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An Unusual Case of Pneumonia
1. AIDS CLINICAL ROUNDS
The UC San Diego AntiViral Research Center sponsors weekly
presentations by infectious disease clinicians, physicians and
researchers. The goal of these presentations is to provide the most
current research, clinical practices and trends in HIV, HBV, HCV, TB
and other infectious diseases of global significance.
The slides from the AIDS Clinical Rounds presentation that you are
about to view are intended for the educational purposes of our
audience. They may not be used for other purposes without the
presenterβs express permission.
2.
3. ο 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
ο Cough p/o green and black sputum; occ hemoptysis
ο Pleuritic CP
ο Dyspnea
ο F/C/NS
ο All sx similar to admissions in 4/09 and 1/11
ο Bronch β silver stain negative, AFB negative. MTD PCR negative
ο Quantiferon, Crag, cocci, & histo negative
ο Responded as if CAP
4. ο Teeth have been falling out for the past 3 mo
ο + weight loss β d/t poor dentition & anorexia
ο ROS: Poor historian
ο No HA or photophobia
ο Vision is βfairβ
ο No odynophagia
ο No N/V/D
ο +Abd pain
ο Poor memory β fell out of care b/c he couldnβt remember to
make appointments
6. ο Meds: ARVs β canβt remember names β hasnβt been taking
them
ο SHx:
ο Tob: 1PPD
ο Drugs: smokes meth β last used ~ 2 weeks ago
ο No etoh
ο Not currently sexually active
ο Lives in Rosarito with his mom and step-father
7. 103 116 99/60 28 93% RA
ο Cachetic
ο Horrible dentition; white plaques c/w candida
ο Coarse rhonchi heard throughout with ? Of rales at the L
base
ο No supraclavicular or axillary LAD
ο Tachy but no M
ο Soft, NT, ND, NABS; no HSM
ο No rash
8. Labs
ο WBC 7.1 S86 B11 L1
ο H/H = 9.9/29.4 MCV = 84
ο Plt = 217
ο NA 129; K 3.4 BUN 7; Cr 0.59 AG = 5
ο Alb = 2.6 SGOT/SGPT = 148/60
ο LDH = 232
ο 7.52/29/122 on RA
10. Hosp Course
ο Started on Vanc/Zosyn, TMP/SMP
ο Fluconazole 100mg for thrush
ο Admitted to resp isolation
ο Crag, Cocci, urine histo sent
ο Of note, all previously negative 4/09 and 1/11;
ο CSF Crag negative 6/09
11. Chest CT
ο Multifocal consolidation predominantly in the upper lobes &
LLL.
ο There are multiple areas of cavitation within the consolidation.
The LUL consolidation may invade the anterior chest wall.
ο There are multiple micronodules, some with tree-in-bud
configuration
ο Background of moderate centrilobular emphysema
ο L pleural effusion
ο Multiple enlarged mediastinal and hilar lymph nodes
16. Cavitary Lung Disease in HIV+ pts
ο 3 studies β Spain, USA, Taiwan
ο Cavity definition: a gas containing space within the lung
surrounded by a wall of at least 1mm & >1cm
ο Pts with bacterial causes had higher CD4 counts
ο Pts with nonbacterial causes had lower CD4 counts
ο Mycobacteria accounted for 25-30% of the disease at all
sites
ο No malignancies identified
17. Cavitary Lung disease in HIV+:
Spain 1998
ο 78 cases of cavitation in 73 pts with HIV admitted from
1/89-12/94
ο 31 pts with unilobar cavity; 47 with multilobar
ο Multiple cavities in 40 cases and solitary in 38
ο 7 cases (9%) d/t endocarditis
ο 93% of pts were IDUs
ο Median CD4 = 30 (10-560)
19. Cavitary Lung Disease in HIV+ pts
USA β01
ο Miami
ο Reviewed chest CTs April β96 β March β98
ο 25 patients
ο 20 with definitive diagnoses
ο Median CD4 = 106 (2-934)
ο No comment on HIV risk factor
21. Cavitary Lung Dis in HIV+ pts
Taiwan β09
ο Time Period June β94 β March β08
ο Open Cohort study
ο 66 pts with 73 episodes of cavitary lung disease out of 1790
pts (3.7%)
ο Median CD4 = 25 (1-575)
ο 95% had AIDS
ο 10% IDUs
ο 70% naΓ―ve to ARVs
ο 1 case possibly d/t IRIS
28. Dx of invasive fungal infections
ο Proven: fungal elements detected by histological analysis
or culture of tissue from diseased tissue
ο Probable - host factor & clinical criterion & mycological
criterion
ο Possible - host factor & clinical criterion but no
mycological criteria
29. Dx of invasive fungal infections
ο Probable and possible depend on 3 criteria:
ο Host factors
ο Immunosuppression
ο Clinical manifestations
ο Findings on imaging +/- exam findings
ο Mycological evidence
ο Direct test (cytology, direct microscopy or culture)
ο Indirect test (detection of antigen or cell wall constituents)
ο Aspergillus Galactomannan (GM) in blood, BAL or CSF
ο Ξ²-D-glucan in serum for diseases other than crypto or zygomycosis
30. Galactomannan
ο Galactomannan (GM) is a fungal antigen produced by
Aspergillus during its growth
ο GM is a validated criterion for the diagnosis of probable
invasive aspergillosis in immunocompromised pts
ο Several studies have demonstrated false + serum GM in
pts on pip/tazo in β03-β04
ο Pip/tazo itself has GM in it
ο 1 study demonstrated false + GM in both serum and BAL
31. False + GM in serum & BAL
ο Intubated pts who did not meet diagnostic criteria for IA
(proven, probable or possible)
ο 73 pts on at least 1 abx for at least 3 days
ο 14 pts not on abx
ο False + GM in serum:
ο Pip/Tazo, AMP/CLA
ο Cefipime, cefoperazone/sulbactam
ο False + GM in BAL:
ο Pip/tazo, AMP/CLA
ο Ceftriaxone & cefipime
32. Really a false +?
ο Pip/tazo seems to be no longer responsible for false-positive
results in Journal of Antimicrobial Chemotherapy, 4/12
ο 10/09-10/10
ο Pip/tazo manufactured by Pfizer
ο Tested serum from HSCT pts both off & on pip/tazo
ο 25/1606 (1.6%) drawn in the absence of pip/tazo tested +
ο 10/394 (2.5%) while on pip/tazo tested +
ο 90 vials from 30 randomly selected batches tested negative
ο UCSD uses pip/tazo manufactured by Baxter for Wyeth
ο Studies suggest repeating test at least 5 days after last dose
33. (1-3) Ξ²-D-glucan
ο A major component of the cell wall of most fungal species
except cryptococcus and zygomycetes
ο Levels are elevated in blood with systemic infections
ο Consistently negative levels in pts with mucosal
candidiasis but no systemic disease
ο Sensitive marker of PCP
ο More sensitive than GM in pts with invasive aspergillosis
34. Ξ²-D-glucan: False Positives
ο Hemodialysis β cellulose membranes contain BG
ο IVIG, albumin or other commercial blood components
ο BG is released from cellulose filters used during the
manufacturing process
ο Gauze used intraoperatively (see false + in the first 3 days
after surgery)
ο Antibiotics:
ο Pip/tazo
ο Cefazolin, SMP/TMZ, cefotaxime, cefepime, amp/sul β all + at
reconstituted vial concentrations but not when diluted to usual
plasma concentrations
35. Transbronchial biopsy
ο Path
ο No Atypical or Malignant cells
ο Respiratory mucosa and alveolar tissue with acute and
chronic inflammation, edema, and fibrosis, see comment
38. Cryptococcus & GM
ο Glucuronoxylomannan in crypto
ο 90% of capsular mass
ο Governs serotype
ο Prominent virulence factor
ο Galactoxylomannan β the OTHER polysaccharide
ο 7% of the capsular mass
ο Galactoxylomannan cross reacts with GM assays
39. GM in pts with Crypto &
Penicillium marneffei
ο Tested serum samples from 48 HIV+ pts for GM
ο 15 with penicilliosis β 73% had OD >0.5
ο 22 with crypto β 14% had OD >0.5
ο 11 w/o fungal infection β 9% had OD >0.5
ο No pts with aspergillus or on PIP/tazo or amox/clav
ο GM strongly + for penicilliosis pts
ο OD range 0.16 - >20, median = 4.4
ο + for crypto
ο OD range 0.11-3.8; median 0.25
40. Hosp course contβd
ο Serum Crag negative on 6/3 and 6/12
ο CSF Crag negative
ο Serum GM negative 6 days after last dose of pip/tazo
ο Treated with fluconazole 400mg bid
ο Treated with vanc for 6-8 weeks
ο Lung biopsy by IR non-diagnostic; cx negative
ο TEE negative
42. Serum Crag
ο Latex particles covered with anti-cryptococcal globulin
ο Latex reacts with the antigen, causing visible
agglutination
ο 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 +)
ο False negative rarely reported (none since β96)
ο False + with trichosporonosis
43. Serum Crag
ο Sensitivity ranges from 83-97% in pts with cx+ disease
ο Sensitivity = 82% in pulmonary disease
ο Specificity ranges from 93-100%
ο Animal studies:
ο Low titers or negative titers in pulmonary infection that has
not disseminated
ο High titers seen in mice with pulmonary infection that has
disseminated
ο Intratracheal administration of crypto did not result in
measurable levels
44. Pulmonary Cryptococcosis
ο 25-55% of cryptococcal meningitis has pulm involvement
ο Clinical manifestations:
ο Asymptomatic colonization to severe pneumonia/resp failure
ο Typically:
ο Cough, dyspnea, hemoptysis, chest pain
ο Fever, weight loss, night sweats
ο Onset:
ο Weeks to months in immunocompetent
ο Subacute to rapidly progressive in immunocompromised
46. Crypto: Radiography - AIDS
ο Diffuse interstitial infiltrates
ο Ground glass opacities
ο Lobar, often mass-like infiltrates
ο Pulmonary nodules; diffuse reticulonodular opacities
ο Mediastinal and hilar lymphadenopathy
ο Cavitation in only 10-15% of cases
ο Infiltrates or effusion often assβd with disseminated
disease
47. After the fact
ο Ξ²-D glucan + at 88pg/ml (drawn 8 days after last dose of
Pip/tazo)
ο 6/09 Crag 1:4 at San Ysidro
ο CSF negative with nl chemistries & cell counts
ο 7/09 treated with flucon 800mg qday
ο 8/09 Crag 1:8; flucon decreased to 400mg qday
ο Notes after that say Crag negative