Translating Data From an Electronic Prescribing and Medicines Administration System Into Knowledge: Application to Doctor-Nurse Time Discrepancy in Antibiotic Ordering and Administration.

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.

Efficacy and safety of a Belgian tertiary care outpatient parenteral antimicrobial therapy (OPAT) program.

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%.

Outpatient parenteral antimicrobial therapy and antibiotic stewardship: opponents or teammates?

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.

Protein aggregation as an antibiotic design strategy.

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.

Validation of the Child HCAHPS survey to measure pediatric inpatient experience of care in Flanders.

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.

Performance of strip-based glucose meters and cassette-based blood gas analyzer for monitoring glucose levels in a surgical intensive care setting.

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.

Protein aggregation in bacteria: the thin boundary between functionality and toxicity.

Misfolding and aggregation of proteins have a negative impact on all living organisms. In recent years, aggregation has been studied in detail due to its involvement in neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's diseases, and type II diabetes--all associated with accumulation of amyloid fibrils. This research highlighted the central importance of protein homeostasis, or proteostasis for short, defined as the cellular state in which the proteome is both stable and functional. It implicates an equilibrium between synthesis, folding, trafficking, aggregation, disaggregation and degradation. In accordance with the eukaryotic systems, it has been documented that protein aggregation also reduces fitness of bacterial cells, but although our understanding of the cellular protein quality control systems is perhaps most detailed in bacteria, the use of bacterial proteostasis as a drug target remains little explored. Here we describe protein aggregation as a normal physiological process and its role in bacterial virulence and we shed light on how bacteria defend themselves against the toxic threat of aggregates. We review the impact of aggregates on bacterial viability and look at the ways that bacteria use to maintain a balance between aggregation and functionality. The proteostasis in bacteria can be interrupted via overexpression of proteins, certain antibiotics such as aminoglycosides, as well as antimicrobial peptides--all leading to loss of cell viability. Therefore intracellular protein aggregation and disruption of proteostatic balance in bacteria open up another strategy that should be explored towards the discovery of new antimicrobials.

Performance of cassette-based blood gas analyzers to monitor blood glucose and lactate levels in a surgical intensive care setting.

BACKGROUND: With the use of a traditional blood gas analyzer (BGA) (ABL800 Radiometer) for blood glucose monitoring, tight glucose control (TGC) reduced in-hospital mortality and morbidity of surgical intensive care unit (ICU) adult and pediatric patients. Such BGAs are now superseded by cassette-based BGAs. We assessed the analytical reliability of cassette-based BGAs to monitor patient's metabolic status in an ICU setting. METHODS: We evaluated recovery/linearity, imprecision/repeatability and relative accuracy vs. comparison methods for glucose [coupled hexokinase glucose-6-phosphate dehydrogenase (HK/G6PD) assay] and lactate (lactate dehydrogenase assay) in ICU patient samples with two cassette-based BGAs [RP500 (Siemens) and ABL90 (Radiometer)] and with the ABL800 BGA. RESULTS: Recovery of spiked glucose up to 348 mg/dL (19.3 mmol/L) was complete for all BGAs. Repeatability of ABL800 and ABL90 was comparable with the comparison method (about 1%), but higher for RP500 (about 2.4%). All BGAs were in agreement with the comparison method, with all glucose measurements falling within preset 10% criteria suggested by Karon. Recovery of spiked lactate (up to 25 mmol/L) was incomplete at all levels. Repeatability of ABL800 and ABL90 was comparable with the comparison method (about 4%), and 5.5% for RP500. All BGAs were in agreement with the comparison method, with >98% of the lactate measurements falling within 30% biological-variation-based criteria. CONCLUSIONS: The cassette-based BGAs quantified blood glucose and lactate levels in ICU patients within the acceptable error ranges. Cassette-based BGAs can be used for monitoring patient's metabolic status in an ICU setting.

High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial.

