Primary cutaneous zygomycosis due toAbsidia corymbifera in a child with acute leukemia

A 2-year-old boy with acute lymphoblastic leukemia and neutropenia on intensive induction chemotherapy, developed a necrotizing skin lesion under an armboard used to stabilize an intravenous line. The necrotizing skin lesion was refractory to itraconazole and fluconazole therapy, and the skin biopsy and cultures grewAbsidia corymbifera as the etiologic organism on day 26. Since the organism was highly susceptible to amphotericin B, he was treated with systemic and local amphotericin B as well as granulocyte colony-stimulating factor (G-CSF) followed by debridement of the ulcerated lesion and skin grafting. The zygomycotic lesion cleared on day 45. There was no evidence of recurrent fungal disease. Systemic and local amphotericin B and G-CSF were effective in clearing the skin lesion. We would like to emphasize that meticulous local hygiene and frequent inspection of covered areas is of great importance in preventing skin lesions by such nonvirulent environmental fungi. The use of G-CSF should also be included in the treatment regimen of primary cutaneous zygomycosis in neutropenic patients.     

Cutaneous zygomycosis due to Rhizopus oryzae in a patient with acute lymphoblastic leukemia

We report herein a case of primary cutaneous zygomycosis caused by Rhizopus oryzae in a 7-year-old girl with acute lymphoblastic leukemia (ALL) receiving intensive chemotherapy. The diagnosis was based on observation of hyphal elements in cutaneous biopsy and isolation of the fungus in culture. The patient responded to surgical intervention and treatment with amphotericin B.     

Kitten-transmitted Bordetella bronchiseptica infection in a patient receiving temozolomide for glioblastoma

Bordetella bronchiseptica is a gram negative coccobacillus that can be transmitted from domestic animals and cause severe infections in immunocompromised patients. A 56-year-old man with a left parietal glioblastoma was treated with resection, radiation and concomitant and adjuvant temozolomide chemotherapy. He received bevacizumab for progression, and dose dense metronomic temozolomide was added for additional progression. He developed chronic cough and was diagnosed with B. bronchiseptica infection. This is the first reported case of B. bronchiseptica infection in a patient receiving temozolomide. The infection was likely acquired from an infected kitten. Patients receiving temozolomide should be counseled on the risks of acquiring zoonotic infections, including B. bronchiseptica, from their pets.     

Combined antifungal therapy,iron chelation and surgical resection as treatment of hepatic zygomycosis in a patient with haematological malignancy

We describe the case of a 19‐year‐old boy with acute leukaemia who developed primary hepatic zygomycosis. The patient presented with febrile neutropenia and severe abdominal tenderness. Despite the administration of antibiotics and liposomal Amphotericin‐B (L‐AmB), the CT scan demonstrated an increase in the size of liver lesions. A wide surgical resection was carried out and liver specimens demonstrated a branching, filamentous fungus that was identified as Rhizomucor pusillus by both phenotypic and molecular methods. The patient was treated with L‐AmB combined with posaconazole, and deferasirox was subsequently added given the potential synergistic effect of this iron chelator in combination with L‐AmB. Three months after surgical intervention, an allogeneic stem‐cell transplantation was successfully carried out. The present case confirms that an early surgical management combined with antifungal agents is crucial to optimise the outcome of patients with zygomycosis and the use of deferasirox is a promising alternative.     

Therapy for fungal infections in leukemia

Invasive fungal infections remain a common cause of morbidity and mortality among patients with leukemia who become further compromised by neutropenia. Candida and Aspergillus spp account for the vast majority of these infections, but other, less commonly recognized fungi can cause life-threatening infection in these hosts as well. The earlier, more limited antifungal armamentarium of ketoconazole, flucytosine, and amphotericin B has been substantially augmented by the availability of fluconazole, itraconazole, and the lipid-associated amphotericin formulations. Intense clinical study has focused on the use of these agents in empiric treatment, treatment of suspected or proven infection, and prophylaxis. Recognition of the limitations of antifungal therapy in the neutropenic host has led to evaluation of the adjunctive role of immunotherapy.     

