Echinocandin susceptibility testing of Candida isolates collected during a 1-year period in Sweden

The susceptibilities of Candida isolates to the echinocandins anidulafungin, caspofungin, and micafungin were determined by using the recently revised CLSI breakpoints and Etest on 238 clinical bloodstream Candida isolates collected between September 2005 and August 2006. The isolates represent approximately 95% of all non-albicans Candida bloodstream infections and one-third of Candida albicans bloodstream infections during this 1-year period in Sweden. The collection included 81 C. albicans, 81 C. glabrata, 36 C. parapsilosis, 14 C. dubliniensis, 8 C. tropicalis, 8 C. lusitaniae, 5 C. krusei, 2 C. guilliermondii and 2 C. inconspicua isolates as well as 1 C. pelliculosa isolate. The MICs were largely consistent with the global epidemiology of bloodstream Candida isolates. All C. albicans and C. glabrata isolates were susceptible to all 3 echinocandins (MIC ≤ 0.016 μg/ml in all instances). Resistance (MIC ≥ 8 μg/ml) to anidulafungin alone was observed for 4 (11.1%) C. parapsilosis isolates and for 1/2 C. guilliermondii isolates. Intermediate susceptibility to caspofungin alone was observed for 2/5 C. krusei isolates. One of the eight C. tropicalis isolates was classified as being intermediately susceptible to micafungin (MIC, 0.5 μg/ml) and as being resistant to anidulafungin and caspofungin (MIC ≥ 1 μg/ml). This isolate harbored a heterozygous FKS1 hot spot mutation (S80P) known to confer echinocandin resistance. This first study to apply the revised CLSI breakpoints for Etest endpoints showed that the breakpoints worked successfully in detecting an isolate with a hot spot mutation. Acquired echinocandin resistance is rare in Sweden. Echinocandin MICs against C. parapsilosis and C. guilliermondii were lowest for micafungin.     

Invasive fungal infections: evolving challenges for diagnosis and therapeutics

Invasive fungal infections (IFI) parallel the explosive increase in the immunocompromized patient population, and are characterized by diagnostic difficulties and extreme mortality. Candidemia in a tertiary referral hospital in the Middle East confirms the current epidemiologic shift in this common blood stream pathogen towards non-malignancy cases (38%) and antifungal prophylaxis failure (20%), high presentation sepsis scores and attributable mortality (32%). Invasive aspergillosis (IA) is also associated with high mortality. Use of non-invasive computerized tomographic (CT) radiologic scanning linked to early administration of high dose liposomal amphotericin B (LAB) is associated with a reduced mortality of 9.5% compared to historical experience of 28%.Life threatening invasive aspergillosis also occurs in patients who are less obviously immunocompromized. Investigations may reveal subtle immune deficits which could place the patient at some risk for an invasive mycosis. Antifungal treatment used in combination with progenitor cell growth factors and gamma-interferon has proved successful in such situations of progressive fungal disease unresponsive to antifungal therapy alone.Pharmacologic remodeling of existing compounds by lipidisation reduces both the toxicity denominator and the efficacy numerator of the therapeutic index when compared to the parent drug. A comparative dose study of liposomal amphotericin B in aspergillosis has demonstrated equi-efficacy, generated debate over the ability of the controlled clinical trial to be capable of assessing antifungal efficacy, and illustrated that recovery from an invasive fungal infection may require maximum tolerated doses and immunomanipulation.Several new antifungal strategies are under clinical investigation. These include reformulating existing antifungals, exploitation of the growing knowledge of virulence factors to synthesize antagonists, immune reconstitution and immunoprotection. An interim analysis of an ongoing placebo controlled study of recombinant interleukin-11 to assess its efficacy in reducing sepsis in leukemia patients through prevention of chemotherapy induced gut epithelial cell apoptosis, has demonstrated a difference in the two study arms in sepsis rates and preservation of gastrointestinal epithelial cell integrity.The unique and special challenges presented by the dynamic epidemiologics of invasive fungal infections are demanding and attracting considerable responses, in the fields of diagnosis and therapeutics. Current strategies need considerable improvement, yet ongoing collaborative efforts will have a positive impact on our understanding of the fungus-host interaction and ultimately our ability to offer better care for our patients with invasive mycoses.     

