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1.
J Antimicrob Chemother ; 77(Suppl_2): ii21-ii34, 2022 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-36426674

RESUMEN

Advances in medicine have led to a growing number of people with compromised or suppressed immune systems who are susceptible to invasive fungal infections. In particular, severe fungal infections are becoming increasingly common in ICUs, affecting people within and outside of traditional risk groups alike. This is exemplified by the emergence of severe viral pneumonia as a significant risk factor for invasive pulmonary aspergillosis, and the recognition of influenza-associated pulmonary aspergillosis and, more recently, COVID-19-associated pulmonary aspergillosis. The treatment landscape for haematological malignancies has changed considerably in recent years, and some recently introduced targeted agents, such as ibrutinib, are increasing the risk of invasive fungal infections. Consideration must also be given to the risk of drug-drug interactions between mould-active azoles and small-molecule kinase inhibitors. At the same time, infections caused by rare moulds and yeasts are increasing, and diagnosis continues to be challenging. There is growing concern about azole resistance among both moulds and yeasts, mandating continuous surveillance and personalized treatment strategies. It is anticipated that the epidemiology of fungal infections will continue to change and that new populations will be at risk. Early diagnosis and appropriate treatment remain the most important predictors of survival, and broad-spectrum antifungal agents will become increasingly important. Liposomal amphotericin B will remain an essential therapeutic agent in the armamentarium needed to manage future challenges, given its broad antifungal spectrum, low level of acquired resistance and limited potential for drug-drug interactions.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Infecciones Fúngicas Invasoras , Micosis , Aspergilosis Pulmonar , Humanos , Micosis/tratamiento farmacológico , Micosis/epidemiología , Micosis/diagnóstico , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/epidemiología , Azoles/uso terapéutico , Hongos , Aspergilosis Pulmonar/tratamiento farmacológico
2.
Internist (Berl) ; 60(7): 684-689, 2019 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-31119309

RESUMEN

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.


Asunto(s)
Antifúngicos/uso terapéutico , Aspergilosis , Mucormicosis , Micosis/tratamiento farmacológico , Infecciones Oportunistas , Aspergilosis/diagnóstico , Aspergilosis/tratamiento farmacológico , Humanos , Mucormicosis/diagnóstico , Mucormicosis/tratamiento farmacológico , Micosis/diagnóstico , Neutropenia
3.
Ann Oncol ; 29(6): 1354-1365, 2018 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-29688266

RESUMEN

Infectious complications are a significant cause of morbidity and mortality in patients with malignancies specifically when receiving anticancer treatments. Prevention of infection through vaccines is an important aspect of clinical care of cancer patients. Immunocompromising effects of the underlying disease as well as of antineoplastic therapies need to be considered when devising vaccination strategies. This guideline provides clinical recommendations on vaccine use in cancer patients including autologous stem cell transplant recipients, while allogeneic stem cell transplantation is subject of a separate guideline. The document was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) by reviewing currently available data and applying evidence-based medicine criteria.


Asunto(s)
Antiinfecciosos/uso terapéutico , Enfermedades Transmisibles/tratamiento farmacológico , Neoplasias Hematológicas/terapia , Neoplasias/terapia , Guías de Práctica Clínica como Asunto/normas , Trasplante de Células Madre/efectos adversos , Vacunación/normas , Enfermedades Transmisibles/etiología , Humanos , Pronóstico
4.
Ann Hematol ; 97(1): 31-49, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29177551

RESUMEN

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.


Asunto(s)
Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/terapia , Neoplasias/complicaciones , Adulto , Enfermedades Transmisibles/terapia , Alemania , Hematología/organización & administración , Hematología/normas , Humanos , Oncología Médica/organización & administración , Oncología Médica/normas , Neoplasias/diagnóstico , Neoplasias/terapia , Guías de Práctica Clínica como Asunto , Sociedades Médicas/organización & administración , Sociedades Médicas/normas
5.
Infection ; 46(6): 897-899, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30218311

RESUMEN

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.


Asunto(s)
Candidiasis/terapia , Fungemia/terapia , Antifúngicos/uso terapéutico , Catéteres Venosos Centrales , Manejo de la Enfermedad , Equinocandinas/uso terapéutico , Humanos
7.
Ann Hematol ; 96(11): 1775-1792, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28856437

RESUMEN

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.


