Infection prevention-how can we prevent transmission of community-onset methicillin-resistant Staphylococcus aureus?

BACKGROUND: Staphylococcus aureus is a versatile organism, capable of existing as a commensal organism while also possessing pathogenic potential. The emergence of clinically and genetically distinct strains of methicillin-resistant S. aureus (MRSA), termed community-onset MRSA (CO-MRSA), resulted in an epidemic of invasive and skin and soft tissue infections (SSTI) in otherwise healthy individuals without traditional risk factors. Colonization with S. aureus is a risk factor for developing infection and also a source of transmission to close contacts. Outbreaks of S. aureus SSTI have been described in crowded settings and within households. Thus, preventive strategies are essential to interrupt recurrent infections. OBJECTIVES: The objective of this narrative review is to provide a comprehensive, evidence-based approach to prevent transmission of CO-MRSA. We highlight key clinical trials that emphasize the importance of household and environmental S. aureus colonization in propagating household transmission. Finally, we highlight research priorities to prevent S. aureus infection. SOURCES: We cite primary literature from peer-reviewed publications as sources for this review. CONTENT: Our recommended approach to the management of individuals presenting with skin abscesses includes optimal treatment of the initial infection and hygiene education. Decolonization measures should be recommended for individuals with recurrent SSTIs or whose household members have SSTIs. Targeted decolonization with topical antimicrobials should be prescribed to all affected individuals within the household. IMPLICATIONS: S. aureus infections result in substantial mortality and morbidity because of the high incidence of recurrent skin infections. Although current decolonization strategies are beneficial, interventions are often costly to families and effectiveness wanes over time. Results from a recently completed trial evaluating integrated periodic decolonization and household environmental hygiene will further add to our understanding of what constitutes a sustainable decolonization approach. In addition, novel preventive strategies are being developed such as S. aureus vaccines, lytic agents, probiotics, microbiota transplants, and phage therapy.

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.

Diagnostic and commensal Staphylococcus pseudintermedius genomes reveal niche adaptation through parallel selection of defense mechanisms.

Staphylococcus pseudintermedius is historically understood as a prevalent commensal and pathogen of dogs, though modern clinical diagnostics reveal an expanded host-range that includes humans. It remains unclear whether differentiation across S. pseudintermedius populations is driven primarily by niche-type or host-species. We sequenced 501 diagnostic and commensal isolates from a hospital, veterinary diagnostic laboratory, and within households in the American Midwest, and performed a comparative genomics investigation contrasting human diagnostic, animal diagnostic, human colonizing, pet colonizing, and household-surface S. pseudintermedius isolates. Though indistinguishable by core and accessory gene architecture, diagnostic isolates harbor more encoded and phenotypic resistance, whereas colonizing and surface isolates harbor similar CRISPR defense systems likely reflective of common household phage exposures. Furthermore, household isolates that persist through anti-staphylococcal decolonization report elevated rates of base-changing mutations in - and parallel evolution of - defense genes, as well as reductions in oxacillin and trimethoprim-sulfamethoxazole susceptibility. Together we report parallel niche-specific bolstering of S. pseudintermedius defense mechanisms through gene acquisition or mutation.

Priorities and Progress in Gram-positive Bacterial Infection Research by the Antibacterial Resistance Leadership Group: A Narrative Review.

The Antibacterial Resistance Leadership Group (ARLG) has prioritized infections caused by gram-positive bacteria as one of its core areas of emphasis. The ARLG Gram-positive Committee has focused on studies responding to 3 main identified research priorities: (1) investigation of strategies or therapies for infections predominantly caused by gram-positive bacteria, (2) evaluation of the efficacy of novel agents for infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci, and (3) optimization of dosing and duration of antimicrobial agents for gram-positive infections. Herein, we summarize ARLG accomplishments in gram-positive bacterial infection research, including studies aiming to (1) inform optimal vancomycin dosing, (2) determine the role of dalbavancin in MRSA bloodstream infection, (3) characterize enterococcal bloodstream infections, (4) demonstrate the benefits of short-course therapy for pediatric community-acquired pneumonia, (5) develop quality of life measures for use in clinical trials, and (6) advance understanding of the microbiome. Future studies will incorporate innovative methodologies with a focus on interventional clinical trials that have the potential to change clinical practice for difficult-to-treat infections, such as MRSA bloodstream infections.

