Invasive colonic mucormycosis in early induction therapy of childhood acute lymphoblastic leukemia

Sellappan, Boopathi; Bakhshi, Sameer; Safaya, Rajni; Gupta, Arun Kumar; Arya, L. S.

doi:10.1007/bf02760587

Cited by 9 publications

(6 citation statements)

References 11 publications

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“…Furthermore, the infecting dose was likely to be rather substantial, because in at least two of our cases (cases 1 and 2), the onset of invasive diseases occurred immediately after the first cycle of induction chemotherapy for acute leukemia. This phenomenon was also shown in a recent case report (40). Since the duration of the neutropenic phase was less than 2 weeks in our cases (cases 1 and 2), the risk of invasive fungal infection should not have been high unless there was a significant load of microbial exposure (14).…”

Section: Discussionsupporting

confidence: 86%

Outbreak of Intestinal Infection Due to Rhizopus microsporus

Cheng

Chan²,

Ngan³

et al. 2009

J Clin Microbiol

119

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Sinopulmonary and rhinocerebral zygomycosis has been increasingly found in patients with hematological malignancies and bone marrow transplantation, but intestinal zygomycosis remains very rare in the literature. We investigated an outbreak of intestinal infection due to Rhizopus microsporus in 12 patients on treatment for hematological malignancies over a period of 6 months in a teaching hospital. The intake of allopurinol during hospitalization (P < 0.001) and that of commercially packaged ready-to-eat food items in the preceding 2 weeks (P < 0.001) were found to be independently significant risk factors for the development of intestinal zygomycosis. A total of 709 specimens, including 378 environmental and air samples, 181 food samples, and 150 drug samples, were taken for fungal culture. Among them, 16 samples of allopurinol tablets, 3 prepackaged ready-to-eat food items, and 1 pair of wooden chopsticks were positive for Rhizopus microsporus, which was confirmed by ITS1-5.8S-ITS2 rRNA gene cluster (internal transcribed spacer [ITS]) sequencing. The mean viable fungal counts of allopurinol obtained from wards and pharmacy were 4.22 ؋ 10 3 CFU/g of tablet (range, 3.07 ؋ 10 3 to 5.48 ؋ 10 3 ) and 3.24 ؋ 10 3 CFU/g of tablet (range, 2.68 ؋ 10 3 to 3.72 ؋ 10 3 ), respectively, which were much higher than the mean count of 2 ؋ 10 2 CFU/g of food. Phylogenetic analysis by ITS sequencing showed multiple clones from isolates of contaminated allopurinol tablets and ready-to-eat food, of which some were identical to patients' isolates, and with one isolate in the cornstarch used as an excipient for manufacture of this drug. We attempted to type the isolates by random amplification of polymorphic DNA analysis, with limited evidence of clonal distribution. The primary source of the contaminating fungus was likely to be the cornstarch used in the manufacturing of allopurinol tablets or ready-to-eat food. Rhizopus microsporus is thermotolerant and can multiply even at 50°C. The long holding time of the intermediates during the manufacturing process of allopurinol amplified the fungal load. Microbiological monitoring of drugs manufactured for highly immunosuppressed patients should be considered.Zygomycosis has become an important emerging infection in patients with hematological malignancy undergoing chemotherapy or bone marrow transplantation (24), especially with the availability of voriconazole as antifungal prophylaxis (25,28,44). Breakthrough zygomycosis in patients on voriconazole prophylactic treatment is usually manifested as sinopulmonary or rhinocerebral disease, since the fungal spores are ubiquitously found in the environment and could therefore be acquired through inhalation or traumatic inoculation through the skin or mucosa. Gastrointestinal zygomycosis has been a rare clinical entity (50, 54), but cases or outbreaks of tongue, gastric, or cutaneous zygomycosis due to Rhizopus microsporus after exposure to contaminated wooden tongue depressors have been reported (23,26,33).The Rhizopus microsporus species gr...

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Section: Discussionsupporting

confidence: 86%

Outbreak of Intestinal Infection Due to Rhizopus microsporus

Cheng

Chan²,

Ngan³

et al. 2009

J Clin Microbiol

119

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“…Mucormycosis can involve any part of the digestive tract [59,160,[258][259][260][261][262][263][264][265][266][267][268][269][270][271][272][273][274][275][276][277], with a mortality rate of 98% according to a published series of 25 accumulated cases [59].…”

Section: O T H E R C L I N I C a L M A N I F E S T A T I O N Smentioning

confidence: 99%

“…Mucormycosis can involve any part of the digestive tract [59,160,258–277], with a mortality rate of 98% according to a published series of 25 accumulated cases [59].…”

Section: Other Clinical Manifestationsmentioning

confidence: 99%

Mucormycosis: an emerging disease?

