Zygomycosis is an important emerging fungal infection, associated with high morbidity and mortality. The Working Group on Zygomycosis of the European Confederation of Medical Mycology (ECMM) prospectively collected cases of proven and probable zygomycosis in 13 European countries occurring between 2005 and 2007. Cases were recorded by a standardized case report form, entered into an electronic database and analysed descriptively and by logistic regression analysis. During the study period, 230 cases fulfilled pre-set criteria for eligibility. The median age of the patients was 50 years (range, 1 month to 87 years); 60% were men. Underlying conditions included haematological malignancies (44%), trauma (15%), haematopoietic stem cell transplantation (9%) and diabetes mellitus (9%). The most common manifestations of zygomycosis were pulmonary (30%), rhinocerebral (27%), soft tissue (26%) and disseminated disease (15%). Diagnosis was made by both histology and culture in 108 cases (44%). Among 172 cases with cultures, Rhizopus spp. (34%), Mucor spp. (19%) and Lichtheimia (formerly Absidia) spp. (19%) were most commonly identified. Thirty-nine per cent of patients received amphotericin B formulations, 7% posaconazole and 21% received both agents; 15% of patients received no antifungal therapy. Total mortality in the entire cohort was 47%. On multivariate analysis, factors associated with survival were trauma as an underlying condition (p 0.019), treatment with amphotericin B (p 0.006) and surgery (p <0.001); factors associated with death were higher age (p 0.005) and the administration of caspofungin prior to diagnosis (p 0.011). In conclusion, zygomycosis remains a highly lethal disease. Administration of amphotericin B and surgery, where feasible, significantly improve survival.

BG antigenemia is superior to Candida score and colonization indexes and anticipates diagnosis of blood culture-negative IAC. This proof-of-concept observation in strictly selected high-risk surgical ICU patients deserves investigation of BG-driven preemptive therapy.

Several subtypes of Mycobacterium kansasii have been described, but their respective pathogenic roles are not clear. This study investigated the distribution of subtypes and the pathogenicity of M. kansasii strains (n ‫؍‬ 191) isolated in Switzerland between 1991 and 1997. Demographic, clinical, and microbiological information was recorded from clinical files. Patients were classified as having an infection according to the criteria of the American Thoracic Society. Subtypes were defined by PCR-restriction enzyme analysis of the hsp65 gene. Subtype 1 comprised 67% of the isolates (n ‫؍‬ 128), while subtypes 2 and 3 comprised 21% (n ‫؍‬ 40) and 8% (n ‫؍‬ 15), respectively. Other subtypes (subtypes 4 and 6 and a new subtype, 7) were recovered from only 4% of patients (n ‫؍‬ 8). M. kansasii subtype 1 was considered pathogenic in 81% of patients, while M. kansasii subtype 2 was considered pathogenic in 67% of patients and other subtypes were considered pathogenic in 6% of patients. The majority of patients with M. kansasii subtype 2 were immunocompromised due to the use of corticosteroids (21% of patients) or coinfection with HIV (62.5% of patients). Subtyping M. kansasii may improve clinical management by distinguishing pathogenic from nonpathogenic subtypes.

Mycobacterium tuberculosis survives and replicates within human macrophages, but the mechanisms whereby tubercle bacilli resist killing are incompletely understood. We tested the general model in which M. tuberculosis evades killing by entering naive macrophages through receptors that are unable to activate cellular microbicidal activities. Complement receptor types 1 (CR1), 3 (CR3), and 4 (CR4) were blocked with monoclonal antibodies, and mannose receptors were blocked with a competitive ligand, mannosylated bovine serum albumin (MBSA). Survival and replication of M. tuberculosis (Erdman) were evaluated after the bacteria were phagocytosed in the presence of blocking agents (directing binding to the unblocked receptors). Although there was significant variation in the growth rate of virulent M. tuberculosis in monocyte-derived macrophages from different donors, the intracellular survival and replication of mycobacteria were equivalent regardless of the receptor(s) used for binding and phagocytosis. We conclude that the mechanisms whereby M. tuberculosis evades killing by human macrophages are independent of the receptor-mediated route of entry, and operate at one or more steps common to all entry pathways. Blocking complement and mannose receptors in combination did not completely abrogate binding of M. tuberculosis to macrophages. However, we found that two polyanionic scavenger-receptor ligands exhibited a concentration-dependent ability to block binding of M. tuberculosis to macrophages. Moreover, blocking class A scavenger receptors abrogated nearly all binding that persisted after blocking complement and mannose receptors. This indicates that class A scavenger receptors are quantitatively important mediators of M. tuberculosis-macrophage interactions. M. tuberculosis has evolved multiple mechanisms to promote its efficient entry into macrophages. This suggests that passage of the organism through macrophages may be an essential early step in the pathogenesis of tuberculosis.

During a 3-month period, small-colony variant phenotypes of both Staphylococcus aureus and Pseudomonas aeruginosa were isolated from respiratory secretions of 8.2% and 9.2%, respectively, of 98 patients with cystic fibrosis, particularly those with advanced pulmonary disease and prolonged antibiotic exposure. Infection of the respiratory tract with Staphylococcus aureusand Pseudomonas aeruginosa plays an important role in the pathogenesis of cystic fibrosis (CF) (7). Recently, subtypes of S. aureus and P. aeruginosa termed small-colony variants (SCV) have been isolated from the respiratory secretions of CF patients (3,5,12). S. aureus SCV have been associated with persistent infections, and they are more resistant to many antibiotics than normal S. aureus strains (9, 11, 13). The small, nonpigmented, nonhemolytic colonies, which may not be recovered in the routine clinical microbiology laboratory (10), were found in the respiratory secretions of 26 (33%) of 78 CF patients followed for 3 years (5). Characteristics of P. aeruginosa SVC (14, 16) include hyperadherence, enhanced biofilm formation, and increased antibiotic resistance (1, 2, 4, 6). These colonies were recovered from respiratory samples of 33 (38%) of 86 CF patients followed for 2 years (3). We wanted to prospectively assess the presence of SCV of both S. aureus and P. aeruginosa in respiratory secretions collected from CF patients during a 3-month period and to correlate microbiology findings with important clinical and laboratory parameters.From 26 July to 29 October, 2000, conventional bacteriologic examinations of all respiratory specimens from our CF patients were complemented by a prospective screen for SCV of both S. aureus and P. aeruginosa. We examined 148 respiratory samples from 106 patients. Seven patients were excluded from analysis because of incomplete medical records, and one patient whose sputum grew SCV of both species was excluded for statistical reasons. Of the remaining 98 patients, 20 contributed more than one sample (two to six samples). For statistical reasons, we studied one sample per patient: either the first sample obtained or, for patients harboring SCV, the first sample that contained SCV. Clinical data and laboratory results were extracted from patients' charts using a standardized questionnaire. For parameters relating to weight (i.e., weight of an underweight patient as a percentage of predicted weight; the body mass index) and pulmonary function (percentage of predicted forced expiratory volume in 1 s [FEV 1 ] and partial pressure of arterial oxygen [PaO 2 ]), the highest value in the year preceding or following sample collection was evaluated. Antibiotic treatment for the preceding 36 months was studied. Patients without SCV served as controls. The study conformed to the policies outlined by the institutional review board of the University Hospital, Inselspital of Bern.Specimens were cultured on Schädler agar under anaerobic conditions and on mannitol salt agar under aerobic conditions for 48 h at 35°C (5). All visibl...