Infectious (7)- Gomez Flashcards
Pneumonia =
lung parenchymal inflammation from any cause
Pulmonary Infectious Diseases - general concepts
Respiratory tract involved in infections more often than any other organ system
Most: upper tract viral disease
Lower tract pneumonia major cause of mortality and morbidity
Increased when defense impaired
One type increases chance of second type
* Elevated CRP or procalcitonin favors bacterial over viral pneumonia
Terminal, nosocomial (hospital-acquired) are common
Pneumonia Agents
Bacterial Mycobacterial Fungal Pneumocystis Viral Chemical Physical (radiation)
Pulmonary host defenses
nasal hair, turbinates, mucociliary apparatus, IgA secretion
Saliva, sloughing of epithelial cells, local complement production, interference from resident flora
cough, epiglottic reflexes, sharp-angled branching of airways, mucociliary apparatus, IgG, IgM, IgA
Alveolar lining fluid (surfactant, Ig, complement, fibronectin), Cytokines (IL-1, tumor necrosis factor), alveolar macrophages, polymorphonuclear leukocytes, cell-mediated immunity.
splenectomy? Immunize against
encapsulated bacteria.
Pneumococcus!
Community-acquired acute pneumonia (alveolar exudates)
strep pneumo + diplococci; MOST COMMON, increased risk with splenectomy/ sickle cell; need vaccine)
H. Influenza- #` in COPD
Moraxella- diplococci
Staph aureus G+ cocci (common post viral pneumonia/ influenza)
Legionalla G- rod (macrophages in small bronchioles)
Enterobacteriacaea- klebsiella- G- rod #1 gram neg seen in debilitated, malnourished with bloody thick mucus
- pseudomonas aeruginosa G- coccobacilli (cystic fibrosis and neutropenia*)
Community-acquired atypical pneumonia (patchy or interstitial inflammation
mycoplasma pneumo- spherical to filamentous w/o cell wall (G-) * have cold agglutinins
Chlamydia (pneumoniae, psittaci, trachomatis)
Coxiella burnetti (Q fever)
Viruses
Nosocomial pneumonia
gram neg rods: enterobactericae (klebsiella, serratia marcascens, e coli), and psudomonas
Staph aureus
Aspiration pneumonia (loss of gag or swallowing reflexes or GERD)- types of agents
anaerobic oral flora, admixed with aerobic bacteria
Necrotizing pneumonia and lung abscess
anaerobic bacteria (staph aur, lebsiella, strep pyo, type 3 pneumococcus)
Chronic pneumonia- 4 causative agents
nocardia, actinomyces, mycobacterium tuberculosis (granulomatous) and atypical mycobacteria
Pneumonia in immunocompromised host - 5 particular pathogens +
cytomegalovirus, pneumocystis jirovecii, mycobacterium avium-intracellulare
invasive aspergillosis
invasive candidiasis
“usual” bacterial, viral and fungal organisms
Streptococci
Gram positive cocci in chains
Exception: S. pneumoniae is lancet-shaped diplococcus
Catalase (-)
Lancefield groupings
S. pneumoniae, S pyogenes & S. agalactiae are encapsulated
Group A=S. pyogenes; β hemolysis-#1 cause of bacterial pharyngitis, impetigo. Can later get rheumatic fever, rheumatic valvular disease and post-streptococcal glomerulonephritis.
Also causes necrotizing fasciitis, & toxic shock syndrome (toxin).
