Pilot Study on Septifast PCR for the Early Diagnosis of Invasive Fungal Infections in Neutropenic Patients with Acute Leukemia

Invasive fungal infections (IFIs) are opportunistic, especially in immunocompromised and hospitalized patients. Children with IFIs are more vulnerable to a fatal outcome. For early diagnosis and treatment, knowledge of the spectrum and frequency of IFIs among children is prerequisite. In this prospective observational study, we enrolled 168 children of 2–59 months old of either sex from March 2018 to December 2019 admitted to the Dhaka hospital, icddr,b. Study participants with suspected IFIs were with or without severe acute malnutrition (SAM) along with sepsis/pneumonia and fulfilled any of the following criteria: (i) failure to respond to injectable antibiotics, (ii) development of a late-onset hospital-acquired infection, (iii) needed ICU care for >7 days, (iv) took steroids/antibiotics for >2 weeks before hospitalization, and (v) developed thrush after taking injectable antibiotics. The comparison group included non-SAM (weight-for-length Z score ≥ −2) children with diarrhea and fever <3 days in the absence of co-morbidity. We performed real-time PCR, ELISA, and blood culture for the detection of fungal pathogen. Study group children with SAM, positive ELISA and PCR considered to have a IFIs. In the study group, 15/138 (10.87%) children had IFIs. Among IFIs, invasive candidiasis, aspergillosis, histoplasmosis detected in 6 (4.53%), 11 (7.97%), and 1 (0.72%) children, respectively, and (3/15 [2.17%]) children had both candidiasis and aspergillosis. Children with IFIs more often encountered septic shock (26.7% vs. 4.9%; p = 0.013) and had a higher death rate (46.7% vs. 8.9%; p < 0.001) than those without IFIs. IFIs were independently associated with female sex (OR = 3.48; 95% CI = 1.05, 11.55; p = 0.042) after adjusting for potential confounders. Our findings thus implicate that, malnourished children with septic shock require targeted screening for the early diagnosis and prompt management of IFIs that may help to reduce IFIs related deaths.

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New approaches to invasive fungal infections in acute leukemia and hematopoietic stem cell transplant patients

Best Practice & Research Clinical Haematology ◽

10.1016/j.beha.2006.11.008 ◽

2007 ◽

Vol 20 (1) ◽

pp. 99-107 ◽

Cited By ~ 16

Author(s):

John R. Wingard

Keyword(s):

Stem Cell ◽

Acute Leukemia ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Fungal Infections ◽

Invasive Fungal Infections ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Transplant Patients

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Amphotericin B prophylaxis against invasive fungal infections in neutropenic patients: A single center experience from 1980 to 1995

Infection ◽

10.1007/bf01716080 ◽

1996 ◽

Vol 24 (5) ◽

pp. 361-366 ◽

Cited By ~ 19

Author(s):

A. De Laurenzi ◽

A. Matteocci ◽

A. Lanti ◽

L. Pescador ◽

F. Blandino ◽

...

Keyword(s):

Amphotericin B ◽

Fungal Infections ◽

Invasive Fungal Infections ◽

Single Center ◽

Single Center Experience ◽

Neutropenic Patients

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Editorial Response: Evolving Risk Factors for Invasive Fungal Infections--All Neutropenic Patients Are Not the Same

Clinical Infectious Diseases ◽

10.1093/clinids/18.5.793 ◽

1994 ◽

Vol 18 (5) ◽

pp. 793-798 ◽

Cited By ~ 56

Author(s):

T. J. Walsh ◽

J. Hiemenz ◽

P. A. Pizzo

Keyword(s):

Risk Factors ◽

Fungal Infections ◽

Invasive Fungal Infections ◽

Neutropenic Patients

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Invasive fungal infections in acute leukemia patients

10.1183/13993003.congress-2021.pa1882 ◽

2021 ◽

Author(s):

Asli Öncel ◽

Yahya Buyukasik ◽

Omrum Uzun ◽

Ahmet Ugur Demir ◽

Lutfi Coplu

Keyword(s):

Acute Leukemia ◽

Fungal Infections ◽

Invasive Fungal Infections

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Itraconazole for Antifungal Prophylaxis in Neutropenic Patients: An Update of a Meta-Analysis with Now 3846 Patients.

