2. CLASSIFICATION OF FUNGAL INFECTIONS
FUNGAL
INFECTIONS
SUPERFICIAL
INFECTIONS
On the surface of
the skin
CUTANEOUS
INFECTIONS
Dermatophytes
Ringworm infections
All Tinea sps
Candida sps
SUB CUTANEOUS
INFECTIONS
DEEP MYCOSAL
INFECTIONS
OR
SYSTEMIC
MYCOSAL
INFECTIONS
3. Invasive fungal infections
Invasive fungal infections are a significant
and often lethal problem in transplant
patients.
They are at risk for these infections as a
result of their general health status,
technical complications of surgery, and
immunosuppression.
4. FUNGAL INFECTIONS IN
TRANSPLANTATION
The incidence of invasive fungal infections in solid organ transplant
recipients varies according to the type of transplant.
Most of these infections are due to Candida spp., Aspergillus spp. or
Cryptococcus spp.
Currently, overall mortality due to invasive fungal infections in solid
organ transplant recipients ranges between 25%-80% and half of
these deaths are directly related to the fungal infection.
5.
6. CANDIDIASIS/ ASPERGILLOSIS
Candidiasis is the most common
invasive fungal infection in SOT
recipients and accounts for 50–60%
infections.
Candida species, particularly Candida
albicans, are frequent colonizers of
the human gastrointestinal,
respiratory and reproductive tracts,
and the skin.
7. CANDIDIASIS/ ASPERGILLOSIS
The majority of invasive candidiasis is
from an endogenous source – usually
the skin or gut.
Aspergillosis is the next most common
infection, accounting for 20–25% of
fungal infections.
In lung transplant recipients,
aspergillosis is the most common
infection
8. INVASIVE CANDIDA INFECTIONS
REPORTED IN VARIOUS TRANSPLANT
TYPESPrevalence,%
Liver Kidney Pancreas Lung Heart
42
17
38
8
12
*Numbers reflect data collected by TRANSNET from 2001 to 2004. Andes D, et al. ICAAC 2004. Abstract M-1014.
0
10
20
30
40
50
60
9. DISTRIBUTION OF FUNGAL PATHOGENS
CAUSING INVASIVE FUNGAL INFECTIONS IN
TRANSPLANT RECIPIENTS
Ther Adv Infect Dis (2013) 1(3) 85105
10. INCIDENCE OF INVASIVE FUNGAL
INFECTIONS
The Transplant-Associated Infection Surveillance Network conducted a 5-year
prospective study among 1,063 organ transplant recipients.
1028 were diagnosed with IFI.
The most common IFIs were:
Invasive candidiasis (53%),
Invasive aspergillosis (IA) (19%),
Cryptococcosis (8%),
Non-Aspergillus molds (8%),
Endemic fungi (5%), and
Zygomycosis (2%)
IA is a life-threatening complication in patients who undergo solid organ
transplantation, having an incidence between 0.5% and 2.2% with a mortality rate of
> 70% and a high case-fatality rate of up to 88%
11. INDIAN PROSPECTIVE
Recipients of solid organ transplants have 6–10% incidence of
opportunistic fungal infections with a very high mortality of
70–100% in the Indian subcontinent.
12. PATHOPHYSIOLOGY
Infection may be due to
reactivation of a previously
quiescent process such as
colonization or subclinical
infection, or from de
novo infection following
inhalation of fungi after
transplantation.
Donor-derived infections are
an increasingly recognized
mode of transmission .
Transplanted organs may act
as reservoirs for potentially
pathogenic fungi.
13. DIAGNOSIS OF FUNGAL INFECTIONS IN
RENAL TRANSPLANT RECIPIENTS
Fungal infections in renal transplant recipients are diagnosed on the
basis of:
Clinical and radiologic signs and symptoms that include:
Tissue invasion
Positive culture results from a deep tissue specimen such as
Blood
Cerebrospinal fluid
Peritoneal fluid, or a biopsy specimen
14. GOALS OF THERAPY IN TRANSPLANT
RECIPIENT
Prevention of fungal infections.
Individual risk assessment
Initiated early in patients with a suspected fungal infection.
Optimize the pharmacokinetics of antifungal drugs.
