Microbiology Flashcards
6-year-old immigrant from Eastern Europe having difficulty breathing. Has fever, not eating or drinking. Neck swelling, palatal paralysis, and gray pharyngeal exudate. No vaccination history.
• Diphtheria (caused by Corynebacterium diphtheriae).
• Acute infection of the naso-oropharynx transmitted via respiratory droplets.
• Pseudomembranous pharyngitis (gray pharyngeal exudate)
• Sx. Sore throat, fever, LAD, upper airway dyspnea, odynophagia.
•Diphtheria toxin has tropism for neural/cardiac tissue –> can cause CNS/cardiac sequelae.
• Diphtheria infection associated with 5-10% mortality rate, esp in young patients or those with myocarditis.
• Cardiomyopathy is the most common cause of death.
• Tx. Diphtheria antitoxin (passive immunization)- inactivates all circulating toxin but ineffective against toxin that has already gained access to cardiac or neural cells.
• Rapid administration of antitoxin essential –> transfer of pre-existing neutralizing antibodies.
• Penicillin or erythromycin kills bacteria, halting release of new exotoxin into bloodstream and preventing transmission.
• TDaP vaccine (active immunization)- provides lasting immunity against future infection.
******
Diphtheria exotoxin
AB toxin that ADP-ribosylates and deactivates elongation factor-2, inhibiting protein synthesis. Tropism for neural and cardiac tissue.
Most common causes of viral meningitis
•Enteroviruses (eg, coxsackievirus, echovirus, poliovirus) –> cause 90% of aseptic meningitis cases
• Arboviruses
•HSV type 2
•Mumps virus, but unlikely in fully immunized child. •Meningitis caused by mumps virus accompanied by parotitis in 50% of cases.
******
Most common causes of bacterial meningitis
Adults: Streptococcus pneumoniae, Neisseria meningitidis
Neonates: Group B streptococcus (S. agalactiae), gram-negative bacilli
CSF profile of viral (aseptic) meningitis
• Sx. Fever, headache, vomiting, stiff neck, typically less severe sx than bacterial meningitis. No focal neurologic signs, seizures, AMS.
• CSF WBC count: less than 500, lymphocytic predominance
• CSF Glucose: normal or slightly reduced
• CSF Protein: usually less than 150 mg/dL
•CSF Gram stain/culture: No organisms identified.
******
CSF profile of bacterial meningitis
• CSF WBC count: greater than 1000, neutrophilic predominance
• CSF Glucose: less than 45 mg/dL
• CSF Protein: greater than 250 mg/dL
•CSF Gram stain/culture: often positive for specific organism
******
Bronchiolitis
•Lower respiratory tract infection most commonly caused by respiratory syncytial virus (RSV) and typically in infants less than 2 years old.
•Presents with low-grade fever, cough, tachypnea, and increased work of breathing (retractions and nasal flaring).
• Apnea in high-risk patients (less than 2 months old or premature).
******
Disseminated mycobacterial disease in infancy or early childhood
•AR deficiencies of IFN-γ receptor (or other elements in IFN-γ signaling pathway) lead to impaired IFN-γ-mediated immunity.
•Can cause disseminated mycobacterial disease in infancy or childhood, including disseminated infection by the BCG vaccine strain if administered.
• Once identified, patients require lifelong treatment with continuous antimycobacterial agents.
• Host defense against mycobacterial infections depends on interactions btw macrophages and T cells through the IFN-γ and IL-12 signaling pathway.
• IFN-γsecreted by TH1 cells or NK cells is key to elimination of these infections.
******
IFN-gamma signaling pathway
• Møs infected by mycobacteria produce IL-12, which stimulates TH1 cells and NK cells to produce IFN-γ.
• IFN-γ binds to its receptor on the Mø, leading to dimerization of receptor and activation of intracellular JAK1 and 2.
• STAT1 activation by JAK1 and JAK2 leads to nuclear translocation of STAT1 and transcription of IFN-γ-regulated genes that promote intracellular killing.
• IFN-γ also enhances viral and parasitic resistance by increasing MHC expression and intrinsic defense factors.
******
C3 deficiency
Predisposes to recurrent infections with encapsulated organisms.
C5-C9 deficiency
Predisposes to recurrent infections with Neisseria meningitidis or N gonorrhoeae. C5-C9 = membrane attack complex (MAC).
Isotype switching
• Isotype switching to IgE induced by IL-4
• Isotype switching to IgA induced by IL-5
•Occurs in naive B lymphocytes on initial exposure to antigen.
• Primarily induced by CD40 interaction with CD40L on T-helper cells, which then secrete IL-4 and IL-5.
******
HBV infection
•Worldwide, countries with high rates of HBV infection have more than 85% of all hepatocellular carcinoma (HCC) cases.
•Korea, Taiwan, Mozambique, and China have the highest annual rates of HCC.
• Individuals who develop HCC in those countries usually have chronic HBV infection acquired through vertical transmission at childbirth.
• In US, HCC normally arises after age 60, while in these countries with high rates of HBV infection, HCC commonly presents in adults 20-40 years old.
• Universal vaccination of children against HBV infection would likely cause a steep decline in worldwide incidence of HCC.
******
HBV phases of infection
- Proliferative phase- entire virion and related antigens of the episomal HBV DNA are present. HBsAg and HBcAg are expressed with MHC Class I molecules on hepatocyte cell surface, activating cytotoxic CD8+ T lymphocytes, which respond by destroying infected hepatocytes.
- Integrative phase- HBV DNA is incorporated into the host genome of those hepatocytes that survived the immune response. Infectivity ceases and liver damage tapers off when the antiviral antibodies appear and viral replication stops. However, risk of HCC remains elevated due to HBV DNA integration into host genome.
* ***********
Features of systemic mycoses
• Cause pneumonia and can disseminate
• Dimorphic fungi: cold=mold, heat=yeast
• Exception: coccidioidomycosis is a spherule (not yeast) in tissue.
• Tx fluconazole/itraconazole for local infection.
• Tx amphotericin B for systemic infection.
• Systemic mycoses can form granulomas (like TB) but cannot spread person-to-person (unlike TB).
******
Histoplasmosis
•Pneumonia-like sx caused by infection with Histoplasma capsulatum
• Location: Mississippi and Ohio River valleys
• Macrophages filled with Histoplasma (organisms smaller than an RBC).
• Histo “hides” within macrophages.
•Associated with bird (eg, starlings) or bat droppings and cave exploring
• Tx fluconazole/itraconazole for local infection
• Tx amphotericin B for systemic infection
******
Blastomycosis
• Pneumonia-like sx caused by infection with Blastomyces dermatitidis
• Location: Eastern US and Central America
•Inflammatory lung disease and can disseminate to skin and bone, causing granulomatous nodules.
• Broad-base budding (same size as an RBC).
• Blasto buds broadly.
******
Coccidioidomycosis
• Pneumonia-like sx caused by infection with Coccidioides immitis or Coccidioides posadasii
•Location: Southwest US, California
• Pneumonia and meningitis, can disseminate to skin and bone
•Case rate increases after earthquakes, b/c spores in the dust are thrown into the air and inhaled by people, forming spherules in the lungs.
• Spherule filled with endospores (much larger than RBC)
•”San Joaquin Valley Fever”
•”Desert bumps” = erythema nodosum
•”Desert rheumatism” = arthralgias associated with dissemination.
******
Paracoccidioidomycosis
•Caused by Paracoccidioides brasiliensis
• Location: Latin America
•Budding yeast with “captain’s wheel” formation (much larger than RBC)
•PARAcoccidio PARAsails with the Captain’s Wheel all the way to Latin America.
•Tx with fluconazole/itraconazole (local), Amphotericin B (systemic)
******
Aerobes
• Nagging Pests Must Breathe • Nocardia • Pseudomonas aeruginosa • MycoBacterium tuberculosis • Reactivation TB ---> predilection for lung apices ******************************
India ink stain
• Cryptococcus neoformans
• Mucicarmine can also be used to stain thick polysaccharide capsule red
******
Exotoxin
• Present in both gram + and gram - bacteria
• Gene for exotoxin on plasmid or bacteriophage
• Polypeptide secreted from cell
• Fatal dose on order of 1 µg
• Induces high-titer antibodies called “antitoxins”
• Toxoids used as vaccines
• Ex. tetanus toxin, botulinum toxin, diphtheria toxin
******
Capsule
• Organized polysaccharide layer that protects against phagocytosis
• Bacillus anthracis is only bacteria to have poly-D-glutamate capsule instead of polysaccharide
******
Charcoal-yeast extract agar buffered with cysteine and iron
• Legionella pneumophila
• Think: “Legionnaire (soldier) with SILVER helmet sitting at a campfire (CHARCOAL) with his IRON dagger - he is no sissy! (CYSTEINE)”
• Silver stain to see legionella, doesn’t gram stain
******
Eosin-methylene blue (EMB) agar
• E. coli colonies grow with green metallic sheen
• Other lactose fermenters grow as purple/black colonies
******
Ecthyma gangrenosum
Rapidly progressive necrotic cutaneous lesion caused by Pseudomonas, typically seen in immunocompromised patients.
