Fusarium fungaemia in severely neutropenic patients

We report two cases of Fusarium infection with evidence of fungaemia in severely neutropenic patients with leukaemia. One patient was a 65-year-old woman with chronic lymphocytic leukaemia infected by Fusarium verticillioides. The other patient was a 45-year-old woman with acute myeloblastic leukaemia infected by Fusarium spp. Fungaemia was the only evident manifestation of these fungal infections.     

Ectopic pregnancy diagnosis in very high risk patients

SETTING: Hepatosplenic abscesses in neutropenic patients, especially during the recovery phase, are almost always attributed to fungal infections. We report similar lesions due to Mycobacterium tuberculosis in neutropenic patients in a tertiary care centre in India. OBJECTIVE: To characterize the features of hepatosplenic tuberculosis in neutropenic patients. DESIGN: Retrospective comparison of disease pattern and response to treatment of hepatosplenic tuberculosis in febrile neutropenia patients (four of 30 with severe prolonged neutropenia) and in non neutropenic patients diagnosed during the same 12-month period (n = 4, control group). RESULTS: The disease in the neutropenic patients typically presented during the recovery phase of neutropenia, with ultrasonic abnormalities similar to those seen in hepatosplenic fungal infections. In contrast to the marked organomegaly and typical granulomatous response found in the control group, the disease in the neutropenic patients was characterised by an absence of organomegaly, non-involvement of other sites, poor inflammatory response and a high bacillary load. The initial response to therapy was satisfactory in both groups. CONCLUSION: Tuberculosis needs to be considered in the diagnostic work-up of hepatosplenic abscesses that occur during the recovery phase of neutropenia.     

Efficacy of fluconazole in the treatment of upper gastrointestinal candidiasis in neutropenic patients with cancer: factors influencing the outcome

Fluconazole has proved to be effective in treating oropharyngeal and esophageal candidiasis in immunocompromised patients. However, sufficient data are lacking regarding the efficacy of this agent in neutropenic hosts. The aim of the present study was to determine the clinical and mycological efficacy of fluconazole and to define the factor(s) affecting the outcome of fluconazole therapy in severely neutropenic patients (peripheral neutrophil count, < 500/microL) with cancer who have oropharyngeal and/or esophageal candidiasis. One hundred eleven patients with 129 episodes of candidal infections were treated with intravenous and consequently oral fluconazole (200 mg/d and 100 mg/d, respectively). Overall clinical cure and mycological eradication rates were 82% and 56%, respectively. Persistent neutropenia (P < .01), infection with a non-albicans strain of Candida (P = .012), and administration of antifungal therapy during the second or a later neutropenic episode (P < .002) were independently associated with a worse outcome. We conclude that fluconazole is effective in the treatment of upper gastrointestinal candidiasis in neutropenic patients with cancer. Effective treatment of the underlying malignancy, with the resultant recovery from neutropenia, and the determination of the species of infecting Candida isolates are required for the prediction of the outcome of antifungal therapy.     

Opportunistic fungal infections: filamentous fungi and cryptococcosis

Older patients with diabetes mellitus or pulmonary diseases and those receiving immunosuppressive drugs are at an increased risk of infection with environmentally-acquired, opportunistic fungal diseases. Aspergillus most often produces invasive pulmonary or sinus infection in severely immuno-compromised patients. Chronic necrotizing pulmonary and sino-orbital aspergillosis present subacutely and are often misdiagnosed. Mucormycosis classically presents with rhinocerebral disease in diabetic patients with ketoacidosis, whereas pulmonary infection mimics invasive pulmonary aspergillosis and occurs mostly in patients who are neutropenic. Cryptococcal meningitis in the older patient may manifest simply as confusion. Amphotericin B is the preferred initial treatment for all three fungal infections.     

Disseminated Blastoschizomyces capitatus infection in acute myeloblastic leukaemia. Report of three cases

Three new cases of Blastoschizomyces capitatus infection occurring in neutropenic patients with acute myeloblastic leukaemia are reported. B. capitatus was isolated from blood cultures in all patients. All three patients were treated with amphotericin B, but only one was cured from the infection. Our study confirms the emergence of B. capitatus as an opportunistic agent of disseminated fungal infection in leukaemic patients.     