Age-related prevalence of complement-fixing antibody to Mycoplasma pneumoniae during an 8-year period.

We determined the age-related prevalence of complement-fixing antibody to Mycoplasma pneumoniae from the computerized laboratory results of our routine diagnostic department. The material consisted of about 58,000 sera from an 8-year period, 1971 to 1978. Among children less than 1 month old, the frequency of complement-fixing antibody of titers greater than or equal to 8 was low (23%), and no decrease representing loss of maternal antibody was seen thereafter. An unexpectedly early increase in the antibody prevalence up to 62% was seen by 6 months of age. The frequency of antibody was high among young children from the age of 4 months, in whom symptomatic infection due to M. pneumoniae is rare. The frequency of higher titers (greater than or equal to 32) and the geometric mean titer increased more slowly, coinciding with the known age distribution of symptomatic M. pneumoniae disease; the frequency of high titers and the geometric mean titer peaked at the age of 7 to 10 years. Two explanations for the high frequency of complement-fixing antibody to M. pneumoniae in young children are discussed. It may be due to an asymptomatic infection caused by M. pneumoniae or to a nonspecific stimulus by lipids of other organisms, plants, or tissues leading to production of antibodies crossreacting with M. pneumoniae, or it may be due to both of the above. During the study, two extensive epidemics due to M. pneumoniae occurred in Finland, but the prevalence of complement-fixing antibody bore no correlation with these peaks of occurrence.     

Epidemiology and antifungal susceptibility of bloodstream fungal isolates in pediatric patients: a Spanish multicenter prospective survey

Data on fungemia epidemiology and antifungal susceptibility of isolates from children are scarce, leading frequently to pediatric empirical treatment based on available adult data. The present study was designed to update the epidemiological, mycological, and in vitro susceptibility data on fungal isolates from children with fungemia in Spain. All fungemia episodes were identified prospectively by blood culture over 13 months at 30 hospitals. Tests of susceptibility to amphotericin B, flucytosine, fluconazole, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, and micafungin were performed at participant institutions by a microdilution colorimetric method. New species-specific clinical breakpoints for fluconazole, voriconazole, and echinocandins were also applied. A total of 203 episodes of fungemia in 200 children were identified. A higher proportion of fungal isolates was from general wards than intensive care units (ICU). Candida parapsilosis (46.8%), Candida albicans (36.5%), Candida tropicalis (5.9%), Candida glabrata (3.9%), and Candida guilliermondii (2.5%) were the leading species. C. parapsilosis was the predominant species except in neonates. C. albicans was the most frequent in neonatal ICU settings (51.9%). Intravascular catheter (79.3%), surgery (35%), prematurity (30%), and neutropenia (11%) were the most frequent predisposing factors. Most Candida isolates (95.1%) were susceptible to all antifungals. When the new species-specific clinical breakpoints were applied, all C. parapsilosis isolates were susceptible to echinocandins except one, which was micafungin resistant. This is the largest published series of fungemia episodes in the pediatric setting. C. parapsilosis is the most prevalent species in Spain, followed by C. albicans and C. tropicalis. Resistance to azole and echinocandin agents is extremely rare among Candida species. The fluconazole resistance rate in Spain has decreased in the last 10 years.     