Obligate intracellular pathogens
• “Stay inside when it’s Really CHilly COld!”
• Rickettsia
• Chlamydia
• Coxiella
• These pathogens rely on host ATP to replicate/survive and thus are obligate intracellular pathogens.
******
Facultative intracellular pathogens
• Some Nasty Bugs May Live FacultativeLY • Salmonella • Neisseria • Brucella • Mycobacterium • Listeria • Francisella • Legionella • Yersinia pestis ******************************
Ziehl-Neelsen stain
• Aka carbol fuchsin stain
• Stains acid-fast bacteria: Mycobacteria (stains mycolic acid in cell wall), Nocardia (weakly), protozoa (eg, cryptosporidium oocysts)
• Cheaper alternative with greater sensitivity but decreased specificity: auramine-rhodamine
******
Hemolytic Uremic Syndrome
• E coli 0157: H7
• Triad of anemia (MAHA), thrombocytopenia (platelet consumption), and acute renal failure (decreased RBF) due to platelet microthrombi on damaged endothelium.
******
EHEC
• Enterohemorrhagic E. coli
• Most common serotype in the US is E coli 0157:H7
• Undercooked meat/raw leafy vegetables
• Shiga-like toxin causes HUS
• Dysentery (toxin alone causes necrosis and inflammation)
• Doesn’t ferment sorbitol, differentiating EHEC from other E. coli
• HUS, Hamburgers, Hemorrhagic diarrhea
******
Sabouraud agar
• Grows fungi
• “Sab’s a fun guy!”
******
MacConkey agar
• MacConKEE'S agar • Klebsiella • E coli • Enterobacter • Serratia (grows weakly/slowly) • Lactose-fermenting enterics (eg, E. coli) grow on this agar • Contains a pH indicator • Fermentation of lactose creates acidic metabolites causing colonies to turn pink ******************************
Spores
• Keratin-like coat over bacterium
• Some bacteria can form spores at the end of the stationary phase when nutrients are limited.
• Only Gram + bacteria.
• Spores highly resistant to dehydration, heat, and chemicals, no metabolic activity
• Dipicolinic acid, peptidoglycan, DNA
• Must autoclave to potentially kill spores by steaming at 121 celsius for 15 mins.
• Bacillus anthracis - Anthrax
• Bacillus cereus - food poisoning
• Clostridium botulinum - botulism
• Clostridium difficile - pseudomembranous colitis
• Clostridium perfringens - gas gangrene
• Clostridium tetani - tetanus
******
Anaerobes
• Anaerobes "Can't Breathe Fresh Air" • Clostridium spp. • Bacteroides fragilis • Fusobacterium • Actinomyces • Foul smelling, difficult to culture, produce gas (CO2, H2) in tissue, normal flora in GI tract • Susceptible to oxidative damage • AminO2glycosides ineffective against anaerobes b/c they require O2 to enter the bacterial cell wall. ******************************
Organisms seen best with silver stain
• Fungi (eg, coccidioides, Pneumocystis jiroveccii)
• Legionella pneumophila
• Helicobacter pylori
******
Gram-negative coccobacilli
• Haemophilus influenzae: requires X and V factors, pleomorphic
• Legionella pneumophila: charcoal/yeast agar with Fe and cysteine, silver stain
• Bordetella pertussis: Bordet-Gengou agar, pertussis toxin, tracheal cytotoxin, anti-FHA vaccine
• Coxiella burnetii: Q fever, spores inhaled from cattle/sheep amniotic fluid, culture-negative endocarditis
• Brucella: aerobic, zoonotic, unpasteurized dairy
• Francisella tularensis: requires cysteine, ticks/rabbits/deer flies
• Pasteurella multocida: oxidase +, catalase +, cellulitis/osteomyelitis, animal/cat/dog bite
• Bartonella henselae: cat scratch disease
******
Gram-negative diplococci
• Neisseria meningitidis: aerobic, maltose and glucose utilizer
• Neisseria gonorrhoeae: aerobic, glucose utilizer only
• Moraxella catarrhalis: aerobic, oxidase +
******
Gram-negative curved bacilli
• Campylobacter jejuni: microaerophilic, oxidase +, catalase +, urease –, grows in 42 C, assoc. with Guillain–Barré syndrome
• Helicobacter pylori: microaerophilic, oxidase +, catalase +, urease +, silver stain
• Vibrio cholerae: oxidase +, glucose +, grows in alkaline media, non-lactose fermenting
******
Gram-negative bacilli
• Bacteroides fragilis: strict anaerobe
• Klebsiella pneumoniae: fast lactose fermenter
• Escherichia coli: fast lactose fermenter, indole +
• Enterobacter spp: fast lactose fermenters
• Citrobacter: slow lactose fermenters
• Serratia: slow lactose fermenters
• Pseudomonas aeruginosa: non-lactose fermenting, oxidase +
• Salmonella typhi, enteritidis: motile, non-lactose fermenting, oxidase –, H2S producing on TSI agar
• Proteus mirabilis: non-lactose fermenting, oxidase –, H2S producing on TSI agar, urease +
• Shigella dysenteriae: non-motile, non-lactose fermenting, oxidase –, non-H2S producing on TSI agar
• Yersinia pestis: non-lactose fermenting, oxidase –, non-H2S producing on TSI agar, bipolar staining
• Yersinia enterocolitica: non-lactose fermenting, oxidase –, non-H2S producing on TSI agar, motile at 25 C, not at 37 C
******
Haemophilus influenzae
• Small gram-negative coccobacillus
• Aerosol transmission, human-to-human
• Cultured on chocolate agar with factors V (NAD+) and X (hematin) for growth –> can also be grown with S aureus, which provides factor V through RBC hemolysis.
• Nontypeable (unencapsulated) strains are the most common cause of mucosal infections (otitis media, conjunctivitis, bronchitis) since Hib vaccine
• Produces IgA protease, protecting organism from secretory IgA
• HaEMOPhilus causes:
• Epiglottitis (“thumbprint sign” on X-ray)
• Meningitis
• Otitis media
• Pneumonia
• Hib vaccine: type B capsular polysaccharide and PRP (polyribosylribitol phosphate) conjugated to diphtheria toxoid: given to 2-18 months old
• Dx: +Quellung reaction, immunofluorescence, or growth on chocolate agar with factor X and V.
• Tx: amoxicillin/clavulanate for mucosal infections, ceftriaxone for meningitis, rifampin prophylaxis for close contacts
• Hib causes meningitis most commonly in infants after maternal Ab protection has declined (6 months) and before they have developed their own Abs.
******
Bordetella pertussis
• Gram-negative aerobic coccobacillus
• Virulence factors: pertussis toxin (disables Gi by ADP-ribosylating it, leading to uninhibited AC and increased cAMP, which causes lymphocytosis and impairs phagocytosis to permit its own survival) and tracheal cytotoxin (kills ciliated cells impairing mucous clearance)
• Whooping cough = child coughs on expiration and whoops on inspiration, mechanism unknown, spreads bacteria
• May be mistaken as viral infection due to lymphocytic infiltrate resulting from immune response
• Filamentous hemagglutinin (FHA) = adherence to ciliate epithelium of respiratory tract
• Tdap and DTaP vaccines (2, 4, 6, 18 months) generate Anti-FHA antibodies
• 3 stages of whooping cough:
• Catarrhal stage (1-2 weeks): flulike sx, highly contagious
• Paroxysmal stage (3rd week-2 months): intermittent bouts of many coughs on a single expiration followed by a whooping inspiration
• Recovery stage (2-3 months): coughing subsides
• Tx. erythromycin only useful before paroxysmal stage aka if already whooping, supportive care
******
Legionella pneumophila
• Gram-negative coccobacillus, gram stains poorly, best seen with silver stain.
• Grows on charcoal yeast extract medium with cysteine and iron
• Detected by urine antigen
• No person-to-person transmission
• Aerosol transmission from contaminated environmental water source (eg, air conditioning systems, hot water tanks), adheres to respiratory epithelium via pili, phagocytosed by alveolar macrophages
• Legionnaires’ disease: severe atypical PNA, CXR reveals nodular infiltrates (micro-abscesses in lungs), fever, GI sx (diarrhea), CNS sx, hyponatremia on labs, common in smokers and patients with chronic lung disease
• Pontiac fever: mild flu-like illness lasting 2-5 days
• CAP in elderly smokers
• Tx. erythromycin, azithromycin (macrolide)
******
Coxiella burnetii
• Small gram-negative coccobacillus
• Obligate intracellular pathogen
• Q fever, presents as pneumonia, no rash
• Most common cause of culture-negative endocarditis
• Spores inhaled as aerosols from cattle/sheep amniotic fluid
• Coxiella genus morphologically similar to Rickettsia but with differences
• No arthropod vector
• Endospores highly resistant to high temperature, osmotic pressure, UV light and can survive outside
• Tx. Doxycycline
******
Francisella tularensis
• Gram-negative coccobacillus, pleomorphic!
• Requires cysteine for growth
• Tularemia- site-specific infection: ulceroglandular tularemia (ulcer with black base), oculoglandular (conjunctival infection), pulmonary tularemia (inhalation), typhoidal tularemia (GI ingestion).
