Safety and tolerability of virucidal hand rubs: a randomized, double-blind, cross-over trial with healthy volunteers.

BACKGROUND: The hands of the medical staff play an important role in transmission of pathogens in the health care environment. Hand hygiene is efficient, easy to perform and cost-effective. Safety, tolerability and acceptance of hand hygiene preparations play a major role in hand hygiene compliance, and apply, in particular, to formulations with high anti-viral activity. AIM: Clinical trial to evaluate the safety and tolerability of different virucidal hand rubs. METHODS: In a randomized, double-blind, four-period cross-over trial, healthy volunteers received three different virucidal hand rubs (P1-P3) and a reference product (R) in randomized sequence over a period of 4 days each with a washout period. The primary endpoint was skin barrier function measured by transepidermal water loss (TEWL) after application. RESULTS: Twenty-two subjects (seven male, 15 female; median age 25, range 21-54) were randomized and started at least one period. TEWL was 22.5; 95 %-confidence interval (CI): 19.6-25.4 after P1, 16.3; 13.5-19.1 after P2, 16.4; 13.4-19.3 after P3, and 24.0; 21.1-27.0 after R; p < 0.0001. The percentage of subjects experiencing at least one adverse event (AE) was 86 % with P1, 25 % with P2, 89 % with P3 and 56 % with R. The majority of AEs were skin reactions classified as of mild severity. No serious AEs were observed. CONCLUSIONS: Results were inconsistent. The number of AEs was higher than expected for all products. In summary, there is room for improvement both for hand rub development and the scientific approaches taken to practically and reproducibly evaluate hand rub safety and tolerability.

Evaluation of an aqueous-ethanolic extract from Pelargonium sidoides (EPs® 7630) for its activity against group A-streptococci adhesion to human HEp-2 epithelial cells.

AIM OF THE STUDY: The root extract of Pelargonium sidoides DC (Geraniaceae), EPs® 7630, is currently used to treat respiratory tract infections. The therapeutic benefits are largely related to the modulation of the non-specific immune system. The present study was designed to investigate the anti-adhesive activity of this herbal medicine with Streptococcus pyogenes as model microorganism and to identify the underlying biologically active principle. MATERIALS AND METHODS: Adherence of fluorescent-labelled group A-streptococci (GAS) to human epithelial (HEp-2) cells was assessed by flow cytometry. Anti-adhesive properties of the parent extract as well as a methanol-soluble (MSF) and a methanol-insoluble fraction (MIF) derived thereof were examined. Treatment with skin powder produced polyphenol-free samples which were included for comparison. Anti-adherence studies were extended to a series of highly purified proanthocyanidins including homogenous epicatechin- and catechin-based polyflavans, a 'mixed' procyanidin sample, an A-type proanthocyanidin mixture as well as a prodelphinidin test substance. RESULTS: After pre-treatment of GAS with EPs® 7630 or its subfractions MIF and MSF at concentrations of 30 µg/ml, adhesion of the pathogen to HEp-2 cells was inhibited by ca. 45%, ca. 35% and ca. 30%, respectively. However, following preincubation of cells with the extract and the fractions no effect was observed. This finding indicates that the anti-adhesive effects are due to interactions with binding factors on the bacterial surface. Since polyphenol-free samples proved to be inactive, proanthocyanidins appear to represent the anti-adhesive principle. Comparative studies with chemically defined proanthocyanidins revealed that the prodelphinidin nature, i.e. the pyrogallol B-ring elements of constituent flavanyl units, represented an important structural feature of the anti-adhesive potential of this herbal medicine. CONCLUSIONS: The current data provide strong evidence for a potent anti-adhesion principle of the Pelargonium sidoides root extract related to specific proanthocyanidins. This finding suggests an interaction with bacterial binding sites in a specific rather than non-specific manner. However, the blocked adhesion molecules remain to be identified. The anti-adhesive mechanism may well contribute to the anti-infective activity of EPs® 7630 at an early time point of a bacterial infection.

Seasonal and ascending trends in the incidence of carriage of extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella species in 2 German hospitals.

