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Background: Over the past decade, the CLSI has updated susceptibility break points for several antimicrobial agents. The purpose of this study was to evaluate the impact of these changes against gram-negative bacteria at our academic medical center. Methods: In this retrospective, IRB-approved study, we collected consecutive, nonduplicate clinical isolates of Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, K. oxytoca, K. pneumoniae, and Pseudomonas aeruginosa for the past decade (2010–2019) at our academic medical center and 3 adult ICUs. Susceptibility testing was performed using the BD Phoenix automated system. For these isolates, susceptibilities for 7 β-lactams (aztreonam, ceftriaxone, ceftazidime, cefepime, piperacillin/tazobactam, ertapenem, and meropenem) and 2 fluoroquinolones (levofloxacin, ciprofloxacin) were calculated based upon CLSI break points in 2010 and current CLSI break points in 2020. Any change >5% in susceptibility was deemed significant for this analysis. Results: In 17.5% of Enterobacteriales isolates tested, at least 1 antimicrobial demonstrated significant decline. Ertapenem was the most commonly affected antimicrobial (45% of the isolates) followed by ceftriaxone (35%) and cefepime (25%). Susceptibilities of aztreonam, ceftazidime, and meropenem were not affected for any of the Enterobacteriales. The most common organism demonstrating a significant impact on change in susceptibility among the Enterobacteriales was E. cloacae (41.7% of the time) followed by E. aerogenes (20.8%), K. oxytoca (12.5%), K. pneumoniae (8.3%) and E. coli (4.2%). Most of the impact was observed hospital-wide (33.3%), followed closely by the MICU (28.6%), the NSICU (23.8%) and the CVICU (14.3%). For P. aeruginosa, the impact of the antimicrobial break-point changes on susceptibility was more pronounced than the Enterobacteriales. Overall, 93.8% of the time there was a significant decline in antimicrobial susceptibility. Each antimicrobial (ciprofloxacin, levofloxacin, meropenem, and piperacillin/tazobactam) demonstrated a significant decline in susceptibility hospital-wide and in each ICU except for the susceptibility of meropenem in the NSICU. Conclusions: Changes in break points had a significant impact on the susceptibility of all antimicrobials for P. aeruginosa at our institution, both hospital-wide and in the adult ICUs. Although the impact was less for the Enterobacteriales, ertapenem, ceftriaxone, and cefepime demonstrated significant susceptibility changes, especially with E. cloacae. Understanding and evaluating the impact of the break-point changes may lead to changes in empiric therapy in other institutions.
Background: A team of infectious diseases physicians, infectious diseases pharmacists, clinical laboratorians, and researchers collaborated to assess the management of lower respiratory tract infections (LRTIs). In 1 sample from our institution, 96.1% of pneumonia cases were prescribed antibiotics, compared to 85.0% in a comparison group. A collaborative effort led to the development of a protocol for procalcitonin (PCT)-guided antibiotic prescribing that was approved by several hospital committees, including the Antimicrobial Stewardship Committee and the Healthcare Pharmacy & Therapeutics Committee in December 2020. The aim of this analysis was to develop baseline information on PCT ordering and antibiotic prescribing patterns in LRTIs. Methods: We evaluated all adult inpatients (March–September 2019 and 2020) with a primary diagnosis of LRTI who received at least 1 antibiotic. Two cohorts were established to observe any potential differences in the 2 most recent years prior to adoption of the PCT protocol. Data (eg, demographics, specific diagnosis, length of stay, antimicrobial therapy and duration, PCT labs, etc) were obtained from the UK Center for Clinical and Translational Science, and the study was approved by the local IRB. The primary outcome of interest was antibiotic duration; secondary outcomes of interest were PCT orders, discharge antibiotic prescription, and inpatient length of stay. Results: In total, 432 patients (277 in 2019 and 155 in 2020) were included in this analysis. The average patient age was 61.2 years (SD, ±13.7); 47.7% were female; and 86.1% were white. Most patients were primarily diagnosed with pneumonia (58.8%), followed by COPD with complication (40.5%). In-hospital mortality was 3.5%. The minority of patients had any orders for PCT (29.2%); among them, most had only 1 PCT level measured (84.1%). The median length of hospital stay was 4 days (IQR, 2–6), and the median duration of antibiotic therapy was 4 days (IQR, 3–6). Conclusions: The utilization of PCT in LRTIs occurs in the minority of patient cases at our institution and mostly as a single measurement. The development and implementation of a PCT-guided therapy could help optimize antibiotic usage in patients with LRTIs.