Fatal systemic mycotic infections in the burned child

Two cases of systemic phycomycotic burn wound infection occurred in severely burned children. Both patients, although treated aggressively, died after systemic colonization through the burn wound by fungi. Modern burn therapy has increased survival of many severely burned children but opportunistic fungal infection remains as an ominous threat. Early recognition, wide excision or amputation, and systemic antifungal agents comprise the current clinical armamentarium against systemic fungal invasion of burn wounds.     

Role play. Providing care to children and their families in the emergency center

A 24-year-old female, in neutropenic phase after chemotherapy for acute myelogenous leukemia (on day 15) was admitted in intensive care unit for infectious pneumonia. Two strains of Stomatococcus mucilaginosus were isolated from peripheral blood cultures. No microorganisms were yielded from bronchoalveolar lavage. Patient's condition improved with prompt instigation of effective antibiotic therapy. This was the first case of septicemia and pneumonia, due to Stomatococcus mucilaginosus, in our unit. Only 26 cases occurring in neutropenic patients with underlying hematologic malignancies were reported in the literature and among these, only five cases with pneumonia were described. The complications of this normal inhabitant of the human oral cavity can be serious and fatal: septic shock, meningitis, acute respiratory distress syndrome. This study illustrate the possible virulence of Stomatococcus mucilaginosus in neutropenic patients.     

Standards, Options, and Recommendations for the management of brief neutropenias. Fedération Nationale des Centres de Lutte Contre le Cancer

CONTEXT: The "Standards, Options and Recommendations" (SOR), initiated in 1993, is a collaborative project between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcomes for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary experts group, with feedback from specialists in cancer care delivery. OBJECTIVE: To develop a clinical practice guideline for the management of neutropenic cancer patients (excluding prolonged neutropenia). METHODS: Data have been identified by literature search using Medline and Current Contents (up to February 1997) and personal reference lists. The main end points considered were mortality, morbidity, risk factors, fever, source of infection, microbiological documentation, incidence and length of hospital stays, quality of life, efficacy of treatment, safety and costs. Once the guideline was defined, the document was submitted to 48 reviewers for peer review and to the medical committees of the 20 French Cancer Centres for review and agreement. RESULTS: The key recommendations are: 1) before receiving cytotoxic chemotherapy, patients must be informed of potential risks and precautions to observe; 2) non-febrile neutropenic patients can be followed at home (except specific context); antibiotic prophylaxis is not recommended; 3) initial empirical antibiotic therapy for febrile patients is mandatory, whether associated beta-lactam and aminoglycoside, or monotherapy with a broad-spectrum beta-lactam (except in case of septic shock or pneumopathy). A glycopeptide can be added in case of overt catheter-related or cutaneous infection, in case of microbiologically documented infection with a oxacillin-resistant Gram positive bacteria, or in case of persistent fever in a clinically deteriorating patient; 4) at the present time, there is insufficient evidence to recommend the management of febrile neutropenic patients at home. We recommend participation in studies to identify predicting factors of low-risk patients and to assess the feasibility and safety of early discharge and home therapy.     

Efficacy of itraconazole in the prevention of fungal infections among neutropenic patients with hematologic malignancies and intensive chemotherapy. A double blind, placebo controlled study

We studied the efficacy and safety of itraconazole for the prevention of fungal infection in neutropenic patients given cytotoxic chemotherapy for hematologic malignancies. Patients were randomly allocated to receive either itraconazole (200 mg bd) or placebo in addition to oral amphotericin B until the patient either developed fungal infection or had completed antileukemic treatment. Forty six patients (83 neutropenic episodes) treated with itraconazole and 46 placebo treated patients (84 neutropenic episodes) were evaluable. No specific toxicity was noted. Nine fungal infections developed in the itraconazole group, of which four were histologically or microbiologically proven and 15 in the patients given placebo (eight proven) (p < 0.12). All these patients received IV amphotericin B. The incidence of Candida albicans infections tended to be lower in the itraconazole group, but overall, there was no measurable improvement in the prevention of fungal infections and mortality by itraconazole.     

