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.

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.

The third-generation P-glycoprotein inhibitor tariquidar may overcome bacterial multidrug resistance by increasing intracellular drug concentration.

OBJECTIVES: The use of efflux pump inhibitors may be a powerful strategy to overcome transporter-mediated bacterial multidrug resistance. In the present study, we set out to investigate the potency of tariquidar, a third-generation P-glycoprotein inhibitor in clinical development, for overcoming bacterial resistance towards ciprofloxacin. METHODS: Staphylococcus aureus 29213 (SA29213) and S. aureus 1199B (SA1199B), which overexpresses the multidrug transporter NorA, as well as Pseudomonas aeruginosa 27853 and Stenotrophomonas maltophilia BAA-85, which expresses SmeDEF, were exposed to ciprofloxacin in the presence and absence of tariquidar or, for comparative reasons, elacridar. Activity of both P-glycoprotein inhibitors was evaluated by determination of MICs and time-kill curves, and by quantification of uptake of ciprofloxacin into bacterial cells. RESULTS: Activity of tariquidar and elacridar was comparable for S. aureus strains, and both dose-dependently increased susceptibility towards ciprofloxacin. Highest effects were observed for SA1199B, where the addition of tariquidar resulted in a 10-fold reduction of the ciprofloxacin MIC, while no effect was observed for P. aeruginosa. For S. maltophilia, elacridar but not tariquidar improved susceptibility. Uptake of [14C]ciprofloxacin and modification of susceptibility showed significant correlations (r=0.89, P<0.0001). Tariquidar had no intrinsic activity against any strain tested. CONCLUSIONS: We conclude that tariquidar has potent inhibitory effect against certain bacterial efflux pumps in vitro. Their high activity at clinically achievable concentrations might yield this class of drugs promising for future applications in infectious diseases.

Import of community-associated, methicillin-resistant Staphylococcus aureus to Europe through skin and soft-tissue infection in intercontinental travellers, 2011-2016.

OBJECTIVES: Recently, following import by travel and migration, epidemic community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has caused nosocomial outbreaks in Europe, sometimes with a fatal outcome. We describe clinico-epidemiological characteristics of CA-MRSA detected by the European Network for the Surveillance of imported S. aureus (www.staphtrav.eu) from May 2011 to November 2016. METHODS: Sentinel surveillance at 13 travel clinics enrolling patients with travel-associated skin and soft-tissue infection (SSTI) and analysing lesion and nose swabs at one central laboratory. RESULTS: A total of 564 independent case-patients with SSTI were enrolled and had 374 (67%) S. aureus-positive lesions, of which 14% (51/374) were MRSA. The majority of CA-MRSA isolates from SSTI were Panton-Valentine leucocidin (PVL) -positive (43/51, 84%). The risk of methicillin-resistance in imported S. aureus varied by travel region (p <0.001) and was highest in Latin America (16/57, 28%, 95% CI 17.0-41.5) and lowest in Sub-Saharan Africa (4/121, 3%, 95% CI 0.9-8.3). Major epidemic clones (USA300 / USA300 Latin-American Variant, Bengal Bay, South Pacific) accounted for more than one-third (19/51, 37%) of CA-MRSA imports. CA-MRSA SSTI in returnees was complicated (31/51 multiple lesions, 61%; 22/50 recurrences, 44%), led to health-care contact (22/51 surgical drainage, 43%; 7/50 hospitalization, 14%), was transmissible (13/47 reported similar SSTI in non-travelling contacts, 28%), and associated with S. aureus nasal colonization (28 of 51 CA-MRSA cases, 55%; 24 of 28 colonized with identical spa-type in nose and lesion, 85%). CONCLUSIONS: Travel-associated CA-MRSA SSTI is a transmissible condition that leads to medical consultations and colonization of the infected host.

Predominance of dfrG as determinant of trimethoprim resistance in imported Staphylococcus aureus.

