Micro Resp Exam I

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Micro Resp Exam I
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• Pharyngitis sore throat ID important
• True Strep Throat Group A strep / strep pyogenes
• Croup larynx, children
• can lead to laryngitis or hoarseness, even
  obstrxn
• Tracheal bronchitis
• below larynx, into trachea, into bronchi, cough
  most important sign, can have with cold
• Infxn tracheal, bronchial mucosa, Viral or
  bacterial
• Bronchiolitis
• bronchial tree, resp tree branching - finer ?
  bronchioles.
• serious LRT disease infants w/ dyspnea, fever
• Resp Syncytial Virus (RSV) and parainfluenza
• RSV yearly epidemic serious in children 1 to 2
  years old.
• Acute Resp Disease military term Cold lt ARD lt
  Flu
• Influenzal Syndrome
• severe malaise, muscle aches, prostration
• Pneumonia infxn lung parenchyma, alveoli

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Common Cold

• Rhinovirus
• Coronavirus
• RSV
• Myxovirus orthomyxovirus, paramyxovirus
• Adenovirus

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• Common Cold
• Mild, SL, catarrhal syndrome
• Cx sinusitis, pharyngitis, LRTI
• Major cause school absenteeism
• Rhinovirus most - ssRNA (picorna)
• Small RNA virus related to poliovirus
• Picorna smallest viruses capable infecting
  animals
• 110 Ag different types
• Optimum growth 33 degrees nasal mucosa
• Multiplies in cytoplasm

5

• Common cold
• Transmission main source kids
• Direct contact
• Infectious droplet nuclei
• Epidemiology world wide, person-person,
• Adults 2-4 colds per year kids 6-8
• Clinical incubation 48-72h
• Nasal discharge, nasal obstrxn, sneezing,
  scratchy throat, cough, anorexia, slight fever
• 5-10 days,
• Complications rare sinusitis, otitis media,
  bronchitis
• No way to differentiate different agents

6

• Coronavirus ssRNA
• Round, petal shaped projections
• Lipid envelopes, labile ether/chloroform
• Difficult to isolate and grow
• SARs new coronavirus
• RSV by age 4
• Infants and children gt adults
• Bronchopneumonia or bronchitis
• Paramyxovirus
• RNA
• Enveloped

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• Myxoviruses
• Orthomyxoviruses influenza virus A,B,C
• Paramyxoviruses 4, env, ssRNA
• Children croup, bronchitis, pneu
• Occasionally adult resp dz
• Adenoviruses
• 47 serological, few cause dz
• Military recruits

8

• Sinusitis acute, inflam paranasal sinuses
• Etio
• Directly contiguous to, communicate with URT
• Acute sinusitis follows rhinitis
• Nasal polyps, deviation nasal septum, tumors,
  FBs, trauma, abrupt change pressure, cystic
  fibrosis, purulent sinusitis
• Bact agents acute sinusitis
• Strep pneu, Hemop influenza
• S. aureus, strep pyogenes
• Chronic anerobic bact combined with aerobes
• Dental anerobic strep, coliform bacilli

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• Pathogenesis Sinusitis
• Obstrxn paranasal sinusal ostia impedes drainage
• Mucous accumulation mucopus irritates mucosa
  edema, aggravates obstrxn
• Epidemiology Adultsgtchildren
• .5 URTI acute sinusitis
• Fall, winter, spring summer swimming
• Clinical Rinsing nose NOT reliable
• Hx URTI, allergic rhinitis, tenderness over
  sinus, purulent discharge
• Dx acute only by culture exudate or rinse sinus
  puncture and aspiration
• TX acute antimicrobial tx - empirical

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• Pharyngitis acute inflam sx of pharynx
• Most viral mild rhinovirus, coronavirus
• Severe adenovirus, herpes simplex
• S.pyogenes 15-30
• UK 30
• Normal throat flora alpha hemolytic greenish,
  opaque hemolysis
• DANGER beta hemolysis clears agar blood
• Group A beta hemolytic strep
• Lancefield Grp A Ag, bacitracin senstive, beta
  hemolysis
• Winter months
• Rhinovirus annual peaks
• Streptococcal resp dz season
• Human reservoir

