trimethoprim--sulfamethoxazole-drug-combination and Granulomatous-Disease--Chronic

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

We report the first case of genetically confirmed chronic granulomatous disease (CGD) in a Kenyan child.. A 7-month-old male infant, the only child of non-consanguineous parents, presented with cough, fever, fast breathing, oral thrush, and axillary lymphadenopathy ipsilateral to the Calmette-Guérin bacillus scar. He had been hospitalized 5 weeks prior for severe pneumonia. Plain chest radiography showed bilateral patchy airspace opacification; chest computed tomography revealed multiple large lung nodules and left axillary lymphadenopathy. HIV ELISA was negative; tuberculin skin test was positive; lymph node biopsy macroscopically revealed caseous granulomas seen on histology; isoniazid- and rifampicin-susceptible. An inborn error of immunity (IEI) was considered given the recurrent fevers and atypical lung nodules. Genetic analysis revealed a hemizygous pathogenic variant on. Genetic testing is relatively accessible and cost-effective for the diagnosis of IEI in low-and-middle-income countries. Expert multi-disciplinary collaboration is key for successful outcomes.

Topics: Aftercare; Child; Granulomatous Disease, Chronic; Humans; Infant; Kenya; Lymphadenopathy; Male; Patient Discharge; Trimethoprim, Sulfamethoxazole Drug Combination

Infections with non-typhoidal Salmonella sp. have been documented in children with chronic granulomatous disease (CGD), but the prevalence of salmonella infection in children with CGD in underdeveloped countries is unknown. We assessed the clinical profiles of CGD patients diagnosed at our tertiary care centre in north India and had Salmonella sp.infections. We found three patients with Salmonella sp. bloodstream infections (2-proven, 1-probable) among the 99 CGD patients. After receiving cotrimoxazole prophylaxis following a CGD diagnosis, we noted that none of our patients experienced non-typhoidal salmonella infection. One patient experienced severe typhoidal bacteremia despite receipt of cotrimoxazole prophylaxis. This patient required numerous hospital admissions and prolonged intravenous antibiotic regimen. We suggest that vaccination with killed typhoidal vaccines should be regularly given to children with CGD in order to avoid typhoidal bacteremia, in addition to cotrimoxazole prophylaxis and a focus on good hand and food hygiene.

Topics: Bacteremia; Child; Granulomatous Disease, Chronic; Humans; Salmonella; Salmonella Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Typhoid Fever

Topics: Anti-Infective Agents; Antifungal Agents; Biopsy; Diagnosis, Differential; Fever; Granulomatous Disease, Chronic; Humans; Infant, Newborn; Itraconazole; Lung; Male; Pulmonary Aspergillosis; Radiography, Interventional; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Voriconazole

Topics: Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Anticoagulants; Arterial Occlusive Diseases; Behcet Syndrome; Diagnostic Errors; Granulomatous Disease, Chronic; Humans; Immunocompromised Host; Lung; Male; Opportunistic Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Granulomatous Disease, Chronic; Humans; Liver Abscess; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Chronic granulomatous disease (CGD) is an inherited disease of the phagocyte NADPH oxidase system that causes defective production of toxic oxygen metabolites, leading to impaired bacterial and fungal killing, and recurrent life threatening infections; mostly by catalase producing organisms. Nocardiosis in CGD is well described, however actinomycosis is rare. We describe a patient of CGD with actinomycosis and nocardiosis coinfection. A 43-year-old male with history of recurrent discharging sinuses presented with fever, dyspnea and cough. He had multiple discharging sinuses over neck and anterior chest wall. There was only partial response to intravenous penicillin. Needle aspirate from chest wall showed co-infection with actinomyces and nocardia. His nitroblue tetrazolium (NBT) reduction test was negative. He was treated with penicillin, amikacin and trimethoprim-sulfamethoxazole and had good clinical and radiological response.

Topics: Actinomycosis; Adult; Amikacin; Anti-Bacterial Agents; Coinfection; Granulomatous Disease, Chronic; Humans; Male; Nocardia Infections; Penicillin V; Trimethoprim, Sulfamethoxazole Drug Combination

Edwardsiella tarda, a catalase-positive bacillus widely distributed throughout nature, is generally susceptible to trimethoprim/sulfamethoxazole. We describe osteomyelitis due to trimethoprim/sulfamethoxazole-resistant E. tarda in a patient with chronic granulomatous disease (CGD). Once E. tarda acquires antibiotic resistance, infected CGD patients may develop severe infections with unforeseeable consequences.

