66 yr old man with cough and RUL infiltrate

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66 yr old man with cough and RUL infiltrate

• Anh Innes

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History

• 61 yo man presents with 1 week of cough
  productive of yellow sputum, SOB, N/V, fevers and
  chills.
• DOE for several weeks prior to admission.
• ROS weight loss 10 lbs over 6 months
  (intentional)
• Admitted to outside hospital, treated with
  clinda/levofloxacin without improvement.

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History, cont.

• PMH
• PPD
• ? TB
• CAD s/p NSTEMI
• PTSD
• Chronic LBP

• Meds
• ASA
• Doxycycline
• Cefuroxime

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History, cont.

• Social
• Served in Vietnam
• Denies travel to southwest US or central valley
• No current or prior tobacco, ETOH, IDU
• 2nd-hand smoke
• Former corrections officer

• Physical Exam
• 102 90 20 93/57 96 RA
• Neck small, shotty supraclavicular nodes b/l
• Lungs RUL mild wheezes, otherwise CTA
• Abd soft, NTND

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Data

• 12.7
• 22.1 475
• 36.1
• 14 segs/2 lymphs/5 eos
• Alb 2.2
• Alk phos 213
• AST 97
• ALT 102
• TB/DB 0.5/0.1

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Data Procedures

• Bronchoscopy
• Subtotal extrinsic compression of RUL posterior
  segment
• Scope unable to pass
• Mild edema of superior segment, RLL, otherwise
  WNL
• Normal left bronchial tree
• No endobronchial lesions noted

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Data, cont.

• Coccidioidal titers
• IgM (by qualitative immunodiffusion)
• IgG (complement fixation) equivocal
• 12 2
• 14 1
• 18 1
• 116 1
• 132 negative

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Coccidioidomycosis

• Dimorphic fungus, Coccidioides immitis, found in
  S. Arizona, central California, SW New Mexico,
  Texas
• Risks of infection
• 3 risk of exposure each year
• Seasonal rainy followed by dry season
• Incubation period of 7-21 days prior to illness
• Wide spectrum of manifestations

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Coccidioidomycosis
Up to Date, 2003
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Coccidioidomycosis

• 50-66 subclinical
• Clinical manifestations valley fever
• 5-10 residual pulmonary sequelae
• Nodules
• Peripheral thin-walled cavities
• 0.5 - 1.0 chronic pulmonary or extrapulmonary
  infection
• Skin
• Skeletal system
• Meninges

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• IgM
• IgG (complement fixation) equivocal
• 12 2
• 14 1
• 18 1
• 116 1
• 132 negative

Pappagianis. Semin Respir Infect 200116(4)
242-50
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Coccidioidomycosis

• Disseminated disease
• Disseminated infection within 1st 2nd year of
  exposure
• Usually hematogenous spread
• Paratracheal and supraclavicular nodes likely
  lymphatic drainage
• Other sites endocrine glands, eye, liver,
  kidneys, genital organs, prostate, peritoneal
  cavity
• Meningitis most serious

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Coccidioidomycosis

• Risk factors for complications
• HIV or AIDS
• Organ transplant recipients
• Corticosteroids
• Lymphoma
• Chemotherapy
• Diabetes mellitus
• Pregnancy (third trimester)
• Dark-skinned persons (African, African-American,
  Philippino)

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Coccidioidomycosis

• Severity of Illness
• gt10 loss of body weight
• Intense night sweats gt 3 weeks
• Prominent or persistent hilar adenopathy
• Infiltrates involving more than half of one lung
  or portions of both lungs
• Anti-Cocci CF gt116
• Failure to develop dermal hypersensitivity to
  cocci antigens
• Persisting symptoms for gt 2 months

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Coccidioidomycosis

• Treatment
• No randomized, controlled trials for
  uncomplicated, early primary infection
• Oral azole antifungals
• Ampho B alternative if lesions rapidly
  progressing or vertebral column involved
• One prospective, randomized, blinded comparison
  of itraconazole vs fluconazole in progressive,
  non-meningeal infections

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Fluconazole in the Treatment of Chronic
Pulmonary and Nonmeningeal Disseminated
Coccidioiomycosis

• Multi-center, open-label, single-arm study
• 78 pts enrolled
• 22 soft tissue
• 42 chronic pulmonary (gt 1 year)
• 14 skeletal
• 7 with HIV, 49 with concomitant disease
• Oral fluconazole 200 mg/d or 400 mg/d, x average
  duration of 1.5 years
• Response reduction in baseline abnormality by
  month 4 and gt 51 reduction by month 8

Catanzaro et al. Am J Med 1995 98249-256
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Fluconazole in the Treatment of Chronic
Pulmonary and Nonmeningeal Disseminated
Coccidioiomycosis

• Pulmonary 40/42 treated with 200 mg
• 28 responded
• 24 tx with 400 mg
• 11/24 (46) responded
• Skin 19/22 tx with 200 mg
• 42 responded
• 10 tx with 400
• 8/10 (80) responded

• 73 of 78 treated 200 mg
• 34 responded at 200 mg
• 41 of 73 tx with 400 mg
• 25/41 (61) responded
• Toxicity
• 50 (67) with none
• 25 (33) with toxicity
• 2 reduced dose, 3 d/cd

Catanzaro et al. Am J Med 1995 98249-256
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Comparison of Oral Fluconazole and Itraconazole
for Progressive, Nonmeningeal Coccidioidomycosis

• Randomized, double-blind, placebo-controlled
  trial
• 198 pts with chronic pulmonary, soft tissue,
  skeletal
• Oral fluconazole (400 mg/d) or itraconazole (200
  mg BID)
• Statistically equivalent efficacy demonstrated
• there was a trend toward slightly greater
  efficacy in itraconazole at doses studied
• Both drugs well-tolerated
• Relapses occurred with both drugs

Galgiani et al. Ann Intern Med 2000 133676-686
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Comparison of Oral Fluconazole and Itraconazole
for Progressive, Nonmeningeal Coccidioidomycosis
Galgiani et al. Ann Intern Med 2000 133676-686
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Coccidioidomycosis

• Primary infection frequently unrecognized
• Certain factors predispose to progressive primary
  infection and dissemination
• Treatment is prolonged and with oral azoles
• Itraconazole slightly more efficacious in
  skeletal infection
• Relapse is common and usually responds to
  restarting therapy

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References

• Catanzaro et al. Fluconazole in the treatment of
  chronic pulmonary and nonmeningeal disseminated
  cocidioidomycosis. Am J Med 1995 98249-256.
• Galgiani et al. Practice guidelines for the
  treatment of coccidioidomycosis. Clin Inf Dis
  2000 30658-61.

• Galgiani et al. Comparison of oral fluconazole
  and itraconazole for progressive, nonmeningeal
  cocidioidomycosis. Ann Intern Med. 2000 133
  676-686.
• Up to Date, 2003.