Mucormycosis of the neonatal gut: A “new” disease or a variant of necrotizing enterocolitis?

Woodward, Aidan J.; McTigue, Christine; Hogg, Geoff; Watkins, Angela S.; Tan, Hwee Cheng

doi:10.1016/s0022-3468(05)80104-6

Cited by 36 publications

(45 citation statements)

References 16 publications

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“…It has mostly occurred in premature neonates and is often associated with disseminated diseases (8,18,35,41). Necrotizing enterocolitis was found in premature neonates (29,43,63) and less frequently in neutropenic adults (47,48). All of our five cases of invasive intestinal zygomycosis had severe necrotizing ileocecitis leading to intestinal perforation with or without retroperitoneal necrosis, which was in contrast to the classical reports of the stomach being the most frequently involved site in adults with gastrointestinal zygomycosis (32).…”

Section: Discussionmentioning

confidence: 99%

Outbreak of Intestinal Infection Due to Rhizopus microsporus

Cheng

Chan²,

Ngan³

et al. 2009

J Clin Microbiol

117

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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: Discussionmentioning

confidence: 99%

Outbreak of Intestinal Infection Due to Rhizopus microsporus

Cheng

Chan²,

Ngan³

et al. 2009

J Clin Microbiol

117

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“…In particular, gastrointestinal mucormycosis has been seen in premature neonates, often in association with widespread disseminated disease (6,27,71,76,128,137). Necrotizing enterocolitis has been described largely in premature neonates (35,71,106,128,139,157,174,177) and more rarely in neutropenic adults (146,152). Rare cases of gastrointestinal mucormycosis have been described in association with other immune-compromising conditions, including AIDS (19), systemic lupus erythematosus (55), and organ transplantation (77,95,97,138).…”

Section: Epidemiology and Disease Manifestationsmentioning

confidence: 99%

Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management

2005

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Mucormycosis is a life-threatening fungal infection that occurs in immunocompromised patients. These infections are becoming increasingly common, yet survival remains very poor. A greater understanding of the pathogenesis of the disease may lead to future therapies. For example, it is now clear that iron metabolism plays a central role in regulating mucormycosis infections and that deferoxamine predisposes patients to mucormycosis by inappropriately supplying the fungus with iron. These findings raise the possibility that iron chelator therapy may be useful to treat the infection as long as the chelator does not inappropriately supply the fungus with iron. Recent data support the concept that high-dose liposomal amphotericin is the preferred monotherapy for mucormycosis. However, several novel therapeutic strategies are available. These options include combination therapy using lipid-based amphotericin with an echinocandin or with an azole (largely itraconazole or posaconazole) or with all three. The underlying principles of therapy for this disease remain rapid diagnosis, reversal of underlying predisposition, and urgent surgical debridement

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“…However, gastrointestinal mucormycosis is rare, being more common at other sites. Cases of gastrointestinal mucormycosis have been described in premature neonates, neutropenic adults, and in the setting of organ transplantation [12,14,[23][24][25]. Mucormycosis has been described in the setting of inflammatory bowel disease, but was, in 1 case, disseminated and in another, cutaneous after therapy for pyoderma gangrenosum [26,27].…”

Section: Discussionmentioning

confidence: 99%