Candidiasis NAPCON.pptx

Pulmonary fungal infections after COVID
CANDIDIASIS
P.S.Shajahan MD, MPhil
Professor of Pulmonary Medicine,
Research Coordinator, Occupational Lung Disease research Center
Government TD Medical College Alappuzha, Kerala

Disclosures
NIL
NAPCON 2021,Varanasi 2 nd April 2022

Not a new disease , but…..
COVID pandemic changed everything in the world
Candida related diseases are no exception- a
substantial increase in occurred nce across the globe

This talk covers only an overview of ……….
Candidiasis related to COVID -
COVID associated Candidiasis
(CAC)

Why should it be discussed ?
 COVID-19 increases the risk for fungal infections because of its effect on the
immune system and treatments for COVID-19 which can weaken the body’s
defenses against fungi.
 Awareness of the possibility of fungal co-infection with COVID-19 is essential to
reduce delay in diagnosis and treatment to prevent severe illness and death from
these infections.
 Candidiasis as fungal pneumonia is hard to diagnose and often underestimated,
however the mortality from COVID-19 associated candidiasis is high (19-40%).
 Fungal infections resistant to antifungal treatment is a major concern in patients
with severe COVID.
Candida infections in COVID-19 patients could affect
patient outcomes and complicate treatment efforts.
Current Microbiology (2022) 79:127
https://doi.org/10.1007/s00284-022-02824-

Prevalence of CAC in different countries

Country Type of
Candidiasis
Underlying
conditions
COVID 19
treatment
Candida
species
recovered
CAC treatment Patient
Outcome
India Candidemia Hypertension
11/15 patients,
IHD 3/15,
Chronic liver
disease 3/15,
Asthma 3/15
COPD 2/15
Hypothyroidism
2/15
Encephalopathy
1/15, acute kidney
disease 1/15
Admission to ICU
15/15 patients,
Broad spectrum
antibiotics 15/15,
Steroid therapy
10/15,
Mechanical
ventilation 8/15,
Immuno
suppressive drugs
3/15,
Convalescent
plasma 5/15
C.Auris 10/15
patients, C.
albicans 3/15,
C.tropicalis
1/15, C krusei
1/15
Amphotericin B
2/15 patients
Micafungin 9/15,
Micafungin +
Amphotericin B
4/15
8/15 died
Mortality
53.3 %
Chowdhary A, Tarai B, Singh A, Sharma A. Multidrug-Resistant Candida auris Infections
in Critically Ill Coronavirus Disease Patients, India, April–July 2020. Emerg Infect Dis.
2020;26(11):2694-2696. https://doi.org/10.3201/eid2611.203504
Current Microbiology (2022) 79:127
https://doi.org/10.1007/s00284-022-02824-

Secondary Infections in hospitalized COVID-19 patients:
Indian experience
 A retrospective study of secondary infections in patients admitted in
intensive care units (ICUs) and wards of ten hospitals of the Indian Council of
Medical Research (ICMR) AMR surveillance network, between June and
August 2020
 Candida spp. were isolated from 6% (61/1006) of admitted COVID 19
patients, and among these, 13 isolates (1.3%) of Candida auris were found.
Secondary Infections in Hospitalized COVID-19 Patients: Indian Experience; Sonam Vijay, Nitin
Bansal, Brijendra Kumar Rao, et al.
Infect Drug Resist. 2021; 14: 1893–1903. Published online 2021 May 24. doi: 10.2147/IDR.S299774

Predisposing factors for CAC
Current Microbiology (2022)
79:127
https://doi.org/10.1007/s0028
4-022-02824-

 Signs and symptoms are nonspecific – share many symptoms of COVID itself
 Invasive disease is difficult to distinguish from colonization
 Available tests are limited by suboptimal sensitivity and/or specificity
Diagnostic challenges

Culture and direct microscopy
Direct Microscopy
• Frequent false negatives and positives
• Lower sensitivity relative to culture
• Often requires expertise
Culture
• Tissue
- Acquisition is challenging
• Blood
- Suitable for fragile patients
- ~50% sensitivity for candidemia
• Can be time-consuming
• Often requires expertise
Guarner J, et al. Clin Microbiol Rev. 2011;24(2):247-280. NAPCON 2021,Varanasi 2 nd April 2022

Culture-independent diagnostic tests:
Sensitivity and Specificity
Diagnostic Test Sensitivity (%) Specificity (%)
Candida
species
β-D-glucan* 75.3 85.0
Mannan/Anti-mannan* 83.0 86.0
PCR* 95.0 92.0
T2-Candida 91.1 99.4
*Meta-analysis
BAL, bronchoalveolar fluid.Pfaller MA. Invasive fungal infections and approaches to their diagnosis. In: Andrew S, Tang Y-W, eds. Methods in
Microbiology. Philadelphia, PA: Elsevier; 2015.

