Pum Lg 3

Front 1

Case 6
A 50-year-old male presents to the clinic with intermittent fever, drenching night sweats, nonproductive cough, and a 10-lb weight loss for the past month. He has hypertension and type 2 diabetes mellitus. On exam he is mildly cachectic and in moderate distress. Temperature is 39°C. Lungs have scattered rhonchi and amphoric sounds over the upper posterior right hemithorax and apex. Chest radiograph is obtained and is shown below:

Back 1

Key findings/interpretation
1. ***intermittent fever, drenching night sweats, nonproductive cough, and a 10-lb weight loss*** for the past month; sx for about a month (4x weeks); more like a subacute process (not acute)
2. hypertension and type 2 diabetes mellitus.
3. PE: mildly cachectic (skinny limbs) and in moderate distress.
4. Temperature is 39°C
5. scattered rhonchi and amphoric sounds (blowing air over empty bottle) over the ***upper posterior right hemithorax and apex

Front 2

CXR (slide 68)

Back 2

1. RUL consolidation with cavitation
2. trachea deviated to right side
3. horizontal fissure turned diagonal
4. V LOSS in RUL
5. more than infiltratel, areas of pocekets of air (dark spots), increased broncho vascular markings in other areas

Front 3

DDX

Back 3

1. WDX: TB(active)
2. fungal infection; histoplasmosis (can mimick TB pul and extrapul)
3. nocardian infection? Looking like TB,
4. Other bacterial and fungal infection:
a. blastomycosis
b. pneumococcus (no, doesn’t cavitate, and doesn’t last for 4x weeks*pneumonia sx won't last that long)
c. S aureus
d. Klebsiella (upper lobe pneumo, actually get bulging instead of V loss),
e. anaerobes (from oral flora, aspiration),

Front 4

Pathogenesis of TB (slide 73)

Back 4

1. Primary tuberculosis - inhaled in droplet nuclei from an active case of tuberculosis
a. Initial multiplication is in the alveoli
b. spread through lymphatic drainage to the hilar lymph nodes.
c. further lymphatic drainage to the bloodstream, the organisms are spread throughout the body.
2. Alveolar macrophage; Ingested bacteria multiply in the nonactivated macrophage.
a. TH1 cellular immune responses attempt to activate the macrophage by secreting cytokines (interferon gamma [IFN-]). dz arrested if works
b. Inflammatory elements of delayed-type hypersensitivity (DTH) are attracted and cause destruction; activation fails, disease and injury continue.
3. Reactivation tuberculosis; Reactivation typically starts in the upper lobes of the lung with granuloma formation. DTH-mediated destruction can form a cavity, which allows the organisms to be coughed up to infect another person.

Front 5

pathology

Back 5

1. (slide 74): Active infection; Granuloma – later caseate (image: cheesy form)
2. (slide 75): cavity disease; Aerated area
3. (slide 76): miliary disease; disseminated, paucity on CXR; granulomatous foci on lungs; disseminated TB most commonly found in lymphs (outside of lungs); also Sterile pyuria, Intestinal ulceration

Front 6

Drug Resistance

Back 6

1. Isonazid, rifampin, ethambutol, FQ resistance present
2. Cavitary disease/spontaneous mutation occurs once the # >10^8 bacilli
3. “fall and rise” phenomenon:
a. different strains of resistant bacteria
b. apply mono therapy and surviving resistant strain to i.e. isonazid proliferate/ over 10^8 there is a spontaneous mutation and one of them becomes resistant to rifampin
c. give rifampin and isonazid resistant strain die off. rifampin resistant strain populate. Multi Drug Resistant TB formation (Resistance to INH and RIF)
3. FQ resistance: gyrA mutations
a. Prevalence estimate (95% CI):
b. MDR-TB strains;1/4 ~ 25.1% (18.9-32.2)
c. 81.5% sensitivity for phenotypic FQ resistance

Front 7

Extensively drug-resistant (XDR-TB)

Back 7

1. annual TB notifications have now reached 2000 cases per 100,000 population; township in Cape Town; community is socially deprived, living in overcrowded, largely informal dwellings located on demarcated plots serviced with water and sanitation; difficult to avoid ill patients
2. MDR-TB + resistance to a FQ (ofloxacin) and at least one of three injectable agents (amikacin, kanamycin, capreomycin)

Front 8

diagnostics

Back 8

SKIN TEST - INDURATION 5MM AS CUT OFF
CXR
1. Sputum smear microscopy; Difficult to get a negative, very insensitive
2. Nucleic acid amplification testing; very high accuracy of diagnosis
3. Automated liquid cultures (slide 91) (WHO-endorsed);
a. Waxy cell wall colonies (mycolic acids) cultured on solid media, Still need cultures, confirm DX and suscebtibility
b. serpentine cord formation (slide 92) typical of M. tuberculosis
c. Why liquid over solid? Results come back fast
d. GenoType MTBDRplus®Hain Lifescience; Rapid test,
Check drug resistance
e. Cartridge-Based Automated NAAT; automated NA test