Cytokines in the treatment of fungal infections

The incidence of invasive fungal infections in the immunocompromized host has increased during the past decade. Even the recently developed antifungal drugs are unable to cure these infections in patients with severely impaired host defense mechanisms. Cytokines have great potential to augment host resistance and as adjunctive therapy of invasive mycoses. We discuss the mechanisms of host defense against invasive candidiasis, aspergillosis, and cryptococcosis, and review the use of cytokines and growth factors in this setting. Interleukin-1 has been shown effective in an animal model of disseminated candidiasis, even during severe granulocytopenia. Interferon-gamma has been very effective as a modulator of resistance against a variety of fungal infections in vitro. The effect of interferon-gamma against disseminated candidiasis has been demonstrated in a mouse model. Activation of neutrophils is the main mechanism by which interferon-gamma enhances the elimination of Candida, and consequently the agent is not effective in severely granulocytopenic animals. Data on the role of colony-stimulating factors against fungal pathogens are accumulating, and trials with these agents for hematologic patients with invasive fungal infections are now being performed.     

TI-201 chloride and Tc-99m ECD brain SPECT in lymphoma with and without massive necrosis

Invasive fungal infections occur frequently in neutropenic patients although only in recent years has the role of emerging fungi been clearly established. We describe two cases of fungemia caused by Trichosporon beigelii and Rhodotorula glutinis respectively in two neutropenic patients with hematological malignancies who were treated with amphotericin B. The first patient, with refractory multiple myeloma, died following massive pneumonia despite therapy with amphotericin B and granulocyte-colony stimulating factor (G-CSF); the second patient, with relapsed acute lymphatic leukemia and persistent fever without any other clinical evidence, finally recovered. Amphotericin B continues to be considered the "gold standard" in the treatment of invasive mycoses although other approaches need to be tested for refractory infections.     

Clinical experiences of infectious scleral ulceration: a complication of pterygium operation

AIMS: To report the special clinical manifestations and determine the appropriate management of infectious scleral ulceration. METHODS: A retrospective study was performed on 30 eyes with infectious scleral ulceration. Information was recorded on patients' age, onset and course of disease, pathogenic organism, clinical presentations, methods of diagnosis, treatment, and outcome. RESULTS: 10 cases (33.3%) were accompanied by corneal involvement. Subconjunctival abscess was noted in 16 cases (53.3%). 17 cases (56.7%) gave positive results of pathogen culture and all were Pseudomonas aeruginosa. Two cases had combined bacterial infections and one case was complicated by fungal infection. A total of 26 cases had surgical debridement in this series. Extensive involvement of the sclera with the presence of a 'tunnel lesion' or a 'satellite subconjunctival abscess' were found during debridement. All of the eyeballs involved were salvaged except one. CONCLUSION: The results of this study were contrary to the poor prognosis presented in previous reports. Early and repetitive surgical debridement is believed to be mandatory in the intractable cases to shorten the admission period and to save these eyes.     

Meropenem versus ceftazidime plus amikacin in the treatment of febrile episodes in neutropenic patients: a randomized study

BACKGROUND AND OBJECTIVE: Meropenem is the first of a new class of carbapenems which may be administered without cilastatin. This study was performed to assess the clinical efficacy and tolerability of meropenem monotherapy (1 g/8 h) compared with the standard combination of ceftazidime (2 g/8 h) plus amikacin (15 mg/kg/day) for the empirical treatment of infective febrile episodes in neutropenic cancer patients. METHODS: This was a three-center, randomized, non-blind parallel group trial. The primary objective was to compare the clinical efficacy of meropenem monotherapy with that of ceftazidime plus amikacin in the empirical treatment of febrile infective episodes in neutropenic patients. This was evaluated by the number of patients surviving on unmodified therapy at 72 h (primary end point) and by the clinical response at the end of therapy (secondary end point). RESULTS: A total of 93 febrile episodes (46 meropenem, 47 ceftazidime/amikacin) were evaluable. Bone marrow transplant patients accounted for 49.5% of all cases. There was a high incidence of Gram-positive infections but no pseudomonal infections. Microbiologically documented infections, clinically documented infections and unexplained fever accounted for 45%, 10% and 45% of episodes, respectively. There was a similar proportion of patients in the meropenem and ceftazidime/amikacin groups on unmodified empiric therapy at 72 h (80.4% vs 76.6%, p = 0.65,) and cured at the end of therapy (37% vs 36.2%, p = 0.9). No significant difference in tolerability was observed between the groups. Meropenem was well tolerated; of note, there were no cases of nausea/vomiting or seizure related to its use. INTERPRETATION AND CONCLUSIONS: Meropenem monotherapy was well tolerated and produced response rates similar to those obtained with ceftazidime/amikacin. The low overall success rates with both treatments concur with those of other recent studies and are probably due to a combination of several factors, including the adoption of strict assessment criteria.     

