The Compromised Host and Infection. II. Deep Fungal Infection

Pd, Hart; Russell, E; Js, Remington

doi:10.1093/infdis/120.2.169

Cited by 346 publications

(99 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mucormycosis in humans is rare in the absence of preexisting disease states known to affect immune competence (1). One such underlying disease is diabetes mellitus, and its specific association with mucormycosis is well documented (2).…”

Section: Introductionmentioning

confidence: 99%

Specific susceptibility to mucormycosis in murine diabetes and bronchoalveolar macrophage defense against Rhizopus.

Waldorf¹,

Ruderman²,

Diamond³

1984

J. Clin. Invest.

198

149

View full text Add to dashboard Cite

Abstract. To assess the influence of diabetes mellitus in predisposing to pulmonary mucormycosis, a murine model of streptozotocin-induced diabetes was used. Intranasal inoculation of Rhizopus oryzae into diabetic mice resulted in mucormycotic infection with histopathology resembling pulmonary mucormycosis observed in humans. There was no mortality nor infection in inoculated normal mice. Diabetic mice had fatal infections caused by R. oryzae but significantly reduced mortality following inoculation with Aspergillus fumigatus. These findings reflect the specific enhanced susceptibility to mucormycosis observed in human diabetics.Normal bronchoalveolar macrophages formed part of an efficient defense against R. oryzae by inhibiting germination, the critical step in the conversion of R. oryzae to its tissue invasive phase. Bronchoalveolar macrophages inhibited spore germination in vitro and appeared to help prevent germination in vivo. In contrast, spore germination occurred in diabetic mice following intranasal inoculation. Diabetic bronchoalveolar macrophages had a decreased ability to attach to hyphae. In diabetic mice, bronchoalveolar macrophages could damage spores or hyphae of R. oryzae, but serum factors appeared to both promote spore germination and impair attachment of macrophages to spores. This murine model ofdiabetes mellitus provides an opportunity for evaluation of the relative importance of cell and serum-mediated host factors in the pathogenesis of mucormycosis.Portions of this work were presented at a meeting of the American

show abstract

Section: Introductionmentioning

confidence: 99%

Specific susceptibility to mucormycosis in murine diabetes and bronchoalveolar macrophage defense against Rhizopus.

Waldorf¹,

Ruderman²,

Diamond³

1984

J. Clin. Invest.

198

149

View full text Add to dashboard Cite

show abstract

“…The incidence of candidemia or invasive pulmonary infection which results from this colonization is unkiiown. However, an increasing problem with disseminated candidiasis and candida pneumonia in these patients has been reported (7,8).Antibiotics, administered to respiratory mucosal surfaces via aerosal spray, have been effective in reducing the incidence of gram-negative bacterial colonization of the respiratory tract in certain groups of patients (6, 9). Attempts at eradicating oropharyngeal candida using local nystatin therapy have been less successful, particularly in leukopenic patients (8).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

5-Fluorocytosine and Amphotericin B in Bronchial Secretions

Pennington

Block

Reynolds

1974

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The penetration into and clearance from bronchial secretions of 5-fluorocytosine and amphotericin B were studied in a dog model. After a single intravenous dose of 35 mg/kg, 5-fluorocytosine intrabronchial concentrations were greater than the minimal inhibitory concentration for 80 to 90% of Candida species. These inhibitory concentrations persisted up to 3 h. In contrast, amphotericin B in intravenous doses of 0.6 and 1.2 mg/kg penetrated the blood-bronchus barrier poorly.Colonization of the tracheobronchial tree with Candida species (usually C. albicans) is not uncommon in debilitated and immunosuppressed patients. Endotracheal intubation or tracheostomy (9), and the use of broad-spectrum antibiotics (18), render patients especially prone to candida colonization. The incidence of candidemia or invasive pulmonary infection which results from this colonization is unkiiown. However, an increasing problem with disseminated candidiasis and candida pneumonia in these patients has been reported (7,8).Antibiotics, administered to respiratory mucosal surfaces via aerosal spray, have been effective in reducing the incidence of gram-negative bacterial colonization of the respiratory tract in certain groups of patients (6, 9). Attempts at eradicating oropharyngeal candida using local nystatin therapy have been less successful, particularly in leukopenic patients (8). Effective control of mucosal candida colonization and infection may depend upon using systemic therapy in such patients (8).Although low-dose amphotericin B therapy has been advocated for certain superficial candida infections (14), use of this potentially toxic drug in a debilitated patient is usually reserved for life-threatening fungal infection. Fivefluorocytosine (5-FC) has proven to be clinically useful in treating candida infections and is relatively nontoxic (1). To assess the potential value of 5-FC in controlling respiratory tract colonization with candida, a study of 5-FC penetration into bronchial secretions was done, using a dog model. For comparison, amphotericin B concentrations in bronchial secretions were also evaluated.MATERIALS AND METHODS Animal studies. A dog model (15) for the study of antibiotic diffusion into and clearance from normal bronchial secretions was used in this study. American foxhounds (approximately 20 kg) were anesthetized with 2.5% sodium thiamylal and intubated with a rubber endotracheal tube. Subcutaneous pilocarpine HCl was given (0.5 mg/kg every 45 min) to stimulate an adequate flow of bronchial secretions (about 1 ml/h) for specimen collection. Volumes were small so that significant dilution did not occur. Previous work has demonstrated little change in the constituents of bronchial secretions after pilocarpine administration (15). Bronchial secretion specimens were aspirated via the endotracheal tube using a small-bore (1.25 mm) plastic catheter inserted to maximal depth within a mainstem bronchus. A syringe attached to the catheter provided adequate suction. Bronchial secretion specimens were each approximately 0....