Staphylococcus aureus Bacteremia in Pediatric Patients: Uncovering a Rural Health Challenge.

Background: Staphylococcus aureus bacteremia poses significant risk for morbidity and mortality. This may be exacerbated in rural populations facing unique health challenges. Methods: To investigate factors influencing S. aureus bacteremia outcomes, we conducted a retrospective cohort study of children admitted to St. Louis Children's Hospital (SLCH) from 2011 to 2019. Exposures included rurality (defined by the Rural-Urban Continuum Code), Area Deprivation Index, and outside hospital (OSH) admission before SLCH admission. The primary outcome was treatment failure, a composite of 90-day all-cause mortality and hospital readmission. Results: Of 251 patients, 69 (27%) were from rural areas; 28 (11%) were initially admitted to an OSH. Treatment failure occurred in 39 (16%) patients. Patients from rural areas were more likely to be infected with methicillin-resistant S. aureus (45%) vs urban children (29%; P = .02). Children initially admitted to an OSH, vs those presenting directly to SLCH, were more likely to require intensive care unit-level (ICU) care (57% vs 29%; P = .002), have an endovascular source of infection (32% vs 12%; P = .004), have a longer duration of illness before hospital presentation (4.1 vs 3.0 days; P = .04), and have delayed initiation of targeted antibiotic therapy (3.9 vs 2.6 days; P = .01). Multivariable analysis revealed rural residence (adjusted odds ratio [aOR], 2.3; 95% CI, 1.1-5.0), comorbidities (aOR, 2.9; 95% CI, 1.3-6.2), and ICU admission (aOR, 3.9; 95% CI, 1.9-8.3) as predictors of treatment failure. Conclusions: Children from rural areas face barriers to specialized health care. These challenges may contribute to severe illness and worse outcomes among children with S. aureus bacteremia.

Healthcare worker perceptions surrounding Staphylococcus aureus transmission and prevention practices in the neonatal intensive care unit.

OBJECTIVE: To understand healthcare worker (HCW) perceptions surrounding Staphylococcus aureus transmission and prevention in the neonatal intensive care unit (NICU). DESIGN: Qualitative case study with focus groups. SETTING: A level IV, 150-bed NICU at a Midwestern academic medical center that conducts active surveillance and decolonization of S. aureus-positive patients. PARTICIPANTS: NICU HCWs, including bedside nurses, nurse managers, therapy services personnel, pediatric nurse practitioners, clinical fellows, and attending neonatologists. METHODS: Semistructured focus group interviews, assembled by occupation, were conducted by 2 study team members. Interviews were video recorded and transcribed. Deductive coding and thematic analyses were performed using NVivo software. RESULTS: In total, 38 HCWs participated in 10 focus groups (1-12 participants each), lasting 40-90 minutes. Four main themes emerged: (1) Methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) are inconsistently described as high risk. (2) Infection prevention interventions are burdensome. (3) Multiple sources of transmission are recognized. (4) opportunities exist to advance infection prevention. HCWs perceived MSSA to be less clinically relevant than MRSA. Participants expressed a desire to see published data supporting infection prevention interventions, including contact precautions, environmental cleaning, and patient decolonization. These practices were identified to be considerable burdens. HCWs perceived families to be the main source of S. aureus in the NICU, and they suggested opportunities for families to play a larger role in infection prevention. CONCLUSIONS: These data highlight opportunities for HCW and parental education, research, and reevaluating interventions aimed at improving infection prevention efforts to reduce the burden of S. aureus in NICU settings.

Adherence to and experiences of K-12 students in modified and standard home quarantine during the SARS-CoV-2 pandemic in Missouri.

