Background: Propolis consists of a complex mixture of resinous substances collected by honeybees from different plant sources. The objective of this study was to investigate the chemical composition, biological activities, and synergistic properties with antibiotics of propolis samples collected from various geographic origins (Germany, Ireland, and Czech Republic). Methods: The chemical composition of the propolis was analyzed by Gas Liquid Chromatography-Mass Spectrometry (GLC-MS) and High-performance liquid chromatography (HPLC). The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were evaluated by the standard broth microdilution method, while synergistic interactions were assessed by checkerboard dilution and time-kill curve assays. Results: HPLC and GLC-MS analyses revealed that ethanol extract of propolis (EEP) and water extracts of propolis (WEP) contained more than 100 different phytochemicals. The most abundant compounds were aromatic alcohols, aromatic acids, cinnamic acid and its esters, fatty acids, and flavanone (chrysin). Czech propolis showed the highest phenolic content (129.83 ± 5.9 mg CAE/g) followed by Irish propolis and German propolis. Furthermore, Irish propolis exhibited the highest value of total flavonoid content (2.86 ± 0.2 mg QE/g) and antioxidant activity (IC50 = 26.45 µg/mL). All propolis samples showed moderate antibacterial effect against Gram-positive microorganisms with MIC ranging from 0.08 mg/mL to 2.5 mg/mL. Moreover, EEP exhibited moderate activity against Gram-negative bacteria with MIC between 0.6 mg/mL to 5 mg/mL. In addition, EEP displayed moderate antifungal activity (MIC values between 0.6–2.5 mg/mL). The results obtained from time kill-kinetic assay and checkerboard dilution test of two-drug combinations between EEP and antibiotics such as vancomycin, oxacillin, and levofloxacin indicate mainly synergistic interactions against drug-resistant microbial pathogens including MRSA and VRE. Conclusions: The propolis extract synergistically enhanced the efficacy of antibiotics, especially those acting on cell wall synthesis (vancomycin and oxacillin) against drug-resistant microorganisms.

Background: In August 2006, a case of leptospirosis occurred in an athlete after a triathlon held around Heidelberg and in the Neckar river. In order to study a possible outbreak and to determine risk factors for infection an epidemiological investigation was performed. Methods: Participants of the triathlon were contacted by e-mail and were asked to fill out a standardized questionnaire. In addition, they were asked to supply a serum sample for laboratory diagnosis of leptospirosis. A confirmed case patient was defined as a clinical case (i.e. fever and at least one additional symptom suggestive for leptospirosis) with at least two of the following tests positive: ELISA IgM, latex agglutination testing, or microscopic agglutination testing. Rainfall and temperature records were obtained. Results: A total of 142 of 507 triathletes were contacted; among these, five confirmed leptospirosis cases were found. Open wounds were identified as the only significant risk factor for illness (p = 0.02). Heavy rains that preceded the swimming event likely increased leptospiral contamination of the Neckar River. Discussion: This is the first outbreak of leptospirosis related to a competitive sports event in Germany. Among people with contact to freshwater, the risk of contracting leptospirosis should be considered by health care providers also in temperate countries, particularly in the summer after heavy rains.

Fungi are of increasing importance in sepsis. However, culture-based diagnostic procedures are associated with relevant weaknesses. Therefore, culture- and next-generation sequencing (NGS)-based fungal findings as well as corresponding plasma levels of β-d-glucan, interferon gamma (INF-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, -4, -6, -10, -17A, and mid-regional proadrenomedullin (MR-proADM) were evaluated in 50 septic patients at six consecutive time points within 28 days after sepsis onset. Furthermore, immune-response patterns during infections with Candida spp. were studied in a reconstituted human epithelium model. In total, 22% (n = 11) of patients suffered from a fungal infection. An NGS-based diagnostic approach appeared to be suitable for the identification of fungal pathogens in patients suffering from fungemia as well as in patients with negative blood cultures. Moreover, MR-proADM and IL-17A in plasma proved suitable for the identification of patients with a fungal infection. Using RNA-seq., adrenomedullin (ADM) was shown to be a target gene which is upregulated early after an epithelial infection with Candida spp. In summary, an NGS-based diagnostic approach was able to close the diagnostic gap of routinely used culture-based diagnostic procedures, which can be further facilitated by plasmatic measurements of MR-proADM and IL-17A. In addition, ADM was identified as an early target gene in response to epithelial infections with Candida spp.