Front 9

TX: Targeted Therapy (part 1)

Back 9

1. “Early bactericidal therapy” – kill as much as possible (first few weeks), take the infectious agents; Decreases infectiousness; INH most potent (+ rifampin)
2. “Sterilizing activity” - Kill bacilli persisting beyond early months of therapy; those that went into the tissues; Decreases risk of relapse (from those left in tissue); RIF and PZA are best sterilizers with additive activity only during initial 2 months of therapy; basis of directly-observed treatment, short course (DOTS)
3. Fully susceptible TB (HIV status unknown)1:
a. Median time to culture conversion on 37 days of first-line DOTS
b. 10% remained culture positive at day 60

Front 10

TX: Targeted Therapy (part 2)

Back 10

Need the first 2; In the tissues/in the cells; not infectious (latent infection, not infectious), once become active, will spread (sterilization needed)

1. Induction period: Pt started on INH, RIF, PZA, ETB
a. INH/RIF highly active, cidal and sterilization,
b. PZA assists sterilization; ETB used in case INH is resisted
2. 2 weeks later, culture is +, sensitivity is pan sensitive
3. So with 2 weeks out;
a. keep on 4 durgs for 2 months,
b. stop the ETB, continue everything else
4. INH sensitive confirmed, no reason for the ETB; if 2 month of induction period and all 4 kept; neuropathy, optic neuritis
5. Pt improved, stop the PZA; INH and RIF kept for 4 months (end up as 6 months of total therapy time)
*if couldn’t use PZA initially, 7 months after the first 2, (ending up the classical 9 month treatment time)
*bad liver disease, pregnancy, hyperurecemia - contraindications of PZA

Front 11

Relapse

Back 11

1. To become culture-positive; experience clinical or radiographic deterioration consistent with active TB --> after completion of therapy
Most within 6-12 months after completion
2. True relapses due to failure to sterilize tissues
3. Sometimes re-infection
4. Risks:
a. CD4+ count <100¹
b. Cavitary disease at diagnosis
c. Positive sputum AFB culture @ 2 months of therapy

Front 12

TMC207

Back 12

1. Investigational diarylquinoline specifically inhibiting mycobacterial ATP synthase
2. Kills dormant and replicating bacilli
3. Phase 2 RCT¹ of 47 patients with MDR-TB on standard, 5-drug second-line regimen*:
4. Results:
Reduced time to sputum conversion
Increased proportion with sputum conversion (48% vs. 8%)
5. Resistance develops at rate similar to rifampin²

Front 13

TB-HIV

Back 13

1. ~33 million people HIV-infected, 1/3 ~11 million are infected with TB
2. 20-30 times more likely to develop active TB than those without HIV
3. Patient survival: must start anti-retroviral-therapy ART simultaneously with TB treatment
4. presentation:
a. w/ HIV upper lobe may not be involved, even normal looking lungs
b. Smear may be negative
c. More “subclinical” disease
d. Less cavitary disease

Front 14

Clinical predictors of TB

Back 14

1. Independent predictors (on regression analysis):
a. Fever >7 days duration (OR, 3.9)
b. Weight loss (OR, 3.6)
c. Cavitary infiltrate (OR, 21.1)
2. Combination of variables:
Cough > 7 days + night sweats (spec. 86%; OR, 3.1)

Front 15

Microscopic-Observation Drug-Susceptibility (MODS)

Back 15

diagnostics in a resource limited area, how to DX?
Look for cord like structures (serpentine) not bacilli

Front 16

HIV-TB: TX Challenges

Back 16

1. Duration/frequency of administration
2. Drug-drug interactions
3. Overlapping toxicities
4. Risk for acquired resistance1
a. CD4+ count <100
b. Highly intermittent therapy (once or twice weekly)
c. Low drug levels
5. Immune reconstitution inflammatory syndrome (IRIS)

Front 17

Tuberculosis IRIS

Back 17

1. pt initially Hi RNA, Lo CD4, small induration; active TB not suggestible
2. 4 weeks later; 90% drop in RNA, CD4 above normal; new sx (Fever, Cough, Dyspnea, Generalized lymphadenopathy, Abdominal pain)
3. IRIS: Transient worsening of symptoms/signs of TB, or x-ray deterioration after starting ART (Subside HIV, TB reading showing up)
4. Types:
a. Unmasking undiagnosed TB
b. Paradoxical deterioration of existing disease or new lesions after improvement (extrapulmonary/CNS)
5. Exuberant production of IFN-alpha
a. Reduction in viral load
b. Immunologic recovery