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• Pharyngitis Clinical
• Mild moderate no discomfort 3-4d dur
• No exudates, no LA
• Pharynx normal, mild erythema
• Rhinorrhea, PND present
• With Influenza 3-4d dur
• Sore throat major complaint, coryza
• Temp elev children, adults
• Edema, erythema NOT marked
• NO exudates, painful cervical adenopathy

12

• Pharyngocongunctival Fever
• Adenovirus more severe major agent
• DNA viruses stable 47 Ag distinct types
• Acute, febrile, SL
• Pharyngoconjunctival
• Pertussis-like Sx similar to B.pertussis
• Marked sore throat
• Temp elev 5-6 days
• 1/3 ½ confjunctivities bilateral,
  follicular
• ARD cough, hoarseness, substernal pain
• Military recruits
• Other dz epidemic deratoconjunctivities,
  hemorrhagic cystitis, gastroenteritis, rashes

13

• Acute Herpetic Pharyngitis
• HSV 1ary infxn may have acute pharis
• Large DNA virus, humans/animals
• Lipid-containing capsids inactivated by ether
• Eosinophillic intranuclear inclusion bodies
• Recurrent fever blisters
• Mimics strep pharis
• Vesicles, shallow ulcers on palate herpes
• Gingivostomatis on labial, buccal mucosa

14

• Herpangina uncommon pharyngitis
• Coxsackieviruses - cause
• Small vesicles soft palate, uvula, anterior
  tonsillar pillars
• Primarily children severe, febrile illness,
  sore throat, dysphagia (difficulty swallowing)
• Coxsackieviruses Picornaviruses
• Aseptic meningitis, myocarditis, URTI
• Herpangina 2, 4, 5, 6, 8, 10
• Grp A, type 10 summer febrile dz kids
• Acute lymphonodular pharyngitis

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• Infectious Mononucleosis - Exudative tonsillitis
  or pharis - Nearly 50 cases
• Fever, cervical adenopathy
• Enlargement of spleen about ½ cases
• Epstein Barr Virus (Board Review)
• 1st human virus related to malignancy
• Burkitts lymphoma in children
• EBV in saliva ? infxn oropharynx epi cells
• Pharyngitis, shedding virus in saliva
• Infxn B-cells ? B-cell proliferation
• Heterophile Ab (agglutinates sheep/horse RBCs)
• Expression EBV early proteins ?T-cell activation
  ? atypical lymphocytes, enlargement spleen,
  liver, LNs

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• Streptococcal Pharyngitis - Severe cases
• marked phayrngeal pain, dysphagia, Tempgt39.4 C
• Pharnygeal membrane fiery red
• Thick exudate posterior pharynx, tonsillar area
• Uvula pronounced edema
• Tender, enlarged cervical nodes
• Leukocyte count gt 12,000/mm3 acute suppurative
  bacterial infxn
• S. pyogenes Gram positive, non-motile cocci
• most virulent of Grp A, beta hemolytic
  streptococci
• small, opaque colonies - large zone of beta
  hemolysis
• Highly sensitive to bacitracin
• Non-immunogenic cell wall
• SPEs strep pyrogenic exotoxins, A, B, C - rash
  of scarlet fever
• Cytolytic toxins, exoenzymes
• Streptolysin O Oxygen labile, damages mammalian
  cells, ASO test for Rheumatic Fever
• Streptolysin S Oxygen Stable lyses
  erythrocytes culture hemolysis

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• Anaerobic Pharyngitis
• (Vincents Angina/Peritonsillitis/Peritonsillar
  Abecces Quinsy)
• Pharyngeal and tonsillar infxn
• Mixture anaerobic bacteria/spirochetes
• Purulent exudate coats membrane
• Foul odor to breath
• Abscess severe pain, dysphagia
• Usually unilateral, when biliateral partial
  obstrxn pharynx

