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An Unusual Case of Pneumonia
1. AIDS CLINICAL ROUNDS
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presentations by infectious disease clinicians, physicians and
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current research, clinical practices and trends in HIV, HBV, HCV, TB
and other infectious diseases of global significance.
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2.
3. DC is a 37yo with a h/o AIDS, (CD4= 6, VL = 527,104 1/11)
who presented with 1 mo h/o fever and cough
Cough p/o green and black sputum; occ hemoptysis
Pleuritic CP
Dyspnea
F/C/NS
All sx similar to admissions in 4/09 and 1/11
Bronch – silver stain negative, AFB negative. MTD PCR negative
Quantiferon, Crag, cocci, & histo negative
Responded as if CAP
4. Teeth have been falling out for the past 3 mo
+ weight loss – d/t poor dentition & anorexia
ROS: Poor historian
No HA or photophobia
Vision is “fair”
No odynophagia
No N/V/D
+Abd pain
Poor memory – fell out of care b/c he couldn’t remember to
make appointments
6. Meds: ARVs – can’t remember names – hasn’t been taking
them
SHx:
Tob: 1PPD
Drugs: smokes meth – last used ~ 2 weeks ago
No etoh
Not currently sexually active
Lives in Rosarito with his mom and step-father
7. 103 116 99/60 28 93% RA
Cachetic
Horrible dentition; white plaques c/w candida
Coarse rhonchi heard throughout with ? Of rales at the L
base
No supraclavicular or axillary LAD
Tachy but no M
Soft, NT, ND, NABS; no HSM
No rash
8. Labs
WBC 7.1 S86 B11 L1
H/H = 9.9/29.4 MCV = 84
Plt = 217
NA 129; K 3.4 BUN 7; Cr 0.59 AG = 5
Alb = 2.6 SGOT/SGPT = 148/60
LDH = 232
7.52/29/122 on RA
10. Hosp Course
Started on Vanc/Zosyn, TMP/SMP
Fluconazole 100mg for thrush
Admitted to resp isolation
Crag, Cocci, urine histo sent
Of note, all previously negative 4/09 and 1/11;
CSF Crag negative 6/09
11. Chest CT
Multifocal consolidation predominantly in the upper lobes &
LLL.
There are multiple areas of cavitation within the consolidation.
The LUL consolidation may invade the anterior chest wall.
There are multiple micronodules, some with tree-in-bud
configuration
Background of moderate centrilobular emphysema
L pleural effusion
Multiple enlarged mediastinal and hilar lymph nodes
16. Cavitary Lung Disease in HIV+ pts
3 studies – Spain, USA, Taiwan
Cavity definition: a gas containing space within the lung
surrounded by a wall of at least 1mm & >1cm
Pts with bacterial causes had higher CD4 counts
Pts with nonbacterial causes had lower CD4 counts
Mycobacteria accounted for 25-30% of the disease at all
sites
No malignancies identified
17. Cavitary Lung disease in HIV+:
Spain 1998
78 cases of cavitation in 73 pts with HIV admitted from
1/89-12/94
31 pts with unilobar cavity; 47 with multilobar
Multiple cavities in 40 cases and solitary in 38
7 cases (9%) d/t endocarditis
93% of pts were IDUs
Median CD4 = 30 (10-560)
19. Cavitary Lung Disease in HIV+ pts
USA ’01
Miami
Reviewed chest CTs April ‘96 – March ‘98
25 patients
20 with definitive diagnoses
Median CD4 = 106 (2-934)
No comment on HIV risk factor
21. Cavitary Lung Dis in HIV+ pts
Taiwan ‘09
Time Period June ‘94 – March ‘08
Open Cohort study
66 pts with 73 episodes of cavitary lung disease out of 1790
pts (3.7%)
Median CD4 = 25 (1-575)
95% had AIDS
10% IDUs
70% naïve to ARVs
1 case possibly d/t IRIS
28. Dx of invasive fungal infections
Proven: fungal elements detected by histological analysis
or culture of tissue from diseased tissue
Probable - host factor & clinical criterion & mycological
criterion
Possible - host factor & clinical criterion but no
mycological criteria
29. Dx of invasive fungal infections
Probable and possible depend on 3 criteria:
Host factors
Immunosuppression
Clinical manifestations
Findings on imaging +/- exam findings
Mycological evidence
Direct test (cytology, direct microscopy or culture)
Indirect test (detection of antigen or cell wall constituents)
Aspergillus Galactomannan (GM) in blood, BAL or CSF
β-D-glucan in serum for diseases other than crypto or zygomycosis
30. Galactomannan
Galactomannan (GM) is a fungal antigen produced by
Aspergillus during its growth
GM is a validated criterion for the diagnosis of probable
invasive aspergillosis in immunocompromised pts
Several studies have demonstrated false + serum GM in
pts on pip/tazo in ‘03-’04
Pip/tazo itself has GM in it
1 study demonstrated false + GM in both serum and BAL
31. False + GM in serum & BAL
Intubated pts who did not meet diagnostic criteria for IA
(proven, probable or possible)
73 pts on at least 1 abx for at least 3 days
14 pts not on abx
False + GM in serum:
Pip/Tazo, AMP/CLA
Cefipime, cefoperazone/sulbactam
False + GM in BAL:
Pip/tazo, AMP/CLA
Ceftriaxone & cefipime
32. Really a false +?
Pip/tazo seems to be no longer responsible for false-positive
results in Journal of Antimicrobial Chemotherapy, 4/12
10/09-10/10
Pip/tazo manufactured by Pfizer
Tested serum from HSCT pts both off & on pip/tazo
25/1606 (1.6%) drawn in the absence of pip/tazo tested +
10/394 (2.5%) while on pip/tazo tested +
90 vials from 30 randomly selected batches tested negative
UCSD uses pip/tazo manufactured by Baxter for Wyeth
Studies suggest repeating test at least 5 days after last dose
33. (1-3) β-D-glucan
A major component of the cell wall of most fungal species
except cryptococcus and zygomycetes
Levels are elevated in blood with systemic infections
Consistently negative levels in pts with mucosal
candidiasis but no systemic disease
Sensitive marker of PCP
More sensitive than GM in pts with invasive aspergillosis
34. β-D-glucan: False Positives
Hemodialysis – cellulose membranes contain BG
IVIG, albumin or other commercial blood components
BG is released from cellulose filters used during the
manufacturing process
Gauze used intraoperatively (see false + in the first 3 days
after surgery)
Antibiotics:
Pip/tazo
Cefazolin, SMP/TMZ, cefotaxime, cefepime, amp/sul – all + at
reconstituted vial concentrations but not when diluted to usual
plasma concentrations
35. Transbronchial biopsy
Path
No Atypical or Malignant cells
Respiratory mucosa and alveolar tissue with acute and
chronic inflammation, edema, and fibrosis, see comment
38. Cryptococcus & GM
Glucuronoxylomannan in crypto
90% of capsular mass
Governs serotype
Prominent virulence factor
Galactoxylomannan – the OTHER polysaccharide
7% of the capsular mass
Galactoxylomannan cross reacts with GM assays
39. GM in pts with Crypto &
Penicillium marneffei
Tested serum samples from 48 HIV+ pts for GM
15 with penicilliosis – 73% had OD >0.5
22 with crypto – 14% had OD >0.5
11 w/o fungal infection – 9% had OD >0.5
No pts with aspergillus or on PIP/tazo or amox/clav
GM strongly + for penicilliosis pts
OD range 0.16 - >20, median = 4.4
+ for crypto
OD range 0.11-3.8; median 0.25
40. Hosp course cont’d
Serum Crag negative on 6/3 and 6/12
CSF Crag negative
Serum GM negative 6 days after last dose of pip/tazo
Treated with fluconazole 400mg bid
Treated with vanc for 6-8 weeks
Lung biopsy by IR non-diagnostic; cx negative
TEE negative
42. Serum Crag
Latex particles covered with anti-cryptococcal globulin
Latex reacts with the antigen, causing visible
agglutination
Pronase, a proteolytic enzyme, reduces the number of
false + tests by eliminating nonspecific interference w/
globulins (such as RF and other immune complexes which
could cause false +)
False negative rarely reported (none since ‘96)
False + with trichosporonosis
43. Serum Crag
Sensitivity ranges from 83-97% in pts with cx+ disease
Sensitivity = 82% in pulmonary disease
Specificity ranges from 93-100%
Animal studies:
Low titers or negative titers in pulmonary infection that has
not disseminated
High titers seen in mice with pulmonary infection that has
disseminated
Intratracheal administration of crypto did not result in
measurable levels
44. Pulmonary Cryptococcosis
25-55% of cryptococcal meningitis has pulm involvement
Clinical manifestations:
Asymptomatic colonization to severe pneumonia/resp failure
Typically:
Cough, dyspnea, hemoptysis, chest pain
Fever, weight loss, night sweats
Onset:
Weeks to months in immunocompetent
Subacute to rapidly progressive in immunocompromised
46. Crypto: Radiography - AIDS
Diffuse interstitial infiltrates
Ground glass opacities
Lobar, often mass-like infiltrates
Pulmonary nodules; diffuse reticulonodular opacities
Mediastinal and hilar lymphadenopathy
Cavitation in only 10-15% of cases
Infiltrates or effusion often ass’d with disseminated
disease
47. After the fact
β-D glucan + at 88pg/ml (drawn 8 days after last dose of
Pip/tazo)
6/09 Crag 1:4 at San Ysidro
CSF negative with nl chemistries & cell counts
7/09 treated with flucon 800mg qday
8/09 Crag 1:8; flucon decreased to 400mg qday
Notes after that say Crag negative