ID Case Presentation 24 March, 2003

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ID Case Presentation24 March, 2003

• Munshi Moyenuddin
• Fellow, Infectious Diseases
• Wake Forest University Hospital

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Case1 78 y/o male with increasing cough and SOB

• The pt with longstanding CLL treated with
  multiple chemotherapy.
• Diagnosed with pulmonary mucormycosis in 9/02 by
  bronchoscopic culture and biopsy.
• Treated initially with ampho-B, then with abelcet
  rifampin with clinical and radiographic
  improvement.
• Frequency of abelcet was decreased from
  4-times/wk to 2-times/wk.
• Re-admitted in 01/03 with increasing cough and
  SOB with occasional hemoptysis.

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Case 1 HP (contd)

• Tm 98.4, P 94, R 26, BP 122/77, Sat 96 on 3 L
  O2.
• Gen- tachypneic, ill appearing.
• CV- RRR with II/VI sm
• Lungs- Ins/exp wheeze in upper lobes RgtL.
• Abdomen- soft, NT, BS
• Ext- no edema.

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Case 1 Labs

• Chest CT (1/26/03) worsening tree in bud
  interstitial disease with associated
  bronchiectetic RUL mass and increasing LUL
  nodule.
• Bronch (2/3/03) RUL endobronchial mass with bx
  and cx for mucor.
• Wbc 2.9, seg 0.8, plt 18, cr 2.2, AST 57, ALT 85
• Sputum AFB smear negative X 3
• BAL AFB smear and PCP IFA were negative.
• Blood cx negative.

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Case 1 Hospital course

• Abelcet dose was increased to 10 mg/kg/d
• Aerosolized ampho-B was started.
• G-CSF was started.
• Pt tolerated the treatment.
• Respiratory symptoms were improved.
• Pt was having intermittent low-grade fever (99.8
  to 100.4).
• RUL mass bx cx in broth for AFB stain.

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Case 2 47 y/o male with cavitary lung lesion

• The pt with alcoholic liver disease, h/o
  substance abuse was transferred for LE-DVT and
  RUL cavitary lung lesion with 13mm nodular
  density.
• Denied fever/chill/night sweat/cough but noted
  involuntary wt-loss (20 lbs over 6-months).
• c/o swelling of abdomen and diarrhea.
• Tm 99.2, P 73, R 18, BP 97/61, sat 96 RA.

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Case 2 HP (contd)

• Gen Ill appearing, thin male, NAD
• Neck/Axilla no adenopathy.
• CV RRR, no murmur.
• Lungs CTA
• Abdomen distended, ascitis
• Ext no edema
• Meds enoxaparin, lasix, aldactone, coumadin, B1.

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Case 2 (contd)

• Wbc- 5.3, Hg 9.6, Plt 136, INR 1.7, cr 0.7, AP
  209
• BAL and bronchial brush-AFB and fungal smears
  were negative.
• BAL/br brush cx- normal throat flora
• HIV ab was negative.
• Pt required Chest tube for bx induced
  pneumothorax.
• FNA of RUL nodule few AFB on smear.

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Case 3 29 y/o female with abdominal pain,
nausea, fever, and weight-loss

• HIV since 1993, CD4 nadir- 0, VL- 1,150,550 in
  8/02.
• Off HAART for 5-months for GI symptoms.
• ROS- positive for abd pain, 30-lb wt-loss, loss
  of appetite, intermittent fever (101.8 3-days
  ago), some diarrhea.
• Abd pain-diffuse, crampy (8/10 max), no
  radiation, comes and goes, no change with food.
• Home meds- TMP/SMX DS 1 po qd, azithromycin 1200
  mg q wk.

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Case 3 HP (contd)

• Tm 100.5, P 83, R 20, BP 94/69, sat 99 RA.
• Gen- thin black femal, NAD
• Neck/ Axilla- no adenopathy
• CV- RRR, Lungs- CTA
• Abd- soft, diffuse tenderness- all quadrant, no
  organomegaly.
• Wbc 5.8, 80 seg, 6 band, Hg 9.2, Plt 442, cr
  1.0, LFT-nml
• CT abd/pelvis- multiple enlarged lymph nodes
  (2.5-3.5 cm) in the mesentery, ant to the aorta
  3 cm lesion in R-lobe of the liver.

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Case 3 Hosp Course

• Pt spiked temp to 102
• Blood cx-neg
• UA- unremarkable
• Stool O P- neg
• CXR- pending
• CT guided bx of mesenteric lymph node for AFB.

