Pulmonary Infiltrates in Immunocompromised Px

Morning Report
Ryan Dunn
Dr. David Pitrak
21-Oct-2011
PLEASE SWIPE!!

A 25-year 25 year-old old pregnant woman at 25 weeks’ weeks
gestation undergoes a new-patient new patient evaluation. She
has recently diagnosed HIV infection and has
never taken antiretroviral therapy. Her current
CD4 cell count is 550/µL, 550/ L, and her HIV RNA viral
load is 20,000 copies/mL copies/ mL. . She takes no
medications except for a daily prenatal vitamin.
Physical examination, including vital signs, is
normal.

1.
2.
3.
4.
MKSAP
Which of the following is the most appropriate
management of this patient?
Initiate antiretroviral therapy when CD4 cell
count is

Please make your selection...
1.
2.
3.
4.
Initiate antiretroviral
therapy when CD4 cell
count is

MKSAP
This patient should receive immediate therapy
with zidovudine, zidovudine,
lamivudine, and lopinavir-
ritonavir. ritonavir.
Antiretroviral therapy is recommended
in all pregnant women with HIV infection,
regardless of virologic, virologic,
immunologic, or clinical
parameters, to prevent mother-to mother to-child child
transmission. Therefore, initiating antiretroviral
treatment at delivery or when the CD4 cell count
drops below 500/µL 500/ L is not appropriate.

MKSAP
The treatment principles used in management of
nonpregnant
adults with HIV infection also apply
to pregnant women with HIV infection; however,
the benefits versus the risks to the woman, fetus,
and infant must be weighed. Some agents are
harmful to the mother or the fetus and must be
avoided during pregnancy. Early fetal exposure to
efavirenz-containing efavirenz containing regimens has been reported
to cause neural tube defects. Efavirenz
is the only
antiretroviral agent listed as a U.S. Food and Drug
Administration pregnancy risk category D drug.

47 year old female presents with nausea and
vomiting from clinic

Pertinent positives
Five days of nausea and vomiting 2-3 times a day
one day of loose stools
Complains of some mild fatigue during that time
Has had a low-grade, mild non-productive cough for last few days
Pertinent negatives
No shortness of breath, no fevers/chills, no other URI symptoms
besides a mild non-productive cough, No abdominal pain,
No abdominal pain, No diarrhea. No dysuria or flank pain
No myalgias or rash, no neck stiffness or photophobia
No recent antibiotic exposure

Past medical hx –
Autoimmune myelofibrosis
Type 2 DM
HL
Psoriasis
PSH - NC
Allergies –NC
Family Hx -NC
Social Hx – On disability. Married with 2 children. No drugs,
smoking or ETOH abuse. No pets or recent travel.
Medications: Campath (for > 6 months), Famiciclovir,
Esomeprazole, Simvastatin

Vitals –37.3, 122, 123/74, 16, Sp02 – 97% RA
General – Frail African american female NAD
HEENT –Oropharynx mildly erythemtous w/o exudate. No
cervical adenopathy, nasopharynx clear. No sinus
tenderness
CV – Tachycardic. Soft murmur but no S3/S4, neck veins
flat.
Pulm – Non-labored. Soft crackles noted over mid-lung
fields bilaterally. No rhonchi/or wheezes.
Abd – Soft, NT. Obese. No hepatosplenomegaly on exam.
+bs.
MSK – No edema. Warm. 2+LE pulses. Brisk cap refill
Neuro – Ax0 x3. No focal deficits. CN2-12 intact. No
meningismus

8.3
131 94
4.2 22
13
Labs
UA – Dark yellow, 3+blood, 2+protein, (+) leuk est, est,
(-) ( ) nitrite, WBC 10-20, 10 20, Few bacteria
Blood cultures and urine cultures pending
C.Diff PCR – Pending
20
0.9
150
115
PMN: 95%
Lymp: 1%
Ca 10.6
Anything make you more concerned for this patient?
40.1 13.5
1.3
8.1
0.5 0.3/0.2
25 33
47
3.9

Differential?

