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Cancer patients frequently suffer from gastrointestinal complications. In this manuscript, we update our 2013 guideline on the diagnosis and management of gastrointestinal complications in adult cancer patients by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). An expert group was put together by the AGIHO to update the existing guideline. For each sub-topic, a literature search was performed in PubMed, Medline, and Cochrane databases, and strengths of recommendation and the quality of the published evidence for major therapeutic strategies were categorized using the 2015 European Society for Clinical Microbiology and Infectious Diseases (ESCMID) criteria. Final recommendations were approved by the AGIHO plenary conference. Recommendations were made with respect to non-infectious and infectious gastrointestinal complications. Strengths of recommendation and levels of evidence are presented. A multidisciplinary approach to the diagnosis and management of gastrointestinal complications in cancer patients is mandatory. Evidence-based recommendations are provided in this updated guideline. [ABSTRACT FROM AUTHOR]

Fever may be the only clinical symptom at the onset of infection in neutropenic cancer patients undergoing myelosuppressive chemotherapy. A prompt and evidence-based diagnostic and therapeutic approach is mandatory. A systematic search of current literature was conducted, including only full papers and excluding allogeneic hematopoietic stem cell transplant recipients. Recommendations for diagnosis and therapy were developed by an expert panel and approved after plenary discussion by the AGIHO. Randomized clinical trials were mainly available for therapeutic decisions, and new diagnostic procedures have been introduced into clinical practice in the past decade. Stratification into a high-risk versus low-risk patient population is recommended. In high-risk patients, initial empirical antimicrobial therapy should be active against pathogens most commonly involved in microbiologically documented and most threatening infections, including Pseudomonas aeruginosa, but excluding coagulase-negative staphylococci. In patients whose expected duration of neutropenia is more than 7 days and who do not respond to first-line antibacterial treatment, specifically in the absence of mold-active antifungal prophylaxis, further therapy should be directed also against fungi, in particular Aspergillus species. With regard to antimicrobial stewardship, treatment duration after defervescence in persistently neutropenic patients must be critically reconsidered and the choice of anti-infective agents adjusted to local epidemiology. This guideline updates recommendations for diagnosis and empirical therapy of fever of unknown origin in adult neutropenic cancer patients in light of the challenges of antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

Purpose: Clostridium difficile associated diarrhoea (CDAD) is the most common cause of health-care-associated infectious diarrhoea. In the context of the German health-care system, direct and indirect costs of an initial episode of CDAD and of CDAD recurrence are currently unknown. Methods: We defined CDAD as presence of diarrhoea (≥3 unformed stools/day) in association with detection of Clostridium difficile toxin in an unformed faecal sample. Patients treated with metronidazole (PO or IV) and/or vancomycin (PO) were included. Comprehensive data of patients were retrospectively documented into a database using the technology of the Cologne Cohort of Neutropenic Patients (CoCoNut). Patients with CDAD were matched to control patients in a 1:1 ratio. Analysis was split in three groups: incidence group (CDAD patients without recurrence), recurrence group (CDAD patients with ≥1 recurrence) and control group (matched non-CDAD patients). Results: Between 02/2010 and 12/2011, 150 patients with CDAD (114 patients in the incidence and 36 (24 %) in the recurrence group) and 150 controls were analysed. Mean length of stay was: 32 (95 %CI: 30-37), 94 (95 %CI: 76-112) and 24 days (95 %CI: 22-27; P = <0.001), resulting in mean overall direct treatment costs per patient of €18,460 (95 %CI: €14,660-€22,270), €73,900 (95 %CI: €50,340-€97,460) and €14,530 (95 %CI: €11,730-€17,330; P = <0.001). In the incidence and recurrence group, the mean cumulative number of antibiotic CDAD treatment days was 11 (95 %CI: 10-12) and 36 (95 %CI: 27-45; P = <0.001). Conclusions: Especially CDAD recurrence was associated with excessive costs, which were mostly attributable to a significantly longer overall length of stay. Innovative treatment strategies are warranted to reduce treatment costs and prevent recurrence of CDAD. [ABSTRACT FROM AUTHOR]

Objectives: Little data exist about the quality of care for HIV-infected subjects in Germany. We investigated the clinical course of HIV-infected subjects newly presenting in our HIV outpatient clinic. Methods: Antiretroviral therapy (ART)-naïve HIV-infected subjects presenting between 2007 and 2008 were followed until June 2012. Clinical data and laboratory parameters were collected prospectively and analysed retrospectively. Results: From 281 subjects included, 34 patients (12 %) were lost to follow-up. 247 subjects remained, and 171 patients were followed for 1,497 days [1,121/1,726] (all data: median [interquartile range]). ART was started in 199 patients (81 %) 182 days [44/849] after HIV diagnosis, and all patients were treated according to European guidelines or within clinical trials. The CD4 cell count at first presentation was 320/µL [160/500] and declined to 210/µL [100/300] at ART start. 12 months thereafter, the CD4 cell count increased to 410/µL [230/545]. The HIV RNA was suppressed below 50 copies/mL after 108 days [63/173] in 182 patients (91 %). Initial ART was changed in 71 patients (36 %) after 281 days [99/718], in five patients (7 %) due to virological failure, in 66 patients (93 %) due to other reasons, e.g. side effects or patient's request. Conclusion: Two-thirds of the included patients were followed for more than 3 years, and ART was initiated in 81 % of the patients leading to complete virological suppression in most patients. Compliance of physicians with treatment guidelines was high. Late presentation with a severely compromised immune function remains a problem and impairs the otherwise good prognosis of HIV infection. [ABSTRACT FROM AUTHOR]

Purpose: Causes of death in human immunodeficiency virus (HIV)-infected subjects have changed in countries with high resources over the last several years. Acquired immunodeficiency syndrome (AIDS)-related diseases have become less prevalent, whereas deaths due to non-AIDS causes are increasing. The aim of the present study was to analyse causes of death in the Cologne-Bonn cohort. Methods: Causes of death from the Cologne-Bonn cohort between 2004 and 2010 were systematically recorded using the CoDe algorithm (The Coding Causes of Death in HIV Project). Results: In 3,165 patients followed from 2004 to 2010, 182 deaths occurred (5.7 %, 153 males, 29 females). The median age at the time of death was 47 years (range 24-85 years). The most frequent causes of death were AIDS-defining events ( n = 60, 33 %), with non-Hodgkin lymphoma (NHL) ( n = 29, 16 %) and infections ( n = 20, 11 %) being the leading entities in this category. Non-AIDS malignancies accounted for 16 % ( n = 29), non-HIV-related infections for 10 % ( n = 18), cardiovascular diseases for 7 % ( n = 14), suicide or accident for 4 % ( n = 7) and liver diseases for 3 % ( n = 5) of deaths (unknown n = 47, 26 %). Although the majority of patients (92.5 %) was on antiretroviral therapy (ART), only 50 % were virologically suppressed (HIV-RNA <50 copies/mL) and 44 % had a decreased CD4+ count (<200/μL) at their last visit before death. Conclusion: One-third of the causes of death in our cohort between 2004 and 2010 was AIDS-related. Since most of these deaths occur with severe immune suppression, they can possibly be prevented by the early diagnosis and treatment of HIV infection. Care providers must be aware of an increased risk for a broad range of diseases in HIV-infected patients and should apply appropriate preventive measures. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate a newly implemented infectious disease (ID) consultation service in terms of patient care, outcome and antibiotic prescription and to describe factors influencing adherence to recommendations. Methods: Data from consultations during the first 6 months of the ID consultation program were collected and evaluated. Consultation requests, diagnostic results, treatment outcomes and antibiotic recommendations were categorised. Diagnostic and therapeutic recommendations were assessed and rated for adherence and outcome. Statistical analysis was performed to identify factors influencing adherence and treatment outcome. Results: A total of 251 consultations were assessed. In most cases, ID specialists were asked for further advice regarding a previously initiated anti-infective treatment ( N = 131, 52 %). In 54 of 195 (28 %) first consultations, the ID specialist proposed a differential diagnosis that differed from that of the working diagnoses submitted with the consultation request, and which was subsequently confirmed in 80 % of these cases. Diagnostic and therapeutic recommendations were made in 190 (76 %) and 240 (96 %) of the consultations, respectively. A change in the current treatment was recommended in 66 % of consultations; 37 % of recommendations were cost-saving and 26 % were cost-neutral. Compliance with diagnostic and therapeutic recommendations was rated as good by pre-specified criteria in 65 and 86 % of consultations, respectively. Treatment outcome was correlated with adherence to diagnostic recommendations ( P = 0.012). Twenty-nine patients (16 %) died during the same hospital stay. Conclusion: Infectious disease consultations may help to establish the correct diagnosis, resulting in the appropriate treatment being provided to a severely sick patient population. Treatment outcome was improved in cases of good diagnostic adherence to the recommendations of the ID specialist. [ABSTRACT FROM AUTHOR]

Invasive fungal disease (IFD) causes increasing morbidity and mortality in haematological cancer patients. Reliable cost data for treating IFD in German hospitals is not available. Objective of the study was to determine the institutional cost of treating the IFD. Data were obtained by retrospective chart review in German hospitals. Patients had either newly diagnosed or relapsed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Direct medical cost was calculated from hospital provider's perspective. A total of 108 patients were enrolled at 5 tertiary care hospitals, 36 IFD patients and 72 controls. The vast majority of IFD patients (74%) were diagnosed with invasive aspergillosis. On average, the hospital stay for IFD patients was 12 days longer than in control patients. All patients in the IFD group and 89% of patients in the control group received antifungal drugs. Mean direct costs per patient were €51 517 in the IFD group and €30 454 in the control group. Incremental costs of €21 063 were dominated by cost for antifungal drugs (36%), hospital stay (32%) and blood products (23%). From the perspective of hospitals in Germany the economic burden of IFD in patients with AML or MDS is substantial. Therefore, prevention of IFD is necessary with respect to both clinical and economic reasons. [ABSTRACT FROM AUTHOR]

Purpose: Liver involvement in syphilis has been studied in cohorts of human immunodeficiency virus (HIV)-negative individuals despite the scarcity of data on such HIV-infected patients. Th aim of this study was to assess hepatic involvement of HIV-infected patients diagnosed with syphilis. Methods: Patients with syphilis and liver involvement, including all stages of syphilis, were systematically identified in our HIV cohort between 2004 and 2008. Results: Of the 1,599 HIV-infected patients identified during the study period, 100 were diagnosed with acute syphilis, all of whom were male. Of these 100 patients, 84 % were men who have sex with men. Laboratory parameters of liver involvement were present in 19 of the 100 HIV-infected patients with syphilis; these resolved after successful antibiotic treatment. Among these 19 patients, six were diagnosed to be in the latent stage, with elevated liver enzymes and parameters of inflammation representing the only distinctive feature. Conclusions: Based on our results, syphilis should be included in the differential diagnosis of increased liver enzymes in HIV-infected patients. [ABSTRACT FROM AUTHOR]

Summary The objectives of this study were to identify unsolved issues in the management of invasive candidiasis, identify controversies and achieve consensus. The German Speaking Mycological Society (Deutschsprachige Mykologische Gesellschaft, DMykG e.V.) asked other German infectious diseases (ID) and mycological societies to submit unsolved issues concerning the diagnosis and treatment of fungal infections. Based on these contributions, a digital web-based questionnaire of 12 questions on Candida infections was designed to be completed by experts of the participating societies. Controversial results were identified by a mathematical model and were discussed at a consensus conference during the 43rd Annual Meeting of the DMykG e.V. in Cologne, Germany. Forty-two individuals completed the questionnaire. Analysis showed a strong consensus on treatment indications, choice of antifungals for clinical situations, handling of central venous catheters, duration of treatment and role of susceptibility testing. Opinions diverged on: initial treatment of haemodynamically stable neutropenic and haemodynamically unstable non-neutropenic patients, step down to oral treatment and the differential role of the echinocandins. These questions were presented for discussion at the expert consensus conference. In three of four questions, consensus was achieved. A two-step approach - web-based survey plus classical panel discussion - allows to capture expeditiously the opinions of a large and diverse group of individuals, to identify controversial issues and to resolve them in a personal, interactive setting. Thus, expert consensus was achieved on nine of 12 important questions on how to treat invasive candidiasis. [ABSTRACT FROM AUTHOR]

Background: Highly active antiretroviral therapy (HAART) has improved the prognosis of HIV-infected patients. We studied the changes in the incidence and prognosis of cytomegalovirus (CMV) disease preceding and during the first few years of HAART in a clinic cohort. Patients and Methods: All patients with CMV disease diagnosed between 1993 and 1999 from a clinic cohort in Cologne, Germany, were included. The patients were followed until death or until December 31, 2001. The time period from 1993-1996 was classified as pre-HAART, the period from 1997-1999 as the HAART era. Survival was analyzed with a Cox-proportional hazard model. Results: From a total of 1,279 HIV-infected patients, 127 patients with CMV disease were enrolled. The incidence of CMV disease declined rapidly and significantly from 7.34 cases per 100 patient years (py) in the pre-HAART era to 0.75 cases per 100 py in the HAART era. The median survival time in the pre-HAART era was 9.5 months; the median survival was not yet reached at 4 years of follow-up in the HAART era. The only risk factors influencing survival were CD4-cell count and antiretroviral therapy before and after diagnosis of CMV disease. Treatment naive patients had a better prognosis than pretreated patients and patients treated with triple combination therapy survived longer than patients with other treatment modalities. Conclusion: A rapid decline in the incidence of new CMV manifestations and a better prognosis of patients with CMV disease, especially if they were treatment naive and treated with triple combination therapy, were observed in the HAART era. [ABSTRACT FROM AUTHOR]

Background: Surgical site infections (SSIs), mainly caused by Staphylococcus aureus, pose a significant economic burden in Europe, leading to increased hospitalization duration, mortality, and treatment costs, particularly with drug-resistant strains such as meticillin-resistant S. aureus., Aim: To conduct a case-control study on the economic impact of S. aureus SSI in adult surgical patients across high-volume centres in France, Germany, Spain, and the UK, aiming to assess the overall and procedure-specific burden across Europe., Methods: The SALT study is a multinational, retrospective cohort study with a nested case-control analysis focused on S. aureus SSI in Europe. The study included participants from France, Germany, Italy, Spain, and the UK who underwent invasive surgery in 2016 and employed a micro-costing approach to evaluate health economic factors, matching S. aureus SSI cases with controls., Findings: In 2016, among 178,904 surgical patients in five European countries, 764 developed S. aureus SSI. Matching 744 cases to controls, the study revealed that S. aureus SSI cases incurred higher immediate hospitalization costs (€8,810), compared to controls (€6,032). Additionally, S. aureus SSI cases exhibited increased costs for readmissions within the first year post surgery (€7,961.6 versus €5,298.6), with significant differences observed. Factors associated with increased surgery-related costs included the cost of hospitalization immediately after surgery, first intensive care unit (ICU) admission within 12 months, and hospital readmission within 12 months, as identified through multivariable analysis., Conclusion: The higher rates of hospitalization, ICU admissions, and readmissions among S. aureus SSI cases highlight the severity of these infections and their impact on healthcare costs, emphasizing the potential benefits of evidence-based infection control measures and improved patient care to mitigate the economic burden., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Aspergillus fumigatus is the most common agent of invasive aspergillosis (IA). In recent years, resistance to triazoles, the mainstay of IA therapy, has emerged in different countries worldwide. IA caused by azole-resistant A. fumigatus (ARAF) shows an exceedingly high mortality. In this study, IA due to ARAF isolates in HSCT recipients in Germany was investigated., Methods: The epidemiology of azole resistance in IA was analysed in two German haematology departments. Between 2012 and 2013, 762 patients received HSCT in Essen (n = 388) and Cologne (n = 374). Susceptibility testing of A. fumigatus isolates was performed by Etest, followed by EUCAST broth microdilution testing if elevated MICs were recorded. In all ARAF isolates the cyp51A gene was sequenced and the genotype was determined by microsatellite typing using nine short tandem repeats., Results: In total, A. fumigatus was recovered from 27 HSCT recipients. Eight patients had azole-resistant IA after HSCT, and seven of the cases were fatal (88%). All except one patient received antifungal prophylaxis (in five cases triazoles). TR34/L98H was the most common mutation (n = 5), followed by TR46/Y121F/T289A (n = 2). In one resistant isolate no cyp51A mutation was detected. Genotyping revealed genetic diversity within the German ARAF isolates and no clustering with resistant isolates from the Netherlands, India and France., Conclusions: This report highlights the emergence of azole-resistant IA with TR34/L98H and TR46/Y121F/T289A mutations in HSCT patients in Germany and underscores the need for systematic antifungal susceptibility testing of A. fumigatus., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

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., (© 2015 Blackwell Verlag GmbH.)

Background: In patients with haematological or oncological malignancies, we aimed to assess the rate of intestinal colonisation and blood stream infections (BSI) with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) and vancomycin-resistant enterococci (VRE), mortality and risk factors associated with ESBLE/VRE BSI, as well as the impact of faecal screening for ESBLE and VRE in combination with adapted empiric treatment of febrile neutropenia., Methods: Within 72 h of admission to our department, an ESBLE and VRE screening stool sample was collected. In the case of neutropenic fever, blood cultures were drawn. Data of all admitted patients were prospectively documented. Explorative forward-stepwise logistic regression analyses were used to identify risk factors for progression from intestinal colonisation to BSI., Results: During the study period, 1,805 stool samples were obtained from 513 patients during 1,012 inpatient stays, and 2,766 blood cultures were obtained from 578 patients during 1,091 inpatient stays. Ninety (17.5 %) of these patients were colonised with ESBLE and 51 (9.9 %) with VRE. Proportions of 40 % (36/90) of ESBLE and 61 % (31/51) of VRE colonisations were healthcare-associated. Six of 90 (6.6 %) ESBLE-colonised patients and 1/51 (2 %) VRE-colonised patients developed BSI with the respective organism. None of these patients died after receiving early appropriate empiric antibiotics based on colonisation status. Colonisation with ESBLE or VRE was associated with increased risk ratios (RR) towards developing ESBLE BSI [RR 4.5, 95 % confidence interval (CI): 2.89-7.04] and VRE BSI (RR 10.2, 95 % CI: 7.87-13.32), respectively. Acute myelogenous leukaemia and prior treatment with platinum analogues or quinolones were identified as independent risk factors for ESBLE BSI in colonised patients., Conclusions: Intestinal ESBLE/VRE colonisation predicts BSI. Faecal screening in haematology/oncology patients in combination with directed empiric treatment may reduce ESBLE BSI-related mortality.

We report the first culture-proven case of invasive aspergillosis (IA) caused by azole-resistant Aspergillus fumigatus in a patient with acute myeloid leukaemia in Germany. IA presented as breakthrough infection under posaconazole prophylaxis. Analysis of the resistance mechanism revealed the TR/L98H mutation in the cyp51A gene, which indicates an environmental origin of the strain. This case underscores the need for monitoring azole resistance in Aspergillus spp. and for routine susceptibility testing of moulds.

Aspergillus terreus may be resistant to amphotericin B and is associated with significant morbidity and mortality in immunocompromised patients. Local incidence is influenced by the density of airborne Aspergillus spp. spores which may in turn depend on meteorological factors. Once-weekly environmental samples were collected prospectively inside and outside the University Hospital of Cologne, Germany (UHC) and haematological patients were screened for nasal Aspergillus spp. colonisation and monitored for invasive fungal disease (IFD). RAPD (rapid amplification of polymorphic DNA)-polymerase chain reaction (PCR) and amphotericin B susceptibility testing were performed on all A. terreus isolates. A total of 4919 colony-forming units (cfu) were isolated (2212 indoors, 2707 outdoors). Further identification revealed A. fumigatus (73.5%), A. niger (4.3%), A. flavus (1.7%), A. terreus (0.2%) and non-Aspergillus fungi (20.3%). RAPD-PCR did not reveal clonal relationships between the A. terreus isolates. All A. terreus isolates displayed complete resistance to amphotericin. The B. Aspergillus spp. conidia exposure was lowest in June and highest in November inside and outside UHC. Conidia load correlated with the season and the relative humidity, with increasing spore counts during dry periods. One out of 855 nasal swabs was positive for A. niger. The patient did not develop IFD. A. terreus is unlikely to be a relevant pathogen at the UHC. Results from RAPD-PCR suggested a wide epidemiological variety of strains rather than a common source of contamination. Nasal swab surveillance cultures for early detection of Aspergillus spp. colonisation were not useful in identifying patients who may develop IFD. The risk of IFD at the UHC may increase in autumn and during dry periods., (Copyright © 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Large randomized controlled trials have shown significant decreases in morbidity and mortality in leukaemia patients with posaconazole prophylaxis. However, the value of prophylaxis has been questioned in centres with a low incidence of invasive fungal diseases (IFDs) and pre-emptive treatment strategies., Methods: We prospectively evaluated the epidemiology of IFDs in acute myelogenous leukaemia (AML) patients undergoing first remission-induction chemotherapy before and after posaconazole prophylaxis had been introduced as a standard of care. Patients admitted from January 2003 to December 2005 received topical polyenes as antifungal prophylaxis (first group), while those admitted between January 2006 and December 2008 received 200 mg of oral posaconazole three times daily (second group). Other diagnostic and therapeutic standard operating procedures remained unchanged., Results: A total of 82 patients in the polyene prophylaxis group and 77 in the posaconazole prophylaxis group were included in the final analysis. Baseline characteristics were well matched between groups. Patients receiving topical polyene prophylaxis were more likely to experience breakthrough IFDs (19.5% and 3.9%; P = 0.003) or breakthrough aspergillosis (13.4% and 2.6%; P = 0.018) than patients receiving systemic posaconazole prophylaxis. They also had more febrile days (mean 10.7 +/- 9.66 and 7.3 +/- 5.73; P = 0.007), longer need for inpatient treatment (mean 53.0 +/- 24.16 and 46.0 +/- 14.39; P = 0.026) and a shorter fungal-free survival (78.7 and 90.4 days; P = 0.024). No significant differences were observed for persistent fever, pneumonia, lung infiltrates indicative of invasive pulmonary aspergillosis, or attributable and overall mortality., Conclusions: After introduction of posaconazole prophylaxis for patients with AML, the number of febrile days, the incidence rate of IFDs and aspergillosis and the duration of hospitalization decreased significantly.

Aim: The clinical trial is the link between research and medical practice and facilitates evidence-based therapies. There are specific difficulties to be faced when executing clinical trials related to surgical services (learning curve of the surgeon, blinding etc.). As a result, surgical randomised controlled clinical trials (RCT) are underrepresented in the total number of RCTs., Method: To make it easier to implement surgical RCT, the Clinical Trial Unit for Orthopaedics and Trauma Surgery was established. Training of the supporting physicians was reached by rotations in the structures of CHIR-Net, a BMBF-funded network created to build up a region-wide surgical research infrastructure., Result/conclusion: Supported by the regional CHIR-Net Center and the regional Clinical Trial Center, a research institute was thus founded with the aim of contributing to a long-term improvement in clinical research in orthopaedics and trauma surgery.

Introduction: CHIR-Net is a German national surgical network for clinical trials. It is supported by the Federal Ministry for Education and Research (BMBF 01GH0605) to establish infrastructure and expertise in the conduct of clinical trials within the surgical disciplines. An important aspect of this network is a qualified advanced training for physicians deployed at the CHIR-Net as part of a job rotation., Methods: A catalog of activities for the time of rotation within the network has been developed in cooperation with the CHIR-Net, the deployed physicians and cooperating regional clinical trials centers (ZKS/KKS)., Result: The focal points of the physicians' rotation in the CHIR-Net are outlined in a curriculum that has been established and evaluated in the network since January 2008., Conclusion: After the rotation time at the CHIR-Net the skilled physicians act as multipliers of specialized knowledge on clinical research. In this way the acquired expertise will be transferred into clinical practice and treatment of patients within research projects will benefit directly.

Objective: To investigate the economic impact of micafungin (MICA) for treatment of invasive candidiasis and candidaemia (systemic Candida infections), a health economic analysis was conducted comparing MICA with liposomal amphotericin B (L-AMB)., Research Design and Methods: The model was based on a phase III, randomised, double-blind, clinical trial which compared MICA with L-AMB. The model entailed a period of 14-20 weeks starting from initiation of treatment and was analysed from a German hospital perspective., Main Outcome Measures: The main outcome measures were defined as the percentage of patients achieving clinical and mycological response after initial treatment and who were alive at the end of the study (EOS), and the total treatment-associated costs over the study period., Results: The health economic analysis shows that with MICA, 52.9% of patients are successfully treated and were alive at EOS compared to 49.1% for L-AMB. In addition, MICA has, on average, lower treatment-associated costs than L-AMB with euro43 243 and euro49 216 per patient, respectively. Because the costs are lower and the effectiveness is higher for MICA in comparison with L-AMB, MICA is more cost-effective than L-AMB. However, the results of the probabilistic sensitivity analysis show that the differences cannot be considered significant due to a large variance, although MICA remained the most cost-effective option throughout the one-way sensitivity analyses., Conclusions: The lower costs and higher effectiveness reported for MICA versus L-AMB in this analysis indicate that MICA may be a more cost-effective therapy in the treatment of invasive candidiasis and candidaemia when compared with L-AMB.

To assess the long-term outcome and influence of clinical management of patients with Staphylococcus aureus bacteremia (SAB), 229 patients with blood cultures positive for Staphylococcus aureus between January 1997 and December 2000 were retrospectively identified and followed up. Risk factors, source of infection, treatment, clinical course, and outcome were recorded by chart review. For the assessment of 1-year survival, a questionnaire was sent to family doctors and government registration offices. Time of initial antibiotic therapy, duration of antibiotic treatment and performance of echocardiography were regarded as indicators of the quality of the clinical management of SAB. Among the 229 patients studied, 218 were evaluable for 1-year survival. Crude mortality after 1 year was 37.6% year. Within 30 days 43 (19.7%) patients had died, and 39 (17.9%) additional patients died thereafter. Using multivariate analysis, the following variables were associated with death: malignant disease (odds ratio [OR] 4.8; 95% confidence interval [CI], 2.6-8.9), pneumonia (OR, 3.6; 95%CI, 1.2-10.2), age >60 years (OR, 2.6; 95%CI, 1.5-4.5), and known source of infection (OR, 2.3; 95%CI, 1.3-4.1). Among 160 patients with a completely assessable treatment course 73 (46%) had received antibiotics for at least 14 days. A delay of antibiotic treatment of 1 day or more after microbiological diagnosis was observed in 28.3% of patients (i.e., 60 of 212 patients who received at least 1 dose of antibiotics). Echocardiography was performed in 101 (44.1%) cases. Overall, the findings indicate that standard guidelines for the management of SAB are followed only in part in clinical practice. In order to reduce the considerable mortality associated with SAB and to improve short- and long-term outcome, efforts should be made to increase adherence to recommendations.