Bouza

Muñóz

Guinea

2006

Clinical Microbiology and Infection

137

127

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A B S T R A C TMucormycosis is the third invasive mycosis in order of importance after candidiasis and aspergillosis and is caused by fungi of the class Zygomycetes. The most important species in order of frequency is Rhizopus arrhizus (oryzae). Identification of the agents responsible for mucormycosis is based on macroscopic and microscopic morphological criteria, carbohydrate assimilation and the maximum temperature compatible with its growth. The incidence of mucormycosis is approximately 1.7 cases per 1000 000 inhabitants per year, and the main risk-factors for the development of mucormycosis are ketoacidosis (diabetic or other), iatrogenic immunosuppression, use of corticosteroids or deferoxamine, disruption of mucocutaneous barriers by catheters and other devices, and exposure to bandages contaminated by these fungi. Mucorales invade deep tissues via inhalation of airborne spores, percutaneous inoculation or ingestion. They colonise a high number of patients but do not cause invasion. Mucormycosis most commonly manifests in the sinuses (39%), lungs (24%), skin (19%), brain (9%), and gastrointestinal tract (7%), in the form of disseminated disease (6%), and in other sites (6%). Clinical diagnosis of mucormycosis is difficult, and is often made at a late stage of the disease or post-mortem. Confirmation of the clinical form requires the combination of symptoms compatible with histological invasion of tissues. The probable diagnosis of mucormycosis requires the combination of various clinical data and the isolation in culture of the fungus from clinical samples. Treatment of mucormycosis requires a rapid diagnosis, correction of predisposing factors, surgical resection, debridement and appropriate antifungal therapy. Liposomal amphotericin B is the therapy of choice for this condition. Itraconazole is considered to be inappropriate and there is evidence of its failure in patients suffering from mucormycosis. Voriconazole is not active in vitro against Mucorales, and failed when used in vivo. Posaconazole and ravuconazole have good activity in vitro. The overall rate of mortality of mucormycosis is approximately 40%.

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“…Vadeboncoeur et al described a fatal small intestinal mucormycosis in a 31-month-old boy with large cell anaplastic lymphoma early after chemotherapy presented with a gangrenous ileo-ileal intussusception [ 16 ]. Sellappan et al reported a colonic mucormycosis in a 10-year-old male child with Down's syndrome and B-precursor-ALL during induction chemotherapy with a fatal outcome [ 17 ]. Totadri et al described a fatal small intestinal mucormycosis in a 10-year-old male child with B-precursor-ALL during the consolidation phase of chemotherapy [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Case reports of invasive mucormycosis associated neutropenic enterocolitis in leukemic children: diagnostic and treatment challenges and review of literature

et al. 2021

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Background Bacterial enterocolitis is one of the most common neutropenic fever complications during intensive chemotherapy. Despite aggressive antibacterial treatments, this complication usually imposes high morbidity and mortality in cancer patients. Management of bacterial neutropenic enterocolitis are well known; however, management of fungal neutropenic enterocolitis may be more challenging and needs to be investigated. Prompt diagnosis and treatment may be life-saving, especially in patients at risk of mucormycosis-associated neutropenic enterocolitis. Case presentation We report two mucormycosis-associated neutropenic enterocolitis cases in pediatric leukemic patients receiving salvage chemotherapy for disease relapse. Both patients' clinical signs and symptoms differ from classical bacterial neutropenic enterocolitis. They were empirically treated as bacterial neutropenic enterocolitis with anti-gram-negative combination therapy. Despite broad-spectrum antimicrobial treatment, no clinical improvement was achieved, and both of them were complicated with severe abdominal pain necessitating surgical intervention. Mucormycosis is diagnosed by immunohistopathologic examination in multiple intraoperative intestinal tissue biopsies. Both patients died despite antifungal treatment with liposomal amphotericin-B and surgical intervention. Conclusion Mucormycosis-associated neutropenic enterocolitis is one of the most unfavorable and untreatable side effects of salvage chemotherapy in leukemic children with disease relapse. This report could be of considerable insight to the clinicians and scientists who counter the enigma of fungal infections during febrile neutropenia and help to understand better diagnosis and management.

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Invasive colonic mucormycosis in early induction therapy of childhood acute lymphoblastic leukemia

Cited by 9 publications

References 11 publications

Outbreak of Intestinal Infection Due to Rhizopus microsporus

Outbreak of Intestinal Infection Due to Rhizopus microsporus

Mucormycosis: an emerging disease?

Case reports of invasive mucormycosis associated neutropenic enterocolitis in leukemic children: diagnostic and treatment challenges and review of literature

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