Group B neonatal septicemia, meningitis & pneumonia
Group D
S. pneumoniae; α hemolysis-#1 cause of bacterial pneumonia in adults (virulence via capsule), #1 cause of otitis media in children, meningitis in adults
S. viridans species dental caries, subacute endocarditis
Haemophilus
Gram-negative coccobacilli
Capsule is major virulence determinant
Pneumonia, acute epiglottitis, bacteremia, meningitis, septic arthritis, cellulitis, otitis media, purulent pericarditis, endocarditis, arthritis and osteomyelitis
Nonencapsulated strains are (by definition) nontypable
H. influenzae type b - most common cause of bacterial meningitis in children 6 months-2 years
Unencapsulated strains produce ear, sinus and respiratory infections (usually chronic smokers, alcoholics or elderly)
H. ducreyi
h. parainfluenze
H. aegypticus
Moraxella and Kingella
Gram-negative diplococcus
Moraxella catarrhalis
Common – common cold, otitis media and sinusitis
Less common – laryngitis, bronchitis and pneumonia in children and adults chronic lung disease
Staphylococci
Gram positive cocci in clusters
Catalase (+) [H202→H20+02]
S. aureus: coagulase positive (+)
Skin (furuncle=boil, carbuncles, scalded skin syndrome, impetigo) infections, deep abscesses, sepsis, pneumonia, meningitis, acute endocarditis, osteomyelitis, toxic shock syndrome, food poisoning,
Virulence factors
Have developed resistance to penicillins (methicillin) and vancomycin
Legionella
Gram-negative bacilli
are ubiquitous aquatic saprophytes that can live in amoebae and biofilms
Infections are associated with aerosolized water
Legionnaires’ disease (Philadelphia 1976) is a severe lobar pneumonia with non-productive cough, fever, fever which lead to multi-organ disease and death if not treated
Pontiac fever was epidemic flu-like condition (Pontiac, Michigan 1968) with fever, chills, headache and malaise that lasted 2-5 days and resolved
Klebsiella
Gram-negative bacilli
Ferment lactose (reddish on McConkey’s agar)
Encapsulated
Most common cause of nosocomial respiratory tract infections
Hemorrhagic pneumonia with red currant jelly (capsule) colored sputum
Second-most frequent cause of gram-negative bacteremia and urinary tract infections
Capsular types 1 and 2 associated with bacterial pneumonia
K. oxytoca
Causes granuloma inguinale (donovanosis)
Pseudomonas
Gram negative rods
Oxidase-positive
Nonfermentative
Antiphagocytic exopolysaccharide (alginate) slime biofilm Many strains produce pigments (fluorescent pyoverdin and pyocyanin)
Nosocomial infections , opportunistic,
Commonly present in lungs of patients with cystic fibrosis
Hot tub folliculitis (P. aeruginosa)
Dx – culture (often have fruity grape odor and some produce pigments)
Rx – antibiotics (resistance in cystic fibrosis patients)
Mycoplasmataceae
Lack a cell wall around their cell membrane
Believed they originated as Gram positive bacteria but evolutionarily lost cell wall
appear as gram negative (red) on gram staining
Mycoplasma pneumoniae
Causes atypical “walking” pneumonia, acute tracheobronchitis, and bronchiolitis
Associated with cold agglutinin (anti-I IgM) production
Chlamydia
Obligate coccoid to rod intracellular bacteria (parasites)
Gram negative
Infectious elementary bodies attach and are internalized by susceptible host cells
Intracellular reticulate (initial) bodies - replicative form
Steals host cell’s ATP via ATP/ADP translocator
Chlamydia cannot produce ATP
C. pneumoniae, strain TWAR
Upper and lower (atypical pneumonia) respiratory tract infections
C. trachomatis - Trachoma conjunctivitis, kids in Africa and Asia
- Nongonococcal urethritis, epididymitis, pharyngitis, cervicitis, salpingitis, endometritis, pelvic inflammatory disease, inclusion conjunctivitis (paratrachoma), sexually transmitted lymphogranuloma venereum - Small, painless papule or pustule followed by tender lymphadenitis (buboes)
C. psittaci
