trimethoprim--sulfamethoxazole-drug-combination and Aspergillosis

Aspergillus myofasciitis is a rare infection of the muscles and their fascial sheaths that has been reported in patients with immune deficiencies of various kinds but, until now, not with chronic granulomatous disease (CGD). Patients affected by CGD are at high risk of invasive aspergillus infections. The case described involves a 14-year-old boy with a severe autosomal recessive CGD who was admitted to hospital with an Aspergillus myofasciitis of the left forearm. He was treated with liposomal amphotericin for 14 days and then with oral voriconazole for three months with an excellent clinical outcome. He did not evidence any recurrence in the following 30 months using itraconazole prophylaxis.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Combined Modality Therapy; Debridement; Drug Therapy, Combination; Fasciitis; Forearm; Granulomatous Disease, Chronic; Humans; Interferon-gamma; Itraconazole; Male; Pyomyositis; Trimethoprim, Sulfamethoxazole Drug Combination

Invasive aspergillosis is an important cause of morbidity and mortality in patients who have undergone lung transplantation. Aspergillus infections usually involve the respiratory tract, with vascular invasion and subsequent dissemination. However, acute appendicitis associated with localized aspergillosis is rare, especially among patients who have undergone prophylaxis with voriconazole. We present a case of primary Aspergillus appendicitis diagnosed by histologic examination in a patient who underwent lung transplantation. A 51-year-old woman with dermatomyositis underwent lung transplantation for acute interstitial pneumonitis. According to our institution's protocol, the patient was treated with immunosuppressive therapy and prophylaxis with voriconazole, ganciclovir, and trimethoprim sulfamethoxazole during the post-transplantation period. Twenty-eight days after transplantation, the patient developed mild abdominal pain and paralytic ileus. There was no apparent infection sign. Abdominal computerized tomography indicated a wall defect of the appendix with multifocal fluid collection, mesenteric leave thickening, and pneumoperitoneum. These findings were consistent with perforated appendicitis, and the patient underwent an appendectomy. The histopathology examination of the resected appendix showed inflammation and abscess. Periodic acid-Schiff-positive and Grocott-Gomori methenamine silver-positive fungal hyphae with acute-angle branching were observed, demonstrating muscular invasion. A galactomannan antigen test obtained on the same day had negative results. The trough level of voriconazole was well maintained and was subsequently adjusted through monitoring of circulating drug concentration. Simultaneously, other potential sites of disseminated Aspergillus were considered and examined, but no other site of systemic Aspergillus infection was detected. Voriconazole treatment was maintained for 3 months, and no aspergillosis relapse or other invasive fungal infections were observed.

Topics: Appendectomy; Appendicitis; Aspergillosis; Female; Ganciclovir; Humans; Immunocompromised Host; Immunosuppressive Agents; Lung Transplantation; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Voriconazole

Topics: Adult; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Aspergillosis; Exons; Female; Genes, X-Linked; Genetic Counseling; Granulomatous Disease, Chronic; Heterozygote; Humans; Itraconazole; Risk; Trimethoprim, Sulfamethoxazole Drug Combination

Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised patients receiving intensive care. The double-sandwich ELISA for galactomannan is reported to have a high sensitivity (96.5%) for the detection of invasive aspergillosis when a cut-off value of 0.8 ng/ml is used. However, we have experienced a case of lethal disseminated aspergillosis in a patient that presented with a negative galactomannan (GM) test and persistent elevation of beta-D glucan (BG) levels. A 63-year-old female was admitted to our Intensive Care Unit (ICU) in acute respiratory failure and elevated BG. She had been receiving medication for Good-pasture syndrome based on anti-glomerular basement membrane antibodies and myeloperoxidase-antineutrophil cytoplasmic antibodies for 9 months and was receiving long-term prednisolone therapy (20 mg/day). On admission, her trachea was immediately intubated, and a PCR analysis of the bronchoalveolar lavage sample revealed Pneumocystis jiroveci. Trimethoprimsulfamethoxazole therapy was started for Pneumocystis pneumonia. The levels of BG remained elevated (> 100 pg/ml) during the treatment period despite the clinical resolution of Pneumocystis pneumonia, raising concerns of another complicated invasive fungal disease; consequently, fosfluconazole was administered empirically. The serum BG levels, however, did not decrease. Blood cultures did not detect a fungal infection. Serum GM levels measured by a double-sandwich ELISA on the 6th, 11th, and 24th days in the ICU were negative (< 0.2 ng/ml). The patient ultimately died of multiple organ failure on the 45th ICU day. Postmortem examination revealed a disseminated fungal infection with aggressive vascular invasion of the lungs, heart, and brain. In situ hybridization with a 568-bp probe of the alkaline proteinase sequence of Aspergillus fumigatus showed specific positive staining within the fungus present in the infected lung tissue, revealing that this patient may have had a systemic infection by A. fumigatus or A. flavus. This is a case of serum GM-negative disseminated aspergillosis pathologically proven by autopsy. Persistent elevated BG levels (> 100 pg/ml) refractory to trimethoprim-sulfamethoxazole and fosfluconazole may suggest possible Aspergillus infection and should prompt the initiation of empiric anti-aspergillosis therapies in patients at risk for fungal infection.

