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.

[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.

[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.

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.

Modulation of innate and antigen-specific immune functions directed against Listeria monocytogenes by fungal toxins in vitro.

Mycotoxins, a large group of secondary fungal metabolites, are ubiquitously present in the environment and are potentially harmful to exposed humans and animals. Despite increasing interest in this group of fungal metabolites it is still difficult to estimate the relative toxic potential of one individual mycotoxin compared with others. We therefore compared the effects of some of the most important mycotoxins on effector cells of the innate and adaptive immune system in an in vitro model. Our data show clear differences of various mycotoxins in regard of their immunotoxic potential on mouse macrophages and T cells. Our results also indicate differences in the susceptibility of specific immune effector functions of macrophages and T cells exposed to mycotoxins. Thus, our results enhance the understanding of role of mycotoxins in the pathogenesis of human and animal diseases.

[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.

[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.

[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.

[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.

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.

[Laboratory survey on the incidence of Pneumocystis jirovecii - obviously a peculiar fungus, but also a rare pathogen?]. / Laborerhebung zur Häufigkeit von Pneumocystis jirovecii - Zwar ein besonderer Pilz, aber auch ein seltener Erreger?

Pneumocystsis jirovecii is a peculiar fungus for a variety of reasons. This opportunistic pathogen multiplies in humans only under certain conditions; a defect in the T-cell defense system creates a predisposition to this infection. In 2010 a data survey (IFT as well as PCR) from a few laboratories in Germany revealed 412 positive individuals. Even if only a few patients test positive for the colonization stage of this pathogen, the sheer number of individuals testing positive for other stages of infection indicate that the incidence of pneumocystosis in immunocompromised patients in Germany is underestimated.

Outcome analysis of patients with primary breast cancer initially treated at a certified academic breast unit.

INTRODUCTION: Evaluation of oncological outcome and prognostic factors of patients with primary breast cancer treated at a certified academic breast unit. PATIENTS AND METHODS: We prospectively collected data of 3338 patients, diagnosed with primary breast cancer between 01.01.2003 and 31.12.2010 and treated at the Breast Unit Heidelberg, Germany, in order to analyze outcome in clinical practice. We evaluated local control rate (LCR), disease-free survival (DFS), distant disease-free survival (DDFS), observed overall survival (OS) and age-adjusted relative overall survival (ROS). In addition, the impact of known prognostic factors on these outcome variables was examined in univariate and multivariate analyses. RESULTS: Of all patients, 368 (11.0%) had carcinoma in situ (CIS) and 197 (5.9%) had bilateral cancers. For the 2970 patients with invasive cancer, of which 49 patients (1.7%) had metastastic disease at time of diagnosis, DFS, LCR, DDFS, OS and ROS at 5 years were 79.8%, 84.7%, 81.2%, 86.3%, and 89.8%, respectively. In multivariate analysis age, pT category, nodal status, hormone receptor status and grading were identified as independent prognostic factors for OS. CONCLUSION: Compared with recent population-based reports from Germany, more favourable patient characteristics and nominally higher survival was found among this large cohort of patients with primary breast cancer treated at a single certified breast unit.

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.

[Pneumococcal sepsis in aged patients - implications for the vaccination of seniors against pneumococci]. / Pneumokokkensepsis im Alter - Implikationen für die Impfung alter Menschen gegen Pneumokokken.

In the years 2005-2010 pneumococci were isolated in the Limbach laboratory/Heidelberg from blood cultures of 1,085 patients. Obviously, older patients are more prone to these bacteria, since 66 % of the patients were older than 60 years. All isolates were susceptible to cefotaxime; 3 % of isolates were resistant to penicillin, 2 % were resistant to levofloxacin and 15 % were resistant to erythromycin. From 457 out of the isolates serotyping was achieved: more than 80 % of the isolates were covered by the 23-valent vaccine. This means that particularly old people should be vaccinated against pneumococci, because they will profit probably most from such preventive measurements.

[Immunity against tetanus is often lacking in the elderly]. / Fehlende Immunität gegen Tetanus im Alter.

BACKGROUND AND OBJECTIVE: It is generally recommended to vaccinate elderly people against tetanus. Is this really essential? PATIENTS AND METHODS: The levels of antibodies to tetanus toxin in serum of 2936 individuals of various age groups were determined by means of an ELISA. RESULTS: Obviously, the antibody titers definitely diminish in the old individuals. About 50 % of people > 80 years possess antibody titers < 0.5 IU/ml and about 30 % antibody titers < 0.1 IU/ml, which means that they are not absolutely protected against tetanus. CONCLUSION: This, however is not due to a general decline of antibodies, since levels of immunoglobulins of the classes IgG, IgM and especially of IgA are higher with growing age.It can be assumed that the awareness for the necessity for vaccination is lacking.

Change of aesthetic and functional outcome over time and their relationship to quality of life after breast conserving therapy.

PURPOSE: We analyzed changes in aesthetic and functional outcome over time after breast conserving therapy. Our special interest resides in the question of whether these aspects gain or loose their influence on quality of life (QoL) with temporal progress. PATIENTS AND METHODS: This prospective single centre cohort study included 138 patients, treated with breast conserving surgery and consecutive radiotherapy. Patients completed two questionnaires one week and one year after surgery: the BCTOS (Breast Cancer Treatment Outcome Scale) to measure Functional, Aesthetic, and Breast Sensitivity Status and the EORTC (European Organisation for Research and Treatment of Cancer) C30-BR23 to assess QoL. We applied correlation and multiple regression analysis as statistical methods. RESULTS: Aesthetic and Functional Status did not change significantly over one year, whereas Breast Sensitivity Status and several QoL subscales showed significant improvement (p < 0.0001). Correlations between BCTOS scales and EORTC subscales remain similar over time. Functional and Aesthetic Status kept a strong impact on global health (Spearman's Rho = -0.28 to -0.45 depending on time of assessment). Increasing age and poorer Functional Status shortly after surgery are predictors of a decline in global health over one year (p < 0.001). CONCLUSION: Functional and aesthetic outcome after breast conserving surgery maintain their impact on QoL over a one year follow-up period and are valuable predictors of QoL.

[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.

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.