Treating patients with confirmed fungal disease with effective antifungal agents is crucial to reduce morbidity and mortality. Several investigations described a significant link between early reliable diagnosis and treatment of IFIs and improved outcomes of patients at risk

1. The Rising Emad Zarief MD
Anesthesia and intensive care d.
Assiut Faculty of Medicine
Enemy

2. Agenda
• Rising Risk
• Candida
• Aspergillus
• Pneumocystis
• Mucor mycosis

3. Traditionally, antimicrobial resistance
programs excluded antifungals because
fungi have been widely neglected as a threat
to public health !!!
Fisher Matthew C et al. . Nat Rev Microbiol.2022;20(9):557–571.
Emad Zarief 2023

4. Emad Zarief 2023
• Most environmental fungi cause no noticeable
pathophysiological events in healthy individuals
Fisher Matthew C et al. . Nat Rev Microbiol.2022;20(9):557–571.
isn't it?
• Some patients are susceptible to a spectrum of
disease including superficial, allergic, chronic
and life-threatening invasive fungal infections
(IFI) .

5. Emad Zarief 2023
Fisher Matthew C et al. . Nat Rev Microbiol.2022;20(9):557–571.
Those with immune systems compromised by
HIV, cancer chemotherapy or transplant-
necessitated immune suppression
therapy, those with severe infections with
influenza virus and COVID-19.
• Central venous catheter technology and
other invasive procedures.

6. Early symptoms of fungal bloodstream infection
lack specificity, and low culture-positive rates can
lead to a misdiagnosis
Infection. 2016;44:205–213.
Emad Zarief 2023
isn't it?

7. Emad Zarief 2023
Fisher Matthew C et al. . Nat Rev Microbiol.2022;20(9):557–571.
• Antifungal tolerant and resistant fungal
infections are an emerging threat.
• Novel resistant variants of previously susceptible
pathogens Aspergillus fumigatus.
isn't it? • Entirely new emerging species that
are resistant to multiple antifungal drugs
Candida auris

8. Emad Zarief 2023
Fisher Matthew C et al. . Nat Rev Microbiol.2022;20(9):557–571.
isn't it?

9. • Fungal epidemiology varies in different geographical regions and
dependent on multiple factors e.g.,
Sci Transl Med 2012; 4 :165rv13
Emad Zarief 2023

10. Emad Zarief 2023
• Although surveillance of such infections is essential, data in the
Middle Eastern and North African (MENA) region remain scarce.
• IFIs landscape changed dramatically in ICU over the past two
decades.
Braz J Microbiol (2020) 51:1771–1789

11. Emad Zarief 2023

12. • Candida infections accounts for approximately 70 to 90% of
total IFIs
• Candida spp. are 3rd leading cause of nosocomial
bloodstream infections but rank 1st in terms of mortality.
Lamoth F et al. J. Antimicrob. Chemother. 2018, 73, i4–i13.
Emad Zarief 2023

13. • The incidence of candidemia (3.5-16.5/1000 admissions)
depending on different studies and countries
• It is of higher incidence in ICUs (5.1/1000 admissions),
compared to tertiary care centers (0.96/1000 admissions).
• The incidence of candidemia has ↑↑ by 50% over the past 10
years
Emad Zarief 2023

14. ▪ Can colonize on inert surfaces
▪ Resistant to the commonly used chlorine-based disinfectants
▪ Has potential to be misidentified by current diagnostic systems.
▪ Non-susceptibility to any or all the systemic antifungal drugs
available currently
Pappas PG et al. Nat Rev Dis Primers. 2018;11;4:18026.
Emad Zarief 2023

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16. Emad Zarief 2023

17. • The impact of delaying antifungal treatment is well-known in
candidemia
• Mortality with candidemia → 10% if antifungals are introduced in the 12 h
following the first positive blood culture sample versus >30% if treatment is
delayed for more than 48 h
Agents Chemother. 2005, 49, 3640–3645.
Mortality
Emad Zarief 2023

18. In the case of septic shock, mortality around 60% at D28 if treatment
is introduced in the 24 h following the diagnosis of candidemia with
adequate control of the infection source, to 90% in the case of a delay of
more than 24 h
Clin. Infect. Dis. 2012, 54, 1739–1746
Emad Zarief 2023

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20. • 20 years ago, IA was mainly seen in immunosuppressed
patients, e.g., hematological disorders and cancer, especially
during periods of neutropenia.
• The prevalence of IA has ↓↓as a result of antifungal prophylaxis.
• But IA is still associated with high mortality rates
Aspergillosis
Invasive
Indian J Med Res. 2014 Feb;139(2):195-204.
Emad Zarief 2023

21. Emad Zarief 2023

22. Braz J Microbiol (2020) 51:1771–1789
Emad Zarief 2023
• Asp. Fumigatus (The commonest worldwide)
• A. flavus
• A. niger
• A. terreus
• A. versicolor.
• Despite the growing concern of aspergillosis, it is not thoroughly reported in
most MENA countries.

23. o Pulmonary
o Sino- orbital- cerebral
o Cardiac
o Disseminated
o Endophthalmitis
o Invasive cutaneous
Medical Mycology 2011, 49(Suppl. 1), S35–S47
Emad Zarief 2023

24. Emad Zarief 2023
Braz J Microbiol (2020) 51:1771–1789

25. • Invasive A. fumigatus predominated hospital discharges in both
Lebanon and Saudi Arabia (60%)
• A Fumigatus was responsible for 53% of IA in Bahrain.
• A. flavus was predominant in 75% of BAL samples in Iran and 79%
among clinical samples of hematology patients in Tunisia
Braz J Microbiol (2020) 51:1771–1789
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F
.

26. ▪ IFI an important cause of morbidity and mortality among high-risk
groups including SOT recipients and hematological malignancy patients.
▪ Mortality rates were the highest for IA (67–82%) as well as cerebral forms
of mucormycosis (73.5%)
Emad Zarief 2023
SOT solid organ transplantation

27. C. neoformans is the most common fungal agent
that causing meningoencephalitis in the immunocompromised
individuals worldwide
Lancet Infect Dis. 2013; 13:629–637
Emad Zarief 2023

28. ▪ Cm is a rare fungal infection, it could not be estimated in
Jordan, Iraq.
▪ It could probably be affecting <10 patients in Saudi Arabia.
▪ In Qatar, CM had a low estimated incidence rate of 0.43
cases per 100,000
Braz J Microbiol (2020) 51:1771–1789
Emad Zarief 2023

29. Eur J Clin Microbiol Infect Dis 2017;36:971–974
Emad Zarief 2023

30. A 2016 cross-sectional study in Tunisia
declared that CM was responsible for 11%
out of 70.4% deaths associated with HIV
Braz J Microbiol (2020) 51:1771–1789
Emad Zarief 2023
Morocco :CM accounted for 20% of
neurological disorders involved that was
suggestive of HIV infection in 68.8% cases .
Eur J Clin Microbiol Infect Dis 2017;36:971–974

31. Emad Zarief 2023
https://www.infectiousdiseaseadvisor.com/home/topics/hiv-aids/global-burden-hiv-cryptococcal-
meningitis-deaths/

33. ▪ IFI ordinarily seen in individuals with underlying predisposing risk factors
including DM and hematological malignancies → Disseminated forms
▪ Rhino-sinusoidal and cutaneous forms may occur in all individuals
Krishnappa D, Naganur S, Palanisamy D, Kasinadhuni G (2019) Cardiac mucormycosis: a case report. Eur
Heart J Case Rep 3
Emad Zarief 2023

34. ▪ Estimated incidence rates were scarce. The highest estimated
rate was in Iran at 9.2 per 100,000 population, then in Iraq
and Algeria at 0.2 per 100,000.
Karzan MA, Ismael HM, Shekhany K, Al-Attraqhchi AAF, Abdullah S, Aldabbagh R, Denning DW (2014)
Burden of serious fungal infection in Iraq
Emad Zarief 2023

35. • Proven mucormycosis developed in 45 patients in which 90% of the cases had
hematological malignancies.
• Mucormycosis-related mortality was 33%
Mycoses. 2019 Nov;62(11):984-9.
Emad Zarief 2023

36. ▪ IFI an important cause of morbidity and mortality among high-risk
groups including SOT recipients and hematological malignancy patients.
▪ Mortality rates were the highest for IA (67–82%) as well as cerebral forms
of mucormycosis (73.5%)
Emad Zarief 2023
SOT solid organ transplantation

37. Emad Zarief 2023

38. Emad Zarief 2023
Final Words
Histopathological
confirmation still
plays an
important role in
this field.
There is a need for risk
stratification to target groups of
patients with the highest risk of
IFI

39. Emad Zarief 2023
Journal of Fungi. 2022; 8(9):946.
• A big need to develop and adapt tools suitable for use in low- and
middle-income countries.
• Increase availability of rapid and simple antifungal resistance
screening techniques suitable for local clinical laboratories
Fisher Matthew C et al. . Nat Rev Microbiol.2022;20(9):557–571.

40. • Treating patients with confirmed fungal disease with effective
antifungal agents is crucial to reduce morbidity and mortality.
• Several investigations described a significant link between early
reliable diagnosis and treatment of IFIs and improved outcomes of
patients at risk
Early diagnosis / treatment of IFI
Cole DC et al. The Lancet Infectious Diseases. 2017;17(12):e412-9.
Emad Zarief 2023

41. Emad Zarief 2023
• A need to appoint National reference laboratories to monitor
antifungal resistance
Nat Rev Microbiol.2022;20(9):557–571.
Journal of Fungi. 2022; 8(9):946.
• The misuse of new sensitive tools → Overestimation of the real
prevalence of a disease and overtreatment→ Resistance.
• Increase fundamental research to identify molecular mechanisms
of antifungal resistance and associated diagnostic markers

42. Thank You
emadzarief@aun.edu.eg

43. Thank You
emadzarief@aun.edu.eg