Transcript Clinical Grand Rounds

Clinical Grand Rounds
Allison Liddell, MD
March 10th, 2004
Case Presentation
51 yo WM w/widely metastatic
esophageal CA to lung, abdomen and
brain
 Admit 12/7/03 SOB, cough productive
of yellow sputum for 1 week
 No fever, rash, palpable nodes,
neurologic symptoms
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Case Presentation
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PMH
– Esoph CA dx July 2002; s/p radiation/XRT, then
taxol/carboplatin stopped in October ’03 due to
progression of disease. Isolated brain met
resected 3/03.
– CCK, appy, MVA w/ankle fracture requiring
hardware and bilateral THR
– FH multiple malignancies
– Remote smoker, occasional ETOH, mechanic,
married with adult children, lives in Mabank
Case Presentation
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Medications:
– Dexamethasone
– Vicodin
– Ativan
– Ambien
– Tessalon
– Advair
– Combivent
Case Presentation
PE notable for Cushingoid faces, no
fever, BP 113/80, P 100, O2 saturation
is 92% on 2L/min NC, bilateral crackles
with dullness in bases
 CXR bilateral lower lobe infiltrates
 Chest CT dense lingular infiltrate, new
cavitary lesion, new bilateral cavitary
lesions
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Case Presentation
Initial Rx cefepime
 Discharged on levaquin plus Bactrim for
PCP prophylaxis
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Case Presentation
12/18 (day 8) Sputum growing Gram +
beaded filamentous bacterium-Bactrim
increased
 Readmit 12/20 with continued cough,
SOB, marked malaise and N/V
 CXR increased bibasilar infiltrates
 Chest CT “increasing pulmonary
infiltrates and pulmonary nodules,
particularly in the left lung”
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Case Presentation
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Rx High dose iv Bactrim and ceftriaxone
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Continued severe N/V directly attributed to
infusion of iv Bactrim
Changed Bactrim to amikacin
Discharged to complete initial 4 weeks iv dual
therapy while awaiting susceptibilities of
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Nocardia asteroides complex
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12/21 sputum had few branching G variable
rods on Gram stain
Nocardia
epidemiology
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Aerobic bacteriaactinomycetales
order
ubiquitous, soilborne
500-1000 cases/yr
in U.S. (1976)
IDU asso. in HIV
Pulmonary entry
most common
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often opportunistic
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solid organ recipients
AIDS
BMT
pulmonary disease
corticosteroid
therapy
– many others
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association with
invasive fungal
infection
Nocardia
taxonomy
N. brasiliensis
 N. otitidiscaviarum (T/S resis)
 N. transvalensis
 N. asteroides complex
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– N. asteroides sensu stricto
– N. farcinica (virulent)
– N. nova
Nocardia
Microbiology
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Variably acidfast
Gram positive
filamentous
beading
grow in 2-4
weeks
Nocardia
pathogenesis
Facultative intracellular pathogens
 Complex cell wall glycolipids protect
against oxidative burst
 Inhibits phagocyte functions
 predilection for CNS
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Nocardiosis
Clinical presentation
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Fever
productive cough
weight loss
dyspnea
pleuritic chest pain
hemoptysis
soft tissue masses
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Lymphadenopathy
cutaneous ulceration
neurologic deficits
NO pathognomonic
clinical feature,
radiographic feature
or lab result
Uttamchandani et al CID
1994;18 (HIV)
Pulmonary nocardiosis
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Acute, subacute or chronic
Pneumonia, abscess, empyema (25%)
Variable nonspecific symptoms
Radiographic findings widely variable-alveolar,
interstitial, cavitary
Path: mixed cellular response, sometimes
granulomas +/- necrosis
Other- sinusitis, tracheitis, bronchitis,
pleuropulmonary fistula, mediastinitis
Figure 244-2 Chest radiograph (A) and computed
tomography scan (B) from a heavily immunosuppressed
patient with systemic lupus erythematosus, demonstrating
multiple pulmonary abscesses due to Nocardia farcinica.
Skin/Soft tissue nocardiosis
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Cutaneous/subcut nodules after trauma or
due to hematogenous spread.
Cellulitis
abscesses
paronychia
sporotrichoid form
Keratitis/endophthalmitis
Wound infections (outbreak post-transplant
Germany)
N. brasiliensis
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Responsible for most progressive or invasive
skin infections
Southern US
Invasive disease
– ?new taxon based on different antimicrobial
susceptibility
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Mycetoma
– Chronic, destructive infection of skin, subQ, fascia,
bone, muscle after local trauma
– Suppurative granulomas and sinus tracts
– Eumycetoma (fungi) or aerobic actinomycetes
(Nocardia, Actinomadura, Streptomyces)
Figure 82-2 A, Nocardia actinomycetoma of the foot. B, Hemisection
of the foot showing advanced destruction of the bones. (Courtesy of
the Armed Forces Institute of Pathology, Photograph Neg. No. N77646.)