Topics: Antifungal Agents; Aspergillosis; Aspergillus; beta-Glucans; Brain; Fatal Outcome; Female; Galactose; Heart; Humans; Immunosuppressive Agents; Intensive Care Units; Lung; Mannans; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisolone; Trimethoprim, Sulfamethoxazole Drug Combination

In this paper, we examined the details of severe infections, treatment efficacies, and the prognoses of 23 Japanese patients with chronic granulomatous disease (CGD). We described the mean ages at diagnosis and follow-up, which were 2.8 years (range, 0.7-10 years) and 14.9 years (range, 0.2-28.4 years), respectively. There were three deaths, two from Aspergillus pneumonia and one from liver abscess. Eighteen of the 23 patients (78%) had a complete loss of gp91phox, and three had p22-phox and one had p67phox deficiencies. Aspergillus species were found in 45% of 174 severe infections. The mean height and weight of the 20 surviving patients were -0.8 +/- 1.3SD and -1.9 +/- 1.9SD below the means for age, respectively. Short stature and underweight (below the 10th percentile of the means) for age were seen in 22% and 17% of the patients, respectively. This growth retardation reflects the severity of the disease. At 20 years of age, there was 87% survival. Ongoing prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) or antifungal drugs was given in 16 and 11 patients, respectively. Interferon-gamma (IFN-gamma) was given once a week to 14 patients. Four patients underwent hematopoietic stem cell transplantation (HSCT) and are currently well. There were infections observed in three of 21 identified related carriers of X-linked CGD. A carrier with a liver abscess had 5% normal neutrophils during the acute phase of infection, which returned to 40% normal neutrophils after recovery. The high survival rate in this hospital results from regular follow-up and prophylaxis with TMP-SMX and anti-fungal drugs beginning at the time of diagnosis, along with treatment with weekly IFN-gamma.

Topics: Adolescent; Adult; Anti-Infective Agents; Antifungal Agents; Antiviral Agents; Aspergillosis; Biomarkers; Body Height; Child; Child, Preschool; Drug Therapy, Combination; Female; Follow-Up Studies; Genetic Diseases, X-Linked; Granulomatous Disease, Chronic; Growth Disorders; Hospitals, Pediatric; Hospitals, State; Humans; Interferon-gamma; Japan; Male; Membrane Glycoproteins; NADPH Oxidase 2; NADPH Oxidases; Opportunistic Infections; Phosphoproteins; Prognosis; Stem Cell Transplantation; Survival Analysis; Thinness; Trimethoprim, Sulfamethoxazole Drug Combination

We present the case of a 74-y-old HIV-negative female who suffered simultaneously from multiple opportunistic infections and a Klebsiella pneumoniae sepsis during high-dose steroids for giant cell arteritis. The patient was treated with a purine analog due to hairy cell leukaemia 10 y previously. Purine analog therapy can lead to long lasting defects in cell-mediated immunity. In these patients, treatment with steroids should be closely monitored with CD4 counts.

Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Cladribine; Cytomegalovirus; Dexamethasone; Esophagitis; Female; Giant Cell Arteritis; Herpes Simplex; Humans; Klebsiella Infections; Klebsiella pneumoniae; Leukemia, Hairy Cell; Methylprednisolone; Opportunistic Infections; Pneumocystis carinii; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Aspergillosis; Aspergillus flavus; Aspergillus fumigatus; Dapsone; Humans; Microbial Sensitivity Tests; Pentamidine; Trimethoprim, Sulfamethoxazole Drug Combination