Invasive fungal infections in the paediatric and neonatal population: diagnostics and management issues

Invasive fungal infections in children appear to have increased over the past few decades. Especially neonates and children with primary and secondary immunodeficiencies are at risk. Candida and Aspergillus spp. are the most commonly isolated organisms. In addition, Malassezia may cause systemic infections in newborns and zygomycosis is important because of its rising incidence and high case fatality rate. Timely diagnosis and initiation of appropriate antifungal therapy is imperative for improving outcomes. However, traditional techniques are time-consuming and representative sample material, using invasive procedures, may be difficult to obtain in the paediatric setting. This review provides an overview of the advances in detection and rapid species identification, with a focus on issues relevant in these settings. Subsequently, the current antifungal treatment options for neonates and children are discussed in light of the antifungal spectrum of the available agents and the specific pharmacokinetic properties in different age groups. Although a multitude of newer antifungal compounds have become available within the last decade, further studies are necessary to clearly establish the role for each of these agents among neonates and children.     

Invasive fungal disease in university hospital: a PCR-based study of autopsy cases

Invasive fungal disease (IFD) has high mortality rate, especially in the growing population of immunocompromised patients. In spite of introduction of novel diagnostic approaches, the intravital recognition of IFD is challenging. Autopsy studies remain a key tool for assessment of epidemiology of visceral mycoses. We aimed to determine species distribution and trends of IFD over the last 10 years in unselected autopsy series from a large university hospital. Forty-five cases of visceral mycoses, confirmed by histopathology and panfungal PCR, were found in 587 consecutive autopsies. Major underlying diseases were diabetes mellitus (20%), hematologic malignancies (15.6%) and systemic lupus erythematosus (15.6%). There was a high risk for disseminated IFD in immunocompromised patients stayed in the hospital over 1 month with a fever longer than 3 weeks. The most common fungi were Aspergillus spp. (58%), Candida spp. (16%), Mucorales (14%) and Fusarium spp. (10%). We found significant increase in Aspergillus flavus (P = 0.04) and Mucorales (P < 0.01) infections over the last 5 years. Concordance rate between histopathology and panfungal PCR was 89.5% to the genus level. All 6 cases of fusariomycosis were misinterpreted as aspergillosis by histology alone. The precise species identification, necessary for targeted antifungal treatment, was rendered only by the molecular technique. Panfungal PCR showed high performance on formalin-fixed paraffin-embedded specimens, providing important epidemiological data in retrospective autopsy series. Rapid detection of fungi by panfungal PCR assay has high potential for intravital diagnostics of IFD in surgical and biopsy specimens.     

Invasive infections with Fusobacterium necrophorum including Lemierre's syndrome: an 8-year Swedish nationwide retrospective study

ObjectivesWe aimed to evaluate the nationwide incidence and a potential increase in invasive infections with Fusobacterium necrophorum. Secondly, we aimed to describe epidemiology, clinical characteristics and outcomes for the different presentations: Lemierre's syndrome (LS), invasive head and neck-infection without LS and invasive non-head and neck-infection.MethodsA retrospective multicentric population-based study of all invasive infections with F. necrophorum diagnosed in Sweden from 2010 to 2017 with 6 months of follow-up was performed through reviews of medical records. Invasive infections were defined and identified by a positive blood culture or sequencing of 16S rDNA, targeted PCR or culture from normally sterile sites. Incidence calculations were performed, including comparisons between 2010–13 and 2014–17, age groups and clinical presentations. Patient and infection characteristics, treatment and clinical outcomes were analysed.ResultsInvasive infections with F. necrophorum were diagnosed in 300 cases in Sweden 2010–17. The incidence increased from 2.9 to 5.0 cases/million/year from 2010–13 to 2014–17 (p 0.001). A total of 104/300 (35%) patients developed LS, 102/300 (34%) invasive head and neck infection without LS and 94/300 (31%) invasive non-head and neck infection. The median age was 20, 25 and 64 years, respectively. Among patients with LS 72/96 (75%) had thrombocytopenia on admission, 86/104 (83%) had sepsis, 19/104 (18%) developed septic shock and 45/104 (43%) needed intensive care. 30-day mortality in LS was 2/104 (2%).ConclusionWe describe an increased incidence of invasive infections with F. necrophorum in Sweden and highlight its full spectrum of invasive clinical presentations. LS, in particular, causes considerable morbidity in young and previously healthy patients.     