• Transmission from rabbits to humans by tick bite/infected animal, bacteria phagocytosed, localize to RES, cause caveating granulomas (conjunctiva, lungs, GI tract), regional LAD and long-lasting fever.
• Papule develops into ulcer with black base, erythematous tender surrounding, axillary LNs on same side enlarged
• Vector = ticks
• Source: deer flies, rabbits (eg, rabbit farm)
• Dx. Skin test (delayed-type hypersensitivity response), serology
• Tx. streptomycin, live-attenuated vaccine for high-risk individuals
• F. tularensis and BCG (for TB) are the only live-attenuated vaccines for bacteria.
• Most cases occur in Arkansas, Oklahoma, Missouri
******
Pasteurella multocida
• Gram-negative coccobacilli with “bipolar staining”, oxidase +, catalase +
• Cellulitis or osteomyelitis (sharp cat’s teeth can directly implant into bone) following cat/dog bite with local LAD
• Inhabits oral cavity of animals, enters human skin via bite, elicits inflammatory response at inoculation site and spreads locally.
• May progress to septicemia
• Transmission: animal bite
• Source: cats, dogs
• Dx, Gram stain
• Tx. penicillin G, clean and drain wound, suturing wound could worsen infection by creating closed anaerobic environment
******
Brucella spp.
• Gram-negative aerobic coccobacillus, facultative intracellular
• Brucellosis- undulant fever, fatigue, spinal tenderness, anorexia, enlarged LNs
• Undulating fever- fever rises during the day and peaks after dinner, declines at night, lasts for months
• Phagocytosed in macrophages –> caseating granulomas and abscess formation
• Unpasteurized dairy (eg, imported goat cheese)
• Brucellergin skin test (delayed-type hypersensitivity response) indicates current or previous exposure
• Tx. doxycycline + gentamicin
• Osteomyelitis is most common complication
******
Bartonella henselae
• Gram-negative coccobacillus best seen with silver impregnation stains
• Varying clinical presentations of “cat scratch disease”: regional lymphadenopathy and FUO in immunocompetent patients
• Cats are natural reservoir–> inoculate humans with bite/saliva/scratch causing primary cutaneous lesion–> regional LAD from local skin infection
• Disseminated infection in HIV+ patients: ocular infection (Parinaud’s oculoglandular syndrome, granulomatous conjunctivitis, periauricular LAD, optic neuritis), bacillary angiomatosis (bxp of skin lesions show granulomatous inflammation with clusters of bacilli), CNS infection (encephalitis, transverse myelitis, cerebellar ataxia), myalgias, arthralgias, osteomyelitis, necrotizing granulomas causing HSM or peliosis hepatis (blood-filled cavities throughout liver)
• Dx based on serology, blood cx, PCR or bxp of lesion showing granulomatous inflammation with bacilli
• Doxycycline or Azithromycin
• Cat fleas implicated in transmission between cat, and flea feces implicated in transmission to humans
******
Quellung reaction
Biochemical reaction in which antibodies bind to bacterial capsule of Streptococcus pneumoniae, Klebsiella pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Escherichia coli, and Salmonella. Antibody reaction allows these species to be visualized under a microscope. If reaction is positive, capsule becomes opaque and appears to enlarge.
HACEK organisms
• Gram-negative bacilli of normal oral flora that can infect heart valves • Most common gram-negative causes of endocarditis in non-IV drug users •Haemophilus species • Actinobacillus actinomycetemcomitans • Cardiobacterium hominis • Eikenella corrodens • Kingella ******************************
Neisseria meningitidis
• Gram-negative diplococci within PMNs
• Meningococcemia = fever with petechial hemorrhages and gangrene of toes
• IgA protease allows N. meningitidis to cross mucosa into bloodstream via phagocytic vacuoles–> meningococcemia –> endotoxin release leads to vascular necrosis and hemorrhage in skin –> petechial rash
• Pathogens may have tropism for meninges–> meningitis
• Waterhouse-Friederichsen syndrome = fulminant meningococcemia with vascular necrosis and hemorrhage in adrenal glands causing adrenal insufficiency, fever, DIC, and shock –> multiorgan failure
• LP reveals increased PMNs, increased protein, decreased glucose and gram-negative intracellular diplococci
• Dx. selectively grows on Thayer-Martin media, metabolizes maltose AND glucose (MeninGitidis vs. N. gonorrhoeae)
• Tx. Ceftriaxone or penicillin G, rifampin for close contacts as prophylaxis, vaccine with capsular polysaccharides
• Most common causes of meningitis from 6-60 years old: N. meningitidis, Enterovirus, S. pneumoniae.
******
Neisseria gonorrhoeae
• Gram-negative diplococci within PMNs
• Local gonorrhea = may be asymptomatic, urethritis/dysuria (in men), cervicitis (in women), or ophthalmia neonatorum (risk for blindness)
• Systemic gonorrhea = septic arthritis, organisms can invade submucosa and enter bloodstream, collecting in synovial fluid
• In women, cervicitis may progress to uterus, fallopian tubes, and ovaries, causing pelvic inflammatory disease and increased risk for ectopic pregnancies
• Complications: PID, ectopic pregnancy, sterility, Fitz-Hugh-Curtis syndrome (bacterial infection from fallopian tubes may spill into the peritoneal cavity causing infection of the liver capsule)
• Virulence factors: specialized pili (allows attachment to mucosal cells of urethra/vagina, antigenic variation to evade host defense, prevent phagocytosis), IgA protease, endotoxin
• Dx. selectively grows on Thayer-Martin media, metabolizes glucose but not maltose (vs. N. meningitidis)
• Tx. ceftriaxone (+ doxycycline (or azithromycin) for probable concurrent Chlamydia coinfection)
• Prophylactic erythromycin eye drops for all neonates to prevent blindness
• Antigenic variation of pili makes vaccine development difficult and prevents immunity, allowing for recurrent gonorrhea infections.
******
Neisseria gonorrhoeae vs. Neisseria meningitidis
• Both gram-negative diplococci, oxidase +
• Gonococci ferment Glucose only
• MeninGococci ferment Maltose and Glucose
• Gonococci have no capsule
• Meningococci have a polysaccharide capsule
• Gonococci have no vaccine due to antigenic variation of pilus proteins
• Meningococci have a vaccine against polysaccharide capsule
• Gonococci are sexually or perinatally transmitted
• Meningococci are transmitted via respiratory/oral secretions and are more common in close quarters (eg, army bases, college dorms)
• Gonorrhea is treated with ceftriaxone (+doxycycline, erythromycin eye ointment in neonates to prevent conjunctivitis and blindness
• Meningococcemia is tx with ceftriaxone, prophylaxis with rifampin, ciprofloxacin, or ceftriaxone given to close contacts of infected patients.
******
Moraxella catarrhalis
• Gram-negative diplococci
• Otitis media, sinusitis, pneumonia
• Normally colonizes nasopharynx–> spreads to contiguous mucosal surfaces and releases endotoxin, stimulating an inflammatory response
• Virulence factors: specialized pili (antigenic variation to evade immunity), endotoxin
• Dx. hydrolyzes tributyrin, produces DNAse, reduces nitrite/nitrate, dose not utilize sucrose/glucose/maltose/lactose
• Tx. amoxicillin-clavulanate (95% produce beta-lactamase), 2nd or 3rd gen cephalosporins, TMP-SMX
• Second most common cause of bacterial PNA in patients with COPD behind nontypeable H. influenzae
******
Gardnerella vaginalis
•Pleomorphic gram variable rod
• Causes bacterial vaginosis (BV) - gray vaginal discharge with fishy odor, nonpainful, not sexually transmitted, overgrowth of anaerobic bacteria in vagina
• Dx. “clue cells” on wet mount (vaginal epithelial cells covered with Gardnerella), amine whiff test (10% KOH) –> fishy odor
• Tx. metronidazole or clindamycin
******
Campylobacter jejuni
• Gram-negative curved S-shaped rod with polar flagellum (motile), oxidase +, urease –
• Presents clinically with bloody or secretory diarrhea
• Carried by poultry/cattle –> transmitted by fecal-oral route or unpasteurized milk –> colonizes terminal ileum/colon and often invades –> may release enterotoxin and cytotoxin
• Grows best at 42 C, microaerophilic (lower oxygen than atmospheric)
• Tx. erythromycin, ciprofloxacin
• Many cases of Guillain-Barré syndrome (GBS) thought to be complications of Campy infections
• Can also cause reactive arthritis
• Rotavirus, ETEC, and C. jejuni are most common causes of diarrhea world-wide
• Major cause of bloody diarrhea in children
******
Helicobacter pylori
• Gram-negative spiral-shaped bacilli with polar flagellum (motile), oxidase +, urease +, catalase + (triple positive)
• May present as acute gastritis or chronic antrum gastritis, pangastritis, or peptic ulcers
• Organism colonizes gastric antrum but does not invade–> produce ammonia (via urease) to protect from acidic environment –> host inflammatory response leads to mucosal damage and loss of mucus-secreting cells –> acute gastritis
•If gastritis limited to antrum –> somatostatin secretion by D cells in antrum decreases, causing acid hypersecretion and risk of duodenal ulcers
• If pangastritis –> acid hyposecretion –> chronic infection and inflammation –> risk of gastric ulcers and gastric carcinoma
• Chronic H. pylori gastritis is associated with gastric adenocarcinoma and MALT lymphoma
• Dx. urease + breath test (C14-labeled urea breath test, urea ingested and labeled CO2 exhaled if urease bacteria present), or fecal antigen, IgG titer in serum, biopsy showing gram-negative rods
• Tx. Amoxicillin + Clarithromycin + PPI (Antibiotics Cure Pylori)
• Tx. If allergic to penicillin: PPI + BMT (bismuth, metronidazole, tetracycline)
• 100% of duodenal ulcers vs. 70% of gastric ulcers are associated with H. pylori infection
• Ulcers associated with infection have “punched-out” appearance and smooth borders, while ulcers associated with malignancies have heaped borders.