Front 18

decrease nosocomial spread of TB in resource-limited settings

Back 18

Sunlight bad for TB, good ventilation, less likely of transmission

Front 19

Bovine TB

Back 19

1. Mycobacterium bovis
2. Clinically indistinguishable from MTB
3. Inhalation of aerosols
4. Reactive tuberculin skin test
5. Resistant to PZA
6. "Cattle and bison" maintain infection
7. Rare in developed world unless acquired in developing world

Front 20

Case 7
A 40-year-old male presents with 10 days of nonproductive cough, dyspnea on exertion, fever, and night sweats. On exam he is mildly cachectic and in moderate distress. Temperature is 39°C. Oropharynx has exudative thrush. Lungs have coarse rales throughout both hemithoraces. Arterial blood gas analysis obtained while breathing room air at rest is: pH 7.50/pCO2 28/pO2 60. WBC count is 3,000 (absolute lymphocyte count is 100), hemoglobin 10 g/dL, and platelets are 140,000. Serum lactate dehydrogenase level is 400 U/L. Chest radiograph is shown:

Back 20

key findings (Pneumocystis pneumonia)
1. 10 days of nonproductive cough, dyspnea on exertion, fever, and night sweats
2. mildly cachectic and in moderate distress, Temperature is 39°C. ***Oropharynx has exudative thrush
3. coarse rales throughout both hemithoraces
4. pH 7.50/pCO2 28/pO2 60s (respiratory alkalosis, lot of diffusion problem)
5. ***WBC count is 3,000 (absolute lymphocyte count is 100), hemoglobin 10 g/dL, and platelets are 140,000.
6. Serum lactate dehydrogenase level is 400 U/L*****(PcP)

Front 21

CXR (slide 123)
CT (slide 124, 125)

Back 21

1. Grossly abnormal
2. Diffuse recitular nodular infiltrate
3. Multiple lobes bilat
4. (slide 124) "ground-glass opacification" in an HIV-infected patient + PcP.
5. (slide 125) a patient w/ (HIV) demonstrates multiple thin-walled cysts + pneumatoceles related to Pneumocystis pneumonia.

Front 22

DDX

Back 22

1. WDX: PCP
2. LDH elevated; could be coming from RBC, lungs, liver, heart
3. Diffuse pneumonic process, normal LDH, no sign of hemolysis, LDH probably coming from the lung, not seen on every type of infection (lung involved)

Front 23

PCP vs bacterial pneumonia

Back 23

1. PCP Independent predictors
a. **Oral thrush
b. Exertional dyspnea
c. **Interstitial infiltrate (starts in alv and extends into interstitial inflamed)
2. PCP Combination of variables
exertional dypsnea + **interstitial infiltrate
3. bacterial pneumonia
a. Fever <7 d
b. Toxic appearance (OR, 9.1)
c. Rhonchi
d. Lobar infiltrate
4. bacterial pneumonia
**Lobar infiltrate + fever <7 d

Front 24

Pathology/histology

Back 24

1. slide 127: Can’t culture this in a sputum; must resort to Induced sputum (hypoertonic saline solution), need silver stain
2. slide 128: foamy honeycomb material; seen in alveolar spaces in Pneumocystis pneumonia

Front 25

Tx

Back 25

High dose bactrim (primer)
TMP - SMX

Front 26

Case 8
A 65-year-old male with diabetes mellitus is admitted to the hospital with severe left lower lobar pneumonia. He is empirically started on moxifloxacin. Sputum and blood cultures are negative. After 5 days, fever persists and the patient reports worsening dyspnea and left sided chest pain which intensifies with inspiration. Lung exam reveals decreased breath sounds, flat percussion at left lower lung fields and hyperresonant at left upper lung fields. Repeat chest radiograph is obtained (see image).

Back 26

key findings
1. diabetes mellitus
2. severe left lower lobar pneumonia
3. empirically started on moxifloxacin
4. 5 days, fever persists and the patient reports worsening dyspnea and left sided chest pain which intensifies with inspiration
5. ***decreased breath sounds, flat percussion (large PE) at left LOWER lung fields and hyper resonant (emphysema, pneumothorax) at left UPPER lung fields
*Moxi if appropriate
Non-responder to TX; even getting worse with complications of (1) pneumo and (2) abscess or (3) pleaural effusion related to pneumo, not free flowing/inflam; Blood culture neg is okay

Front 27

CXR, Thoracentesis, gram stain (slide 131), CT (slide 132)

Back 27

1. X ray show pleural effusion on the left
2. thoracenthesis: performed under ultrasound guidance. Pleural fluid reveals pH 7.1, LDH 1,000 U/L, and glucose 30 mg/dL. (low pH, hi LDH, low glucose)
3. Gram stain; Purple, GP diplococci, S pneumoccocus, EMPYEMA
4. CT: Less dense region on CT scan; Empyema, following pneumonia,