Inhalational systemic zoonotic infections with atypical pneumonia and associated systemic symptoms
Psittacosis - In psittacine birds (parrots, lovebirds, & parakeets)
Ornithosis – In non-psittacine birds (domestic fowl, ducks, pigeons, turkeys, and many wild birds)
DX- +/- identification of inclusion bodies
Prevention – condoms and be careful handling birds
Coxiella burnetii
Gram negative Not a Rickettsia Obligate intracellular parasite Requires host ATP Replicate only in the phagolysosome Worldwide zoonosis usually in cattle, sheep or goats and spread via inhalation of aerosolized organisms, unpasteurized milk products,
Has an endospore-like state
Highly resistant to environmental factors
Causes Q fever (asymptomatic, flu-like syndrome or atypical pneumonia)
Anthrax
Bacillus anthracis
Large gram + bacillus in chains
Infection via dormant endospores
Pulmonary anthrax (inhalation)
Rx- 3 concurrent antimicrobials
Anthrasil (anthrax immune globulin intravenous [human]) for inhalational anthrax
vaccine: Ava/BioThrax (used for combatants)-
Yersinia
Gram negative, bipolar staining coccobacilli
Non-lactose fermenter
Glucose fermenter
Y. enterocolitica and Y. pseudotuberculosis
Y. pestis Bubonic plague (black death) maintained among rodent populations (ground squirrels, prairie dogs, great gerbils/black rats for exam questions) transmitted by infected fleas (regurgitate biofilm from gut)
F1 antigen and the V & W antigens (both required for virulence)
Bubonic plague
septicemic plague
Pneumonic plague occurs under crowded conditions when contaminated respiratory droplets expelled by infected persons are directly inhaled by another person; shorter incubation period and greater mortality (90% in 1 day) than bubonic plague
Prevention - Vector control and inactivated Y. pestis vaccine for lab personnel
Mycobactericea
Part of the CMN group (corynebacteria, mycobacteria and nocardia)
Contain polymer complex composed of peptidoglycan, arabinogalactan and mycolic acids
Rod-like to filamentous
Mycobacteria are gram ? [gram (+) due to cell wall structure vs gram (-) via DNA]
Mycobacteria and nocardia are acid fast
Use Ziehl-Neelsen stain for identification
Cord factors - dimycolates of trehalose give rise to growth in serpentine cords
M. tuberculosis complex: M. tuberculosis, M. bovis
M. tuberculosis – tuberculosis (Spread by airborne droplets and can cause prolonged productive cough)
M. bovis – oropharyngeal and intestinal tuberculosis via unpasteurized cow milk
M. leprae - tuberculoid or lepromatous leprosy (Hansen disease)
Nontuberculous mycobacteria
Tuberculosis
Primary Infection
Ghon complex (parenchymal lesion & involved lymph node)
Granulomatous response, usually asymptomatic and self-limiting but clinically symptomatic in 5%
Secondary Infection
Reactivation of old walled-off lesions, usually apical (high ppO2)
Variable course: cavitary caseous necrosis with subsequent scarring or progressive disease
Miliary TB occurs when tubercle erodes into a vessel
In immunosuppressed may see TB without granulomas
Dissemination in 10-15% of mildly immunosuppressed
Dissemination in >50% of severely immunosuppressed
Dx – PPD test, acid-fast stain on sputum, mycobacterial cultures
Rx - Isoniazid, rifampin and ethambutol (drug resistance has emerged)
Prevention - bacillus Calmette–Guérin (BCG) vaccine (will cause a positive PPD test)
Bacterial Pneumonia Two basic types:
Bronchopneumonia and Lobar pneumonia
Bronchopneumonia predominant type
Stages of bacterial pneumonia
A, Acute pneumonia. The congested septal capillaries and numerous intra-alveolar neutrophils are characteristic of early red hepatization. Fibrin nets have not yet formed.
B, Early organization of intra-alveolar exudate, seen focally to be streaming through the pores of Kohn
C, Advanced organizing pneumonia. The exudates have been converted to fibromyxoid masses rich in macrophages and fibroblasts.