Topics: Adolescent; Anti-Bacterial Agents; Drug Resistance, Bacterial; Edwardsiella tarda; Enterobacteriaceae Infections; Granulomatous Disease, Chronic; Humans; Infant, Newborn; Leg; Magnetic Resonance Imaging; Male; Osteomyelitis; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antibiotic Prophylaxis; Antifungal Agents; Child, Preschool; Granulomatous Disease, Chronic; Humans; Lupus Erythematosus, Discoid; Male; Pyrimidines; Triazoles; 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

A retrospective clinical and immunological survey was conducted in 60 patients with Chronic Granulomatous Disease. A prospective controlled non-randomized study of the efficacy of long-term IFNgamma treatment was carried out. The mean age at the time of diagnosis was 4.4 years; mean duration of follow-up was 10.4 years. Lung and skin infections were the most frequent manifestations both prior to diagnosis and during follow-up. Aspergillus species was the first cause of infection and of death in our cohort. The mortality rate was 13%. Long term prophylaxis with IFNgamma did not significantly change the rate of total infection per patient-year compared to controls (p=0.07). Our data provide clear evidence that protocols of continuing intensive surveillance and monitoring of compliance with anti-infective regimens may significantly improve the quality of life and long-term survival in patients with CGD. No evidence justifying long-term prophylaxis with IFNgamma was obtained.

Topics: Anti-Infective Agents; Antifungal Agents; Antiviral Agents; Bacterial Infections; Child; Child, Preschool; Cohort Studies; Female; Follow-Up Studies; Granulomatous Disease, Chronic; Humans; Infant; Interferon-gamma; Italy; Itraconazole; Kaplan-Meier Estimate; Male; Retrospective Studies; Treatment Outcome; 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

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by recurrent infections with certain types of bacteria and fungi. Presented herein is the case of a 29 year old woman with CGD who suffered from bacteria-associated haemophagocytic syndrome and a septic pulmonary embolism following a uterine infection and sepsis, caused by Burkholderia cepacia complex.

Topics: Adult; Anti-Bacterial Agents; Antifungal Agents; Burkholderia cepacia complex; Burkholderia Infections; Echinocandins; Female; Granulomatous Disease, Chronic; Humans; Lipopeptides; Lipoproteins; Lymphohistiocytosis, Hemophagocytic; Micafungin; Minocycline; Peptides, Cyclic; Pulmonary Embolism; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination

Chronic granulomatous disease (CGD) is characterized by defective bactericidal activity of white blood cells, specifically, a defect in superoxide production. Patients experience infections, predominantly caused by catalase-positive bacteria and fungal organisms, that may be severe and life-threatening. Most cases of CGD are diagnosed in children; however, it may rarely go undiagnosed until adulthood in individuals with unexplained infections and granulomatous inflammation.. To describe an adult with Crohn disease and recurrent infections who was newly diagnosed as having CGD.. A 53-year-old woman with a history of liver abscesses and Crohn disease presented with Burkholderia cepacia pneumonia and required a right middle lobe resection. Nitroblue tetrazolium test results confirmed the diagnosis of CGD, and Western blot analysis revealed the absence of the 47-phagocyte oxidase protein. Levels of Crohn-associated specific antibodies to Saccharomyces cerevisiae and Escherichia coli outer membrane porin C were elevated.. The patient, newly diagnosed as having CGD, was given intravenous trimethoprim-sulfamethoxazole, after which she improved clinically and was discharged from the hospital in stable condition to receive daily oral trimethoprim-sulfamethoxazole treatment.. The concomitant occurrence of Crohn disease and CGD, both characterized by granulomatous inflammation, is noteworthy. This case study demonstrates that CGD should be considered in adults with recurrent infections, especially those caused by catalase-positive organisms, such as B cepacia.

Topics: Anti-Infective Agents; Burkholderia cepacia; Burkholderia Infections; Crohn Disease; Female; Granulomatous Disease, Chronic; Humans; Middle Aged; Pneumonia, Bacterial; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Child, Preschool; Fever; Granulomatous Disease, Chronic; Humans; Male; Periapical Periodontitis; Trimethoprim, Sulfamethoxazole Drug Combination

Chronic granulomatous disease (CGD) is an inherited disease characterized by severe and recurrent bacterial and fungal infections. Phagocytic cells of CGD patients are unable to produce superoxide anion, and their efficiency in bacterial killing is significantly impaired. In these patients, the prophylactic and therapeutic validity of a long-term use of trimethoprim-sulfamethoxazole (TMP-SMX) has been well established. However a role of nitric oxide (NO) produced by phagocytic cells from CGD patients is unknown, and the mechanism of TMP-SMX in CGD is unclear. We have directly measured NO production in whole human blood by using 4,5-diaminofluorescein as a novel fluorescent indicator for intracellular NO. Intracellular NO production of gated neutrophils increased time dependently when stimulated by lipopolysaccharide (LPS) and calcium ionophore. Although all polymorphonuclear leukocyte (PMN) specimens from patients with CGD failed to generate hydrogen peroxide, NO production by CGD PMNs was significantly increased compared with that of control PMNs (p<0.05). TMP-SMX with LPS significantly increased compared with LPS-stimulated samples at clinical (n=5, p<0.05) and 10-fold clinical concentrations (n=5, p<0.01). TMP-SMX with LPS in CGD PMNs significantly increased the production of NO in comparison with the LPS stimulation at 10-fold clinical concentrations (n=5, p<0.05). In conclusion, our data indicate the possibility that NO production by neutrophils from patients with CGD treated with TMP-SMX has a role of bactericidal activity instead of O(2)(-) in host defense mechanism.

Topics: Adolescent; Adult; Anti-Infective Agents; Calcimycin; Child; Child, Preschool; Enzyme Inhibitors; Fluoresceins; Fluorescence; Granulomatous Disease, Chronic; Humans; Hydrogen Peroxide; Indazoles; Infant; Isothiuronium; Lipopolysaccharides; Male; Neutrophils; Nitric Oxide; Trimethoprim, Sulfamethoxazole Drug Combination

Two patients with chronic granulomatous disease who had previously been intolerant to trimethoprim-sulfamethoxazole because of various adverse reactions completed a desensitisation protocol with a favourable clinical outcome.

Topics: Adolescent; Anti-Infective Agents; Child; Granulomatous Disease, Chronic; Humans; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Generalised prepubertal periodontitis is a rare entity that is usually a consequence of severe systemic diseases. Chronic granulomatous disease is one of the extremely rare inherited immunodeficiency diseases, which predisposes the patient to recurrent severe bacterial and fungal infections.. The purpose of this report is to describe a 5-year old male patient suffering from prepubertal periodontitis associated with chronic granulomatous disease, who was referred to the Department of Periodontology for treatment of severe gingival inflammation.. A detailed past history was obtained and thorough clinical and laboratory examinations were performed.. Medical tests revealed the only immunodeficiency sign as the extremely low burst test result. The patient was diagnosed as having an autosomal recessive (AR) form of chronic granulomatous disease. He was put on prophylactic treatment with trimethoprim-sulfamethoxazole (TMP-SMX) and also a periodontal maintenance regimen with regular 1-month intervals.. This case report emphasises the importance of the differential diagnosis of severe immunodeficiency in the background of prepubertal periodontitis.

Topics: Aggressive Periodontitis; Anti-Infective Agents; Child, Preschool; Diagnosis, Differential; Disease Susceptibility; Follow-Up Studies; Genes, Recessive; Gingivitis; Granulomatous Disease, Chronic; Humans; Male; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

We report the first case of HIV infection in a patient with underlying X-linked chronic granulomatous disease (CGD) who presented with hepatopulmonary nocardiosis. Despite the coexistence of CGD and HIV, the response to therapy was normal, and no unusual sequelae were noted. The patient's high virus burden was successfully repressed with antiretroviral therapy, suggesting that the nicotinamide adenine dinucleotide phosphate oxidase system is not essential for active viral replication or response to antiretroviral agents.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Granulomatous Disease, Chronic; Humans; Liver; Male; Nocardia; Nocardia Infections; Radiography, Thoracic; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; X Chromosome

We describe a patient who suffered from chronic progressive granulomatous lung disease. He had no clinical or microbiological evidence of infection. After failure of treatment with interferon-gamma and trimethoprim-sulfamethoxazole, he responded dramatically to corticosteroids.