Identification of fungal pathogens in a patient with acute myelogenic leukemia using a pathogen detection array technology

Invasive zygomycosis in immunocompromised patients results in a high mortality rate, and early identification is crucial to optimize therapy and to reduce morbidity. However, diagnosing specific species of zygomycetes fungi possess challenge in the clinical laboratories. A need for a rapid and sensitive diagnostic tool for early recognition of a zygomycetes fungus in clinical samples to the species level will lead to prompt and accurate therapy and the PathoChip provides one such platform. We utilized a pathogen array technology referred to as PathoChip, comprised of oligonucleotide probes that can detect all the sequenced viruses as well as known pathogenic bacteria, fungi and parasites and family-specific conserved probes, thus providing a means for detecting previously uncharacterized members of a family. We rapidly identified a zygomycetous fungus, Rhizomucor pusillus, an otherwise challenge for the clinical laboratories, predominantly in a patient with acute myelogenous leukemia. This report highlights the value of PathoChip as a diagnostic tool to identify micro-organisms to the species level, especially for those difficult to identify in most clinical laboratories. It will also help clinicians to obtain a critical snapshot of the infection profile of a patient to plan treatment strategies.     

Gastric diffuse large B-cell lymphoma after the diagnosis of primary MALT lymphoma of the breast��One case report

Primary breast and gastric lymphomas as manifestations of primary extranodal lymphomas are rare malignancies, and their diagnosis, prognosis, and treatment modalities remain unclear. We report for the first time the simultaneous co-occurrence of these diseases in one patient. A 60-year-old woman was diagnosed with gastric diffuse large B-cell lymphoma (DLBCL) 2.5 years after she was found to have primary mucosa-associated lymphoid tissue (MALT) lymphoma of the breast. Although the patient underwent chemotherapy, she died of leukemia that caused irreversible cytopenia of three lineages. The data show that her MALT lymphoma apparently transfigured into gastric DLBCL. This case highlights the importance of evaluating patients for Helicobacter pylori infection when they present with extranodal MALT lymphomas, except gastric ones. Positive test findings should prompt anti-H. pylori therapy to prevent MALT lymphomas from transforming into DLBCLs.     

Chronic oral ulcer associated with Candida

In the patients with HIV infection, fungal diseases may cause ulceration in the oral cavity; however, there have been few studies on oral ulcerative lesions associated with Candida in the patients without HIV infection. Our study included six patients with chronic oral ulcer of unknown origin; these patients were referred to our department after topical steroid therapy to the lesion was ineffective. Cases of traumatic ulcers and recurrent aphthous stomatitis were excluded. Blood, histopathological, culture and direct cytological examinations were performed. All the patients were treated with topical miconazole gel. Histopathological examination revealed no specific findings besides inflammatory cellular infiltration with positive haematoxylin–eosin staining in all cases. Candida spp. were isolated in four cases by culture test, and fungal pseudohyphae were revealed in four cases by direct examination. The anti‐fungal treatment produced a satisfactory outcome with complete remission in five cases and remarkable response in one case. These results suggested that Candida should be considered as playing an important role in a certain oral ulcer.     

Zygomycosis--a case report and overview of the disease in India

A case of zygomycosis caused by Rhizopus oryzae in a diabetic patient previously misdiagnosed as invasive pulmonary aspergillosis and an overview of the disease in India are presented. The case was diagnosed by direct microscopy, histopathologic examination and culture. Following surgical resection of pulmonary cavity under cover of amphotericin B administration, the patient recovered completely. Of 461 cases reported to-date, approximately 70% had been diagnosed at the Postgraduate Institute of Medical Education and Research, Chandigarh, in north India. This may be attributed to better awareness, expertise and infrastructural facilities for mycological diagnosis than to any particular regional preponderance of the disease. Rhino-orbito-cerebral manifestations were the most common feature of zygomycosis (269 cases), followed by cutaneous disease (66 cases), which is in conformity with the pattern prevalent worldwide. The etiologic agents encountered were Rhizopus oryzae, Apophysomyces elegans, Saksenaea vasiformis, Cunninghamella bertholletiae, Absidia corymbifera, Basidiobolus ranarum and Conidiobolus coronatus. In contrast to cases from the developed world where transplant recipients and patients with haematological malignancies seem to be most vulnerable to zygomycosis, the most common risk factor in India was uncontrolled diabetes mellitus. Amphotericin B was the mainstay of various treatment modalities employed. The relevance of a strong clinical suspicion and early diagnosis of zygomycosis for favourable prognosis can hardly be over-emphasised.     

