Appropriateness of acute-care antibiotic prescriptions for community-acquired infections and surgical antibiotic prophylaxis in England: analysis of 2016 national point prevalence survey data.

BACKGROUND: Estimates of inappropriate prescribing can highlight key target areas for antimicrobial stewardship (AMS) and inform national targets. OBJECTIVES: To (1) define and (2) produce estimates of inappropriate antibiotic prescribing levels within acute hospital trusts in England. METHODS: The 2016 national Healthcare-Associated Infections (HAI), Antimicrobial Use (AMU) and AMS point prevalence survey (PPS) was used to derive estimates of inappropriate prescribing, focusing on the four most reported community-acquired antibiotic indications (CAIs) in the PPS and surgical prophylaxis. Definitions of appropriate antibiotic therapy for each indication were developed through the compilation of national treatment guidelines. A Likert-scale system of appropriateness coding was validated and refined through a two-stage expert review process. RESULTS: Antimicrobial usage prevalence data were collected for 25,741 individual antibiotic prescriptions, representing 17,884 patients and 213 hospitals in England. 30.4% of prescriptions for the four CAIs of interest were estimated to be inappropriate (2054 prescriptions). The highest percentage of inappropriate prescribing occurred in uncomplicated cystitis prescriptions (62.5%), followed by bronchitis (48%). For surgical prophylaxis, 30.8% of prescriptions were inappropriate in terms of dose number, and 21.3% in terms of excess prophylaxis duration. CONCLUSIONS: The 2016 prevalence of inappropriate antibiotic prescribing in hospitals in England was approximated to be 30.4%; this establishes a baseline prevalence and provided indication of where AMS interventions should be prioritized. Our definitions appraised antibiotic choice, treatment duration and dose number (surgical prophylaxis only); however, they did not consider other aspects of appropriateness, such as combination therapy - this is an important area for future work.

Detection, survival, and persistence of Staphylococcus capitis NRCS-A in neonatal units in England.

BACKGROUND: The multidrug-resistant Staphylococcus capitis clone, NRCS-A, is increasingly associated with late-onset sepsis in low birthweight newborns in neonatal intensive care units (NICUs) in England and globally. Understanding where this bacterium survives and persists within the NICU environment is key to developing and implementing effective control measures. AIM: To investigate the potential for S. capitis to colonize surfaces within NICUs. METHODS: Surface swabs were collected from four NICUs with and without known NRCS-A colonizations/infections present at the time of sampling. Samples were cultured and S. capitis isolates analysed via whole-genome sequencing. Survival of NRCS-A on plastic surfaces was assessed over time and compared to that of non-NRCS-A isolates. The bactericidal activity of commonly used chemical disinfectants against S. capitis was assessed. FINDINGS: Of 173 surfaces sampled, 40 (21.1%) harboured S. capitis with 30 isolates (75%) being NRCS-A. Whereas S. capitis was recovered from surfaces across the NICU, the NRCS-A clone was rarely recovered from outside the immediate neonatal bedspace. Incubators and other bedside equipment were contaminated with NRCS-A regardless of clinical case detection. In the absence of cleaning, S. capitis was able to survive for three days with minimal losses in viability (<0.5 log10 reduction). Sodium troclosene and a QAC-based detergent/disinfectant reduced S. capitis to below detectable levels. CONCLUSION: S. capitis NRCS-A can be readily recovered from the NICU environment, even in units with no recent reported clinical cases of S. capitis infection, highlighting a need for appropriate national guidance on cleaning within the neonatal care environment.

Paediatric antimicrobial stewardship programmes in the UK's regional children's hospitals.

A survey was conducted in UK regional children's hospitals with paediatric intensive care and paediatric infectious disease (PID) departments to describe the characteristics of paediatric antimicrobial stewardship (PAS) programmes. A structured questionnaire was sent to PAS coordinators. 'Audit and feedback' was implemented in 13 out of 17 centres. Microbiology-led services were more likely to implement antimicrobial restriction (75% vs 33% in PID-led services), to focus on broad-spectrum antibiotics, and to review patients with positive blood cultures. PID-led services were more likely to identify patients from e-prescribing or drug charts and review all antimicrobials. A PAS network has been established.

Rapid diagnostic tests for common infection syndromes: less haste, more speed.

Rapid diagnostic tests, which accurately distinguish bacterial from viral infections, are being heralded as the solution to antibiotic overuse, which is a key driver of antimicrobial resistance. We have concerns that this approach is oversimplistic. Rapid diagnostic tests are complex interventions, with clinical context, patient flow, access and timing affecting their impact. There is little robust evidence that they reduce antibiotic prescribing in real-world settings. We suggest that prior to introducing these costly tests, emphasis should be placed on optimizing the implementation of efficient evidence-based antimicrobial stewardship interventions, such as increasing the use of proven automated clinical infection syndrome prediction tools by clinicians, supporting patients to self-care by providing them with high-quality safety-netting resources, providing front-line clinicians with individual prescribing data to facilitate peer benchmarking and setting specific and purposeful antibiotic prescribing targets to improve the quality of antimicrobial prescribing. The stakes are high and time is running out; let's start by getting the basics right.

Dental maturity in Belgian children using Demirjian's method and polynomial functions: new standard curves for forensic and clinical use.

Dental maturity was studied from dental panoramic radiographs of 2523 Belgian children (1255 girls and 1268 boys) aged 2 to 18 years. The aim was to compare the efficiency of two methods of age prediction: Demirjian's method, using differently weighted scores, and polynomial functions. The two methods present some differences: Demirjian is used to determine the maturity score as a function of age and polynomial functions are used to determine age as a function of the maturity score. We present, for each method, gender-specific dental maturity tables and curves for Belgian children. Girls always present advanced dental maturity compared with boys. The polynomial functions are highly reliable (0.21% of incorrect classifications) and the percentile method, using Belgian weighted scores, is very accurate (+/- 2.08 years on average, between 2 and 16 years of age).

A single H:CDR3 residue in the anti-digoxin antibody 26-10 modulates specificity for C16-substituted digoxin analogs.

We constructed Fab libraries of bacteriophage-displayed H:CDR3 mutants in the high-affinity anti-digoxin antibody 26-10 to determine structural constraints on affinity and specificity for digoxin. Libraries of mutant Fabs randomized at five or 10 contiguous positions were panned against digoxin and three C16-substituted analogs, gitoxin (16-OH), 16-formylgitoxin and 16-acetylgitoxin. The sequence data from 83 different mutant Fabs showed highly restricted consensus patterns at positions H:100, 100a and 100b for binding to digoxin; these residues contact digoxin in the 26-10:digoxin co-crystal structure. Several mutant Fabs obtained following panning on digoxin-BSA showed increased affinity for digoxin compared with 26-10 and retained the wild-type (wt) Trp at position 100. Those Fabs selected following panning on C16-substituted analogs showed enhanced binding to the analogs. Replacement of H:Trp100 by Arg resulted in mutants that bound better to the analogs than to digoxin. This specificity change was unexpected, as C16 lies on the opposite side of digoxin from H:CDR3. Substitution of wt Trp by Arg appears to alter specificity by allowing the hapten to shift toward H:CDR3, thereby providing room for C16 substituents in the region of H:CDR1.

Longitudinal post-eruptive mandibular tooth movements of males and females.

Unbiased estimates of post-eruptive eruption and migration of the mandibular teeth for large representative samples are presently unavailable. The purpose of this study was to evaluate pure tooth movements of untreated children and adolescents longitudinally. Lateral cephalograms of 214 French-Canadians, followed bi-annually between 8 and 15 years of age, were traced, and the positions of the mandibular permanent central incisors and first molars were digitized. Temporal changes in tooth position were evaluated relative to naturally stable mandibular reference structures, using the mandibular reference line for orientation. The statistical analyses included t-tests to assess gender differences and Pearson product-moment correlations to evaluate associations. The results showed that the incisors proclined significantly more for males (6 degrees) than females (3 degrees). The incisor tips displayed early mesial movements that were countered by later distal movements. The incisor apex showed a consistent pattern of distal migration between 8 and 15 years. Mandibular arch length decreased over the 7-year observation period. Rates of mesial molar migration accelerated until 11 years of age and then decelerated. There was no significant change in the mandibular occlusal plane angle between 8 and 15 years of age. Incisor eruption showed the greatest rates during adolescence, attaining peaks at approximately 12 years for females and 14 years for males. The molars erupted approximately 5 mm between 8 and 15 years of age. The greatest gender differences occurred at the older ages, with males showing greater eruption potential than females. It was concluded that the mandibular teeth show significant migration and eruption during childhood and adolescence, with gender differences in the amount, direction, and timing of movement.

Incremental growth charts for condylar growth between 6 and 16 years of age.

This study provides sex specific reference data for the incremental growth of the mandibular condyle. The results pertain to a mixed-longitudinal sample of 113 males and 108 females followed annually between 6 and 16 years of age (total of 1647 observations). Growth of condylion was evaluated using naturally stable mandibular reference structures. The mean growth curves were estimated by multilevel models using iterative least squares procedures; between subject variation was estimated based on the sample's percentile distributions. Mean yearly velocities of condylar growth for males ranged between 2.1 and 3.1 mm/year. Growth rates decreased during childhood, increased during adolescence, and attained a maximum of 3.1 mm/year at approximately 14.3 years of age. Females showed a more constant rate of condylar growth during childhood (2.0-2.7 mm/year), a smaller adolescent peak (2.3 mm/year) at approximately 12.2 years and rapid deceleration after the peak. These reference data offer orthodontists an objective means of evaluating growth potential and treatment outcome in individual patients. Charts are provided for evaluating condylar growth of individual patients.