Topics: Adrenal Cortex Hormones; Anti-Infective Agents; Antiviral Agents; Child; Disease Progression; Drug Resistance; Granulomatous Disease, Chronic; Humans; Interferon-gamma; Lung Diseases; Male; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Outcomes for children with chronic granulomatous disease (CGD) have historically been poor, but significant improvements have occurred with the use of effective antibacterial prophylaxis. The present study aimed to document the clinical course of a cohort of children diagnosed with CGD since 1990 in a single centre. Twenty-one patients were identified, with a median age at last assessment of 4 years and 5 months. A third of these children were diagnosed in infancy because of a positive family history. Of the remaining, there was a median delay between the onset of symptoms and diagnosis of 13 months. No invasive or fungal infections were documented after diagnosis, nor were there any deaths in this cohort. A variety of non-infectious complications were noted, which responded well to steroids. As a group, these children were thriving and weight and height distributions fell within the population norm. All patients were receiving antibacterial prophylaxis, 90% with co-trimoxazole, and all but one patient were receiving a prophylactic anti-fungal agent (itraconazole). Both drugs were well tolerated. In conclusion, this cohort of patients, diagnosed in the last decade, tolerated antibacterial and anti-fungal prophylaxis well and on this regimen have a significantly decreased incidence of infection when compared with historical cohorts. Careful follow up of patients who have had aggressive antibacterial and anti-fungal prophylaxis should continue. The data reported on this cohort of patients should inform the debate about the use of more aggressive treatments, such as bone marrow transplantation, in this disease.

Topics: Adolescent; Anti-Infective Agents; Antifungal Agents; Child; Child, Preschool; Cohort Studies; Female; Follow-Up Studies; Granulomatous Disease, Chronic; Humans; Infant; Itraconazole; Male; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the clinical long-term course in patients with chronic granulomatous disease (CGD) with respect to different CGD subtypes and currently used antimicrobial prophylactic measures.. The records of 39 patients with CGD who were monitored during a period of 22 years were reviewed. All infections, infectious complications, and clinical outcomes were documented for a total observation period of 610 patient-years and were stratified with respect to different CGD subtypes.. Lymphadenitis, skin abscesses, and pneumonia occurred in 87%, 72%, and 59% of the patients, respectively. In 151 microbiologic isolates Staphylococcus aureus, Aspergillus species, Candida species, Pseudomonas species, and Salmonella species were the most frequently detected microorganisms. There were 167 severe infections requiring hospitalization and intravenous antimicrobial treatment, resulting in an incidence of 3.7 severe infections per 100 patient months (SI/100 PM). Long-term antibiotic prophylaxis significantly reduced the incidence of severe bacterial infections from 4.8 SI/100 PM to 1. 6 SI/100 PM (P =.0035). In contrast, fungal infections increased under antibiotic prophylaxis from a mean incidence of 0.2 SI/100 PM to 1.9 SI/100 PM (P =.04). We found a 50% survival rate through the fourth decade of life, with a plateau after the third decade of life. Patients with a complete absence of cytochrome b(558) showed an earlier manifestation of their disease and a higher incidence of infections and had significant lower survival than patients with only diminished cytochrome b(558) or autosomal recessive CGD.. Infections with Aspergillus species have become the major cause of infectious complications and death in patients with CGD. Prophylactic and therapeutic measures are needed to further increase life expectancy and quality for patients with CGD.

Topics: Adolescent; Adult; Age of Onset; Antibiotic Prophylaxis; Antifungal Agents; Child; Child, Preschool; Follow-Up Studies; Granulomatous Disease, Chronic; Humans; Infant; Itraconazole; Opportunistic Infections; Survival Analysis; 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

Topics: Child; Female; Granulomatous Disease, Chronic; Humans; Infant; Male; NADP; 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

Recent studies have shown clinical benefit resulting from recombinant interferon gamma (rIFN-gamma) therapy in patients affected by chronic granulomatous disease (CGD), which represents an important adjunct to conventional therapy. In order to evaluate the effect of interferon gamma therapy, we investigated clinical and haematological parameters in a child with X-linked CGD, McLeod phenotype (kell negative) and hyper-IgE, before and after 8 months of therapy. Our results show no significant effect of rIFN-gamma on the respiratory burst of peripheral polymorphonuclear leukocytes. This notwithstanding, we observed improved clinical and haematological conditions. These results support the view that interferon gamma may benefit these subjects by influencing oxygen-independent antimicrobial activity or other immunological parameters.

