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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. Case Presentation. PMH

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Clinical Grand Rounds

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  1. Clinical Grand Rounds Allison Liddell, MD March 10th, 2004

  2. 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

  3. Case Presentation • 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

  4. Case Presentation • Medications: • Dexamethasone • Vicodin • Ativan • Ambien • Tessalon • Advair • Combivent

  5. 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

  6. Case Presentation • Initial Rx cefepime • Discharged on levaquin plus Bactrim for PCP prophylaxis

  7. 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”

  8. Case Presentation • Rx High dose iv Bactrim and ceftriaxone • 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 Nocardia asteroides complex • 12/21 sputum had few branching G variable rods on Gram stain

  9. Aerobic bacteria-actinomycetales order ubiquitous, soil-borne 500-1000 cases/yr in U.S. (1976) IDU asso. in HIV Pulmonary entry most common often opportunistic solid organ recipients AIDS BMT pulmonary disease corticosteroid therapy many others association with invasive fungal infection Nocardiaepidemiology

  10. Nocardiataxonomy • N. brasiliensis • N. otitidiscaviarum (T/S resis) • N. transvalensis • N. asteroides complex • N. asteroides sensu stricto • N. farcinica (virulent) • N. nova

  11. Variably acid-fast Gram positive filamentous beading grow in 2-4 weeks NocardiaMicrobiology

  12. Nocardiapathogenesis • Facultative intracellular pathogens • Complex cell wall glycolipids protect against oxidative burst • Inhibits phagocyte functions • predilection for CNS

  13. Fever productive cough weight loss dyspnea pleuritic chest pain hemoptysis soft tissue masses Lymphadenopathy cutaneous ulceration neurologic deficits NO pathognomonic clinical feature, radiographic feature or lab result NocardiosisClinical presentation Uttamchandani et al CID 1994;18 (HIV)

  14. Pulmonary nocardiosis • 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

  15. 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.

  16. Skin/Soft tissue nocardiosis • Cutaneous/subcut nodules after trauma or due to hematogenous spread. • Cellulitis • abscesses • paronychia • sporotrichoid form • Keratitis/endophthalmitis • Wound infections (outbreak post-transplant Germany)

  17. N. brasiliensis • Responsible for most progressive or invasive skin infections • Southern US • Invasive disease • ?new taxon based on different antimicrobial susceptibility • 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)

  18. Figure 82-2A, 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. N-77646.)

  19. Systemic Nocardiosis • Primary pulmonary focus may resolve • Progressive lesions • CNS • Skin/subQ • Eyes • Kidneys • Joints • Bones • Heart

  20. 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

  21. Case Presentation • Marked initial improvement in cough/sputum • N/V resolved with discontinuation of Bactrim • Continued pain, edema, anorexia

  22. Case Presentation • Kirby-Bauer • Susc: amikacin, cefotaxime, ceftriaxone, gentamicin, imipenem, sulfisoxazole, tobramycin • Intermed: Augmentin, doxycycline, minocycline • Microdilution MIC • Susc:amikacin, ceftriaxone, imipenem, linezolid, meropenem, sulfamethoxazole, tobramycin • Intermed: cefotaxime, Augmentin, gatifloxacin, minocycline • Resis: ciprofloxacin, clarithromycin

  23. Sulfonamides Trim/Sulfa 5-15mg/kg/d Sulfisoxazole 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 nova susc to ECN and cephs, but not Augmentin Clinical data supports sulfas are superior Experimental models Carbapenems superior Combinations superior to single agent NocardiosisTreatment

  24. NO controlled trials Most would begin with 2 drugs for severe disease while awaiting ID/susc Duration at least 3 months, usually 6-12 months in normal At least 12 months in immunosupp 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

  25. Bactrim is mainstay For severe disease, combination T/S Imipenem Amikacin (synergy) after 3-6 weeks change to oral therapy IV alternatives cephalosporins Oral alternatives minocin (low therapeutic index) Augmentin (low therapeutic index) clarithromycin (nova) flouroquinolones Treatment

  26. Linezolid • 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

  27. Kaplan. Pediatric Infectious Disease JournalVolume 22 • Number 9 • September 2003

  28. Linezolid • In vitro data confirms linezolid effective for multiple strains (AAC 2001:45) • Case reports (Wallace et al CID 2003:36) • 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

  29. Linezolid • Limitations: • Lack of data for long-term safety • Cost ($35,000 for 12 months)

  30. Prophylaxis primary-some recommend post-transplant if >3% incidence secondary-if remains on steroids, HIV, prolonged immunosuppression Bactrim DS daily (TIW not effective) Nocardiosisprevention

  31. References: • 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. TheJournal of Infection 2003;46(3):199-202

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