******
Vibrio cholerae
• Gram-negative, flagellated, comma-shaped rod, single flagella
• Oxidase +, grows in alkaline media, lactose non-fermenter, glucose fermenter
•Water, food, shellfish –> very sensitive to stomach acid –> large inoculum is required (ID50), but much lower inoculum required in people on chronic PPIs or H2 blockers with less acidic stomach pH –> produces mucinase to digest mucous coat on intestinal cells –> attaches to proximal small intestine with little competition from other bacteria
• Endemic to developing countries
• Cholera toxin (carried on bacteriophage): ribosylates Gs –> permanent Gs activation –> increased AC activity –> increased cAMP –> crypt cells secrete more Cl- into bowel lumen, villous cells absorb less Na+ –> osmotic H2O efflux –> “rice-water” diarrhea and severe dehydration
• Flat yellow colonies on TCBS agar
• Tx. oral rehydration solution (glucose + Na) or IV fluids to prevent hypovolemic shock/death, tetracycline
• ORS capitalizes on Na-glucose cotransporters in small intestine
• Blood group O patients are more vulnerable!
• Vibrio parahaemolyticus = similar but associated with raw seafood consumption (Japan), grows in 8% NaCl and more invasive
******
Bacteroides fragilis
• Gram-negative obligate anaerobic rod
• Large capsule gives colonies mucoid appearance
• Only gram-negative rod without typical endotoxin (inactive LPS); Listeria monocytogenes is only gram+ with endotoxin
• Presents clinically with peritonitis or GI/pelvic abscesses (below the diaphragm)
• Normal GI flora (make vitamin K) –> ruptured intestinal mucosa (trauma, surgery, perforation) –> spills into peritoneum with GI facultative anaerobes –> catalase and SOD allow pathogen to survive in oxygen environment until all O2 used up and organism thrives –> purulent abscess formation
• Tx. drain abscess + repair lesions + metronidazole/clindamycin
• May cause pelvic abscesses 2/2 septic abortions or IUDs
******
Klebsiella pneumoniae
• Gram-negative rod, fast lactose fermenter
• Presents as pneumonia or nosocomial UTI
• Aspiration of intestinal flora in elderly, unconscious, or alcoholics –> pneumonia (most frequently right upper lobe) –> large antiphagocytic capsule causes mucoid colonies –> stimulates inflammation, necrosis, forms cavity –> bloody “currant jelly” sputum
• Klebsiella causes UTIs when all competing bacteria are killed (eg, hospital-administered antibiotics) and when urinary tract is blocked by catheter or stone
• Tx. third-generation cephalosporin, very drug-resistant
• 4 A’s of KlebsiellA: Aspiration PNA, Abscess in lungs/liver, Alcoholics, diAbetes
• Similar nosocomial infections are caused by the lactose fermenters: Klebsiella, Serratia marcescens, Enterobacter
******
EIEC
• Gram-negative rod, fast lactose fermenter
• Enteroinvasive E. coli
• Invasive –> adhere to colonic epithelium –> invade mucosa causing necrosis and inflammation
• Dysentery aka bloody diarrhea
• Similar presentation to Shigella –> bloody diarrhea with leukocytes in stool
• Tx. rehydration
******
EPEC/EAEC
• Gram-negative rod, fast lactose fermenter
• Enteropathogenic E. coli, Enteroaggregative E. coli
• No toxin produced
• Adhere to ileal epithelium but do not invade –> induce structural changes in mucosa –> flatten intestinal villi (effacement) causing malabsorption and diarrhea
• EPEC = “infants diarrhea” in newborn nurseries
• EAEC = diarrhea in children
• Think E”P”EC in “P”pediatrics!
• Tx. rehydration
******
ETEC
• Gram-negative rod, fast lactose fermenter
• Enterotoxigenic E. coli
• E”T”EC = Traveler’s diarrhea, produces enTeroToxins
• Watery diarrhea (like Vibrio cholerae), no invasion/inflammation
• Adhere to jejunum/ileum but do not invade
• Produce heat-labile toxin (LT) and heat-stable toxin (ST) enterotoxins, which both contribute to watery diarrhea
• LT = similar to cholera toxin: ADP ribosylates Gs –> activates AC –> increased cAMP –> crypt cells secrete more Cl-, villous cells absorb less Na+ –> osmotic loss of water to lumen –> watery diarrhea
• ST = similar to Yersinia enterocolitica toxin: activates guanylate cyclase –> increased cGMP –> decreased cotransport of NaCl into cells –> water remains in lumen of gut –> watery diarrhea
• Tx. rehydration
******
EHEC
• Gram-negative rod, fast lactose fermenter
• Enterohemorrhagic E. coli
• Adhere to colonic epithelium but do not invade –> secrete cytotoxic Shiga-like toxins 1 and 2 –> inflammation, bleeding –> hemorrhagic colitis –> SLTs and endotoxin may enter bloodstream, spreading to kidneys and causing damage aka HUS = fever, hemolytic anemia, thrombocytopenia, acute renal failure
• SLT (verotoxin): inactivates 60S ribosome subunit –> blocks protein synthesis –> cell death –> hemorrhagic colitis
• SLT = Shiga-like toxin
• Tx. rehydration
******
What are the different types of Enterovirulent Escherichia coli (EEC)?
• Gram-negative rod, fast lactose fermenter, green metallic sheen on EMB agar, light purple on MacConkey agar, serology (O and H antigens)
• EnteroInvasive E. coli (EIEC) invades intestinal wall to produce severe bloody diarrhea
• EnteroHemorrhagic E. coli (EHEC): E. coli 0157:H7 causes bloody diarrhea and HUS
• EnteroToxigenic E. coli (ETEC) produces toxins that act on the intestinal lining, and is the most common cause of traveler’s diarrhea.
• EnteroPathogenic E. coli (EPEC) causes diarrhea outbreaks in newborn nurseries.
•Enteroaggregative E. coli (EAEC) causes acute and chronic (long-lasting) diarrhea in children.
