An Unusual Case of Pneumonia

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AIDS CLINICAL ROUNDS

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

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

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

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

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

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

CXR

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

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

Chest CT

Ddx?

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

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)

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)

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

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%)

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

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%

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

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

Maintained on vanc (pip/tazo d/c’d after 3 days)

Cough and SOB improve significantly

Defervesces w/in 24 hours

MRSA Pneumonia Risk Factors

Bronch Procedure unremarkable

BAL cultures:

Heavy MRSA

AFB smears/culture negative

Cytology negative for PCP

CMV Shell Vial culture negative

Aspergillus Galactomannan +

Start vori?

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

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

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

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

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

(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

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

Transbronchial biopsy Path

No Atypical or Malignant cells

Respiratory mucosa and alveolar tissue with acute and chronic inflammation, edema, and fibrosis, see comment

Comment

Comment

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

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

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

Post CXR

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

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

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

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%

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

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

The End