18

• Gonococcal Pharyngitis
• Most infxn Asymptomatic
• Occasional mild pharyngitis
• Neisseria gonorrhoeae

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• Diphtheria (Corynebacterium diphtheria)
• Unvaccinated populations in US
• Low-grade fever
• Tonsillar, pharygeal pseudomembrane
• Light to dark gray
• Firmly attached to tonsil, pharyngeal mucosa
• DO NOT REMOVE
• Board Notes

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• Mycoplasma pneumoniae
• Mild pharyngitis
• Bronchitis
• Primary atypical pneumonia

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• Resp Airway Infxn
• laryngitis, epiglottitis, laryngotracheobronchtis
• Acute inflam dz upper airway
• Danger obstrxn airway
• Bacteria/viruses, individually, in combo
• Haemophilus influenzae
• Corynebacterium diphtheriae
• Bordetella pertussis
• Strep pneu
• Parainfluenza viruses
• Influenza viruses
• RSV

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• HaEMOPhilus influenzae
• Gram negative, non-motile, rod
• 6 antigenic types capsular polysacs, a-f
• Type b serious infxn humans
• 1987 Vaccine
• Requires
• X factor protoporphyrin
• V factor pyridine nucleotide causes
• Epiglottitis, Meningitis, Otitis Media, Pneu
• TX
• Chloramphenicol, ampicillin, penicillin G,
  tetracycline, sulfonamides

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• Corynebacterium diphtheriae
• Gram positive rod
• Granules Chinese letters
• Larynx, pharynx classic sites
• Pseudomembrane phyryngitis
• Streptococcous Pneumonia
• Major cause bacterial pneumonia adults and
  children

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• Bordetella pertussis
• Gram negative rod
• Small, ovoid, non-motile, non-sporeforming
• Freshly isolated phase I toxins
• Only phase I vaccine new vaccine accellular
• Lab smooth to rough transition Phase IV -
  pleomorphic, noncapsulated, avirulent
• Special bronchitis
• Un-immunized children
• Destrxn ciliated epi cells ? ?clearance mucous
• Virulence factors
• FHA pilli rod
• Toxin unlocks cell

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• Parainfluenza Viruses
• Paramyxoviruses
• RNA core, ether-sensitive envelope
• Multiply in cytoplasm
• Types 1, 2, 3, 4 infxn in humans
• Antigenically stable, homogenous
• Croup 1, 2, 3
• Common cold 1, 3, 4
• Pharyngitis 1, 3, 4
• Bronchitis 1, 3
• Bronchopneumonia 1, 3

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• Influenza Viruses
• Typically cause LRTI adults, children
• RSV
• Can cause croup
• Acute obstruction of upper airway in infants and
  children characterized by a barking cough with
  difficult and noisy respiration.
• Laryngotracheobronchitis in infants and young
  children caused by parainfluenza viruses 1 and 2.
• Usually causes bronchiolitis and
  bronchiopnuemonia in infants

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• Acute Laryngitis
• Barking cough, hoarseness
• Airway obstrxn young childrengtgt adults
• Common cold and influenzal syndromes
• All resp viruses cause hoarseness
• DX exam larynx
• TX
• Resting the voice
• Inhalation moistened air
• NO value in antimicrobials

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• Epiglottitis - Acute rapidly progressive
  cellulitis of epiglottis, adjacent structures
• Abrupt, complete airway obstrxn
• Clinical
• 2-4 yo child, 6-12 h hx fever, dysphagia
• DX edematous cherry-red epiglottis
• Lab leukocytosis, cultures blood and
  epiglottis, thumb sign, pneu on CXR
• Haemophilus influenzae type b(Hib)
• 100 children with epiglottitis
• Pneumococci, staph, strep
• TX adequate airway, control infxn
• IV Antibiotic vs. H.flu
• Immunity episode serum Abs to capsular polysac
• Vaccine HITB

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• Acute Laryngotracheobronchitis (croup)
• Inflam subglottis area, young children
• 3 mos 3 years peak year 2
• Hoarseness, deep, non-prod, brassy-tone cough
• Pair of barking seals
• Parainfluenza - 1 cause
• Adenovirus
• Influenza A
• Broader range, more hospital, tracheotomy
• RSV
• NB Mycoplasma
• DX clinical picture