BACKGROUND: Extended-spectrum ß-lactamase (ESBL)-producing strains of bacteria have become a major public health concern. In the present study, the incidence of carriage of ESBL-producing strains was analyzed for general trends and seasonality. METHODS: Monthly data on ESBL-producing strains were collected retrospectively at 2 large university hospitals in Germany. The mean monthly temperatures for the 2 settings were collected from Germany's national meteorological service. Multivariable time series analyses were performed to explain variations in the monthly incidence densities of carriage of ESBL-producing bacteria (number of cases involving ESBL-producing Escherichia coli and/or Klebsiella species per 1,000 patient days). For the final models, we incorporated variables for the ascending linear trends and other variables representing the mean monthly temperature. RESULTS: Our models demonstrated that there was an increasing trend in the incidences of carriage of ESBL-producing bacteria. In addition, the incidences of carriage of all ESBL-producing bacteria responded positively to the mean temperature, meaning that during the summer, more cases involving ESBL-producing bacteria were detected than during the winter. The same methodology was also applied to the incidence of methicillin-resistant Staphylococcus aureus carriage, but no association was found with the mean temperature. CONCLUSIONS: In the present study, we demonstrated that the monthly incidence of carriage of ESBL-producing bacteria was highly correlated with the mean monthly temperature, a fact that should be considered in experimental studies as an additional parameter influencing the incidence of ESBL-producing bacteria.

Are short training sessions on hand hygiene effective in preventing hospital-acquired MRSA? A time-series analysis.

We tested the impact of short hand hygiene training sessions and bed occupancy rates on the spread of hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) using a multivariate time-series analysis. According to our model, bed occupancy rates within general ward and intensive care unit settings correlated positively with the incidence of hospital-acquired MRSA, whereas alcohol-based hand rub use and MRSA showed a negative correlation. Furthermore, our model shows that 2 hand hygiene campaigns based on short training sessions effected a long-run reduction in the incidence of hospital-acquired MRSA.

Two time-series analyses of the impact of antibiotic consumption and alcohol-based hand disinfection on the incidences of nosocomial methicillin-resistant Staphylococcus aureus infection and Clostridium difficile infection.

OBJECTIVE: To determine the impact of antibiotic consumption and alcohol-based hand disinfection on the incidences of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection and Clostridium difficile infection (CDI). METHODS: Two multivariate time-series analyses were performed that used as dependent variables the monthly incidences of nosocomial MRSA infection and CDI at the Freiburg University Medical Center during the period January 2003 through October 2007. The volume of alcohol-based hand rub solution used per month was quantified in liters per 1,000 patient-days. Antibiotic consumption was calculated in terms of the number of defined daily doses per 1,000 patient-days per month. RESULTS: The use of alcohol-based hand rub was found to have a significant impact on the incidence of nosocomial MRSA infection (P< .001). The multivariate analysis (R2=0.66) showed that a higher volume of use of alcohol-based hand rub was associated with a lower incidence of nosocomial MRSA infection. Conversely, a higher level of consumption of selected antimicrobial agents was associated with a higher incidence of nosocomial MRSA infection. This analysis showed this relationship was the same for the use of second-generation cephalosporins (P= .023), third-generation cephalosporins (P= .05), fluoroquinolones (P= .01), and lincosamides (P= .05). The multivariate analysis (R2=0.55) showed that a higher level of consumption of third-generation cephalosporins (P= .008), fluoroquinolones (P= .084), and/or macrolides (P= .007) was associated with a higher incidence of CDI. A correlation with use of alcohol-based hand rub was not detected. CONCLUSION: In 2 multivariate time-series analyses, we were able to show the impact of hand hygiene and antibiotic use on the incidence of nosocomial MRSA infection, but we found no association between hand hygiene and incidence of CDI.

The impact of antimicrobial drug consumption and alcohol-based hand rub use on the emergence and spread of extended-spectrum beta-lactamase-producing strains: a time-series analysis.

BACKGROUND: The aim of this study was to explore the temporal relationship between the consumption of different antibiotics, alcohol-based hand disinfection and the incidence of nosocomial bacterial strains producing extended-spectrum beta-lactamases (ESBLs). METHODS: Time-series analysis was performed based on monthly data available from January 2005 to October 2007. The incidence of nosocomial ESBL (cases/1000 patient-days) was regressed on the different antibiotic agents and the volume of alcohol-based hand rub orders. Antibiotic consumption was defined as monthly defined daily doses (DDD)/1000 patient-days, while alcohol-based hand rub was quantified in litres/1000 patient-days. RESULTS: The multivariate analysis showed that using alcohol-based hand rub for hand disinfection had a significant influence on the ESBL incidence (P = 0.002). A higher volume of alcohol-based hand rub use was subsequently associated with a lower incidence of ESBL-producing strains. Additionally, the model showed that temporal increase in the use of third-generation cephalosporins (P = 0.022) and fluoroquinolones (P = 0.001) is, after a time lag of up to 3 months, followed by temporal variations in the incidence of nosocomial ESBLs. Furthermore, the incidence of patients admitted with ESBL was also shown to have an influence on the incidence of nosocomial ESBLs (P < 0.001). The final model explained 75% of the monthly variations in the incidence of nosocomial ESBLs. CONCLUSIONS: The analysis identifies selective pressure caused by the use of different antimicrobial agents as a driving factor in the emergence and spread of ESBLs. Furthermore, the study confirms that hand disinfection is key to the prevention of nosocomial ESBLs.

