chronic necrotizing pneumonia: abscesses, MTB, NTM Flashcards
chronic pneumo hallmarks
slow, insidious (wks-mod), fever mild-high, night sweats, malaise/fatigue, anorexia (10-20 lb), dyspnea, chronic cough may become prod, hemoptytic, CP (pleur/nonpleur)
foul smelling sputum is pathognomonic for
anaerobes
chronic pneumo CXR
consolidation/infiltrates OR cavitary lesions
Apical or subapical consolidation/infiltrates in the upper lobes or superior- posterior segments of the lower lobes +/- caviation (MTB, syst. mycoses), occur over several mos
lung lesions are NOT
NOT visualized by Gs
NOT Cx on blood agar
NOT tx w. PCN, cephs
tx chronic pneumo empirically?
NO; tx too toxic, wait til dx
lung abscess (hole): (cavitary lesions often have air-water interface)
local suppurative(pussy) necrotizing collection w/in lung parenchyma
cavitary lesions caused by
90%: anaerobes, facult anaerobes (G+ cocci, G- rods)
via aspiration, wks-2mos
CAN visual by Gs, blood agar if facult., tx w. PCN, cephs
also caused by: prim. SCC of lung (>45yo, 30%)
in chronic nec. pneumo, facultative anaerobes are…
more virulent w/ shorter onset (2wks)
anaerobic bacteria are less virulent and onset is 4-6 wks
abscess pneumo s/s
classic chronic pneumo + foul sputum (50-60%), altered sensorium if progressed
poor dent. hyg., trauma/inj/disease
abscess pneumo CXR
solitary cavitary lesion about 4cm in diameter w/ air-fluid level
abscess pneumo comps
empyema formation from bronchopleural fistula
massive hemoptysis
spont. rupture into uninv. lung segments
non-resolution of abscess cavity
abscess pneumo tx
abx targeting orogingival anaerobes
B-lactamase-inhib/B-lactam OR 2nd/3rd gen. CEPH + clindamycin/metronidazole for 6-8 wks
past: (IV PCN + clindamycin)
if abx unsuccessful for abscess tx
resect lung/drain absecs via bronchial airway (if thru chest, non-healing open wound in lung
MTB spectrum
no illness: LTBI
localized: pulmonary/meningeal TB
massive systemic dissemination: miliary TB
MTB staining
poorly via Gx
acid-fast : resistant to destain with acid alcohol
MTB cell wall structure
- PTG, G- wall w/ lypophilic substances
- virulence factors:
1. mycolic acids (LCFAs (branched), lipids bound to arabinogalactan-PTG polymers) INH target resp. for acid-fastness
2. trehalose dimycolate (cord factor)
MTB deets
facult. IC in macrophages, obligate areobe, slow growth (2-3 wks), sp. media, resistant to drying, acids, alkalis, disinf.
sens. to UV light and moist heat (pasteurization)
TB transmission only occurs from person with..
ACTIVE pulmonary or laryngeal TB via inhalation of 1-10um airborne droplets of 1-3 bacilli (cough) AFB smear neg or pos pts! (need contact for hours) (humans sole host)
also: ingestion of m. bovis milk
TB affects what age groups..
young imm.COMPETENT (65 as REACTIVATION (pulmonary TB)
most MTB-infected pts control or cure their infection?
CONTROL
10% will reactivate (LTBI–>TB) (esp. 0-2 yrs post inf)
90% remain LTBI for life
(some will not control–>TB)
risk factors for ACQUIRING TB
foreign born (Africa, Asia, LA)
low-income (homeless, malnutr., crowding)
nursing home, correctional, homeless shelters
HCW or persons employed above
risk factors for developing TB once infected w. MTB
65,
T cell compromise(HIV, maln, chemo, steroids, SOT, old, blood ca)
IVDU, certain diseases
MTB patho
facult. IC of alveolar endothelial/epithelial cells and macrophages
- inh. TB must reach alveolar spaces (periphery), MTB are phago (not killed) by macros and PMNs, multi. IC, disseminate: locally (lungs and LNs) or systemically/lymphohematogenous (any organ)
MTB replication occurs in orgs/tissues w.