Topics: Amoxicillin; Child; Chromosome Aberrations; Chromosome Disorders; Granulomatous Disease, Chronic; Humans; Immunoglobulin E; Interferon-gamma; Lymphocytes; Male; Nitroblue Tetrazolium; Trimethoprim, Sulfamethoxazole Drug Combination; X Chromosome

Fine-needle aspiration cytology (FNAC) of enlarged cervical lymph nodes of a 9-yr-old boy complaining of progressive weight loss showed a combination of a necrotizing granulomatous process and pigmented histiocytes. The diagnosis of chronic granulomatous disease (CGD) of childhood was proposed, and it was later confirmed by histology. Although the NBT test was negative, the patient responded well to prolonged bactericidal therapy with trimethoprim-sulfamethoxazole associated with parenteral nutrition, indicating a rare case of CGD with a negative Nitro-Blue Tetrazolium (NBT) test. The cytologic findings appear to be unique for this disease.

Topics: Biopsy, Needle; Child; Cytodiagnosis; Granulomatous Disease, Chronic; Histiocytes; Humans; Lymph Nodes; Male; Nitroblue Tetrazolium; Parenteral Nutrition, Total; Trimethoprim, Sulfamethoxazole Drug Combination

From July 1988 to December 1989, six boys with chronic granulomatous disease were diagnosed in our institutions. Their clinical features were reviewed in order to delineate the pattern of infections which seems to have both similarities and differences when compared with published reports of Caucasian patients. The most striking differences was the lack of skin sepsis and chronic lymphadenitis in our six patients. Gram-negative organisms were the commonest pathogens while Staphylococci sp. were not isolated. Clinical features which should alert one to the diagnosis were also highlighted. Prophylactic co-trimoxazole was effective in reducing the frequency of bacterial infections. Early diagnosis is not only essential for optimal patient management but also for genetic counselling for the extended family.

Topics: Anti-Bacterial Agents; Bacterial Infections; Granulomatous Disease, Chronic; Hong Kong; Humans; Infant; Infant, Newborn; Male; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Long-term oral antimicrobial prophylaxis is accepted practice in the management of patients with chronic granulomatous disease (CGD). Reports of adverse outcome with trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis in other patient groups, and the recent occurrence of several severe fungal infections in patients followed at the National Institutes of Health (NIH), prompted a review of the NIH experience to examine the incidence of nonfungal and fungal infections in CGD patients with and without TMP-SMX prophylaxis. Prophylaxis decreased the incidence of nonfungal infections from 7.1 to 2.4 per 100 patient-months in patients with autosomal CGD (P less than .01) and from 15.8 to 6.9 infections per 100 patient-months (P = .06) in X-linked CGD patients. There was no significant change in the incidence of fungal infection in CGD patients on TMP-SMX (1.5-0.3 fungal infections/100 patient-months in autosomal CGD and 1.7-0.2 fungal infections/100 patient-months in X-linked CGD patients). TMP-SMX prophylaxis is indicated for the management of patients with CGD and decreases the incidence of non-fungal infections without increasing the incidence of fungal infections.

Topics: Genetic Linkage; Granulomatous Disease, Chronic; Humans; Infection Control; Mycoses; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; X Chromosome

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

Topics: Child; Colic; Granulomatous Disease, Chronic; Humans; Hydronephrosis; Male; Nephrostomy, Percutaneous; Rifampin; Trimethoprim, Sulfamethoxazole Drug Combination; Ureteral Obstruction

We retrospectively analyzed the frequency and nature of infections occurring in 48 patients with chronic granulomatous disease. The long-term use of trimethoprim-sulfamethoxazole and ketoconazole as a preventive therapy for infections has also been evaluated. Lymphadenitis, lung infections, dermatitis, enteral infections, and hepatic abscesses were the most frequent infections. Staphylococcus aureus, Salmonella, and Aspergillus were the main microorganisms encountered. Twelve patients died: five from lung aspergillosis, three from hepatic abscesses, two from pneumonopathy of unknown origin, one from salmonellosis, and one from another probable infection that could not be proved. The actuarial survival rate was 50% at 10 years of age, with a prolonged plateau thereafter. There was no difference in survival rates between patients with X-linked and those with autosomal recessive chronic granulomatous disease. The 8-year actuarial survival rate was significantly higher for patients born in 1978 or afterward than for patients born before 1978 (92.9% vs 70.5%). A retrospective analysis of the occurrence of bacterial and fungal infections in patients who received trimethoprim-sulfamethoxazole and ketoconazole as infection prophylaxis indicated that the former was effective against bacterial infections but that ketoconazole provided no protection against Aspergillus infections.