BACKGROUND: Low serum 25-hydroxyvitamin D (25-[OH]D) levels have been associated with lower FEV(1), impaired immunologic control, and increased airway inflammation. Because many patients with chronic obstructive pulmonary disease (COPD) have vitamin D deficiency, effects of vitamin D supplementation may extend beyond preventing osteoporosis. OBJECTIVE: To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations. DESIGN: Randomized, single-center, double-blind, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00666367) SETTING: University Hospitals Leuven, Leuven, Belgium. PATIENTS: 182 patients with moderate to very severe COPD and a history of recent exacerbations. INTERVENTION: 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year. MEASUREMENTS: The primary outcome was time to first exacerbation. Secondary outcomes were exacerbation rate, time to first hospitalization, time to second exacerbation, FEV(1), quality of life, and death. RESULTS: Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group (mean between-group difference, 30 ng/mL [95% CI, 27 to 33 ng/mL]; P < 0.001). The median time to first exacerbation did not significantly differ between the groups (hazard ratio, 1.1 [CI, 0.82 to 1.56]; P = 0.41), nor did exacerbation rates, FEV(1), hospitalization, quality of life, and death. However, a post hoc analysis in 30 participants with severe vitamin D deficiency (serum 25-[OH]D levels <10 ng/mL) at baseline showed a significant reduction in exacerbations in the vitamin D group (rate ratio, 0.57 [CI, 0.33 to 0.98]; P = 0.042). LIMITATION: This was a single-center study with a small sample size. CONCLUSION: High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations. In participants with severe vitamin D deficiency at baseline, supplementation may reduce exacerbations. PRIMARY FUNDING SOURCE: Applied Biomedical Research Program, Agency for Innovation by Science and Technology (IWT-TBM).

Exploiting the aggregation propensity of beta-lactamases to design inhibitors that induce enzyme misfolding.

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.

Vaccination with SesC decreases Staphylococcus epidermidis biofilm formation.

The increased use of medical implants has resulted in a concomitant rise in device-related infections. The majority of these infections are caused by Staphylococcus epidermidis biofilms. Immunoprophylaxis and immunotherapy targeting in vivo-expressed, biofilm-associated, bacterial cell surface-exposed proteins are promising new approaches to prevent and treat biofilm-related infections, respectively. Using an in silico procedure, we identified 64 proteins that are predicted to be S. epidermidis surface exposed (Ses), of which 36 were annotated as (conserved) hypothetical. Of these 36 proteins, 5 proteins-3 LPXTG motif-containing proteins (SesL, SesB, and SesC) and 2 of the largest ABC transporters (SesK and SesM)-were selected for evaluation as vaccine candidates. This choice was based on protein size, number of antigenic determinants, or the established role in S. epidermidis biofilm formation of the protein family to which the candidate protein belongs. Anti-SesC antibodies exhibited the greatest inhibitory effect on S. epidermidis biofilm formation in vitro and on colonization and infection in a mouse jugular vein catheter infection model that includes biofilms and organ infections. Active vaccination with a recombinant truncated SesC inhibited S. epidermidis biofilm formation in a rat model of subcutaneous foreign body infection. Antibodies to SesC were shown to be opsonic by an in vitro opsonophagocytosis assay. We conclude that SesC is a promising target for antibody mediated strategies against S. epidermidis biofilm formation.

Detection of Pseudomonas aeruginosa in sputum headspace through volatile organic compound analysis.

INTRODUCTION: Chronic pulmonary infection is the hallmark of cystic fibrosis lung disease. Searching for faster and easier screening may lead to faster diagnosis and treatment of Pseudomonas aeruginosa (P. aeruginosa). Our aim was to analyze and build a model to predict the presence of P. aeruginosa in sputa. METHODS: Sputa from 28 bronchiectatic patients were used for bacterial culturing and analysis of volatile compounds by gas chromatography-mass spectrometry. Data analysis and model building were done by Partial Least Squares Regression Discriminant analysis (PLS-DA). Two analysis were performed: one comparing P. aeruginosa positive with negative cultures at study visit (PA model) and one comparing chronic colonization according to the Leeds criteria with P. aeruginosa negative patients (PACC model). RESULTS: The PA model prediction of P. aeruginosa presence was rather poor, with a high number of false positives and false negatives. On the other hand, the PACC model was stable and explained chronic P. aeruginosa presence for 95% with 4 PLS-DA factors, with a sensitivity of 100%, a positive predictive value of 86% and a negative predictive value of 100%. CONCLUSION: Our study shows the potential for building a prediction model for the presence of chronic P. aeruginosa based on volatiles from sputum.

Genomic copy number determines functional expression of {beta}-defensin 2 in airway epithelial cells and associates with chronic obstructive pulmonary disease.

RATIONALE: Copy number variations of the cluster of beta-defensin genes have been associated with psoriasis and inflammatory bowel disease. Controversy still exists on whether the beta-defensins genes determine susceptibility for chronic obstructive pulmonary disease (COPD). OBJECTIVES: We investigated whether genomic copy number variations of the beta-defensin gene cluster have a functional role in airway epithelial cells and associate with the presence of COPD. METHODS: Baseline and inflammatory induced transcript expression of DEFB4 was studied in nasal epithelial cell cultures and its effect on Pseudomonas aeruginosa inhibition was assessed. Subsequently, relevant functional cut-offs for copy numbers were used to explore associations with COPD in two independent case-control studies. MEASUREMENTS AND MAIN RESULTS: Copy number variation in the beta-defensin encoding genes correlated with baseline mRNA DEFB4 expression levels (R(2) = 0.96; P = 0.02), with a plateau effect from five copies or more. Only when higher copy numbers of beta-defensin genes were present, transcription was significantly up-regulated by tumor necrosis factor-alpha (P < 0.0001), which resulted in better antimicrobial activity in vitro. When comparing healthy smokers with COPD patients, a copy number greater than or equal to 5 was associated with increased risk for COPD with an adjusted odds ratio of 1.8 (confidence interval, 1.1-2.8; P = 0.02), which was confirmed by a second independent case-control study. CONCLUSIONS: Genomic copy number variation of beta-defensin encoding genes has a functional role in airway epithelial cells, which may contribute to the pathogenesis of COPD.

Cervicofacial actinomycosis following third molar removal: case-series and review.

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.

Myeloablative conditioning predisposes patients for Toxoplasma gondii reactivation after allogeneic stem cell transplantation.

BACKGROUND: Toxoplasmosis is an often fatal opportunistic infection following allogeneic hematopoietic stem cell transplantation and is largely due to deferred diagnosis. In addition, breakthrough infections occur during prophylaxis with trimethoprim-sulfamethoxazole. METHODS: From November 2001 onwards, we routinely monitored all stem cell transplant recipients who were seropositive for Toxoplasma gondii and/or who received a transplant from a donor who was seropositive for T. gondii reactivation by polymerase chain reaction of peripheral blood samples. The aim of this study was to evaluate the incidence of and the risk factors for Toxoplasma reactivation in this population not receiving specific prophylaxis. We also studied the feasibility of a preemptive treatment approach based on this routine monitoring. RESULTS: We report a toxoplasmosis incidence of 8.7% (18 of 208 patients). Twelve patients (5.8%) had a T. gondii infection at diagnosis; 6 patients (2.9%) had Toxoplasma disease, including cerebral toxoplasmosis (n = 5) and cardiopulmonary toxoplasmosis (n = 1). We identified myeloablative conditioning and conditioning with high-dose total body irradiation (10-12 Gy) as risk factors for T. gondii reactivation, whereas patients with a seropositive donor were less likely to experience reactivation. Patients with T. gondii disease had a significantly higher number of transcripts in blood than did patients with a T. gondii infection. Finally, with a strategy of routine monitoring and preemptive treatment with clindamycin-pyrimethamine, we only had 3 Toxoplasma-related deaths among our patients, which is a much lower rate than that reported in the literature. CONCLUSIONS: Systematic monitoring with polymerase chain reaction is a good means to detect T. gondii reactivation and could reduce T. gondii-related mortality among hematopoietic stem cell transplant recipients.

Candida albicans biofilm formation in a new in vivo rat model.

Device-associated microbial growth, including Candida biofilms, represents more than half of all human microbial infections and, despite a relatively small risk of implant-associated diseases, this type of infection usually leads to high morbidity, increased health-care costs and prolonged antimicrobial therapy. Animal models are needed to elucidate the complex host-pathogen interactions that occur during the development of attached and structured biofilm populations. We describe here a new in vivo model to study Candida biofilm, based on the avascular implantation of small catheters in rats. Polyurethane biomaterials challenged with Candida cells were placed underneath the skin of immunosuppressed animals following only minor surgery. The model allowed the study of up to ten biofilms at once, and the recovery of mature biofilms from 2 days after implantation. The adhering inoculum was adjusted to the standard threshold of positive diagnosis of fungal infection in materials recovered from patients. Wild-type biofilms were mainly formed of hyphal cells, and they were unevenly distributed across the catheter length as observed in infected materials in clinical cases. The hyphal multilayered structure of the biofilms of wild-type strains was observed by confocal microscopy and compared to the monolayer of yeast or hyphal cells of two well-known biofilm-deficient strains, efg1Delta/efg1 Delta cph1Delta/cph1Delta and bcr1Delta /bcr1Delta, respectively. The subcutaneous Candida biofilm model relies on the use of implanted catheters with accessible, fast and minor surgery to the animals. This model can be used to characterize the ability of antimicrobial agents to eliminate biofilms, and to evaluate the prophylactic effect of antifungal drugs and biomaterial coatings.

Detection of large numbers of pneumococcal virulence genes in streptococci of the mitis group.

