Automated Insulin Delivery Technology in the Hospital: Update on Safety and Efficacy Data.

OBJECTIVE: Automated insulin delivery (AID) systems are a rapidly growing component in the area of continuous subcutaneous insulin infusion (CSII) therapy. As more patients use these systems in the outpatient setting, it is important to assess safety if their use is allowed to continue in the inpatient setting. METHODS: Analysis was conducted of the records of patients using AID technology upon admission to our hospital between June 2020 and December 2022. Adverse events and glycemic control of AID users were compared with patients using non-AID systems and with patients who had CSII discontinued. RESULTS: There were 185 patients analyzed: 64 on AID, 86 on non-AID, and 35 who had CSII discontinued. The number of patients on AID increased over the course of the observation period, whereas non-AID users decreased. Pairwise comparisons indicated that patient-stay mean glucose levels and percentage of hypoglycemic events were similar between all groups, but the percentage of patient hyperglycemic measurements was significantly lower in the AID cohort. No adverse events (diabetic ketoacidosis, pump site complications, equipment malfunction) were reported in any either CSII cohort. CONCLUSION: The type of CSII technology encountered in the hospital is shifting from non-AID toward AID technologies. This analysis supports earlier findings that outpatient AID systems can be successfully transitioned into the inpatient setting. Further study is needed to define if AID systems offer any advantage in glycemic control.

A feasibility randomised waitlist-controlled trial of a personalised multi-level language treatment for people with aphasia: The remote LUNA study.

BACKGROUND: Stroke survivors with aphasia want to improve their everyday talking (discourse). In current UK practice, 90% of speech and language therapists believe discourse assessment and treatment is part of their role but are hampered by barriers in resources, time and expertise. There is a clinical need for well-articulated discourse assessment and treatments. LUNA is a multi-level treatment targeting words, sentences and discourse macrostructure in personal stories that addresses this clinical need. OBJECTIVES: This study aimed to assess the feasibility and acceptability of LUNA trial procedures in a randomised waitlist-controlled trial; and to evaluate preliminary efficacy. METHODS: This paper reports a phase II, waitlist-controlled, proof-of-concept feasibility trial. Participants with chronic aphasia (n = 28) were recruited from the community and randomised to an Immediate (n = 14) or Delayed (n = 14) group. LUNA treatment was delivered twice weekly for 10 weeks via the videoconferencing technology, Zoom. Feasibility was assessed in terms of participant recruitment and retention, adherence, missing data, and treatment fidelity. Preliminary treatment efficacy was assessed in terms of between group differences in outcome measures relating to discourse, language, and psychosocial state. RESULTS: The remote LUNA trial was feasible: 85% of those eligible consented to the trial; trial retention was 86%; 87% of treatment sessions were delivered as scheduled, and 79% of participants completed 80%+ of the treatment programme; data was missing only for participants who withdrew; treatment fidelity was high at 92% adherence; and only one clinical outcome measure demonstrated ceiling effects. ANCOVA analysis of the clinical outcome measures revealed group differences with medium and large effect sizes, indicating, improvements in the production of words, sentences, discourse macrostructure, overall language functioning (WAB-R), and psychosocial state (VAMS) following LUNA treatment. For most outcomes measured, similar treatment benefits were suggested in a secondary, non-parametric analysis. CONCLUSIONS: Large-scale evaluation of the clinical efficacy and cost-effectiveness of LUNA is warranted and supported by these findings. TRIAL REGISTRATION: Clinical trials registration: NCT05847023 (clinical trials.gov).

Dietary and Lifestyle Factors of Brain Iron Accumulation and Parkinson's Disease Risk.

Purpose: Iron is an essential nutrient which can only be absorbed through an individual's diet. Excess iron accumulates in organs throughout the body including the brain. Iron dysregulation in the brain is commonly associated with neurodegenerative diseases like Alzheimer's disease and Parkinson's Disease (PD). Our previous research has shown that a pattern of iron accumulation in motor regions of the brain related to a genetic iron-storage disorder called hemochromatosis is associated with an increased risk of PD. To understand how diet and lifestyle factors relate to this brain endophenotype and risk of PD we analyzed the relationship between these measures, estimates of nutrient intake, and diet and lifestyle preference using data from UK Biobank. Methods: Using distinct imaging and non-imaging samples (20,477 to 28,388 and 132,023 to 150,603 participants, respectively), we performed linear and logistic regression analyses using estimated dietary nutrient intake and food preferences to predict a) brain iron accumulation score (derived from T2-Weighted Magnetic Resonance Imaging) and b) PD risk. In addition, we performed a factor analysis of diet and lifestyle preferences to investigate if latent lifestyle factors explained significant associations. Finally, we performed an instrumental variable regression of our results related to iron accumulation and PD risk to identify if there were common dietary and lifestyle factors that were jointly associated with differences in brain iron accumulation and PD risk. Results: We found multiple highly significant associations with measures of brain iron accumulation and preferences for alcohol (factor 7: t=4.02, pFDR=0.0003), exercise (factor 11: t=-4.31, pFDR=0.0001), and high-sugar foods (factor 2: t=-3.73, pFDR=0.0007). Preference for alcohol (factor 7: t=-5.83, pFDR<1×10-8), exercise (factor 11: t=-7.66, pFDR<1×10-13), and high sugar foods (factor 2: t=6.03, pFDR<1×10-8) were also associated with PD risk. Instrumental variable regression of individual preferences revealed a significant relationship in which dietary preferences associated with higher brain iron levels also appeared to be linked to a lower risk for PD (p=0.004). A similar relationship was observed for estimates of nutrient intake (p=0.0006). Voxel-wise analysis of i) high-sugar and ii) alcohol factors confirmed T2-weighted signal differences consistent with iron accumulation patterns in motor regions of the brain including the cerebellum and basal ganglia. Conclusion: Dietary and lifestyle factors and preferences, especially those related to carbohydrates, alcohol, and exercise, are related to detectable differences in brain iron accumulation and alterations in risk of PD, suggesting a potential avenue for lifestyle interventions that could influence risk.

Invasive Community-Onset Gram-Positive Infections From July 2018 Through December 2022 at 2 Children's Hospitals.

Background: Invasive infections caused by Streptococcus pyogenes (invasive group A streptococcus [iGAS]) and Streptococcus pneumoniae (invasive pneumococcal disease [IPD]) decreased substantially at the beginning of the COVID-19 pandemic. Our study sought to evaluate the extent of this decrease and the trends of these infections since reversion of societal adjustments incident to the pandemic. We also wanted to compare the frequency of these infections with invasive community-onset Staphylococcus aureus (I-CO-SA) infections and common respiratory viral infections in this period. Methods: Cases of iGAS, IPD, and I-CO-SA infections were identified prospectively and retrospectively at 2 large US children's hospitals by positive cultures from July 2018 through December 2022. Admission data were used to estimate frequency. For comparison, rates of respiratory syncytial virus (RSV), influenza, and SARS-CoV-2 were estimated by the number of positive viral test results at each institution. Results: I-CO-SA infections showed little variation in the study period. Rates of iGAS infection and IPD decreased by 46% and 44%, respectively, from 2019 to 2020, coinciding with a substantial decrease in RSV and influenza. In 2022, RSV and influenza infection rates increased to prepandemic winter season rates, coinciding with a return to prepandemic rates of IPD (225% increase from 2021 to 2022) and a surge above prepandemic rates of iGAS infections (543% increase from 2021 to 2022). Conclusions: The COVID-19 pandemic had an unexpected influence on IPD and iGAS infections that was temporally related to changes in rates of viral infections.

Seeing Yourself Through the Learner's Eyes: Incorporating Smart Glasses Into Objective Structured Teaching Exercises for Faculty Development.

INTRODUCTION: Although physicians gain clinical knowledge in their specialty, it does not mean they receive adequate instruction to teach and provide feedback. Using smart glasses (SG) to provide educators with a first-person learner perspective has not been explored in faculty development such as Objective Structured Teaching Exercises (OSTEs). METHODS: Integrated within a 6-session continuing medical education-bearing certificate course, this descriptive study involved one session where participants provided feedback to a standardized student in an OSTE. Participants were recorded by mounted wall cameras (MWCs) and SG. They received verbal feedback on their performance based on a self-designed assessment tool. Participants reviewed the recorded content and identified areas for improvement, completed a survey about their experience with SG, and wrote a narrative reflection. RESULTS: Seventeen physicians at the assistant professor level participated in the session; data were analyzed on the 14 who had both MWC and SG recordings and who also completed the survey and reflection. All were comfortable with the standardized student wearing SG and indicated it did not affect communication. Eighty-five percent of the participants felt the SG provided additional feedback not available with the MWC, with majority noting additional feedback was related to eye contact, body language, voice inflection, and tone. Eighty-six percent see value in using SG for faculty development, and 79% felt that periodically using SG in their teaching would improve quality. CONCLUSION: Use of SG during an OSTE on giving feedback was a nondistracting and positive experience. SG provided affective feedback otherwise not perceived from a standard MWC.

Going Back in Time: Increasing Penicillin Susceptibility among Methicillin-Susceptible Staphylococcus aureus Osteoarticular Infections in Children.

In the late 1940s to 1950s, Staphylococcus aureus isolates first-gained resistance to penicillin. Recently, some centers have described an increase in the proportion of methicillin susceptible S. aureus (MSSA) which are also susceptible to penicillin (PSSA). There are little data on the frequency of PSSA infections in children. We investigated the prevalence of penicillin susceptibility among pediatric MSSA acute hematogenous osteoarticular infection (OAI) isolates. MSSA OAI isolates were obtained through surveillance studies at Texas Children's and St. Louis Children's Hospitals from January 2011 to December 2019. All isolates underwent PCR for blaZ ß-lactamase, PVL genes and agr group. All blaZ negative isolates then underwent penicillin MIC determination. blaZ negative isolates with penicillin MIC ≤ 0.125 µg/mL were considered PSSA. Multilocus sequence typing (MLST) was conducted on a subset of isolates. A total of 329 unique isolates were included in the study. The median patient age was 9.2 years (IQR:5.1 to 12.2). Overall, 6.7% of isolates were penicillin susceptible. No PSSA were detected prior to 2015 but increased yearly thereafter. By the final study year, 20.4% of isolates were PSSA (P = 0.001). PSSA were similar to penicillin-resistant MSSA (PR-MSSA) isolates in terms agr group and PVL carriage as well as clinical presentation and outcomes. PSSA were of distinct sequence types compared to PR-MSSA. PSSA appears to be increasing among OAI in U.S. children. Overall, PSSA isolates are associated with a similar clinical presentation as penicillin-resistant isolates. The potential for use of penicillin treatment in PSSA OAI warrants further study.

Hybrid Closed-Loop Insulin Pump Technology Can Be Safely Used in the Inpatient Setting.

BACKGROUND: Hybrid closed-loop (HCL) systems, also known as automated insulin delivery systems, are a rapidly growing technology in diabetes management. Because more patients are using these systems in the outpatient setting, it is important to also assess inpatient safety to determine whether HCL use can be continued when those patients become hospitalized. METHODS: The records of patients using HCL technology on admission to our hospital between June 1, 2020, and June 30, 2021, were analyzed. RESULTS: The final analysis included 71 patients divided into 3 categories based on their pump use as an inpatient: (1) HCL users; (2) manual pump users; and (3) pump removed. All cohorts were similar in age, sex, race, hemoglobin A1C at admission, and in Medicare Severity Diagnosis Related Group. Pairwise comparisons indicated that patient-stay mean glucose levels, frequency of patient-specific hyperglycemic measurements, and frequency of hypoglycemic events were similar between all groups. No adverse events, particularly occurrences of diabetic ketoacidosis, pump site complications or infection, or equipment malfunction, were reported. CONCLUSION: This preliminary case series review indicates that continued use of HCL technology in the hospital is safe. Moreover, glycemic control in HCL users was comparable with that in those using insulin pump with manual settings and those converted to basal-bolus insulin therapy.

Modifications to student quarantine policies in K-12 schools implementing multiple COVID-19 prevention strategies restores in-person education without increasing SARS-CoV-2 transmission risk, January-March 2021.

OBJECTIVE: To determine whether modified K-12 student quarantine policies that allow some students to continue in-person education during their quarantine period increase schoolwide SARS-CoV-2 transmission risk following the increase in cases in winter 2020-2021. METHODS: We conducted a prospective cohort study of COVID-19 cases and close contacts among students and staff (n = 65,621) in 103 Missouri public schools. Participants were offered free, saliva-based RT-PCR testing. The projected number of school-based transmission events among untested close contacts was extrapolated from the percentage of events detected among tested asymptomatic close contacts and summed with the number of detected events for a projected total. An adjusted Cox regression model compared hazard rates of school-based SARS-CoV-2 infections between schools with a modified versus standard quarantine policy. RESULTS: From January-March 2021, a projected 23 (1%) school-based transmission events occurred among 1,636 school close contacts. There was no difference in the adjusted hazard rates of school-based SARS-CoV-2 infections between schools with a modified versus standard quarantine policy (hazard ratio = 1.00; 95% confidence interval: 0.97-1.03). DISCUSSION: School-based SARS-CoV-2 transmission was rare in 103 K-12 schools implementing multiple COVID-19 prevention strategies. Modified student quarantine policies were not associated with increased school incidence of COVID-19. Modifications to student quarantine policies may be a useful strategy for K-12 schools to safely reduce disruptions to in-person education during times of increased COVID-19 community incidence.

Association of Genetic Variant Linked to Hemochromatosis With Brain Magnetic Resonance Imaging Measures of Iron and Movement Disorders.

Importance: Hereditary hemochromatosis (HH) is an autosomal recessive genetic disorder that leads to iron overload. Conflicting results from previous research has led some to believe the brain is spared the toxic effects of iron in HH. Objective: To test the association of the strongest genetic risk variant for HH on brainwide measures sensitive to iron deposition and the rates of movement disorders in a substantially larger sample than previous studies of its kind. Design, Setting, and Participants: This cross-sectional retrospective study included participants from the UK Biobank, a population-based sample. Genotype, health record, and neuroimaging data were collected from January 2006 to May 2021. Data analysis was conducted from January 2021 to April 2022. Disorders tested included movement disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10], codes G20-G26), abnormalities of gait and mobility (ICD-10 codes R26), and other disorders of the nervous system (ICD-10 codes G90-G99). Exposures: Homozygosity for p.C282Y, the largest known genetic risk factor for HH. Main Outcomes and Measures: T2-weighted and T2* signal intensity from brain magnetic resonance imaging scans, measures sensitive to iron deposition, and clinical diagnosis of neurological disorders. Results: The total cohort consisted of 488 288 individuals (264 719 female; ages 49-87 years, largely northern European ancestry), 2889 of whom were p.C282Y homozygotes. The neuroimaging analysis consisted of 836 individuals: 165 p.C282Y homozygotes (99 female) and 671 matched controls (399 female). A total of 206 individuals were excluded from analysis due to withdrawal of consent. Neuroimaging analysis showed that p.C282Y homozygosity was associated with decreased T2-weighted and T2* signal intensity in subcortical motor structures (basal ganglia, thalamus, red nucleus, and cerebellum; Cohen d >1) consistent with substantial iron deposition. Across the whole UK Biobank (2889 p.C282Y homozygotes, 485 399 controls), we found a significantly increased prevalence for movement disorders in male homozygotes (OR, 1.80; 95% CI, 1.28-2.55; P = .001) but not female individuals (OR, 1.09; 95% CI, 0.70-1.73; P = .69). Among the 31 p.C282Y male homozygotes with a movement disorder, only 10 had a concurrent HH diagnosis. Conclusions and Relevance: These findings indicate increased iron deposition in subcortical motor circuits in p.C282Y homozygotes and confirm an increased association with movement disorders in male homozygotes. Early treatment in HH effectively prevents the negative consequences of iron overload in the liver and heart. Our work suggests that screening for p.C282Y homozygosity in high-risk individuals also has the potential to reduce brain iron accumulation and to reduce the risk of movement disorders among male individuals who are homozygous for this mutation.

Longitudinal Dynamics of Skin Bacterial Communities in the Context of Staphylococcus aureus Decolonization.

Decolonization with topical antimicrobials is frequently prescribed in health care and community settings to prevent Staphylococcus aureus infection. However, effects on commensal skin microbial communities remains largely unexplored. Within a household affected by recurrent methicillin-resistant S. aureus skin and soft tissue infections (SSTI), skin swabs were collected from the anterior nares, axillae, and inguinal folds of 14 participants at 1- to 3-month intervals over 24 months. Four household members experienced SSTI during the first 12-months (observational period) and were prescribed a 5-day decolonization regimen with intranasal mupirocin and bleach water baths at the 12-month study visit. We sequenced the 16S rRNA gene V1-V2 region and compared bacterial community characteristics between the pre- and post-intervention periods and between younger and older subjects. The median Shannon diversity index was stable during the 12-month observational period at all three body sites. Bacterial community characteristics (diversity, stability, and taxonomic composition) varied with age. Among all household members, not exclusively among the four performing decolonization, diversity was unstable throughout the year post-intervention. In the month after decolonization, bacterial communities were changed. Although communities largely returned to their baseline states, relative abundance of some taxa remained changed throughout the year following decolonization (e.g., more abundant Bacillus; less abundant Cutibacterium). This 5-day decolonization regimen caused disruption of skin bacteria, and effects differed in younger and older subjects. Some effects were observed throughout the year post-intervention, which emphasizes the need for better understanding of the collateral effects of decolonization for S. aureus eradication. IMPORTANCE Decolonization with topical antimicrobials is frequently prescribed to prevent Staphylococcus aureus infection, but the effects on commensal skin bacteria are undetermined. We found that decolonization with mupirocin and bleach water baths leads to sustained disruption of bacterial communities.

Food for thought: Eating before saliva collection and interference with SARS-CoV-2 detection.

Saliva is a promising specimen for the detection of viruses that cause upper respiratory infections including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to its cost-effectiveness and noninvasive collection. However, together with intrinsic enzymes and oral microbiota, children's unique dietary habits may introduce substances that interfere with diagnostic testing. To determine whether children's dietary choices impact SARS-CoV-2 molecular detection in saliva, we performed a diagnostic study that simulates testing of real-life specimens provided from healthy children (n = 5) who self-collected saliva at home before and at 0, 20, and 60 min after eating 20 foods they selected. Each of 72 specimens was split into two volumes and spiked with SARS-CoV-2-negative or SARS-CoV-2-positive clinical standards before side-by-side testing by reverse-transcription polymerase chain reaction matrix-assisted laser desorption ionization time-of-flight (RT-PCR/MALDI-TOF) assay. Detection of internal extraction control and SARS-CoV-2 nucleic acids was reduced in replicates of saliva collected at 0 min after eating 11 of 20 foods. Interference resolved at 20 and 60 min after eating all foods except hot dogs in one participant. This represented a significant improvement in the detection of nucleic acids compared to saliva collected at 0 min after eating (p = 0.0005). We demonstrate successful detection of viral nucleic acids in saliva self-collected by children before and after eating a variety of foods. Fasting is not required before saliva collection for SARS-CoV-2 testing by RT-PCR/MALDI-TOF, but waiting for 20 min after eating is sufficient for accurate testing. These findings should be considered for SARS-CoV-2 testing and broader viral diagnostics in saliva specimens.

Demystifying the Complexity of Aphasia Treatment: Application of the Rehabilitation Treatment Specification Systemx.

A considerable body of research supports the use of behavioral communication treatment as the standard of care for aphasia. In spite of robust progress in clinical aphasiology, many questions regarding optimal care remain unanswered. One of the major challenges to progress in the field is the lack of a common framework to adequately describe individual treatments, which, if available, would allow comparisons across studies as well as improved communication among researchers, clinicians, and other stakeholders. Here, we describe how aphasia treatment approaches can be systematically characterized using the Rehabilitation Treatment Specification System (RTSS). At the core of the RTSS is a tripartite structure that focuses on targets (the behavior that is expected to change as a result of treatment), ingredients (what a clinician does to affect change in the target), and mechanism(s) of action (why a given treatment works by linking the ingredients to the target). Three separate articles in the current issue specifically describe how the RTSS can be used to describe different kinds of aphasia treatment approaches: functional approaches, cognitive-linguistic approaches, and biological approaches. It is our hope that the application of the RTSS in clinical aphasiology will improve communication in published studies, grant proposals, and in the clinical care of persons with aphasia.

Evaluating Cognitive-Linguistic Approaches to Interventions for Aphasia Within the Rehabilitation Treatment Specification System.

The Rehabilitation Treatment Specification System (RTSS) provides a framework to identify specific components of treatments developed within various rehabilitation disciplines (eg, physical, occupational, or speech-language therapy). Furthermore, this framework offers the opportunity to identify the target and active ingredients of a therapy approach as well as the mechanism of action by which it is hypothesized to effect change in abilities or functions. In this article, we apply the RTSS framework to the characterization of a sample of treatments for aphasia that are based on cognitive-linguistic models of language processing. Our discussion of these applications centers on the benefits of this classification system and additional criteria to consider when evaluating cognitive-linguistic treatments for aphasia.

Factors associated with progression to infection in methicillin-resistant Staphylococcus aureus-colonized, critically ill neonates.

OBJECTIVE: To identify factors associated with development of symptomatic infection in infants colonized with methicillin-resistant Staphylococcus aureus (MRSA) in the Neonatal Intensive Care Unit (NICU). STUDY DESIGN: This case-control study was performed at St. Louis Children's Hospital NICU from 2009 to 2019. The MRSA-colonized infants who developed symptomatic MRSA infection (cases) were matched 1:3 with MRSA-colonized infants who did not develop infection (controls). Demographics and characteristics of NICU course were compared between groups. Longitudinal information from subsequent hospitalizations was also obtained. RESULTS: Forty-two infected cases were compared with 126 colonized-only controls. Cases became colonized earlier in their NICU stay, were less likely to have received mupirocin for decolonization, and had a longer course of mechanical ventilation than controls. Longitudinally, cases had a more protracted NICU course and were more likely to require hospital readmission. CONCLUSION: Progression from MRSA colonization to symptomatic infection is associated with increased morbidity and may be mitigated through decolonization.

Creating a Theoretical Framework to Underpin Discourse Assessment and Intervention in Aphasia.

Discourse (a unit of language longer than a single sentence) is fundamental to everyday communication. People with aphasia (a language impairment occurring most frequently after stroke, or other brain damage) have communication difficulties which lead to less complete, less coherent, and less complex discourse. Although there are multiple reviews of discourse assessment and an emerging evidence base for discourse intervention, there is no unified theoretical framework to underpin this research. Instead, disparate theories are recruited to explain different aspects of discourse impairment, or symptoms are reported without a hypothesis about the cause. What is needed is a theoretical framework that would clarify the specific linguistic skills that create completeness, coherence, and complexity (i.e., richness) in discourse, and illuminate both the processes involved in discourse production and the reasons for breakdown. This paper reports a review and synthesis of the theoretical literature relevant to spoken discourse in aphasia discourse, and we propose a novel theoretical framework which unites these disparate sources. This framework is currently being tested as the foundation for Linguistic Underpinnings of Narrative in Aphasia (LUNA) treatment research. In this paper, we outline the novel framework and exemplify how it might be used to guide clinical practice and research. Future collaborative research is needed to develop this framework into a processing model for spoken discourse.

Patterns of Sharps Handling and Disposal Among Insulin-Using Patients With Diabetes Mellitus.

BACKGROUND: The objective of this study was to assess disposal patterns for "sharps" among a cohort of patients with diabetes mellitus (DM) receiving insulin therapy. METHOD: A convenience sample of inpatients and outpatients was surveyed about how they disposed of sharps, how often they reused lancets and needles, and what education they had received about proper disposal. Safe disposal was defined as discarding sharps into a formal sharps or sealable container; otherwise, disposal was categorized as unsafe. RESULTS: Of 150 respondents, 56% were men and 75% were white. The mean (SD) age was 56 (15) years; duration of DM, 20 (13) years; and hemoglobin A1c, 8.1% (2.0%). Half the respondents reused a lancet two or more times, and 21% reused an insulin needle two or more times. Thirty-eight percent of respondents discarded lancets unsafely, and 33% discarded insulin needles unsafely, typically by throwing these items into household trash. Most respondents (75%) discarded insulin pens, vials, cartridges, insulin pump supplies, and continuous glucose monitor sensors into household trash. Most (64%) indicated that they had not received education on safe sharps-disposal practices, and 84% had never visited their municipal website for information on medical waste disposal. CONCLUSION: Approximately one-third of patients unsafely disposed of sharps. Unsafe disposal could cause millions of sharps to appear in the municipal solid waste stream, thereby posing a substantial public health hazard. Point-of-care patient education is important, but a broader public health campaign may be required.

HOME2 Study: Household Versus Personalized Decolonization in Households of Children With Methicillin-Resistant Staphylococcus aureus Skin and Soft Tissue Infection-A Randomized Clinical Trial.

BACKGROUND: A household approach to decolonization decreases skin and soft tissue infection (SSTI) incidence, though this is burdensome and costly. As prior SSTI increases risk for SSTI, we hypothesized that the effectiveness of decolonization measures to prevent SSTI when targeted to household members with prior year SSTI would be noninferior to decolonizing all household members. METHODS: Upon completion of our 12-month observational Household Observation of Methicillin-resistant Staphylococcus aureus in the Environment (HOME) study, 102 households were enrolled in HOME2, a 12-month, randomized noninferiority trial. Pediatric index patients with community-associated methicillin-resistant Staphylococcus aureus (MRSA) SSTI, their household contacts, and pets were enrolled. Households were randomized 1:1 to the personalized (decolonization performed only by household members who experienced SSTI during the HOME study) or household (decolonization performed by all household members) approaches. The 5-day regimen included hygiene education, twice-daily intranasal mupirocin, and daily bleach-water baths. At 5 follow-up visits in participants' homes, swabs to detect S. aureus were collected from participants, environmental surfaces, and pets; incident SSTIs were ascertained. RESULTS: Noninferiority of the personalized approach was established for the primary outcome 3-month cumulative SSTI: 23 of 212 (10.8%) participants reported SSTI in household approach households, while 23 of 236 (9.7%) participants reported SSTI in personalized approach households (difference in proportions, -1.1% [95% confidence interval, -6.7% to 4.5%]). In multivariable analyses, prior year SSTI and baseline MRSA colonization were associated with cumulative SSTI. CONCLUSIONS: The personalized approach was noninferior to the household approach in preventing SSTI. Future studies should interrogate longer durations of decolonization and/or decontamination of the household environment to reduce household MRSA burden. CLINICAL TRIALS REGISTRATION: NCT01814371.

Cefazolin Inoculum Effect and Methicillin-Susceptible Staphylococcus aureus Osteoarticular Infections in Children.

