Dalbavancin exposure in vitro selects for dalbavancin-non-susceptible and vancomycin-intermediate strains of methicillin-resistant Staphylococcus aureus

ObjectivesDalbavancin is a lipoglycopeptide active against methicillin-resistant Staphylococcus aureus (MRSA). Its long half-life (8.5–16 days) allows for once-weekly or single-dose treatments but could prolong the mutant selection window, promoting resistance and cross-resistance to related antimicrobials such as vancomycin. The objective of this study was to evaluate the capacity of post-distributional pharmacokinetic exposures of dalbavancin to select for resistance and cross-resistance in MRSA.MethodsWe simulated average, post-distributional exposures of single-dose (1500 mg) dalbavancin (fCmax 9.9 μg/mL, β-elimination t_1/2 204 h) in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model for 28 days (672 h) against five MRSA strains and one methicillin-susceptible strain (MSSA). Samples were collected at least daily, and surviving colonies were enumerated and screened for resistance on drug-free and dalbavancin-supplemented medium respectively. Isolates from resistance screening plates were subjected to whole-genome sequencing (WGS) and susceptibly testing against dalbavancin, vancomycin, daptomycin, and six β-lactams with varying penicillin-binding protein (PBP) affinities.ResultsDalbavancin was bactericidal against most strains for days 1–4 before regrowth of less susceptible subpopulations occurred. Isolates with eight-fold increases in dalbavancin MIC were detected as early as day 4 but increased 64–128-fold in all models by day 28. Vancomycin and daptomycin MICs increased 4–16-fold, exceeding the susceptibly breakpoints for both antibiotics; β-lactam MICs generally decreased by two-to eight-fold, suggesting a dalbavancin–β-lactam seesaw effect, but increased by eight-fold or more in certain isolates. Resistant isolates carried mutations in a variety of genes, most commonly walKR, apt, stp1, and atl.ConclusionsIn our in vitro system, post-distributional dalbavancin exposures selected for stable mutants with reduced susceptibility to dalbavancin, vancomycin, and daptomycin, and generally increased susceptibility to β-lactams in all strains of MRSA tested. The clinical significance of these findings remains unclear, but created an opportunity to genotype a unique collection of dalbavancin-resistant strains for the first time. Mutations involved genes previously associated with vancomycin intermediate susceptibility and daptomycin non-susceptibility, most commonly walKR-associated genes.     

Perinatal depression screening practices in a large health system: identifying current state and assessing opportunities to provide more equitable care

The purpose of this study was to assess the prevalence of prenatal and postpartum depression screening in a large health system and to identify covariates for screening, with a specific focus in understanding disparities in practice. A retrospective cohort of women with deliveries in 2016 was created using electronic health records. Primary outcomes were depression screening during pregnancy and the first 3 months postpartum. Generalized linear mixed models with women nested within clinic were used to determine the effect of maternal and clinical characteristics on depression screening. The sample included 7548 women who received prenatal care at 35 clinics and delivered at 10 hospitals. The postpartum sample included 7059 women who returned within 3 months for a postpartum visit. Of those, 65.1% were screened for depression during pregnancy, and 64.4% were screened postpartum. Clinic site was the strongest predictor of screening, accounting for 23–30% of the variability in screening prevalence. There were no disparities identified with regard to prenatal screening. However, several disparities were identified for postpartum screening. After adjusting for clinic, women who were African American, Asian, and otherwise non-white (Native American, multi-racial) were less likely to be screened postpartum than white women (AOR (CI)’s 0.81 (0.65, 1.01), 0.64 (0.53, 0.77), and 0.44 (0.21, 0.96), respectively). Women insured by Medicaid/Medicare, a proxy for low-income, were less likely to be screened postpartum than women who were privately insured (AOR (CI) 0.78 (0.68, 0.89)). National guidelines support universal depression screening of pregnant and postpartum women. The current study found opportunities for improvement in order to achieve universal screening and to deliver equitable care.

     

Consulting the community: public expectations and attitudes about genetics research

Genomic discoveries and technologies promise numerous opportunities for improving health. Key to these potential health improvements, however, are health-care consumers'' understanding and acceptance of these new developments. We identified community groups and invited them to a public information-consultation session in order to explore public awareness, perception and expectations about genetics and genomics research. One hundred and four members of seven community groups in Newfoundland, Canada took part in the community sessions. Content analysis of participant comments revealed they were largely hopeful about genetics research in its capacity to improve health; however, they did not accept such research uncritically. Complex issues arose during the community consultations, including the place of genetics in primary care, the value of genetics for personal health, and concerns about access to and uses of genetic information. Participants unequivocally endorsed the value of public engagement with these issues. The rapid pace of discoveries in genomics research offers exciting opportunities to improve population health. However, public support will be crucial to realize health improvements. Our findings suggest that regular, transparent dialog between researchers and the public could allow a greater understanding of the research process, as well as assist in the design of efficient and effective genetic health services, informed by the public that will use them.     

Dealing with Difficult Patients: Do Customer Service Initiatives Improve Patient Satisfaction at an Interdisciplinary Pain Center?

Chronic pain patients can be difficult to manage due to complicated medical and psychiatric comorbidities. This study focused on strategies designed to improve patient treatment satisfaction within a tertiary urban hospital‐based pain management center. Information was obtained of monthly patient satisfaction and Press Ganey scores in 2009 based on patient perceptions of staff and telephone access, frequency of returned phone calls, staff empathy and responsiveness, and overall patient experience with their pain treatment. Information was also obtained of the number of formal complaints made to the Patient Relations Department of the hospital. A customer service program designed to target patient's phone access, response to phone calls, improved patient experiences, and service friendliness was initiated in March 2010. Six hundred eleven patients (n = 611) were randomly surveyed 3 months after their treatment between 2009 and 2012 and rates of formal patient complaints were monitored. Thirty‐three (n = 33) staff members were encouraged to attend monthly 1.5‐hour customer service meetings and participate in specialized work teams between March 2010 and December 2012. Patient satisfaction scores rose from a low of 80.3 (average of 83.5%) in 2009 to a high of 91.2 (average 88.9%) in 2012. Annual formal complaints to Patient Relations decreased by 40.5% over 4 years (112 in 2009 to 30 in 2012). Phone abandonment rates also decreased by 20% and the center scored 12% higher than average total practice scores in patient satisfaction based on secret shopper ratings. This study demonstrates that customer service initiatives that engage staff participation and that are designed to target specific improvements in patient satisfaction can effectively change the way pain patients perceive treatment at an interdisciplinary anesthesia‐based pain center.     

CD31 expression in plasmacytic/plasmablastic lesions

Although CD31 has been considered one of the better, if not the best, immunohistochemical marker of endothelial cells and thereby vascular neoplasia, it is not unequivocally specific to this group of tumors. We examined CD31 staining in 34 plasmacytic lesions including 15 plasma cell myelomas, 1 extraosseous plasmacytoma, 10 plasmablastic variants of myeloma, 5 plasmablastic non-Hodgkin lymphomas, and 3 reactive plasmacytic infiltrates. All reactive plasma cellular infiltrates, 93% of plasma cell myelomas, 80% of plasmablastic variants of myelomas, and 20% of plasmablastic non-Hodgkin lymphoma cases were CD31 positive with usually diffuse and strong membranous staining. When ERG staining was performed, none were ERG positive. Plasmablastic variant of myeloma is another large cell malignancy that has the potential to be mistaken for a poorly differentiated epithelioid vascular neoplasm if CD31 is presumed to be an explicit marker of endothelial cells.