• Tx. rehydration
******
Escherichia coli
• Gram-negative rod, fast lactose fermenter
• May present as enteritis (watery/bloody diarrhea depending on strain), UTI, pneumonia, neonatal meningitis, septic shock (endotoxin release), HUS
• Normal flora of humans –> virulent strains transmitted via fecal-oral route –> use pili to adhere
• Virulence factors: K antigen = capsule, O antigen = component of LPS in outer membrane, H antigen = flagella, pili mediate attachment to specific sites, endotoxin (lipid A component of LPS) causes septic shock
• UTIs caused by pathogen adhering to urethra (urethritis) –> may ascend to bladder (cystitis) –> or kidneys (pyelonephritis)
• E. coli toxins: ST and LT in ETEC, SLT in EHEC
• Dx. green metallic sheen on EMB agar, light purple colonies on MacConkey agar, serology (O and H antigens)
• Tx. rehydration for diarrhea, TMP-SMX or penicillin for UTIs, third-generation cephalosporin for meningitis/sepsis
• E. coli is the most common cause of UTI and gram-negative sepsis
******
Most common causes of neonatal meningitis and neonatal pneumonia
• Neonatal meningitis: Group B Streptococcus, E. coli, Listeria
• Neonatal pneumonia: Group B streptococcus, E. coli
******
Salmonella spp. (not S. typhi)
• Eg, Salmonella enteritidis
•Gram-negative flagellated (motile) rod, non-lactose fermenter, oxidase –, H2S-producing
• Human and animal reservoir (poultry, eggs, pets, turtles)
• Hematogenous spread
• Virulence factors: endotoxin, H antigen (flagella)
•High infectious dose (ID50, inoculum) required
• Immune response = PMNs
• Gastroenteritis/diarrhea usually caused by non-typhoidal Salmonella
• Tx. aggressive rehydration, antibiotics not indicated as prolong the duration of fecal excretion (carrier state)
• Tx. only for patients with risk of invasive disease or neonates
• Turtles or uncooked chicken are common sources of Salmonella gastroenteritis
• No vaccine
******
Salmonella typhi
• Gram-negative flagellated (motile) rod, non-lactose fermenter, oxidase –, H2S-producing
• Asx carriers, vs. typhoid fever vs. osteomyelitis in patients with SCD (functionally asplenic)
• Human reservoir only –> fecal-oral transmission –> penetrate colonic mucosa (hematogenous spread) –> capsular Vi polysaccharide allows survival in phagocytes of Peyer’s patches –> spread via phagocytes to gallbladder, liver, spleen –> release endotoxin –> typhoid fever –> may progress to carrier state
• Carrier state: stored in gallbladder (esp gallstones) –> may reenter bowel to spread via feces–> may present with S. typhi-induced necrotizing cholecystitis
• Virulence factors: endotoxin, Vi capsule, H antigen (flagella)
•High infectious dose (large inoculum) required to overcome gastric acid defense
• Immune response = monocytes
• Constipation followed by diarrhea
• Tx. abx prolong duration of fecal excretion and increase chance of relapse
• Ciprofloxacin/ampicillin may be used for carriers or cholecystectomy may be necessary
• Oral vaccines are killed or live attenuated, IM vaccine (Vi capsular polysaccharide)
• Typhoid fever = rose spots on abdomen, constipation, GI pain, fever, followed by diarrhea
• Tx with ceftriaxone/fluoroquinolone for resistant strains
******
Shigella spp
• Gram-negative non-lactose fermenter, oxidase –, does not produce H2S, no flagella, non-motile
• Four F’s for transmission: Fingers, Flies, Food, Feces
• Human reservoir only –> fecal-oral –> endocytosed by colonic epithelium –> escapes vesicles –> replicate intracellularly and spread cell-to-cell (no hematogenous spread) –> mucosal ulcers and bleeding –> damage prevents fluid reabsorption –> bloody diarrhea
• Virulence factors: endotoxin, Shiga toxin (inactivates 60S ribosomes, further damage to mucosa), invasion is the key to pathogenesis (little toxin-mediated effects)
• O antigen: polysaccharide in outer membrane used to classify Shigella genus into 4 groups
• Low infectious dose (small inoculum) required, resistant to gastric acid, hypochlorhydric patients not at increased risk
• Immune response = PMNs
• Bloody diarrhea (dysentery)
•Tx. antibiotics shorten duration of fecal excretion, rehydration for moderate cases, fluoroquinolones for severe cases
• No vaccine
• Order of decreasing virulence for Shigella spp: Shigella dysenteriae, S. flexneri, S. boydii, S. sonnei (least amount of toxin produced)
• Shiga toxin (like SLTs produced by EHEC) can cause HUS
******
Yersinia enterocolitica
• Gram-negative rod, non-lactose fermenter, oxidase –, does not produce H2S, motile at 25 C not at 37 C
• Transmitted from pet feces, contaminated milk, pork
• Acute diarrhea (enterocolitis) or mesenteric adenitis
• Raw milk or fecal-oral route –> terminal ileum –> heat-stable enterotoxin –> diarrhea –> invades and spreads to colon –> ulceration and bleeding –> bacteria carried to mesenteric LNs by lymphatics –> replicates in LNs –> swelling of mesenteric LNs (adenitis)
• Pseudo-appendicitis - RLQ abdominal pain 2/2 mesenteric adenitis or terminal ileitis
• Rarely causes septicemia, usually self-limiting
• Most common complication is arthritis
******
Pseudomonas aeruginosa
• Gram-negative rod, non-lactose fermenter, oxidase +
• Aerobic, flagellated (motile), produces pyocyanin pigment (blue-green colonies), grape-like odor
• Associated with moisture (eg, respiratory equipment, visitor’s flowers, endoscopes)
• Endotoxin (shock), pyocyanin (generates ROS)
• Exotoxin A: ADP ribosylates host EF2 –> paralyzes host cell protein machinery (similar to diphtheria toxin)
• Phospholipase C: cleaves phosphates from phospholipids –> damages host cell membrane –> phosphates feed microorganism
• Elastase: cleaves elastin, collagen, complement components, Igs –> dissemination
• Inhabits many environments: soil, water, colon
• CP: chronic pneumonia (CF patients); UTI (hospital patients); burn wound infection (ecthyma gangrenosum), septicemia; endocarditis (IVDUs); osteomyelitis (DM, IVDUs); malignant external otitis (DM); hot tub folliculitis; other ifxns in hosts with weakened immunity
• Mucoid polysaccharide capsule creates biofilms
• AERuginosa = AERobic
• Tx. CAMP FIRE
• Carbapenems (imipenem, monopenem), Aminoglycosides (gentamicin), Monobactams (Aztreonam), Polymyxins (colistin), Fluoroquinolones, thIRd generation cephalosporins (ceftazidime, cefepime), Extended-spectrum penicillins (piperacillin, ticaricillin)
• Tx. anti-pseudomonal penicillin + aminoglycoside (eg, piperacillin + gentamicin) or fluoroquinolones
******
PSEUDOMONAS
• Pneumonia (CF pts), pyocyanin (ROS), phospholipase C
• Sepsis (due to endotoxin)
• Ecthyma gangrenosum, Exotoxin A, Endotoxin
• UTIs (hospital patients)
• Diabetes/IVDU (endocarditis)
• Osteomyelitis (eg, puncture wounds)- DM/IVDU
• Mucoid polysaccharide capsule, Motile
• Otitis externa (swimmer’s ear or malignant OE in DM), Oxidase +
• Nosocomial infections, Non-lactose fermenter
• Aerobic, exotoxin A
• Skin –> hot tub folliculitis
******
Proteus mirabilis
•Gram-negative rod, non-lactose fermenter, oxidase –, urease +, many flagella, very motile, “swarming” growth
• Normal GI flora –> enter through urethra –> urease splits urea to form ammonium hydroxide, increasing urinary pH –> precipitation of ammonium magnesium phosphate stones –> struvite calculi –> stones backlog urine causing damage to kidney and serving as sites of persistent infection
• O antigen used in Weil-Felix reaction used to diagnose Rickettsia –> Proteus antigens cross-react with patient’s serum antibodies against Rickettsia
• Large radiopaque stones (struvite stones) in urinary tract
• Alkaline urine (high pH)
• Tx. TMP-SMX, ampicillin
******
Yersinia pestis
• Gram-negative rod, lactose non-fermenter, bipolar staining (looks like a safety-pin)
• Bubonic plague, fleas are the vector, rodents and prairie dogs are the reservoir
• Causes fever, dark black skin patches, enlarged, painful LNs in groin
• Endotoxin causes DIC –> cutaneous hemorrhagic necrosis causing black color (“Black Death”)
• Regional lymphadenitis = buboes, often in groin
• Capsular F-1 antigen prevents phagocytosis, generates antibody response
• Streptomycin, tetracycline
• Vaccine: killed and attenuated vaccines available, generate antibodies against F1 antigen
******
Anaplasma spp.
• Ixodes tick is vector (mice and deer)
• Granulocytes with morulae in cytoplasm ("MEGA berry")
• Monocytes = Erlichiosis
• Granulocytes = Anaplasmosis
• Tx. doxycycline
******************************Ehrlichia chafteensis
• Lone Star tick is vector
• Monocytes with morulae in cytoplasm, mulberry-like inclusions, ("MEGA berry")
• Monocytes = Erlichiosis
• Granulocytes = Anaplasmosis
• Tx. doxycycline
******************************Gram-positive bacilli
• Bacillus cereus: spore-forming, aerobic, motile
• Bacillus anthracis: spore-forming, aerobic, non-motile
• Clostridium tetani: spore-forming, obligate anaerobe, motile
• Clostridium botulinum: spore-forming, obligate anaerobe, motile
• Clostridium difficile: spore-forming, obligate anaerobe, motile
• Clostridium perfringens: spore-forming, obligate anaerobe, non-motile
• Listeria monocytogenes: non-spore forming, motile
• Corynebacterium diphtheriae: non-spore forming, non-motile
******
Gram-positive branching filaments
• Actinomyces: anaerobic, not acid-fast
• Nocardia: aerobic, weakly acid-fast
******
Gram-positive cocci (all aerobic)
• Staphylococcus aureus: catalase +, coagulase +, β-hemolytic
• Staphylococcus epidermidis: catalase +, coagulase –, novobiocin sensitive
• Staphylococcus saprophyticus: catalase +, coagulase –, novobiocin resistant
• Streptococcus pyogenes (Group A): catalase –, β-hemolytic, bacitracin sensitive
• Streptococcus agalactiae (Group B): catalase –, β-hemolytic, bacitracin resistant
• Streptococcus pneumoniae: catalase –, α-hemolytic, optochin sensitive, bile soluble, encapsulated
• Streptococcus mutans/mitis (Viridans streptococci): catalase –, α-hemolytic, optochin resistant, bile soluble, not encapsulated
• Enterococcus faecium/faecalis: catalase –, γ-hemolytic, grows in 40% bile, grows in 6.5% NaCl
• Streptococcus bovis (Group D streptococcus): catalase –, γ-hemolytic, grows in 40% bile, does not grow in 6.5% NaCl
******
Bacillus cereus
• Gram-positive, spore-forming rod, aerobic, motile
• Causes food poisoning - “reheated rice syndrome”
• Bacteria contaminate uncooked food (eg, rice) –> during high-temperature cooking form protective spores –> when food rewarmed later results in spore germination and enterotoxin secretion
• Toxin type determines syndrome
• Heat-stable enterotoxin (like Staph enterotoxin) –> emetic syndrome –> N/V within 1-5 hours of ingesting reheated rice/pasta, caused by preformed toxin cereulide
• Heat-labile enterotoxin (like ETEC LT) –> increased cAMP concentration causes reabsorption of NaCl in gut lumen –> diarrheal syndrome –> watery, non-bloody diarrhea within 8-20 hours of ingestion
• Tx. rehydration, avoid reheating rice, etc.