Assess for potential side effects.
16. ECHINOCANDINS
Newer antifungal agents that inhibit the fungal cell wall
synthesis
During fermentation process, some metabolites were found
to inhibit Candida sp., and they were named Echinocandins
The echinocandins have potent activity against Aspergillus
and most Candida species, including those species resistant
to azoles. However, they have minimal activity against other
fungi.
17. Caspofungin, micafungin, and anidulafungin are semisynthetic
echinocandin derivatives with clinical use due to their solubility,
antifungal spectrum, and pharmacokinetic properties.
All these preparations so far have low oral bioavailability, so
must be given intravenously only.
ECHINOCANDINS
18. MECHANISM OF
ACTION
Inhibits the synthesis of β 1,3 – D- glucan via noncompetitive inhibition of
the enzyme 1,3-β glucan synthase and are thus called "penicillin of
antifungals“ resulting in the inhibition of cell wall, leading to lysis and
death.
19. FUNGICIDAL AND
FUNGISTATIC ACTION
Echinocandins exhibit fungicidal activity against Candida species,
including triazole-resistant isolates, and fungistatic activity against
Aspergillus species.
20. PHARMACOKINETICS
Due to the large molecular weight of echinocandins, they have poor
oral bioavailability and are administered by intravenous infusion.
In addition, their large structures limit penetration into cerebrospinal
fluid, urine, and eyes.
In plasma, echinocandins have a high affinity to serum proteins.
Echinocandins do not have primary interactions with CYP450 or P-
glycoprotein pumps.
21. Caspofungin has triphasic nonlinear pharmacokinetics.
Micafungin and anidulafungin have linear elimination.
22. • Broad range (especially against all Candida), thus can be given
empirically in febrile neutropenia and stem cell transplant.
• Can be used in case of azole-resistant Candida or use as a second-
agent for refractory aspergillosis
• Long half-life
Not an inhibitor, inducer, or substrate of the cytochrome P450 system,
or P-glycoprotein, thus minimal drug interactions
No dose adjustment is necessary based on age, gender, race
ADVANTAGES OF
ECHINOCANDINS
26. INDICATIONS
Anidulafungin is indicated in adults for the treatment of:
Candidemia and other forms of Candida infections (intra-abdominal
abscess and peritonitis)
Esophageal candidiasis
27. DOSAGE IN CANDIDA
INFECTIONS
200 mg loading dose on Day 1,
followed by 100 mg daily dose
thereafter for at least 14 days
after the last positive culture
28. DOSAGE IN OES0PHAGEAL
CANDIDIASIS
100 mg loading dose on Day 1,
followed by 50 mg daily dose
thereafter for a minimum of 14
days and for at least 7 days
following resolution of
symptoms
The rate of infusion should not exceed 1.1 mg/minute [equivalent to 1.4 mL/minute or 84
mL/hour when reconstituted and diluted per instructions]
29. RECONSTITUTION
Anidulafungin for Injection must
be reconstituted with sterile Water
for Injection and subsequently
diluted only with 5% Dextrose
Injection, USP or 0.9% Sodium
Chloride Injection, USP (normal
saline).
30. HOW TO ADMINISTER
Dose No. of vials
required
Total
reconstituted
volume
required
Infusion
volume
Total
infusion
volume
Rate of
infusion
Minimum
duration
of
infusion
100
mg
1 30 ml 100 ml 130 ml 1.4 ml/min
or 84 ml/hr
90 min.
200
mg
2 60 ml 200 ml 260 ml 1.4 ml/min
or 84 ml/hr
180 min.
32. SUMMARY
Wider spectrum of action and lower toxicity than caspofungin.
Good in vitro antifungal activity against Candida and Aspergillus spp.
One of the most interesting features of anidulafungin in solid organ
transplant recipients is that this drug is not metabolized by or eliminated
through the kidney so that dosage adjustments are not required in these
patients, who frequently show renal function alterations.
33. SUMMARY
Moreover, anidulafungin is not metabolized in the liver and is consequently
free of interactions with other drugs metabolized in this organ.
Equally, dosage adjustments are not required in patients with severe liver
disease or in those administered immunosuppressive agents such as
prednisone, cyclosporine A, tacrolimus, mofetil mycophenolate or sirolimus.
Hence anidulafungin will be highly useful in the clinical management of
solid organ transplant recipients.
37. INDICATIONS
Micafungin is indicated for adults and paediatric patients of 4 months or
older for:
Treatment of Patients with Candidemia, Acute Disseminated
Candidiasis, Candida Peritonitis and Abscesses
Treatment of Patients with Esophageal Candidiasis
Prophylaxis of Candida Infections in Patients Undergoing
Hematopoietic Stem Cell Transplantation (HSCT)
38. ADVERSE EFFECTS
Most common adverse reactions include diarrhoea, nausea,
vomiting, pyrexia, thrombocytopenia, and headache.
Histamine-mediated symptoms including rash, pruritus, facial
swelling, and vasodilatation
The drug has no significant effect on renal function.
39. DOSAGE
Indication Dose
Adult Paediatrics 30 kg
or less
Paediatrics greater
than 30 kg
Candidemia, Acute
Disseminated Candidiasis,
Candida Peritonitis and
Abscesses
100 mg daily*
2 mg/kg/day
(maximum 100 mg daily)
Esophageal Candidiasis 150 mg daily 3 mg/kg/day 2.5 mg/kg/day
(maximum 150 mg
daily)
40. DOSAGE
Indication Dose
Adult Paediatrics 30 kg
or less
Paediatrics greater
than 30 kg
Prophylaxis of Candida
Infections in HSCT
Recipients
50 mg daily** 1 mg/kg/day
(maximum 50 mg daily)
*100 mg micafungin is equivalent to 101.73 mg micafungin sodium.
**50 mg micafungin is equivalent to 50.86 mg micafungin sodium
41. SPECIAL POPULATION
Micafungin is administered intravenously as a 1-h infusion
once daily.
Dose adjustments are not required for elderly persons or for
patients with renal dysfunction.
Likewise, mild to moderate hepatic impairment does not
warrant changes in dose.
42. SPECIAL POPULATION
Pregnancy - No human data. Adverse effects in animals. Use if
potential benefits of treatment outweigh potential fetal risk
Nursing Mothers - Caution should be exercised if administered to
a nursing woman
Safety and effectiveness in paediatric patients less than 4 months
of age have not been established
43. CONTRAINDICATION
Micacord is contraindicated
in persons with known
hypersensitivity to micafungin
sodium, any component of
micafungin, or other
echinocandins.
44.
45. Safe and effective agent for the treatment of
newly diagnosed and refractory cases of
candidemia.
46. GUIDELINES
RECOMMENDATIONS
Infectious Diseases
Society of America
(IDSA)
Candidemia in Non-neutropenic Patients
Micafungin: 100 mg daily is recommended as initial therapy for most adult
patients
Candidemia in Neutropenic Patients
Micafungin: 100 mg daily is recommended for most patients
Empirical Treatment for Suspected Invasive Candidiasis in
Non-neutropenic Patients
Micafungin (100 mg daily) is recommended as initial therapy
Stem cell transplant recipients with neutropenia,
Micafungin (50 mg daily) is recommended during the period of risk of
neutropenia
European Society of
Clinical Microbiology
and Infectious Disease
(ESCMID)
Micafungin
recommended in the treatment of candidaemia
recommended in neutropenic patients
recommended in the treatment of mucosal oropharyngeal or oesophageal
candidiasis
European Conference
on Infections in
Leukemia (ECIL)
Recommends micafungin as an alternative for empirical antifungal treatment in
febrile neutropenic patients
47. SUMMARY
US FDA approved since 2005
Fungicidal as well as fungistatic property
Effective in solid organ transplant recipients
Convenient dosing, no loading dose needed
Excellent safety profile
Recommended by IDSA, ESCMID and ECIL in the management of invasive
fungal infections.
Remarkably few drug interactions
48. SUMMARY
Equally effective as fluconazole for the treatment of esophageal candidiasis
Effective for the treatment of newly diagnosed or refractory candidemia
Better tolerated compared to Amphotericin B
Effective and safe antifungal drug in treating Invasive Aspergillosis
Equally Safe and Effective as Caspofungin
