Costs and resource utilization patterns in surgical site infections: a pre-COVID-19 perspective from France, Germany, Spain, and the UK.

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

COVID-19 in cancer patients: clinical characteristics and outcome-an analysis of the LEOSS registry.

INTRODUCTION: Since the early SARS-CoV-2 pandemic, cancer patients have been assumed to be at higher risk for severe COVID-19. Here, we present an analysis of cancer patients from the LEOSS (Lean European Open Survey on SARS-CoV-2 Infected Patients) registry to determine whether cancer patients are at higher risk. PATIENTS AND METHODS: We retrospectively analyzed a cohort of 435 cancer patients and 2636 non-cancer patients with confirmed SARS-CoV-2 infection, enrolled between March 16 and August 31, 2020. Data on socio-demographics, comorbidities, cancer-related features and infection course were collected. Age-, sex- and comorbidity-adjusted analysis was performed. Primary endpoint was COVID-19-related mortality. RESULTS: In total, 435 cancer patients were included in our analysis. Commonest age category was 76-85 years (36.5%), and 40.5% were female. Solid tumors were seen in 59% and lymphoma and leukemia in 17.5% and 11% of patients. Of these, 54% had an active malignancy, and 22% had recently received anti-cancer treatments. At detection of SARS-CoV-2, the majority (62.5%) presented with mild symptoms. Progression to severe COVID-19 was seen in 55% and ICU admission in 27.5%. COVID-19-related mortality rate was 22.5%. Male sex, advanced age, and active malignancy were associated with higher death rates. Comparing cancer and non-cancer patients, age distribution and comorbidity differed significantly, as did mortality (14% vs 22.5%, p value < 0.001). After adjustments for other risk factors, mortality was comparable. CONCLUSION: Comparing cancer and non-cancer patients, outcome of COVID-19 was comparable after adjusting for age, sex, and comorbidity. However, our results emphasize that cancer patients as a group are at higher risk due to advanced age and pre-existing conditions.

Treatment outcomes of integrase inhibitors, boosted protease inhibitors and nonnucleoside reverse transcriptase inhibitors in antiretroviral-naïve persons starting treatment.

OBJECTIVES: Although outcomes of antiretroviral therapy (ART) have been evaluated in randomized controlled trials, experiences from subpopulations defined by age, CD4 count or viral load (VL) in heterogeneous real-world settings are limited. METHODS: The study design was an international multicohort collaboration. Logistic regression was used to compare virological and immunological outcomes at 12 ± 3 months after starting ART with an integrase strand transfer inhibitor (INSTI), contemporary nonnucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI/b) with two nucleos(t)ides after 1 January 2012. The composite treatment outcome (cTO) defined success as VL < 200 HIV-1 RNA copies/mL with no regimen change and no AIDS/death events. Immunological success was defined as a CD4 count > 750 cells/µL or a 33% increase where the baseline CD4 count was ≥ 500 cells/µL. Poisson regression compared clinical failures (AIDS/death ≥ 14 days after starting ART). Interactions between ART class and age, CD4 count, and VL were determined for each endpoint. RESULTS: Of 5198 ART-naïve persons in the International Cohort Consortium of Infectious Diseases (RESPOND), 45.4% started INSTIs, 26.0% PI/b and 28.7% NNRTIs; 880 (17.4%) were aged > 50 years, 2539 (49.4%) had CD4 counts < 350 cells/µL and 1891 (36.8%) had VL > 100 000 copies/mL. Differences in virological and immunological success and clinical failure among ART classes were similar across age groups (≤ 40, 40-50 and > 50 years), CD4 count categories (≤ 350 vs. > 350 cells/µL) and VL categories at ART initiation (≤ 100 000 vs. > 100 000 copies/mL), with all investigated interactions being nonsignificant (P > 0.05). CONCLUSIONS: Differences among ART classes in virological, immunological and clinical outcomes in ART-naïve participants were consistent irrespective of age, immune suppression or VL at ART initiation. While confounding by indication cannot be excluded, this provides reassuring evidence that such subpopulations will equally benefit from contemporary ART.

[Fungal infections]. / Pilzinfektionen.

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.

Morbidity and mortality of candidaemia in Europe: an epidemiologic meta-analysis.

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.

Impact of single-room contact precautions on hospital-acquisition and transmission of multidrug-resistant Escherichia coli: a prospective multicentre cohort study in haematological and oncological wards.

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.

Pretreatment human immunodeficiency virus type 1 (HIV-1) drug resistance in transmission clusters of the Cologne-Bonn region, Germany.

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.

Pelvic cellulitis caused by Raoultella planticola in a neutropenic patient.

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.

Healthcare burden of probable and proven invasive mucormycosis: a multi-centre cost-of-illness analysis of patients treated in tertiary care hospitals between 2003 and 2016.

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.

Diagnosis and management of gastrointestinal complications in adult cancer patients: 2017 updated evidence-based guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).

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.

Impact of choice, timing, sequence and combination of broad-spectrum antibiotics on the outcome of allogeneic haematopoietic stem cell transplantation.

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.

Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).

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.

A prospective international Aspergillus terreus survey: an EFISG, ISHAM and ECMM joint study.

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.

Serial assessment of pulmonary lesion volume by computed tomography allows survival prediction in invasive pulmonary aspergillosis.

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.

Measles, mumps, rubella and VZV: importance of serological testing of vaccine-preventable diseases in young adults living with HIV in Germany.

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.

Diagnosis of invasive fungal infections in haematological patients by combined use of galactomannan, 1,3-ß-D-glucan, Aspergillus PCR, multifungal DNA-microarray, and Aspergillus azole resistance PCRs in blood and bronchoalveolar lavage samples: results of a prospective multicentre study.

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.

Domestic mould exposure and invasive aspergillosis-air sampling of Aspergillus spp. spores in homes of hematological patients, a pilot study.

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.

Identification of invasive fungal diseases in immunocompromised patients by combining an Aspergillus specific PCR with a multifungal DNA-microarray from primary clinical samples.

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.

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

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.

Our 2015 approach to invasive pulmonary aspergillosis.

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.