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Topics of discussion

• Airborne precautions.
• When to start treatment.
• Pulmonary disease by non-TB mycobacteria.
• Pulmonary MAC in HIV-negative pts.
• Tuberculous lymphadenitis.
• Disseminated MAC in HIV-positive pts.

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Airborne Precautions

• Indicated for pts with documented or suspected
  tuberculosis (pulmonary or laryngeal) (Infect
  Control Hosp Epidemiol 1996 17 53-80).
• Smear positive suspects must be kept in negative
  pressure isolation rooms untill they have
  converted the AFB smears to negative and they
  have demonstrated a clinical and/or radiographic
  response to therapy (Am J Respir Crit Care Med
  2002).

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Airborne Precautions

• Pts who are infected with (or at high risk for)
  HIV with fever, cough, and a pulmonary infiltrate
  should be placed under airborne precautions until
  tuberculosis is ruled out.
• The clinical and radiographic presentations of TB
  are often atypical in persons with HIV
  (especially when CD4 lt200) and in pts with
  impaired cell-mediated immunity, such pts have an
  increased frequency of extrapulmonary TB and can
  have pulmonary disease despite a normal chest
  X-ray. (CID 199725242).

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Airborne Precautions

• Pts with nontuberculous mycobacterial pulmonary
  disease need not be isolated.
• TB isolation rooms Negative pressure is employed
  to prevent the escape of droplet nuclei. Doors
  must be kept closed, negative presure should be
  verified daily. Anterooms are desirable. There
  must be atleast six air exchanges per hour. Air
  should be exhausted to the exterior, far from any
  intake vents MMWR 199443(RR-13).

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Airborne Precautions

• Respiratory Protection Masks The masks must
  filter particles 1 micron in diameter with
  atleast 95 efficiency given flow rates upto 50 L
  /minute, must fit to a persons face with lt10
  seal leakage.
• Persons entering a TB isolation room must wear
  the mask.
• Persons present during a cough-inducing procedure
  on such pts must wear the mask.

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Airborne Precautions

• Discontinuation of TB isolation When the pt is
  on effective therapy, improving clinically, and 3
  consecutive sputum samples obtained on different
  days, and are smear negative for AFB.
• Pts with MDR-TB should remain in isolation for
  the duration of their hospital stay.
• Pts with severe cavitary disease, persistent
  cough, or laryngeal TB, and those who will return
  to an environment with high risk indivi
  (children, immunosuppressed pts) isolation should
  be maintained for atleast 1-month.

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Airborne precautions

• Studies demonstrated that smear-negative,
  culture-positive cases can transmit tuberculosis.
• Study in San Francisco showed that 17 of cases
  resulted from a smear-negative source (Lancet
  199753444).

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Airborne Precautions

• Pts with known or suspected measles, varicella,
  disseminated zoster, or immunocompromised pts
  with localized zoster require airborne isolation
  (Infect Control Hosp Epidemiol 1996 17 53).

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When to start treatment

• Diagnosis should be relatively established before
  initiation of treatment.
• In severely ill pts with presumed tuberculosis,
  treatment should be initiated immediately.
• Periodic CXR are helpful.
• Beginning 1 month after therapy, an early morning
  sputum culture should be obtained to monitor
  conversion or if positive, to detect drug
  resistance (Am Rev Respir Dis 1984129264).

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Pulmonary disease by non-TB Mycobacteria (NTM)

• Chronic pulmonary disease is the most common
  localized clinical manifestation of NTM.
  Mycobacterium avium complex, followed by M.
  kansasii is the most frequent pathogen causing
  lung disease in the U.S (Clin Microbiol Rev
  19969177).
• NTM tend to cause thin-walled cavities with less
  surrounding parenchymal infiltrate, less
  bronchogenic but more contiguous spread, and more
  involvement of pleura over the involved areas of
  lungs.
• Occasionally produce dense pneumonic disease or a
  solitary pulmonary nodule without cavitation
  (Radiol Clin North Am 199533719).

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Pulmonary Mycobacterium avium complex (MAC) in
HIV-negative patients

• Most reported infections are in persons with
  predisposing lung conditions.
• Chr. Bronchitis, emphysema, pulm TB,
  bronchiectasis, pneumoconioses, fibrotic lung
  disorders have been associated with the disease
  (Ann Rev Respir Dis 1988137149).
• The clinicoradiologic presentation includes
  several patterns cavitary/destructive form
  multinodular bronchiectatic form
  transition/combination forms (pulmonary nodules)
  J Computer Assist Tomogr 199519353.