Select methicillin-susceptible Staphylococcus aureus (MSSA) strains may produce ß-lactamases with affinity for first-generation cephalosporins (1GCs). In the setting of a high inoculum, these ß-lactamases may promote the cleavage of 1GCs, a phenomenon known as the cefazolin inoculum effect (CzIE). We evaluated the prevalence and impact of CzIE on clinical outcomes among MSSA acute hematogenous osteomyelitis (AHO) cases. MSSA AHO isolates obtained from two children's hospitals between January 2011 and December 2018 were procured through ongoing surveillance studies. Isolates were tested for CzIE via a broth macrodilution assay using an inoculum of 107 CFU/ml; CzIE was defined as a cefazolin MIC of ≥16 µg/ml. Isolates were characterized by accessory gene regulator group (agr). The progression from acute to chronic osteomyelitis was considered an important outcome. A total of 250 cases with viable isolates were included. Notably, 14.4% of isolates exhibited CzIE with no observed temporal trend; and 4% and 76% of patients received a 1GC as an empirical and definitive therapy, respectively. CzIE isolates were more often resistant to clindamycin, belonged to agrIII, and associated with the development of chronic osteomyelitis. In multivariable analyses, agrIII, multiple surgical debridements, delayed source control, and CzIE were independently associated with progression to chronic osteomyelitis. A higher rate of chronic osteomyelitis was observed with CzIE isolates regardless of definitive antibiotic choice. CzIE is exhibited by 14.4% of MSSA AHO isolates in children. CzIE is independently associated with progression to chronic osteomyelitis in cases of AHO irrespective of final antibiotic choice. These data suggest that negative outcomes reported with CzIE may more accurately reflect strain-dependent virulence factors rather than true antibiotic failure.

Environmental Methicillin-resistant Staphylococcus aureus Contamination, Persistent Colonization, and Subsequent Skin and Soft Tissue Infection.

Importance: The longitudinal association among persistent Staphylococcus aureus colonization, household environmental contamination, and recurrent skin and soft tissue infection (SSTI) is largely unexplored to date. Objectives: To identify factors associated with persistent S aureus colonization and recurrent SSTI in households with children with community-associated methicillin-resistant S aureus (MRSA) SSTI. Design, Setting, and Participants: This 12-month prospective cohort study included 150 children with community-associated MRSA SSTI, 542 household contacts, and 154 pets enrolled from January 3, 2012, through October 20, 2015. A total of 5 quarterly home visits were made to 150 households in the St Louis, Missouri, region. Statistical analysis was performed from September 18, 2018, to January 7, 2020. Exposures: Covariates used in S aureus strain persistence and interval SSTI models included S aureus colonization and contamination measures, personal hygiene and sharing habits, health history, activities external to the home, and household characteristics (eg, cleanliness, crowding, home ownership, and pets). Serial samples to detect S aureus were collected from household members at 3 anatomic sites, from pets at 2 anatomic sites, and from environmental surfaces at 21 sites. Main Outcomes and Measures: Molecular epidemiologic findings of S aureus isolates were assessed via repetitive-sequence polymerase chain reaction. Individual persistent colonization was defined as colonization by an identical strain for 2 consecutive samplings. Longitudinal, multivariable generalized mixed-effects logistic regression models were used to assess factors associated with persistent S aureus personal colonization, environmental contamination, and interval SSTI. Results: Among 692 household members in 150 households, 326 (47%) were male and 366 (53%) were female, with a median age of 14.82 years (range, 0.05-82.25 years). Of 540 participants completing all 5 samplings, 213 (39%) were persistently colonized with S aureus, most often in the nares and with the strain infecting the index patient at enrollment. Nine pets (8%) were persistently colonized with S aureus. Participants reporting interval intranasal mupirocin application were less likely to experience persistent colonization (odds ratio [OR], 0.44; 95% credible interval [CrI], 0.30-0.66), whereas increasing strain-specific environmental contamination pressure was associated with increased individual persistent colonization (OR, 1.17; 95% CrI, 1.06-1.30). Strains with higher colonization pressure (OR, 1.47; 95% CrI, 1.25-1.71) and MRSA strains (OR, 1.57; 95% CrI, 1.16-2.19) were more likely to persist. Seventy-six index patients (53%) and 101 household contacts (19%) reported interval SSTIs. Individuals persistently colonized with MRSA (OR, 1.56; 95% CrI, 1.17-2.11), those with a history of SSTI (OR, 2.55; 95% CrI, 1.88-3.47), and index patients (OR, 1.54; 95% CrI, 1.07-2.23) were more likely to report an interval SSTI. Conclusions and Relevance: The study findings suggest that recurrent SSTI is associated with persistent MRSA colonization of household members and contamination of environmental surfaces. Future studies may elucidate the effectiveness of specific combinations of personal decolonization and environmental decontamination efforts in eradicating persistent strains and mitigating recurrent SSTIs.