Posaconazole as first line treatment for disseminated zygomycosis

We describe the first case report of posaconazole use as first line agent in the treatment of disseminated zygomycosis with prosthetic hip joint and pulmonary involvement due to Rhizopus microsporus. This infection occurred in a heavily immunosuppressed patient with systemic lupus erythematosus.     

Non-cardiogenic pulmonary edema complicating intermediate and high-dose Ara C treatment for relapsed acute leukemia

Infection, hemorrhage and adult respiratory distress syndrome (ARDS) are pulmonary complications occurring after remission induction therapy for acute leukemia. The aim of this study was to analyze the incidence of these causes by serial roentgenogram, clinical, microbiological and laboratory tests in 21 patients (pts) with relapsed acute leukemia (18 x myeloid, 3 x lymphoblastic), an AML-pt (acute myeloid leukemia) suffering from secondary leukemia, and three pts with primary refractory leukemia following treatment with intermediate (IM) and high-dose cytosine arabinoside (HD-Ara C), in combination with amsacrine (AMSA) (n = 19), etoposide (VP 16) (n = 5) or Mitoxantrone (n = 1). Eleven out of 25 pts developed pulmonary complications, one of them with massive hemoptysis and roentgenographic signs of pulmonary bleecling, one suffering from protracted shock after a tumor lysis syndrome, two pts showing symptoms of a cardiogenic pulmonary edema complicating severeCandida pneumonia in one case and legionnaires’ disease in the other. Seven of the eleven pts had a noncardiogenic pulmonary edema with respiratory failure 1–14 days after cessation of induction or consolidation therapy. In six of the seven, there were no signs of cardiogenic, infectious or metabolic reasons, inclucling fluid overload, for the pulmonary edema, one had as a contributing factor aCandida infection of the lung. Three of the seven patients recovered, four died (two following IM and two after HD-Ara C). Other adverse side effects, clearly attributable to HD-Ara C, included delirious state (n = 3), generalized erythema (n = 3), acute pancreatitis (n = 2), acute abdomen (n = 1) and conjunctivitis in almost all patients. In conclusion, the most frequent (7/25) and serious complication following HD-Ara C treatment in our series was a toxic, non-cardiogenic edema of the lung. In our opinion, the clinical evidence for this type of toxicity might have been misinterpreted in many instances in the past, and it should draw close attention in the future.     

生存五年以上死亡急性白血病17例报告

目的:探讨急性白血病(AL)生存五年以上死亡原因。方法:采用回顾性系列研究,统计本院生存五年以上死亡急性白血病患儿的发病年龄、性别、化疗前病程、分型、病史、临床表现、血常规、骨髓象、并发症、微小残留病灶检测(MRD)、染色体检测、诱导方案、完全缓解(CR)时间、复发时间、直接死因等进行分析。结果:急性淋巴细胞白血病、男性、白细胞数过高、化疗强度不够、出现髓外白血病、MRD(+)易复发,复发后放弃治疗或不规则治疗易全身浸润造成多器官脏器功能衰竭(MOF)死亡,化疗后骨髓抑制易出血、感染死亡。结论:白血病应坚持规范化、个体化长期治疗,停药后仍应定期监测以防复发,复发再诱导缓解后应进行干细胞移植根治白血病。     

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.     

Long Term Treatment with Clarithromycin for Cryptosporidiosis and Emergence of Drug Resistant Disseminated Infection Due to Mycobacterium avium: Case Report

Abstract

Macrolide resistance in disseminated Mycobacterium avium infection is of major concern in AIDS patients as these drugs represent the main component of combination therapy. Clarithromycin and azithromycin should not be used alone for the treatment and prophylaxis of the disease because of the risk of selecting resistant strains. We report the case of a clarithromycin resistant disseminated M. avium infection in an AIDS patient, acquired after long term monotherapy with clarithromycin for the treatment of cryptosporidiosis.     

