Peritonitis in a neonate due to Cyberlindnera fabianii, an ascomycetic yeast.

The ascomycetous yeast Cyberlindera fabianii is not only present in the environment, but is also occasionally pathogenic. Especially, neonates seem to be prone to infection. Here, we describe a case of peritoneal infection of a neonate after congenital heart surgery. The correct identification of this peculiar species is made by MALDI-TOF and especially by molecular biology methods, whereas the standard biochemical identification methods fail.The neonate with a hypoplastic left heart syndrome had a Norwood palliation followed by transient ECMO therapy for 3 days. The patient developed a renal insufficiency, so that peritoneal dialysis was initiated. After a few days, a peritoneal infection due to C. fabianii emerged. The proper source of this rare and particular yeast remains obscure. In spite of a reasonable antimycotic therapy, the patient developed a capillary leak syndrome and died finally in septic shock with multiorgan failure. One reason is probably that the yeast population, which was highly susceptible to all common antimycotic drugs at the beginning of therapy with fluconazole (and for a short period with caspofungin and liposomal amphotericin B), became rapidly resistant.

Guideline: vulvovaginal candidosis (AWMF 015/072), S2k (excluding chronic mucocutaneous candidosis).

The oestrogenised vagina is colonised by Candida species in at least 20% of women; in late pregnancy and in immunosuppressed patients, this increases to at least 30%. In most cases, Candida albicans is involved. Host factors, particularly local defence mechanisms, gene polymorphisms, allergies, serum glucose levels, antibiotics, psycho-social stress and oestrogens influence the risk of candidal vulvovaginitis. Non-albicans species, particularly Candida glabrata, and in rare cases also Saccharomyces cerevisiae, cause less than 10% of all cases of vulvovaginitis with some regional variation; these are generally associated with milder signs and symptoms than normally seen with a C. albicans-associated vaginitis. Typical symptoms include premenstrual itching, burning, redness and odourless discharge. Although itching and redness of the introitus and vagina are typical symptoms, only 35-40% of women reporting genital itching in fact suffer from vulvovaginal candidosis. Medical history, clinical examination and microscopic examination of vaginal content using 400× optical magnification, or preferably phase contrast microscopy, are essential for diagnosis. In clinically and microscopically unclear cases and in chronically recurring cases, a fungal culture for pathogen determination should be performed. In the event of non-C. albicans species, the minimum inhibitory concentration (MIC) should also be determined. Chronic mucocutaneous candidosis, a rarer disorder which can occur in both sexes, has other causes and requires different diagnostic and treatment measures. Treatment with all antimycotic agents on the market (polyenes such as nystatin; imidazoles such as clotrimazole; and many others including ciclopirox olamine) is easy to administer in acute cases and is successful in more than 80% of cases. All vaginal preparations of polyenes, imidazoles and ciclopirox olamine and oral triazoles (fluconazole, itraconazole) are equally effective (Table ); however, oral triazoles should not be administered during pregnancy according to the manufacturers. C. glabrata is not sufficiently sensitive to the usual dosages of antimycotic agents approved for gynaecological use. In other countries, vaginal suppositories of boric acid (600 mg, 1-2 times daily for 14 days) or flucytosine are recommended. Boric acid treatment is not allowed in Germany and flucytosine is not available. Eight hundred-milligram oral fluconazole per day for 2-3 weeks is therefore recommended in Germany. Due to the clinical persistence of C. glabrata despite treatment with high-dose fluconazole, oral posaconazole and, more recently, echinocandins such as micafungin are under discussion; echinocandins are very expensive, are not approved for this indication and are not supported by clinical evidence of their efficacy. In cases of vulvovaginal candidosis, resistance to C. albicans does not play a significant role in the use of polyenes or azoles. Candida krusei is resistant to the triazoles, fluconazole and itraconazole. For this reason, local imidazole, ciclopirox olamine or nystatin should be used. There are no studies to support this recommendation, however. Side effects, toxicity, embryotoxicity and allergies are not clinically significant. Vaginal treatment with clotrimazole in the first trimester of a pregnancy reduces the rate of premature births. Although it is not necessary to treat a vaginal colonisation of Candida in healthy women, vaginal administration of antimycotics is often recommended in the third trimester of pregnancy in Germany to reduce the rate of oral thrush and napkin dermatitis in healthy full-term newborns. Chronic recurrent vulvovaginal candidosis continues to be treated in intervals using suppressive therapy as long as immunological treatments are not available. The relapse rate associated with weekly or monthly oral fluconazole treatment over 6 months is approximately 50% after the conclusion of suppressive therapy according to current studies. Good results have been achieved with a fluconazole regimen using an initial 200 mg fluconazole per day on 3 days in the first week and a dosage-reduced maintenance therapy with 200 mg once a month for 1 year when the patient is free of symptoms and fungal infection (Table ). Future studies should include Candida autovaccination, antibodies to Candida virulence factors and other immunological experiments. Probiotics with appropriate lactobacillus strains should also be examined in future studies on the basis of encouraging initial results. Because of the high rate of false indications, OTC treatment (self-treatment by the patient) should be discouraged.

[Effect of systematic information about psychosocial support services during outpatient radiotherapy. A controlled trial]. / Effekte systematischer Informationen über psychosoziale Angebote während der ambulanten Strahlentherapie. Eine kontrollierte Studie.

BACKGROUND: Up to 50 % of all cancer patients require psychosocial support during the course of their disease. However, only a proportion of these patients make use of the existing services. This is partly because patients are unaware that psychosocial support services are available to them. We investigated whether systematically providing printed information concerning psychosocial support can increase the knowledge and usage of these services, as well as health-related self-efficacy. MATERIALS AND METHODS: In a controlled trial, 108 breast cancer patients were assigned alternately to either an intervention- or a control group. At two predefined time points before and during radiotherapy, patients in the intervention group received correspondence informing them about psychosocial services (psycho-oncology, clinical social work and the Cancer Information Service).The control group received no systematic information. Using a standardized questionnaire, all patients were subsequently questioned about their knowledge of psychosocial support services, their perceived self-efficacy and their use of psychosocial support services. RESULTS: We found that systematic provision of information had a positive effect on the knowledge of psychosocial support services (p = 0.042; d = 0.45) and self-efficacy (p = 0.047; d = 0.42). However, no increase in the actual usage of these services was observed (p = 0.661; d = 0.10). CONCLUSION: The systematic provision of information in the form of written correspondence can easily be implemented into clinical routine and is an effective way to increase cancer patients' knowledge of psychosocial support services. Furthermore, providing information about the services had a positive impact on patients' perceived self-efficacy. However, simply making this information available did not increase the usage of psychosocial support services.

[Fungal pneumonias: do they exist?]. / Pilzpneumonien: Gibt's die?

As typical opportunistic pathogens fungi, for example Pneumocystis jirovecii, infect predominantly immunocompromised hosts. There are, however, others, for example Coccidioides immitis and Cryptococcus neoformans, which endanger otherwise healthy people, too. Fungi are not mentioned as causative agents of pneumonias in the german guidelines for community acquired pneumonia. In the german guidelines for nosocomial pneumonia only very few, namely Aspergillus spp. and Candida spp., are shortly discussed. In case of severe courses of community-acquired pneumonias especially in patients with co-morbidities, which do not respond adequately to antibacterial therapy, fungi have to be included in the differential diagnostic considerations.

[Candida infections in the elderly]. / Candida-Infektionen im hohen Alter.

Candida infections of the skin, mucous membranes as well as of internal organs may be more frequent and more serious in the elderly. There are several biological reasons for this, for example, alterations in the immune system. Whereas Candida albicans remains the major pathogen, there has been a relative increase of Candida glabrata infections. This species is associated with higher mortality. Furthermore, C. glabrata is in general less susceptible to fluconazole, so that this drug does not represent the agent of first choice for the treatment of yeast infections. The choice of the antimycotic agent must take into consideration their inherent side effects and interaction profiles; echinocandins play a particular role in the treatment of yeast infections in the elderly. These drugs have low toxicities, low potential for interactions with co-medications, as well as broad and good activities against yeasts.

[Severe pneumococcal infections in the elderly - preventable by vaccination]. / Schwere Pneumokokkeninfektionen im Alter - impfpräventabel.