******
Bacillus anthracis
• Gram-positive rod in chains, spore-forming, aerobic, non-motile, only medically-relevant bacterium with polypeptide capsule (poly-D-glutamate)
• Endospore- spores destroyed by boiling but survive for years in dry earth or goat skin
• Anthrax toxin: protective antigen (PA) and edema factor (EF) or lethal factor (LF)
• PA binds cell membranes and mediates endocytic entry of EF or LF
• EF increases AC activity, leading to increased cAMP, causing edema and inhibition of PMNs
• LF causes cell death
• Spores from goat/cow products enter via cutaneous abrasion –> germinate and multiply –> secrete anthrax toxin –> tissue hemorrhage/necrosis/edema –> cutaneous anthrax –> painless papule/pustule surrounded by vesicles –> painless, necrotic ulcer with black eschar
•Spores ingested –> germinate and multiply in intestines/oropharynx causing lesions in throat and dysentery 2/2 anthrax toxin (GI anthrax)
• Spores inhaled –> germinate and multiply in respiratory tract –> enter bloodstream with anthrax toxin secreted systemically –> fever, dyspnea, cough –> 100% mortality
• Pulmonary anthrax (woolsorter’s disease)–> inhalation of spores leads to flu-like symptoms, rapidly progresses to fever, pulmonary hemorrhage, mediastinitis and shock
• Tx. Parenteral penicillin G
• Px. anti-PA vaccine
******
Clostridium tetani
• Gram-positive rod, spore-forming, obligate anaerobe, motile, large terminal spore (shaped like a “tennis racket”)
• Spores survive in soil/feces for years –> enter through skin injury –> bacteria germinate and release tetanospasmin –> tetanospasmin travels retrogradely on axons of peripheral motor neurons and through bloodstream –> spinal cord –> tetanus progresses from head to trunk to extremities (determined by length of neurons) –> masseter muscle most sensitive (lockjaw)
• Tetanospasmin = exotoxin protease that cleaves SNAREs –> blocks vesicular release of inhibitory GABA and glycine from Renshaw cell interneurons of spinal cord–> motor neurons hyperexcited –> spastic paralysis and tetanus (sustained muscle contraction) –> trismus (lockjaw), risus sardonicus (raised eyebrows, open grin)
• Prophylaxis: DTaP vaccine administered at 2, 4, 6, 18 months, with 10 year boosters, tetanus toxoid
• Tx. antitoxin (human anti-tetanospasmin Ig), wound debridement, +/- DTaP vaccine booster, diazepam (GABA agonist) to tx muscle spasms, penicillin/metronidazole
• “Looks sort of odd, spore-forming rod, anaerobic, makes you so sick, it overrides gangliosides, your jaw is locked, GABA is blocked!”
******
Clostridium botulinum
• Gram-positive rod, spore-forming, obligate anaerobe, motile, large terminal spore (shaped like a “tennis racket”)
• Botulinum toxin = heat-labile exotoxin protease that cleaves SNAREs at the NMJ, inhibiting vesicular release of ACh at the NMJ–> Botulism (descending flaccid paralysis)
• Adult botulism –> food poisoning caused by preformed toxin ingestion –> heat-labile toxin released in anaerobic environment (eg, canned foods) –> ingestion contaminated food –> neurotoxin enters vascular system and spreads to peripheral cholinergic nerve terminals w/i 12-36 hours –> blocks ACh release at CNs (diplopia, dysarthria, dysphagia), NMJs (symmetric descending paralysis spreading from head to extremities), postganglionic parasympathetic nerve endings (dizziness, dry throat, ptosis)
• Infant botulism –> preformed spores often ingested with contaminated honey –> spores germinate in large intestine, release toxin –> toxin slowly absorbed over days, blocking ACh release –> constipation, floppy baby syndrome (descending flaccid paralysis) –> good prognosis with supportive care
•No fever, bacteria do not invade
•Dx. check for toxin in uneaten food or mouse test: inject patient serum into mouse and check for paralysis/death
• Tx. antitoxin + respiratory support
• Watch out for swollen food cans! Bacteria generate gas.
• Local botox (BOtulinum TOXin) injection used to tx focal dystonia, achalasia, strabismus, muscle spasms, wrinkles
******
Clostridium difficile
• Gram-positive rod, spore-forming, obligate anaerobe, motile, large terminal spore (shaped like a “tennis racket”)
• Associated with PPI use and antibiotic use (clindamycin, ampicillin)
• Normal GI flora –> abx tx disrupts normal flora, but C. diff survives by forming spores –> spores germinate after tx and grow rapidly due to fewer competing microorganisms –> secrete two toxins
• Toxin A = enterotoxin = binds to brush border of gut, altering fluid secretion –> watery diarrhea
• Toxin B = cytotoxin = cytoskeletal disruption via actin depolymerization, cytotoxic to epithelial cells –> pseudomembrane formation
• Toxin release causes diarrhea and pseudomembranous colitis –> pseudomembranes are yellow-white plaques
• Dx. detection of toxin B in stool sample by PCR
• Tx. metronidazole or oral vancomycin (not absorbed), withdraw causative agent (often clindamycin)
• Tx for recurrence: fidaxomicin or fecal transplant
• Inflammation by toxin A can sometimes cause hypoalbuminemia
******
Clostridium perfringens
• Gram-positive rod, spore-forming, obligate anaerobe, non-motile
• Cellulitis, gas gangrene (myonecrosis with crepitus), food poisoning
• Cellulitis: spores in soil –> bacteria infect anaerobic environment of necrotic skin wound –> release collagenase, hyaluronidase –> slow, painless infection and gas production –> forms collections of gas under skin that crackle when touched (crepitus)
• Gas gangrene: spores in soil –> introduced via deep muscle laceration (military wounds, auto accidents, crude abortions) –> growth in anaerobic environment –> release α-toxin (lecithinase-phospholipase) myonecrosis and hemolysis, degradative enzymes cause subQ gas bubbles (crepitus) –>gangrenous muscles –> black fluid exudate –> shock
• Tx. surgical debridement, hyperbaric oxygen to kill anaerobic bacteria, penicillin, clindamycin (effective only in local, weak infections)
• Food poisoning: spores in meat/poultry can survive in undercooked food and germinate –> when ingested cause food poisoning by releasing heat-labile enterotoxin in GI tract –> enterotoxin inhibits glucose transport and damages epithelium –> diarrhea, gastric pain, nausea (no fever)
******
Listeria monocytogenes
• Gram-positive rod, non-spore forming, motile, facultative intracellular bacillus, catalase +
• Only gram+ with endotoxin
• Ingestion of unpasteurized dairy or cold deli meats –> mild self-limiting gastroenteritis in healthy individuals, sepsis/meningitis in immunocompromised patients or neonates
• Patients deficient in cell-mediated immunity (pregnant women, neonates, AIDS) have ineffective phagocytosis –> Listeria invades phagocytes of GI mucosa and grows intracellularly –> spreads through blood –> tropism for neural tissue (meningitis)
• Transplacental (amnionitis, spontaneous abortion) or transvaginal transmission at birth possible (granulomatosis infantiseptica, neonatal meningitis)
• Forms “rocket tails” via actin polymerization to allow intracellular movement and cell-to-cell spread avoiding antibody opsonization –> “tumbling” motility in cultures
• Tx. ampicillin +/- gentamicin in infants, immunocompromised, and elderly patients for empiric tx of meningitis, TMP-SMX
• Listeria and β-hemolytic streptococci look similar on blood agar plates but Listeria is catalase +
******
Corynebacterium diphtheriae
• Gram-positive rod, non-spore forming, non-motile, aerobic
• “Chinese letters” appearance on culture
• Black colonies on cystine-tellurite agar
• Enters nasopharynx via respiratory droplets –> creates gray fibrinous exudate composed of bacteria, WBCs, necrotic mucosa –> may obstruct airway –> secretes diphtheria toxin
•Diphtheria toxin = potent exotoxin encoded by β-prophage, inhibits protein synthesis in all cells via ADP-ribosylation of EF-2–> myocarditis, cranial and peripheral nerve palsies
• Sx. sore throat, difficulty breathing/swallowing, large gray mucous film on oropharynx (pseudomembranous pharyngitis), LAD, myocarditis, arrhythmias, polyneuritis
• Dx. Gram + rods with metachromic (blue + red) granules, Elek test + for toxin
• Tx. antitoxin, penicillin or erythromycin, DTaP booster
• Do not scrape pseudomembrane –> toxin spread
• Preventable with DTaP vaccine: diphtheria toxoid
• ADP-ribosylation (of EF2)
• β-prophage (encodes exotoxin)
• Corynebacterium
• Diphtheriae
• Elongation