BACKGROUND: In November 2020, during the SARS-CoV-2 pandemic, Missouri allowed local public health jurisdictions the option to implement a modified quarantine policy allowing kindergarten through 12 (K-12) students with low-risk exposures to continue in-person learning. We assessed adherence to quarantine among participants in modified quarantine and standard home quarantine and the psychosocial impacts of quarantine on students and families. METHODS: In January-March 2021, as part of an investigation of in-school transmission of SARS-CoV-2, parents of 586 participating K-12 students identified as a close contact with a person with SARS-CoV-2 were sent a survey to assess their activities and psychosocial impacts to the child and family. RESULTS: Among the 227 (39%) survey respondents, 26 (11%) participated in modified quarantine and 201 (89%) participated in standard home quarantine. Forty-six percent of students in modified quarantine and 72% of students in standard home quarantine reported abstaining from non-school activities during quarantine. Parents of 17 (65%) students in modified quarantine and 80 (40%) in standard home quarantine reported low or neutral levels of stress in their children. Parents of students in standard home quarantine described greater stress, negative impacts to family functioning, and interruptions to educational opportunities for students. CONCLUSIONS: Students in modified quarantine reported lower adherence to quarantine recommendations but lower daily impact and stressors than those in standard home quarantine. Because in-school transmission of SARS-CoV-2 has been shown to be low when layered prevention strategies are in place regardless of the use of modified or standard home quarantine, this modified quarantine approach provides a reasonable option for balancing the needs of students and families with SARS-CoV-2 prevention measures.

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.

Perceived barriers and facilitators to the adoption of telemedicine infectious diseases consultations in southeastern Missouri hospitals.

INTRODUCTION: Telemedicine infectious diseases consultations (tele-ID consults) improves access to healthcare for underserved/resource-limited communities. However, factors promoting or hindering implementation of tele-ID consults in low-resource settings are understudied. This study sought to fill this gap by describing perceived barriers and facilitators tele-ID consults at three rural hospitals in southeastern Missouri. METHODS: Twelve in-depth, semi-structured interviews were conducted with a purposively sampled group of information-rich hospital stakeholders from three rural, southeastern Missouri hospitals with partial or no on-site availability of ID physicians. Our literature-informed interview guide elicited participants' knowledge and experience with tele-ID consults, perceptions on ID consultation needs, and perceived barriers to and facilitators of tele-ID consults. Interview transcripts were coded using an iterative process of inductive analysis to identify core themes related to barriers and facilitators. RESULTS: Perceived barriers to adopting and implementing tele-ID consults included logistical challenges, technology and devices, negative emotional responses, patient-related factors, concerns about reduced quality of care when using telemedicine, lack of acceptance or buy-in from physicians or staff, and legal concerns. Key facilitators included perceived need, perceived benefits to patients and physicians, flexibility and openness to change among staff members and patients, telemedicine champions, prior experiences, and enthusiasm. DISCUSSION: Our findings demonstrate that rural hospitals need tele-ID consults and have the capacity to implement tele-ID consults, but operational and technical feasibility challenges remain. Adoption and implementation of tele-ID consults may reduce ID-physician shortage-related service gaps by permitting ID physician's greater geographic reach.

Implementation of Telemedicine Infectious Diseases Consultation in a Rural Hospital Using the Active Implementation Framework.

In this pilot study, guided by the Active Implementation Framework, telemedicine infectious diseases consultation was provided to hospitalized inpatients at a rural Missouri hospital. Measured outcomes included the implementation outcomes of feasibility, acceptability, appropriateness, and fidelity, as well as clinical outcomes of readmissions and death.

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.

The impact of infectious diseases consultation for children with Staphylococcus aureus bacteremia.

