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We have investigated the effect of isoprenaline on the amplitude of the transient contraction of isolated arteries induced by releasing the intracellular Ca with an agonist during incubation in a Ca-free solution. Under some conditions this force development is an indication of the amount of Ca in the intracellular store. Loading the store in high K solution in the presence of isoprenaline increases the amplitude of the subsequent contraction in Ca-free solution by 6 to 16% as compared to the control. The presence of isoprenaline during the loading procedure in the control solution with 5.9 mM K does not affect the amplitude of the subsequent contraction of the rabbit ear artery. In the rabbit coronary artery such pretreatment with isoprenaline inhibits the contraction to 40% of the control. These results indicate that β-agonists may stimulate the Ca uptake in the intracellular store and, depending on the tissue, inhibit the influx of Ca. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Although many women with recurrent vulvovaginal candidiasis initially benefit from prophylactic intermittent treatment with antimycotics, most of them experience relapse after cessation of therapy, and often they return to the pretreatment recurrence rate. The purpose of this study was to demonstrate the efficacy and safety of an individualized, degressive, prophylactic regimen in 136 women with recurrent vulvovaginal candidiasis. STUDY DESIGN: After an induction dose of 600 mg fluconazole during the first week, 117 women started maintenance therapy: 200 mg fluconazole weekly for 2 months, followed by 200 mg biweekly for 4 months, and 200 mg monthly for 6 months, according to their individual response to therapy. All women were tested for recurrences monthly with wet mount microscopy and vaginal culture during the first 6 months and bimonthly during the next 6 months. Patients were allowed to move on to the next level of maintenance therapy only if they were symptom free and microscopy and culture negative. RESULTS: Of the women who were cured successfully after the induction phase, 101 women (90%) were disease-free after 6 months of maintenance therapy with this degressive regimen, and 80 women (77%) were disease-free after 1 year. The weekly incidence of the first clinical relapse was 0.5% during any period of the maintenance phase, and the rate of all new relapses, which included evidence of mycologic or microscopic colonization, was 1% per week. Women who experienced several relapses (poor responders) had experienced more relapses before entering the study compared with the optimal responders (odds ratio, 4.9; 95% CI,1.8-13.7; P = .002), experienced the disease for a longer period of time (6.5 vs 3.7 years; P = .06), and harbored significantly more Candida non-albicans during maintenance therapy (P = .001). No serious side-effects were noted. CONCLUSION: Individualized, degressive, prophylactic maintenance therapy with oral fluconazole is an efficient treatment regimen to prevent clinical relapses in women with recurrent vulvovaginal candidiasis. [ABSTRACT FROM AUTHOR]

Abstract: We describe the development and application of a rapid and universal molecular technique for direct identification of multiple bacteria in clinical samples. Amplification of the 16S–23S rRNA spacer-region using universal primers led to fragment patterns distinct for different bacterial species and that were analyzed with fluorescent amplicon length analysis (FALA). 136 pure cultures of clinical isolates and 20 culture collection strains belonging to 22 different medically important species were used to create a primary database of fragments with sizes between 100 and 1000 bp. Subsequently, 127 respiratory samples were analyzed with culture-based techniques and via FALA of the 16S–23S rRNA spacer-region. Two DNA extraction methods were evaluated: Instagene® (FALA-I) and Fastprep™ (FALA-P). Of the 127 samples, 26 culture-negative samples were also negative with FALA-P. Of 18 samples with growth of commensal oral flora, 10 gave a mixed oral flora pattern with FALA-P and 8 gave a negative result. For 54 samples with growth of a single bacterial species, FALA-P gave an identical result for 46. For 29 samples with growth of more than one bacterial species, identical results were obtained in 19 samples. False-negative results with FALA-P were mostly due to paucity (less than 103 CFU/ml) of bacteria (12 out of 18 false-negatives) or difficulties with homogenization of viscous samples (6 out of 18 false-negatives).With regard to identification of all significant pathogens of clinical samples tested, the sensitivity of FALA-P was 77% and its specificity was 100%. With FALA-I, the number of false-negative results was higher than with FALA-P due to less efficient extraction of DNA, particularly with Staphylococcal species. FALA-P allows rapid and direct identification of multiple species directly from clinical samples; pauci-cellular samples may give false-negative results. [Copyright &y& Elsevier]

Clinical microbiology should have a physical presence, but not necessarily on-site diagnostic laboratory facilities, in each hospital to ensure a quality laboratory-based infection service and strong professional interaction with clinicians. The adoption of industrial practices and the introduction of new costly molecular techniques raise the possibility that non-microbiological functions of laboratory management could be left to management professionals. This remains highly controversial; the advantages must be contrasted with the potential to disrupt the traditional managerial responsibility of the microbiologist and the links between the laboratory and clinical staff. Managers and healthcare professionals must resolve this issue, perhaps with the support of the ESCMID. Views varied, according to current professional arrangements and size of the laboratory and population served, on whether there should be a common laboratory for microbiology and other pathology disciplines with joint access to new high-technology techniques, or whether microbiology must continue as a separate facility. Clinical microbiology and infection control were viewed as core services that must be present even in smaller hospitals. Larger community hospitals and teaching centres require a full complement of expertise in laboratory and clinical practice. Integration of these disciplines within a department of infection is an emerging concept. A concern was the shortfall in trained expertise because of the ageing nature of current specialists. The importance of recruiting talented new graduates was emphasised. The importance of this topic led to a recommendation that an ESCMID working party be established to investigate the current arrangements of infection services in Europe and to make recommendations for the future organisation. [ABSTRACT FROM AUTHOR]

Quinolones are one of the largest classes of antimicrobial agents used worldwide. This review considers the quinolones that are available currently and used widely in Europe (norfoxacin, ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin) within their historical perspective, while trying to position them in the context of recent and possible future advances based on an understanding of: (1) their chemical structures and how these impact on activity and toxicity; (2) resistance mechanisms (mutations in target genes, efflux pumps); (3) their pharmacodynamic properties (AUC/MIC andCmax/MIC ratios; mutant prevention concentration and mutant selection window); and (4) epidemiological considerations (risk of emergence of resistance, clonal spread). Their main indications are examined in relation to their advantages and drawbacks. Overall, it is concluded that these important agents should be used in an educated fashion, based on a careful balance between their ease of use and efficacy vs. the risk of emerging resistance and toxicity. However, there is now substantial evidence to support use of the most potent drug at the appropriate dose whenever this is required. [ABSTRACT FROM AUTHOR]