Saprochaete clavata infections in patients undergoing treatment for haematological malignancies: A report of a monocentric outbreak and review of the literature

Saprochaete clavata is a rare cause of fungaemia with deep organ involvement in patients with haematological malignancies with reported mortality rates of 60%‐80%. We describe four cases of S clavata infection in a haematology unit over several months that were treated with voriconazole‐based regimens. We also review the literature on factors that could contribute to earlier recognition and effective treatment of S clavata. We included all cases of culture‐positive S clavata from sterile sites with associated signs of infection in patients undergoing treatment for a haematological malignancy. Isolates were identified by MALDI‐TOF MS, and spectrum profiles were used to prepare clustering analysis of isolates. Susceptibility testing was performed using a commercial microtitre methods. Saprochaete clavata was isolated from the bloodstream in three cases and bronchial alveolar lavage (BAL) fluid in one case. Clustering analysis suggested strains of S clavata were clonal without evidence of divergence although a common source was not identified. Susceptibility testing yielded elevated MICs to fluconazole (8 mg/L) and echinocandins (>1‐8 mg/L). All patients were treated with voriconazole‐based regimens resulting in survival of 3/4 patients, who continued chemotherapy for their underlying malignancy without evidence of relapse. Saprochaete clavata is a rare but aggressive cause of breakthrough yeast infection in patients undergoing treatment for haematological malignancies, particularly patients with a prior history of echinocandin treatment. Timely initiation of appropriate treatment, aided by more rapid identification in microbiology laboratory, can reduce the risk of deep organ dissemination and patient death.     

Rhino-cerebral zygomycosis resistant to antimycotic treatment: a case report

We report a fatal case of a rhino-cerebral zygomycosis, caused by Rhizopus arrhizus (oryzae). The patient was suffering from idiopathic thrombopenic purpura, diagnosed 1 year earlier. He was already treated with methylprednisolone 5 months prior to his admission to the hospital for a loss of vision and pain in the left eye as well as left orbital cellulitis. After an initial empirical treatment with broad spectrum antibiotics and voriconazole (infection of unknown origin), the patient was treated with liposomal amphotericin as soon as a positive fungal culture revealed a zygomycete. Unfortunately, the mould was resistant to amphotericin B (MIC: 16 μg ml⁻¹) and probably to posaconazole (MIC: 4 μg ml⁻¹), which was co-administrated a few days later.     

Emerging Antimicrobial Resistance in the Surgical Compromised Host

Abstract

Improvements in the treatment of compromised patients have resulted in their prolonged survival in a debilitated state. Patients have repeated courses of antibiotics and become colonised with multiresistant pathogens during a stay in the intensive care unit. Surgical wound infections can then be very difficult to treat. Methicillin-resistant Staphylococcus aureus is now common although wide variations in prevalence exist between countries and regions. Klebsiella spp with multiple resistance is a common cause of septicemia and can be associated with cephalosporin use. Acinetobacter spp and vancomycin-resistant enterococci can cause infections resistant to all readily available antibiotics. The prevalence of infection with each of these pathogens is increasing. Control measures should include hand washing, universal precautions for infection control, source isolation, restrictive antibiotic policy and antibiotic rotation. Although new agents currently in trials may be effective in the long term, the future for antibiotic treatment or prophylaxis of surgical infections is in doubt.     

Glutaminase-free asparaginase from vibrio succinogenes: An antilymphoma enzyme lacking hepatotoxicity

Successful treatment of neoplastic disease has been impeded by the lack of therapeutic agents which specifically destroy tumor cells. Enzymes which selectively deplete substrates required by tumor cells, but not by normal tissue, could improve therapeutic indices dramatically. Presently, microbial asparaginases are used clinically for treating acute lymphocytic leukemia. While these enzymes should destroy neoplastic cells and spare normal tissues, their use is accompanied by many toxic effects and immunosuppression. The administration of Escherichia coli or Erwinia carotovora asparaginase depletes circulating glutamine as well as asparagine. It has been suggested that this glutaminase activity may be responsible for the observed toxicities. We have isolated a glutaminase-free asparaginase from Vibrio succinogenes with potent antilymphoma activity. Previously, we demonstrated that administration of Vibrio asparaginase does not cause the immunosuppression of humoral or cell-mediated responses associated with treatment by other microbial enzymes. In the present communication we have evaluated the hepatotoxic effects of different asparaginases since liver damage is the major toxicity associated with treatment by these microbial enzymes. BALB/c mice treated with 50 IU of E. coli asparaginase daily for 4 days exhibited diffuse microfatty infiltration within hepatocytes throughout the liver. Cross-sections of liver from V. succinogenes asparaginase-treated mice appeared normal as compared to specimens from control animals. Quantitation of the total amount of extractable lipid from the livers of E. coli asparaginase-treated animals indicated a 45% and 127% increase in lipid concentration as compared to controls after 4 and 5 days of treatment, respectively. The Vibrio enzyme did not cause a change in extractable lipid concentration as compared to control animals. Plasma antithrombin III activity and albumin, triglyceride and cholesterol concentrations all decreased in E. coli asparaginase-treated mice, confirming hepatotoxicity. No modifications in plasma proteins were observed in mice treated with asparaginase from V. succinogenes. The plasma lipids did decrease minimally but only the levels of cholesterol were shown to be statistically significant from those of controls. The data strongly support the concept that specific asparagine depletion is not significantly hepatotoxic. More importantly, the asparaginase from V. succinogenes may serve as a potent antileukemic agent without causing damage to normal tissues.     

Evidence on the infectious etiology of childhood leukemia: the role of low herd immunity (Greece)

Objective: Acute lymphoblastic leukemia (ALL) among children may be a rare outcome of a delayed non-specific infection in situations of overall low herd immunity. We evaluated the hypothesis as to whether newly diagnosed ALL cases, compared to their controls, are characterized by lower herd immunity, as reflected in a more seronegative spectrum to several agents, with the exception of a strongly positive response to a single infectious agent, assumed to trigger ALL. Methods: The study included 94 incident cases of ALL, from all pediatric hematology–oncology units of Greece, and 94, matched for age and gender, controls hospitalized with minor non-infectious conditions. The past exposure to common infections was assessed using 10 serological markers. Results: There was little evidence for an association of ALL with the serology of any of the studied infectious agents among the very young children. In contrast, among children aged 5 years or older, leukemia was inversely associated with seropositivity to Epstein–Barr virus, human herpes virus-6, Mycoplasma pneumoniae and parvovirus B19. Conclusions: Among children aged 5 years or older the risk of leukemia may be higher when the low herd immunity for several agents is challenged by late infection from an agent that, as a rule, would attack children at a younger age.     

86例急性白血病患者死亡情况分析

目的 :探讨急性白血病病死率和死亡原因。方法 :5 6 8例急性白血病患者住院中死亡 86例患者的资料进行分析。结果 :总病死率 15 %。慢粒急变 44 % ,复治 2 3% ,初治 12 .5 % (P <0 .0 1)。早期死亡病死率 38%。颅内出血 48.8% ,感染 31.4%。颅内出血发生率 :早期死亡 91% ,急非淋 5 5 % ,急淋 2 5 % (P<0 .0 5 )。M3 85 % (P<0 .0 1)。初治及复治的颅内出血发生率为 5 0 %、40 % (P>0 .0 5 )。严重血小板减少、高白细胞血症、凝血机制异常是颅内出血的重要原因。感染是后期死亡的主要原因 (4 9% )。G-菌感染率 :血 87% ,呼吸道 79% ,皮肤软组织 6 2 % ,真菌感染率48%。结论 :1急性白血病的病死率高 ,且慢粒急变 >复治 >初治 ,相互之间差异有显著性 (P<0 .0 1)。2颅内出血是急性白血病的重要死亡原因和早期死亡主要原因 ,且与 FAB分型是有关。3感染是急性白血病第 2位的死亡原因。G-菌是急性白血病感染的主要原因 ,且真菌感染也不可忽视