high O2 levels: apical-post. areas of lung, LN
also: kidney, brain, bone
MTB immunity
CMI (both CD4+ and CD8+)
exposure–>MTB-sp. CD4+ cells proc. IFN-y–>activate macros–>prod. ROIs that kill MTB cells phagocyt. by act. macros
MTB-sp. CD8+ cells kill MTB-inf. NON-ACT. macros–>rel. MTB cells, killed by act. macros
CMI resp. for most tissue damage and symptoms of disease, MTB does NOT produce toxins
host attempts to contain MTB infections–>inflammatory response–>adaptive response–>
GRANULOMA (caseation-seen in histo biopsy not CXR/CT/MRI)
made of macrophage-derived epithelioid cells, lymphocytes
viable MTB @ center (w. CMI: arrested, but viable for years)
if inadequate CMI: LTBI–>TB
CMI response converts granuloma–>organized granulomas: tubercles
dynamic, continuous process
core: dormant MTB, lymphos, epithel. histocytes, multinuc. Langerhans giant cells
periphery: fibroblasts, monocytes (blood), lymphos,
zone cells alive, must be replenished
over time tubercles can heal
> 1 yr
fibrosis–>scarring–>calcification (can now see on XR)
primary pulm. TB
happens when IR fails to form granuloma (inade. CMI)
old, T cell compromised, immunocompetent kiddos
(less common in US)
reactivation pulmonary TB due to
systemic immunosuppression:
advanced HIV/AIDS, Ca, old, chronic ill health
immunosupp–>brkdwn of granulomas w. LTBI–>reactivation
most common TB in US
miliary TB
massive disseminated inf. involving multiple organs (foci-size of millet seed)
other: extrapulmonary refers to other organ system
if infection progresses in pulmonary TB…
consolidation happens–>cavitary lesions–>bronchiectasis
in reactivation TB, the caseous center continues to enlarge as MTB multiply–>liquifies tissues–>
- formation of air-liquid filled cavities: huge inc. in MTB #s–>abx resistance, spread
- rupture into airways–>hemoptysis, release of caesium (spread)
- inhal. of MTB to other parts of lung (tuberculous bronchopneumonia)
- erosion of vein wall and leak of caesium into blood–>hemoptysis, miliary TB
LTBI clinical manifestations
absence of s/s
CXR norm or shows evidence of past TB
neg. stain/sputum Cx
LTBI proven only by
positive PPD
positive Quantiferon test
(CANNOT distinguish btw LTBI and active TB disease)
i.e. disease may or may not be present
TB disease (active) dx by
s/s, AFB in sputum, Cx
TB disease (active) s/s (only after inf. has progressed)
slow, insidious, fever (of “unknown origin”: FUO), night sweats, malaise, fatigue, anorexia + weight loss
chronic persistant cough, pleuritic pain, pleural effusions (MTB inf or IR), dyspnea
TB in late stage of HIV/AIDS
mostly pulm. TB, but coin-like or cavitary lesions uncommon
diffuse pulmonary infiltrates happen due to poor CMI
(disseminated TB 1/3 cases, inc. mortality)
PPD
not 100% sp/sn, injected intradermally (into not under skin)
1st detected 3-8 wks post-primary infection
positive PPD
induration (50% monos/macros, 50% MTB-sp Th1 cells) 48 hrs post-inf
> 15 mm for all pops not specified
> 10 mm for foreign born (see above), IVDU, med-underserved, low income, HCW etc (see above), residents of (see above), certain conditions, kiddos
>5 mm for HIV+, close TB contacts, abnorm. CXR (upper lobe fibrosis), immunsuppr. w. at leat 15 mg prednisone/day last 1 mo
QuantiFERON-TB Gold test
in vitro, measure amount of INF-y prod. by cells in whole blood that have been stim. by MTB peptides
- mimics ESAT-6 and CFP-10 proteins, present in MTB but not BCG and NTM
- dx for MTB, NOT dx for LTBI vs active TB
- no boosting effect
new IGRAs (IFN-y release assay)
dx both LTBI and active TB (MTB)
-QFT-GIT and T-SPOT TB test
detection of DISEASE (active)
med hx, s/s CXR
report to HD
active TB CXR
-consolidation/infiltrates in apical/subapical in upper lobes or sup-post segments of lower lobes +/- cavitation (or nodular/cavitary lesion w. no surrounding infiltrates)
-immunocompetent: solitary pulm. nodule 1 cm in diam. surrounded by lung parenchyma, no other abnorm., opaque due to calcification
(granuloma form. evident in biopsy specimen)
ddx active MTB (based on CXR)
infectious: nocardia, actinomyces israelii, systemic mycosis (fungi) - infection, not disease
lung cancer
hamartoma/adenochondroma
in HIV/AIDS pts, no cavitations but
diffuse infiltrate is common
lab dx MTB
AFB in sputum (consid. infectious, quantified) positive Cx (confirms dx)-->drug susc/abx sens test, monitor tx response
if extrapulm. TB suspected
blood cx to see if disseminating
nucleic acid amplification (NAA) testing
detects MTB 1+ wks earlier than Cx, cannot dist. btw live/dead
MTB-sp. CD4+ T cells expressed immune markers
CD38, HLA-DR, Ki-67+
MTB tx for who?