BACKGROUND: Despite clear benefit of improved outcomes in adults, the impact of infectious diseases (ID) consultation for Staphylococcus aureus bacteremia in children remains understudied. METHODS: To assess the impact of pediatric ID consultation on management and outcomes, we conducted a cohort study of children with S. aureus bacteremia at St. Louis Children's Hospital from 2011 to 2018. We assessed adherence to six established quality-of-care indicators (QCIs). We applied propensity score methodology to examine the impact of ID consultation on risk of treatment failure, a composite of all-cause mortality or hospital readmission within 90 days. RESULTS: Of 306 patients with S. aureus bacteremia, 193 (63%) received ID consultation. ID consultation was associated with increased adherence to all QCIs, including proof-of-cure blood cultures, indicated laboratory studies, echocardiography, source control, targeted antibiotic therapy, and antibiotic duration. Obtaining proof-of-cure blood cultures and all indicated laboratory studies were associated with improved outcomes. In propensity score-weighted analyses, risk of treatment failure was similar among patients who did and did not receive ID consultation. However, the number of events was small and risk estimates were imprecise. CONCLUSIONS: For children with S. aureus bacteremia, ID consultation improved adherence to QCIs, some of which were associated with improved clinical outcomes. IMPACT: In children with Staphylococcus aureus bacteremia, consultation by an infectious diseases (ID) physician improved adherence to established quality-of-care indicators (QCIs). The current literature regarding ID consultation in pediatric S. aureus bacteremia is sparse. Three prior international studies demonstrated improved quality of care with ID consultation, though results were disparate regarding clinical outcomes. This article impacts the current literature by strengthening the evidence that ID consultation in children improves adherence to QCIs, and demonstrates that adherence to QCIs improves clinical outcomes.

Skin and Soft Tissue Infection Treatment and Prevention Practices by Pediatric Emergency Medicine Providers.

OBJECTIVE: The aim of the study was to evaluate skin and soft tissue infection (SSTI) treatment and prevention practices among pediatric emergency medicine (PEM) clinicians in the context of current clinical practice guidelines and contemporary evidence. METHODS: This was a cross-sectional survey of PEM clinicians belonging to the American Academy of Pediatrics Section on Emergency Medicine Survey listserv. Four varying hypothetical clinical scenarios of children with SSTI were posed to respondents; subsequent items assessed SSTI treatment and prevention practices. Provider demographics were collected. RESULTS: Of 160 survey respondents, more than half stated that they would prescribe oral antibiotics for each clinical scenario, particularly for more complex presentations (small uncomplicated abscess, 51.8%; large uncomplicated abscess, 71.5%; recurrent abscess, 83.5%; febrile abscess, 90.3%; P < 0.001). Most commonly selected antibiotics were clindamycin and trimethoprim-sulfamethoxazole. Across scenarios, more than 80% selected a duration of treatment 7 days or more. Of the 121 respondents who prescribe preventive measures, 85.1% recommend hygiene measures; 52.5% would prescribe decolonization with topical antibiotic ointment and 77.5% would recommend antiseptic body washes. Half of the respondents reported that their institution has standard guidance for SSTI management. CONCLUSIONS: Although current evidence supports adjuvant antibiotics for all drained SSTI and decolonization for the index patient and household contacts, PEM clinicians do not consistently adhere to these recommendations. In light of these findings, development and implementation of institutional guidelines are necessary to aid PEM clinicians' point-of-care decision making and improving evidence-based practice.

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.

Perceptions of Telemedicine and Costs Incurred by a Visit to a General Infectious Diseases Clinic: A Survey.

BACKGROUND: The costs of attending in-person general infectious diseases clinics and preferences for visit type (telemedicine vs in-person) are not well known. We aimed to measure the time-related, monetary, social, and societal costs associated with travel to an in-person clinic visit and to assess patients' preferences, questions, and concerns regarding telemedicine. METHODS: Patients (≥18 years, living ≥25 miles from clinic at time of clinic visit) were recruited for this survey study from the general infectious diseases (ID) clinic at Washington University from June 2019 to February 2020. We calculated time and money potentially saved by telemedicine, as well as carbon dioxide emissions, with the assistance of Google Maps (low/high estimates). We also determined patient preferences regarding telemedicine for ID care. RESULTS: Seventy-five patients completed the study. The round-trip mean travel distance was 227.2 ±â€…142.6 miles, mean travel time was 3.6 ±â€…2.0 hours to 4.5 ±â€…2.3 hours (low and high estimates from Google Maps), travel costs were $131.34 ±â€…$82.27, and mean carbon dioxide emissions were 91.79 ±â€…57.60 kg. Fifty-eight patients (77.3%) said they would be willing to have a telemedicine visit in the future, and 30 (40.5%) said they would rather have had their visit the day the survey was completed as a telemedicine visit. CONCLUSIONS: Telemedicine has the potential to significantly reduce patient costs, both monetary and time-related, and offers substantial environmental benefits, while being an acceptable method of care delivery to most patients at a general ID clinic.

