Wolfgang Poeppl

CCI-779 plus Cisplatin Is Highly Effective against Human Melanoma in a SCID Mouse Xenotranplantation Model

Background: This study set out to investigate the antitumor effects of a treatment strategy combining the mTOR inhibitor CCI-779 with cisplatin in vitro and in a human melanoma SCID mouse model. Methods: In vitro 518A2, Mel-JUSO or 607B cell lines were incubated with CCI-779, cisplatin and CCI-779 plus cisplatin. Based on these results, a 4-group, parallel, controlled experimental study design was initiated in vivo. SCID mice were injected with melanoma cells, and after the development of tumors the mice received daily injections of CCI-779 or solvent. On treatment days 2 and 6 cisplatin or mock solution were administered. Results: In vitro a synergistic antitumor effect was observed for the treatment regimen of CCI-779 plus cisplatin. In SCID mice after 2 weeks of therapy with CCI-779 plus cisplatin 4 of 6 tumors of the 518A2 cell line were completely eradicated. In the two remaining 518A2 xenografts this treatment strategy reduced the tumor weight by 94 ± 9% compared to solvent. CCI-779 plus cisplatin also exerted a significant antitumor effect in Mel-JUSO and 607B xenografts compared to mock-treated animals. Conclusion: We provide circumstantial evidence that the use of CCI-779 plus cisplatin might qualify as a promising strategy in the treatment of human melanoma.

Daptomycin, Fosfomycin, or Both for Treatment of Methicillin-Resistant Staphylococcus aureus Osteomyelitis in an Experimental Rat Model

ABSTRACT The in vivo activities of daptomycin, fosfomycin, and a combination of both antibiotics against a clinical isolate of methicillin-resistant Staphylococcus aureus (daptomycin MIC, 0.25 μg/ml; fosfomycin MIC, 0.5 μg/ml) were evaluated in a rat model of osteomyelitis. A total of 37 rats with experimental osteomyelitis were treated for 4 weeks with either 60 mg/kg of body weight of daptomycin subcutaneously once daily, 75 mg/kg fosfomycin intraperitoneally once daily, a combination of both drugs, or a saline placebo. After the completion of treatment, animals were euthanized, and the infected tibiae were processed for quantitative bacterial culture. Bone cultures were found to be positive for methicillin-resistant S. aureus in 9 of 9 (100%) animals of the placebo group, in 9 of 9 (100%) animals treated with daptomycin, in 1 of 10 (10%) fosfomycin-treated rats, and in 1 of 9 (22.2%) rats comprising the combination group. Results of bacterial counts in the bone samples were expressed as log10 CFU/g of bone and analyzed by using the Mann-Whitney U test followed by Bonferronis multiple-comparison test. Based on bacterial counts, treatment with daptomycin was significantly superior to placebo, although it remained inferior to treatment with fosfomycin. No synergistic or antagonistic effect was observed for the combination therapy. No development of resistance against daptomycin or fosfomycin was observed after the 4-week treatment period.

Hepatitis E virus seroprevalence in Austrian adults: a nationwide cross-sectional study among civilians and military professionals.

Background Hepatitis E Virus (HEV) infection is globally increasing. The present study was performed to investigate the HEV seroprevalence, exposure risks as well as occupational risks for military personnel in Austria, a Central European country. Methods and Findings A nationwide cross-sectional seroprevalence study was performed in 997 healthy Austrian adults, professional soldiers and civilians. Routine laboratory and HEV specific antibodies were determined. In addition, epidemiological information on possible risk factors for exposure to HEV was obtained. The overall seropositivity for HEV antibodies was 14.3% and significantly increased with age. Seroprevalence was significantly higher among individuals with previous military employments abroad (21.4% vs. 9.9%) and among professional soldiers aged 30–39 years (20.2% vs. 7.3%). No association was found for private travel, occupational or private animal contact or regular outdoor activities. Individuals who tested positive for antibodies against HEV had significantly higher laboratory values regarding liver enzymes, lipid levels and blood fasting glucose. Conclusions Exposure to HEV is common in Austria. Military employment abroad could be a potential risk factor for HEV infection. Further studies are required to investigate the significance of pathological laboratory results found among asymptomatic individuals previously exposed to HEV.

Efficacy of Fosfomycin in Experimental Osteomyelitis Due to Methicillin-Resistant Staphylococcus aureus

ABSTRACT The activity of fosfomycin was evaluated in an experimental methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis model. Eighteen rats were treated for 4 weeks with 150 mg of fosfomycin/kg of body weight intraperitoneally once daily or with saline placebo. After treatment, animals were euthanized and the infected tibiae were processed for quantitative bacterial culture. Bone cultures were positive for methicillin-resistant S. aureus in all 9 (100%) untreated controls and in 2 of 9 (22.2%) fosfomycin-treated rats. Thus, fosfomycin treatment was significantly more efficacious than placebo. No development of resistance was observed after the 4-week treatment period.

Penetration of doripenem in human brain: an observational microdialysis study in patients with acute brain injury

Concentration-time profiles of unbound doripenem were determined by microdialysis in the cerebral interstitium of five patients with acute brain injury. The ratio of the area under the concentration-time curve in brain to that in plasma (AUC(brain)/AUC(plasma)) was 0.17 in one patient and 0.01 in the remaining four patients. Based on the percentage of the dosing interval during which the doripenem concentration exceeded a certain minimum inhibitory concentration (T>MIC), a value of ≥35% of the dosing interval was reached for pathogens with MICs up to 0.05 mg/L. The present data indicate that breakpoints based on concentrations of doripenem in plasma may overestimate antimicrobial activity in brain parenchyma.

High need for MMR vaccination in HIV infected adults in Austria.

Current guidelines recommend screening for HIV infected patients susceptible for vaccine preventable diseases and offering of immunization. However, data regarding the vaccination coverage among this group are largely missing. This study analyzed the serostatus for Measles, Mumps and Rubella of more than 700 HIV infected patients residing in Austria. These patients were representative for the Austrian HIV cohort regarding sex, age, transmission risk and HIV progression markers. 73.6% were on suppressive HAART, mean CD4 cell count was 603c/μl. Seronegativity was 8.4% for Measles, 33.4% for Mumps and 18.8% for Rubella. In total, out of the 713 HIV infected adults analyzed, almost half (47.8%) would require MMR vaccination. In a multivariate analysis migration was significantly associated with seronegativity for Measles (OR 0.5, CI 0.27-0.9) and Mumps (OR 0.57, CI 0.39-0.81). Importantly due to the well preserved immune status of nearly all participants vaccination would be feasible in the majority of the seronegative patients. Thus, a proactive approach would largely reduce the number of patients at risk for vaccine-preventable diseases.

Influenza vaccination perception and coverage among patients with malignant disease

BACKGROUND Patients with malignancies are at increased risk of serious influenza related complications with higher rates of hospitalization and mortality than healthy cohorts. Although annual vaccination against influenza infection is recommended, vaccination rates among cancer patients are apparently low. The reasons for the low compliance to influenza vaccine and the influenza vaccination rate among Austrian cancer patients have not been studied in detail yet. PATIENTS AND METHODS From July 1, 2013 to October 31, 2013, 444 patients treated in the outpatient departments of the Clinical Division of Oncology and the Clinical Division of Haematology and Haemostaseology of the General Hospital Vienna participated in a survey on different aspects of influenza vaccination. RESULTS In total, only 80 out of 444 patients (18%) had received influenza vaccination in the previous year. The influenza vaccination rate was higher amongst patients with haematological malignancies (22%) compared to patients with solid tumours (13%). Higher age was significantly associated with a higher probability for being vaccinated. Collecting information about influenza vaccination primarily from media or the internet was not significantly associated with influenza vaccination status. Information through a medical consultation or a recommendation by the attending physician resulted in significant higher influenza vaccination coverage rates. Only 199 out of the 444 patients (44.8%) were informed by a physician about influenza vaccination and only 18 out of 337 patients (5.3%) with a diagnosis of a malignant disease were informed by their treating oncologist. The main reasons for influenza vaccination denial were concerns about interaction with the malignant disease and potential side-effects. CONCLUSION Information about influenza vaccination during a medical consultation and a clear recommendation by the attending physician are highly predictive for acceptance of influenza vaccination. Increased awareness among physicians, especially oncologists is of utmost importance to effectively improve IVR in patients with malignant disease.

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis

The impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection.

Low tetanus, diphtheria and acellular pertussis (Tdap) vaccination coverage among HIV infected individuals in Austria.

Current management guidelines of HIV infected adults include recommendation to immunization against common vaccine preventable diseases. This effort is hindered by the scarce knowledge regarding the immunization status of this especially vulnerable patient group. This study analyzed the serostatus for pertussis, diphtheria and tetanus of more than 700 HIV infected individuals residing in Austria. These individuals were representative for the Austrian HIV cohort regarding sex, age, transmission risk and HIV progression markers. Overall, 73.6% were on suppressive HAART, mean CD4 cell count was 603c/μl. Seropositivity was 84% for diphtheria, 51% for tetanus and 1% for pertussis. Migrants had a lower chance of tetanus seropositivity (OR 0.30 (CI 0.21 to 0.43)). Increase in CDC classification were associated with increased diphtheria seropositivity (OR 1.42 (CI 1.02 to 1.98)) and a CD4 nadir<200c/μl was associated with increased pertussis seropositivity (OR 12.2, 95% CI 1.2 to 121). Importantly due to the well preserved immune status of nearly all participants vaccination would be feasible in the majority of the seronegative patients. In patients with a CD4 count>200c/μl, 95% lacked seroprotection to at least one of the antigens included in the triple vaccine Tdap and could be vaccinated. Thus, a proactive approach would largely reduce the number of patients at risk for these vaccine-preventable diseases.

Exposure to Echinococcus multilocularis, Toxocara canis, and Toxocara cati in Austria: A Nationwide Cross-Sectional Seroprevalence Study

Despite emerging risks for the spread of zoonotic diseases, data on human exposure to Echinococcus multilocularis and Toxocara spp., the causative parasites of the two most important helminthozoonoses in Central Europe, are limited. To investigate risk factors and exposure, we conducted a nationwide, cross-sectional serological study in 1046 healthy individuals, of which 425 were soldiers and 621 were civilians. Serum samples and information on possible risk factors for exposure, including previous foreign military assignments, residential area, animal contact, and regular outdoor activities, were obtained. Immunoglobulin G antibodies against Echinococcus multilocularis and Toxocara spp. were examined with an enzyme-linked immunosorbent assay (ELISA). Samples reactive in the ELISA for antibodies against Echinococcus multilocularis were considered positive only after confirmation by western blot. Overall, 66 (6.3%) individuals tested positive in the serologic screening for Toxocara spp. Occupational animal contact was the only risk factor significantly associated with a higher risk for being seropositive. None of the individuals were positive for antibodies against Echinococcus multilocularis. In conclusion, the present study demonstrates that exposure to Toxocara spp. is widespread in Austria and occupational animal contact is a risk factor for seropositivity.