Hyper-IgE syndrome (HIE) and chronic granulomatous disease (CGD) are congenital immunodeficiency diseases with increased susceptibility to bacterial and fungal infections. Both carry significant morbidity and mortality rates because of invasive infections by Aspergillus species. We encountered 2 patients, one with HIE and one with CGD, in whom detection of sensitization to Aspergillus species preceded the diagnosis of immunodeficiency. With high-dose systemic corticosteroids for allergic bronchopulmonary aspergillosis (ABPA), an inflammatory disorder caused by sensitization to Aspergillus species, pulmonary abscesses developed in the patient with HIE, and the patient with CGD succumbed to an overwhelming Aspergillus species-induced pneumonia.. We sought to assess the prevalence of sensitization to Aspergillus fumigatus and the presence of diagnostic criteria for ABPA in patients with CGD and HIE.. We measured A fumigatus-specific serum IgE, IgG, and precipitating antibodies as indicators for A fumigatus sensitization in the sera of 18 patients with neutrophil disorders (7 with HIE and 11 with CGD). Hospital records were reviewed for the presence of other diagnostic criteria for ABPA (asthma, elevated total serum IgE concentration, and radiographic abnormalities).. Twelve (67%) of 18 patients were sensitized to A fumigatus, as evidenced by precipitating A fumigatus-specific antibodies. Six (33%) of 18 patients had serologic evidence of ABPA. Five of those 6 patients had radiologic abnormalities consistent with a diagnosis of ABPA. One patient with HIE also had asthma, thus fulfilling minimal essential criteria for concurrent ABPA.. Patients with HIE syndrome and CGD have a high incidence of sensitization to Aspergillus species. A clinical picture indistinguishable from ABPA may coexist or emerge in patients with CGD or HIE and create a major management dilemma because systemic corticosteroids may accelerate tissue damage and invasive fungal infections. It is important to distinguish individuals with congenital neutrophil disorders from uncomplicated classic ABPA.

Topics: Adult; Antibiotic Prophylaxis; Aspergillosis; Aspergillus fumigatus; Female; Granulomatous Disease, Chronic; Humans; Immunity, Innate; Immunization; Job Syndrome; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Chronic granulomatous disease (CGD) represents an innate immunodeficiency: the reduced production of oxygen radicals in phagocytosing cells results in decreased ability to kill pathogenic microorganisms. The patients concerned suffer from severe recurrent infections due to bacteria and fungi. Prophylactic administration of trimethoprim-sulfamethoxazole, as usual in CGD-patients, has markedly reduced the incidence of bacterial infections. Now as before, however, there is a high risk to become affected by invasive fungal infections, mainly due to Aspergillus spp. which often are lethal. Therefore, a well-compatible antimycotic long-term prophylaxis effective against Aspergillus would be attractive. In the present study the compatibility of the oral triazole itraconazole was tested in 8 CGD-patients with high risk of Aspergillus infections. Itraconazole was administered in capsules with a dosage of 5.1 mg/kg body weight per day on an average for a mean range of 23 months. Periodically liver enzymes, renal retention and electrolytes were assessed as well as itraconazole serum levels. Aspergillus serology tests included complement fixation tests, IgG-ELISA, precipitation tests, IgE determination and Aspergillus-RAST. During the prophylactic treatment in all of the 8 patients no gastrointestinal side effects or hypersensitivity reactions were observed. Renal retention and serum electrolytes as well as liver enzyme values were in normal ranges with all patients. Itraconazole serum levels showed a marked intra- and interindividual variability. However, 82% of the peak levels were in ranges regarded as therapeutically effective for itraconazole. Under prophylaxis a clear decrease of Aspergillus IgG-ELISA values was observed in 5 of 7 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Aspergillosis; Bacterial Infections; Child; Child, Preschool; DNA, Fungal; Enzyme-Linked Immunosorbent Assay; Granulomatous Disease, Chronic; Humans; Immunoglobulin G; Incidence; Itraconazole; Opportunistic Infections; Trimethoprim, Sulfamethoxazole Drug Combination

A case is reported of rapid onset concomitant pulmonary infection with Nocardia and Aspergillus fumigatus in a patient six weeks after the institution of immunosuppressive therapy for renal vasculitis. Pulmonary lesions completely resolved on treatment with a combination of imipenem, cotrimoxazole and a prolonged course of itraconazole.

Topics: Adult; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Cyclophosphamide; Drug Therapy, Combination; Humans; IgA Vasculitis; Imipenem; Immunocompromised Host; Itraconazole; Ketoconazole; Kidney Failure, Chronic; Lung; Lung Diseases, Fungal; Male; Nocardia Infections; Pneumonia; Prednisolone; Radiography; Renal Dialysis; Trimethoprim, Sulfamethoxazole Drug Combination

An 18-year-old boy with X-linked chronic granulomatous disease (CGD) developed Aspergillus fumigatus pneumonia and multifocal osteomyelitis. Treatment with amphotericin B resulted in only moderate improvement of the lesions and was accompanied by considerable toxicity. In contrast, administration of the new triazole drug itraconazole led to complete disappearance of all signs of infection. We conclude that itraconazole may be a valuable new drug for treating invasive aspergillosis in patients with CGD, although the duration of treatment remains to be established.

Topics: Adolescent; Amphotericin B; Aspergillosis; Aspergillus fumigatus; Chromatography, High Pressure Liquid; Granulomatous Disease, Chronic; Humans; Itraconazole; Ketoconazole; Lung Diseases, Fungal; Male; Osteomyelitis; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination