INITIATING

ANTIFUNGAL
THERAPY
Case Summary

■ 55-year-old lady , K/c/o Ca Esophagus – s/p Radiotherapy, was admitted for elective surgery-

esophagectomy.

■ K/C/O HTN

■ Underwent Transthoracic Esophagectomy under GA on 09/03/2022.

■ Central venous catheter was placed intraoperatively.

■ Patient was extubated on the same day.

■ Patient was started on TPN in the subsequent days.

Case Summary

■ She did well the following week

■ From POD 13 – 14, patient had chyle leak from right chest drain.

■ Underwent Inguinal lymphangiography- embolization on 23/03/2022

■ The chyle leak persisted, and eventually she had to undergo mini thoracotomy and
thoracic duct ligation on 26/03/2022

■ Patient had left sided pleural effusion: therapeutic tapping was done twice.
Case Summary
■ ~ POD 20, patient developed fever f/b shock, and respiratory distress.

■ Patient was shifted to ICU , and was put on NIV and vasopressor support

■ Patient was worked up for Sepsis ,PTE and cardiac dysfunction.

■ After securing a PICC line, jugular CVC was removed; blood/urine/pleural fluid
cultures were sent.

■ Antibiotics were escalated to meropenem, tigecycline.

■ In view of CANDIDA score ~4 , IV fluconazole was started empirically in

therapeutic doses (IDSA 2016).
■ subsequently, culture reported Candida tropicalis.

■ Pleural fluid / urine cultures yielded no growth.

■ Under antifungal cover patient gradually recovered from this point with multidisciplinary involvement
and optimization, without any further invasive intervention.

■ She was discharged in stable condition on 18/04/2022.

 Piperacillin +
Cefoperazone + sulbactum Meropenem
Tazobactum
Metronidazole Amikacin Tigecycline

Fluconazole Tab Voriconazole

FEVER, rising counts, Shock

Chyle Leak
CVC removed

Thoracic duct ligation

ESOPHAGECTOMY

Empirical Antifungal

DISCHARGED
Embolisation

CVC tip Culture

C. Tropicalis

TC- TC- 10.1 PCT- TC- 15.4 TC- 11.5 PCT- TC- 7.5
5.1 N-82% 0.05 N- 93.1 N- 91.1 0.09 N- 82%
N-88%

07/03 09/03 23/03 26/03 31/03 03/04 18/04

 Invasive fungal infections
• HEALTHCARE
COST HIGH
• RESISTANCE
MORTALITY ~80%
• UNDUE A/E

DIFFICULT
DIAGNOSIS

UNWARRENTED THERAPY
THERAPY DELAYED
Invasive fungal infections

Decreasing immunity
ICU patients/ post
surgical
Candidiasis
70 - 90%

Aspergillosis
Hematological 10-20%
Malignancy/BMT
Flückiger E et al. Swiss Med Wkly 2006;136:447-463.
Chamilos et al. Haematologica. 2006;91:986–989.
Neofytos D Transplant Infect Dis 2010;12(3):220-229
 COLONIZATION CANDIDA INFECTION

■ Candida species isolated in non- ■ Blood culture -Candida species

significant samples - oropharynx,
■ Isolation of Candida species in
urine, or tracheal aspirates.
significant samples (e.g., pleural
■ Unifocal colonization - Isolated from
fluid, pericardial fluid, Candidal
one focus
peritonitis or histology based.
■ Multifocal colonization -
Simultaneously isolated from various ■ Endophthalmitis on ophthalmic

noncontiguous foci examination-

Candida score
A bedside scoring system for early antifungal treatment in non-neutropenic critically ill
patients.
■ (0.908) 1 for TPN
■ (0.997) 1 for SURGERY
■ (1.112) 1 for MULTIFOCAL COLONISATION
■ (2.038) 2 for CLINICAL SEVERE SEPSIS

Cut-off value > 2.5 (sensitivity 81% , specificity 74% ) , 7.75 times to have proven
infection
Cut-off of < 3.0 has Negative Predictive Value IC in non-neutropenic ICU patients

Leon C, et al. Crit Care Med. 2006;34:730-7.

Leon C, et al. Crit Care Med. 2009;37:1624-33
BIOMARKERS ++ Good NPV -- Costly
1, 3, Beta-D-glucan Galactomannan
■ Polysaccharide cell wall component of many ■ Polysaccharide cell wall component of
fungi aspergillus

■ Candida OR Aspergillus ■ Aspergillus

■ Sen- 55-95%, Spec- 77-96% ■ NPV > 90%, sen-82 %. Spec-81%

■ False +ve ■ False +ve

• Penicillin antibiotics • Beta lactum antibiotics
• Gauze packing of serosal surfaces • IVIG
• HD with cellular membranes • GI mucositis, Intestinal GVHD
• IVIG, Albumin
Diagnosis
Blood Culture remains “gold standard”
– But up to 50% of cases may be missed

– Upto 72H delay before positive culture.

– Additional 24-48H delay before species identification and susceptibility results are known.

■ RAPID DIAGNOSIS

1) Polymerase Chain Reactions (PCR)- 60 minutes

2) Matrix-Assisted Laser Desorption/Ionization-Time Of Flight (MALDI-TOF) – 5 minutes

3) Fluorescence In Situ Hybridization Using Peptide Nucleic Acid Probes ( PNA FISH) – 90 minutes
Antifungal TARGETED -
Treatment TAR
DIAGNOSIS
DRIVEN

Strategies

Mycoses. 2008 Sep;51 Suppl 2:46-51.

Antifungal Treatment Strategies
Culture/
Sign/ Radiological/
High Risk Histo-path
Symptom Serological
positive
Prophylactic
FEAR
Yes No No No

Empiric
FEVER
Yes Yes ± (Usually No) No

Pre-emptive
EVIDENCE
Yes ± (Usually Yes) Yes No

Targeted
DIAGNOSIS
Yes Yes ± Yes

Mycoses. 2008 Sep;51 Suppl 2:46-51.

Empiric Treatment for Suspected Invasive
Candidiasis in Non-neutropenic patients

■ Critically ill patients with risk factors for invasive candidiasis and
having no other known cause of persistent fever , having serologic
markers/ culture data from non-sterile site.

■ Echinocandin- 1st choice

■ Fluconazole- in a relatively stable patient , ( if no recent azole

exposure/azole resistance not documented)

■ Stop Rx- if no response in 4-5 days/ negative biomarker/ culture.

IDSA 2016
Treatment for Candidemia in Non-
neutropenic Patients
• ECHINOCANDINS (Caspofungin/ Micafungin/ Anidulafungin)

De-escalate to fluconazole (usually within 5–7 days) in stable patients, or culture isolates
that are susceptible to fluconazole, or get a negative culture after Rx.
• FLUCONAZOLE: for patients who are not critically ill / no recent azole exposure / not
colonized with azole-resistant Candida species.
• VORICONAZOLE: effective for candidemia, but offers little advantage over
fluconazole as initial therapy
• LIPID AMP-B – in resistant cases / optimize as per culture and response.
• Duration of treatment –minimum of two weeks after blood cultures come negative, and
longer in metastatic foci of infection.
IDSA 2016
 Invasive Aspergillosis (IA)- initial Rx
guidelines
■ Voriconazole - 6 mg/kg IV 12th hourly for 1 day, followed by 4 mg/kg IV 12th hourly; oral therapy

can be used at 200 mg every 12 h, Alternatively

■ Liposomal AmB - 3–5 mg/kg/day IV

■ Isavuconazole - 200 mg 8th hourly for 6 doses, then 200 mg daily. Can switch over between IV/Oral.

■ Salvage: Individualized to each case. Switch over to different class drug /combination.

■ No role of Echinocandin monotherapy, can be used in combination.

■ Longer duration of treatment – 6-12 weeks, depending on degree and duration of immunosuppression,

site of disease, and evidence of disease improvement IDSA 2016