Dr Muhammad J Motiwala MD, FACP, Al Mafraq Hospital Abu Dhabi-UAE - PowerPoint PPT Presentation

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Dr Muhammad J Motiwala MD, FACP, Al Mafraq Hospital Abu Dhabi-UAE

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Recent Update In The Management Of Invasive Candidiasis * * * CI is ratio of # of sites positive to total number of sites tested. CCI is CI times the ratio of # of ... – PowerPoint PPT presentation

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Title: Dr Muhammad J Motiwala MD, FACP, Al Mafraq Hospital Abu Dhabi-UAE


1
Dr Muhammad J MotiwalaMD, FACP,Al Mafraq
HospitalAbu Dhabi-UAE
  • Recent Update In The Management Of Invasive
    Candidiasis

2
Overview
  • Invasive Fungal Infections
  • Antifungal Agents
  • Polyenes
  • Azoles
  • Glucan Synthesis Inhibitors
  • IDSA Treatment Guidelines

3
Review of our Fungal Players
  • Opportunistic fungi
  • Normal flora
  • Candida spp.
  • Ubiquitous in our environment
  • Aspergillus spp.
  • Cryptococcus spp.
  • Mucor spp.
  • Endemic geographically restricted
  • Blastomyces sp.
  • Coccidioides sp.
  • Histoplasma sp.
  • Newly emerging fungi
  • Fusarium
  • Scedosporidium
  • Trichosporin

4
Rank order of nosocomial bloodstream pathogens
and their associated mortality
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7
Predisposing Factors to Fungal Infections (IFI)
  • Broad spectrum antibiotics
  • Immunosuppression
  • Corticosteroids
  • Prolonged hospitalization (ICU Stay)
  • TPN (intravascular catheter use)
  • Prolonged neutropenia
  • Hemodialysis /Acute Renal Failure
  • Diabetes Mellitus
  • Mechanical Ventilation
  • Recent gastrointestinal / Cardiac surgery
  • Burns
  • Colonization

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9
Incidence of Invasive Fungal Infections
  • Solid Organ Transplant 5 - 42
  • Kidney 5 14
  • Heart 5 32
  • Heart-Lung/Lung 15 36
  • Pancreas 18 38
  • Liver 7 42
  • Bone Marrow Transplant 15 - 25
  • Intensive Care Unit 17
  • Singh, N. CID 2000 31545-53
  • Vincent JL. Intensive Care Med 1998 24 206-216

10
Mortality Rates
  • Candidemia has a mortality rate of 40.
  • Invasive aspergillosis continues to be a highly
    lethal opportunistic infection
  • 375 increase in mortality due to Aspergillus
    species from 1980 to 1997.
  • Overall mortality rate in patients with invasive
    aspergillosis is reported to be 58.
  • Mortality continues to be high regardless of the
    antifungal therapy used.

Edmond MB et al. CID 199929239-44. National
Center for Health Statistics (1980-1997) Lin S et
al. CID 200132358-66.
11
Challenges
  • Delaying antifungal therapy until blood cultures
    are positive is associated with increased
    mortality
  • Diagnostic limitations

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13
Clinical approaches to assess risk
  • Fungal colonizing index the greater the number
    of positive sites, the greater the increased risk
    for invasive infection
  • Combine colonization with other risk factors
    surgery on admission, TPN, and sepsis
  • No colonisation index but include variables 4
    days in ICU, CVC, DM, new hemodialysis, TPN, and
    broad-spectrum antibiotics

Pittet D. Ann Surg. 1994220751-758. Paphitou
NI. Med Mycol. 200543235-243
14
Colonization in ICU patients
  • Prevalence of colonization in ICU is high (50 to
    70 or more) compared with relatively low rate of
    infection, so predictive value of colonization is
    poor
  • However colonisation with unexplained fever,
    leukocytosis, and hypotension ? may indicate
    invasive candidiasis

Ostrosky-Zeichner L. Crit Care Med.
200634857-863 Eggimann P. Lancet Infect Dis.
20033685-702
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16
Which antifungal to choose?
  • Candida speciation may take up to 5 days
  • and fluconazole susceptibility testing may take
    an additional 5 days 