Advantages and disadvantages of diagnostic Tests
Technique Advantages Disadvantages
Culture Methods
Gold standard; allows
susceptibilities
Delay in diagnosis; low sensitivity
PCR Methods Highest accuracy Low commercial ability
β-D-glucan
Panfungal marker; high sensitivity
and specificity
Many false-positive results;
methodological concerns
Candida mannan
antigens
High Sensitivity, Specificity Not useful for non-hematologic illnesses
Mannan + Antimannan
Good specificity and sensitivity with
combined use
Variable results; limited experience

The management
The management of invasive candidiasis in patients with COVID-19 is
similar to that of non-COVID-19 patients.

Timeline of antifungal development
1957
Amphotericin B (AMB)
1989
Lipid AMB
2005
Micafungin
1979
Miconazole
1992
Itraconazole
2001
Caspofungin
2006
Anidulafungin
1964
Flucytosine
1980
Ketoconazole
1990
Fluconazole
2002
Voriconazole
1995-97
Lipid AMB Salvage
Aspergillosis
2015
Isavuconazole
2006
Posaconazole
Adapted from: Chapman SW, et al. Trans Am Clin Climatol Assoc. 2008;119:197-215.

Antifungal indications by class
Class Agent Candidiasis Aspergillosis Mucormycosis
Polyenes Amphotericin B   
Triazoles
Fluconazole 
Itraconazole  
Voriconazole  
Posaconazole  
Isavuconazole

 
Echinocandins
Caspofungin  
Anidulafungin 
Micafungin  
Nucleic acid
analogues
Flucytosine 
Nett JE, et al. Infect Dis Clin North Am ;30(1);51-83. NAPCON 2021,Varanasi 2 nd April 2022

 Initial therapy
 An echinocandin - caspofungin: loading dose 70 mg, then 50 mg daily; micafungin: 100
mg daily; anidulafungin: loading dose 200 mg, then 100 mg daily
 Fluconazole in select patients (not critically ill and unlikely to be infected with a
fluconazole-resistant strain)- intravenous or oral, 800-mg (12 mg/kg) loading dose,
then 400 mg (6 mg/kg) daily.
 Susceptibility testing
 Azole in clinically relevant Candida isolates and candidemia
 Echinocandin with prior echinocandin treatment, or C. glabrata or
C. parapsilosis
Treatment for invasive Candidiasis
Pappas PG, et al. 2016 IDSA Guidelines. Clin Infect Dis. 2016;62(4):409-417.

 Lipid formulation amphotericin B (AmB) (3–5 mg/kg daily) is a reasonable
alternative if there is intolerance, limited availability, or resistance to other
antifungal agents .
 Empiric therapy - Fluconazole for high-risk patients in adult ICUs with >5% rate
of invasive candidiasis
 Recommended duration of therapy for candidemia without obvious metastatic
complications is for 2 weeks after documented clearance of Candida species
from the bloodstream and resolution of symptoms attributable to candidemia.
Treatment for invasive Candidiasis……
L-AmB, liposomal amphotericin B.
Pappas PG, et al. 2016 IDSA Guidelines. Clin Infect Dis. 2016;62(4):409-417.

Future modalities
 Therapy working to inhibit gene expression
 Treatment targeting the host’s micronutrient acquisition – iron chelators
 Identifying substances that can inactivate or hinder biofilm formation.
 Develop methods that inhibit antifungal-resistant mechanisms of Candida
species.
 The expansion of our limited range of antifungal treatment.

Is it preventable ?
 The majority of candidemia occurred due to nosocomial and/or iatrogenic
conditions rather than reasons associated with immune suppression .
 This suggests that the primary focus to prevent fungal co-infection should be
related to medical interventions.
 The surge of global COVID-19 cases has resulted in a shortage of PPE and
decreased practicing of routine health guidelines, such as proper hand hygiene .
 An increased focus on ensuring strict health guidelines like controlled antimicrobial
use, isolating patients infected with multi-drug resistant organisms, use of aseptic
techniques, and the conduction of regular microbiological tests on COVID-19
patients may contribute to the prevention of co-infections

Preventive measures …..
 Healthcare professionals in the COVID-19 unit must use eye protection,
gloves, gown, and must remove all PPE and perform hand hygiene before
exiting the unit.
 Mobiles, computers and medical equipment must always be disinfected
between uses.
 Infected catheters must be removed in the absence of alternative
treatments, such as antifungal lock therapy .
 Furthermore, a rapid diagnosis of CAC is required to prevent further fungal
transmission to non-infected individuals and enable timely treatment of the
infected patient to prevent poor prognosis.

to conclude
 Candidiasis has become more prevalent as the world continues to tackle COVID-19.
 The transition of Candida species from commensal to pathogen, the ability to switch
morphology and form biofilms, the progression of Candida spp. infection, and its
virulence factors are not yet entirely elucidated.
 Patients hospitalized for COVID-19 are at risk for candidemia. They are more likely to
have acute risk factors linked to COVID-19 care, including medicines that suppress the
immune system.
 Despite best of treatment mortality is very high. Prevention is the key.
 Further research is required to curb the rapid increase of Candidiasis and lessen the
burden of CAC in the world

Candidiasis NAPCON.pptx

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