Abstract Objectives: Porphyromonas gingivalis , one of the key pathogens in the development of periodontitis, produces a number of virulence factors that might explain its pathogenicity. One of them is the ability to adhere and invade pocket epithelium. The aim of this study was to follow, over time, the association of P. gingivalis and consequent morphological changes of the pocket epithelium cells. Material and Methods: The association capacity of four P. gingivalis serotypes [K1, K2, K4, K- (nonencapsulated)] with in vitro cultured mono-layers from periodontal pocket epithelial cells of patients with periodontitis, was followed by fluorescence microscopy and bacterial culture. The contact time between bacteria and epithelium cells ranged from 45 min to 8 h. The microscopic evaluation allowed differentiation between dead and living cells (bacteria as well as epithelium) and description of the morphological changes after association. Results: A highly significant difference in the number of associating bacteria was found between dead and living epithelium cells, and between non-capsulated and capsulated strains. A significant increase in the proportion of dead pocket epithelium cells was found with prolonged association time. The morphological changes (rounding of the epithelial cell, detachment from the glass cover-slip and loss of intercellular contact) occurred faster for mono-layers inoculated with the non-encapsulated P. gingivalis strain. Conclusions: This study indicates that dead pocket epithelium cells harbor more P. gingivalis cells, and that a positive correlation exists between contact time and cell death. For the P. ginigvalis species, non-encapsulated strains associate in higher number. As a result, the damage they cause to the host cell seems to occur faster than occurs in encapsulated strains. As such, cell death can be seen as the end-result of bacterial association. [ABSTRACT FROM AUTHOR]

A challenge panel of bacterial strains useful for clinical laboratories to validate their European Committee on Antimicrobial Susceptibility Testing (EUCAST) antimicrobial susceptibility test (AST) system was established. A total of 117 strains, obtained from Belgian Reference Centres ( n = 57) and from routine clinical samples ( n = 60) was selected based on resistance pattern. These strains were analysed in seven different laboratories by three different automated AST systems (Vitek ( n = 2), Phoenix ( n = 2) and Microscan ( n = 2)) and by disc diffusion from five different manufacturers (Rosco ( n = 2), Becton-Dickinson ( n = 2), Biomérieux ( n = 1), Bio-rad ( n = 1) and i2a ( n = 1)). To select the challenge panel, selection criteria were set for categorical agreement between the different systems and the number of very major errors, major errors and minor errors. Very major and major errors for at least two antibiotics were observed in 43% of all strains, leading to the exclusion of these strains from the selected panel. In only 10% of all tested strains was there 100% categorical agreement for all antibiotics. Finally, 28 strains (14 Gram-positive and 14 Gram-negative) covering a wide spectrum of resistance mechanisms were selected. Pilot-testing of this challenge panel in 20 laboratories mainly confirmed the results of the validation study. Only six strains withheld for the pilot study could not be used as challenge strain due to an overall (very) major error rate of >5% for a particular antibiotic ( n = 5) or for two antibiotics ( n = 1). To conclude, this challenge panel should facilitate the implementation and use of EUCAST breakpoints in laboratories. [ABSTRACT FROM AUTHOR]

Biofilm-associated bacteria display a decreased susceptibility towards antibiotics. Routine assessment of antibiotic susceptibility of planktonic bacteria therefore offers an insufficient prediction of the biofilm response. In this study, in vitro biofilms of eight clinical Staphylococcus epidermidis strains were subjected to treatment with vancomycin, teicoplanin, oxacillin, rifampicin and gentamicin. In addition, the biofilms were subjected to combinations of an antibiotic with rifampicin. The effects on the biofilms were assessed by crystal violet staining to determine the total biofilm biomass, staining with XTT to determine bacterial cell viability, and microscopy. Combining these methods showed that treatment of S. epidermidis biofilms with glycopeptides increased the total biofilm biomass and that these antibiotics were not effective in killing bacteria embedded in biofilms. The decreased killing efficacy was more pronounced in biofilms produced by strains that were classified as ‘strong’ biofilm producers. Rifampicin, oxacillin and gentamicin effectively killed biofilm-associated bacteria of all tested strains. Combining antibiotics with rifampicin increased the killing efficacy without influencing the total biofilm biomass. When vancomycin or teicoplanin were combined with rifampicin, the increase in biofilm biomass was neutralised and also the killing efficacy was influenced in a positive way. We conclude that the combined methodology used in this study showed that glycopeptides were not effective in eradicating S. epidermidis biofilms but that combination with rifampicin improved the killing efficacy in vitro. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to determine the proportion of influenza-like illness (ILI) attributable to specific viruses during the influenza A(H1N1)2009 pandemic and to describe the demographic and clinical characteristics of ILI due to respiratory viruses in Belgium. Nasopharyngeal swabs were collected from ILI patients by general practitioners (GPs) and paediatricians (PediSurv) and analysed for viruses. Of 139 samples collected from children <5 years of age by PediSurv, 86 were positive, including 28 influenza (20%), 27 respiratory syncytial virus (RSV) (19%), 21 rhinovirus (17%), 12 human metapneumovirus (hMPV) (9%) and ten parainfluenza virus (PIV) (7%). Of 810 samples received from GPs, 426 were influenza (53%). Of 312 influenza-negative samples, 41 were rhinovirus (13%), 13 RSV (4%), 11 PIV (4%) and three hMPV (1%). Influenza mostly affected the 6-15 years old age group. Other respiratory viruses were commonly detected in the youngest patients. Similar clinical symptoms were associated with different respiratory viruses. Influenza A(H1N1)2009 was the most detected virus in ILI patients during the 2009-2010 winter, suggesting a good correlation between ILI case definition and influenza diagnosis. However, in children under 5 years of age, other respiratory viruses such as RSV were frequently diagnosed. Furthermore, our findings do not suggest that the early occurrence of the influenza A(H1N1)2009 epidemic impacted the RSV epidemic in Belgium. [ABSTRACT FROM AUTHOR]

