Infectious Disease Case Conference 16 June, 2003

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Infectious Disease Case Conference- 16 June, 2003

• Munshi Moyenuddin, M.D.
• Sect. of Infectious Diseases
• WFU Baptist Med Center

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Case 1 A 31 y/o AAF with HIV and persistent
fever

• The patient was admitted initially with 2-weeks
  of fever (100.8 to 102), intermittent abdominal
  pain and sore throat.
• The abdominal pain was colicky, felt in L-flank
  and L-lower abdomen, not relieved by food or
  positional change.
• Also, night sweats and mild headache. Some
  odynophagia, which was subsided with diflucan
  100mg/day.

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Case 1 HP (contd)

• PMH HIV, DM, h/o syphilis, genital herpes.
• PSH TAH/BSO- 7 years ago.
• Soc Hx Tobacco and cocaine use.
• Present Meds Trizivir, Glucophage, Bactrim,
  Valtrex, diflucan.
• Vitals BP- 98/62, P-89, R-22, T-100.5, Pox- 98
  RA.

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Case 1 HP (contd)

• Gen- No acute distress.
• HEENT- Unremarkable.
• Neck- 0.5 to 2 cm in diameter lymphadenopathy
  bilaterally.
• Skin- no rash.
• Chest- Clear.
• Heart- Regular, No murmur/rub/ gallops.

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Case 1 HP (contd)

• Abdomen soft, tenderness in LLQ, no CVA
  tenderness, no rebound/ guarding, positive bowel
  sound.
• Rectal exam unremarkable.
• 0.5 to 2 cm lymphadenopathy in axillary and
  inguinal areas.
• Extremity no edema/clubbing.

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Case 1 Labs

• CD4- 80, VL- 364,829
• Wbc- 5.1, seg 83, no band, Hg- 12.3, plt-139.
• Gl- 94, Cr- 1.0, TB- 1.1, AP- 65, AST- 44, ALT-
  22, Lactate-2.5
• Amylase- 144, Lipase- 10, LDH-392
• UA- wbc 0 to 2, rbc 0 to1.
• CXR and KUB- unremarkable.

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Case 1 Labs

• CT abdomen/pelvis- a small L-kidney stone,
  several mesenteric and retroperitoneal
  lymphnodes, bilateral inguinal adenopathy,
  possible gallstone.
• FNA of a cervical node- lymphocytic hyperplasia.
• Blood culture x 1- no growth.

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Case 1 Hospital course

• Fever continued (around 101).
• CT of sinus opacification of only L-middle
  ethmoid air cells, minimal mucosal thickening in
  R-maxillary sinus, no fluid levels in any
  sinuses.
• Blood culture was repeated.
• Naprosyn 375mg bid was given and the fever was
  decreased.
• The pt was D/Cd on home meds.

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Case 1 Disease course

• Blood culture x 2 grew 0.25 cfu C. parapsilosis.
• The pt was readmitted with fever (upto 102),
  chill, and night sweat.
• T-100, BP- 127/73, P-73, R-20, Pox 99 in RA.
• Exam was unremarkable except lymphadenopathy in
  cervical, axillary areas unchanged from before.

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Case 1 MICs to Candida parapsilosis

• Amphotericin B - 0.5
• Fluconazole - 2
• Itraconazole - 0.125
• Ketoconazole - 0.06
• 5 Fluorocytosine -0.25

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Topics of discussion

• 1. Candidemia- introduction.
• 2. Diagnosis of candidemia.
• 3. General management of candidemia.
• 4. Treatment of candidemia.

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Candidemia (Arch Intern Med 19951552429 CID
1997 2543 Inf Cont Hosp Epi 1998 19846)

• Candida in a blood culture should never be viewed
  as a contaminant.
• For many patients candidemia is a manifestation
  of disseminated candidiasis.
• High mortality in patients who were untreated or
  received delayed treatment.

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Diagnosis of Candidemia

• Blood cultures The gold standard for diagnosis.
• Earlier studies showed that blood cxs were
  positive in appx 50 of pts who had disseminated
  candidiasis at autopsy (Clin Microbiol Rev
  1990332).
• Lysis-centrifugation method (Dupont Isolator
  tube) improved the detection of yeast.

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Diagnosis of Candidemia

• BACTEC and BactiAlert systems also allow enhanced
  growth.
• A drawback is it takes from 1 to 4 days for
  growth.
• Antibody assay- no sensitive and specific assay
  available.
• Antigen assays- for cell wall components, such as
  mannan, not sensitive or specific for diagnosis.

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Diagnosis of Candidemia

• Antigen assays- Immunoassay for the cytoplasmic
  antigen, enolase, lack sensitivity.
• PCR assay- sensitivity is close to that of blood
  culture (Clin Microbiol Rev 1993 6 311).

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Diagnosis clinical menifestations

• Hematogenous spread of candida may manifest as
  characteristic eye lesions, skin lesions, and
  muscle abscesses.
• Skin lesions appear as clusters of painless
  pustules on an erythematous base.
• The lesions vary from tiny pustules to nodular
  and appear necrotic in the center
• In severe neutropenic pts, the lesions may be
  macular rather than pustular.