Elderly people are more susceptible to pneumococcal infections. Data in Germany from 2005-2010 shows that especially seniors are prone to develop serious complications such as sepsis. Women are obviously less affected than men. Most of the infections occurred during the winter months. The majority of isolates, i.e., about 80%, possess capsular polysaccharide antigens which are represented in the 23-valent vaccine. Consequently, it could be assumed that the severe complications ensuing long hospital stays and associated with a high mortality could have been avoided, if the elderly people would have been vaccinated, which, however, was only true in a small proportion (28%). Recently, a new conjugated vaccine was introduced to the market. In principle, several antibiotics are available for direct antibacterial treatment. All isolates are susceptible to cefotaxime as well as to ceftriaxone. Resistance to penicillin as well as ampicillin is very rare in Germany. The vast majority of isolates are susceptible to quinolones such as levofloxacin and moxifloxacin. Resistance to macrolides, for example to erythromycin, occurs to a certain extent but the percentage has been declining in recent years. Nevertheless, in many instances therapy is too late. Thus, prevention is of great importance.

Diagnosis of invasive fungal infections in hematology and oncology--guidelines from the Infectious Diseases Working Party in Haematology and Oncology of the German Society for Haematology and Oncology (AGIHO).

Invasive fungal infections (IFIs) are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of IFI in immunocompromised patients is particularly challenging and time consuming, but delayed initiation of antifungal treatment increases mortality. The limited overall outcome has led to the strategy of initiating either 'empirical' or 'preemptive' antifungal therapy before the final diagnosis. However, diagnostic procedures have been vastly improved in recent years. Particularly noteworthy is the introduction of newer imaging techniques and non-culture methods, including antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples. Though varying widely in cancer patients, the risk of IFI is highest in those with allogeneic stem cell transplantation and those with acute leukemia. The AGIHO presents recommendations for the diagnosis of IFIs with risk-adapted screening concepts for febrile episodes in patients with haemato-oncological disorders.

Differentiation of Candida dubliniensis from Candida albicans by means of MALDI-TOF mass spectrometry.

BACKGROUND: Species specific differentiation of the two closely related yeasts, Candida albicans and C. dubliniensis, is difficult in routine diagnosis. METHODS AND RESULTS: Here we show that MALDI-TOF MS is a practical and useful tool for the discrimination of C. albicans and C. dubliniensis, demonstrated by the analysis of reference strains from type culture collections and other well characterized isolates. The spectra of C. albicans and C. dubliniensis further revealed that each species consists of several clades. CONCLUSIONS: Reliable, routinely applicable methods for species specific differentiation of C. albicans and C. dubliniensis appear to be of particular importance to better understand the epidemiology and virulence of C. dubliniensis.

Mycoses in the elderly.

Infections with dermatophytes are more prevalent in the elderly than in non-elderly adults; risk factors include local trophic disturbances, underlying diseases such as diabetes and a reduced oxygen supply due to diminished blood circulation. Vaginal mycoses are seldom found. In systemic yeast infections in patients of advanced age, Candida glabrata plays a relatively important role. The dimorphic fungus Coccidioides immitis is more prevalent in the elderly in endemic areas. Although there is no higher susceptibility to moulds in this age group, there are certain situations increasing the risk. The manifestations and symptoms of infection often differ from those of younger patients, which may hamper diagnosis. Deficits in organ function may influence the antifungal drug therapy. Preventive measures such as altering the social environment, avoiding malnutrition, as well as efforts to retard immunosenescence and to improve hygiene are important.

[Radiation therapy of lung carcinoma]. / Strahlentherapie des Bronchialkarzinoms.

At first presentation and primary diagnosis approximately 50% of patients with non-small cell lung carcinoma (NSCLC) and 25% of patients with small cell lung carcinoma (SCLC) have a potentially curable tumor stage. Definitive, adjuvant and neoadjuvant radio- (chemo-)therapy play an important role as part of multimodal treatment approaches. High radiation doses can be achieved in tumor areas with modern radiotherapy planning and treatment techniques without an increase of side-effects. The 3 year overall survival after primary radiotherapy is approximately 50% for patients with NSCLC in stage I and 20% in stage IIIA. Radiotherapy can be used in patients with progressive metastatic disease after insufficient response to systemic therapy with threatening thoracic symptoms and for palliative treatment of cerebral, lymphatic and osseous metastases.

Developments in the epidemiolgy of invasive fungal infections - implications for the empiric and targeted antifungal therapy.

Invasive fungal infections are significant causes of morbidity and mortality in hospitalized, immunocompromised patients. Whereas in hematologic patients aspergilli represent the major problem along with Candida spp., in surgery departments yeast infections are more prevalent. For the empiric as well as the targeted therapy of mould infections with high mortality rates, several antifungals can be given alone or in combination. So far, resistance among aspergilli is uncommon. In yeast infections one has to respect that a relatively large number of causative agents, especially Candida glabrata and C. krusei, can be resistant to azoles, in particular to fluconazole; cross-resistance with other triazoles, such as voriconazole, may occur as well. Coverage of most pathogens involved in life-threatening fungal infections is crucial for empiric treatment. Since caspofungin has a broad spectrum of antifungal activities and is effective even against fungi with azole resistance, this drug should be preferred for initial, empiric therapy of yeast infections, since there are practically no caspofungin resistant strains among clinical isolates. Early start with an adequate empirical antifungal therapy is associated with an improved survival of patients with invasive Candida infections. Once the diagnosis is completed and a susceptibility pattern of the causative agent is available, a targeted therapy can be given respecting pharmacology, side effects and interactions with co-administered drugs.

Breakpoints for posaconazole susceptibility testing: background and discussion about the need of establishing values.

Posaconazole is a new antifungal agent, which exhibits a broad spectrum of activity against fungi including Aspergillus terreus, some zygomycetes and dematiaceous fungi. Out of the group of triazole antifungal agents, it is the only compound for which interpretive breakpoints have not been established have not yet been established for Candida spp. As reliable breakpoints are useful in the practical management of patients with fungal infections, it is desirable to establish the same for all available substances. However, the underlying data of the existing breakpoints for other antifungal agents are of varying quality because of limited clinical data available. Furthermore, these breakpoints are not equally suitable for all testing methods available and they may not be suitable for all species to be tested. From the practical point of view, it is therefore important not only to establish breakpoints for the reference method but also for the inexpensive and easy to perform testing methods, which are suitable for smaller laboratories.

Modulation of very low density lipoprotein production and clearance contributes to age- and gender- dependent hyperlipoproteinemia in apolipoprotein E3-Leiden transgenic mice.

Apolipoprotein E3-Leiden (APOE*3-Leiden) transgenic mice have been studied to identify factors modulating chylomicron and VLDL remnant lipoprotein metabolism. Transient elevated levels of VLDL/LDL-sized lipoproteins occurred in these mice with maximal levels during the period of rapid growth (optimum at 45 d of age). After about 100 d of age, serum cholesterol and triglyceride levels stabilized to slightly elevated levels as compared to control mice. The expression of the APOE*3-Leiden transgene was not age-dependent. In young mice the in vivo hepatic production of VLDL-triglycerides was 50% increased as compared to older mice. This is sustained by in vivo VLDL-apo B turnover studies showing increased (75%) VLDL-apo B secretion rates in young mice, whereas the VLDL-apo B clearance rate appeared not to be age dependent. On a high fat/cholesterol diet, females displayed significantly higher cholesterol levels than males (10 versus 7.0 mmol/liter, respectively). Serum levels of VLDL/LDL sized lipoproteins increased upon administration of estrogens, whereas administration of testosterone gave the opposite result. As compared to male mice, in female mice the hepatic VLDL-triglyceride production rate was significantly elevated. Injection of estrogen in males also resulted in increased VLDL-triglyceride production, although not statistically significant. In vivo VLDL-apo B turnover experiments showed that the VLDL secretion rate tended to be higher in females. Although, the fractional catabolic rate of VLDL-apo B is not different between males and females, administration of estrogens in males resulted in a decreased clearance rate of VLDL, whereas administration of testosterone in females resulted in an increased clearance rate of VLDL. The latter presumably due to an inhibiting effect of testosterone on the expression of the APOE*3-Leiden transgene. We conclude that hyperlipidemia in APOE*3-Leiden transgenic mice is strongly affected by age via its effect on hepatic VLDL production rate, whereas gender influences hyperlipidemia by modulating both hepatic VLDL production and clearance rate.

[Candiduria! What now? : Therapy of urinary tract infections with Candida]. / Candidurie! Was nun? : Zur Therapie von Harnwegsinfektionen durch Candida.

BACKGROUND: Yeasts are found in urine specimens relatively often, especially in the elderly and patients under treatment with broad spectrum antibiotics, i. e. especially in intensive care unit (ICU) patients. In some cases, the number of pathogens is very high, i. e. >105/ml. The clinical relevance of detecting Candida in urine is difficult to assess. In the German S3 guidelines it is apodictically stated that an ascending infection of the urinary tract by yeasts does not occur but this may undoubtedly happen in certain instances in patients at risk, for example in the elderly, in diabetic persons and in the case of foreign bodies in the urinary tract. A hematogenous spread of yeasts can lead to pyelonephritis, which accompanies candiduria. In rare cases this can be induced by prostatitis and epididymitis. Therapy is indicated in all cases when a urological manipulation is planned, particularly those with injury to the mucosal barrier, in order to prevent an intraoperative spread of pathogens. AIM: The antimicrobial agents suitable for therapy of candiduria are limited, namely flucytosine, amphotericin B, which is also used for irrigation and fluconazole. MATERIAL AND METHODS: The in vitro effect of nitroxoline on 100 isolates of yeasts from urine was tested by an agar diffusion test. RESULTS: Nitroxoline exerted a good activity against all yeast isolates. DISCUSSION: The antibiotic nitroxoline has a good antifungal activity. It achieves high concentrations in urine and in addition, it is effective at low pH as well as against pathogens in biofilms, which most antimycotics cannot achieve. Hence, nitroxoline is suitable for termination of candiduria. Foreign bodies in the urinary tract, on which biofilms are formed, should be removed whenever possible.

[Nitroxoline - an option for the antibiotic treatment of urinary tract infections]. / Nitroxolin ­ eine Option zur antibiotischen Therapie von Harnwegsinfektionen.

BACKGROUND: Resistance of uropathogenic bacteria against the common antibiotics is considerable-especially in the elderly. OBJECTIVES: In Germany nitroxoline is licensed for the treatment of acute urinary tract infections and for prophylaxis of recurrent infections. What is the actual resistance pattern of uropathogenic bacteria? MATERIALS AND METHODS: The in vitro susceptibility of 477 uropathogenic bacteria from patients in 2015 was determined by means of the agar diffusion method. RESULTS: Obviously, this agent is still active against the vast majority of uropathogenic bacteria and in particular against strains of Escherichia coli (E. coli). Pseudomonas aeruginosa and enterococci are not really within the spectrum of nitroxoline. One has to keep in mind, however, that even among E. coli and other enterobacteriaceae there are single resistant isolates. This applies in particular to problem strains resistant to many other antibiotics. DISCUSSION: Nitroxoline is a reasonable alternative and a promising option for calculated treatment of urinary tract infections-especially of the elderly, although this drug is not recommended in the current guideline. Laboratory testing of clinical isolates should be requested-at least when treatment fails.

Lentinan has a stimulatory effect on innate and adaptive immunity against murine Listeria monocytogenes infection.

Lentinan, a (1-3)-beta glucan from Lentinus edodes, is licensed as an immunostimulatory drug. We tested the effect of lentinan in the well-established model system of the murine Listeria monocytogenes infection. Pre-treatment of bone marrow macrophages and dendritic cells with lentinan resulted in increased production of TNF-alpha and IL-12 after L. monocytogenes infection in vitro. After lentinan treatment bone marrow macrophages showed increased NO-production and enhanced cytotoxic activity against L. monocytogenes. Pre-treatment of mice with lentinan resulted in increased concentrations of TNF-alpha, IL-12 and IFN-gamma and also an increased number of L. monocytogenes specific CD8 T cells in the spleen. The bacterial burden in spleen and liver of mice was significantly reduced during primary and secondary Listeria infection after lentinan pre-treatment of mice. In summary these results show that lentinan enhances the protective CD8 T-cell response against L. monocytogenes probably by a mechanism that involves the IL-12-mediated augmentation of the specific antilisterial CD8 T-cell response.

Preparation and properties of concanavalin A-binding glycopeptides derived from rat brain glycoproteins.

Mannose-rich glycopeptides derived from brain glycoproteins were recovered by affinity chromatography on Concanavalin A-Sepharose. These glycopeptides, which adsorb to the lectin and are eluted with alpha-methylmannoside, constitute about 25--30% of the total glycopeptide material recovered from rat brain glycoproteins. They contain predominately mannose and N-acetylglucosamine (mannose/N-acetylglucosamine = 3), as well as small amounts of galactose and fucose. Approx. 65% of the Concanavalin A-binding glycopeptide carbohydrate was recovered after treatment with leucine aminopeptidase, gel filtration on Biogel P-4, and ion-exchange chromatography on coupled Dowex 50-hydrogen and Dowex 1-chloride columns. The purified glycopeptide fraction contained six mannose and two N-acetylglucosamine residues per aspartic acid and possessed an apparent molecular weight of about 2000 as assessed by gel filtration and amino acid analysis. Galactose and fucose were absent. Treatment of the purified glycopeptides with alpha-mannosidase drastically reduced their affinity for Concanavalin A, suggesting the presence of one or more terminal mannose residues.

Quantitative analysis of lung and tumour mobility: comparison of two time-resolved MRI sequences.

The purpose of this study was to describe the use of parallel imaging technique (PAT) using dynamic MRI in lung and tumour mobility during the breathing cycle. 20 patients with stage I non-small cell lung carcinoma were investigated using two dynamic gradient echo sequences with PAT (TrueFISP (fast imaging with steady precession), and fast low angle shot (FLASH). Craniocaudal distance from the apex to the diaphragm of the thorax and tumour mobility during the breathing cycle were measured. Signal-to-noise ratio (SNR) of the tumour was determined. In spite of the different temporal resolutions both trueFISP and FLASH sequence proved to be adequate to continuously measure lung motion and tumour mobility. SNR of the tumour was significantly higher using the trueFISP sequence than FLASH sequence (20.7+/-3.6 vs 5.8+/-2.3, p<0.01). Mobility of the tumour bearing hemithorax was significantly lower compared with the non-tumour bearing hemithorax (p<0.05). Dynamic MRI using PAT allows for continuous quantitative documentation of tumour mobility and lung motion. Because of the higher SNR, trueFISP sequence provides a better delineation of intrapulmonary lesions with a sufficient temporal resolution.

[Treatment of metastases--the place of radiotherapy]. / Weniger Schmerzen--länger uberleben.

Radiotherapy has a permanent place in the treatment of metastases. Irradiation--both in palliative and curative intent--is applied mainly to treat brainand bone metastases. In the case of the latter, an appreciable reduction in pain, but also recalcification of osteolytic lesions posing a threat to bone stability can be induced. The neurological symptoms of cerebral metastases, as well as overall survival, are also improved. Here, local tumor control is largely equal to that achieved with surgical treatment of metastases. Through the use of very precise stereotactic irradiation techniques sparing normal tissue, side effects can also be kept low. Similar techniques of precision irradiation are now also being applied to visceral metastases. Impressive remission rates have been achieved in the lungs and liver.

Intracerebral targets and immunomodulation of murine Listeria monocytogenes meningoencephalitis.

In humans, infection with Listeria monocytogenes (L. monocytogenes) can severely affect the central nervous system (CNS). In the present study we have employed a murine model of CNS listeriosis to characterize the intracerebral distribution of L. monocytogenes. Following intracerebral application of a low dose of L. monocytogenes (serovar 1/2a, EGD strain) a severe fatal leptomeningitis, ventriculitis, and encephalitis developed. Listeria were detectable both intracellularly in different cell types of the CNS and extracellularly in the cerebrospinal fluid. Ultrastructural analysis revealed macrophages, granulocytes, plexus epithelial cells, ependymal cells, and neurons as target cells. An inflammatory reaction with macrophages and granulocytes developed in the brains of these animals but was not sufficient to prevent the fatal outcome of the disease. However, active immunization of mice prior to an intracerebral challenge infection significantly reduced the mortality. Immunized animals showed an early recruitment of a significant number of CD8+ and, to a lesser degree, CD4+ T cells within 24 hours p.i. as well as a strong activation of microglial cells and macrophages. These findings may provide an interesting model for studies on the pathogenesis of cerebral listeriosis.