Infectious Diseases Case Conference

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Infectious DiseasesCase Conference

• Jason H. Kettler
• Wake Forest University
• October 20, 2003

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Case Presentation 1

• 57 year old white male
• History of AML, diagnosed March 2002
• S/P chemotherapy with complete remission
  documented May 2002
• Underwent autologous peripheral blood stem cell
  transplant in July 2002
• Relapsed in January 2003
• Additional chemo

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Case Presentation 1

• A second remission documented in April of 2003
• Underwent an allogeneic peripheral blood stem
  cell transplant from his daughter in April
• Post-transplant course complicated by persistent
  GVHD to include the liver, colon, skin for which
  he had been maintained on steroids since May (on
  10 mg/d at the time of admission in September)

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Case Presentation 1

• Other post-transplant complications have included
  pulmonary alveolar hemorrhage, urosepsis, acute
  onset of atrial flutter
• Admitted August 21-28 for management of latter
  after presenting with CP/SOB ? a CXR demonstrated
  a R perihilar infiltrate

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Case Presentation 1

• CT scan demonstrated multiple bilateral pulmonary
  nodules which had developed over a 3 month
  period, worrisome for an infectious process

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Case Presentation 1

• Pt. underwent bronchoscopy on August 22
• Routine cultures all finalized as negative by
  August 25, except the BAL had gt100K yeast
• PCP by IMF negative x 3
• Initially all fungal/AFB smears negative
• Viral cultures also negative

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Case Presentation 1

• On August 28 (6 days following the procedure),
  the team was alerted that one of the specimens
  was AFB smear positive!
• What was to be made of this? Was this TB? A
  non-TB mycobacterium? Something else altogether?

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Brief Review

• The rapidly growing mycobacteria consist of

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Brief Review

• The rapidly growing mycobacteria consist of M.
  fortuitum, M. chelonae, and M. abscessus
• M. fortuitum is the most common of this group
  encountered in clinical practice
• M. abscessus is a common respiratory pathogen
• M. fortuitum, M. abscessus, and M. chelonae are
  resistant to all the antituberculous drugs
• Recent studies have shown that all isolates of M.
  abscessus, M. chelonae, and approximately 80
  percent of isolates of M. fortuitum are
  susceptible in vitro to clarithromycin (Brown AAC
  1992)

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Case Presentation 1

• Upon discharge, patient was clinically stable and
  a broad-spectrum empiric antimicrobial regimen
  was designed
• Abelcet for yeast in the BAL
• Levofloxacin, clarithromycin, and minocycline for
  the AFB organism
• Dapsone and VGCV for prophylaxis (? ?ed LFTs
  secondary to TMP/SMX)
• (Prednisone at 10 mg/d)

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Case Presentation 1

• Pt. doing marginally well at home after discharge
  but clinic notes indicate worsening fatigue
• On evening prior to this hospitalization, pt.
  developed fever at home as well as increasing
  dyspnea
• A curious finding came to light at around that
  same time

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ID Consult Questions to Answer

• What exactly is Nocardia?
• How does one acquire infection with these
  organisms?
• Who is at risk for infection with Nocardia?
• What are the implications of a pulmonary
  infection and does further diagnostic testing
  need to be done?
• How is it treated and for how long?
• Can it be prevented?
• (By the way) Can how frequently does TMP/SMX
  cause abnormal LFTs?

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What exactly is Nocardia?

• Nocardiae are aerobic actinomycetes, which are
  bacteria belonging to the order Actinomycetales
• Nocardia is a genus in the family Nocardiaceae
• Both the aerobic actinomycetes and even Nocardiae
  themselves have a very complex taxonomy

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What exactly is Nocardia?

• These organisms were formerly misclassified as
  fungi, because they branch into filaments,
  erroneously thought to be and still sometimes
  incorrectly referred to as hyphae
• Hyphae are extensions of fungal germ tubes, a
  uniquely fungal characteristic
• On the basis of their cell wall components,
  Nocardiae are indisputably aerobic bacteria
• They are often weakly acid fast

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How does one acquire infection with these
organisms?

• Nocardiae are found worldwide in soil and
  decaying organic plant matter
• Pathogenic Nocardia organisms can be found in
  house dust, beach sand, garden soil, swimming
  pools (McNeil Clin Microbiol Rev 1994)
• The organisms are most commonly introduced
  through the respiratory route
• N. asteroides is the predominant human pathogen
• Two distinct subgroups of the N. asteroides
  complex, N. farcinica and N. nova, have been
  accepted as distinct species

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Who is at risk for infection with Nocardia?