Viral Pneumonias
Usually self limiting “chest cold” but can be lethal
Often co-existing laryngobronchitis, bronchilolitis, tonsilitis
Can be epidemic as in influenza pandemic 1918 (swine flu/H1N1)
40 MILLION dead (antigenic shift)
(drift with minor neurominidase or hemagglutinin mutations and shifts with animal virus RNA recombination/replacement of both)
Swine Flu – H1N1 and H3N2 influenza A
June 11, 2009 pandemic H1N1
Bird Flu – Avian influenza A
Orthomyxovirus; Influenza
ssRNA w envelope; viral RNA-dependent RNA polymerase; reproduce in nucleus
One genus (influenza) and 3 types A, B and C
Nucleoprotein antigen that determines the virus type (A, B or C)
Envelope with surface glycoproteins hemagglutinin (H) and neuraminidase (N)
Transmission is airborne and leads to acute respiratory disease aided by hemagglutinin attachment to respiratory mucosa
Neuraminidase produces mucus liquefaction leading to local viral spread
Can progress to pneumonia from initial URI
1.Antigenic drift - mutations in the RNA → minor changes in the antigenic character of H and N molecules
2.Antigenic shift - rearrangement of genome segments →major changes in the antigenic character of the H and N molecules
1957 Asian flu (H2N2), 1968 Hong Kong flu (H3N2), 1977 Russian flu (H1N1), 2009 swine flu (H1N1) [had partial protection in U.S. population due to H1NI swine flu outbreak in 1988 and 1977 Russian flu]
Next pandemic? – possibly avian flu (1997 H5N1 or 32013 H7N9)
CHILD + FLU (or chickenpox) + ASPIRIN → REYE SYNDROME
Prevention: Yearly inactivated vaccines
Paramyxoviruses
ssRNA with envelope Parainfluenza Mumps Measles Respiratory syncytial virus Human metapneumovirus
Paramyxoviruses 1- Human metapneumovirus
Can cause common cold, bronchiolitis and pneumonia in children and adults
Paramyxoviruses 2- ParainfluenzaParamyxovirus; -ssRNA with envelope
Local infection of ciliated respiratory epithelium
Cause 30-40% of acute respiratory infections in infants and children
Mild cold-like to life-threatening (croup, bronchiolitis, pneumonia)
Most common cause of croup laryngotracheobronchitis (barking cough, steeple sign)
Paramyxoviruses 3- Respiratory Syncytial Virus
Paramyxovirus ; -ssRNA with envelope
Local infection in ciliated epithelia (upper or lower respiratory tract), nose, eye and mouth
Major cause of bronchiolitis and pneumonia in infants (#1 cause in age < 6 months)
Severe disease may present as bronchiolitis, pneumonia or croup
Reinfection in adults usually involves the upper respiratory tract (common cold)
- Strongly suspect in infants with lower respiratory tract infection
Paramyxoviruses 5- Measles (Rubeola)
Paramyxovirus ; -ssRNA with envelope
Enters oropharynx from human secretions followed by viremia to skin, mucosae, CNS, lymphatic & respiratory systems
Koplik spots of mouth precede T-cell mediated rash
Usually have fever, maculopapular rash, +/- conjunctivitis that can lead to blindness, and sometimes pneumonia
Adenoviridae
Naked dsDNA with numerous serotypes
Respiratory and oral-fecal transmission
Acute respiratory disease – serotypes 4,7 &21) upper respiratory infections in kids/young adults that can progress to pneumonia
Gastroenteritis - adenoviruses that lead to diarrhea
Pharyngoconjunctivitis – pink eye and sore throat
Picornaviruses
small, naked +ssRNA
Heparnavirus – discussed with hepatitis viruses
Rhinoviruses (100 serotypes)
Infection occurs person to person via the nasopharynx
Attach via ICAM-1 receptor to respiratory epithelial cells
Cause common cold
Cytomegalovirus
owl-eye basophilic intranuclear inclusions
