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1. Fungal infections

Author

Koehler, P., Cornely, O. A., Vehreschild, J. J., Koehler, P., Cornely, O. A., and Vehreschild, J. J.

Abstract

Background. Invasive aspergillosis, mucormycosis, and cryptococcosis are severe opportunistic infections in patients with long phases of neutropenia and also after allogeneic stem cell and organ transplantation. Due to the late appearance of clinical signs and the often poor outcome, these diseases require special attention and proactive interventions. Material and methods. Published guidelines and selected current literature were reviewed for this article. Results. Invasive aspergillosis and mucormycosis are typically observed in the upper and lower airways of severely immunocompromized patients. When invasive fungal diseases are suspected, sectional imaging and, if possible, serological testing should be performed as soon as possible. If imaging or serological tests confirm the suspected diagnosis, pre-emptive antimycotic treatment should be started and further confirmation of the diagnosis sought via microbiological and/or histological investigations. Treatment depends on comedication, comorbidity and risk factors, primarily with voriconazole, isavuconazole and liposomal amphotericin B. With the advent of antiretroviral treatment, a decrease of cryptococcosis cases in people with human immunodeficiency virus was observed; however, increasing cases have been reported in patients with new forms of immunosuppression. Cryptococcus spp. predominantly cause central nervous system infections but also pneumonia and bloodstream infections. Diagnostics include blood and cerebrospinal fluid cultures and antigen tests. First line treatment consists of a combination therapy with amphotericin B and flucytosine. Conclusion. An interdisciplinary approach with microbiologists, infectious diseases specialists and radiologists is needed for diagnostics and treatment of invasive fungal diseases.

Published
2019

2. Mucormycosis in patients with diabetes mellitus

Author

Mellinghoff, S. C., Koehler, P., Seidel, D., Cornely, O. A., Mellinghoff, S. C., Koehler, P., Seidel, D., and Cornely, O. A.

Abstract

Mucormycoses are caused by moulds of the orders Mucorales and Entomophthorales. These fungi are ubiquitous in nature and are transmitted via inhalation, ingestion, or traumatic inoculation. Infections occur almost exclusively in immunosuppressed patients. Patients with diabetes mellitus are a particular group at risk. Mucormycoses can cause cutaneous, gastrointestinal, or pulmonary disease. In diabetic patients, rapidly progressive sinu-orbito-cerebral infection is typical, often leading to loss of central vision. Mucormycosis is frequently lethal due to delayed diagnosis. The purpose of this article is to provide an overview of mucormycosis, while focusing on patients with diabetes mellitus. The European guideline on the diagnosis and management of mucormycosis as well as selected current literature on the topic were reviewed for this article. Mucormycosis is an ultra-orphan disease associated with high mortality. Aggressive, invasive fungal growth often exceeds organ boundaries. The drug of choice for first-line therapy is liposomal amphotericin B. In the case of treatment failure, switching to or the addition of posaconazole should be considered. Isavuconazole, a well-tolerated alternative drug, has also been available since 2016. Ongoing clinical trials are currently focusing on new antifungal drugs and immunotherapy as a novel approach of treatment. Furthermore, investigations are underway to determine whether combining different drugs improves efficacy.

Published
2018

3. Essentials in Candida bloodstream infection

Author

Mellinghoff, Sibylle C., Cornely, O. A., Jung, N., Mellinghoff, Sibylle C., Cornely, O. A., and Jung, N.

Abstract

Aims Due to the increase of severely immunocompromised patients, of invasive procedures including central intravascular catheters, and of the use of broad-spectrum antibiotics, the incidence of Candida bloodstream infections has risen intensely in the last decades. Candida bloodstream infection is a serious disease with high mortality. Optimized diagnostic and therapeutic management can improve outcome. Thus, the aim of our mini-review is to highlight important and often missed opportunities in the management of Candida bloodstream infection. Methods We searched the published literature and describe the essentials in the management of Candida bloodstream infection. Results Four essentials were identified: (1) isolation of Candida spp. from a blood culture should always be considered relevant and requires treatment. Daily blood cultures should be drawn to determine cessation of candidemia. (2) Central venous catheter (CVC) and/or other indwelling devices should be removed. (3) Echinocandins are the first choice. Antifungal treatment should be continued for at least 14 days after cessation of fungemia. Susceptibility testing should be performed to identify resistance and to facilitate transition to oral treatment. (4) In persistent candidemia, echocardiography is an important investigation; ophthalmoscopy should be considered. Conclusion Further efforts should be undertaken to increase the adherence to the essentials in the management of Candia bloodstream infection.

Published
2018

4. Economic burden of Clostridium difficile associated diarrhoea: a cost-of-illness study from a German tertiary care hospital

Author

Heimann, S. M., Vehreschild, J. J., Cornely, O. A., Wisplinghoff, H., Hallek, M., Goldbrunner, R., Boettiger, B. W., Goeser, T., Hoelscher, A., Baldus, S., Mueller, F., Jazmati, N., Wingen, S., Franke, B., Vehreschild, M. J. G. T., Heimann, S. M., Vehreschild, J. J., Cornely, O. A., Wisplinghoff, H., Hallek, M., Goldbrunner, R., Boettiger, B. W., Goeser, T., Hoelscher, A., Baldus, S., Mueller, F., Jazmati, N., Wingen, S., Franke, B., and Vehreschild, M. J. G. T.

Abstract

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. We defined CDAD as presence of diarrhoea (a parts per thousand yen3 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 a parts per thousand yen1 recurrence) and control group (matched non-CDAD patients). 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 a,not sign18,460 (95 %CI: a,not sign14,660-a,not sign22,270), a,not sign73,900 (95 %CI: a,not sign50,340-a,not sign97,460) and a,not sign14,530 (95 %CI: a,not sign11,730-a,not sign17,330; 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). 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.

Published
2015

5. Causes of death in HIV-infected patients from the Cologne-Bonn cohort

Author

Ehren, K., Hertenstein, C., Kuemmerle, T., Vehreschild, J. J., Fischer, J., Gillor, D., Wyen, C., Lehmann, C., Cornely, O. A., Jung, N., Gravemann, S., Platten, M., Wasmuth, J. C., Rockstroh, J. K., Boesecke, C., Schwarze-Zander, C., Faetkenheuer, G., Ehren, K., Hertenstein, C., Kuemmerle, T., Vehreschild, J. J., Fischer, J., Gillor, D., Wyen, C., Lehmann, C., Cornely, O. A., Jung, N., Gravemann, S., Platten, M., Wasmuth, J. C., Rockstroh, J. K., Boesecke, C., Schwarze-Zander, C., and Faetkenheuer, G.

Abstract

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. 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). 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/mu L) at their last visit before death. 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.

Published
2014

6. Clinical course and quality of care in ART-na < ve patients newly presenting in a HIV outpatient clinic

Author

Platten, M., Linnemann, R., Kuemmerle, T., Jung, N., Wyen, C., Ehren, K., Gravemann, S., Gillor, D., Cornely, O. A., Fischer, J., Lehmann, C., Rockstroh, J. K., Faetkenheuer, G., Vehreschild, J. J., Platten, M., Linnemann, R., Kuemmerle, T., Jung, N., Wyen, C., Ehren, K., Gravemann, S., Gillor, D., Cornely, O. A., Fischer, J., Lehmann, C., Rockstroh, J. K., Faetkenheuer, G., and Vehreschild, J. J.

Abstract

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. Antiretroviral therapy (ART)-na < ve HIV-infected subjects presenting between 2007 and 2008 were followed until June 2012. Clinical data and laboratory parameters were collected prospectively and analysed retrospectively. 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/A mu L [160/500] and declined to 210/A mu L [100/300] at ART start. 12 months thereafter, the CD4 cell count increased to 410/A mu L [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. 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.

Published
2014

7. Prediction of overactive bladder treatment outcome by using long-term urodynamics

Author

Wille, S., Tenholte, D., Cornely, O. A., Muthen, N., Engelmann, U. -H., Mehner, J., Eminaga, O., Herden, J., Schumacher, P., Paas, J., Wille, S., Tenholte, D., Cornely, O. A., Muthen, N., Engelmann, U. -H., Mehner, J., Eminaga, O., Herden, J., Schumacher, P., and Paas, J.

Abstract

In Germany, overactive bladder (OAB) syndrome affects around 6.5 million people over the age of 40. The primary treatment consists of anticholinergics or beta-3-receptor agonists. After an anticholinergic treatment period of around 4 months, compliance is around 40%, which is probably due a larger proportion of nonresponders. One condition of an efficient medication treatment is the presence of detrusor overactivity (DO). However, the detection rate of DO during standard urodynamics is very low. The primary goal in the future is to target OAB treatment by detection of DO. Using the Wille Capsule (WiCa) in an in vitro model, DO could be detected over a time period of 72 h, which would ensure a higher compliance to the OAB treatment in a positive way.

Published
2014

9. Evaluation of an infectious disease consultation programme in a German tertiary care hospital

Author

Vehreschild, J. J., Morgen, G., Cornely, O. A., Hartmann, P., Koch, S., Kalka-Moll, W., Wyen, C., Vehreschild, M. J. G. T., Lehmann, C., Gillor, D., Seifert, H., Kremer, G., Faetkenheuer, G., Jung, N., Vehreschild, J. J., Morgen, G., Cornely, O. A., Hartmann, P., Koch, S., Kalka-Moll, W., Wyen, C., Vehreschild, M. J. G. T., Lehmann, C., Gillor, D., Seifert, H., Kremer, G., Faetkenheuer, G., and Jung, N.

Abstract

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. 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. 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. 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.

Published
2013

10. Liver involvement in HIV-infected patients diagnosed with syphilis

Author

Jung, N., Kuemmerle, T., Brengelmann, S. D., Gielen, J., Lehmann, C., Wyen, C., Birtel, A., Fischer, J., Gillor, D., Koch, S., Vehreschild, J. J., Cornely, O. A., Faetkenheuer, G., Jung, N., Kuemmerle, T., Brengelmann, S. D., Gielen, J., Lehmann, C., Wyen, C., Birtel, A., Fischer, J., Gillor, D., Koch, S., Vehreschild, J. J., Cornely, O. A., and Faetkenheuer, G.

Abstract

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. Patients with syphilis and liver involvement, including all stages of syphilis, were systematically identified in our HIV cohort between 2004 and 2008. 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. Based on our results, syphilis should be included in the differential diagnosis of increased liver enzymes in HIV-infected patients.

Published
2012

11. Intestinal colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) in patients with haematological and oncological malignancies

Author

Liss, B. J., Vehreschild, J. J., Cornely, O. A., Hallek, M., Faetkenheuer, G., Wisplinghoff, H., Seifert, H., Vehreschild, M. J. G. T., Liss, B. J., Vehreschild, J. J., Cornely, O. A., Hallek, M., Faetkenheuer, G., Wisplinghoff, H., Seifert, H., and Vehreschild, M. J. G. T.

Abstract

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

Published
2012

12. Essentials in Candida bloodstream infection.

Author

Mellinghoff SC, Cornely OA, and Jung N

Subjects
Antifungal Agents therapeutic use, Central Venous Catheters, Disease Management, Echinocandins therapeutic use, Humans, Candidiasis therapy, Fungemia therapy
Abstract

Aims: Due to the increase of severely immunocompromised patients, of invasive procedures including central intravascular catheters, and of the use of broad-spectrum antibiotics, the incidence of Candida bloodstream infections has risen intensely in the last decades. Candida bloodstream infection is a serious disease with high mortality. Optimized diagnostic and therapeutic management can improve outcome. Thus, the aim of our mini-review is to highlight important and often missed opportunities in the management of Candida bloodstream infection., Methods: We searched the published literature and describe the essentials in the management of Candida bloodstream infection., Results: Four essentials were identified: (1) isolation of Candida spp. from a blood culture should always be considered relevant and requires treatment. Daily blood cultures should be drawn to determine cessation of candidemia. (2) Central venous catheter (CVC) and/or other indwelling devices should be removed. (3) Echinocandins are the first choice. Antifungal treatment should be continued for at least 14 days after cessation of fungemia. Susceptibility testing should be performed to identify resistance and to facilitate transition to oral treatment. (4) In persistent candidemia, echocardiography is an important investigation; ophthalmoscopy should be considered., Conclusion: Further efforts should be undertaken to increase the adherence to the essentials in the management of Candia bloodstream infection.

Published
2018
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13. Economic burden of Clostridium difficile associated diarrhoea: a cost-of-illness study from a German tertiary care hospital.

Author

Heimann SM, Vehreschild JJ, Cornely OA, Wisplinghoff H, Hallek M, Goldbrunner R, Böttiger BW, Goeser T, Hölscher A, Baldus S, Müller F, Jazmati N, Wingen S, Franke B, and Vehreschild MJ

Subjects
Adult, Aged, Aged, 80 and over, Clostridium Infections epidemiology, Clostridium Infections microbiology, Diarrhea epidemiology, Diarrhea microbiology, Female, Germany epidemiology, Humans, Length of Stay, Male, Middle Aged, Retrospective Studies, Tertiary Care Centers, Young Adult, Clostridioides difficile isolation & purification, Clostridium Infections economics, Cost of Illness, Diarrhea economics
Abstract

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.

Published
2015
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14. Clinical course and quality of care in ART-naïve patients newly presenting in a HIV outpatient clinic.

Author

Platten M, Linnemann R, Kümmerle T, Jung N, Wyen C, Ehren K, Gravemann S, Gillor D, Cornely OA, Fischer J, Lehmann C, Rockstroh JK, Fätkenheuer G, and Vehreschild JJ

Subjects
Adult, Ambulatory Care Facilities statistics & numerical data, CD4 Lymphocyte Count, Drug Therapy, Combination, Female, Germany, HIV immunology, HIV physiology, HIV Infections immunology, HIV Infections virology, Humans, Male, Anti-HIV Agents therapeutic use, Clinical Competence, Guideline Adherence, HIV Infections drug therapy, Time-to-Treatment
Abstract

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.

Published
2014
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15. Causes of death in HIV-infected patients from the Cologne-Bonn cohort.

Author

Ehren K, Hertenstein C, Kümmerle T, Vehreschild JJ, Fischer J, Gillor D, Wyen C, Lehmann C, Cornely OA, Jung N, Gravemann S, Platten M, Wasmuth JC, Rockstroh JK, Boesecke C, Schwarze-Zander C, and Fätkenheuer G

Subjects
Adult, Aged, Aged, 80 and over, Cohort Studies, Female, Germany epidemiology, Humans, Male, Middle Aged, Young Adult, Cause of Death, HIV Infections mortality
Abstract

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.

Published
2014
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16. Evaluation of an infectious disease consultation programme in a German tertiary care hospital.

Author

Vehreschild JJ, Morgen G, Cornely OA, Hartmann P, Koch S, Kalka-Moll W, Wyen C, Vehreschild MJ, Lehmann C, Gillor D, Seifert H, Kremer G, Fätkenheuer G, and Jung N

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Anti-Infective Agents therapeutic use, Child, Child, Preschool, Communicable Diseases drug therapy, Female, Germany, Guideline Adherence, Hospital Departments standards, Humans, Infant, Male, Middle Aged, Tertiary Healthcare, Treatment Outcome, Young Adult, Communicable Diseases diagnosis, Referral and Consultation standards
Abstract

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.

Published
2013
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17. Intestinal colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) in patients with haematological and oncological malignancies.

Author

Vehreschild MJ, Liss BJ, and Cornely OA

Subjects
Female, Humans, Male, Aged, Bacteremia microbiology, Enterobacteriaceae isolation & purification, Enterobacteriaceae Infections microbiology, Gastrointestinal Tract microbiology, Vancomycin Resistance, beta-Lactamases metabolism
Published
2013
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18. Intestinal colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) in patients with haematological and oncological malignancies.

Author

Liss BJ, Vehreschild JJ, Cornely OA, Hallek M, Fätkenheuer G, Wisplinghoff H, Seifert H, and Vehreschild MJ

Subjects
Adolescent, Adult, Aged, 80 and over, Anti-Bacterial Agents therapeutic use, Bacteremia drug therapy, Cohort Studies, Cross Infection complications, Cross Infection epidemiology, Enterobacteriaceae drug effects, Enterobacteriaceae enzymology, Enterobacteriaceae Infections drug therapy, Feces microbiology, Female, Germany, Humans, Logistic Models, Male, Middle Aged, Neoplasms complications, Prospective Studies, Risk Factors, Vancomycin therapeutic use, Young Adult, Aged, Bacteremia microbiology, Enterobacteriaceae isolation & purification, Enterobacteriaceae Infections microbiology, Gastrointestinal Tract microbiology, Vancomycin Resistance, beta-Lactamases metabolism
Abstract

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.

Published
2012
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19. Liver involvement in HIV-infected patients diagnosed with syphilis.

Author

Jung N, Kümmerle T, Brengelmann SD, Gielen J, Lehmann C, Wyen C, Birtel A, Fischer J, Gillor D, Koch S, Vehreschild JJ, Cornely OA, and Fätkenheuer G

Subjects
Adult, Cohort Studies, Diagnosis, Differential, Germany epidemiology, HIV Infections complications, HIV Infections enzymology, HIV Infections epidemiology, Humans, Liver Diseases enzymology, Liver Diseases epidemiology, Liver Diseases virology, Liver Function Tests, Male, Middle Aged, Retrospective Studies, Syphilis complications, Syphilis enzymology, Syphilis epidemiology, HIV Infections microbiology, Liver Diseases microbiology, Syphilis microbiology
Abstract

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.

Published
2012
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20. Aspergillus to Zygomycetes: causes, risk factors, prevention, and treatment of invasive fungal infections.

Author

Cornely OA

Subjects
Drug Resistance, Fungal, Fungi drug effects, Humans, Risk Factors, Antifungal Agents therapeutic use, Fungi physiology, Mycoses drug therapy, Mycoses microbiology, Mycoses prevention & control
Abstract

Invasive fungal infections (IFIs) are an important cause of morbidity and mortality, particularly in patients with underlying risk factors (e.g., neutropenia, cancer chemotherapy, transplantation, AIDS). Although Candida species remain a relevant cause of IFI, other organisms (particularly moulds) have become increasingly prevalent. In particular, Aspergillus species are the leading cause of mould infections although other moulds including Fusarium species and Zygomycetes are increasing in frequency, and are associated with a high mortality rate. Options available for the prevention and treatment of these infections include standard and liposomal formulations of amphotericin B, but toxicity concerns limit their use; fluconazole is effective for the prevention and treatment of candidiasis but its inactivity against moulds and increasing resistance are limiting factors. Newer azoles, particularly voriconazole and posaconazole, have an enhanced spectrum of activity that includes Candida species, Aspergillus species, Cryptococcus species, dimorphic fungi, Fusarium species, and, for posaconazole, Zygomycetes. Recent data suggest that these agents are highly effective in a variety of clinical settings. Echinocandins have good activity against Candida species and Aspergillus species but their spectrum generally does not include Fusarium species, Cryptococcus species, Trichosporon species, Zygomycetes, and dematiaceous moulds. While these agents are unlikely to exhibit crossresistance with polyenes or azoles, they must be administered intravenously. Knowledge of the pathogenesis of IFIs and the activity, efficacy, and limitations of available treatment options will allow the selection of an appropriate antifungal agent for individual patients.

Published
2008
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21. A prospective, randomized multicenter trial of the empirical addition of antifungal therapy for febrile neutropenic cancer patients: results of the Paul Ehrlich Society for Chemotherapy (PEG) Multicenter Trial II.

Author

Schiel X, Link H, Maschmeyer G, Glass B, Cornely OA, Buchheidt D, Wilhelm M, Silling G, Helmerking M, Hiddemann W, Ostermann H, and Hentrich M

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Neutropenia etiology, Prospective Studies, Antifungal Agents therapeutic use, Fever of Unknown Origin etiology, Neoplasms complications, Neutropenia drug therapy
Abstract

Background: The aim of the study was to compare the efficacy of empirical antifungals in combination with broad spectrum antibiotics with that of antibiotics alone in high risk febrile neutropenic cancer patients not responding to initial antibacterial therapy., Patients and Methods: A prospective, randomized controlled trial was conducted at 22 cancer centers in Germany. Patients with fever of unknown origin were randomized to either piperacillin (Pip) plus an aminoglycoside (AMG) (arm A) or a third generation cephalosporin (Ceph) plus AMG (arm B). Patients not responding after 4-6 days were randomized to either imipenem (Imi) plus glycopeptide (GLP) (arm C), or Imi/GLP plus amphotericin B deoxycholate (AmB) plus 5-flucytosine (5-FC) (arm D), or Imi/GLP plus fluconazole (Fluco) (arm E). A successful outcome was defined as resolution of fever., Results: In arm A, 192 of 373 patients (51.5%) responded as compared to 176 of 344 patients (51.2%) in arm B. The response rates of 155 patients randomized for further empirical treatment were 55.6%, 77.8% and 62.5% in arm C, D and E, respectively. The difference between arm C and D was of borderline statistical significance (p = 0.06) after correction for multiple testing., Conclusion: In neutropenic cancer patients with persistent fever the combination of antibiotics with AmB/5-FC is superior to salvage antibacterial therapy alone. There is no difference in efficacy between Pip and third generation Ceph given as initial empirical therapy in combination with an AMG.

Published
2006
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22. Incidence and prognosis of CMV disease in HIV-infected patients before and after introduction of combination antiretroviral therapy.

Author

Salzberger B, Hartmann P, Hanses F, Uyanik B, Cornely OA, Wöhrmann A, and Fätkenheuer G

Subjects
AIDS-Related Opportunistic Infections diagnosis, AIDS-Related Opportunistic Infections mortality, Adult, CD4 Lymphocyte Count, Cohort Studies, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections mortality, Female, Germany epidemiology, HIV Infections mortality, Humans, Incidence, Male, Middle Aged, Prognosis, Risk Factors, Survival Rate, AIDS-Related Opportunistic Infections epidemiology, Antiretroviral Therapy, Highly Active, Cytomegalovirus Infections epidemiology, HIV Infections complications, HIV Infections drug therapy
Abstract

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.

Published
2005
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23. Seroprevalence and disease association of antineutrophil cytoplasmic autoantibodies and antigens in HIV infection.

Author

Cornely OA, Hauschild S, Weise C, Csernok E, Gross WL, Salzberger B, Fätkenheuer G, Diehl V, and Schrappe M

Subjects
AIDS-Related Opportunistic Infections diagnosis, Adult, Antibodies, Antineutrophil Cytoplasmic isolation & purification, Antigens, Viral isolation & purification, Cohort Studies, Enzyme-Linked Immunosorbent Assay, Epitopes blood, Female, Fluorescent Antibody Technique, Indirect, HIV Infections blood, HIV Infections epidemiology, Humans, Male, Prospective Studies, Seroepidemiologic Studies, Antibodies, Antineutrophil Cytoplasmic blood, Antigens, Viral blood, HIV Infections immunology
Abstract

This prospective study was designed to determine the role of antineutrophil cytoplasmic autoantibodies (ANCA) in HIV-infected patients. Immunofluorescence tests (IFT) and enzyme-linked immunosorbent assays (ELISA) were applied to sera of 199 consecutive outpatients. In the IFT 20% were positive. An atypical ANCA pattern was demonstrated in 67% of these, 33% revealed a perinuclear staining (pANCA). Specific ELISA revealed proteinase 3 (n = 2), myeloperoxidase (n = 1), lysozyme (n = 2), lactoferrin (n = 1), cathepsin G (n = 1), and human leukocyte elastase (HLE, n = 6). The target antigen remained unidentified in 26 patients. Perinuclear ANCA-positive patients showed atypical antigens in eight of 13 cases; all six patients with anti-HLE revealed a pANCA pattern. The antigens of atypical ANCA-positive patients remained unidentified in 21 of 26 (81%) cases. No signs of vasculitis were present in the ANCA-positive patients. ANCA are frequently found in the sera of HIV-positive patients. They bind to a variety of antigens. No correlation was found between ANCA positivity and autoimmune or opportunistic diseases.

Published
1999
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