Recently, the predation of Bdellovibrio bacteriovorus on a periodontal pathogen has been described. The current study explores the potential antimicrobial activity of a range of predatory bacteria against key periodontal pathogens. A number of representatives from the Bdellovibrio, Bacteriovorax and Peredibacter lineages (called 'BALOs') were tested for their activity towards a group of key periodontal pathogens and an optimal multiplicity of infection was established. As the oral cavity contains a wide variety of bacteria that are not preyed upon, it was investigated if they can have an effect on the predation efficiency of BALOs. It was concluded that a number of important variables involved in bacterial predation are found to be compatible with the composition of the oral microbiota. This finding makes the case for continued study of the potential for BALOs to combat periodontal pathogens. [ABSTRACT FROM AUTHOR]

Introduction: Microbial interactions are considered to be important for bacterial colonization. Interactions that inhibit colonization of pathogens could possibly be used as a new treatment approach for periodontitis. The aim of this study was to test this hypothesis on soft surfaces in vitro, taking into account the hydrodynamic forces continuously present in vivo. Methods: Cultured epithelial cells were precolonized with Streptococcus sanguinis KTH-4, Streptococcus cristatus CC5A, Streptococcus salivarius TOVE and Streptococcus mitis BMS before Aggregatibacter actinomycetemcomitans colonization. Experiments were performed in a modified Robbins-device-type flow cell. Bacterial colonization and the number of epithelial cells were evaluated by microbial culturing and quantitative polymerase chain reaction. Results: The streptococci were able to inhibit A. actinomycetemcomitans colonization on soft tissue surfaces under flow conditions. Statistically significant differences were found between streptococcal pretreatments and the controls, with the most pronounced effect caused by S. sanguinis. Conclusion: These data confirm the possibility of applying beneficial bacteria in periodontal treatment. [ABSTRACT FROM AUTHOR]

Introduction: Oral bacteria must attach to hard and soft tissues to colonize the oral cavity in the presence of a variety of forces caused by shear and flow. In vitro models mimicking this dynamic process are indispensable to study factors that might interfere with the first step towards infection. For extrapolation purposes the comparability between the dynamics of colonization on hard vs. soft surfaces needs to be evaluated. Methods: The colonization of glass and epithelial cell surfaces by the periodontal pathogen Aggregatibacter actinomycetemcomitans was followed in time with two flow cell models: a modified Robbins device (MRD) and an in situ image analysis system. Results: The number of A. actinomycetemcomitans recovered from the soft surfaces in the MRD experiments was higher than on glass. The amount of bacteria on the hard surfaces kept increasing with time, while on soft surfaces saturation was reached. The microscope-mounted flow cell allowed real-time in situ monitoring of the colonization process of both surfaces. Conclusion: These experimental models may have a great contribution to make in the development of new treatment approaches for periodontal diseases. Colonization by A. actinomycetemcomitans could be studied under flow conditions and its dynamics showed important surface-dependent characteristics. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is a major cause of nosocomial infections. This organism shows a remarkable capacity to resist antibiotics, either intrinsically (because of constitutive expression of β-lactamases and efflux pumps, combined with low permeability of the outer-membrane) or following acquisition of resistance genes (e.g., genes for β-lactamases, or enzymes inactivating aminoglycosides or modifying their target), over-expression of efflux pumps, decreased expression of porins, or mutations in quinolone targets. Worryingly, these mechanisms are often present simultaneously, thereby conferring multiresistant phenotypes. Susceptibility testing is therefore crucial in clinical practice. Empirical treatment usually involves combination therapy, selected on the basis of known local epidemiology (usually a β-lactam plus an aminoglycoside or a fluoroquinolone). However, therapy should be simplified as soon as possible, based on susceptibility data and the patient's clinical evolution. Alternative drugs (e.g., colistin) have proven useful against multiresistant strains, but innovative therapeutic options for the future remain scarce, while attempts to develop vaccines have been unsuccessful to date. Among broad-spectrum antibiotics in development, ceftobiprole, sitafloxacin and doripenem show interesting in-vitro activity, although the first two molecules have been evaluated in clinics only against Gram-positive organisms. Doripenem has received a fast track designation from the US Food and Drug Administration for the treatment of nosocomial pneumonia. Pump inhibitors are undergoing phase I trials in cystic fibrosis patients. Therefore, selecting appropriate antibiotics and optimising their use on the basis of pharmacodynamic concepts currently remains the best way of coping with pseudomonal infections. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to examine the accuracy of the presence of high-risk human papillomavirus (HR-HPV) DNA (HR-HPV DNA test) postconisation as prediction of recurrent or residual cervical intraepithelial neoplasia (CIN) after treatment of high-grade cervical intraepithelial lesions (CIN2+) in a prospective study and to compare this with follow-up cytology and the marginal status of the excised tissue. Design Prospective follow-up study. Setting Unselected women presenting at colposcopy clinic of University Hospital Gasthuisberg, Leuven. Population Seventy-two women treated with conisation for CIN2 or CIN3. Methods Women were followed by HR-HPV DNA test (Hybrid Capture II test of Digene®) every 3 to 6 months. The same vial was used for cytology and the HR-HPV DNA test (SurePath™). All women were further followed by colposcopy and cytology for 24 months at 6-month intervals. The outcome of the study was presence of >CIN2, proven with colposcopy-directed biopsy occurring within 24 months after treatment. HR-HPV status was correlated with recurrent or residual CIN2+. Main outcome measures Sensitivity, specificity, predictive values and diagnostic odds ratios to predict treatment failure or cure were computed for HR-HPV testing, marginal status and follow-up cytology. HR-HPV status was also correlated with section margins postconisation and with the first cervical smear. Results In 6 of the 72 treated women (8%), residual or recurrent CIN occurred. Women with recurrence were significantly older than women without a recurrence (51.5 ± 9.6 versus 39.8 ± 12.2 years, P= 0.007). All six women with recurrence were HR-HPV positive, four had a positive follow-up smear (≥atypical squamous cells of uncertain significance = ASCUS+) and only two had involved section margins. Among the 66 cured women, 15 were HR-HPV positive, 6 had an abnormal smear and 12 had positive section margins. Sensitivity of cytology, positive section margins and HR-HPV DNA positivity was 66.7, 33.3 and 100% to predict treatment failure. Specificity of the three tests was, respectively, 90.9, 81.8 and 77.3%. Women with HR-HPV DNA at 3 to 6 months showed recurrent or residual CIN in 15% (2/13) if they had normal follow-up Pap smears and in 50% (4/8) if they had abnormal Pap smears. Margin status was not statistically significantly associated with human papillomavirus status. Conclusion Persistence or clearance of HR-HPV DNA is an early valid prognostic marker of failure or cure after treatment for CIN2+ and is more accurate than cytology or section margin status at the time of conisation. The absence of HR-HPV DNA has a 100% negative predictive value. Higher age at conisation may be a previously unrecognised risk factor for recurrence. [ABSTRACT FROM AUTHOR]