Infectious (up to 50-75% of pts
in some studies*)
Bacteria (pneumococcus, s.aureus,
gram negatives, Nocardia)
Fungal (aspergillus, mucor, candida,
cryptococcus, pneumocystis jiroveci,
endemic fungi)
Viral (HSV, CMV, RSV, influenza,
HMPV)
Mycobacterial (MAI or TB)
*CHEST January 2004 vol. 125 no. 1 260-271
Non-infectious
Atypical pulmonary edema
Alveolar hemorrhage
COP/BOOP
PTLD
Engraftment syndrome
Drug toxicity
Extension of underlying malignancy –
solid tumors, lymphoma,
bronchoalveolar cancer
Iatrogenic – Medication toxicity

Conventional bacteria – 37%
Fungi – 14%
Viruses - 15%
Pneumocystis jirovcii – 8%
Nocardia - 7%
Mycobacterium tuberculosis –
Mixed infections – 20 %
1%
Highly dependent on population –
Neutropenia, HIV…..etc.
SOT, HSCT,

Immunodeficiency Predominant pulmonary
infection
Humoral
Phagocytic
Cell-mediated
Cell mediated
immunodeficiency
immunodeficiency Pyogenic
bacterial
pneumonia
cell deficiency Bacterial and fungal
pneumonias (esp ( esp
Aspergillus), Aspergillus),
candidemia
with pulmonary
involvement, cryptococcus
PCP PNA, legionella, legionella,
Nocardia, Nocardia,
CMV,
cryptococcus,
cryptococcus,
Mycobacterial
Clinical settings
Hypogammaglobulinemia,
Hypogammaglobulinemia,
CLL, Multimple
myeloma
Chemo-induced
Chemo induced
neutropenia, neutropenia,
AML
Lymphoma, ALL, high-dose high dose
steroids, Organ
transplantation, advanced
HIV (AIDS), Campath
therapy

Imaging?
Other tests?
Empiric coverage?

Lingular consolidation, two right upper lobe
nodules, trace left pleural effusion

•
•
•
Patient started on Vancomycin, Meropenem,
Valgancyclovir and Voriconazole
Sputum cultures sent, Sputum PCP assay,
Urinary strep pneumo Ag, Urinary Legionella
Ag and Urinary Histo Ag – Negative
Further tests?

Historically the reported yield as been
suggested to range from 15% - 93%
Role of Flexible Bronchoscopy, in Immunocompromised
Patients With Lung Infiltrates
Jain et al; CHEST February, 2004;

Etiology Final
diagnosis
Dx
by FB Dx
by SLB Clinical Dx
Infectious 47(36.7) 38(80.9) 4(8.5) 5(10.6)
Bacterial 23(18) 18(78.3) 1(4.3) 4(17.4)
Fungal 10(7.8) 8(80) 1(10) 1(10)
Viral 12(9.4) 10(83.3) 2(16.7)
PCP 2(1.5) 2(100)
DAH 19(14.8) 17(89.5) 2(10.5)
Other 86 27 17 40
Total 128 72(56.2) 17(13.3) 39(30.5)

Diagnostic yield of flexible bronchoscopy was
56% - Higher for infectious vs. non-infectious
causes [ (81%) vs. (40%)].
BAL and TBB (Transbronchial bx) yielded
similar diagnostic yields with the combination
being better than BAL alone.
BAL is best for bacterial and viral etiologies but
is less sensitive for fungal pathogens (only dx
40% of cases)
Protected-specimen brush (PSB) sampling did
not improved diagnostic yield.

Chest, 2002; Rano
et al.
Studied prognostic factors in Non-HIV IC hosts
with pulmonary infiltrates
Prospective, observational study with 200 pts
out of Spain.
Main goal: Investigate prognostic factors
related to mortality using a multiple logistic
regression model

Key findings – 3 variables were significantly
associated with mortality
1) APACHE score > 20 (OR 5.5)
2.) Need for Mechanical Ventilation (OR 28)
3.) Delay of > 5 days in establishing a specific
diagnosis (OR 3.4)
Remained true when adjusted for
patients “too sick” to undergo
bronchosopy in study