The prevalence of metabolic syndrome in patients with gout: a multicenter study

It has been suggested that hyperuricemia and possibly gout are associated with the metabolic syndrome, but there have been no direct studies. This study was undertaken to obtain the prevalence of the metabolic syndrome in patients with gout and to compare it with those from the general population studies. This was a 4-institutional case-historical control study composed of 168 patients with gout. We assessed the prevalence of metabolic syndrome according to the ATP III criteria and compared the prevalence with that of the historical controls. To elucidate the factors in gout that were associated with metabolic syndrome, a multivariate analysis was done. The age-adjusted prevalence of metabolic syndrome in gout patients was 43.6%, which was significantly higher than that of the Korean control population (5.2%) from the previous studies. Patients with gout had more components of metabolic syndrome than did the controls. Body mass index (BMI, OR = 1.357 (95%CI 1.111-1.657)) and high density lipoprotein (HDL, OR = 0.774 (95%CI 0.705-0.850)) were the variables most significantly associated with the occurrence of metabolic syndrome in gout, but alcohol consumption did not show such associations. Gout is associated with the metabolic syndrome, and furthermore, obesity and dyslipidemia were the factors most associated with the syndrome in these patients.     

Listeria monocytogenes isolates from invasive infections: variation of sero- and genotypes during an 11-year period in Finland

Listeria monocytogenes strains that were isolated from 314 human listeriosis cases in Finland during an 11-year period were analyzed by O:H serotyping and pulsed-field gel electrophoresis (PFGE). Serotyping divided the isolates into five serotypes, the most common being 1/2a (53%) and 4b (27%). During the study period, the number of cases caused by serotype 1/2a increased from 22% in 1990 to 67% in 2001, and those caused by serotype 4b decreased from 61 to 27%, respectively. PFGE with restriction enzyme AscI divided the strains into 81 PFGE genotypes; among strains of serotypes 1/2a and 4b, 49 and 18 PFGE types were seen, respectively. PFGE type 1 (serotype 1/2a) was the most prevalent single type (37 strains). Together with six other, closely related PFGE types, PFGE type 1 formed a group of 71 strains, representing 23% of all 314 strains. Strains of PFGE type 1 have also been isolated from cold smoked fish, suggesting a source of human infections caused by this type. Moreover, PFGE type 24 (serotype 1/2c) was significantly associated with gender: 5% of 180 male subjects but none of 132 female subjects (P = 0.012). An electronic database library was created from the PFGE profiles to make possible the prompt detection of new emerging profiles and the tracing of potential infection clusters in the future.     

Serum hormones and physical performance capacity in young boy athletes during a 1-year training period

Summary Serum hormones and physical performance capacity in boy athletes (AG;n = 19) were investigated during a 1-year training period (between the ages of 11.6 and 12.6 years). Six young untrained boys served as the control group (CG). The mean serum testosterone concentration increased significantly in AG (P<0.05) following the training period from 2.92 nmol·l^–1, SD 1.04 to 5.81 nmol·l^–1, SD 1.33. Significant differences were not observed in the cortisol, sex hormone binding globulin and growth hormone levels during the follow-up period. The AG clearly increased speed (P<0.001), speed-strength (P<0.01-P<0.001) and anaerobic capacity (P<0.001) whereas CG had only slight increases (NS) in physical performance capacity during a 1-year period. During the last 6-month training period significant positive correlations (r=0.490–0.58;P<0.05 -P<0.01) were observed in AG between the relative changes in testosterone, testosterone: cortisol ratio and growth hormone and the relative performance change in speed, maximal isometric force and endurance, respectively. At the end of the period significant positive correlations were observed in all subjects between the level of testosterone and speed-strength (r=0.52–0.64;P<0.01 -P<0.001) and anaerobic capacity (r=0.49;P<0.05). It was concluded that an increase in anabolic activity with the synchronous training already has positive effects on trainability and physical performance capacity at an early stage in puberty.