• Factor 2 (+ Elek) (inhibits protein synthesis)
• Granules (metachromic)
******
Actinomyces israelii
• Gram-positive anaerobic branching filaments, yellow “sulfur” granules, not acid-fast
• Found in normal oral, reproductive, and GI flora –> trauma/surgery disrupts mucosal barrier –> local infection –> yellow sulfur granules develop surrounded by PMNs –> forms pus-filled abscess –> slow expansion to contiguous tissue without respect to tissue planes –> sinus tracts through skin, muscle, bone, organs
• Causes facial abscesses that drain yellow fluid through sinus tracts
•Can cause abscesses in mouth, lungs, GI tract, GU tract
• Forms yellow-orange “sulfur” granules–> eosinophilic proteinaceous coating over filamentous actinomycetes, no actual sulfur present
• Can cause PID with IUDs
• Tx with penicillin G, surgical abscess drainage
• Tx is a SNAP: Sulfonamides Nocardia: Actinomyces Penicillin
******
Nocardia asteroides, N. brasiliensis
• Gram-positive weakly acid-fast aerobic branching filaments
• Found in soil –> inhaled –> phagocytosed –> mycelia acid cell wall allows for intracellular survival and proliferation –> caseous granulomas in lungs –> may spread via blood to adjacent tissues –> abscesses in kidneys, brain
• Intracellular survival –> caseous granulomas
• Pulmonary infections in immunocompromised patients, mimics TB but PPD negative and beaded filamentous growth
• Cutaneous infections after trauma in immunocompetent patients
• Tx with TMP-SMX, surgical abscess drainage
• Tx is a SNAP: Sulfonamides Nocardia: Actinomyces Penicillin
******
Staphylococcus aureus
•Gram-positive β-hemolytic cocci in clusters, aerobic, catalase +, coagulase +
• Protein A binds Fc-IgG –> inhibits complement activation and phagocytosis
• Coagulase –> forms fibrin coat around organism
• Hemolysins, leukocidins –> destroy RBCs, WBCs
• Hyaluronidase –> breaks down connective tissue
• Staphylokinase –> lyses formed clots
• Lipase –> breaks down fat
• Colonizes the nares
• Skin infections: impetigo, cellulitis, folliculitis, furuncles, carbuncles
• Organ abscesses, PNA after influenza (with cavitations)
• Systemic infxns: acute endocarditis, meningitis, septic arthritis, osteomyelitis (leading cause in children/adults)
• MRSA - altered PBPs, methicillin/nafcillin resistant, tx with vancomycin
• Tricuspid valve endocarditis frequently affects IV drug users
******
Staphylococcus aureus toxin-mediated diseases
• Toxic Shock Syndrome –> tampon/nasal packing/surgery introduce bacteria –> TSST-1 released and diffuses systemically –> TSST-1 is super antigen that promotes excess cytokine (TNF, IL-1) release –> acute fever, vomiting, rash, desquamation on palms and soles, hypotensive shock, end organ failure due to hypoperfusion
• Scalded Skin Syndrome –> skin wound/ cutting umbilicus in neonates promotes local epidermal infection–> exfoliative toxins (ET-A, ET-B) released systemically –> epidermis separates and skin sloughs off –> fluid loss and potential secondary infection –> 50% mortality rate
• Ritter’s syndrome –> most severe form of SSS in neonates –> S. aureus colonizes umbilicus and releases ET-A, B systemically
• Rapid-onset food poisoning –> bacteria release heat-stable enterotoxins (SE-A) in food –> non-bloody diarrhea and emesis when ingested–> self-limited, 8-24 hour nausea, vomiting, diarrhea, abdominal pain
• Dx. detection of toxin production by in vitro culture, BCx negative b/c organism doesn’t invade bloodstream
• Tx. remove foreign bodies, drain abscesses, penicillinase-resistant penicillins
• Abx not curative, kill bacteria but do not remove already-released exotoxin
******
Staphylococcus epidermidis
• Gram-positive cocci in clusters, aerobic, catalase +, coagulase –, novobiocin sensitive, urease +
• Normal skin flora –> often contaminates BCx
• Adhesin polysaccharide promotes adherence to inserted indwelling medical devices (prosthetic heart valves, hip joints, Foley catheters) and IV lines with adherent biofilms
• Indwelling device inoculates bacteria to internal site, causing inflammation at site of device
• Endocarditis with a prosthetic heart valve: S. epidermis within 60 days of valve replacement, Viridans streptococci after 60 days of valve replacement
• Tx. vancomycin (most strains resistant to penicillins and cephalosporins), removal of foreign device
• Neutropenic patients most susceptible –> bacteremia
******
Staphylococcus saprophyticus
• Gram-positive cocci in clusters, aerobic, catalase +, coagulase –, novobiocin resistant, urease +
• Normal flora of female genital tract and perineum
• 2nd most common cause of uncomplicated UTI in young women (most common is E. coli)
• Most common causes of cystitis among sexually active young women also: 1. E. coli, 2. S saprophyticus
• Bacteria enter urinary tract by sexual activity, may spread to bladder
• Tx. TMP-SMX
******
Streptococcus pyogenes aka Group A Beta-Hemolytic Strep (GABHS)
• Gram-positive β-hemolytic cocci in chains, catalase –, aerobic, bacitracin sensitive, ASO+, pyrrolidonyl arylamidase (PYR) +
• Pyogenic: pharyngitis, impetigo, erysipelas, cellulitis
• Toxigenic: scarlet fever, toxic shock-like syndrome, necrotizing fasciitis
• Normal flora of skin/oropharynx
• Pharyngitis –> human-to-human via droplets –> adhere to epithelium via pili –> sore throat, enlarged cervical LNs due to inflammation –> either spontaneous recovery, bacterial spread (bacteremia, meningitis, otitis), toxin release (scarlet fever, TSS), or anti-streptococcal antibody immunologic reactions (PSGN, rheumatic fever)
• Skin infections–> trauma inoculates skin –> pustular lesions with honeycomb-like crusts (impetigo) –> deeper infection causes erysipelas/cellulitis –> may cause anti-streptococcal Ab reactions (PSGN, not rheumatic fever)
• Virulence factors: streptokinase (converts plasminogen to plasmin causing fibrinolysis), M protein (resists phagocytosis), hyaluronidase (breaks down connective tissue), DNase digests DNA
• Dx. Throat/skin culture, anti-streptolysin O antibody titer detects recent infection with S. pyogenes
• Tx. penicillin G
• While “strep throat” (GABHS pharyngitis) is usually self-limited, tx mandatory to prevent complications
******
Streptococcus pyogenes toxin-mediated diseases
• Scarlet fever: S. pyogenes pharyngitis –> systemic release of pyrogenic exotoxins A, B, C –> fever, “sandpaper” rash (begins on trunk and spreads outward, spares soles/palms), strawberry tongue within first 2 days, desquamation of palms and soles after rash subsides
• Toxic shock syndrome: S. pyogenes skin infection (eg, cellulitis) –> systemic release of pyrogenic exotoxin A (superantigen) –> polyclonal activation of T cells –> acute fever, shock, multiorgan failure
• Necrotizing fasciitis: trauma/surgery inoculates bacteria in fascia investing muscles –> release of exotoxin B (protease) –> rapid necrosis along fascial planes, no damage to muscles
• Streptolysin O and Streptomycin S: destroy RBCs, WBCs
• Tx. penicillin G, clindamycin added in TSS to prevent toxin production, surgical debridement in necrotizing fasciitis
******
Scarlet fever
• GABHS (S. pyogenes) pharyngitis + blanching, sandpaper body rash, strawberry tongue, and circumoral pallor
• Erythrogenic toxin
******
Jones criteria for diagnosis of acute rheumatic fever
• 2 major criteria or one major + two minor criteria and evidence of prior infection:
• JONES major criteria
• Joints - migratory polyarthritis
• O - carditis (endocarditis, myocarditis, or pericarditis)
• Nodules - subcutaneous nodules
• Erythema marginatum rash
• Sydenham’s chorea
• Minor criteria: fever, arthralgia, elevated ESR/CRP, prolonged PR interval, ASO +
******
5 most common pediatric diseases with rash
- Measles (measles virus)
- Rubella (rubella virus)
- Scarlet fever (S. pyogenes infection)
- Roseola (HHV-6)
- Erythema infectiosum (parvovirus B19)
* ***********
Streptococcus pyogenes immune-mediated disease
• Post-streptococcal glomerulonephritis (PSGN): S. pyogenes skin infection/pharyngitis –> anti-streptococcal antibodies generated –> immune complexes form –> deposit on glomerular BM –> glomerular inflammation –> 2-3 weeks after infection, develop hematuria, hypertension, periorbital edema –> complete recovery likely
• C3 complement levels low, BUN and Cr bump, RBC casts in urine, EM would reveal sub epithelial humps “lumpy-bumpy” in glomerulus