Seven streptococcal isolates from the mitis group were analyzed for the presence of pneumococcal gene homologues by comparative genomic hybridization studies with microarrays based on open reading frames from the genomes of Streptococcus pneumoniae TIGR4 and R6. The diversity of pneumolysin (ply) and neuraminidase A (nanA) gene sequences was explored in more detail in a collection of 14 S. pseudopneumoniae and 29 mitis group isolates, respectively. The mitis group isolates used in the microarray experiments included a type strain (NCTC 12261), two S. mitis isolates from the nasopharynxes of children, one S. mitis isolate from a case of infective endocarditis, one S. mitis isolate from a dental abscess, and one S. oralis isolate and one S. pseudopneumoniae isolate from the nasopharynxes of children. The results of the microarray study showed that the 5 S. mitis isolates had homologues to between 67 and 82% of pneumococcal virulence genes, S. oralis hybridized to 83% of pneumococcal virulence genes, and S. pseudopneumoniae hybridized to 92% of identified pneumococcal virulence genes. Comparison of the pneumolysin, mitilysin (mly), and newly identified pseudopneumolysin (pply) gene sequences revealed that mly and pply genes are more closely related to each other than either is to ply. In contrast, the nanA gene sequences in the pneumococcus and streptococci from the mitis group are closely clustered together, sharing 99.4 to 99.7% sequence identity with pneumococcal nanA alleles.

Supervised teaching and feedback improve physiotherapists' reporting of the International Classification of Functioning, Disability and Health in physiotherapeutic electronic patient records: A proof-of-concept randomized controlled trial.

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; ß, 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; ß, 3.03; 95% CI, 1.52-4.54), "participation" (50% versus 14% completion; ß, 3.67; 95% CI, 1.79-5.55), and "personal factors" (35% versus 20% completion; ß, 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; ß, 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.

Inhibition of Staphylococcus epidermidis biofilm formation by rabbit polyclonal antibodies against the SesC protein.

Several well-studied proteins with defined roles in Staphylococcus epidermidis biofilm formation are LPXTG motif-containing proteins. Here, we investigate the possible use of the LPXTG motif-containing protein SesC (S. epidermidis surface protein C; accession no. NP_765787) as a target for antibodies to prevent biofilm formation. In vitro and in a in vivo rat model of catheter infection, gene and protein expression analysis showed that SesC is expressed more strongly in biofilm-associated cells than in planktonic cells and is expressed particularly during the late phase of in vivo biofilm formation. Polyclonal rabbit antibodies raised against SesC reduced the fibrinogen-binding ability of S. epidermidis RP62A and Staphylococcus aureus RN4220 transformants expressing SesC, inhibited in vitro biofilm formation by S. epidermidis strains 10b and 1457, and significantly reduced the numbers of bacteria in a 1-day-old in vivo biofilm (P < 0.001, one-way analysis of variance). Our findings revealed that SesC is a promising target for prevention and treatment of S. epidermidis biofilms because it affects both the primary attachment and biofilm accumulation phases. The precise role of SesC in biofilm formation remains to be identified.

Bronchoalveolar lavage fluid galactomannan for the diagnosis of invasive pulmonary aspergillosis in patients with hematologic diseases.

BACKGROUND: Prompt diagnosis of invasive pulmonary aspergillosis (IPA) remains a challenge. Galactomannan (GM) detection in bronchoalveolar lavage (BAL) fluid by the Platelia enzyme immunoassay aims to further improve upon the test's utility by applying it directly to specimens from the target organ. METHODS: A retrospective analysis of the Platelia assay was performed on BAL samples from 99 evaluable high-risk hematology patients, including 58 with proven or probable IPA. RESULTS: BAL GM demonstrated an improved sensitivity profile (91.3% with an optical density [OD] index cutoff of >or=1.0) in comparison with culture and microscopy (50% and 53.3%, respectively). The diagnostic accuracy as given by the area under the receiver operating characteristic curve was 0.93 (95% confidence interval, 0.88-0.99); further decreasing the OD index cutoff to 0.5 compromised specificity more than it improved sensitivity. Estimates of the positive and negative predictive value of the Platelia assay on BAL samples (OD index, >or=1.0) were 76% and 96%, respectively. The mean BAL GM OD index was not different in neutropenic versus nonneutropenic case patients (3.9 and 4.5, respectively; P = .3); however, a trend toward decreased sensitivity in patients receiving mold-active prophylaxis was noted. CONCLUSION: BAL GM is a valuable adjunctive diagnostic tool to other conventional microbiologic and radiologic studies.