During a 4-month period we prospectively investigated the frequency of polyclonal catheter infections with Staphylococcus epidermidis. Of each catheter with pure growth of S. epidermidis, six colonies were genotypically analyzed with pulsed-field gel electrophoresis. Two out of 12 patients with catheter infection had a polyclonal infection. Both clones of each catheter had a clearly different antibiotic susceptibility. This study shows that polyclonal catheter infections are not exceptional. Further studies are needed to define the clinical consequences of polyclonal catheter infection. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of this project was to study the influence of pneumococci on nasopharyngeal epithelial integrity as a function of time and pneumococcal density. Materials and methods Cell layers of an in vitro model of human nasopharyngeal epithelium were inoculated with different pneumococcal strains. The transepithelial electrical resistance (TEER), a measure of the integrity of the cell layers, and the pneumococcal concentration in the apical fluid on the epithelial cells were measured at different times after inoculation. Results Pneumococci caused a decrease in the TEER when a density of 1 × 107 CFU mL -1 was reached. The growth rate of pneumococci in our in vitro model differed between the strains tested and, for the same strain, between in vitro culture on the epithelial cells and broth culture. Differences in timing of the onset of decrease in the TEER between strains were the result of differences in growth rate on the epithelial cells. Antibiotic-induced lysis of pneumococci caused an immediate decrease in the TEER of the cell layers. Conclusion Pneumococci cause a decrease in the TEER at a density of 1 × 107 CFU mL -1 . Our hypothesis is that this decrease in the TEER is the result of quorum-induced lysis of the pneumococci. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the usefulness of detecting two genes involved in biofilm formation (icaA and aap ) and one gene involved in initial adhesion (atlE ) for discrimination between contaminant, colonizing and invasive Staphylococcus epidermidis isolates involved in catheter-related infections. Patients: The first group contained 29 isolates that were isolated from the skin of healthy volunteers (contaminant isolates). The second group contained 16 isolates recovered from catheters (>1000 CFUs on quantitative catheter culture) from asymptomatic patients without bacteremia. These isolates were considered to be colonizing isolates. The third group contained 34 isolates grown in ≥2 different blood cultures from patients with a systemic inflammatory response. These isolates were considered to be invasive isolates. Results: The prevalence of atlE did not differ between the three groups. The icaA and aap genes were significantly more prevalent in colonizing isolates (88% aap ; 88% icaA ) than in invasive isolates (68% aap , P = 0.179; 59% icaA , P = 0.055) and than in skin isolates (52% aap , P = 0.02; 38% icaA , P = 0.002). Conclusions: The high prevalence of aap and icaA in skin isolates and their higher prevalence in colonizing than in invasive isolates led to a low specificity when these genes were used to differentiate between contamination, colonization and invasive infection. We conclude that, although the prevalence of these genes differs in the three groups, their presence cannot be used for clinical decision-making. [ABSTRACT FROM AUTHOR]

Objective To follow the evolution of capsular types and resistance of Streptococcus pneumoniae, isolated from deep sites. Methods More than 100 Belgian laboratories permanently collect S. pneumoniae strains isolated from puncture specimens (blood, cerebrospinal fluid, middle ear fluid, etc.) and forward them to the reference center in Leuven, in order to determine the capsular serogroups and types (SGTs) and their resistance. Results From 1994 to 1998, the 5486 S. pneumoniae strains examined belonged to 39 of the 46 currently identified SGTs. The 10 most frequent SGTs accounted for 78.9% of the isolates, and 97% of all isolates belonged to SGTs included in the 23-valent vaccine. Overall mortality of patients with pneumococcal bacteremia or meningitis was 9.7%, and 23.8% in patients over 80 years. From 1994 to 1998, resistance to penicillin (P) increased from 7.6% to 14.2%, to tetracycline (T) from 14.9% to 28.0%, and to erythromycin (E) from 22.9% to 31%. Triple resistance (PTE) increased from 0.9% in 1994 to 6.6% in 1998. Five SGTs (6, 9, 14, 19 and 23) accounted for 50% of the isolates, but for > 90% of the penicillin-resistant or erythromycin-resistant isolates. Conclusions Resistance of S. pneumoniae to penicillin, erythromycin and tetracycline is steadily increasing and is concentrated in five serotypes included in the 23-valent pneumococcal vaccine. Increasing resistance and high mortality of invasive infections are an incentive to vaccinate vulnerable groups. [ABSTRACT FROM AUTHOR]

Introduction/Background Documentation of the International Classification of Functioning, Disability and Health (ICF) components in physiotherapeutic electronic health records may improve interdisciplinary productivity and efficiency We examine the effect of targeted teaching and personalized feedback on physiotherapists’ completion of physiotherapeutic patient records and description of these components. Material and method A randomized controlled trial in a tertiary care hospital in Belgium Ten physiotherapists were included in the intervention group and five physiotherapists were in the control group The intervention (2015–2016) included targeted teaching and weekly personalized feedback for a period of four weeks regarding reporting of ICF components in electronic patient records At baseline, after targeted training, after each round of personalized feedback, and at long-term follow-up, electronic patient records for 10 random patients per physiotherapist in the intervention group were reviewed for completion of a physiotherapeutic patient record and reporting of ICF components Data for the control group were collected at baseline, after the third round of feedback, and at long term follow-up 670 and 140 patient records from 729 unique patients were reviewed for the intervention and control group, respectively. Results In the intervention group, all outcomes improved (Table 1 and Fig. 1) Although reporting declined for several components between personalized feedback and at long-term follow-up, at both occasions patient record completion and reporting of ICF components of activity, participation, and personal factors were significantly higher compared to the control group For environmental factors, the significant effect after personalized feedback disappeared at long-term follow-up Reporting of body functions and structures improved similarly across groups. Conclusion Targeted teaching and personalized feedback improved completion of physiotherapeutic patient records and reporting of ICF components Intervention strategies should factor in regular reminders to ensure continued reporting of ICF components in the long term. [ABSTRACT FROM AUTHOR]