show abstract

“…Blood culture techniques are relatively insensitive with only 50 % positivity in autopsy proven disseminated cases [9,10]. Recent introduction of lysis-centrifugation method improved detection rates of yeast in comparison to blood culture systems.…”

mentioning

confidence: 99%

A Case of Pediatric Acute Lymphoblastic Leukemia with Invasive Candidiasis: Short Review

Verma

Dubashi

Parameswaran

et al. 2013

Indian J Hematol Blood Transfus

View full text Add to dashboard Cite

Mortality rate associated with invasive fungal infections is very high. Early suspicion for fungal infections is important during intensive chemotherapy for acute leukemia. Empirical treatment with antifungals amphotericin B or caspofungin should be started if patient is not responding to broad spectrum antibiotics and if expected duration of neutropenia is prolonged. We are reporting a 3 years old girl child with diagnosis of pre-B acute lymphoblastic leukemia who developed invasive candidiasis with typical clinical and radiological findings during induction chemotherapy. Candida non-albicans was isolated and she was treated with amphotericin B followed by caspofungin. Patient deteriorated after initial response and succumbed to death. Species identification and sensitivity pattern of fungus can help in selecting appropriate antifungal drug.Keywords Invasive candidiasis Á Acute lymphoblastic leukemia Á Candida non-albicans This 3-year old girl presented in June 2012 at JIPMER with fever off and on and progressive abdominal distension for 2 months. Fever was high grade intermittent associated with significant lethargy. There was no history of headache, vomiting, cough, expectoration, chest pain, diarrhea, abdominal pain or any urinary symptoms. Patient developed progressive paleness of body over 2 months. There was no history of bleeding, join pain or arthralgia. At presentation blood pressure was 100/70 mm of Hg and pulse rate was 126/minute regular. Patient had marked pallor, facial puffiness and multiple cervical and axillary lymph nodes, maximum 2.0 9 1.5 cm in size. Systemic examination showed moderate hepatosplenomegaly.Hemogram showed Hb = 11.3 gm/dl, TLC-5400/cmm and platelets-5000/cmm differential count showed 60 % blasts with morphololgy suggestive of lymphoblast. Bone marrow aspiration differential showed 90 % blasts. Bone marrow flocytometry showed positivity of CD19, CD34, HLA-DR, CD10 and cCD79 suggestive of pre-B acute lymphoblastic leukemia. CSF examination was normal. Baseline chest X-ray was normal and USG abdomen showed hepatosplenomegaly.Patient was started on tumor lysis measures followed by MCP-841 acute lymphoblastic leukemia (ALL) induction protocol. Initially patient tolerated chemotherapy well and became afebrile from day-3 onwards. Day-20 of induction therapy patient developed high grade fever in background of severe neutropenia (ANC \ 100/mm 3 ). Bacterial and fungal blood cultures were sent. Patient was started on empirical IV antibiotics (ceftazidime and amikacin). After two days patient developed papulonodular skin rashes all over the body predominantly on extremities ( Fig. 1) with progressive splenomegaly. Peripheral smear did not show any blasts. There was no evidence of oral candida and fundus examination was normal. She was started empirically on amphotericin B. Blood culture showed candida non-albicans. FNAC from skin lesions showed budding yeast. Candida sub-species identification and drug sensitivity pattern could not be done due to unavailability of test. Abdomina...

show abstract

The Compromised Host and Infection. II. Deep Fungal Infection

Cited by 346 publications

References 51 publications

Specific susceptibility to mucormycosis in murine diabetes and bronchoalveolar macrophage defense against Rhizopus.

Specific susceptibility to mucormycosis in murine diabetes and bronchoalveolar macrophage defense against Rhizopus.

5-Fluorocytosine and Amphotericin B in Bronchial Secretions

A Case of Pediatric Acute Lymphoblastic Leukemia with Invasive Candidiasis: Short Review

Contact Info

Product

Resources

About