Case report. Rhinocerebral zygomycosis

A case of rhinocerebral zygomycosis treated with liposomal amphotericin B is described.     

A probable cause of paradoxical thrombosis in zygomycosis

Invasive zygomycoses (syn. mucormycoses) are rather rare but life-threatening diseases which often take a peracute course. Particularly endangered are diabetics and patients suffering from siderophilia. Zygomycosis is regularly complicated by thrombosis and subsequent necrosis. Usually it evolves from sinusitis in a rhinocerebral form. With the use of a clinical isolate (Rhizopus microsporus) and sera of the same female survivor, we investigated possible sources of the typical blood clotting. The results suggest that coagulation is probably initiated in a bimodal manner by an extracellular serine proteinase of the fungus and by elastase from the patients' leukocytes. The former causes a partial hydrolysis of fibrinogen, while the latter activates coagulation factor XIII (fibrin stabilizing factor). Both proteinases were present in the patient at the site of infection, and in vitro they jointly bring about regular clotting of fibrinogen.     

Fluconazole in the treatment of pulmonary zygomycosis

Summary. Pulmonary zygomycosis is an aggressive, often terminal infection that may be found in patients who are immunocompromised as a result of cytotoxic chemotherapy. Conventional treatment is by surgical debridement augmented with high-dose intravenous amphotericin B, but even with such treatment the course is usually fulminant with a high mortality rate. Recent work has suggested that the new antifungal triazole, fluconazole, may be of benefit in treating zygomycete infection. The case of a 15-year-old boy who developed pulmonary zygomycosis while on chemotherapy for acute lymphoblastic leukaemia, and who survived for 11 months with oral fluconazole therapy alone, is suppotive of this proposal.
Zusammenfassung. Die pulmonale Zygomykose ist eine aggressive, oftmals terminale Infektion, die bei Patienten auftritt, die mit Chemotherapeutika behandelt werden und somit immunsupprimiert sind. Die herkömmliche Therapie schließt das chirurgische Debridement, verbunden mit hochdosierter intravenöser Gabe von Amphotericin, ein. Doch selbst mit dieser Therapie ist der klinische Verlauf fulminant und mit einer hohen Mortalität verknüpft. Das neue anti-mykotische Triazol Fluconazol wird seit einiger Zeit zur Behandlung von Infekdonen mit Zygomyzeten empfohlen.
Hier wird der Fall eines 15 Jahre alten Jungen beschrieben, der während einer Chemotherapie für akute lymphoblastische Leukämie eine pulmonale Zygomykose entwickelte und elf Monate überlebte, obwohl er lediglich mit oral verabreichtem Fluconazol behandelt wurde.     

Risk factor for invasive zygomycosis in patients with hematologic malignancies

Zygomycosis (mucormycosis) is a relatively uncommon infection in immunocompromised patients most often diagnosed in patients with haematological malignancies and neutropenia. Postmortem series demonstrate a high mortality rate up to 80%. Pulmonary involvement mimicking the more frequently diagnosed invasive aspergillosis is the typical clinical presentation. Other risk factors for the development of zygomycosis that have been described in other patient populations include diabetic ketoacidosis, iron overload, use of deferoxamine and steroids. If these factors are also associated with zygomycosis in patients with haematological malignancies has not been described. In a retrospective case-control study including 13 patients with zygomycosis and 13 control patients with the same underlying diseases, without zygomycosis we determined the frequency of various risk factors. Patients with zygomycosis experienced a longer period of neutropenia (17 vs. 13 days) and lymphopenia (23 vs. 20 days). A relapse of their underlying disease was diagnosed more frequently in patients with zygomycosis (7/13 vs. 3/13) as were a diagnosis of diabetes mellitus (6/13 vs. 3/13) and a cardiovascular disease (6/13 vs. 1/13). The previous use of steroids was more frequent in patients with zygomycosis (8/13 vs. 4/13) as was a systemic antifungal prophylaxis with itraconazole (9/13 vs. 4/13). Knowledge of these risk factors may be of benefit in diagnosing and monitoring zygomycosis in patients with haematological malignancies.     

Cerebral zygomycosis

Fifty-six patients with cerebral zygomycosis (mucormycosis) were seen during the period 1971-2001 in two tertiary care hospitals located in south India with tropical climate and catering to neurological diseases. Forty-four patients had rhinocerebral and twelve patients had isolated central nervous system (CNS) zygomycosis. Of these, ten were culture proven (Rhizopus oryzae in eight and Mucor in two); 30 were diagnosed as probable and 16 were diagnosed possible; mixed infections were seen in three patients. Diabetes mellitus was the predisposing condition in a majority (31/44) of patients with the rhinocerebral form of zygomycosis. The tissue obtained at biopsy/autopsy in either form showed necrotic/infarcted tissue with neutrophilic infiltration with broad non-septate hyphae showing irregular branching. The outcome was poor despite surgical excision and antifungal therapy. The high concentration of spores in a mouldy environment, the bird population and improper disposal of hospital waste may facilitate healthy hosts presenting with primary CNS disease.     

Estimation of renal function and its potential impact on carboplatin dosing in children with cancer

Renal function-based carboplatin dosing is used routinely in paediatric oncology clinical practice. It is important that accurate assessments of renal function are carried out consistently across clinical centres, a view supported by recently published British Nuclear Medicine Society (BNMS) guidelines for measuring glomerular filtration rate (GFR). These guidelines recommend the use of a radioisotope method for GFR determination, with between two and five blood samples taken starting 2 h after radioisotope injection and application of the Brochner-Mortensen (BM) correction factor. To study the likely impact of these guidelines, we have investigated current practices of measuring GFR in all 21 Children's Cancer and Leukaemia Group (CCLG) paediatric oncology centres in the United Kingdom. This information was used to evaluate the potential impact on renal function-based carboplatin dosing using raw 51Cr-EDTA clearance data from 337 GFR tests carried out in children with cancer. A questionnaire survey revealed that between two and four samples were taken after isotope administration, with BM and Chantler corrections used in 38% (8/21) and 28% (6/21) of centres, respectively. A change from Chantler to BM correction, based on the BNMS guidelines, would result in a > 10% decrease in carboplatin dose in at least 15% of patients and a > 25% decrease in 2% of patients. A greater proportion of patients would have an alteration in carboplatin dose when centres not using any correction factor implement the BM correction. The increase in estimated 51Cr-EDTA half-life observed by omitting the I h sample decreases carboplatin dose by > 10% in 23-52% of patients and by > 25% in 3% of patients. This study highlights current variations in renal function measurement between clinical centres and the potential impact on carboplatin dosing. A standard methodology for estimating GFR should be followed to achieve uniform dosing in children with cancer.     

Paediatric radiotherapy in Australia and New Zealand: An anachronism in 2003?

This report reviews the activities of the Paediatric Special Interest Group of the Royal Australian and New Zealand College of Radiologists in terms of its involvement with the Australian and New Zealand Children's Cancer Study Group and its research and educational activities. Examples of when and how radiotherapy is currently used in the management of paediatric malignancies are provided. Some thoughts for the future of both paediatric radiotherapy and our subspecialty are also presented.     

Cutaneous zygomycosis in immunocompetent patients in Mexico

Summary We report three cases of traumatic cutaneous zygomycosis related to soil‐contaminated skin lesions occurring after automobile accidents in individuals with no underlying disorders, which showed delayed development and diagnosis in comparison with typical zygomycosis cutaneous lesions.     

Candidosis, aspergillosis and zygomycosis in an oncology department

The incidence, aetiology and treatment of fungal infections in a 60-bed department of clinical oncology over 2 years is reported. During the second year, after the moving of the department from an old to a new building with an improved epidemiologic regimen, the incidence decreased rapidly, although the mortality due to systemic disseminated mycosis did not change.     

Adaptive dosing and platinum-DNA adduct formation in children receiving high-dose carboplatin for the treatment of solid tumours

A pharmacokinetic-pharmacodynamic study was carried out to investigate the feasibility and potential importance of therapeutic monitoring following high-dose carboplatin treatment in children. High-dose carboplatin was administered over 3 or 5 days, with the initial dose based on renal function, to achieve target area under the plasma concentration-time curve (AUC) values of 21 or 20 mg ml(-1).min, respectively. Dose adjustment was carried out based on observed individual daily AUC values, to obtain the defined target exposures. Platinum-DNA adduct levels were determined in peripheral blood leucocytes and toxicity data were obtained. Twenty-eight children were studied. Based on observed AUC values, carboplatin dose adjustment was performed in 75% (21 out of 28) patients. Therapeutic monitoring resulted in the achievement of carboplatin exposures within 80-126% of target AUC values, as compared to estimated exposures of 65-213% of target values without dose adjustment. The carboplatin AUC predicted with no dose modification was positively correlated with pretreatment glomerular filtration rate (GFR) values. Higher GFR values were observed in those patients who would have experienced AUC values >25% above the target AUC than those patients attaining AUC values >25% below the target AUC, following renal function-based dosing. Platinum-DNA adduct levels correlated with observed AUC values on day 1 of carboplatin and increased over a 5-day course of treatment. Real-time monitoring of carboplatin pharmacokinetics with adaptive dosing is both feasible and necessary for the attainment of consistent AUC values in children receiving high-dose carboplatin treatment. Pharmacodynamic data suggest a strong correlation between carboplatin pharmacokinetics and the drug-target interaction.     

Successful multimodal therapy of invasive pulmonary and central nervous system aspergillosis in a neutropenic surgical patient: case report and review of the literature

Invasive aspergillosis predominantly occurs in patients with impaired host defence and is often resistant to different therapeutically strategies. However, mortality significantly increases if the central nervous system is affected. In this report, we describe a case of successful treatment of invasive aspergillosis with cerebral involvement. The treatment consists of a medication of voriconazole and lipid-associated amphotericin B as well as a stereotactic neurosurgical procedure to drain an intracranial abscess.     

Rhinocerebral zygomycosis in a patient with acute lymphoblastic leukemia

We report a case of a 28-year-old man with acute lymphoblastic leukemia whodeveloped rhinocerebral zygomycosis during induction chemotherapy. Thislife-threatening fungal infection is an infrequent cause of neutropenic fever,and is occasionally found in patients with leukemia and lymphoma, or patientswith severely compromised defence mechanisms due to other diseases. Itis caused by moulds belonging to theMucoraceaefamily, and ischaracterized by local destruction of the affected organ. In our patient, theinfection spread from the paranasal sinuses to the right orbit, destroyedintraorbital structures and resulted in blindness within days. Biopsy from theright maxillary sinus was performed and mucormycosis was suspected throughmicroscopic examination. Culture of the resected specimen identifiedRhizopus arrhizusas the causing agent.Treatment of zygomycosis should consist of radical surgical debridement ofthe infected tissue, together with intensive broad-spectrum antimycotictherapy with amphotericin B. What could be learned from this case is, thataggressive approaches to identify the cause of infection is necessary, andthat aggressive treatment strategies are inevitable to overcome the infection.Furthermore, treatment of the underlying disease should be continued as soonas possible.     

Primary zygomycosis of the pericardium in an immunocompetent host

The fungi in the order Mucorales commonly target immunocompromised hosts, especially diabetics and produce fulminating respiratory and/or central nervous system infections, which are often fatal. We report primary zygomycotic pericarditis accompanied by osteomyelitis of the sternum in an immunocompetent female: a rare site and a rare setting. The disease was clinically thought to be of tuberculous aetiology and had evaded diagnosis for a year.     

Coccidioidomycosis: Imported and possible domestic cases in China: A case report and review, 1958‐2017

We report a case of imported pulmonary coccidioidomycosis caused by Coccidioides posadasii in a patient who was misdiagnosed as tuberculosis and mistreated with antituberculosis medications for 18 months. The symptoms were not relieved until antifungal treatment was started. An extensive review of the coccidioidomycosis cases occurring in China reveals 38 cases, 16 of which had no associated history of travel to any traditional endemic areas. We speculate that some factors may drive Coccidioides spp. transference to China, which then causes those domestic infections. Moreover, we indicate the first, to the best of our knowledge, possible endemic areas in China.     

Monitoring plasma voriconazole levels may be necessary to avoid subtherapeutic levels in hematopoietic stem cell transplant recipients

BACKGROUND: Low voriconazole levels have been associated with a higher failure rate in patients with confirmed fungal infections. METHODS: Steady-state plasma trough voriconazole levels were measured after at least 5 days of therapy in 87 patients with hematologic malignancies on 201 separate occasions (1-5 levels per patient; median, 2). Most patients (90%) had undergone allogeneic hematopoietic stem cell transplantation. The daily voriconazole dose, administered in 2 divided doses, was 200 mg (n = 4), 400 mg (n = 151), 500 mg (n = 20), 600 mg (n = 18), and 800 mg (n = 8); corresponding to 2.0-16.3 (median, 5.4) mg/kg. Plasma voriconazole levels were 0-12.5 microg/mL (median, 1.2). Voriconazole was undetectable (<0.2 mug/mL) in 15%. RESULTS: The correlation between dose and levels was weak (r = 0.14; P = .045). The median absolute daily drug dose (400 mg) was identical in groups of patients with levels of 0, 0.2 to 0.5, >0.5 to 2.0, >2.0 to 5.0, and >5.0. Whereas the daily drug dose in mg/kg was significantly higher when the levels were >5.0 microg/mL, there was no consistent relation between dose and level below that threshold. In adult patients getting standard doses of voriconazole orally, the drug levels are highly variable. Based on limited available data, between a quarter and two-thirds of these levels could potentially be associated with a lower likelihood of response or a higher likelihood of failure. CONCLUSIONS: Future voriconazole studies should incorporate prospective therapeutic drug monitoring and consideration should be given to checking levels in patients receiving the drug for confirmed, life-threatening fungal infections.