There is an arms race between beta-lactam antibiotics development and co-evolving beta-lactamases, which provide resistance by breaking down beta-lactam rings. We have observed that certain beta-lactamases tend to aggregate, which persists throughout their evolution under the selective pressure of antibiotics on their active sites. Interestingly, we find that existing beta-lactamase active site inhibitors can act as molecular chaperones, promoting the proper folding of these resistance factors. Therefore, we have created Pept-Ins, synthetic peptides designed to exploit the structural weaknesses of beta-lactamases by causing them to misfold into intracellular inclusion bodies. This approach restores sensitivity to a wide range of beta-lactam antibiotics in resistant clinical isolates, including those with Extended Spectrum variants that pose significant challenges in medical practice. Our findings suggest that targeted aggregation of resistance factors could offer a strategy for identifying molecules that aid in addressing the global antibiotic resistance crisis., (© 2023. Springer Nature Limited.)

Actinomycosis is an opportunistic infection caused by bacteria of the Actinomyces spp., commonly A. israelii. These are non-pathogenic commensals in the mouth, gut, and female genital tract. An infection may arise following trauma or surgery, such as tooth extraction. More than half of cases of actinomycosis occur in the perimandibular area and are termed cervicofacial actinomycosis. Initially, the infection develops as a painful, rapidly progressive swelling. The lesion may then indurate and is often painless while the overlying skin discolors red to purple-blue. Prolonged treatment with antibiotics and surgery are often required for resolution, unless treatment is promptly started. However, diagnosis may be delayed or missed because of difficult bacterial culturing and frequent confusion with malignancy and other infections. This case study describes six patients who developed cervicofacial actinomycosis following third molar extraction. The purpose of this study is to inform clinicians on this stubborn and deceitful disease entity and to highlight the importance of clinical recognition for quick resolution with minimal morbidity.

Purpose: Evidence supports the implementation of outpatient parenteral antimicrobial therapy (OPAT) as standard of care. Until 2015 the overall experience with OPAT in Belgium remained limited. The aim of this study was to evaluate the efficacy and safety of a Belgian 'OPAT at home' program, which was implemented in University Hospitals Leuven starting from January 2017., Methods: A mono-centric, prospective, observational study was carried out. All OPAT cases discharged between 10 January 2017 and 10 January 2019 were included in the study. Relevant demographic and clinical patient data were collected. The outcomes were clinical cure rate, OPAT related readmission rate, adverse event rate and patients' satisfaction., Results: Over the two-year study period, 152 OPAT episodes were started in 130 patients, resulting in 3153 avoided hospitalization days which corresponds to 5.4 freed hospital beds. Urinary tract infections accounted for 40.8% of OPAT courses and temocillin was the most frequently used antibiotic (24.3%). Cure was achieved in 97.9% of the OPAT episodes. During 22 (14.5%) OPAT episodes, patients experienced adverse events, including line related adverse events (7.9%) and adverse drug events (6.6%). An OPAT related readmission rate of 9.2% was observed, mostly related to line-associated adverse events. All patients who completed the satisfaction survey (n = 23) were very satisfied with their OPAT course., Conclusion: The University Hospitals Leuven OPAT program is associated with a high level of clinical cure and low all-cause readmission and adverse event rates. Improvement actions are described to further reduce the readmission rate to less than 5.0%.

Rationale, Aims, and Objectives: The International Classification of Functioning, Disability and Health (ICF) is a landmark for physiotherapy to describe the full spectrum of human functioning, but ICF patient record completion could improve. In this study, we examine the effect of supervised teaching and personalized feedback on physiotherapists' completion and reporting of ICF in electronic patient records., Method: In this proof-of-concept randomized controlled trial, the intervention group (10 physiotherapists) received supervised teaching and four rounds of personalized feedback on reporting of ICF components in electronic patient records. In the intervention group, review on patient record completion (n = 670 records) was performed at baseline, after teaching, after each of four feedback rounds, and at long-term follow-up. In the control group (five physiotherapists), which received no supervised teaching nor personalized feedback, review (n = 140 records) was performed at baseline, after the third feedback round of the intervention group, and at follow-up., Results: After the third round of feedback (95% vs 72% completion; β, 2.68; 95% CI, 0.62-4.74), patient record completion was significantly higher in the intervention group. This was also true for following ICF components: "activity" (93% versus 64% completion; β, 3.03; 95% CI, 1.52-4.54), "participation" (50% versus 14% completion; β, 3.67; 95% CI, 1.79-5.55), and "personal factors" (35% versus 20% completion; β, 2.10; 95% CI, 0.63-3.57). These statistically significant and clinically relevant effects persisted at long-term follow-up. For "environmental factors," effects after the third round of feedback (75% vs 30% completion; β, 1.88; 95% CI, 0.63-3.13) disappeared at follow-up. Reporting of "body functions and structures" improved similarly across groups., Conclusions: Supervised teaching and personalized feedback are active ingredients of an intervention to improve reporting of ICF components in physiotherapeutic patient records., (© 2019 John Wiley & Sons, Ltd.)