Front 28

TX

Back 28

Why complicate on TX? Besides drug resistance
1. DM, have a hard time fighting bacteria; hyperglycemia (acute infection) lead to neutrophil dysfunction
2. Bug can persist anyway, if there was subpleural involvement already, this could happen
3. No longer just an Antibiotic problem, Antibiotic cannot get to the bug well with empyema
4. THUS: Drain it, catheter in it, clear out the pleaural space to cure it

Front 29

Case9
A 70-year-old male with known heavy alcohol abuse is brought by EMS to the ED with obtundation and hypothermia. The police said they found him unconscious on the sidewalk. On physical exam, temperature is 34°C; he has severe gingivitis, several loose teeth, extensive dental caries, and foul-smelling breath. The right lower lung field has dullness to percussion, amphoric breath sounds, rales, and whispered pectoriloquy. WBC count is 22, 000/mm3. Chest radiograph is shown (see image). Sputum Gram stain shows many neutrophils and a mixture of Gram-positive cocci, Gram-positive rods, and Gram-negative rods. Sputum culture grows “normal mouth flora.” He has no known drug allergies.

Back 29

key findings (community‐acquired aspiration pneumonia)
1. heavy alcohol abuse
2. obtundation and hypothermia, found unconscious
3.*** severe gingivitis, several loose teeth, extensive dental caries, and foul-smelling breath
4. right lower lung field has dullness to percussion, amphoric breath sounds, rales, and whispered pectoriloquy
5.*** WBC count is 22, 000/mm3
6.***Sputum Gram stain shows many neutrophils and a mixture of Gram-positive cocci, Gram-positive rods, and Gram-negative rods

Front 30

CXR (slide 135)

Back 30

1. RLL (key finding 4)
2. Why not RML? right heart border visible
3. Horizontal line, air fluid level (both existing in a hole) – area necrosed, abscess

Front 31

Gram stain (slide 136)

Back 31

1. presence of mixed flora, without significant growth of pathogens on routine culture, may suggest anaerobic involvement
2. In "community‐acquired aspiration pneumonia" and lung abscesses, anaerobic oral flora. etc predominates.
3. In hospitalized patients, nosocomial pathogens, such as enteric gram‐negative bacilli, Pseudomonas, and Staphylococcus aureus, may also be involved.

Front 32

CT (slide 137)

Back 32

patient with an anaerobic lung abscess showing two contiguous thick-walled cavitary lesions in the right lower lobe RLL with "air-fluid" levels.

Front 33

Necrotizing pneumonia cavity form (slide 138)

Back 33

TANKS
TB, Anaerobes, Nocardia, Klebsiella, S. Aureus
figures (clockwise)
TB, klebsiella, S aureus, nocardia

Front 34

Pathology (slide 139)

Back 34

1. (left): Confluent anaerobic necrotizing bronchopneumonia with lung abscess; “pulmonary gangrene” and is often associated with empyema. Patients are usually toxic appearing, with putrid sputum.
2. (right): The upper lobe of the lung is diffusely consolidated by intra-alveolar acute inflammatory exudate; 2.5 cm abscess
a. A lung abscess: cavitary lesion resulting from tissue necrosis accompanied by acute suppurative inflammation.
b. Abscess formation in lobar pneumonia; more with Klebsiella pneumonia > pneumococcus

Front 35

Pathology (slide 140)

Back 35

1. (left): upper lobe; extensive diffuse consolidation typical of lobar pneumonia; abscess (definition on prev slide).
2. Upper lobe lobar necrotizing pneumonia with abscess formation: characteristic feature of Klebsiella infection
3. (right): The abscess cavity might be filled with suppurative debris.

If there is communication with an air passage, the contained exudate may be partially drained to create an air-containing cavity.

Superimposed saprophytic infections are prone to flourishing within the already necrotic debris of the abscess cavity. Continued infection leads to large, fetid, green-black, multilocular cavities with poor demarcation of their margins, designated gangrene of the lung. The cardinal histologic change in all abscesses is suppurative destruction of the lung parenchyma within the central area of cavitation (Fig. 15-35). In chronic cases considerable fibroblastic proliferation produces a fibrous wall.

Front 36

TX (primer, look up klemsiella TX)

Back 36

1. Clindamycin
2. Think of pneumocccus (unlikely to cavitate and cause lungs abscess)
3. Mixed anaerobe from mouth
4. Pseudomona not from mouth
5. Erbapanem, pip tezom, mitranidozole

Q is besides RX – (like drainage of empyema) what else is good? How to drain the abscess? Close space infection.
What to do? Could there be complicated puenmo
Start on RX, CT scan, bronchoscopy (look at it to make sure theres noobstruction (cancer or anything else), check for pus because location of pus is where is drained, postural drainage, endo bronchia route, not a needle through chest