• Nocardiosis is chiefly an opportunistic
  infection, especially in patients with
  hematologic malignancies
• Pts. w/ impaired pulmonary defenses, e.g. COPD,
  bronchiectasis, and alveolar proteinosis
• Almost any condition requiring long-term
  corticosteroid therapy

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Who is at risk for infection with Nocardia?

• Systemic immunosuppression, esp. CMI, seen in
  transplant patients, DM, and HIV, predisposes to
  invasive nocardiosis
• IDU
• Many other systemic illnesses, e.g. Goodpastures
  syndrome, cirrhosis, Cushings disease, UC are
  described (Lerner CID 1996)
• Nocardial pneumonia can occur without concurrent
  diseases or therapies (Lerner)

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Nocardia infections after BMT

• Chouciño C, SA Goodman et al. Nocardia
  Infections in Bone Marrow Transplant Recipients.
  CID 1996.
• Nocardia infection after BMT infrequently
  reported in the literature
• 6 Cases reviewed the 4 previously reported
  cases
• All 10 patients had received immunosuppression

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Chouciño et al

• All but one allogeneic BMT recipient had acute or
  chronic GVHD
• 7 of 10 died, but death was less often due to
  nocardial infection than complications of GVHD or
  infection with Aspergillus
• TMP/SMX prophylaxis does not reliably protect
  against nocardiosis

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Pulmonary Infection

• Can be acute, subacute, or chronic
• Presentation may include pneumonia, abscess
  formation, or both
• Clinical manifestations are variable and
  nonspecific
• Radiographs may demonstrate fluffy infiltrates,
  irregular densities, reticulonodular infiltrates
  
• Indolent, progressive fibrosis occurs in
  adequately treated patients

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Pulmonary Infection

• Respiratory tract colonization has been
  described in patients with CA, CF, TB, ABPA,
• Infection may not occur unless steroid therapy is
  employed
• When repeatedly cultured, and/or found in an
  immunocompromised host, therapy should be
  initiated

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Implications

• Pulmonary nocardiosis may erode into blood
  vessels and disseminate
• The most common sites of dissemination are the
  CNS, skin/soft tissues, kidney, bones/joints,
  heart
• Approximately 45 of patients w/ systemic
  nocardiosis have CNS infections
• The s/sxs of brain involvement are variable
• Silent/at autopsy, mimic tumors, classic brain
  abscess or meningitis

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Implications

• The most common CNS finding is

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Implications

• The most common CNS finding is a brain abscess
• Secondary cerebral localization and silent
  destructive infection are sufficiently common
  that cerebral imaging, preferably MRI, should be
  performed in all cases of pulmonary or
  disseminated nocardiosis. (Mandell)

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How is it treated and for how long?

• There are many problems and pitfalls to
  antimicrobial susceptibility testing of Nocardia
  isolates
• The treatment of these infections has not been
  evaluated in controlled clinical trials
• Sulfonamides (alone or in combination with
  trimethoprim) are the antimicrobial agents of
  choice based upon accumulated clinical
  experience, including several large series of
  patients who have been successfully treated

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How is it treated and for how long?

• Potential alternatives to sulfonamides
• Minocycline excellent in vitro activity against
  the majority of pathogenic Nocardia species
• Varying combinations of amikacin, imipenem,
  cefotaxime display in vitro synergy against most
  strains (Lerner)
• Amox/clav is moderately active against many
  strains of N. asteroides
• No reliable activity from anti-TB drugs,
  antifungal agents, or rifampin

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How is it treated and for how long?

• Optimal duration of therapy is uncertain, but
  long-term therapy is the rule because nocardial
  infections tend to relapse
• Nonimmunosuppressed patients w/ pulmonary or
  systemic nocardiosis ? minimum of 6-12 months
  CNS infection ? 12 months all immunosuppressed
  patients, whatever their syndrome ? 12 months

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Can it be prevented?

• No, not really
• Avoid dust, sand, gardening, soil, swimming pools
• No evidence of person-to-person transmission

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(By the way) Can how frequently does TMP/SMX
cause abnormal LFTs?

• TMP/SMX rarely causes hepatotoxicity, but
  hepatitis, acute hepatic failure, and hepatic
  necrosis are all described

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Our patient

• Underwent MRI of brain
• CT of chest overall appearance c/w improving
  pulmonary nocardiosis
• Placed initially on TMP/SMX IV at 15 mg/kg/d q8
  hrs (D/C clarithro, levofloxacin, mino, dapsone)
• Team switched him to po TMP/SMX by the next day
• D/Cd 6 days after we saw him
• LFTs stable
• No f/u as yet in Heme/Onc clinic