Predictors for and coverage of influenza vaccination among HIV-positive patients: a cross-sectional survey.

OBJECTIVES: Influenza vaccination is recommended for HIV-infected patients, but limited data about vaccination rates are available. The aim of this study was to evaluate the coverage of and predictors for influenza vaccination among HIV-positive patients. METHODS: All HIV-positive patients who visited the HIV out-patient department of the University Hospital of Vienna, Austria, between June and August 2015 were asked to participate in this survey by completing a questionnaire. RESULTS: A total of 455 HIV-positive patients completed a questionnaire, with 359 male and 96 female participants with a mean age of 46 years. The influenza vaccination rate for the previous season (2014/2015) was 11.9% [n = 54/455; 95% confidence interval (CI) 9.2-15.2%]. Older age was significantly associated with a positive influenza vaccination status. Obtaining information through a medical consultation or receiving a direct recommendation for vaccination by a physician had a significant impact on vaccination behaviour. The probability of being vaccinated against influenza was about 13 times higher among patients who received a recommendation for vaccination by their family physician or by their HIV specialist (P < 0.001). Important reasons for declining vaccination were fear of side effects (39%), not considering influenza as a severe disease (36%) and reasons related to HIV: 17% were worried that the vaccine could worsen the course of HIV infection and 16% believed vaccination would fail because of their compromised immune system. CONCLUSIONS: A low influenza vaccination rate of 11.9% was detected in this HIV-positive cohort. The most effective impact for a positive vaccination status was direct recommendation of the influenza vaccine by the attending physician.

Compatibility of fosfomycin with different commercial peritoneal dialysis solutions.

For treatment of peritoneal dialysis-related peritonitis, intraperitoneal administration of antibiotics remains the preferable route. For home-based therapy, patients are commonly supplied with peritoneal dialysis fluids already containing antimicrobial agents. The present study set out to investigate the compatibility of fosfomycin with different peritoneal dialysis fluids, namely, Extraneal®, Nutrineal®, Physioneal® 1.36% and Physioneal® 2.27%, under varying storage conditions. The peritoneal dialysis fluid bags including 4 g fosfomycin were stored over 14 days at refrigeration temperature (6°C) and room temperature (25°C) and over 24 h at body temperature (37°C). Drug concentrations over time were determined by using high-performance liquid chromatography coupled to a mass spectrometer. In addition, drug activity was assessed by a disk diffusion method, diluent stability by visual inspection and drug adsorption by comparison of the measured and calculated concentrations. Blank peritoneal dialysis fluids and deionized water were used as comparator solutions. Fosfomycin was stable in all peritoneal dialysis fluids and at each storage condition investigated over the whole study period. The remaining drug concentrations ranged between 94% and 104% of the respective initial concentrations. No significant drug adsorption was observed for any peritoneal dialysis fluid at any storage condition. No relevant reduction of antimicrobial activity was observed. Fosfomycin is compatible with Extraneal®, Nutrineal® and Physioneal® for up to two weeks at refrigeration or room temperature and may be used for home-based therapy. No dose adjustment is needed due to adsorption or degradation.

The influence of different peritoneal dialysis fluids on the in vitro activity of ampicillin, daptomycin, and linezolid against Enterococcus faecalis.

Intraperitoneal administration of antibiotics is recommended for the treatment of peritoneal dialysis-related peritonitis. However, little data are available on a possible interference between peritoneal dialysis fluids and the activity of antimicrobial agents. Thus, the present in vitro study set out to investigate the influence of different peritoneal dialysis fluids on the antimicrobial activity of ampicillin, linezolid, and daptomycin against Enterococcus faecalis. Time-kill curves in four different peritoneal dialysis fluids were performed over 24 h with four different concentrations (1 × MIC, 4 × MIC, 8 × MIC, 30 × MIC) of each antibiotic evaluated. Cation-adjusted Mueller-Hinton broth was used as the comparator solution. All four peritoneal dialysis fluids evaluated had a bacteriostatic effect on the growth of Enterococcus faecalis. Compared to the cation-adjusted Mueller-Hinton broth comparator solution, the antimicrobial activity of all antibiotics tested was reduced. For ampicillin and linezolid, no activity was found in any peritoneal dialysis fluid, regardless of the concentration. Daptomycin demonstrated dose-dependent activity in all peritoneal dialysis fluids. Bactericidal activity was observed at the highest concentrations evaluated in Dianeal® PDG4 and Extraneal®, but not in concentrations lower than 30 × MIC and not in Nutrineal® PD4 and Physioneal® 40. The antimicrobial activity of ampicillin and linezolid is limited in peritoneal dialysis fluids in vitro. Daptomycin is highly effective in peritoneal dialysis fluids and might, thus, serve as an important treatment option in peritoneal dialysis-related peritonitis. Further studies are needed to evaluate the clinical impact of the present findings.

In vitro activity of doripenem plus fosfomycin against drug-resistant clinical blood isolates.

The in vitro activity of doripenem in combination with fosfomycin was evaluated against a wide range of clinical blood isolates. Bacterial isolates of methicillin-resistant Staphylococcus aureus (MRSA; n = 39), Pseudomonas aeruginosa (n = 18), multidrug-resistant Escherichia coli (n = 10), Enterobacter cloacae (n = 3) and Klebsiella pneumoniae (n = 5) were investigated. For synergism testing the checkerboard test was applied and determined by calculation of the fractional inhibitory concentration index. Checkerboard results were verified by time-kill curve tests on selected isolates. Among MRSA, E. coli and K. pneumoniae, 94.9, 80 and 100% of isolates demonstrated synergism, respectively. Selected isolates demonstrated synergism in time-kill curve tests. P. aeruginosa isolates demonstrated no interaction in all isolates. Doripenem plus fosfomycin shows high efficacy with promising results in vitro.

High prevalence of antibodies against Leptospira spp. in male Austrian adults: a cross-sectional survey, April to June 2009.

To assess the distribution of specific antibodies against Leptospira spp. in Austrian adults, we conducted an explorative nationwide cross-sectional serological study in 400 healthy individuals. Antibody titres against Leptospira spp. were determined in a microscopic agglutination test using a panel of 14 serovar cultures. Sera of 18 participants were excluded because the samples were unsuitable for testing; the remaining 382 participants comprised 166 professional soldiers and 216 civilians. Overall, 88 (23%) individuals tested positive in serological screening. The subjects' sera reacted most frequently with serovars Canicola (16.5%) and Hardjo (11.8%). Epidemiological information was obtained from a questionnaire: no correlation was found for area of residence, travel abroad, regular outdoor activities, occupational animal contact, or ownership of companion animals. The proportion of seropositive samples was significantly lower among professional soldiers (15.7%) than among civilians (28.7%) (p=0.003). Our data demonstrate serological evidence of a high rate of exposure to Leptospira spp. among the Austrian population. No increased risk of exposure to Leptospira spp. was detected in military personnel.

Pre- and post-pandemic prevalence of antibodies to the 2009 pandemic influenza A (H1N1) virus in Austrian adults.

Antibody prevalence to the 2009 pandemic influenza A (H1N1) virus was determined in a sample of the Austrian population to assess the post-pandemic seropositivity rate, the infection attack rate, and the proportion of subclinical infections during the 2009/2010 influenza pandemic in Austrian adults. A total of 480 sera from individuals aged between 18 and 57 years from all nine federal states of Austria were collected between April and June 2010. Information on demographic characteristics, vaccination history, and history of suspected or verified influenza virus infection was ascertained. Antibodies were determined using a commercial ELISA and compared with 80 age-matched adult sera collected before the pandemic began. The overall seropositivity rate was 28% and was highest among young adults aged 18-29 years, followed by adults aged 50-57 years. Among seropositive unvaccinated individuals, infection was asymptomatic in more than 80%. Extrapolation to the overall Austrian adult population indicates that more than 1.3 million persons aged 18-57 years became infected in 2009. Compared with the pre-pandemic seropositivity rate, the infection rate was highest among young adults but low in those aged 30-57 years. Among 69 individuals previously vaccinated with the 2009 pandemic influenza A (H1N1) virus, 71% had specific antibodies. The study demonstrates that infection rates based on surveillance of clinical cases considerably underestimated the infection attack rate during the 2009 H1N1 pandemic in Austria and that vaccination against this virus elicited long-lasting seropositivity in more than 70% of adults.

Comparative in vitro antimicrobial activity of vancomycin, teicoplanin, daptomycin and ceftobiprole in four different peritoneal dialysis fluids.

Peritoneal dialysis used in the treatment of patients with end-stage renal failure is often complicated by peritonitis. Staphylococcus aureus peritonitis is severe, particularly if caused by a methicillin-resistant strain (MRSA). Intraperitoneal administration of drugs for treatment of peritonitis is preferable to intravenous or oral routes because of the resulting higher local antibiotic concentrations. However, peritoneal dialysis fluids (PDFs) have a bacteriostatic effect, which may compromise the efficacy of antibiotics. The bactericidal efficacy of vancomycin, teicoplanin, daptomycin and ceftobiprole was studied in the PDFs Dianeal PD4® (glucose 1.36%), Physioneal 40® (glucose 1.36%), Extraneal® (7.5% icodextrin), and Nutrineal PD4® (1.1% amino acid) using time-kill curves. To simulate in vivo conditions, human serum albumin was added at a final concentration of 2 g/l. All four PDFs had a bacteriostatic effect on the growth of the MRSA test isolate. All antibiotics showed less activity in PDFs compared to control broth. Vancomycin and teicoplanin achieved the greatest reduction in bacterial numbers in the amino-acid containing PDF Nutrineal PD4®. Daptomycin showed its highest activity in Extraneal® and better overall efficacy than the other tested antibiotics. Ceftobiprole showed no killing activities in any of the four PDFs. Based on these in vitro data we conclude that the choice of PDFs for intraperitoneal administration is not trivial and could be crucial for therapy outcome.

Efficacy of fosfomycin in experimental osteomyelitis due to methicillin-resistant Staphylococcus aureus.

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.

Daptomycin, fosfomycin, or both for treatment of methicillin-resistant Staphylococcus aureus osteomyelitis in an experimental rat model.

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 log(10) CFU/g of bone and analyzed by using the Mann-Whitney U test followed by Bonferroni's 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.

Clinical aspects of 2009 pandemic influenza A (H1N1) virus infection in Austria.

PURPOSE: To describe the clinical features, risk factors for severe disease and effectiveness of oseltamivir in patients with 2009 pandemic influenza A (H1N1) virus infection. METHODS: In a prospective, cross-sectional, multicentre study, data on 540 patients with confirmed 2009 H1N1 infection from seven Austrian hospitals were collected using a standardised online case-history form. RESULTS: The median age of the patients was 19.3 years (range 26 days-90.8 years); point-of-care testing yielded false-negative results in 60.2% of the 176 cases tested. The most common symptoms were fever, cough, fatigue and headache. Overall, 343 patients (63.5%) were hospitalised, 49 (9.1%) were admitted to an intensive care unit (ICU) and 14 (4.1%) died. Case fatality rates were highest (9.1%) in those aged 65 years or older. Factors significantly associated with a higher risk for ICU admission included age, neurological disease, adipositas, and both interstitial pathology and lobular pathology on chest X-ray. No association with pregnancy, malignancy or immunosuppressive therapy was detected. Antiviral treatment significantly reduced the duration of fever by 0.66 days and lowered the risk of ICU admission, but had no significant benefit on survival. CONCLUSIONS: During the 2009 H1N1 influenza pandemic, elderly or obese patients and those with neurological disease had an increased risk for severe H1N1 infection in Austria. Pregnancy was not associated with a higher risk for severe disease in the later phase of the 2009 H1N1 pandemic. Antiviral treatment provided a minimal effect on the symptoms of influenza but reduced the risk of admission to an ICU.

Leishmania infections in Austrian soldiers returning from military missions abroad: a cross-sectional study.

OBJECTIVES: The incidence of leishmaniasis is known to increase in conflict areas. The aims of this study were to determine the exposure to Leishmania species in Austrian soldiers returning from missions abroad and to assess possible risk factors. METHODS: A retrospective explorative cross-sectional serologic study was conducted in 225 healthy Austrian soldiers returning from UN or EU peacekeeping missions in Syria, Lebanon and Bosnia and Herzegovina (BIH). Sera were tested for anti-Leishmania antibodies using a commercial enzyme-linked immunosorbent assay. All positive individuals were screened for Leishmania DNA by PCR targeting the ITS1 region using EDTA blood samples. RESULTS: In total, 13.3% (30/225) of the individuals tested were either positive (8%, 18/225) or borderline (5.3%, 12/225) in the enzyme-linked immunosorbent assay, with the highest seroprevalence in soldiers returning from Syria (17.8%, 18/101; 12 positive, six borderline), second from Lebanon (11.1%, 7/63; four positive, three borderline) and lowest from BIH (8.2%, 5/61; two positive, three borderline). Ten soldiers returning from Syria and one from BIH were also positive for Leishmania DNA. Six of these were identified as Leishmania donovani/infantum complex, two as L. tropica and another three as mixed infections by DNA sequencing. Epidemiologic data were collected via a questionnaire, and seropositivity was correlated with a history of insect bites that took a long time to heal (odds ratio, 5.33; 95% confidence interval, 1.23-23.04; p 0.025). CONCLUSIONS: Although pretravel serologic data were not available in this study, the exposure of soldiers to Leishmania spp. during their missions can be assumed to be considerable. Because even asymptomatic infections may resurge in case of emerging immunodeficiencies, adequate prevention measures seem important.

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.

Hepatosplenic Abscesses and Osteomyelitis of the Spine in an Immunocompetent Adult with Cat Scratch Disease.

We present an 18-year-old, immunocompetent Austrian military conscript with cervical lymphadenopathy, fever, back-pain, and persistent inflammation markers despite two weeks of antimicrobial therapy with ampicillin/sulbactam. All specific laboratory investigations for identification of a specific etiology, including blood cultures and autoantibodies, were inconspicuous. Abdominal computed tomography showed multiple hypodense hepatosplenic lesions and osteomyelitis of the thoracic and lumbar spine with base plate fracture. Based on the patient's history, clinical presentation, and radiological findings, serology for cat scratch disease (CSD) was performed and high B. henselae specific IgM and IgG antibodies were detected. Due to its variety of clinical presentations, diagnosis of CSD is challenging, especially in the absence of a history of specific exposure. This case report shall remind the physician that cat scratch disease is a common disease, mainly presenting with fever and lymphadenopathy in young patients. Nevertheless CSD has many different and rare forms of presentations, including hepatosplenic lesions and bone involvement as shown in this case.

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.

Azithromycin suppresses CD4(+) T-cell activation by direct modulation of mTOR activity.

Advanced macrolides, such as azithromycin (AZM) or clarithromycin (CLM), are antibiotics with immunomodulatory properties. Here we have sought to evaluate their in vitro influence on the activation of CD4(+) T-cells. Isolated CD4(+) T-cells were stimulated with agonistic anti-CD3/anti-CD28 monoclonal antibodies in the presence of 0.6 mg/L, 2.5 mg/L, 10 mg/L or 40 mg/L AZM or CLM. Cell proliferation, cytokine level in supernatants and cell viability was assessed. Intracellular signaling pathways were evaluated using reporter cell lines, FACS analysis, immunoblotting and in vitro kinase assays. AZM inhibited cell proliferation rate and cytokine secretion of CD4(+) T-cells in a dose-dependent manner. Similarly, high concentrations of CLM (40 mg/L) also suppressed these T-cell functions. Analysis of molecular signaling pathways revealed that exposure to AZM reduced the phosphorylation of the S6 ribosomal protein, a downstream target of mTOR. This effect was also observed at 40 mg/L CLM. In vitro kinase studies using recombinant mTOR showed that AZM inhibited mTOR activity. In contrast to rapamycin, this inhibition was independent of FKBP12. We show for the first time that AZM and to a lesser extent CLM act as immunosuppressive agents on CD4(+) T-cells by inhibiting mTOR activity. Our results might have implications for the clinical use of macrolides.

Clinical findings and management of imported cutaneous leishmaniasis: report of 14 cases from Austria.

BACKGROUND: The management of cutaneous leishmaniasis in non-endemic countries is challenging due to the wide variety of clinical manifestations and little information available on treatment modalities for travellers. METHODS: Retrospective analysis and follow-up investigation in patients with imported cutaneous leishmaniasis managed at the General Hospital Vienna from 2004 to 2010. RESULTS: In total, 14 patients with cutaneous leishmaniasis were analyzed. The time to diagnosis ranged between weeks and several months and up to four consultations were necessary before diagnosis was accomplished. Histological investigations performed in all patients were diagnostic for CL in 8 (57%) patients. PCR analyses were performed in 12 patients and were positive in 10 (83%) patients. All six patients with negative histological results for CL tested positive in the PCR analysis. Treatment regimens applied included systemic therapy with liposomal amphotericin B, miltefosine, or fluconazole, and local therapy with cryotherapy, paromomycin ointment, photodynamic therapy, surgery, and various combinations. CONCLUSIONS: The present analysis strongly suggests that awareness of CL among physicians and travellers remains low and highlights the need to harmonize diagnostic and treatment guidelines for cutaneous and mucosal leishmaniasis in European travellers. Diagnostic outcome can be improved by combining histology and PCR in patients with suspected cutaneous leishmaniasis.

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.

Seroprevalence and asymptomatic carriage of Leishmania spp. in Austria, a non-endemic European country.

Leishmaniasis is a rare disease in Central Europe and is diagnosed almost exclusively in travellers or migrants coming from tropical or subtropical countries. We conducted an explorative cross-sectional serological study, using a commercial ELISA, in 1048 healthy Austrian individuals to assess the distribution of specific antibodies against Leishmania spp. in humans in Austria. Overall, 47 individuals (4.5%) tested positive, and an additional 32 (3.1%) showed borderline results. After 12 months, sera from 42 of the 79 individuals who had initially tested seropositive/borderline were tested by ELISA a second time: 18 were persistently positive, nine were borderline. Those whose sera were persistently positive/borderline were then screened for potential carrier status using a commercial oligochromatographic PCR test to detect parasite DNA. Four samples were PCR positive and were subjected to a second PCR allowing parasite identification after DNA sequencing: two samples were identified as Leishmania donovani/infantum complex and Leishmania (Viannia) guyanensis, respectively. Epidemiological information was obtained with a questionnaire: no correlation was found for the number of holiday trips within the previous 6 months, but a significant risk of exposure to Leishmania spp. was found for travel to the New World, particularly to the Caribbean. Our data demonstrate that Leishmania spp. seroprevalence in non-endemic countries has been considerably underestimated.

Clinical Challenges in the Management of Leishmania/HIV Coinfection in a Nonendemic Area: A Case Report.

We report on a 37-year-old male HIV-positive patient with generalized cutaneous leishmaniasis undiagnosed for several years. Upon presentation, visceral leishmaniasis was diagnosed in addition to cutaneous manifestation of the disease. Over a period of three years, several different treatment regimens including liposomal amphotericin B, liposomal amphotericin B with miltefosine, liposomal amphotericin B with interferon, and pentamidine combined fluconazole and allopurinol were applied until Leishmania PCR from blood turned negative. This case supports the necessity of multidrug combinational and sequential therapy over a very prolonged period of time in severely immunosuppressed patients infected with Leishmania and highlights the tremendous individual but also economic burden of this disease.