Background: Carbapenem-resistant Enterobacteriaceae (CRE) remain among the most urgent infectious threats according to the CDC Threats Reports. Although focus has often been placed on carbapenemase-producing phenotypes, there is increasing interest in distinguishing the optimal treatment and outcomes of carbapenemase-producing (CP) and non–carbapenemase-producing (NCP) CRE. We compare antimicrobial susceptibility patterns between CP-CRE and NCP-CRE isolated from patients at our academic medical center. Methods: All CRE isolates of Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, K. oxytoca, and K. pneumoniae in adult inpatients from 2010 to 2019 were included in this study. Susceptibility testing was performed using the BD Phoenix Automated System (BD Diagnostics, Sparks, MD). CLSI susceptibility break points were utilized in the susceptibility analyses of all antimicrobials tested. To determine carbapenemase production, isolates resistant only to ertapenem were considered NCP-CRE, and those resistant to both ertapenem and meropenem were considered CP-CRE. Statistical comparisons of susceptibility profiles were performed using either the χ2 test or the Fisher exact test. All data preprocessing and statistical analyses were performed using Python software. Results: Over the decade, we identified 291 CRE isolates (216 isolates resistant only to ertapenem and 75 resistant to ertapenem and meropenem). The ertapenem-resistant–only phenotype comprises ~66% of the total CRE population and is largely composed of E. cloacae (67%). As expected, most β-lactam susceptibilities were negligibly low between the 2 groups; however, other clinically relevant antimicrobials (aminoglycosides, fluoroquinolones, and sulfamethoxazole/trimethoprim) exhibited starkly different susceptibility profiles (P value Conclusions: These findings suggest that the most predominant CRE phenotype at our institution is not carbapenemase production. Evaluation of outcomes between CP- and NCP-CRE should be pursued further. The large differences in the MIC distributions may lead to differing outcomes for the affected patients.
Background: Despite the development of new β-lactam agents, gram-negative resistance continues to be an increasing concern in the healthcare setting. The understanding and optimizing antimicrobial pharmacokinetics and pharmacodynamics are essential to enhance activity of appropriate therapy, improve clinical outcomes, and reduce the development of resistance. Methods: A pharmacodynamic analysis was performed for 4 β-lactams (aztreonam, cefepime, piperacillin/tazobactam, and meropenem) and 14 dosage regimens as either intermittent bolus (IB) or prolonged infusion (PI) against 7 gram-negative pathogens: Klebsiella pneumoniae, K. oxytoca, Escherichia coli, Enterobacter cloacae, E. aerogenes, Acinetobacter baumannii, and Pseudomonas aeruginosa. Unit-specific minimum inhibitory concentration (MIC) distribution data were generated using antibiogram data over a decade for 4 intensive care units within our institution: medical ICU, cardiovascular ICU, surgical ICU, and neurosurgical ICU. Published pharmacokinetic parameter estimates in critically ill patients, combined with this MIC distribution data, were utilized to perform Monte Carlo simulations for each antimicrobial regimen. The percentage of time for which the unbound concentration of antibiotic remained above the MIC (ƒT>MIC) was utilized as the pharmacodynamic target for each agent: 40% ƒT>MIC for meropenem, 50% ƒT>MIC for piperacillin/tazobactam, 60% ƒT>MIC for aztreonam, and 70% ƒT>MIC for cefepime. Regimens were modeled using Oracle Crystal Ball software to determine the likelihood of achieving >90% probability of target attainment (PTA). Because resistance rates were significantly higher for P. aeruginosa and A. baumannii, cumulative PTAs for K. pneumoniae, K. oxytoca, E. coli, E. cloacae, and E. aerogenes were analyzed separately to determine the relative PTA for Enterobacterales in each ICU. Results: No intermittent infusion regimens of piperacillin/tazobactam, aztreonam, or cefepime achieved >90% PTA for any organism. Piperacillin/tazobactam 4.5 g infused over 4 hours (PI q6h) and aztreonam 2 g PI q6h failed to achieve adequate PTA for Enterobacterales with only 84% and 85% PTA, respectively. For Enterobacterales, the only regimens to achieve >90% PTA included cefepime 2 g infused over 3 hours (PI q8h) and meropenem 1g IB q8h with 95% and 99% PTA, respectively. Meropenem 2 g PI q8h was the only regimen capable of achieving >90% PTA for both A. baumannii and P. aeruginosa with 97% and 92% PTA, respectively. Conclusions: Although utilization of high doses and prolonged infusions dramatically improve the pharmacodynamics of β-lactam therapy, the only regimen capable of achieving adequate PTA for all organisms analyzed was meropenem 2g PI q8h. To reduce carbapenem use, combination therapy may be considered for critically ill patients receiving aztreonam, cefepime, or piperacillin/tazobactam for empiric treatment of gram-negative infections.
A review of Australian mental health services identified a gap in routine outcome measures addressing social, emotional and behavioural domains for pre-schoolers and infants. A Child and Adolescent Mental Health Information Development Expert Advisory Panel working group developed the Health of the Nation Outcome Scales for Infants (HoNOSI), a clinician-reported routine outcome measure for infants 0–47 months. Prior face validity testing showed that the HoNOSI was considered useful in measuring mental health outcomes.
To examine the concurrent validity of the HoNOSI.
Mental health clinicians providing assessment and treatment to infants in routine clinical practice participated in the study. The mental health status of 108 infants were rated by a minimum of 26 clinicians with the HoNOSI, the Parent-Infant Relationship Global Assessment Scale (PIR-GAS) and measures of symptom severity and distress.
The HoNOSI was statistically significantly correlated with the PIR–;GAS, rs = −0.73; Clinical Worry, rs = 0.77; and Severity Judgement ratings, rs = 0.85; P < 0.001. A good level of internal consistency was found. Using the COsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria for judging instrument acceptability, the HoNOSI meets the standard for both concurrent validity and internal consistency.
There has been a clear need for a routine outcome measure for use with infants. This study provides positive evidence of aspects of validity. These findings, along with those from the prior face validity study, support a controlled release of the HoNOSI accompanied by further research and development.
This chapter will develop the role that deliberative public engagement should have in health research regulation. The goal of public deliberation is to mobilise the expertise that members of public have, to explore their values in relation to specific trade-offs, with the objective of recommendations that respect diverse interests. Public deliberation requires that a small group is invited to a structured event that supports informed, civic-minded consideration of diverse perspectives on public interest. Ensuring that the perspectives considered are inclusive of perspectives that might otherwise be marginalised or silenced requires explicitly designing the small group in relation to the topic. Incorporating public expertise enhances the trustworthiness of policies and governance by explicitly acknowledging and negotiating diverse public interests. Trustworthiness is distinct from trust, so the chapter begins by exploring that distinction in the context of the example of care.data and the loss of trust in the English National Health Service’s (NHS) use of electronic health records for research. While better public engagement prior to the announcement might have avoided the loss of trust, subsequent deliberative public engagement may build trustworthiness into the governance, and contribute to re-establishing trust.