Extract of Pelargonium sidoides (EPs 7630) displays anti-infective properties by enhanced phagocytosis and differential modulation of host-bacteria interactions.

EPs 7630 is an aqueous-ethanolic extract of the roots of PELARGONIUM SIDOIDES that displays well-documented benefits in the treatment of upper respiratory tract infections (URTI). IN VITRO and animal investigations have revealed various anti-infective properties of EPs 7630. The present review sums up recently published IN VITRO investigations that have shown positive effects on the activity of human peripheral blood phagocytes (PBP) and differential modulation of the interactions between group A streptococci and the host's epithelial barrier.

[Pelargonium sidoides-extract (EPs 7630): registration confirms efficacy and safety]. / Pelargonium sidoides-Extrakt (EPs 7630): Zulassung bestätigt Wirksamkeit und Verträglichkeit.

For centuries the roots of Pelargonium sidoides DC have been used in South African ethno-medicine for the treatment of respiratory diseases. In Germany, a medicinal product containing a special extract of this substance is among the group of self-medication products most widely bought at chemist's shops. In December 2005, the Federal Institute for Drugs and Medical Devices (BfArM, Bonn) approved a new license for its use as a drug. The following review focuses on the current pharmacological, toxicological and clinical data covering the efficacy and innocuousness of this drug when administered for the treatment of acute bronchitis.

Extract of Pelargonium sidoides (EPs 7630) inhibits the interactions of group A-streptococci and host epithelia in vitro.

EPs 7630 is an extract of the root of the South African geranium Pelargonium sidoides. Clinical data have shown that this herbal drug preparation can be used to treat upper respiratory tract infections (URTI). The objective of this study was to investigate the impact of EPs 7630 on group A-streptococci (GAS) adhering to and invading host epithelial cells in vitro. Adhesion was assessed by a flow cytometric adhesion assay using calcein-AM-stained S. pyogenes (DSM 2071) as test organism, and HEp-2 cells and buccal epithelial cells (BEC) as substrata. For cell invasion, HEp-2 cell monolayers were infected with S. pyogenes. Intracellular bacteria were determined using a penicillin/gentamicin-protection assay. EPs 7630 was applied in therapeutically relevant concentrations between 0 and 30 microg/ml in both test systems. Compared to controls, EPs 7630 significantly reduced GAS adhesion to HEp-2 cells in a concentration-dependent manner by up to 46% (p<0.001). This was semi-quantitatively confirmed by fluorescence microscopy. Adhesion kinetics additionally indicated a specific antagonistic effect on GAS adhesion. Pre-treatment of epithelial cells or GAS with EPs 7630 showed that it targets GAS rather than HEp-2 cells. However when using BEC as substrata, GAS adhesion increased 7-fold under the influence of EPs 7630 (p<0.001). In viability assays, HEp-2 suspension contained over 90% vital cells, whereas only 10% of the BEC were viable. EPs 7630 reduced GAS invasion of HEp-2 cells significantly when the data taken at time points 60, 120, and 180 min (p=0.026) were analyzed. In conclusion, EPs 7630 develops complementary anti-infective properties: Firstly, EPs 7630 reduces bacterial adhesion to intact epithelial cells and thus protects the organism from bacterial colonization and infection/super-infection. Secondly, EPs 7630 enhances the attachment of bacteria to decaying BEC. In this way pathogens may be trapped and rendered inactive. Thirdly, the inhibition of GAS invasion of epithelial cells protects the host from microorganisms that may have evaded host defences and antibiotic treatment, and therefore prevents recurrent infections. Thus, our investigations provide a rational basis for the treatment of URTI with EPs 7630.

Extract of Pelargonium sidoides (EPs 7630) improves phagocytosis, oxidative burst, and intracellular killing of human peripheral blood phagocytes in vitro.