To investigate the global occurrence of trimethoprim-sulfamethoxazole resistance and the genetic mechanisms of trimethoprim resistance, we analysed Staphylococcus aureus from travel-associated skin and soft-tissue infections treated at 13 travel clinics in Europe. Thirty-eight per cent (75/196) were trimethoprim-resistant and 21% (41/196) were resistant to trimethoprim-sulfamethoxazole. Among methicillin-resistant S. aureus, these proportions were 30% (7/23) and 17% (4/23), respectively. DfrG explained 92% (69/75) of all trimethoprim resistance in S. aureus. Travel to South Asia was associated with the highest risk of acquiring trimethoprim-sulfamethoxazole-resistant S. aureus. We conclude that globally dfrG is the predominant determinant of trimethoprim resistance in human S. aureus infection.

The role of glycopeptides in the treatment of intravascular catheter-related infections.

There is increasing concern over multiresistant staphylococcci in catheter-associated infections. Local infections due to coagulase-negative staphylococci are usually resolved by removal of the intravascular catheter. However, if the device should remain for a certain period of time, e.g. to complete a course of chemotherapy, the antibiotic lock technique with a glycopeptide should be considered. In case of septic embolism to the lung caused by a multiresistant Staphylococccus aureus or Enterococcus faecium, systemic therapy with glycopeptides, streptogramins or linezolid must be employed.

[Tissue penetration of antibiotics. Does the treatment reach the target site?]. / Gewebepenetration von Antibiotika. Erreicht die Behandlung den Zielort?

BACKGROUND: For critically ill patients, infections still imply a major challenge for the treating physician. One key factor of successful treatment is sufficient exposure of the employed antimicrobial agent at the site of infection. In most cases, this is the interstitial space of the infected organ or a body cavity; much rarer vital bacteria are located within body cells. METHODS: Different methods for assessment of tissue pharmacokinetics of antimicrobial agents in the human body are described, including tissue biopsy, bronchoalveolar lavage and microdialysis, and their implication on interpretation of obtained data are discussed. Tissue pharmacokinetics of the hydrophilic beta-lactam meropenem and the lipophilic fluoroquinolone levofloxacin are compared. RESULTS: Differences in pharmacokinetics between plasma and tissue, healthy volunteers and critically ill patients but also between data obtained in the same organ by different methods are discussed. CONCLUSION: In order to use pharmacokinetic data to optimize the treatment of critically ill patients, critical appraisal of the causative pathogen, the location of the infection, and the source of the used pharmacokinetic data is necessary.

Prevalence and risk factor assessment of Tropheryma whipplei in a rural community in Gabon: a community-based cross-sectional study.

Tropheryma whipplei is the causative agent of Whipple's disease and has been detected in stools of asymptomatic carriers. Colonization has been associated with precarious hygienic conditions. There is a lack of knowledge about the epidemiology and transmission characteristics on a population level, so the aim of this study was to determine the overall and age-specific prevalence of T. whipplei and to identify risk factors for colonization. This molecular epidemiological survey was designed as a cross-sectional study in a rural community in Central African Gabon and inhabitants of the entire community were invited to participate. Overall prevalence assessed by real-time PCR and sequencing was 19.6% (95% CI 16-23.2%, n=91) in 465 stool samples provided by the study participants. Younger age groups showed a significantly higher prevalence of T. whipplei colonization ranging from 40.0% (95% CI 27.8-52.2) among the 0-4 year olds to 36.4% (95% CI 26.1-46.6) among children aged 5-10 years. Prevalence decreased in older age groups (p<0.001) from 12.6% (95% CI 5.8-19.4%; 11-20 years) to 9.7% (95% CI 5.7-13.6) among those older than 20. Risk factor analysis revealed young age, male sex, and number of people sharing a bed as factors associated with an increased risk for T. whipplei carriage. These results demonstrate that T. whipplei carriage is highly prevalent in this part of Africa. The high prevalence in early life and the analysis of risk factors suggest that transmission may peak during childhood facilitated through close person-to-person contacts.

Predictors of clinical and microbiological treatment failure in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia: a retrospective cohort study in a region with low MRSA prevalence.