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Pulmonary MAC in HIV-negative patients

• The nodular bronchiectatic form is recognized
  more frequently, in this series, 21/88 pts had no
  apparent underlying disease, 81 of these pts
  were women (N Eng J Med 1989321 863).
• Radiographic findings are frequently located in
  the RML, lingula, and ant segment of the RUL.
• Clinical symptoms include cough and
  expectoration, with few reporting fever, chill,
  or weight loss.

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Pulmonary MAC in HIV-negative patients (treatment)

• In a controlled study of 50 pts, 30 were given
  initial clarithromycin monotherapy, 20 were given
  combination of clarithromycin, ethambutol,
  rifampin, streptomycin. They were treated until
  cx neg for 1-year 92 became sputum neg on
  combination treatment (Am J Respir Crit Care Med
  19961531766).
• Combination therapy with clarithromycin is
  essential, ethambutol is strongly recommended as
  a companion.

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Pulmonary MAC in HIV-negative patients (treatment)

• Azithromycin-containing regimen have been studied
  in combination with rifabutin (or rifampin),
  ethambutol, and initial streptomycin.
• Success (12 months of neg sputum cx) rates varied
  from 55 to 65 (CID 2001321547).
• There is debate about the need to treat the
  non-cavitary, stable infiltrate.
• The ATS recommendations suggest that they do not
  need be treated.
• Reported cases showed progression to cavitary
  disease, thus they recommend therapy (Progress in
  Research and Treatment 1996 45-79).

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Pulmonary MAC in HIV-negative patients

• The ATS criteria for pulmonary MAC diagnosis
  generally require 2 or more sputum samples
  demonstrating AFB and/or moderate to heavy growth
  on sputum culture (Am Rev Respir Dis
  1990142940).

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Tuberculous lymphadenitis

• TB is responsible for upto 43 of all peripheral
  lymphadenopathy in the developing world (Br J
  Surg 199077 911).
• In the US, 5.4 of all TB is extrapulmonary, and
  31 of these cases are lymphatic (Am Rev Respir
  Dis 1990141347).
• In HIV pts, TB intraabdominal lymphadenopathy
  commonly involves lymph nodes in the periportal
  region, followed by peripancreatic and mesenteric
  lymph nodes (Medicine 1991 70384).

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Tuberculous lymphadenitis

• Many HIV-pts with mediastinal and hilar node
  involvement will have concomitant pulmonary TB,
• Such pts, when hospitalized, require respiratory
  precautions, especially when undergoing
  cough-inducing procedure (MMWR 1989 38 236).
• In one report, 9 of 10 HIV-pts with TB
  lymphadenitis had an abnormal CXR on presentation
  (CID 199215601).

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Disseminated MAC in HIV-positive patients

• Presents as a subacute process with fever,
  abdominal pain, diarrhea, and weight loss.
• Unexplained anemia and/or increased alkaline
  phosphatase are suggestive.
• Median CD4 counts range from 10 to 20.
• Radiographic findings include intraabdominal or
  intrathoracic adenopathy, hepatomegaly,
  splenomegaly.
• Diagnosis is made by blood culture. A single
  positive cx detects upto 91 of diss MAC (JID
  1997176126 JCM 199432841).

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Disseminated MAC in HIV-positive patients
(treatment)

• Treatment recommendations by the USPHS and IDSA
  state that 1st line therapy should include
  clarithromycin 500mg twice daily in addition to
  other agents active agaist MAC.
• Ethambutol was suggested as useful 2nd drug,
  other drugs include ciprofloxacin, rifampin or
  rifabutin, and amikacin MMWR 200150(32) 687.
• Therapy is lifelong.

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Disseminated MAC in HIV-positive patients

• Studies showed low risk for recurrence who have
  completed atleast 12-months of treatment, have a
  sustained increase of CD4 count gt100 (JID
  19981781446 AIDS 1999131647).
• Response to therapy is monitored by clinical
  symptoms and qualitative blood cultures.
• Resolution of fever, chill, decrease of alkaline
  phosphatase level within 4 to 8 weeks, and neg
  blood cx by 12 to 16 weeks (Ann Intern Med 1994
  121 905).

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Disseminated MAC in HIV-positive patients

• Antimycobacterial agents commonly used in the
  treatment of MAC infection (Clin Microbiol Rev
  19936266 MAC infection progress in Res and
  treatment 1996)
• Clarithromycin- 500mg BID
• Ethambutol-15mg/kg/day
• Rifabutin- 300mg/day
• Rifampin- 10mg/kg/day
• Ciprofloxacin- 750mg BID
• Azithromycin- 500mg/day
• Amikacin- 7.5-15 mg/kg QD