Blood ◽

10.1182/blood.v106.11.3224.3224 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3224-3224

Author(s):

Axel Glasmacher ◽

Corinna Hahn ◽

Marie von Lilienfeld-Toal ◽

Katjana Orlopp ◽

Ingo Schmidt-Wolf ◽

...

Keyword(s):

Relative Risk ◽

Randomized Clinical Trials ◽

Fungal Infections ◽

Meta Analysis ◽

Cochrane Review ◽

Antifungal Prophylaxis ◽

Invasive Fungal Infections ◽

Significant Difference ◽

Neutropenic Patients ◽

Related Mortality

Abstract Invasive fungal infections, esp. from Aspergillus spp., still are a major cause of mortality and morbidity in neutropenic patients with haematological malignancies. We have published a meta-analysis on the use of itraconazole for antifungal prophylaxis (Glasmacher et al., JCO2003; 21: 4615) and now present updated results. Methods: In a continuous search of electronic databases and abstracts we identified randomized clinical trials in neutropenic patients that compared itraconazole with either nothing, oral polyenes or fluconazole. Again, analysis was restricted to proven invasive fungal infections according to EORTC/MSG criteria. Statistical analyses were performed with the Cochrane Review Manager (Version 2.4.8), relative risk ratios (RR) with their 95% confidence intervals (95%CI) and appropriate P values were reported. Subgroups were defined by itraconazole preparation and the comparator. A RR below 1 indicates better results for itraconazole. Results - New Trials: Two new trials with 54 and 195 evaluable patients (pts) were identified and the data of one unpublished trials was updated. Both studies used itraconazole solution (400 mg/d) and compared it to 400 mg/d fluconazole. One study applied intravenous solutions of both drugs if necessary. No study was powered to detect a significant difference in proven invasive fungal infections between the two drugs. One study reported a reduction of fungal-related mortality in the itraconazole arm (fluconazole 9/12, 75%, vs. itraconazole 5/11, 45%; P=0.154). Results - Meta-Analysis: The incidence of proven invasive fungal infection from all studies and arms was 4.1% and 8.3% if suspected infections were included. The reduction in the incidence of proven breakthrough invasive mycosis was significant (Table 1). As in the original analysis, the relative risk is reduced only in the group provided with itraconazole solution and with a relative risk reduction of 46%. Results - Itraconazole vs. Fluconazole: Table 2 reports a comparison of itraconazole solution vs. fluconazole for different relevant outcomes. There is a significant superiority of itraconazole for the reduction of all proven invasive fungal infections and for invasive Aspergillus infections and reductions are in the same range but not significant for the other outcomes. Conclusions: Itraconazole is still and significantly superior to its comparators, including fluconazole, in reducing the rate of breakthrough invasive fungal infections. This effect is only seen with the itraconazole oral or intravenous solution (at least 400 mg/d) which also reduce the rate of proven invasive Aspergillus infections. Table 1: Incidence of proven invasive fungal infections Subgroup No. Pts (Trials) Relative Risk 95%CI P All studies 3846 (15) 0.62 0.45–0.77 0.003 Itraconazole capsules 735 (5) 0.93 0.51–1.69 0.81 Itraconazole solution 3111 (10) 0.54 0.37–0.77 0.0008 Table 2: Comparison of itraconazole solution vs fluconazole (proven only) Outcome No. of trials Itraconazole (n/N) Fluconazole (n/N) Relative Risk 95%CI P Abbrev.: n= pts. with event; N=total pts. Invasive fungal infections 6 23/883 43/874 0.52 0.32–0.84 0.008 Invasive yeast infections 6 9/851 16//854 0.56 0.25–1.24 0.15 Invasive Aspergillus infections 5 12/850 24/853 0.50 0.26–0.98 0.04 Fungal-related Mortality 4 20/754 31/754 0.64 0.38–1.09 0.10

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