Invasive infections with methicillin-resistant Staphylococcus aureus (MRSA) have been associated with increased morbidity and mortality. The aim of the present study was to identify independent predictors of early mortality and treatment failure in patients with MRSA bacteraemia. A total of 132 adult patients who developed MRSA bacteraemia during hospitalization in the University Hospital of Vienna between 2000 and 2011 were screened and 124 were included in a retrospective cohort study. Patient demographics, source of bacteraemia, antimicrobial treatment and microbiological characteristics were evaluated. The 28-day crude mortality was 30.6%. Predictors of early mortality identified in multivariate Cox regression analysis included higher patient age (adjusted hazard ratio (aHR) 1.03, 95% CI 1.01-1.06, p 0.006), pneumonia (aHR 3.86, 95% CI 1.83-8.12, p <0.001) and failure to use MRSA active treatment (aHR 8.77, 95% CI 3.50-21.93, p <0.001). Ninety-one (73.4%) patients received glycopeptides as specific MRSA treatment. Of 63 patients treated with vancomycin, only 14 (22.6%) patients had aimed trough levels of 15-20 mg/L. Vancomycin MIC ≥2 mg/L was detected in 28.2% and was associated with glycopeptide pretreatment (p 0.001). All MRSA isolates were susceptible to linezolid and tigecycline. Persistent bacteraemia ≥7 days was documented in 25 (20.2%) patients. Independent determinants for microbiological eradication failure in patients with MRSA bacteraemia included endocarditis (p <0.001) and vancomycin trough levels (p 0.014), but not vancomycin MIC. Failure of clinical and microbiological eradication of MRSA among patients with MRSA bacteraemia was associated with clinical entity rather than with bacterial traits. Pharmacokinetic parameters seem to be decisive on microbiological and clinical success.

Quantitative differences in antibiotic resistance between methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains isolated in Hungary, Austria and Macedonia.

The aim of this study was to compare the quantitative susceptibility of methicillin-resistant and -susceptible Staphylococcus aureus (MRSA and MSSA) strains from three European countries to nine antistaphylococcal agents. The antibiotic susceptibility of 274 MRSA and 284 MSSA strains from Hungary, Austria and macedonia was tested by the broth microdilution method. The clonal relationship of strains was determined by pulsed-field gel electrophoresis. Intermediate susceptibility to vancomycin appeared in Macedonian MRSA strains. Macedonian MRSA strains had high-level amikacin and gentamicin resistance. MSSA strains generally were susceptible to all drugs at minimum inhibitory concentrations (MIC(50)) except for gentamicin resistance in Macedonian strains. In Hungary and Austria a common antibiotic resistance phenotype of MRSA predominated, while in macedonia three other phenotypes were also prevalent. Geographical differences in the resistance of S. aureus are still high. Since resistance levels of MRSA and MSSA strains differ extensively, they should be considered separately for antibiotic resistance analysis.

Cellular profile of cytokine production in a patient with visceral leishmaniasis: gammadelta+ T cells express both type 1 cytokines and interleukin-10.

The cytokine profile of CD4+, CD8+ T cells, gammadelta+ T cells and natural killer (NK) cells (CD94+CD3-) was studied in a patient with visceral leishmaniasis (VL). The otherwise healthy, human immunodeficiency virus-negative patient acquired the disease in Tuscany, Italy. Diagnosis was made by demonstration of high concentrations of antibodies against Leishmania antigens in serum. Flow cytometry for the detection of intracellular interferon-gamma (IFN-gamma), interleukin (IL)-2, IL-4, IL-6, IL-10, IL-13 and tumour necrosis factor (TNF)-alpha expression in peripheral blood mononuclear cells stimulated with phorbol 12-myristate 13-acetate and ionomycin was performed, followed by treatment with liposomal amphotericin B. CD4+ cells were identified as major cytokine-expressing cells, capable of producing both type 1 and type 2 cytokines. A high frequency of IL-4- and IL-13-expressing CD8+ cells was noted. NK cells and gammadelta+ T cells, thought to be involved in innate host defences against Leishmania, expressed IFN-gamma and TNF-alpha. Ten per cent of gammadelta+ T cells expressed IL-10, predominantly together with IFN-gamma, suggesting additional immune-regulatory roles for this T-cell subset in VL.