30

• Bronchitis and bronchiolitis
• Acute bronchitis
• Common during flu epidemics, winter
• Rhinoviruses important cause
• Adenovirus military recruits
• Severe myco pneu, B. pertussis
• Clinical
• Cough early, prominent cig smokers long
• Temp elev flu, adenovirus, M.pneu
• DX bronchitis is dx of exclusion
• Hx exposure toxic substances, cig smoking
• TX symptomatic

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• Chronic Bronchitis
• Coughed up sputum most days during at least 3
  months in the past two years
• Incessant cough advanced obese patient
• Emphysema often present
• Cough, XS mucous secretion tracheobronchial tree
• Cig smoking, infxn, inhalation dust, fumes
• Mengtwomen gt40yo 10-25 adults
• Recurrent resp infxn immunocompromised
• Bact not cause perpetuate dz,
• H.flu, S. aureus, beta hemolytic strep

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• Bronchiolitis acute LRTI 1-2 yo
• Starts with coryza (acute rhinitis)
• Dehydration poor oral intake, paroxysms of
  cough vomiting resp distress, lethargy
• 3-4 day improvement, 1-2 week recovery
• Viruses, M. pneu
• 87 RSV, PIV 1, 3, adenoviruses, rhinoviruses,
  M. pneu
• RSV hospitalized cases
• Mirrors seasonal pattern of RSV
• DX clinical findings, nasal wash
• TX no Vx, O2 admin, careful supp care
• Aerosolized ribavirin severe bronchiolitis -
  RSV

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• Influenza RNA, env, orthomyxo
• Acute, febrile, fever, malaise, HA, myalgia
• 8 pieces RNA 8mRNAs 8 proteins
• Ag type/Place/Year/Strain/Surface Ag
• A/Texas/77/H3N2
• A - Pandemic
• B localized epidemic
• C sporadic
• Glycoprotiens spikes
• H will bind to RBC clumps - hemagglutin
• Major Ag, most Ag variation, Site attachment
  virus - host cell
• Abs to Hag prevent infxn, hemagglutination
• N neuraminidases less important
• Cleaves end off sugar, releases virus from debris

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• Influenza - Ag Variation change surface Ag
• A gt B gt C HA gt N, HA most imp
• Ag drift minor, over time, H1, H2, H3, N1, N2
• Ag Shift - Abrupt Pandemic devastating
• Clinical 1-3 incub abrupt fever 39-40C
• Extreme prostation, myalgia, cough
• Infants mild, like cold
• Elderly, COPD, DM, Pregnancy course worsens
• Pneu 2ary S.aureus, H.flu, S.pneu, S.pyogenes
• Immunity IgA, IFN improvement
• HAI complement fixing Abs in serum years to
  decline
• Virus-specific, HLA-restricted cytotoxic T
  lymphos recovery
• Complications myocarditis, severe myositis,
  myoglobinuria, encephalopathy, post-flu asthenia,
  Reyes
• DX four-fold rise HI Ab titer
• Prvn Vx killed Ags attenuated can get virus

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• Pneumonia
• Inflam dz pulm parenchyma, bronchial, alveolar
  spaces, abnormal density CXR
• Nearly 50 LRTI bact origin
• Flu ? S. areus pneu
• COPD ? pneumococci, H.flu
• CF ? pseudomonas, staph
• AIDS ? pneumocystis carinii

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• Acute Pneu
• Common bact S.pneu, S.aureus, H.flu,
• Mixed anearobe bacteroides, fusobacterium,
  peptostreptococus, peotococcus
• Enterobacteriace E.coli, K.pneu, enterobacter
• Kleb Pneu currant Jelly sputum, dark
• Pseudomonas, legionella
• Fungal Aspergillus, Candida, Coccidiodes,
  histoplasma capsulatum,
• Viral Children RSV, Para, Flu-A adults Flu A,
  Flu B, adenovirus
• Rickettsial coxiella burnetti, rickettsia
  rickettsia
• PMNs acute infxn transtracheal aspiration dx,
  gram stain, mucopurulent spututm