Acceptance of Saliva-Based Specimen Collection for SARS-CoV-2 Testing Among K-12 Students, Teachers, and Staff.

OBJECTIVE: Saliva specimens collected in school populations may offer a more feasible, noninvasive alternative to nasal swabs for large-scale COVID-19 testing efforts in kindergarten through 12th grade (K-12) schools. We investigated acceptance of saliva-based COVID-19 testing among quarantined K-12 students and their parents, teachers, and staff members who recently experienced a SARS-CoV-2 exposure in school. METHODS: We surveyed 719 participants, in person or by telephone, who agreed to or declined a free saliva-based COVID-19 reverse-transcription polymerase chain reaction test as part of a surveillance investigation about whether they would have consented to testing if offered a nasal swab instead. We conducted this investigation in 6 school districts in Greene County (n = 3) and St. Louis County (n = 3), Missouri, from January 25 through March 23, 2021. RESULTS: More than one-third (160 of 446) of K-12 students (or their parents or guardians), teachers, and staff members who agreed to a saliva-based COVID-19 test indicated they would have declined testing if specimen collection were by nasal swab. When stratified by school level, 51% (67 of 132) of elementary school students or their parents or guardians would not have agreed to testing if a nasal swab was offered. CONCLUSIONS: Some students, especially those in elementary school, preferred saliva-based COVID-19 testing to nasal swab testing. Use of saliva-based testing might increase voluntary participation in screening efforts in K-12 schools to help prevent the spread of SARS-CoV-2.

Management and Prevention of Staphylococcus aureus Infections in Children.

Staphylococcus aureus is a common skin commensal with the potential to cause severe infections resulting in significant morbidity and mortality. Up to 30% of individuals are colonized with S aureus, though infection typically does not occur without skin barrier disruption. Infection management includes promptly addressing the source of infection, including sites of metastatic infection, and initiation of effective antibiotics, which should be selected based on local antibiotic susceptibility patterns. Given that S aureus colonization is a risk factor for infection, preventive strategies are aimed at optimizing hygiene measures and decolonization regimens for outpatients and critically ill children with prolonged hospitalizations.

Contemporary Clinical Isolates of Staphylococcus aureus from Pediatric Osteomyelitis Patients Display Unique Characteristics in a Mouse Model of Hematogenous Osteomyelitis.

Osteomyelitis can result from the direct inoculation of pathogens into bone during injury or surgery or from spread via the bloodstream, a condition called hematogenous osteomyelitis (HOM). HOM disproportionally affects children, and more than half of cases are caused by Staphylococcus aureus. Laboratory models of osteomyelitis mostly utilize direct injection of bacteria into the bone or implantation of foreign material and therefore do not directly interrogate the pathogenesis of pediatric hematogenous osteomyelitis. In this study, we inoculated mice intravenously and characterized the resultant musculoskeletal infections using two strains isolated from adults (USA300-LAC and NRS384) and five new methicillin-resistant S. aureus isolates from pediatric osteomyelitis patients. All strains were capable of creating stable infections over 5 weeks, although the incidence varied. Micro-computed tomography (microCT) analysis demonstrated decreases in the trabecular bone volume fraction but little effect on bone cortices. Histological assessment revealed differences in the precise focus of musculoskeletal infection, with various mixtures of bone-centered osteomyelitis and joint-centered septic arthritis. Whole-genome sequencing of three new isolates demonstrated distinct strains, two within the USA300 lineage and one USA100 isolate. Interestingly, this USA100 isolate showed a distinct predilection for septic arthritis compared to the other isolates tested, including NRS384 and LAC, which more frequently led to osteomyelitis or mixed bone and joint infections. Collectively, these data outline the feasibility of using pediatric osteomyelitis clinical isolates to study the pathogenesis of HOM in murine models and lay the groundwork for future studies investigating strain-dependent differences in musculoskeletal infection.