17
Targeted anti-fungal therapyThe challenging
wisdom
  • Withhold Antifungal therapy unless positive
    diagnostic test
  • Advantages
  • Directed therapy, ?less cost, less anti-fungal
    toxicity
  • Disadvantages
  • Variable sensitivity and specificity diagnostic
    tests
  • Unproven benefit in reducing mortality, ?costs

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19
Treatment options of invasive fungal infections
in adults.Swiss Med Wkly. 2006 Jul
22136(29-30)447-63
20
Spellberg BJ et al. Clin Infect Dis. 2006 Jan
1542(2)244-51
21
Diagnostic Dilemma
  • Clinical Setting with other risk factors
  • Radiology applicable more for Aspergillus
  • Cultures Low yield and longer time
  • Staining GMS and Calcofluor white
  • PCR Assay not widely available
  • 1-3 Beta Glucan Assay
  • Galactomannan Assay For Aspergillus
  • PNA FISH

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23
PNA FISH Clinical Benefits Summary
  • Rapid and accurate identification of bloodstream
    pathogens direct from positive blood cultures
  • Simple to implement and easy to use
  • Maintains species morphology
  • Actionable PNA FISH results for 95 of BC
  • Development of new therapeutic guidelines
  • Improved patient safety
  • Early appropriate and effective antibiotic
    therapy
  • Reduction in mortality
  • Reduction in unnecessary antimicrobial and
    antifungal use
  • Reduction in hospital length of stay (LOS)
  • Significant cost savings

23
12 June 2013
24
Antifungal choice
  • Organism (proven, suspected)
  • Site of disease
  • Host factors (eg age, neutropenia, mucositis)
  • History of antifungal therapy and/or prophylaxis
  • Tolerability/ side effects
  • Drug-Drug interactions
  • Costs

25
ANTI FUNGAL AGENTS
26
Antifungal Drug Development
1950s
1960s
1970s
1980s
1990s
2000s
Griseofulvin
Ketaconazole
Fluconazole Itraconazole Terbinafine AMB
lipid Formulations Itraconazole
Itra (IV) Caspofung Voricon Micafung Anidul
ofung Posacon Ravucon
Econazole, miconazole(IV)
AMBd 5FC miconazole (top) clotrimazole (top)
27
Antifungal agents
  • Polyenes (cell membrane)
  • Conventional Amphotericin B
  • Lipid formulations
  • Ambisome, Abelcet, Amp B Colloidal Dispersion
  • Triazoles (sterol synthesis)
  • Fluconazole, Itraconazole, Voriconazole,
    Posaconazole
  • Ravuconazole
  • Echinocandins (cell wall)
  • Caspofungin
  • Anidulofungin, Micafungin
  • Allyamines (sterol synthesis)
  • Terbinafine

28
Biochemical Targets for Antifungal Chemotherapy
Arrangement of the biomolecular components of the
cell wall accounts for the individual identity of
the organism. Although, each organism has a
different biochemical composition, their gross
cell wall structure is similar. Antifungal
agents targeted towards Inhibition of fungal
cell wall synthesis caspofungin is a ?-glucan
synthesis inhibitor several more compounds are
under investigation Inhibition of fungal cell
membrane synthesis ergosterol is the target
(cell membranes of fungi and mammals contain
different sterols) polyenes, azoles, triazoles,
alkylamines Inhibition of cell division
microtubule effects griseofulvin DNA
flucytosine.
29
Antifungal Agents- Sites of action
Echinocandins Inhibit fungal cell
wall biosynthesis
Griseofulvin Inhibits mitotic spindle formation
30
B-1,3 Glucan Synthase
Caspofungin
B-1,6 Glucan
B-1,3 Glucan
Phospholipid Bilayer
Cell Wall
AMB
Ergosterol
Zymosterol
14 Me-fecosterol
Lanosterol
Azoles
Azoles
Terbinafine
Squalene
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