Topics: Adolescent; Bacterial Infections; Child; Child, Preschool; Drug Combinations; Genetic Linkage; Granulomatous Disease, Chronic; Humans; Infant; Infant, Newborn; Ketoconazole; Mycoses; Paris; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; X Chromosome

Chronic granulomatous disease (CGD) is a diverse disorder characterized by several clinical presentations and a multitude of metabolic defects. The authors summarize the clinical features and current management of CGD, offer a definition of the disease based on molecular defects of the respiratory burst, and present their experience with trimethoprim/sulfamethoxazole prophylaxis.

Topics: Adolescent; Adult; Bone Marrow Transplantation; Child; Child, Preschool; Drug Combinations; Drug Therapy, Combination; Female; Granulomatous Disease, Chronic; Humans; Infant; Infection Control; Infections; Male; NADH, NADPH Oxidoreductases; NADPH Oxidases; Oxygen Consumption; Phagocytes; Sulfamethoxazole; Superoxides; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Child; Child, Preschool; Drug Combinations; Granulomatous Disease, Chronic; Humans; Pneumonia; Pseudomonas; Pseudomonas Infections; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Blood Bactericidal Activity; Drug Combinations; Granulomatous Disease, Chronic; Humans; Infant; Isoniazid; Male; Neutrophils; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

We report two patients with chronic granulomatous disease (CGD) and life-threatening infections: a 10 10/12-year-old boy had Aspergillus fumigatus spondylitis with destruction of the 11th vertebral body and paravertebral abscess formation, and an 8 5/12-year-old boy had multiple Staphylococcus aureus hepatic abscesses with subphrenic abscess formation. Both patients failed to respond to intense antimicrobial therapy but showed a remarkable recovery following surgical drainage combined with granulocyte transfusions. These results suggest that antimicrobial therapy and surgical drainage followed by granulocyte transfusions may be the ideal mode of treatment for severe infections in patients with CGD.

Topics: Amphotericin B; Blood Transfusion; Child; Drug Combinations; Flucytosine; Granulocytes; Granulomatous Disease, Chronic; Humans; Liver Abscess; Male; Spondylitis; Staphylococcal Infections; Subphrenic Abscess; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

We have followed nine male patients with Chronic Granulomatous Disease at The Hospital for Sick Children, Toronto, since 1972. The diagnosis was established in each case by the failure of neutrophils to reduce nitroblue tetrazolium dye and to kill Staphylococcus aureus normally in vitro. Bacterial infections began between 6 months and 14 years of age. In five of the nine patients, infections began after 4 years of age. The first significant infection in five patients was a liver abscess(es), and one patient each had lymphadenitis, pulmonary aspergillosis, a parapharyngeal abscess, and a draining inguinal incision following surgery. Following diagnosis, all patients were started on Trimethoprim-Sulfamethoxazole at a dose of 2 mg/kg/day of Trimethoprim. The patients have been followed for 50 patient-years. Five of nine patients have been free of infection during 16 years of observation. For the remaining four patients, there have been six infections during 34 years of observation. A possible infection-related death occurred in one patient. The patients reported here appear to differ from those in previous reports. They present later in life, often with a liver abscess. They have a low incidence of subsequent bacterial infections which may, in part, be due to Trimethoprim-Sulfamethoxazole prophylaxis. The patients with chronic granulomatous disease reported here appear to have a better prognosis than previously thought.

Topics: Adolescent; Child; Child, Preschool; Drug Combinations; Granulomatous Disease, Chronic; Humans; Infant; Liver Abscess; Lung Diseases, Fungal; Lymphatic Diseases; Male; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

The value of long-term prophylactic treatment of chronic granulomatous disease (CGD) in childhood cannot be established with certainty, as controlled studies are not available. We describe a boy, presently 15 years old, who suffered from CGD since early infancy. By the clinical, laboratory and genetic features, this case appeared to be a new variant of CGD, combining elements of the "childhood" type with others that characterize the "adult" type of the syndrome. For years, the patient had been almost continuously ill and needed frequent and prolonged hospitalizations because of severe bacterial infections. At age 13 years, long-term prophylactic treatment with trimethoprim-sulfamethoxazole (TMP-SMX) was instituted. With this regimen, the patient was maintained practically infection-free, relapsing only in those instances when he neglected to comply with the prophylactic regimen for 1 to 2 weeks. Thus, the patient served as his own control in demonstrating the efficacy of antimicrobial prophylaxis in CGD. The rationale for employing TMP-SMX for the prophylactic regimen is discussed.

Topics: Adolescent; Drug Combinations; Granulomatous Disease, Chronic; Humans; Male; Sulfamethoxazole; Time Factors; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination