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1.
Clin Microbiol Infect ; 25(10): 1200-1212, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31039444

RESUMO

OBJECTIVES: Candidaemia is a serious hazard to hospitalized patients, but European epidemiological data are restricted to national studies focusing on Northern Europe, population-based surveillance programmes or studies conducted in distinct local areas. The aim was to provide current data on the overall burden and epidemiological development of candidaemia in Europe. METHODS: A Web of Knowledge™ search was carried out from January 2000 to February 2019. Appropriate data were collected on total cases, study duration, incidence, species distribution and/or mortality rates. Meta-analysis was performed to pool individual studies. Heterogeneity was examined using the I2 statistic. Calculations of pooled incidence and mortality rates, subgroup analysis by geographical origin, study period and scenarios were carried out. Daily candidaemia incidence and mortality rates in Europe were extrapolated. Systematic review and meta-analysis were used to determine incidence and mortality of candidaemia in the UN European region. Complete datasets were categorized into population-based and hospital-based epidemiological studies and were analysed separately. Subgroup analyses were performed for geographic distributions and time-dependent developments. RESULTS: In population-based studies, 43 799 cases of candidaemia were diagnosed in 1 885 271 885 person-years, revealing an overall pooled incidence rate of 3.88/100 000. The highest pooled incidence rate was observed in intensive care units (5.5/1000 admissions, Day 30 mortality rate 37%), followed by tertiary care centres (0.96/1000 admissions, pooled Day 30 mortality rate 38%) and the mixed group of teaching and general hospitals (0.52/1000 admissions, pooled Day 30 mortality rate 37%). European incidence of candidaemia was extrapolated to approximately 79 cases per day, of which an estimated 29 patients might have fatal outcome at Day 30. CONCLUSIONS: Pooled incidence rates, species distribution and outcome of candidaemia differ considerably between clinical groups, European regions and over time. We observed an increasing overall pooled incidence rate of candidaemia and a higher proportion of Candida spp. other than C. albicans in the current decade in population-based data.


Assuntos
Candida/classificação , Candida/isolamento & purificação , Candidemia/epidemiologia , Candidemia/mortalidade , Europa (Continente)/epidemiologia , Humanos , Incidência , Análise de Sobrevida
2.
Internist (Berl) ; 60(7): 684-689, 2019 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-31119309

RESUMO

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.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose , Mucormicose , Micoses/tratamento farmacológico , Infecções Oportunistas , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Humanos , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Micoses/diagnóstico , Neutropenia
3.
Clin Microbiol Infect ; 25(8): 1013-1020, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30641228

RESUMO

OBJECTIVES: Colonization and infection with third-generation cephalosporin-resistant Escherichia coli (3GCR-EC) are frequent in haematological and oncological patients. In this high-risk setting, German guidelines recommend single-room contact precautions (SCP) for patients with 3GCR-EC that are non-susceptible to fluoroquinolones (F3GCR-EC). However, this recommendation is controversial, as evidence is limited. METHODS: We performed a prospective, multicentre cohort study at four haematology and oncology departments assessing the impact of SCP on hospital-acquired colonization or bloodstream infection (BSI) with F3GCR-EC. Two sites performed SCP for F3GCR-EC patients including single rooms, gloves and gowns (SCP sites), and two did not (NCP sites). Active screening for 3GCR-EC was performed and isolates were characterized with molecular typing methods including whole genome sequencing and core genome multiple locus sequence typing to assess patient-to-patient transmission. Potential confounders were assessed by competing-risk regression analysis. RESULTS: Within 12 months, 1386 patients at NCP sites and 1582 patients at SCP sites were included. Hospital-acquisition of F3GCR-EC was observed in 22/1386 (1.59%) and 16/1582 (1.01%) patients, respectively (p 0.191). There were 3/1386 (0.22%) patients with BSI caused by F3GCR-EC at NCP sites and 4/1582 (0.25%) at SCP sites (p 1.000). Patient-to-patient transmission occurred in three cases at NCP and SCP sites each (p 1.000). The number of patients needed to screen in order to prevent one patient-to-patient transmission of F3GCR-EC was determined to be 3729. CONCLUSIONS: Use of SCP had no significant impact on hospital-acquisition or patient-to-patient transmission of F3GCR-EC in this high-risk setting.


Assuntos
Infecção Hospitalar/prevenção & controle , Infecções por Escherichia coli/prevenção & controle , Controle de Infecções/métodos , Precauções Universais , Adulto , Idoso , Bacteriemia/prevenção & controle , Bacteriemia/transmissão , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla , Escherichia coli/isolamento & purificação , Feminino , Luvas Protetoras , Hematologia , Unidades Hospitalares/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Serviço Hospitalar de Oncologia , Estudos Prospectivos
4.
J Hosp Infect ; 101(3): 339-346, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30423409

RESUMO

BACKGROUND: Invasive mucormycosis (IM) is a rare invasive fungal infection with a high mortality rate. However, data concerning the clinical and economic burden of IM are scarce. AIM: To evaluate the direct treatment costs and additional expenditures of patients with IM. METHODS: A retrospective cost-of-illness analysis of cases with IM extracted from FungiScope - Global Registry for Emerging Fungal Infections, accessible through the epidemiological research platform www.ClinicalSurveys.net, was undertaken. Results of patients with IM were compared with those of matched patients with similar underlying conditions based on the German Diagnosis Related Group (G-DRG) coding. FINDINGS: Out of 46 patients with probable/proven IM, 31 (67%) patients were male and the median age was 53 years (range 11-88 years). Forty-two patients (92%) had haematological diseases as the most common risk factor. Analysis of cost factors identified antifungal treatment due to IM as the primary cost driver [€22,816, 95% confidence interval (CI) €15,036-32,346], with mean overall direct treatment costs of €53,261 (95% CI €39,660-68,825). Compared with matched patients, patients with IM were treated in hospital for 26.5 additional days (standard deviation 31.8 days; P < 0.001), resulting in mean additional costs of €32,991 (95% CI €21,558-46,613; P < 0.001). Probable IM, as well as absence of chemotherapy, surgical measures due to IM, and antifungal prophylaxis were associated with lower overall costs. Nineteen patients (41.3%) died during hospitalization. CONCLUSION: This study demonstrates the considerable healthcare burden of IM. The choice of antifungal agent for treatment of IM had no impact on overall cost.


Assuntos
Efeitos Psicossociais da Doença , Infecções Fúngicas Invasivas/economia , Infecções Fúngicas Invasivas/epidemiologia , Mucormicose/economia , Mucormicose/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/economia , Antifúngicos/uso terapêutico , Criança , Feminino , Hospitalização/economia , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mucormicose/tratamento farmacológico , Estudos Retrospectivos , Centros de Atenção Terciária , Adulto Jovem
5.
J Infect Chemother ; 25(4): 298-301, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30482700

RESUMO

Raoultella planticola is a gram-negative, encapsulated, aerobic bacterium within the Enterobacteriaceae family. It has been primarily described as pathogen in cases with pneumonia and gastrointestinal infections. Here we describe a case of severe pelvic cellulitis in a patient with neutropenia following induction therapy for myeloid sarcoma. The patient experienced a septic shock and was treated successfully with antibiotic therapy. A literature review is provided to put this case in context with previous reports on R. planticola. This report highlights that awareness for uncommon pathogens is crucial in the clinical management of infections in neutropenic patients.


Assuntos
Antibacterianos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Celulite (Flegmão)/microbiologia , Neutropenia Febril Induzida por Quimioterapia/complicações , Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/isolamento & purificação , Adulto , Celulite (Flegmão)/complicações , Celulite (Flegmão)/diagnóstico , Celulite (Flegmão)/tratamento farmacológico , Neutropenia Febril Induzida por Quimioterapia/diagnóstico , Neutropenia Febril Induzida por Quimioterapia/etiologia , Infecções por Enterobacteriaceae/complicações , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/tratamento farmacológico , Humanos , Imagem por Ressonância Magnética , Masculino , Pelve/diagnóstico por imagem , Sarcoma Mieloide/tratamento farmacológico , Resultado do Tratamento
6.
Clin Microbiol Infect ; 25(2): 253.e1-253.e4, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30315957

RESUMO

OBJECTIVES: In Germany, previous reports have demonstrated transmitted human immunodeficiency virus type 1 (HIV-1) drug-resistance mutations (DRM) in 11% of newly diagnosed individuals, highlighting the importance of drug-resistance screening before the initiation of antiretroviral therapy (ART). Here, we sought to understand the molecular epidemiology of HIV DRM transmission in the Cologne-Bonn region of Germany, given one of the highest rates of new HIV diagnoses in western Europe (13.7 per 100 000 habitants). METHODS: We analysed 714 HIV-1 ART-naive infected individuals diagnosed at the University Hospitals Cologne and Bonn between 2001 and 2016. Screening for DRM was performed according to the Stanford University Genotypic Resistance Interpretation. Shared DRM were defined as any DRM present in genetically linked individuals (<1.5% genetic distance). Phylogenetic and network analyses were performed to infer putative relationships and shared DRM. RESULTS: The prevalence of any DRM at time of diagnosis was 17.2% (123/714 participants). Genetic transmission network analyses showed comparable frequencies of DRM in clustering versus non-clustering individuals (17.1% (85/497) versus 17.5% (38/217)). The observed rate of DRM in the region was higher than previous reports 10.8% (87/809) (p < 0.001), revealing the need to reduce onward transmission in this area. Genetically linked individuals harbouring shared DRM were more likely to live in suburban areas (24/38) than in central Cologne (1/38) (p < 0.001). CONCLUSION: The rate of DRM was exceptionally high. Network analysis elucidated frequent cases of shared DRM among genetically linked individuals, revealing the potential spread of DRM and the need to prevent onward transmission of DRM in the Cologne-Bonn area.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Adulto , Feminino , Alemanha/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade
7.
Bone Marrow Transplant ; 53(1): 52-57, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29131156

RESUMO

Recent data link the incidence of intestinal GvHD (iGvHD) after allogeneic haematopoietic stem cell transplantation (aSCT) to exposure with piperacillin-tazobactam or imipenem-cilastatin. To assess relevance of timing, duration, sequence and combination of antibiotic treatment in this setting, we applied a time-dependent model to our aSCT cohort. Patients from the prospective Cologne Cohort of Neutropenic Patients (CoCoNut) undergoing aSCT from January 2007 to April 2013 were included into a time-dependent multivariate Cox proportional hazards regression model with backward-stepwise selection. In 399 eligible patients, cumulative antibiotic exposure (hazard ratio (HR) 2.46; 95% confidence interval (95% CI) 1.59-3.81; P<0.001) and exposure to sequential treatment with penicillin derivatives and carbapenems (HR 6.22, 95% CI 1.27-30.31), but not to the individual classes, were associated with iGvHD at day 100. Glycopeptides were assessed as a risk factor (HR 3.73, 95% CI 1.51-9.19), but not considered independent, since their use was dependent on previous exposure to penicillin derivatives and carbapenems. Patients with iGvHD presented with increased non-relapse mortality at day 365 (HR 3.51; 95% CI 2.10-5.89; P<0.001). We identified sequential exposure to penicillin derivatives and carbapenems as well as overall exposure to antibiotics as independent risk factors for iGVHD. Confirmation of these findings in larger, prospective cohorts is necessary.


Assuntos
Antibacterianos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
8.
Ann Hematol ; 97(1): 31-49, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29177551

RESUMO

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.


Assuntos
Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Gastroenteropatias/terapia , Neoplasias/complicações , Adulto , Doenças Transmissíveis/terapia , Alemanha , Hematologia/organização & administração , Hematologia/normas , Humanos , Oncologia/organização & administração , Oncologia/normas , Neoplasias/diagnóstico , Neoplasias/terapia , Guias de Prática Clínica como Assunto , Sociedades Médicas/organização & administração , Sociedades Médicas/normas
9.
Ann Hematol ; 96(11): 1775-1792, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28856437

RESUMO

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.


Assuntos
Doenças Transmissíveis/diagnóstico , Febre de Causa Desconhecida/diagnóstico , Hematologia/normas , Oncologia/normas , Neutropenia/diagnóstico , Guias de Prática Clínica como Assunto/normas , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/terapia , Febre de Causa Desconhecida/epidemiologia , Febre de Causa Desconhecida/terapia , Alemanha/epidemiologia , Hematologia/métodos , Humanos , Oncologia/métodos , Neutropenia/epidemiologia , Neutropenia/terapia , Sociedades Médicas/normas
10.
Clin Microbiol Infect ; 23(10): 776.e1-776.e5, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28412383

RESUMO

OBJECTIVES: A prospective international multicentre surveillance study was conducted to investigate the prevalence and amphotericin B susceptibility of Aspergillus terreus species complex infections. METHODS: A total of 370 cases from 21 countries were evaluated. RESULTS: The overall prevalence of A. terreus species complex among the investigated patients with mould-positive cultures was 5.2% (370/7116). Amphotericin B MICs ranged from 0.125 to 32 mg/L, (median 8 mg/L). CONCLUSIONS: Aspergillus terreus species complex infections cause a wide spectrum of aspergillosis and the majority of cryptic species display high amphotericin B MICs.


Assuntos
Aspergilose/epidemiologia , Aspergilose/microbiologia , Aspergillus/classificação , Aspergillus/isolamento & purificação , Anfotericina B/farmacologia , Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Monitoramento Epidemiológico , Europa (Continente)/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Prevalência , Estudos Prospectivos
11.
Eur Radiol ; 27(8): 3275-3282, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28083695

RESUMO

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.


Assuntos
Aspergilose Pulmonar Invasiva/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Aspergilose Pulmonar Invasiva/mortalidade , Masculino , Mananas/metabolismo , Pessoa de Meia-Idade , Pneumonia/diagnóstico por imagem , Valor Preditivo dos Testes , Análise de Sobrevida , Tomografia Computadorizada por Raios X/estatística & dados numéricos
12.
Epidemiol Infect ; 145(2): 236-244, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27780480

RESUMO

Measles, mumps, rubella (MMR) and varicella zoster virus (VZV) infection can cause serious diseases and complications in the HIV-positive population. Due to successful vaccination programmes measles, mumps and congenital rubella syndrome has become neglected in Germany. However, recent outbreaks of measles have occurred from import-associated cases. In this cross-sectional study the serostatus for MMR and VZV in 2013 HIV-positive adults from three different university outpatient clinics in Bonn (n = 544), Cologne (n = 995) and Munich (n = 474) was analysed. Sera were tested for MMR- and VZV-specific immunglobulin G antibodies using commercial immunoassays. Seronegativity was found in 3% for measles, 26% for mumps, 11% for rubella and 2% for VZV. Regarding MMR, 35% of patients lacked seropositivity against at least one infectious agent. In multivariable analysis younger age was strongly associated with seronegativity against all four viruses, measles, mumps, rubella (P < 0·001, P < 0·001 and P = 0·001, respectively) and VZV (P = 0·001). In conclusion, there is high need for MMR and VZV vaccination in people living with HIV in Germany born in 1970 or later. Thus, systematic MMR and VZV antibody screening and vaccination should be implemented in the HIV-positive population to prevent serious disease and complications of vaccine-preventable diseases.


Assuntos
Anticorpos Antivirais/sangue , Varicela/imunologia , Suscetibilidade a Doenças , Infecções por HIV/complicações , Sarampo/imunologia , Caxumba/imunologia , Rubéola (Sarampo Alemão)/imunologia , Adulto , Estudos Transversais , Feminino , Alemanha/epidemiologia , Humanos , Imunoensaio , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos
13.
Clin Microbiol Infect ; 22(10): 862-868, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27393123

RESUMO

High mortality rates of invasive fungal disease (IFD), especially invasive aspergillosis (IA), in immunocompromised haematological patients and current diagnostic limitations require improvement of detection of fungal pathogens by defining the optimal use of biomarkers and clinical samples. Concurrent bronchoalveolar lavage (BAL) and peripheral blood samples of 99 haematological patients with suspected IFD were investigated within a multicentre prospective study. Diagnostic performance of a galactomannan (GM) enzyme immune assay (EIA), a 1,3-ß-D-glucan assay (BDG), an Aspergillus PCR, and a multifungal DNA-microarray (Chip) alone or in combination were calculated. IFD were classified as proven (n=3), probable (n=34), possible (n=33), and no IFD (n=29) according to EORTC/MSG criteria. GM, PCR, and Chip showed superior diagnostic performance in BAL than in blood, whereas specificity of BDG in BAL was poor (48% (14/29)). The combination of GM (BAL) with BDG (blood) showed sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and DOR (diagnostic odds ratio) of 92% (34/37), 93% (27/29), 94%, 90%, and 153.0, respectively. Combining GM (BAL) with PCR (BAL) showed convincing diagnostic potential for diagnosing IA with sensitivity, specificity, PPV, NPV, and DOR of 85% (17/20), 97% (28/29), 94%, 90%, and 158.7. Addition of the DNA-microarray resulted in further detection of two mucormycetes infections. In 1 out of 15 Aspergillus DNA-positive samples a triazole resistance-mediating Cyp51A mutation was found. Combination of biomarkers is superior to their sole use in diagnosing IFD, particularly IA. Integrating blood and BAL samples into a diagnostic algorithm is an advantageous approach.


Assuntos
Aspergilose/diagnóstico , Líquido da Lavagem Broncoalveolar/microbiologia , Infecções Fúngicas Invasivas/diagnóstico , Técnicas Microbiológicas/métodos , Técnicas de Diagnóstico Molecular/métodos , Aspergilose/sangue , Aspergillus/efeitos dos fármacos , Aspergillus/genética , Azóis/farmacologia , Humanos , Infecções Fúngicas Invasivas/sangue , Mananas/análise , Reação em Cadeia da Polimerase Multiplex/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Estudos Prospectivos , Sensibilidade e Especificidade , beta-Glucanas/análise
14.
Med Mycol ; 54(6): 576-83, 2016 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-26941254

RESUMO

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.


Assuntos
Microbiologia do Ar , Aspergillus/isolamento & purificação , Exposição Ambiental , Doenças Hematológicas/complicações , Aspergilose Pulmonar Invasiva/epidemiologia , Aspergilose Pulmonar Invasiva/etiologia , Esporos Fúngicos/isolamento & purificação , Adulto , Idoso , Estudos de Casos e Controles , Contagem de Colônia Microbiana , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Inquéritos e Questionários , Adulto Jovem
15.
Mycoses ; 58(12): 735-45, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26497302

RESUMO

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.


Assuntos
Aspergilose/diagnóstico , Aspergillus fumigatus/isolamento & purificação , Reação em Cadeia da Polimerase Multiplex/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Adulto , Antifúngicos/uso terapêutico , Aspergilose/sangue , Aspergilose/diagnóstico por imagem , Aspergillus fumigatus/genética , Aspergillus fumigatus/imunologia , Sequência de Bases , Biópsia por Agulha , Lavagem Broncoalveolar , DNA Fúngico/isolamento & purificação , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Dados de Sequência Molecular , Radiografia , Sensibilidade e Especificidade
16.
Infection ; 43(6): 707-14, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26123227

RESUMO

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.


Assuntos
Infecções por Clostridium/economia , Clostridium difficile/isolamento & purificação , Efeitos Psicossociais da Doença , Diarreia/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/microbiologia , Diarreia/epidemiologia , Diarreia/microbiologia , Feminino , Alemanha/epidemiologia , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária , Adulto Jovem
17.
Mycoses ; 58(6): 375-82, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25808916

RESUMO

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.


Assuntos
Antifúngicos/administração & dosagem , Quimioprevenção/métodos , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/prevenção & controle , Mananas/análise , Triazóis/administração & dosagem , Aspergillus/isolamento & purificação , Líquido da Lavagem Broncoalveolar/microbiologia , Febre de Causa Desconhecida/diagnóstico , França , Hospitais Universitários , Humanos , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Testes de Sensibilidade Microbiana , Radiografia Torácica , Tomografia Computadorizada por Raios X
18.
Eur J Clin Microbiol Infect Dis ; 34(2): 331-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25213718

RESUMO

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.


Assuntos
Antifúngicos/uso terapêutico , Candidemia/tratamento farmacológico , Equinocandinas/uso terapêutico , Fluconazol/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anidulafungina , Candidemia/economia , Caspofungina , Criança , Pré-Escolar , Feminino , Custos de Cuidados de Saúde , Hospitalização/economia , Humanos , Lactente , Unidades de Terapia Intensiva , Lipopeptídeos/uso terapêutico , Masculino , Micafungina , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
19.
Transpl Infect Dis ; 16(6): 968-74, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25371351

RESUMO

INTRODUCTION: Treatment indications of new antifungals in clinical practice often deviate from the strict criteria used in controlled clinical trials. Under routine clinical conditions, beneficial and adverse effects, not previously described in clinical trials may be observed. The aim of this study was to describe customary prescription and treatment strategies of micafungin (MCFG). METHODS: A registry was set up on www.ClinicalSurveys.net and physicians were invited to provide retrospective information on cases they had treated with MCFG. Documentation comprised demographic information, underlying disease, effectiveness, safety, and tolerability of MCFG. RESULTS: A total of 125 episodes of patients hospitalized between September 2009 and February 2012 were documented, of which 7 had to be excluded because of incomplete documentation. The most common risk factors of patients were hematological malignancy (n = 116, 98.3%) and antibiotic treatment >3 days (n = 115, 97.5%). MCFG was administered as prophylaxis in 106 (89.9%) patients. Median duration of MCFG application as prophylaxis was 21 days (range: 3-78); 53 of the patients (50%) received a dose of 50 mg, while the other 53 (50%) received 100 mg/day. For the different doses, prophylactic outcome was rated as success in 42 (79.2%) vs. 52 (98.1%; P = 0.004) patients. Fifty-five patients (51.9%) were treated with posaconazole before initiation of MCFG. Four patients (7.5%) developed a proven invasive fungal disease (IFD) while being treated with 50 mg MCFG, compared to no patient treated with 100 mg (P = 0.118). At the end of MCFG prophylaxis, 24 (22.6%) patients were switched to fluconazole and 64 (60.3%) patients to posaconazole. CONCLUSION: Our study shows clinical effectiveness of MCFG prophylaxis with low rates of breakthrough fungal infections. In most cases, MCFG was part of a multi-modal antifungal prophylactic strategy. Investigators reported fewer proven IFDs in patients receiving therapeutic doses of MCFG as prophylaxis.


Assuntos
Equinocandinas/administração & dosagem , Equinocandinas/farmacologia , Lipopeptídeos/administração & dosagem , Lipopeptídeos/farmacologia , Micoses/prevenção & controle , Transplante de Células-Tronco/efeitos adversos , Adulto , Idoso , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Antifúngicos/farmacologia , Relação Dose-Resposta a Droga , Equinocandinas/efeitos adversos , Feminino , Alemanha , Hospitais Universitários , Humanos , Internet , Lipopeptídeos/efeitos adversos , Masculino , Micafungina , Pessoa de Meia-Idade , Micoses/etiologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
20.
Infection ; 42(5): 849-57, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24965613

RESUMO

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.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Competência Clínica , Fidelidade a Diretrizes , Infecções por HIV/tratamento farmacológico , Tempo para o Tratamento , Adulto , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Contagem de Linfócito CD4 , Quimioterapia Combinada , Feminino , Alemanha , HIV/imunologia , HIV/fisiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Masculino
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