Pulmonary service consulted and
bronchoscopy with BAL performed
Gram stain – Oral flora
PCP assay – Negative
CMV PCR – Negative
AFB smear – Negative
Day 3 BAL culture
→

Aerobic, filamentous, branching gram positive rod found
world wide in soil frequently indistinguishable from
actinomyces on stain
Nine pathogenic strains of Nocardia sp responsible for
human disease
N. Asteroides complex (actually 5 strains of Nocardia) is most
common cause of systemic and pulmonic disease worldwide
> 60% of cases seen in patients with impaired host immunity
including (usually cell mediated): Lymphoma, HIV
(CD4

Pulmonary disease
Predominant clinical manifestation (40% of cases)
May manifest as endobronchial mass, pneumonia, empyema, lung abcess or
nodular, cavitary disease
Radiographically may appear as nodules (frequent cavitations), reticulonodular
or diffuse infiltrates
“Secondary cerebral localization and clinically silent destructive infection are
sufficiently common that cerebral imaging, preferably magnetic resonance
imaging (MRI), should be performed in all cases of pulmonary and disseminated
nocardiosis.”
ALWAYS IMAGE BRAIN FOR OCCULT DISSEMINATION!
Also beware of dissemination to other organs
Mandell: Principles and Practice
of Infectious Disease, 2009

Mandell: Principles and Practice of Infectious Disease

Primay cutaneous – Similar to staph/strep cutaneous
infections
Lymphocutaneous – “Sporotrichoid Nocardia” (i.e
Lymphangitis)
Cutaneous
involvment
from disseminated disease
Mycetoma – Chronic cutaneous infection typically found
on feet that may also be caused by fungi. Most commonly
caused by N. Brazilinsis

“Madura Foot”

Disseminated disease
Difficult to isolate in blood cultures because it is
fastidious organism
Insidious presentations are not uncommon with a
paucity of systemic or laboratory abnormalities
May be mistaken for malignancy
May also disseminate to other sites (bone, heart
valves, skin, kidneys, joints etc.)
Remember tropism for CNS ( up to 44% of cases)!

Diagnosis rests upon isolating the organism from
tissue or blood cultures
Nocardia sp are fastidious and usually take up 3-5 days
to isolate but may take longer – the microbiology lab
should be notified if Nocardia is suspected
The organism is weakly acid-fast

Lack of clinical trials makes optimal treatment unclear
Trimethroprim/Sulfamethaxazole is historically
backbone of therapy
There may be increasing rates of resistance to
TMP/SMX (as high 42% 6 )
Susceptibility testing should ALWAYS be peformed
Minor disease typically treated with TMP/SMX
Disseminated disease treated with TMP/SMX +
Amikacin or Beta-Lactam +Amikacin
Life threatening disease is treated with triple therapy

Switch to PO regimen at 3-6 weeks
Simple cutaneous
disease: 7-8 weeks
Pulmonary or disseminated disease w/o CNS
involvement: 6 months at least
CNS involvment: 12 months
Mandell: Prince and Practice
Infectious Disease 2009

Cutaneous
Pleuropulmonary
diseases: 100% cure rate
disease: 90% cure rate
Disseminated disease: 60% cure rate
Brain abcess: 50% cure rate
Arch Int Med 1983; 143:711-718

MOA: binds CD52 on lymphocytes and
leukemic cells in causes cell death in leukemic
cells
Uses: B-cell CLL and other
lymphoma/leukemias
Side effects: Causes severe lymphopenia in
97%. Also causes myelosuppression resulting
in other cytopenias less commonly
Patients CD4 counts should be monitored and
they should be provided with TMP/SMX
prophylaxis when below 200

Patient started on TMP/SMX and Imipenem
Speciation and susceptibility of Nocardia
pending.
Patients fever, cough and gastrointestinal
symptoms have resolved. Will follow up in ID
clinic for tailoring of antibiotic therapy.
sp

Recognize the differential for pulmonary infiltrates in
immunocompromised host and the importance of early
diagnosis
Recognized common manifestations of Nocardiosis
and basic management of the disease
Consider type of immunosuppression when
approaching and infected IC host
Campath (Alemtuzamab) causes severe lymphopenia
that should be monitored like AIDS/HIV