A review of Australian mental health services identified a gap in routine outcome measures addressing social, emotional and behavioural domains for pre-schoolers and infants. The Child and Adolescent Mental Health Information Development Expert Advisory Panel Working Group developed the Health of the Nation Outcome Scales for Infants (HoNOSI), a clinician-reported routine outcome measure for use with those aged under 4 years. Prior psychometric testing showed that the HoNOSI was considered to show face validity, and that it met the standards for concurrent validity and internal consistency.
We aimed to investigate the interrater reliability of the HoNOSI.
Forty-five infant mental health clinicians completed HoNOSI ratings on a set of five case vignettes.
Quadratic weighted kappa interrater reliability estimates showed the HoNOSI to have Almost Perfect interrater reliability for the HoNOSI total score. Of the 15 scales, one had Moderate, seven had Substantial and seven had Almost Perfect interrater reliability. Ten of the fifteen scales and the total score exceeded the COnsensus-based Standards for the Selection of Health Measurement INstruments criteria for interrater reliability (κw ≥ 0.7).
There has been a clear need for a routine outcome measure for use with infants and pre-schoolers. This study provides evidence of interrater reliability. The current findings, combined with the face and concurrent validity studies, support further examination of HoNOSI in real-world settings.
The contributions to this Special Issue, and the books to which they relate, are premised on the idea that the Rule of Law relates to private relationships. I challenge that idea. By exploring solely theoretical ideas, I argue that the Rule of Law – as it is usually defined – does not relate to private relationships and, in consequence, the nexus necessary to invoke a Rule of Law-solution in the circumstances outlined in the books is absent.
Mental health (MH) service users have increased prevalence of chronic physical conditions such as cardio-respiratory diseases and diabetes. Potentially Preventable Hospitalisations (PPH) for physical health conditions are an indicator of health service access, integration and effectiveness, and are elevated in long term studies of people with MH conditions. We aimed to examine whether PPH rates were elevated in MH service users over a 12-month follow-up period more suitable for routine health indicator reporting. We also examined whether MH service users had increased PPH rates at a younger age, potentially reflecting the younger onset of chronic physical conditions.
A population-wide data linkage in New South Wales (NSW), Australia, population 7.8 million. PPH rates in 178 009 people using community MH services in 2016–2017 were compared to population rates. Primary outcomes were crude and age- and disadvantage-standardised annual PPH episode rate (episodes per 100 000 population), PPH day rate (hospital days per 100 000) and adjusted incidence rate ratios (AIRR).
MH service users had higher rates of PPH admission (AIRR 3.6, 95% CI 3.5–3.6) and a larger number of hospital days (AIRR 5.2, 95% CI 5.2–5.3) than other NSW residents due to increased likelihood of admission, more admissions per person and longer length of stay. Increases were greatest for vaccine-preventable conditions (AIRR 4.7, 95% CI 4.5–5.0), and chronic conditions (AIRR 3.7, 95% CI 3.6–3.7). The highest number of admissions and relative risks were for respiratory and metabolic conditions, including chronic obstructive airways disease (AIRR 5.8, 95% CI 5.5–6.0) and diabetic complications (AIRR 5.4, 95% CI 5.1–5.8). One-quarter of excess potentially preventable bed days in MH service users were due to vaccine-related conditions, including vaccine-preventable respiratory illness. Age-related increases in risk occurred earlier in MH service users, particularly for chronic and vaccine-preventable conditions. PPH rates in MH service users aged 20–29 were similar to population rates of people aged 60 and over. These substantial differences were not explained by socio-economic disadvantage.
PPHs for physical health conditions are substantially increased in people with MH conditions. Short term (12-month) PPH rates may be a useful lead indicator of increased physical morbidity and less accessible, integrated or effective health care. High hospitalisation rates for vaccine-preventable respiratory infections and hepatitis underline the importance of vaccination in MH service users and suggests potential benefits of prioritising this group for COVID-19 vaccination.