Background: Electronic Prescribing and Medicines Administration (EPMA) systems are being widely implemented to facilitate medication safety improvement. However, translating the resulting big data into actionable knowledge has received relatively little attention., Objective: The objective of this study was to use routinely collected EPMA data in the study of exact time discrepancy between physicians' order and nurses' administration of systemic antibiotics. We evaluated first and follow-up dose administration and dose intervals and examined multifactorial determinants in ordering and administration explaining potential discrepancy., Methods: We conducted an observational study of electronic health records for all medical patient stays with antibiotic treatment from January to June 2018 (n=4392) in a large Belgian tertiary care hospital. Using an EPMA system with Barcode Medication Administration, we calculated time discrepancy between order and administration of first doses (n=6233), follow-up doses (n=87 960), and dose intervals. Multiple logistic regression analysis estimated the association between time discrepancy and various determinants in ordering and administration., Results: Time discrepancy between physician order and nurse administration was <30 minutes for 48.7% of first doses and 61.7% of follow-up doses, with large variation across primary diagnoses. Greater dose intervals, oral versus intravenous administration, and order diversion from regular nurse administration rounds showed strongest association with less timely administration., Conclusions: EPMA systems show huge potential to generate actionable knowledge. Concerning antibiotic treatment, having physicians' orders coincide with regular nurse administration rounds whenever clinically appropriate, further taking contextual factors into account, could potentially improve antibiotic administration timeliness.

This study assessed the compliance of Belgian home care nurses with good practice recommendations to prevent central line-associated bloodstream infections. The compliance to 3 care bundles was 0% (0 out of 7), 13.3% (2 out of 15), and 22.2% (2 out of 9), respectively. This finding is important given the increasing number of home care patients with an intravascular catheter and underscores the need for quality improvement strategies to prevent central line-associated bloodstream infections in home care., (Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Staphylococcus epidermidis is an opportunistic pathogen and a leading cause of morbidity and premature mortality in patients with medical device-related infections, which is a concern in hospitalized patients. Developing a strategy to raise opsonic antibodies against polysaccharide intracellular adhesin (PIA) could be promising for the elimination of colonizing and biofilm-forming S. epidermidis. Following the purification of truncated rSesC protein and PIA, for the first time, PIA was conjugated to rSesC as a carrier to increase the immunogenicity of PIA and its efficacy in mice was evaluated. The structure of the conjugate was analysed using the Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance spectroscopy (H1- NMR) methods. Afterwards, the immune response was evaluated by measuring the total IgG, IgG2a and IgG2b titres., Results: The immunization of mice with the PIA-rSesC conjugate raised the levels of opsonic antibodies, and the vaccinated mice were protected when challenged intravenously by wild-type S. epidermidis strain 1457. Further studies indicated that the conjugated vaccine was able to eliminate S. epidermidis biofilm formation in in vitro or in vivo assays., Conclusion: This study confirms the proposal that the immunization of mice with PIA-rSesC conjugate vaccine could protect against S. epidermidis infection.

Purpose: This narrative review aims to describe barriers of outpatient parenteral antimicrobial therapy at home (OPAT), potentially compromising general standards of antibiotic stewardship (ABS) and facilitators of OPAT for ABS., Methods: After a literature review, five authors determined the barriers and facilitators to discuss in this review., Results: Sixty-six publications were included in the narrative review and seven barriers and five facilitators are discussed in this article. The impracticability of multiple daily dosing during OPAT, the impact of real-life temperature variations, deviations of the infusion rates of elastomeric devices, access to prolonged intravenous antibiotic therapy, not administering loading doses before the initiation of extended or continuous infusions and the transmural nature of care associated with OPAT, can lead to deviations of recommended treatment regimens and sub-optimal clinical and laboratory follow-up, with a risk of inferior clinical outcomes, adverse events, drug-resistance and higher costs. On the other hand, OPAT provides access to treatments with intravenous antibiotics and simultaneously avoids prolonged hospitalization., Conclusion: Implementing ABS guidelines in OPAT programs, e.g., by using a multidisciplinary team approach and facility-specific protocols for OPAT with patient selection criteria and instructions for selection, storage, preparation and administration of antibiotics, can improve appropriate antibiotic use. Additionally, further research should examine the effectiveness of these interventions on outcomes of OPAT.

Efficient diagnosis of allergy and proper treatment need identification of the causative allergens eliciting clinical symptoms. The present study was performed to identify the most common aero- and food allergens and determine the pattern of sensitization among people of Ahvaz (southwestern Iran), one of the most polluted cities worldwide. Based on the physical examination and medical records, patients were referred to the Allergy laboratory for "in vitro" IgE determination. Specific and total IgE was determined by the ImmunoCAP system (Thermo Fisher-Phadia, Uppsala, Sweden). A total of 666 consecutive patients (51.1% female) were tested for 202 different allergens. The majority of requests (57%) belonged to food allergens. Sensitization to at least one allergen was found in 47.6% of patients. In a selected group of allergens for which specific IgE had been tested in at least 100 patients, the most common sensitizing aeroallergens were Russian thistle, grass pollen, and willow; while wheat, honey, and shrimp were the most frequent food allergens, respectively. Sensitization profiles based on measurement of specific IgE indicated that Russian thistle, grasses, and wheat were the most prevalent allergens in people with allergic symptoms living in Ahvaz.

Objectives: The opportunistic pathogen Staphylococcus epidermidis is progressively involved in device-related infections. Since these infections involve biofilm formation, antibiotics are not effective. Conversely, a vaccine can be advantageous to prevent these infections. In view of vaccine development, predicted surface proteins were evaluated on their potential as a vaccine target., Methods: Immunoglobulins directed against S. epidermidis surface proteins SesB, M, O, Q and R were used to firstly affirm their surface location. Further, inhibitory effects of these IgGs on biofilm formation were determined in vitro on polystyrene and polyurethane surfaces and in vivo using a subcutaneous catheter mouse model. We also examined the opsonophagocytotic capacity of these IgGs., Results: Surface localization of the five Ses proteins was demonstrated both for planktonic and sessile cells, though to a variable extent. Ses-specific IgGs added to planktonic cells had a variable inhibitory effect on cell adhesion to polystyrene, while only anti-SesO IgGs decreased cell attachment to polyurethane catheters. Although phagocytic killing was only obtained after opsonization with SesB-specific IgGs, a significant reduction of in vivo formed biofilms was observed after administration of SesB-, SesM- and SesO-specific IgGs., Conclusions: Regardless of their characterization or function, S. epidermidis surface proteins can be adequate targets for vaccine development aiming the prevention of device-related infections caused by invasive S. epidermidis strains., (Copyright © 2018 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Aggregation is a sequence-specific process, nucleated by short aggregation-prone regions (APRs) that can be exploited to induce aggregation of proteins containing the same APR. Here, we find that most APRs are unique within a proteome, but that a small minority of APRs occur in many proteins. When aggregation is nucleated in bacteria by such frequently occurring APRs, it leads to massive and lethal inclusion body formation containing a large number of proteins. Buildup of bacterial resistance against these peptides is slow. In addition, the approach is effective against drug-resistant clinical isolates of Escherichia coli and Acinetobacter baumannii, reducing bacterial load in a murine bladder infection model. Our results indicate that redundant APRs are weak points of bacterial protein homeostasis and that targeting these may be an attractive antibacterial strategy.

