

• Bacterial infections (e.g., pneumonia, urinary tract infections, intra-abdominal infections)

• Fungal or viral causes less common

Sepsis

What has these risk factors

• Age (elderly, infants)

• Immunosuppression (HIV, chemotherapy, corticosteroids)

• Chronic illnesses (diabetes, liver/kidney disease)

• Indwelling devices (catheters, central lines)

Sepsis

What is the initial trigger in the pathophysiology of sepsis

Infection by bacteria, virus, fungi, or parasites

What is the host response in the pathophysiology of sepsis

Immune system launches inflammatory response

What is the key problem in the pathophysiology of sepsis

Dysregulated immune response causes collateral damage

What is the outcome of the pathophysiology of sepsis

Widespread inflammation, coagulation, and tissue injury

What does this refer to

• Pathogen Recognition:

  • PRRs (Pattern Recognition Receptors) detect PAMPs (Pathogen-Associated Molecular Patterns)

  • Common PRR: Toll-like receptors (TLRs)

• Cytokine Storm:

  • Massive release of pro-inflammatory cytokines (TNF-α, IL-1, IL-6)

  • Results in fever, vasodilation, increased vascular permeability

Step 1 – Inflammatory Cascade of the Innate Immune Activation

What does this refer to

• Vasodilation → Hypotension

• Increased capillary permeability → Fluid shifts into tissues → Edema

• Endothelial injury leads to:

  • Leukocyte adhesion

  • Microthrombi formation

  • Reduced perfusion and oxygenation

Step 2 – Vascular and Endothelial Changes (Endothelial Dysfunction)

What does this refer to

• Activation of coagulation cascade

  • Tissue factor expression increases

  • Decreased anticoagulants (Protein C, antithrombin)

• Microvascular thrombosis

  • Organ ischemia and dysfunction

• Risk of DIC: Disseminated intravascular coagulation

Step 3 – Procoagulant State (Coagulation Abnormalities)

What does this refer to

• Mitochondrial injury → impaired ATP production

• Cellular hypoxia despite normal oxygen delivery

• Apoptosis and impaired cellular repair

• Result: Multisystem organ failure (lungs, kidneys, liver, brain)

Step 4 – Mitochondrial and Organ Dysfunction (Cellular dysfunction and organ failure)

What does this refer to

• If controlled:

  • Anti-inflammatory mediators (IL-10, TGF-β) restore balance

  • Immune system regains regulation

• If uncontrolled:

  • Persistent inflammation + immune paralysis

  • Septic shock: profound hypotension, lactate >2 mmol/L, high mortality

Step 5 Resolution or Progression to Septic Shock (Resolution or progression)