Posaconazole therapeutic drug monitoring in a regional hospital setting

BACKGROUND: Posaconazole therapeutic drug monitoring (TDM) is recommended to promote effective antifungal prophylaxis, but its utility has yet to be optimized. Breakthrough invasive fungal infections have been reported with serum concentrations/L, but there is little evidence to determine the optimal serum concentration for efficacy or concentrations associated with toxicity. Challenges for effective monitoring are greater in settings without posaconazole TDM facilities because of the long turnaround time before receipt of results. METHODS: Thirty-eight TDM episodes were performed on 18 patients in a regional center in Australia during a 30-month period. Australian guidelines recommend a trough serum concentration of ≥700 mcg/L. The response to concentrations below the recommendation threshold (700 mcg/L), the final serum plasma concentration for each patient, and the appropriateness of TDM were evaluated. RESULTS: A total of 19 (50%) concentrations were recorded to be \u3c 700 mcg/L. Of these 19 concentrations, the drug dose was increased on only 4 occasions. Eleven of 18 patients (61%) had initial concentrations CONCLUSIONS: The results demonstrate a lack of confidence and consistency in ordering, interpreting, and following up posaconazole concentrations. Therefore, the use of TDM should be carefully considered, especially in regional centers. Such settings should consider the practicalities of posaconazole TDM and try to improve the process to ensure consistency and optimization of patient care

Splink: Latest developments and applications

Funded by ADR UK, a new data linking team at the Ministry of Justice set out to link administrative datasets across the justice space, for internal use and sharing with external researchers. To achieve this aim we sought a linkage implementation that was probabilistic, flexible, scalable and ideally open source. Taking into account the tools available at the MoJ, existing open-source software (and paid alternatives) failed to meet our desired criteria. It was decided to develop a software package that builds on FastLink’s implementation in R of an Expectation-Maximisation algorithm to estimate a Fellegi-Sunter linkage model, adding a range of technical improvements, increased functionality and customisation options. Distributed computing offered by Spark could facilitate comparable linkage jobs that run on much larger datasets and much faster. Working with government data, accountability and transparency are vital, so the data and models are made accessible by a range of intuitive visualizations. The Splink python package has been downloaded over 6 million times. This initially used Spark to deliver its superior performance, but Splink v3 caters for various SQL backends and more potential users. As we have made Splink more intuitive, more accessible, and more extensively documented we continue to receive feedback and contributions from around the world, driving further continuous development. Through technical innovation and user-focused development, Splink has improved access to cutting-edge data linkage, and created groundbreaking research opportunities at MoJ and beyond. The team is grateful to ONS and other collaborators for testing and adopting these tools, and we will present some of the latest developments as well as examples of how Splink has been used worldwide

Genes on the Move: In Vitro Transduction of Antimicrobial Resistance Genes between Human and Canine Staphylococcal Pathogens

Transmission of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP) between people and pets, and their co-carriage, are well-described. Potential exchange of antimicrobial resistance (AMR) genes amongst these staphylococci was investigated in vitro through endogenous bacteriophage-mediated transduction. Bacteriophages were UV-induced from seven donor isolates of canine (MRSP) and human (MRSA) origin, containing tet(M), tet(K), fusB or fusC, and lysates filtered. Twenty-seven tetracycline- and fusidic acid- (FA-) susceptible recipients were used in 122 donor-recipient combinations (22 tetracycline, 100 FA) across 415 assays (115 tetracycline, 300 FA). Bacteriophage lysates were incubated with recipients and presumed transductants quantified on antimicrobial-supplemented agar plates. Tetracycline resistance transduction from MRSP and MRSA to methicillin-susceptible S. pseudintermedius (MSSP) was confirmed by PCR in 15/115 assays. No FA-resistance transfer occurred, confirmed by negative fusB/fusC PCR, but colonies resulting from FA assays had high MICs (≥32 mg/L) and showed mutations in fusA, two at a novel position (F88L), nine at H457[Y/N/L]. Horizontal gene transfer of tetracycline-resistance confirms that resistance genes can be shared between coagulase-positive staphylococci from different hosts. Cross-species AMR transmission highlights the importance of good antimicrobial stewardship across humans and veterinary species to support One Health

What happens when pharmacist independent prescribers lead on medicine management in older people’s care homes: a qualitative study

Objective: Older people in care homes frequently experience polypharmacy, increasing the likelihood of medicine-related burden. Pharmacists working within multidisciplinary primary care teams are ideally placed to lead on medication reviews. A randomised controlled trial placed pharmacists, with independent prescribing rights (PIPs), into older people care homes. In the intervention service, PIPs worked with general practitioners (GPs) and care home staff for 6 months, to optimise medicine management at individual resident and care home level. PIP activity included stopping medicines that were no longer needed or where potential harms outweighed benefits. This analysis of qualitative data examines health and social care stakeholders’ perceptions of how the service impacted on care home medicine procedures and resident well-being. Design: Pragmatic research design with secondary analysis of interviews. Setting: Primary care pharmacist intervention in older people care homes in England, Scotland and Northern Ireland. Participants: Recruited from intervention arm of the trial: PIPs (n=14), GPs (n=8), care home managers (n=9) and care home staff (n=6). Results: There were resonances between different participant groups about potential benefits to care home residents of a medicine service provided by PIPs. There were small differences in perceptions about changes related to communication between professionals. Results are reported through three themes (1) ‘It’s a natural fit’—pharmacists undertaking medication review in care homes fitted within multidisciplinary care; (2) ‘The resident is cared for’—there were subjective improvements in residents’ well-being; (3) ‘Moving from “firefighting” to effective systems’—there was evidence of changes to care home medicine procedures. Conclusion: This study suggests that pharmacist independent prescribers in primary care working within the multidisciplinary team can manage care home residents’ medicines leading to subjective improvements in residents’ well-being and medicine management procedures. Care home staff appreciated contact with a dedicated person in the GP practice

Assessment of Pharmacist Attitudes Regarding Introductory Pharmacy Practice Experience Hours

Introductory pharmacy practice experience (IPPE) hours are a means of integrating experiential education as a key role early on in pharmacy education. The Accreditation Council for Pharmacy Education (ACPE) has offered little guidance on mandatory and specific objectives to accomplish during IPPE hours, thus it is possible that preceptors do not feel adequately prepared, nor do they have a full understanding of what is required of them when they agree to precept an IPPE student. Given the lack of previous research conducted, the objective of this study was to obtain an understanding of the general attitude that preceptors have toward IPPE hours. A self-administered Internet-based questionnaire was completed by 100 respondents. The survey included multiple choice, Likert-type scale (1 =strongly disagree to 7 =strongly agree), sliding scale, and open-ended questions assessing preceptor\u27s knowledge of academic IPPE hour requirements, college of pharmacy expectations, time commitment and work site issues, expectations of the student, formality of IPPE hours, personal experience as a preceptor, an open-ended response and demographic information. Upon analyzing the data, researchers found that respondents presented with a generally positive attitude regarding IPPE hours (5.79 ± 1.03). Respondents expressed a desire to receive a zero to two hour online preceptor training (5.17 ± 1.25). In general, pharmacists indicated sufficient staffing to accommodate IPPE students (3.92 ± 1.38) and were undecided regarding monetary reimbursement (4.39 ± 1.53). Survey participants preferred receiving a guided checklist of activities for completion (S.45 ± 1.27), student resume (5.19 ± 1.30) and previous didactic course work (S.33 ± 1.41); however, survey participants expressed a desire for flexibility in determining the specifics of the experience (5.41 ± 1.11) while having students complete hours in a more concentrated time frame (5.19 ± 1.44). This exploratory research project was conducted to serve as baseline data to stimulate further investigation regarding IPPE hours

Genetic resistance determinants to fusidic acid and chlorhexidine in variably susceptible staphylococci from dogs

Abstract Background Concern exists that frequent use of topically-applied fusidic acid (FA) and chlorhexidine (CHX) for canine pyoderma is driving clinically relevant resistance, despite rare description of FA and CHX genetic resistance determinants in canine-derived staphylococci. This study aimed to determine minimum inhibitory concentrations (MICs) and investigate presence of putative resistance determinants for FA and CHX in canine-derived methicillin-resistant (MR) and -susceptible (MS) staphylococci. Plasmid-mediated resistance genes (fusB, fusC, fusD, qacA/B, smr; PCR) and MICs (agar dilution) of FA and CHX were investigated in 578 staphylococci (50 MR S. aureus [SA], 50 MSSA, 259 MR S. pseudintermedius [SP], 219 MSSP) from Finland, U.S.A., North (NUK) and South-East U.K. (SEUK) and Germany. In all isolates with FA MIC ≥64 mg/L (n = 27) fusA and fusE were amplified and sequenced. Results FA resistance determinants (fusA mutations n = 24, fusB n = 2, fusC n = 36) were found in isolates from all countries bar U.S.A. and correlated with higher MICs (≥1 mg/L), although 4 SP isolates had MICs of 0.06 mg/L despite carrying fusC. CHX MICs did not correlate with qacA/B (n = 2) and smr (n = 5), which were found in SEUK SA, and SP from NUK and U.S.A. Conclusions Increased FA MICs were frequently associated with fusA mutations and fusC, and this is the first account of fusB in SP. Despite novel description of qacA/B in SP, gene presence did not correlate with CHX MIC. Selection pressure from clinical use might increase prevalence of these genetic determinants, but clinical significance remains uncertain in relation to high skin concentrations achieved by topical therapy