The recently developed Child HCAHPS provides a standard to measure US hospitals' performance on pediatric inpatient experiences of care. We field-tested Child HCAHPS in Belgium to instigate international comparison. In the development stage, forward/backward translation was conducted and patients assessed content validity index as excellent. The draft Flemish Child HCAHPS included 63 items: 38 items for five topics hypothesized to be similar to those proposed in the US (communication with parent, communication with child, attention to safety and comfort, hospital environment, and global rating), 10 screeners, a 14-item demographic and descriptive section, and one open-ended item. A 6-week pilot test was subsequently performed in three pediatric wards (general ward, hematology and oncology ward, infant and toddler ward) at a JCI-accredited university hospital. An overall response rate of 90.99% (303/333) was achieved and was consistent across wards. Confirmatory factor analysis largely confirmed the configuration of the proposed composites. Composite and single-item measures related well to patients' global rating of the hospital. Interpretation of different patient experiences across types of wards merits further investigation., Conclusion: Child HCAHPS provides an opportunity for systematic and cross-national assessment of pediatric inpatient experiences. Sharing and implementing international best practices are the next logical step. What is Known: • Patient experience surveys are increasingly used to reflect on the quality, safety, and centeredness of patient care. • While adult inpatient experience surveys are routinely used across countries around the world, the measurement of pediatric inpatient experiences is a young field of research that is essential to reflect on family-centered care. What is New: • We demonstrate that the US-developed Child HCAHPS provides an opportunity for international benchmarking of pediatric inpatient experiences with care through parents and guardians. • Our study findings show considerable variation in experiences for types of pediatric services. Support to share good practices and launch quality improvement initiatives can be obtained by organizing regular two-way feedback sessions with clinicians to place the findings in context.

Most human proteins possess amyloidogenic segments, but only about 30 are associated with amyloid-associated pathologies, and it remains unclear what determines amyloid toxicity. We designed vascin, a synthetic amyloid peptide, based on an amyloidogenic fragment of vascular endothelial growth factor receptor 2 (VEGFR2), a protein that is not associated to amyloidosis. Vascin recapitulates key biophysical and biochemical characteristics of natural amyloids, penetrates cells, and seeds the aggregation of VEGFR2 through direct interaction. We found that amyloid toxicity is observed only in cells that both express VEGFR2 and are dependent on VEGFR2 activity for survival. Thus, amyloid toxicity here appears to be both protein-specific and conditional-determined by VEGFR2 loss of function in a biological context in which target protein function is essential., (Copyright © 2016, American Association for the Advancement of Science.)

Staphylococcus epidermidis is one of the major concerns with respect to hospital-acquired infections. Therefore, a rapid and easy method to identify at species level S. epidermidis isolates out of a broad range of bacteria is necessary. Based on earlier studies, the sesC gene encoding a S. epidermidis surface protein revealed to be a highly conserved gene in this species. By means of an easy and inexpensive PCR assay, the presence of sesC was checked in 438 clinical staphylococcal isolates. Results showed that sesC is specifically present in all S. epidermidis. In conclusion, the sesC gene can be exploited as a genetic marker in order to distinguish S. epidermidis from other isolates., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Taking advantage of the xenobiotic nature of bacterial infections, we tested whether the cytotoxicity of protein aggregation can be targeted to bacterial pathogens without affecting their mammalian hosts. In particular, we examined if peptides encoding aggregation-prone sequence segments of bacterial proteins can display antimicrobial activity by initiating toxic protein aggregation in bacteria, but not in mammalian cells. Unbiased in vitro screening of aggregating peptide sequences from bacterial genomes lead to the identification of several peptides that are strongly bactericidal against methicillin-resistant Staphylococcus aureus. Upon parenteral administration in vivo, the peptides cured mice from bacterial sepsis without apparent toxic side effects as judged from histological and hematological evaluation. We found that the peptides enter and accumulate in the bacterial cytosol where they cause aggregation of bacterial polypeptides. Although the precise chain of events that leads to cell death remains to be elucidated, the ability to tap into aggregation-prone sequences of bacterial proteomes to elicit antimicrobial activity represents a rich and unexplored chemical space to be mined in search of novel therapeutic strategies to fight infectious diseases., (© 2015 John Wiley & Sons Ltd.)

Staphylococcus epidermidis is the most common cause of device-associated infections. It has been shown that active and passive immunization in an animal model against protein SesC significantly reduces S. epidermidis biofilm-associated infections. In order to elucidate its role, knock-out of sesC or isolation of S. epidermidis sesC-negative mutants were attempted, however, without success. As an alternative strategy, sesC was introduced into Staphylococcus aureus 8325-4 and its isogenic icaADBC and srtA mutants, into the clinical methicillin-sensitive S. aureus isolate MSSA4 and the MRSA S. aureus isolate BH1CC, which all lack sesC. Transformation of these strains with sesC i) changed the biofilm phenotype of strains 8325-4 and MSSA4 from PIA-dependent to proteinaceous even though PIA synthesis was not affected, ii) converted the non-biofilm-forming strain 8325-4 ica::tet to a proteinaceous biofilm-forming strain, iii) impaired PIA-dependent biofilm formation by 8325-4 srtA::tet, iv) had no impact on protein-mediated biofilm formation of BH1CC and v) increased in vivo catheter and organ colonization by strain 8325-4. Furthermore, treatment with anti-SesC antibodies significantly reduced in vitro biofilm formation and in vivo colonization by these transformants expressing sesC. These findings strongly suggest that SesC is involved in S. epidermidis attachment to and subsequent biofilm formation on a substrate.