Clinical data show that EPs 7630, an aqueous ethanolic extract from the roots of Pelargonium sidoides, can be used for the treatment of upper respiratory tract infections (URTI). The biological effects of the preparation have not been fully investigated. The objective of this study was to examine the impact of EPs 7630 on the activity of human peripheral blood phagocytes (PBP). A whole blood-based, flow cytometric assay was used to simultaneously assess phagocytosis and oxidative burst. Calcein-AM stained Candida albicans (DSM 1386) were used as target organisms. Oxidative burst was measured by addition of dihydroethidium (DHE). Target organisms and whole blood were co-incubated and analyzed after 0, 2, 4, 6, 10, and 30 min. Intracellular killing of the target organisms was evaluated by determining the number of surviving yeast cells after co-incubation of C. albicans and human whole blood. EPs 7630 was applied in therapeutically relevant concentrations between 0 and 30 microg/ml. Compared with controls EPs 7630 increased the number of phagocytosing PBP during the observed time points between 2 and 10 min in a concentration-dependent manner, with a maximum enhancement of 56% at 2 min (p=0.002). The application of EPs 7630 also led to a significant increase in the number of burst-active PBP for all time points observed beyond 2 min (p<0.001). The maximum augmentation was 120% after application of 30 microg/ml EPs 7630 at 4 min. Using a microbiological assay, intracellular killing was also enhanced by EPs 7630. This was expressed by a significant reduction in the number of surviving target organisms (p<0.001). The maximum reduction in viable yeast cells (-31%) was observed after co-incubation for 120 min with the highest concentration of EPs 7630 (30 microg/ml). In conclusion, the positive effects of EPs 7630 on phagocytosis, oxidative burst, and intracellular killing of yeast cells as test organisms are important components of the compound's biological activity. Our findings constitute a valuable contribution to understanding the clinical effects of EPs 7630.

[In vitro study to evaluate the antibacterial activity of a combination of the haulm of nasturtium (Tropaeoli majoris herba) and of the roots of horseradish (Armoraciae rusticanae radix)]. / In-vitro-Untersuchungen zur antibakteriellen wirksamkeit einer Kombination aus Kapuzinerkressenkraut (tropaeoli majoris herba) und meer- rettichwurzel (armoraciae rusticanae radix).

OBJECTIVE: To evaluate the in-vitro antimicrobial properties of a commercialized preparation (Angocin Anti-Infekt N) containing a combination of the haulm of nasturtium (Tropaeoli majoris herba; N) and of the roots of horseradish (Armoraciae rusticanae radix; H). This preparation can be used to treat upper respiratory tract (URTI) and urinary tract infections (UTI). The active ingredients are volatile mustard oils, which are activated in the gastrointestinal tract after oral intake. Previous research has shown mustard oils derived from either N or H to possess antibacterial activity. METHODS: In order to assess the antimicrobial capacity of phytotherapeutic compounds containing volatile mustard oils, a modified gas-test was used. Native preparations of N and H were applied to the lids of Columbia agar plates (ratio N:H = 2.5:1) and mixed with sterile H20. Thirteen different bacterial species including Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Pseudomonas aeruginosa, Streptococcus pyogenes, methicillin-susceptible and resistant Staphylococcus aureus (MSSA, MRSA) were tested (20 isolates each). The test organisms were plated onto the blood agar plates and placed above the native preparations. The plates were sealed with adhesive tape and incubated at 37 degrees C. Following incubation of 24 h and 92 h, colony forming units (CFU) were counted and the minimal inhibitory concentrationg (MIC90) was determined for each bacterial species. RESULTS: Relevant antimicrobial activities of the combined native preparations were found against H. influenzae (MIC90 50 mg N / 20 mg H), M. catarrhalis (100 mg N / 40 mg H), E. coli (400 mg N / 160 mg H), P aeruginosa (400 mg N / 160 mg H), MSSA (400 mg N 1 160 mg H), MRSA (400 mg N / 160 mg H), and S. pyogenes (400 mg N / 160 mg H). CONCLUSION: Antimicrobial testing of a combination of N and H revealed broad antibacterial activities against clinically relevant pathogens covering both gram-positive and gram-negative organisms, thus confirming previous reports of the antibacterial properties of mustard oils. Additionally, this study demonstrated that the combination of N and H leads to synergistic activity in terms of improved Pseudomonas-susceptibility compared to the previous reported activities of the single compounds. Thus, these results prove that there is a rational basis for treatment of URTI and UTI with a combination of N and H.