Transmission
Transplacental - primary infection pregnant mother
Neonatal - cervical or vaginal secretions during birth
Perinatal -breast milk from a mother who has active infection
Saliva – common during preschool years
Genital - dominant mode after about 15 years of age
***Respiratory secretions
SARS Virus
Severe acute respiratory syndrome (fever >100, flu symptoms)
Severe acute atypical respiratory syndrome: a novel coronavirus
2002/3 – first cases in Asia spread globally
Spread via respiratory droplets and can lead to ARDS
MERS Coronavirus
Middle East Respiratory Syndrome Coronavirus
Asymptomatic to severe acute respiratory syndrome (fever and pneumonia) in person coming from Arabian peninsula or in close contact with MERS patient
2012 – first cases in Jordon and Saudi Arabia
Pulmonary Abscess organisms and other sources
1 Aspiration, usually right lower lobe
Organisms Staphylococcus aureus, many gram-neg Mixed, including anaerobic organisms Bacteroides fragilis Fusobacterium Peptococcus
Other sources:
Neoplasia
Perinatal Infections
Transcervical (Ascending) Infections
Inhalation of infected amniotic fluid (in utero) or infected passing through infected birth canal
Most bacterial, some viral (HSV II)
Pneumonia, sepsis and meningitis common if infected via inhalation
Transplacental (Hematologic) Infections
Includes TORCH group of infections (Toxoplasma, Rubella, CMV, Herpes, Other, i.e. Treponema pallidum)
Pneumonitis, encephalitis, chorioretinitis, myocarditis, dermatitis
Respiratory Syncytial Virus (RSV) Bronchiolitis
Most common cause of bronchiolitis and pneumonia in children < 12 month
Associated otitis media in many children
F (fusion) protein on membrane induces multinucleate syncytia
Chronic Pneumonias
Frequently a localized lesion in immunocompetent patients Many are granulomatous processes: Tuberculosis Leprosy Fungal
Tuberculosis
Primary Infection
Ghon complex (parenchymal lesion & involved lymph node)
Granulomatous response, usually asymptomatic and self-limiting but clinically symptomatic in 5%
Secondary Infection
Reactivation of old walled-off lesions, usually apical (high ppO2)
Variable course: cavitary caseous necrosis with subsequent scarring or progressive disease
Miliary TB occurs when tubercle erodes into a vessel
In immunosuppressed may see TB without granulomas
Dimorphic Fungal Pneumonias
Histoplasma capsulatum 3-5 microns (Ohio, Mss river), soil spores, bird and bat feces
Blastomyces dermatidis 5-15 microns, Centerl and SE USA, Canada, mexico, middle east, africa, india], from soil spores
Coccidioides immitus 50-60 microns, from southwest (san juaquin valley), far west and mexico. Soil spores
Pulmonary Disease in HIV
Can get all the “usual” organisms but more virulent behavior! (bacteria, TB, CD4>200)
Common “unusual” diffuse pneumonias: pneumocystis jirovecii, CMV, mycobacterium avium
Common “unusual” focal pneumonias:
Aspergillus sp
candida albicans
Similar infections with immunocompromised patients with other conditions (chemotherapy, transplants, etc)
Lung Transplants
Used for end stage lung disease Emphysema Idiopathic pulmonary fibrosis Cystic fibrosis Idiopathic/familial pulmonary hypertension
Complications:
Infections
Acute rejection (mononuclear with few PMNs and Eos)
Chronic rejection (bronchiolitis obliterans)
EBV-associated lymphomas
79% 1 year/ 53% 5 year/ 30% 10 year survivals
Pneumocystis Pneumonia
histology
Foamy “cotton candy” exudate and “cup and saucer”-shaped organisms
candida histology
pseudohyphae and blastoconidia (budding yeast– spaghetti and meatballs appearance