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Diagnosis Clinical manifestations

• Less commonly, soreness in a muscle group.
  Examination may reveal warm, swollen, tender
  muscle.
• Stains of biopsy material show budding yeast and
  pseudohyphae.
• Multiorgan system failure may be present.Necropsy
  reveals visceral microabscesses, especially, in
  kidney, heart, liver, spleen, lungs, and brain.

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Management of Candidemia

• All pts with candidemia should undergo a formal
  ophthalmologic examination.
• In a study of 31 pts with candidemia, 26 had
  chorioretinitis and none had endophthalmitis (Eye
  200014 30).
• The prevalence of endophthalmitis varied from 28
  to 45 of hospitalized pts with candidemia (JID
  1981143655
• In some pts, ocular symptoms are the first
  manifestation of disseminated candida infection.

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Management of Candidemia

• Pts with prosthetic cardiac valves, IVDU, and
  indwelling central venous catheters should have
  ECHO to detect endocarditis (J Infect
  19973599).
• Pts with hematologic malignancy and neutropenia
  may develop microabscesses in liver, spleen, and
  kidneys manifested by upper quadrant pain,
  nausea, vomiting, and high spiking fever (Am J
  Med 199191137).

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Management of Candidemia

• If feasible initial management should include
  removal of all existing central venous catheters.
• The evidence for this recommendation is strongest
  in the non-neutropenic pts (Arch Intern Med
  19951552429 CID 199521994).

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Treatment of Candidemia

• Options IV or oral fluconazole, IV amphotericin
  B. Flucytosine could be considered in combination
  with one of these agents for more severe
  infections.
• Itraconazole in hydroxy-propyl-B-cyclodextrin has
  been under study for the treatment of invasive
  candidiasis.

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Treatment of candidemia

• Choice of agents in immunocompetent patients
  Several trials have shown that fluconazole is as
  effective as amphotericin B.
• A study in 206 pts without neutropenia showed
  overall success in 72 and 79 for fluconazole
  and ampho B, respectively (NEJM 1994 331 1325).
• A Canadian study noted success rates of 57 for
  fluconazole and 62 for ampho B (Eur J Clin Micro
  Infect Dis 1997 16 337).

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Treatment of Candidemia

• Choice of agents in immunocompetent patients
  Caspofungin was found comparable to ampho B in a
  randomized double-blind study 83 and 79
  response with caspofungin and ampho B,
  respectively (NEJM 2002347 2020).

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Treatment of Candidemia

• Choice of agents in neutropenic patients A
  randomized trial demonstrated response rates of
  66 and 64 to fluconazole and ampho B,
  respectively (CID 1996 23 964).
• International conference on management of severe
  candidal infections suggested that fluconazole
  should be restricted to clinically stable pts who
  have no visceral infection and who have not
  received fluconazole for prophylaxix (CID 1997
  25 43).

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Treatment of Candidemia

• Neutropenic pts with the following
  characteristics should receive ampho B as the
  antifungal agent of choice
• Those who are clinically unstable
• Those with a visceral focus of infection
• Those who have received fluconazole prophylaxis
  (CID 19972543).

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Treatment of Candidemia

• Ampho B lipid complex (ABLC) and liposomal ampho
  B are indicated for pts intolerant of or
  refractory to conventional antifungal therapy.
• Failure of gt500 mg of ampho B.
• Initial Cr 2.5 or Cr clearance lt25
• Increase of Cr to 2.5 or more while on ampho B.
• Acute toxicity (CID 1998261383).

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Treatment summary (IDSA practice guidelines)

• Choice of therapy depends on the clinical status
  of the pt and the species and antifungal
  susceptibility of the isolate.
• In stable pts who have not recently received
  azole therapy, start fluconazole at 6mg/kg/day
  (400mg/day in a 70 kg pt).

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Treatment summary

• In the unstable pts with an isolate of unknown
  species ampho B at 0.7mg to 1mg/kg/day is
  preferred for broader spectrum.
• For C. glabrata fluconazole at 12mg/kg/day
  (800mg/day) may be suitable, but most authorities
  recommend ampho B at 0.7mg/kg/day as initial
  therapy.

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Treatment summary

• For C. krusei, ampho B at 1mg/kg/day is
  preferred.
• Many isolates of C. lusitaniae are resistant to
  ampho B, so, fluconazole at 6mg/kg/day is
  preferred.
• Outcomes Clearance of bloodstream and other
  clinically evident sites of infection,
  symptomatic improvement, absence of retinal
  findings of candida endophthalmitis, follow-up
  hematogenous spread.

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Treatment summary

• Therapy should be continued for 2-weeks after the
  last positive blood culture and resolution of
  signs and symptoms of infection.
• Ampho B may be switched to fluconazole for
  completion of therapy.
• Neutropenic pts should receive G-CSF or GM-CSF to
  accelerate recovery from neutropenia.