Systemic Nocardiosis
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Primary pulmonary focus may resolve
Progressive lesions
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CNS
Skin/subQ
Eyes
Kidneys
Joints
Bones
Heart
CNS Nocardiosis
45% of systemic cases involve CNS
 1/3 of all cases involve CNS
 Highly variable presentation
 Mimic tumor, brain abscess
 Rarely meningitis (usually w/abscess),
spinal involvement, diffuse involvement
 All pulm/dissem Nocardiosis patients
should have MRI
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Case Presentation
Marked initial improvement in
cough/sputum
 N/V resolved with discontinuation of
Bactrim
 Continued pain, edema, anorexia
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Case Presentation
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Kirby-Bauer
– Susc: amikacin, cefotaxime, ceftriaxone,
gentamicin, imipenem, sulfisoxazole, tobramycin
– Intermed: Augmentin, doxycycline, minocycline
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Microdilution MIC
– Susc:amikacin, ceftriaxone, imipenem, linezolid,
meropenem, sulfamethoxazole, tobramycin
– Intermed: cefotaxime, Augmentin, gatifloxacin,
minocycline
– Resis: ciprofloxacin, clarithromycin
Nocardiosis
Treatment
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Sulfonamides
– nova susc to ECN
and cephs, but not
Augmentin
– Trim/Sulfa 5-15mg/kg/d
– Sulfisoxazole
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species matters
– asteroides highly susc to
T/S
– transvalensis higher
amikacin and T/S
resistance
– farcinica highly
resistant, esp to cephs
– ot-cav resis to T/S
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Clinical data
supports sulfas are
superior
Experimental models
– Carbapenems
superior
– Combinations
superior to single
agent
Treatment
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NO controlled trials
Most would begin
with 2 drugs for
severe disease while
awaiting ID/susc
Duration at least 3
months, usually 612 months in normal
At least 12 months
in immunosupp
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Duration of iv
therapy before oral
is judgement call
surgery in some
cases
Bactrim intolerance
in at least 50%
– hypersensitivity,
gastrointestinal
toxicity, or
myelotoxicity
Treatment
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Bactrim is mainstay
For severe disease,
combination
– T/S
– Imipenem
– Amikacin (synergy)
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after 3-6 weeks
change to oral
therapy
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IV alternatives
– cephalosporins
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Oral alternatives
– minocin (low
therapeutic index)
– Augmentin (low
therapeutic index)
– clarithromycin (nova)
– flouroquinolones
Linezolid
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Oxazolidinone
Useful for MRSA, VRE
Dose 600mg po BID
100% oral bioavailability
Excellent CNS penetration
MOA interferes with translation by binding
50S ribosome
Main toxicities GI and thrombocytopenia
Kaplan. Pediatric Infectious Disease Journal
Volume 22 • Number 9 • September 2003
Linezolid
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In vitro data confirms linezolid effective for
multiple strains (AAC 2001:45)
Case reports (Wallace et al CID 2003:36)
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6 cases (3 asteroides, 2 otit., 1 brasil.)
CGD (2), chronic steroids (2)
Ages 6-63
4 dissem, 1 pneumonia, 1 soft tissue
Bactrim intolerant, resistance
5 cures, 1 recurrence then cure with T/S
Anemia, peripheral neuropathy, lactic acidosis
Linezolid
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Limitations:
– Lack of data for long-term safety
– Cost ($35,000 for 12 months)
Nocardiosis
prevention
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Prophylaxis
– primary-some
recommend posttransplant if >3%
incidence
– secondary-if remains
on steroids, HIV,
prolonged
immunosuppression
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Bactrim DS daily
(TIW not effective)
References:
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Lerner PI. Nocardiosis. CID 1996;22:891-905
Moylett et al. Clinical Experience with Linezolid for
the Treatment of Nocardia Infection. CID
2003;36:313-8
Uttamchandani et al. Nocardiosis in 30 Patients with
Advanced Human Immunodeficiency Virus Infection.
CID 1994;18:339-47
Choucino et al. Nocardiosis in Bone Marrow
Transplant Recipients. CID 1996;23:101209
Multi-system Infection with Nocardia farcinica—
Therapy with Linezolid and Minocycline. The Journal
of Infection 2003;46(3):199-202