Posttraumatic gas-containing brain abscess caused by Clostridium perfringens with unique simultaneous fungal suppuration by Myceliophthora thermophila: case report

OBJECTIVE AND IMPORTANCE: Gas-containing brain abscesses are rare, and the vast majority are caused by Clostridium perfringens. Significant simultaneous fungal infection in a bacterial abscess is even rarer. We present such a case and review the literature. CLINICAL PRESENTATION: A 21-month-old male patient sustained a penetrating head injury in a barnyard, developed a gas-containing left parietal brain abscess, and presented with high fever, galeal swelling, and seizure. INTERVENTION: The patient initially underwent debridement of his wound and then repeated aspirations. The initial cultures revealed pure growth of Clostridium perfringens. Despite appropriate antibiotic therapy, serial neuroimaging did not demonstrate a decrease in the size of the cavity. An excision had to be undertaken 6 weeks after the injury. The culture from the excised specimen revealed an unexpected growth of a saprophytic and opportunistic fungus, Myceliophthora thermophila. Antifungal treatment consisting of the administration of liposomal amphotericin B and itraconazole was then performed. The child was well and neurologically intact 6 months after the excision. CONCLUSION: Our review revealed 38 cases of clostridial brain abscess in the literature. Despite the reputation of the organism, the outcome with clostridial brain abscesses was relatively benign. The main characteristics of clostridial brain abscesses are highlighted, with reference to their optimal treatment. Our review also revealed that fungal infection after a penetrating head injury is extremely rare and often fatal. Our case seems to be the first in the medical literature with growth of M. thermophila as a causative agent for intracranial suppuration.     

Closed rupture of the anterior tibial tendon. A case report

Closed subcutaneous rupture of the anterior tibial tendon is a relatively uncommon injury that requires a thorough clinical examination to diagnose correctly. The authors report a case of this disorder and provide a review of the relevant literature. A method of surgical repair not previously described in the literature is also presented.     

Health effects of airborne pollutants, particularly in swine confinement stalls, from the viewpoint of occupational medicine]

From the point of view of occupational respiratory medicine, an overview on potential health effects of airborne pollutants particularly in swine confinement houses is presented. Airway diseases are the most frequent occupational disorders among farmers in many countries around the world including Germany. Due to various methodological reasons, epidemiological studies in farming populations are more difficult to perform than among non-farmers. Major constituents of swine confinement dust include bacteria, endotoxin, mites, fungal spores, and animal dander. Gaseous pollutants include ammonia, methane, and hydrogen sulfide. In a variety of cross-sectional studies, high prevalences of respiratory symptoms and non-obstructive (and obstructive) bronchitis and Organic Dust Toxic Syndrome have been reported in pig farmers. Nasal and bronchial provocation challenges with swine confinement dust include influx of neutrophils and other inflammatory cells as well as mediators. In cross-sectional and longitudinal studies, endotoxin turns out as the probably most relevant parameter associated with lung function impairment. Further studies are clearly needed focusing on the prognosis of non-obstructive bronchitis in swine farmers and on health effects of reducing airborne contaminants in swine confinement houses.     