LTBI and active TB -confirmed! not close contacts
tx too toxic
MTB tx: 1st line drugs
Isoniazid: interferes w. mycolic acid syn
Rifampin: inhib. RNA syn
Pyrazinamide: bactericidal for repl. orgs
Ethambutol: inhib. cell wall sun and is bacteriostatic
MDR-TB
resistance to Rifampin and INH
XDR-TB
resistant to Rifampin and INH and any FQ and at least 1/3 inj. 2nd line drugs (amikacin, kanamycin, capreomycin)
LTBI/MTB infection (not active) 2 tx regimens
HIV or non-HIV
- INH for 6-9* mos
2. Rifampin for 4 mos for LBTI + close contacts w. INH-res. TB/cannot tolerate INH/pyrazinamide
TB disease (active) tx: drug-sens
- INH alone 18 mod
- INH and Rifampin for 9 mos
- 4 1st LD for 3 mos, 2 1st LD for 4 mos
TB disease (active) tx: DR
combined chemo to prev. MDR-TB
3 drugs 6-9 mos (e.g.,
rifampin, pyrazinamide, INH for 2 months then rifampin and INH for 4 mos -still OK)
TB disease (active) tx: MRD
4-5 drugs for 18-24 mos (2 yrs!)
Tb disease tx monitored via
sputum Cx (3 wks post tx) considered inf. as long as orgs cx, cured when 3 successive neg cx CANNOT monitor with PPD, Quantiferon test
MDR-TB..
due to chromosomal mutations
high mortality rate
extensive tx for XDR-TB
lung resection and antimicrobial tx
DOTS
HCW observe swallowing, monitor progress, short-course (6-9 mos)
BCG vaccine
M. bovis, cannot cause dis. in immcompetent person
life-long, latent infection, can reactivate latent inf–>active in immunocompromised pts
used to tx bladder Ca (IR delays Ca recurrence)
NTM etiology
environment AND human NF (MTB just NF)
NTM spp.
M. kansasii
M. fortuitum
M. avium complex (MAC): M. intracellulare and M. avium
NTM deets
rapid growers: 7 days slow growers >7d-6weeks some AF, cross-reac. Ags to MTB Ag most MDR (esp. MAC) incidence inc. due to HIV/immsuppr pop affects oldies, immsuppr, underlying dis.
NTM transmission
NOT person-person, NO reactivation of latent inf.
resevoir is environ. (all contrast MTB)
NTM patho
may cause slight + PPD, less virulent *rarely causes dis. in immunocompetent person, diff to elim. due to MDR
NTM slow growers: Group 1: photochromogens, Runyon group I (7d-6wks)
M. kansasii: water supplies, MW US, pulm dis., min. contagious (unlike MTB)
M. marinum: skin inf.
M. haemophilum: skin, jt, bone, pulm. inf. in immunocompromised persons and lymphaden. in kiddos
NTM slow growers: Group 2 : scotochromogens (pigment in dark), Runyon group II
M. gordonae
M. scrofulaceum: cervical adenitis
NTM slow growers: Group 3: noncrhomogenic, Runyon group III
MAC: M. avium complex: ubiquitous environ. org
SE US, inhal. and ingestion–>across mucosa–>infects macros of LP–>submucosa–>LN
DMAC
disseminated MAC in HIV/AIDS pts. (20-40% of pts w. CD4 count
DMAC manifests in AIDS pt
fever, night sweats, weight loss-wasting, swollen abd. LNs (unilat), diarrhea, hepsplnmeg, anemia, elev. PB liver enzymes, localized disease LESS common, but rarely in (LRT, pericarditis, GIT, CNS, skin, joints)
Cx for slow growers req.
2-6 wks, alert lab!
nucleic acid testing quicker
NTM rapid growers: (2-7 days) Runyon group IV
M. fortuitum, M. abscessus, M. chelonae, M. massiliense, M. bolletii (fortuitum complex)
contaminant in clinical specimens
sig. opportunistic pathogen of (skin, ST, bone, LRT (chronic), site of wound trauma, surgical prosthetic implants)
-resis to alk. glutaradehyde, low susc. to high lev. disinfect.
NTM dx
Cx must be done, need repeated isolation of org for dx, ID to species level!
NTM tx
depends on ID of species, sensitivity testing must be done on Cx+ isolates