Introduction: The role of reactive carbonyl species, such as methylglyoxal (MG), has been overlooked within the context of the sepsis syndrome. The aims of this study were to assess the impact of MG formation in different inflammatory settings and to evaluate its use for early diagnosis as well as prognosis of the sepsis syndrome. Methods: In total, 120 patients in three groups were enrolled in this observational clinical pilot study. The three groups included patients with septic shock (n = 60), postoperative controls (n = 30), and healthy volunteers (n = 30). Plasma samples from patients with septic shock were collected at sepsis onset and after 24 hours and 4, 7, 14, and 28 days. Plasma samples from postoperative controls were collected prior to surgery, immediately following the end of the surgical procedure as well as 24 hours later and from healthy volunteers once. Plasma levels of MG were determined by high-performance liquid chromatography. Additionally, plasma levels of procalcitonin, C-reactive protein, soluble CD14 subtype, and interleukin-6 were determined. Results: Patients with septic shock showed significantly higher plasma levels of MG at all measured times, compared with postoperative controls. MG was found to identify patients with septic shock more effectively—area under the curve (AUC): 0.993—than procalcitonin (AUC: 0.844), C-reactive protein (AUC: 0.791), soluble CD14 subtype (AUC: 0.832), and interleukin-6 (AUC: 0.898) as assessed by receiver operating characteristic (ROC) analysis. Moreover, plasma levels of MG in non-survivors were significantly higher than in survivors (sepsis onset: *P = 0.018 for 90-day survival; **P = 0.008 for 28-day survival). Plasma levels of MG proved to be an early predictor for survival in patients with septic shock (sepsis onset: ROC-AUC 0.710 for 28-day survival; ROC-AUC 0.686 for 90-day survival). Conclusions: MG was identified as a marker for monitoring the onset, development, and remission of sepsis and was found to be more useful than routine diagnostic markers. Further studies are required to determine the extent of MG modification in sepsis and whether targeting this pathway could be therapeutically beneficial to the patient. Trial registration: German Clinical Trials Register DRKS00000505. Registered 8 November 2010.

Fourier transform infrared (FT-IR) spectroscopy (IR Biotyper; Bruker) allows highly discriminatory fingerprinting of closely related bacterial strains. In this study, FT-IR spectroscopy-based capsular typing of Streptococcus pneumoniae was validated as a rapid, cost-effective, and medium-throughput alternative to the classical phenotypic techniques.

Infections caused by multidrug-resistant bacteria are a global emerging problem. New antibiotics that rely on innovative modes of action are urgently needed. Ranalexin is a potent antimicrobial peptide (AMP) produced in the skin of the American bullfrog Rana catesbeiana. Despite strong antimicrobial activity against Gram-positive bacteria, ranalexin shows disadvantages such as poor pharmacokinetics. To tackle these problems, a ranalexin derivative consisting exclusively of d-amino acids (named danalexin) was synthesized and compared to the original ranalexin for its antimicrobial potential and its biodistribution properties in a rat model. Danalexin showed improved biodistribution with an extended retention in the organisms of Wistar rats when compared to ranalexin. While ranalexin is rapidly cleared from the body, danalexin is retained primarily in the kidneys. Remarkably, both peptides showed strong antimicrobial activity against Gram-positive bacteria and Gram-negative bacteria of the genus Acinetobacter with minimum inhibitory concentrations (MICs) between 4 and 16 mg/L (1.9–7.6 µM). Moreover, both peptides showed lower antimicrobial activities with MICs ≥32 mg/L (≥15.2 µM) against further Gram-negative bacteria. The preservation of antimicrobial activity proves that the configuration of the amino acids does not affect the anticipated mechanism of action, namely pore formation.