On the use of the ratio or the odds ratio of cure rates in therapeutic equivalence clinical trials with binary endpoints

Acutely ill patients who are immunocompromised but not neutropenic most commonly are: (1) diabetic; (2) on chronic high-dose steroid therapy; (3) have lupus; or (4) have impaired or absent splenic function. These patients often present in the CCU because of the severity of their infection. Differential diagnosis may be approached by first considering the patient's underlying disease, i.e., SLE. The next step in the diagnostic process is to appreciate the immune defect associated with these disorders. The nature of the immune defect determines which clinical pathogens are related to the immune defect. Pathogens are associated with a sterotyped pattern of organ involvement. The object of the diagnostic analysis is to determine the most likely organism affecting a particular organ system, given the defect in host defenses associated with the patient's underlying illness. In this way, a useful clinical diagnosis can be made rapidly, and appropriate clinical specimens obtained for diagnostic testing. Often empiric therapy must be started pending the results of diagnostic testing. In such situations, empiric therapy ordinarily is directed against the bacterial pathogens most likely to cause disease relevant to the patient's impaired defenses. Specific therapy for unusual or exotic pathogens should not be empiric and should be based on demonstration of a pathogenic role by the microorganism. In the case of miliary tuberculosis or invasive fungal disease, a case may be made for early empiric therapy to cover these organisms if there is sufficient clinical suspicion based on the presenting signs and symptoms as well as the pattern of organ involvement. As with all infections, but particularly in immunocompromised patients, the early initiation of appropriate antimicrobial therapy is essential and often life-saving.     

Neurotoxicity evoked by N-methyl-D-aspartate in the organotypic static slice cultures of rat cerebral cortices: effect of GABA(A) receptor activation

BACKGROUND: von Recklinghausen's neurofibromatosis is a hereditary disease that may affect any organ or system of the body primarily or secondarily, including the vascular system. Among the rare cerebrovascular abnormalities, the most common is stenosis or occlusion of the cerebral artery. Intracranial aneurysms are uncommon. CASE DESCRIPTION: A case of an intracranial cerebral aneurysm associated with von Recklinghausen's neurofibromatosis is reported. A 55-year-old woman presented with a history of intermittent headache for 2 months and right oculomotor nerve palsy for 1 month. Widespread cutaneous neurofibromas and angiomas were found over her trunk and limbs with prominent cafe-au-lait spots. X-ray showed that her left lung was compressed by a large mass in the left chest with rib defects and lateral spinal curvature. Right internal carotid angiography revealed a saccular aneurysm between C1 and C2. Craniotomy to clip the aneurysm could not be performed because the mass in her chest made intubation for general anaesthesia almost impossible. CONCLUSION: The clinical features of this case are discussed together with a review of 15 similar cases in the literature. There are different theories about this disorder. We agree that the malformations are derived not only from ectodermal, but also from mesodermal pathology. In terms of our case, we consider the progression of this disease to be slow.     

Chronic mycoses of the paranasal sinuses--value of endonasal paranasal sinus surgery

BACKGROUND: Many host factors even in immunocompetent patients may have an influence on development of a fungal diseases within the paranasal sinuses. Fungal sinusitis can occur in an acute form or more often to a chronic type of the disease. These mainly relatively asymptomatic chronic forms and further divided into a chronic noninvasive, chronic allergic, and chronic invasive disease. Endonasal microsurgery has significantly changed the management of chronic fungal sinusitis and allows adequate removal of pathologic tissue even in advanced situations. The aim of this study was to analyze the efficacy of endonasal surgery in chronic fungal sinusitis. MATERIAL AND METHODS: In a retrospective study we assessed a group of 40 patients who had endonasal surgery for chronic fungal sinusitis. Patient records, CT and MRI scans, microbiology and histology as well as the postoperative clinical follow-up including endoscopic photo documentation were evaluated over a period of 5 years. All patients underwent endonasal surgery using endoscopic techniques. The microscopic was of additional help in a few cases with extended disease and multiple dehiscences of the skull base. RESULTS: Twenty-four patients had a chronic noninvasive of fungal sinusitis and 16 patients had a chronic invasive form. All these patients underwent endonasal surgery without external incision. The fungal disease was erradicated in 39 cases, and revision surgery was required in only one case in which involvement of the contralateral side was not initially detected. in two cases scar tissue in the middle meatus was later excised but without evidence of residual fungal disease. Only in 6 cases was antifungal chemotherapy required, where the disease had spread into surrounding tissue or the patient had severe symptoms. CONCLUSIONS: Endonasal microsurgical techniques are today the appropriate approach for managing chronic fungal sinus disease even in severe cases with radiologic evidence of expansion or invasion of surrounding tissue. Additional antifungal chemotherapy is only rarely indicated, specifically when the fungal disease invades surrounding tissue.