Background: We verified the analytical performance of strip-based handheld glucose meters (GM) for prescription use, in a comparative split-sample protocol using blood gas samples from a surgical intensive care unit (ICU)., Methods: Freestyle Precision Pro (Abbott), StatStrip Connectivity Meter (Nova), ACCU-CHEK Inform II (Roche) were evaluated for recovery/linearity, imprecision/repeatability. The GMs and the ABL90 (Radiometer) blood gas analyzer (BGA) were tested for relative accuracy vs. the comparator hexokinase glucose-6-phosphate-dehydrogenase (HK/G6PDH) assay on a Cobas c702 analyzer (Roche)., Results: Recovery of spiked glucose was linear up to 19.3 mmol/L (347 mg/dL) with a slope of 0.91-0.94 for all GMs. Repeatability estimated by pooling duplicate measurements on samples below (n=9), in (n=51) or above (n=80) the 4.2-5.9 mM (74-106 mg/dL) range were for Freestyle Precision Pro: 4.2%, 4.0%, 3.6%; StatStrip Connectivity Meter: 4.0%, 4.3%, 4.5%; and ACCU-CHEK Inform II: 1.4%, 2.5%, 3.5%. GMs were in agreement with the comparator method. The BGA outperformed the GMs, with a MARD of 3.9% compared to 6.5%, 5.8% and 4.4% for the FreeStyle, StatStrip and ACCU-CHEK, respectively. Zero % of the BGA results deviated more than the FDA 10% criterion as compared to 9.4%, 3.7% and 2.2% for the FreeStyle, StatStrip and ACCU-CHEK, respectively. For all GMs, icodextrin did not interfere. Variation in the putative influence factors hematocrit and O2 tension could not explain observed differences with the comparator method., Conclusions: GMs quantified blood glucose in whole blood at about the 10% total error criterion, proposed by the FDA for prescription use.

Background: Accurate quantification of vancomycin in plasma is important for adequate dose-adjustment. As literature suggests between-method differences, our first objective was to develop a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for total vancomycin in human plasma and to compare frequently used immunoassays with this method. Secondly, we investigated the clinical impact of between-method quantification differences., Methods: For LC-MS/MS, lithium heparin plasma was extracted by adding a precipitation reagent containing the internal standard (vancomycin-des-leucine). Analysis was performed on an Acquity TQD mass spectrometer equipped with an Acquity UPLC 2795 separations module. Our method was analytically validated and compared with four frequently used immunoassays from four different manufacturers. Vancomycin concentrations were clinically classified as toxic, therapeutic and sub-therapeutic. Clinical discordance was calculated using LC-MS/MS as a reference., Results: A novel LC-MS/MS method using protein precipitation as sole pretreatment and an analysis time of 5.0 min was developed. The assay had a total imprecision of 2.6-8.5%, a limit of quantification of 0.3 mg/L and an accuracy ranging from 101.4 to 111.2%. Using LC-MS/MS as reference, three immunoassays showed a mean proportional difference within 10% and one showed a substantial mean proportional difference of >20%. Clinical discordant interpretation of the obtained concentrations ranged from 6.1 to 22.2%., Conclusions: We developed a novel LC-MS/MS method for rapid analysis of total vancomycin concentrations in human plasma. Correlation of the method with immunoassays showed a mean proportional difference >20% for one of the assays, causing discordant clinical interpretation in more than 1 out of 5 samples., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Protein aggregation is sequence specific, favoring self-assembly over cross-seeding with non-homologous sequences. Still, as the majority of proteins in a proteome are aggregation prone, the high level of homogeneity of protein inclusions in vivo both during recombinant overexpression and in disease remains surprising. To investigate the selectivity of protein aggregation in a proteomic context, we here compared the selectivity of aggregation-determined interactions with antibody binding. To that purpose, we synthesized biotin-labeled peptides, corresponding to aggregation-determining sequences of the bacterial protein β-galactosidase and two human disease biomarkers: C-reactive protein and prostate-specific antigen. We analyzed the selectivity of their interactions in Escherichia coli lysate, human serum and human seminal plasma, respectively, using a Western blot-like approach in which the aggregating peptides replace the conventional antibody. We observed specific peptide accumulation in the same bands detected by antibody staining. Combined spectroscopic and mutagenic studies confirmed accumulation resulted from binding of the peptide on the identical sequence of the immobilized target protein. Further, we analyzed the sequence redundancy of aggregating sequences and found that about 90% of them are unique within their proteome. As a result, the combined specificity and low sequence redundancy of aggregating sequences therefore contribute to the observed homogeneity of protein aggregation in vivo. This suggests that these intrinsic proteomic properties naturally compartmentalize aggregation events in sequence space. In the event of physiological stress, this might benefit the ability of cells to respond to proteostatic stress by allowing chaperones to focus on specific aggregation events rather than having to face systemic proteostatic failure., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Non-typeable Haemophilus influenzae (NTHi) is a major cause of mucosal infections such as otitis media, sinusitis, conjunctivitis, and exacerbations of chronic obstructive pulmonary disease. In some regions, a strong causal relation links this pathogen with infections of the lower respiratory tract. In the past 20 years, a steady but constant increase has occurred in invasive NTHi worldwide, with perinatal infants, young children, and elderly people most at risk. Individuals with underlying comorbidities are most susceptible and infection is associated with high mortality. β-lactamase production is the predominant mechanism of resistance. However, the emergence and spread of β-lactamase-negative ampicillin-resistant strains in many regions of the world is of substantial concern, potentially necessitating changes to antibiotic treatment guidelines for community-acquired infections of the upper and lower respiratory tract and potentially increasing morbidity associated with invasive NTHi infections. Standardised surveillance protocols and typing methodologies to monitor this emerging pathogen should be implemented. International scientific organisations need to raise the profile of NTHi and to document the pathobiology of this microbe., (Copyright © 2014 Elsevier Ltd. All rights reserved.)