• Rheumatic fever: S. pyogenes pharyngitis left untreated –> autoimmune cross-reaction of anti-streptococcal antibodies with antigen of joints and heart tissue –> 2 weeks after pharyngitis develop inflammatory response at various tissues (eg, mitral valve) –> permanent endocardial damage may present years later as murmur (mitral regurgitation)
• Tx. penicillin prophylaxis to patients with hx of rheumatic fever to prevent further valve damage
• M protein = antiphagocytic protein in cell wall
• Antibodies to M protein enhance host defense against S. pyogenes and confer immunity but give rise to rheumatic fever
•Valves damaged by rheumatic fever susceptible to colonization by enterococci or Viridans streptococci endocarditis
******
Streptococcus agalactiae (Group B β-hemolytic streptococci)
• Gram-positive β-hemolytic cocci in chains, catalase –, aerobic, bacitracin resistant, PYR–, Hippurate test +, produces CAMP factor
• Group B is for Babies
• Colonizes maternal vagina –> causes neonatal pneumonia (respiratory distress, lethargy, hypotension), neonatal meningitis (seizures, irritability), and neonatal sepsis, especially after labor complications
• Most common cause of meningitis in newborns
• Tx. penicillin G
• Screen pregnant women at 35-37 weeks gestation –> if + culture –> intrapartum ampicillin prophylaxis to prevent vertical transmission to neonate
******
Streptococcus pneumoniae aka “pneumococcus”
• Gram-positive α-hemolytic lancet-shaped diplococci, catalase –, optochin sensitive, bile soluble, encapsulated
• Capsule = antiphagocytic, Quellung +, antigens for Pneumovax
• IgA proteases
• Colonizes nasopharynx epithelium esp if clearance hindered by viral infection/allergy/smoking
• Most common cause of: meningitis, otitis media (in children), community-acquired pneumonia (lobar pneumonia), sinusitis
• May also cause osteomyelitis, septic arthritis, endocarditis
• Tx. penicillin or cephalosporins, vancomycin for meningitis
• Associated with rusty sputum
• Sepsis in patients with SCD or splenectomy –> give Pneumovax
******
Streptococcus mutans, S. mitis, S. sanguinis (Viridans group streptococci)
• Gram-positive α-hemolytic cocci, catalase –, optochin resistant, bile soluble, not encapsulated
• Normal oropharynx flora that cause dental caries (S. mutans, S. mitis) and subacute bacterial endocarditis on damaged heart valves (S. sanguinis)
• Optochin resistant unlike S. pneumo
• S. sanguinis makes dextrans that bind to fibrin-platelet aggregates on heart valves
• Physical exam: low-grade fever, general malaise, Janeway lesions (non-painful), Osler’s nodes, Roth’s spots (retina), splinter hemorrhages
• Osler’s nodes- painful, from immune complex vasculitis
• S. intermedium may cause brain/abdominal abscesses, normally inhabits GI tract –> microaerophilic, thrive in low-oxygen brain/liver –> Bcx positive for S. intermedius often indicate presence of abscesses
• Tx. penicillin G
******
Enterococcus faecium, E. faecalis
•Gram-positive γ-hemolytic cocci, catalase –, grows in 40% bile, grows in 6.5% NaCl, PYR +, hardier than non-enterococcal group D
• Capsule prevents bile salt degradation
• Some strains may be α-hemolytic
• Normal flora of intestines, biliary tract, GU tract —> overgrows locally when normal flora suppressed by cephalosporins or when mucosal/epithelial barrier disrupted (subacute endocarditis in IVDUs, infection following biliary/hepatic/GI surgery or procedures) –> UTIs, biliary tract infections, subacute bacterial endocarditis
• Tx. ampicillin or vancomycin + aminoglycosides (synergistic)
• Tx for Vancomycin-Resistant Enterococcus (VRE). linezolid, daptomycin
• 2nd most common cause of nosocomial infections in the US due to high resistance: all strains resistant to cephalosporins, penicillin G, some strains also resistant to vancomycin (VRE)
******
Streptococcus bovis (Group D streptococcus)
•Gram-positive γ-hemolytic cocci, catalase –, grows in 40% bile, does not grow in 6.5% NaCl
• Capsule prevents bile salt degradation
• Bovis in the Blood = Cancer in the Colon
• Colonizes gut –> penetrates epithelium via lesions in the colon (eg, CRC or IBD) –> enters lymphatics and bloodstream –> localizes to aortic valve, adhering to platelet-fibrin aggregates –> endocarditis
• S. gallolyticus (S. bovis biotype I) can cause bacteremia and subacute bacterial endocarditis associated with colorectal cancer
• Tx. penicillin
******
Most common causes of pneumonia in adults and elderly, and most common causes of meningitis in elderly
• Adults (40-65): S. pneumoniae, H. influenzae, Legionella
• Elderly (>65): S. pneumoniae, Gram – rods, H. influenzae
• Meningitis in 60+: S. pneumoniae, Gram – rods, Listeria
******
Streptolysin O
• Streptococcus pyogenes
• Lyses cell membranes
• Protein that degrades all cell membranes, lyses RBCs, contributes to β-hemolysis
• Host antibodies against toxin (anti-streptolysin O antibodies) used to diagnose rheumatic fever
• Do not confuse these antibodies with the immune complexes of post-streptococcal GN
******
Exotoxin A (Streptococcus pyogenes)
• Streptococcus pyogenes
• Superantigen –> binds to MHC class II and TCR outside of the Ag-binding site to cause overwhelming release of IL-1, IL-2, IFN-γ, and TNF-α
• Release of cytokines causes Toxic Shock Syndrome –> fever, rash, shock
******
M protein
• Expressed by Streptococcus pyogenes (GABHS)
• Helps prevent phagocytosis
• Shares similar epitopes to human cellular proteins (molecular mimicry)
• Possibly underlies autoimmune response seen in acute rheumatic fever
******
Protein A
•Expressed by Staphylococcus aureus
• Virulence factor that binds Fc region of IgG
• Prevents opsonization and phagocytosis
******
IgA protease
• Secreted by many bacteria (S. pneumoniae, H. influenzae, Neisseria meningitidis)
• Enzyme that cleaves IgA immunoglobulins to colonize respiratory mucosa
******
Endotoxin (gram negative bacteria)
• Endotoxin not secreted –> released upon cell lysis or bleb detachment from membrane, lipid A = toxic component of LPS
• Part of bacterial chromosome, poorly antigenic so no vaccine
• Edema (C3a activation)
• Nitric oxide (hypotension)
• DIC (TF activation)
• Outer cell membrane (of most gram – bacteria)
• TNF-α –> fever and hypotension
• O-antigen + core polysaccharide + lipid A = LPS
• eXtremely heat stable
• IL-1 and IL-6 –> fever
• Neutrophil chemotaxis (C5a activation)
• Shock/Sepsis by gram – rods
******
3 main effects of endotoxin (lipid A)
- Macrophage activation (TLR4) –> IL-1, IL-6 (fever), TNF-α (fever and hypotension), nitric oxide (hypotension)
- Complement activation –> C3a (histamine release –> edema and hypotension), C5a (neutrophil chemotaxis)
- Tissue factor activation (coagulation cascade –> DIC)
* ***********
Botulinum toxin
• Clostridium botulinum
• Inhibits vesicular release of stimulatory NT –> Ach
• Protease that cleaves SNAREs, a set of proteins required for NT release from vesicles
• Exotoxin prevents release of acetylcholine at NMJ –> symmetric descending flaccid paralysis
• Also prevents ACh release at CNs (diplopia, dysarthria, dysphagia) and postganglionic parasympathetic nerve endings (dizziness, dry throat, ptosis)
• Don’t feed babies honey as may have botulinum spores!
• AB toxin: B binds cell surface receptor, A cleaves SNAREs
******
Tetanospasmin
•Clostridium tetani
• Inhibits vesicular release of inhibitory NTs –> glycine and GABA
• Protease that cleaves SNAREs (synaptobrevin), a set of proteins required for NT release via vesicles into synapse
• Exotoxin prevents release of GABA and glycine from interneuron Renshaw cells in the spinal cord
• Causes spastic paralysis, maintained muscle contraction (tetanus), risus sardonicus, trismus (lockjaw)
• AB toxin: B binds cell surface receptor, A cleaves SNAREs
******
Alpha toxin
• Clostridium perfringens
• Lyses cell membranes
• Phospholipase (lecithinase) that degrades tissue and cell membranes –> degradation of phospholipids –> myonecrosis (“gas gangrene”) and hemolysis (“double zone” of hemolysis on blood agar)
******
Toxic Shock Syndrome Toxin (TSST-1)
• Staphylococcus aureus
• Superantigen –> binds MHC class II and TCR outside of Ag binding site to cause overwhelming release of IL-1, IL-2, IFN-γ, and TNF-α
• Release of cytokines causes Toxic Shock Syndrome –> fever, rash, shock
• TSST-1 causes TSS
• exfoliative toxin causes Scalded Skin Syndrome
• enterotoxin causes S. aureus food poisoning
******