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• Acute Community Acquired Pneumonia
• 50s, winter, early spring,
• 50-90
• S. pneu
• L. pneumophilia
• H. flu
• S. aureus
• Aspiration Pneumonia
• Altered conciousness, No gag/swallowing reflexes
• Anaerobic bacteria 45-58
• Aerobes, facultativess 41-46
• Atypical Pneumonia walking pneu
• Child gt 5yo, young adult
• Mycoplasma most common cause
• Others Para, EBV, RSV, Adeno, Coxiella (Q
  Fever), Chlam pneu, Chlam psittaci,
• Chronic pneu weeks to months, infx agent,
  abnormal CXR
• Elderly patient higher risk, DM, COPD,

38

• Legionnaires Dz -1976 devastating outbreak
• Discrete outbreaks or sporadic cases
• Legionella pneumophilia
• Fastidious, filamentous, flagellated gram
• Parasitize ameobas, MPs, 9 serogroups, SG1
  clinical isolates
• Inhalation aerosols contam w orgs, no
  person-person
• Risk elderly, Chronic lung dz, malignant, renal
  failure
• 2-10 d incub, 1 day prodrome myalgias, malaise,
  HA
• Acute onset high fever, shaking chills, non-prod
  cough, pleuritic pain, Abdominal pain, vomiting,
  diarrhea
• NO meningitis
• Common CNS, GI, Renal
• DX transtracheal aspriates, Ags in urine,
• Indirect immunofluorescence anti-Leg Ab pt serum
  4x rise
• TX erythromycin DOC
• Hyperchlorination doesnt work, superheat and
  flush, no Vx

39

• Hantavirus Pulmonary Syndrome
• 1993 Feltons first year New Mexico
• Deer mice
• Sin Nombre
• Prior Korean hemorrhagic fever
• Fever, hemorrhages, kidney failure
• Febrile prodrome
• Pulmonary edema, fluid in alveoli
• Resp distress, hyptension, shock

40

• Severe Acute Resp Syndrome (SARS)
• Fever, resp illness, recent travel affected area,
  contact suspected SARS patient
• 2003 originated China
• 8100 infected/774 killed (9.5)
• SARS-CoV, animal origin,
• high fever
• Cough
• Resp distress w/ hypoxia
• Diarrhea 10-20
• Close person-person contact
• Coughing, sneezing, contaminated objects
• Serological test for SARS-CoV Abs
• RT-PCR clinical specimens
• Viral culture

41

• Lung Abcesses/necrotizing pneu
• PF, causative agents
• Similar to Asp Pneu risks
• Mixed anaerobic bac Fusobacterium nucleatum,
  Bacteroides melaninogenicus, peptostreptococci,
  microaerophilic strep
• Cough present in all
• Abcess drains in bronchial tree copious,
  foul-smelling sputum
• Chest pain
• DX examination of sputum

42

• Empyema pus in pleural space
• Prurulent inflam exudate pleural cavity, acute or
  chronic
• Direct spread of bronchopulm infxn
• Complication thoracic surgery
• S. aureus most common, Pseud, Kleb pneu, E.coli
  next, mixed
• Dx aspiration pleural fluid, gram stain
• TX get pus out so Ab works

43

• Tuberculosis (mostly Puentes)
• 1980s - good control
• 1990s rise immunocompromised, bad economy,
  lost control
• By 2000 control again negative slope of curve
  when he got involved.
• Active Cases TB 2002
• LA County 1,025, 1/3
• CA 3,169
• US 15,075
• Some states, only 30-40 cases

44

• Goal of CDC for US 1/100,000. Right now
  5.6/100,000
• CA 10/100,000. Max cases was 91-92.
• LA 9 million goes towards TB. HIV 100
  million.
• Race, ethnicity Asian, Latinos more cases.
• know statistics of where you practice.
• TB impacts all ages, both genders equally.
• To measure control, look at young, look at old.
• NBs under five - came out dz-free, was
  exposed,dev disease.
• 2.5/5 will be over 55.
• Middle aged most TB cases.
• TB always in foreign born. About 2/3 of TB
  cases.
• Ask when arrived important how?
• Naturalization process helps screening.
• Undocumented time of coming in is key
• at risk of breaking down in two years.

45

• Agents M.tb, M.bovis, M.africanum
• M.tb obligate parasite
• Aerobic, nonsporeforming, nonmotile bacillus
• High lipid content
• Resist to drying, acids, alkalis, NH4,
• Slow growth 15-20 h generation
• Sensitive UV light wont catch it outside
• smears highly infxs
• TB exposure TB infection latent or active?
• 5-15 infected ? active dz
• TB particle small enough to get into alveoli
  requires droplet nuclei 1-5microns in size.
  Small pox is small. Small is scary. Stay out of
  non-circulating air, or use mask.
• Air-borne transmission, wont get from countertop
• Droplet nuclei sneezing, couging speaking,
  singing, talk loud
• Laryngeal TB who talks, TB who coughs
• Exposure key one massive, chronic small

46

• TB exposure leads to latency -
• Targeted Tuberculin Testing Tine test no longer
  done (similar to smallpox vaccination, prongs)
  now we inject purified protein derivative,
  brought into tuberculin syringe, instill
  solution, subcutaneously intradermal.
• Purpose of TARGETED testing
• find person with LTBI who would benefit from tx
• find person with TB dz who would benefit from TX
• No routine test groups NOT high risk for TB
• HCWs TX latent infxn bc stress increases risk
  of TB dz
• homeless
• malignancies TB test first thing you do
• HIV
• Latency treated with SINGLE drug
• Dz txed with RIPE 4 drugs
• Decision to test is decision to TREAT

47

• TB people tested for LTBI
• higher risk exposure/ infxn TB
• close contacts with active TB
• FB from area where TB common
• Residents and employees of high-risk congregate
  settings dialysis units, jails, residents
• HCWs who serve high-risk clients
• Higher risk for TB disease once infected
• HIV infection
• recently infected with TB negative skin test
  with sx
• medical conditions
• inject illicit drugs
• hx of inadequately txed with TB never finished
  tx

48

• Who will become TB active
• HIV big risk 76/100,000,
• Silicosis 68/100,000 major problem, less now,
  due to laws protecting work force coal miners
• CXR 2-13.6/100,000
• DM 2-4/100,000 leads to immunodeficiency,
  dont activate Tcells places individual at risk
• Gastrectomy 2-5 loss of acidity predisposes to
  TB swallowing phlegm good for you
• Carcinoma of head or neck 16
• Solid organ transplantation -
• LTBI for HIV negative 5-15 LIFETIME
• highest risk within 2 years.
• HIV 8-10 latent to active PER YEAR
  important to screen for TB

49

• Mantoux TB Test
• .1 ml of 5TU PPD tuberculin
• produce wheal 6mm to 10mm in diameter
• UNIVERSAL PRCXNS DO NOT RE-CAP
• Read 48-72 will stay positive 5-6 days.
• Measure induration ONLY not erythema rubor,
  color, dolor, tumor(indurationwheal)
• Anergy - probing IS to see if false
• NOT DONE we only act on PST, not NST
• Consider anergy HIV, overwhelming TB, severe or
  febrile, viral infections, live-virus infxs,
  immunosuppressive tx
• Negative TST does not rule out dx of TB

50

• Two steps in CA for positive LTBI dx
• PST result gt or equal to 5mm
• Regardless of age
• HIV positive
• Recent contacts of a TB case
• Persons with fibrotic changes CXR consistent
  with old TB
• Organ transplants immunocompromised host
• PST equal or gt10
• Recent arrivals
• IV drug users
• Children lt 4 or children and adolescents exposed
• LTBI PST, NCXR, No SX
• Person has to be susceptible host or massive
  expose

51

• TB DZ worst case scenario
• Think TB coughing blood, night sweats, fatigue,
  malaise, fever, persistent cough
• Get med hx, listen for rales, wheezing,
  hoarseness, TST, lab ddx, CXR,
• As dz progresses, granulomas on vocal cords.
• TST useful only if POSITIVE.
• NEGATIVE TEST DOES NOT EXCLUDE TB
• negative TST with active dz due to weak IS.
• LTBI PST, NCXR, No SX
• W/ PST MUST R/O active B4 starting TX!!
• LTBI just one Rx if active - RESISTANCE
• Clinical presentation of pulm TB
• Cough, prolonged gt3weeks, sputum productive later
  in course, pleuritic pain, hemoptysis
• Systemic fever 65-85, chills, seats, fatigue,
  malaise, anorexia, weight loss
• 10-20 patients ASx due to continuum

52

• TX LTBI 9 months Isoniazid (INH)
• 6-month regimen minimum immune-competent
• HIV 9 months
• NB 16-18years 9 month 270 doses in 12
  months
• Cautionary word be careful
• To shorten LBTI Rifampin and Pyrazinamide were
  used to shorten tx course no deaths or liver
  injuries, but have been reports of severe
  hepatitis.
• CDC says to discontinue, limit to HIV, close
  supervision
• If we find PST, we will treat, but we will
  exclude active dz with CXR.
• Prior to TX LTBI, you get CXR, and if positive,
  you need to do something else.
• Determine hx of tx for LTBI or dz

53

• Try to prevent dissemination. Worst case
  scenario TB goes to brain FATAL.
• Structures Potts dzbone TB, kidney, joints,
  lymph nodes.
• Skin test will NOT induce CMI response. No
  memory cells produced.
• CXR upper lobe, typically right. Dogma today
  exposed?latent?tx?lifelong immunity. BUT, with
  HIV , can lose immunity.
• Once youve developed immune response, youre
  protected from developing active disease from
  further exposure.
• Think of it as continuum.
• Latent infection CXR???

54

• M. tb classification
• Runyon growth rate
• I, II, III slow
• IV fast
• Pigment
• I required light for color
• II color w/o light
• III less pigment, not hv related
• M. avium farmers, silicosis, AIDS
• M.scrofulaceum common LAis kids
• M. kansasii most human mybocact
• M. marinum swimming pool
• M.fortuitum, M.chelonae fast growing
• Diff from TB no human-human trx, more resistant
  to first line rx,
• NST from M.tb

55

• TB TX
• LTBI TX w INH, 9 mos, most active vs TB
• 6-month regimen minimum immune-competent
• HIV 9 monhts
• NB 16-18years 9 monht 270 doses in 12
  months
• Cautionary word be careful
• To shorten LBTI Rifampin, Pyrazinamide used
  shorten tx course no death, liver injuries, but
  reports of severe hepatitis.
• CDC says to discontinue, limit to HIV, close
  supervision
• TB difficult to TX
• Slow growth, Abs better vs fast
• Can lie dormant
• Cell wall impermeable to most rx
• Can be intracellular inside MPs
• Develops resist to single rx tx lethal
• Requires tx for gt 6 months

56

• Isoniazid INH Iso-Nicotinic acid Hydraxzide
• Single most active vs. TB
• Effective vs intracell/extracell infx
• MOA penetrates cell walls INH syn mycolic
  acid integral cs cell walls small amt for
  mycobacteria, large amts others
• Mycolic acid acid fast
• 1/106 mutations resistance
• Hydrazine metab by acetylation - ½ people
  deficient
• renal function toxic RX levels, also with
  hepatic insufficiency
• SEFX
• drug induced HEP can be fatal, age-dependent,
  more risk ROHism, preg, post-part
• Peripheral neuritis slow acetylators, DM,
  malnourished
• Pyridoxine deficiency rx forms cx, eliminates
  give vit b6
• Rx-induced SLE reversible
• Convulsions in epileptics
• INH inhibits microsomal Rx metab increases
  levels/TOX other drugs Phenytoin,
  anticoagulants,

57

• Rifampin deriv rifamycin B - streptomyces
• Effective vs G, G- E.coli, Pseuds, proteus,
  kleb, N.men, H.flu, S.aureus, chlam,
• MOA binds DNA-dep RNA pase inh init RNA
  synthesis
• CIDAL vs mycobacteria vs intra/extracell
• Excreted mainly thru bile enterohep recirc
• Parent and metab both active
• Do not give less 2 weeks flu-like sx
• Red-orange urine, feces, saliva, sweat, tears
• Can stain soft contacts
• Cross resistance other rifamycins rifabutin
• Rifamate with INH
• SEFX rash, F, V, V, GI d/c, jaundice, rare
  fatal
• Liver dz, ROHism, age increase risk ENZ
  inducer

58

• Rifapentine
• MOA same as rifampin
• Inh initiation RNA synthesis
• Cidal vs. intracell and extracellular
• Parent and metab active
• Use only with other agents

59

• Ethambutol static
• MOA inh syn arabino galatance
• Enhances pene lipophillic Rifampin and
  fluoroquinolones
• Disrupts intracell metab/ cell replic
• 50 excreted urine
• 50 hepatobiliary excretion
• Adjust dose
• Do not use alone
• SEFX retrobulbur neuritis loss acuity,
  red-green color blind, revers w d/c

60

• Streptomycin
• Aminoglycoside - Sugar w amino group
• Cant get inside extracell ONLY
• Deep IM pain, hot tender masses
• MOA cidal
• Block init protein synthesis
• Can cause misreading
• Faulty proteins insert into cell membrane,
  alter perm, increase RX transport into cell,
  leakage cell death
• Resistance common in hospitals
• SEFX (all aminoglycosides)
• Ototoxic vestibular 20 - IRREV
• Nephrotoxic 8-36 - reversible
• Adjust dose renal fxn, optic nerve damage

61

• Pyrazinamide cidal
• Prodrug metab to pyrazinoic acid
• Not effective neutral ph intracell only
• MPs low pH
• MOA UK
• SEFX HEP-TOX, NVF, hyperuricemia

62

• Alternative 2nd line agents
• Less effective, more SEFX
• Ethionamide inh mycolic acid syn (INH)
• Paraaminosalicylic Acid (PAS) static
• MOA competes with PABA no folate syn
• Humans dont make folate get from diet
• SEFX 10-30 - anorexia, NVD, epigastric pain,
  abdominal distress, fever, malaise, joint pain
• Cycloserine inh alanine racemase
• No l-alanine to d-alanine
• ??CNS TOX HA, tremors, psychoses, conv
• Not with streptomycin
• Kanymcin, Amikacin aminoglycosides
• Amikacin less toxic, low resist, same sefx
  oto/nephroTOX

63

• 2nd lines TB
• Capreomycin IM only PAIN!
• Oto/nephro TOX, not with streptomycin
• Ciprofloxasin fluoroquinolone cidal
• Cartilage damage
• Ofloxacin DNA gyrase inh
• DNA gyrase inh like topoisomerase
• Inhibits rejoining strand scission
• Sefx N, HA, dizziness, rash

64

• Rxs MAC - M.avium, M.intracellularis
• pulm infxn similar to TB, elderly pre-exist dz
• 15-40 AIDS disseminated
• Most common cause systemic bact infxn
• Rifabutin prvn dissem MAC advance HIV
• MOA same as rifampin
• Clarithromycin macrolide, pene tissue, BS
• Azithromycin same, inc stability,
• MOA inh transloc tRNA from acceptor to donor
  ribos.
• Cipro - fluoroquinolone
• Pentamidine
• prophylaxis, TX Pneu carinii AIDS pneu
• MOA inh topoisomerase
• SEFX TOX in tx dose, hist release SOB,
  tachycard, HA, V, dizziness, fainting,
  pancreatitis, hyp/hyper glycemia, nephroTOX,
  thrombocytopenia, neutropenia aerosol cough,
  bronchospasms HIV patients