Asunto(s)
Enfermedades Transmisibles/diagnóstico , Fiebre de Origen Desconocido/diagnóstico , Hematología/normas , Oncología Médica/normas , Neutropenia/diagnóstico , Guías de Práctica Clínica como Asunto/normas , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/terapia , Fiebre de Origen Desconocido/epidemiología , Fiebre de Origen Desconocido/terapia , Alemania/epidemiología , Hematología/métodos , Humanos , Oncología Médica/métodos , Neutropenia/epidemiología , Neutropenia/terapia , Sociedades Médicas/normas
8.
Eur Radiol ; 27(8): 3275-3282, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28083695

RESUMEN

BACKGROUND: Serial chest CT is the standard of care to establish treatment success in invasive pulmonary aspergillosis (IPA). Data are lacking how response should be defined. METHODS: Digital CT images from a clinical trial on treatment of IPA were re-evaluated and compared with available biomarkers. Total volume of pneumonia was added up after manual measurement of each lesion, followed by statistical analysis. RESULTS: One-hundred and ninety CT scans and 309 follow-up datasets from 40 patients were available for analysis. Thirty-one were neutropenic. Baseline galactomannan (OR 4.06, 95%CI: 1.08-15.31) and lesion volume (OR 3.14, 95%CI: 0.73-13.52) were predictive of death. Lesion volume at d7 and trend between d7 and d14 were strong predictors of death (OR 20.01, 95%CI: 1.42-282.00 and OR 15.97, 95%CI: 1.62-157.32) and treatment being rated as unsuccessful (OR 4.75, 95%CI: 0.94-24.05 and OR 40.69, 95%CI: 2.55-649.03), which was confirmed by a Cox proportional hazards model using time-dependent covariates. CONCLUSION: Any increase in CT lesion volume between day 7 and day 14 was a sensitive marker of a lethal outcome (>50%), supporting a CT rescan each one and 2 weeks after initial detection of IPA. The predictive value exceeded all other biomarkers. Further CT follow-up after response at day 14 was of low additional value. KEY POINTS: • CT evaluation offers good prediction of outcome for invasive pulmonary aspergillosis. • Predictive capability exceeds galactomannan, blood counts, and lesion count. • Any progression between day 7 and day 14 constitutes a high-risk scenario.


Asunto(s)
Aspergilosis Pulmonar Invasiva/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Galactosa/análogos & derivados , Humanos , Interpretación de Imagen Asistida por Computador , Aspergilosis Pulmonar Invasiva/mortalidad , Masculino , Mananos/metabolismo , Persona de Mediana Edad , Neumonía/diagnóstico por imagen , Valor Predictivo de las Pruebas , Análisis de Supervivencia , Tomografía Computarizada por Rayos X/estadística & datos numéricos
9.
J Antimicrob Chemother ; 71(4): 913-5, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26668235

RESUMEN

BACKGROUND: 1,3-ß-D-Glucan (BDG) is a fungal cell wall constituent used in the diagnosis of invasive fungal infections. BDG testing, although endorsed by the European Organization for Research and Treatment of Cancer, suffers from limited specificity. False-positive results have been linked to haemodialysis membranes, blood products, antineoplastic agents and antimicrobial use. OBJECTIVES: The aim of this study was to determine whether false-positive BDG results in the context of antimicrobial use are caused by BDG present in infusion solutions. METHODS: We obtained 35 antimicrobial drugs (30 antibiotics and 5 antifungals) and analysed their BDG content using two different assays. RESULTS: Twenty-five antimicrobials (20 antibiotics and all the tested antifungals) contained enough BDG to trigger a positive test. Depending on the substance, BDG varied between 9 and 2818 pg/mL. CONCLUSIONS: A majority of the available antimicrobial substances contained BDG, potentially limiting the utility of BDG testing in the context of prior exposure to these drugs. As the cumulative effects of repeated BDG exposure are unknown, efforts to reduce contamination should be considered.


Asunto(s)
Antiinfecciosos/análisis , beta-Glucanos/análisis , Antibacterianos/análisis , Antifúngicos/análisis , Contaminación de Medicamentos , Reacciones Falso Positivas , Inmunoensayo , Infusiones Intravenosas , Prueba de Limulus , Soluciones Farmacéuticas/análisis , Proteoglicanos
10.
J Antimicrob Chemother ; 71(1): 213-9, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26433782

RESUMEN

OBJECTIVES: The aim of this study was to evaluate the susceptibilities of Clostridium difficile isolates to cadazolid, a novel antibiotic for the treatment of C. difficile infection. METHODS: Ribotyping and susceptibilities were determined for C. difficile isolates from a multicentre, double-blind, Phase 2 study of oral cadazolid in patients with C. difficile infection (NCT01222702, ClinicalTrials.gov; EudraCT 2010-020941-29, European Clinical Trials Database). Patients were randomized to receive 250, 500 or 1000 mg of cadazolid twice daily or 125 mg of vancomycin four times daily, for 10 days. MICs of cadazolid, vancomycin, fidaxomicin, linezolid and moxifloxacin were determined at baseline for all patients and post-baseline for patients with clinical failure or recurrence, using the agar dilution method. RESULTS: Seventy-eight of 84 patients had an evaluable toxigenic C. difficile isolate at baseline. The most frequent PCR ribotype was 027 (15.4%). Cadazolid MICs for baseline isolates (including epidemic strain 027) ranged from 0.06 to 0.25 mg/L. Baseline cadazolid MICs were similar to those of fidaxomicin and lower than those of vancomycin, linezolid and moxifloxacin. For each clinical outcome group (clinical cure, clinical failure, sustained clinical response and clinical failure or recurrence), the baseline cadazolid MIC range was 0.06-0.25 mg/L. Mean (min-max) cadazolid faecal concentration (µg/g) on day 5 was 884 (101-2710), 1706 (204-4230) and 3226 (1481-12 600) for the doses 250, 500 and 1000 mg, respectively. CONCLUSIONS: For all cadazolid doses, the faecal concentration was in excess of several thousand-fold the MIC90 for C. difficile. The MIC of cadazolid for all C. difficile isolates, including epidemic strains, was low and in the same narrow range regardless of treatment outcome.


Asunto(s)
Antibacterianos/administración & dosificación , Clostridioides difficile/efectos de los fármacos , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/microbiología , Oxazolidinonas/administración & dosificación , Vancomicina/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Clostridioides difficile/clasificación , Clostridioides difficile/genética , Clostridioides difficile/aislamiento & purificación , Método Doble Ciego , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Oxazolidinonas/farmacología , Ribotipificación , Vancomicina/farmacología , Adulto Joven
11.
Med Mycol ; 54(6): 576-83, 2016 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-26941254

RESUMEN

UNLABELLED: Aspergillus spp.-related morbidity and mortality remains a major challenge in the management of neutropenic patients. Little is known about the impact of domestic Aspergillus spp. EXPOSURE: In this controlled prospective study, fungal spores were collected from homes of neutropenic patients. Cases were defined as patients with probable or proven controls as patients with no invasive pulmonary aspergillosis, while patients with possible disease were evaluated as a third group. Forty patients were enrolled and returned questionnaires on high-risk activities and mould exposure. A. fumigatus was detected in concentrations of 0 to 76 cfu/m(3) in every home. A. terreus was detected in nine (18%) homes. Mean Aspergillus spp. cfu/m(3) according to EORTC criteria were: proven/probable IA (15 patients) - 36; possible IA (12 patients) - 42; no IA (13 patients) - 42. Of the seven patients with self-reported moulded walls at home, four had probable and three had possible aspergillosis; the risk ratio of developing IA was 1.65 (95% CI: 1.25-2.17). In conclusion self-reported domestic mould exposure was associated with a high incidence of IA and may be a feasible tool for identifying high-risk patients. There was no correlation between domestic ambient-air spore counts and IA.


Asunto(s)
Microbiología del Aire , Aspergillus/aislamiento & purificación , Exposición a Riesgos Ambientales , Enfermedades Hematológicas/complicaciones , Aspergilosis Pulmonar Invasiva/epidemiología , Aspergilosis Pulmonar Invasiva/etiología , Esporas Fúngicas/aislamiento & purificación , Adulto , Anciano , Estudios de Casos y Controles , Recuento de Colonia Microbiana , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Encuestas y Cuestionarios , Adulto Joven
12.
Mycoses ; 59(1): 39-42, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26576502

RESUMEN

1,3-ß-D-glucan (BDG) is increasingly used to diagnose invasive fungal infections (IFI), although false positive results are a concern. To evaluate the potential interaction of blood products with the BDG assay, human albumin (HA), fresh frozen plasma (FFP), undiluted platelet transfusion (UPT) and packed red blood cells (PRBC) were tested for their BDG content using two different b-D-glucan tests. UPTs tested negative, FFP, PBRC and HA tested positive for BDG. In serial dilution, BDG concentration correlated with blood product concentration. To investigate the clinical impact of blood product transfusions, we measured BDG levels before and after the transfusion in three patients (2 PRBC, 1 HA). In the patients receiving PRBC transfusions, BDG values increased from 13 and 17 pg ml(-1) to 183 and 361 pg ml(-1), the HA transfusion increased the serum level from 42 to 58 pg ml(-1). BDG concentrations measured in blood products can be used to predict false positive BDG results.


Asunto(s)
Transfusión de Componentes Sanguíneos , Plaquetas/química , Eritrocitos/química , Plasma/química , Albúmina Sérica/química , beta-Glucanos/análisis , Reacciones Falso Positivas , Humanos , Micosis/diagnóstico
13.
J Antimicrob Chemother ; 70(5): 1522-6, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25630644

RESUMEN

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.


Asunto(s)
Antifúngicos/farmacología , Aspergillus fumigatus/efectos de los fármacos , Azoles/farmacología , Farmacorresistencia Fúngica , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Aspergilosis Pulmonar Invasiva/epidemiología , Adulto , Anciano , Sustitución de Aminoácidos , Aspergillus fumigatus/clasificación , Aspergillus fumigatus/genética , Aspergillus fumigatus/aislamiento & purificación , Sistema Enzimático del Citocromo P-450/genética , Femenino , Proteínas Fúngicas/genética , Genotipo , Alemania/epidemiología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Repeticiones de Microsatélite , Persona de Mediana Edad , Tipificación Molecular , Proteínas Mutantes/genética , Técnicas de Tipificación Micológica , Análisis de Secuencia de ADN
14.
Eur J Clin Microbiol Infect Dis ; 34(2): 331-8, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25213718

RESUMEN

Direct treatment costs caused by candidemia in German intensive care unit (ICU) patients are currently unknown. We analyzed treatment costs and the impact of antifungal drug choice. Comprehensive data of patients who had at least one episode of candidemia while staying in the ICU between 01/2005 and 12/2010 were documented in a database using the technology of the Cologne Cohort of Neutropenic Patients (CoCoNut). A detailed analysis of all disease-associated treatment costs was performed. Patients treated with echinocandins (i.e., anidulafungin, caspofungin, micafungin) or fluconazole were analyzed separately and compared. Forty-one and 64 patients received echinocandins and fluconazole, respectively. The mean Acute Physiology and Chronic Health Evaluation (APACHE) IV score was 114 (95 % confidence interval [CI]: 106-122) vs. 95 (95 % CI: 90-101, p = <0.001). Twenty-three (56 %) and 33 (52 %, p = 0.448) patients survived hospitalization, while 17 (41 %) and 22 (34 %, p = 0.574) survived one year after diagnosis. In the echinocandin and fluconazole groups, the mean costs per patient of ICU treatment were 20,338 (95 % CI: 12,893-27,883) vs. 11,932 (95 % CI: 8,016-15,849, p = 0.110), and the total direct treatment costs per patient were 37,995 (95 % CI: 26,614-49,376) vs. 22,305 (95 % CI: 16,817-27,793, p = 0.012), resulting in daily costs per patient of 1,158 (95 % CI: 1,036-1,280) vs. 927 (95 % CI: 828-1,026, p = 0.001). Our health economic analysis shows the high treatment costs of patients with candidemia in the ICU. Sicker patients had a prolonged hospitalization and were more likely to receive echinocandins, leading to higher treatment costs. Outcomes were comparable to those achieved in less sick patients with fluconazole.


Asunto(s)
Antifúngicos/uso terapéutico , Candidemia/tratamiento farmacológico , Equinocandinas/uso terapéutico , Fluconazol/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anidulafungina , Candidemia/economía , Caspofungina , Niño , Preescolar , Femenino , Costos de la Atención en Salud , Hospitalización/economía , Humanos , Lactante , Unidades de Cuidados Intensivos , Lipopéptidos/uso terapéutico , Masculino , Micafungina , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
15.
Infection ; 43(6): 707-14, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26123227

RESUMEN

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.


Asunto(s)
Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/economía , Costo de Enfermedad , Diarrea/economía , Adulto , Anciano , Anciano de 80 o más Años , Infecciones por Clostridium/epidemiología , Infecciones por Clostridium/microbiología , Diarrea/epidemiología , Diarrea/microbiología , Femenino , Alemania/epidemiología , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Centros de Atención Terciaria , Adulto Joven
16.
Mycoses ; 58(8): 445-50, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26207423

RESUMEN

Candida glabrata is a pathogenic yeast with several unique biological features. This article provides an up-to-date review on current data and reasoning aspects of this clinically problematic organism. Haploidy, absence of pseudohyphae, facultative anaerobe growth of C. glabrata, as well as its intrinsically low susceptibility to azole antifungals require specific consideration in diagnosis and treatment approaches. As C. glabrata today represents a sizeable percentage of pathogens in candidaemia, the use of azole antifungals in upfront therapy of invasive yeast infections is discouraged by recent guidelines. While the selection of C. glabrata mutants with impaired susceptibility to echinocandins has been described, analyses of several clinical studies indicate an association of improved outcomes with the use of echinocandins as the primary treatment for invasive yeast infections with potential or documented involvement of C. glabrata.


Asunto(s)
Antifúngicos/uso terapéutico , Candida glabrata/patogenicidad , Candidiasis Invasiva/tratamiento farmacológico , Azoles/uso terapéutico , Candida glabrata/efectos de los fármacos , Candida glabrata/genética , Candida glabrata/fisiología , Candidiasis Invasiva/diagnóstico , Candidiasis Invasiva/epidemiología , Candidiasis Invasiva/microbiología , Farmacorresistencia Fúngica , Equinocandinas/uso terapéutico , Humanos , Pruebas de Sensibilidad Microbiana , Mutación
17.
Mycoses ; 58 Suppl 1: 1-15, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25711406

RESUMEN

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.


Asunto(s)
Antifúngicos/administración & dosificación , Candida albicans/efectos de los fármacos , Candidiasis Vulvovaginal/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/diagnóstico , Antifúngicos/uso terapéutico , Candida glabrata/efectos de los fármacos , Candidiasis Vulvovaginal/diagnóstico , Candidiasis Vulvovaginal/microbiología , Femenino , Alemania , Humanos , Recién Nacido , Pruebas de Sensibilidad Microbiana , Microscopía de Contraste de Fase , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/microbiología , Excreción Vaginal
18.
Mycoses ; 58(6): 375-82, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25808916

RESUMEN

At the University Hospital of Cologne, in general two patient groups at high risk for invasive aspergillosis receive posaconazole prophylaxis: Acute myelogenous leukaemia patients during remission induction chemotherapy and allogeneic haematopoietic stem cell transplant recipients. Other patients at risk undergo serum galactomannan testing three times weekly. At 72-96 h of persisting fever despite broad-spectrum antibiotics, or at onset of lower respiratory tract symptoms a thoracic computed tomography (CT) scan is performed. Without lung infiltrates on CT, IPA is ruled out. In lung infiltrates not suggestive for IPA mycological confirmation is pursued. In patients without posaconazole prophylaxis empiric caspofungin will be considered. CT findings typical for IPA prompt targeted treatment, and mycological confirmation. Bronchoalveolar lavage (BAL) is most important for cultural identification and susceptibility testing, and facilitates diagnosing other pathogens. BAL performance is virtually independent of platelet counts. If despite suggestive infiltrates BAL does not yield the diagnosis, CT-guided biopsy follows as soon as platelet counts allow. Surgery can also be beneficial in diagnosis and treatment of IPA. If the diagnosis of IPA is not established, mucormycosis is a valid concern. In patients with breakthrough IPA during posaconazole prophylaxis liposomal amphotericin B is the drug of choice. If no posaconazole prophylaxis was given, voriconazole is the treatment of choice for IPA.


Asunto(s)
Antifúngicos/administración & dosificación , Quimioprevención/métodos , Aspergilosis Pulmonar Invasiva/diagnóstico , Aspergilosis Pulmonar Invasiva/prevención & control , Mananos/análisis , Triazoles/administración & dosificación , Aspergillus/aislamiento & purificación , Líquido del Lavado Bronquioalveolar/microbiología , Fiebre de Origen Desconocido/diagnóstico , Francia , Galactosa/análogos & derivados , Hospitales Universitarios , Humanos , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Radiografía Torácica , Tomografía Computarizada por Rayos X
19.
Mycoses ; 58(12): 735-45, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26497302

RESUMEN

The increasing incidence of invasive fungal diseases (IFD), most of all invasive aspergillosis (IA) in immunocompromised patients emphasises the need to improve the diagnostic tools for detection of fungal pathogens. We investigated the diagnostic performance of a multifungal DNA-microarray detecting 15 different fungi [Aspergillus, Candida, Fusarium, Mucor, Rhizopus, Scedosporium and Trichosporon species (spp.)] in addition to an Aspergillus specific polymerase chain reaction (PCR) assay. Biopsies, bronchoalveolar lavage and peripheral blood samples of 133 immunocompromised patients (pts) were investigated by a multifungal DNA-microarray as well as a nested Aspergillus specific PCR assay. Patients had proven (n = 18), probable (n = 29), possible (n = 48) and no IFD (n = 38) and were mostly under antifungal therapy at the time of sampling. The results were compared to culture, histopathology, imaging and serology, respectively. For the non-Aspergillus IFD the microarray analysis yielded in all samples a sensitivity of 64% and a specificity of 80%. Best results for the detection of all IFD were achieved by combining DNA-microarray and Aspergillus specific PCR in biopsy samples (sensitivity 79%; specificity 71%). The molecular assays in combination identify genomic DNA of fungal pathogens and may improve identification of causative pathogens of IFD and help overcoming the diagnostic uncertainty of culture and/or histopathology findings, even during antifungal therapy.


Asunto(s)
Aspergilosis/diagnóstico , Aspergillus fumigatus/aislamiento & purificación , Reacción en Cadena de la Polimerasa Multiplex/métodos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Adulto , Antifúngicos/uso terapéutico , Aspergilosis/sangre , Aspergilosis/diagnóstico por imagen , Aspergillus fumigatus/genética , Aspergillus fumigatus/inmunología , Secuencia de Bases , Biopsia con Aguja , Lavado Broncoalveolar , ADN de Hongos/aislamiento & purificación , Femenino , Humanos , Huésped Inmunocomprometido , Masculino , Datos de Secuencia Molecular , Radiografía , Sensibilidad y Especificidad
20.
Internist (Berl) ; 56(11): 1271-6, 2015 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-26432089

RESUMEN

Particularly in the area of hematology/oncology and intensive care medicine, infections due to resistant fungi are to be expected. Emergence of resistance in fungi is a less dynamic process than in bacteria; it can, however, have an equally important impact on treatment strategies. In the following article, the most important resistance patterns of yeasts and molds (Candida albicans , Aspergillus fumigatus, the order Mucorales and the genus Fusarium) will be presented and discussed. Their diagnosis mostly being based on blood cultures, resistance testing for yeasts is usually readily available. Culture-based therapeutic adjustments in mold infections are, however, only rarely possible, as most antifungal therapies for these infections are initiated on an empirical basis after identification of typical infiltrates on a CT scan. Response to therapy is then evaluated on the basis of clinical signs and symptoms in combination with follow-up CT scans. In case of therapeutic failure or appearance of suspicious infiltrates under antifungal prophylaxis, an open or CT-guided biopsy is recommended to allow efficient adaptation of antifungal treatment. In individual cases, particularly in patients diagnosed with mucormycosis, resection of the focus of infection may be necessary to achieve a satisfactory treatment response.


Asunto(s)
Antifúngicos/administración & dosificación , Farmacorresistencia Fúngica/efectos de los fármacos , Hongos/clasificación , Hongos/aislamiento & purificación , Micosis/diagnóstico , Micosis/terapia , Terapia Combinada/métodos , Diagnóstico Diferencial , Humanos , Micosis/microbiología
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