An Unusual Case of Pneumonia
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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 presenter’s express permission.
AIDS CLINICAL ROUNDS
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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
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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
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PMHx: AIDS
PCP
Hepatitis C
Neurosyphilis
Thrombocytopenia – ITP vs myelosuppression d/t etoh
Pancytopenia
BMbx 4/09 unremarkable
Alcohol abuse
Meth abuse
Non-compliance
NKDA
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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
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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
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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
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CXR
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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
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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
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Chest CT
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Ddx?
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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
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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)
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Cavitary Lung Dis in HIV+ pts Spain ‘98
Pathogens:
Fungi – 15 cases (19%)
PCP (11), Crypto (2), Aspergillus (2)
Bacteria – 33 cases (42%)
Staph (14), Pseudomonas (13), Rohodococcus (6), anaerobes (5)
Salmonella (3), Strep pneumo (2), Strep milleri (1)
Mycobacteria 23 cases (30%)
TB (22), M. kansasii (1)
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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
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Cavitary Lung Disease in HIV+ Pts USA ‘01
Pathogens:
Fungi - 4 cases (16%)
Candida (2), Aspergillus (1), PCP (1)
Bacteria – 17 cases (68%)
Staph Aureus (5), Pseudomonas (5), Klebsiella (4), Nocardia (3),
Enterobacter (2), E. Coli (2), Rhodococcus (1)
Mycobacteria – 8 cases (32%)
TB (4), MAI (3), M. kansasii (1), M. fortuitum (1)
Viruses – 3 cases (12%)
CMV
Polymicrobial in 17 pts (85%)
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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
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Cavitary Lung Dis in HIV+ pts Taiwan ‘09
81(!) pathogens found
Fungi - 34 cases (42%)
Penicillium marneffei (19), Cryptococcus neoformans (11)
PCP (2), Aspergillus (2)
Bacteria - 24 cases (30%)
SA (7), Rhodococcus (6), Pseudomonas (4)
Strep Pneumo (3), Klebsiella (2), Nocardia (1)
Mycobacteria - 21 cases (26%)
TB (11), MAC (9), kansasii (1)
CMV 2%
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Cavitary Lung Dis in HIV+ pts Taiwan ‘09
15% were polymicrobial
Penicillium + PCP
Pseudomonas + MAC
Pseudomonas + PCP
Propensity to cavitate by bug
11/205 (5.4%) of TB
19/36 (53%) of P. marneffi
11/64 (17%) of crypto
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Updated Labs/Course AFB smear negative x 3
Modified AFB negative
Crag, Cocci, histo negative
Quantiferon negative
Sputum growing MRSA
Blood cultures negative
TTE: normal valves; no e/o vegetation
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Maintained on vanc (pip/tazo d/c’d after 3 days)
Cough and SOB improve significantly
Defervesces w/in 24 hours
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MRSA Pneumonia Risk Factors
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Bronch Procedure unremarkable
BAL cultures:
Heavy MRSA
AFB smears/culture negative
Cytology negative for PCP
CMV Shell Vial culture negative
Aspergillus Galactomannan +
Start vori?
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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
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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
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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
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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
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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
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(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
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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
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Transbronchial biopsy Path
No Atypical or Malignant cells
Respiratory mucosa and alveolar tissue with acute and chronic inflammation, edema, and fibrosis, see comment
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Comment
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Comment
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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
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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
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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
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Post CXR
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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
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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
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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
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Crypto Radiography: Non-AIDS
Solitary or multiple pulmonary nodules – 60-80%
Size varies
Appearance varies: smooth to spiculated
Peripheral predominance
Focal or multifocal consolidation - 10-30%
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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
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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
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The End