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.

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.

Potent, specific MEPicides for treatment of zoonotic staphylococci.

Coagulase-positive staphylococci, which frequently colonize the mucosal surfaces of animals, also cause a spectrum of opportunistic infections including skin and soft tissue infections, urinary tract infections, pneumonia, and bacteremia. However, recent advances in bacterial identification have revealed that these common veterinary pathogens are in fact zoonoses that cause serious infections in human patients. The global spread of multidrug-resistant zoonotic staphylococci, in particular the emergence of methicillin-resistant organisms, is now a serious threat to both animal and human welfare. Accordingly, new therapeutic targets that can be exploited to combat staphylococcal infections are urgently needed. Enzymes of the methylerythritol phosphate pathway (MEP) of isoprenoid biosynthesis represent potential targets for treating zoonotic staphylococci. Here we demonstrate that fosmidomycin (FSM) inhibits the first step of the isoprenoid biosynthetic pathway catalyzed by deoxyxylulose phosphate reductoisomerase (DXR) in staphylococci. In addition, we have both enzymatically and structurally determined the mechanism by which FSM elicits its effect. Using a forward genetic screen, the glycerol-3-phosphate transporter GlpT that facilitates FSM uptake was identified in two zoonotic staphylococci, Staphylococcus schleiferi and Staphylococcus pseudintermedius. A series of lipophilic ester prodrugs (termed MEPicides) structurally related to FSM were synthesized, and data indicate that the presence of the prodrug moiety not only substantially increased potency of the inhibitors against staphylococci but also bypassed the need for GlpT-mediated cellular transport. Collectively, our data indicate that the prodrug MEPicides selectively and robustly inhibit DXR in zoonotic staphylococci, and further, that DXR represents a promising, druggable target for future development.

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.

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.

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.

National Trends in Incidence of Purulent Skin and Soft Tissue Infections in Patients Presenting to Ambulatory and Emergency Department Settings, 2000-2015.

Nationally representative data from 2000-2015 demonstrated a rise in the incidence of outpatient visits for skin infections, peaking in 2010-2013, followed by a plateau. While cephalexin was the most frequently prescribed antibiotic at the beginning, trimethoprim-sulfamethoxazole was most frequently prescribed by the end of the study period.

Antibiotic Duration, but Not Abscess Size, Impacts Clinical Cure of Limited Skin and Soft Tissue Infection After Incision and Drainage.

Antibiotics are frequently prescribed following incision and drainage of cutaneous abscesses. In subgroup analyses from a recent clinical trial, we observed higher likelihood of cure with antibiotic courses beyond 5 or 7 days (up to 10). Among this cohort, for abscesses ≤5 cm, size did not modify the antibiotic effect.

Incidence and treatment of hemophagocytic lymphohistiocytosis in hospitalized children with Ehrlichia infection.

We report a large cohort of pediatric patients with human monocytic ehrlichiosis (HME), enabling an estimated incidence of secondary hemophagocytic lymphohistiocytosis (HLH) in hospitalized children with HME. Among 49 children with PCR-confirmed Ehrlichia infection, 8 (16%) met current criteria for HLH. Those with HLH had more significant hematologic abnormalities and longer durations from symptom onset to admission and definitive anti-infective therapy. Among these eight, three received chemotherapy plus doxycycline, one of whom died; the other five were treated with doxycycline without chemotherapy, and all survived without HLH recurrence. Our findings demonstrate that antimicrobial therapy alone can successfully resolve Ehrlichia-associated HLH.

Emergency Department Environmental Contamination With Methicillin-Resistant Staphylococcus aureus After Care of Colonized Patients.

STUDY OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) transmission dynamics in the emergency department (ED) are not well defined; environmental surfaces may serve as reservoirs for transmission. This study investigates the effect of patients with a history of MRSA colonization or infection on subsequent MRSA contamination of the ED environment. METHODS: Adult ED patients with evidence of an MRSA-positive surveillance result or clinical microbiologic culture in the year preceding their current ED visit were enrolled. Cultures from 5 anatomic sites were obtained to detect active MRSA colonization. After patients' discharge and before environmental disinfection, up to 16 prespecified surfaces in their ED rooms were cultured. Strain typing was performed by repetitive-sequence polymerase chain reaction on all recovered MRSA isolates to determine concordance with the corresponding patient strain. RESULTS: Of 42 patients enrolled, 25 (60%) remained colonized with MRSA. Nineteen of the 25 ED rooms (76%) occupied by MRSA-colonized patients contained greater than or equal to 1 MRSA-contaminated environmental surface on patient discharge. Surfaces were more likely to be contaminated when rooms were occupied by patients colonized with MRSA at 1 body site (odds ratio 11.7; 95% confidence interval 1.5 to 91.5) and greater than or equal to 2 body sites (odds ratio 16.3; 95% confidence interval 3.1 to 86.8) compared with noncolonized patients. In 16 of the 19 ED rooms (84%) where MRSA was recovered, all environmental strains were concordant with the corresponding patient strain. CONCLUSION: Contamination of the ED environment with MRSA from actively colonized patients is common. Improved environmental surface disinfection may help reduce transmission of MRSA to ED health care professionals and patients during emergency care.

Impact of Systemic Antibiotics on Staphylococcus aureus Colonization and Recurrent Skin Infection.

Background: Staphylococcus aureus colonization poses risk for subsequent skin and soft tissue infection (SSTI). We hypothesized that including systemic antibiotics in the management of S. aureus SSTI, in conjunction with incision and drainage, would reduce S. aureus colonization and incidence of recurrent infection. Methods: We prospectively evaluated 383 children with S. aureus SSTI requiring incision and drainage and S. aureus colonization in the anterior nares, axillae, or inguinal folds at baseline screening. Systemic antibiotic prescribing at the point of care was recorded. Repeat colonization sampling was performed within 3 months (median, 38 days; interquartile range, 22-50 days) in 357 participants. Incidence of recurrent infection was ascertained for up to 1 year. Results: Participants prescribed guideline-recommended empiric antibiotics for purulent SSTI were less likely to remain colonized at follow-up sampling (adjusted hazard ratio [aHR], 0.49; 95% confidence interval [CI], .30-.79) and less likely to have recurrent SSTI (aHR, 0.57; 95% CI, .34-.94) than those not receiving guideline-recommended empiric antibiotics for their SSTI. Additionally, participants remaining colonized at repeat sampling were more likely to report a recurrent infection over 12 months (aHR, 2.37; 95% CI, 1.69-3.31). Clindamycin was more effective than trimethoprim-sulfamethoxazole (TMP-SMX) in eradicating S. aureus colonization (44% vs 57% remained colonized, P = .03) and preventing recurrent SSTI (31% vs 47% experienced recurrence, P = .008). Conclusions: Systemic antibiotics, as part of acute SSTI management, impact S. aureus colonization, contributing to a decreased incidence of recurrent SSTI. The mechanism by which clindamycin differentially affects colonization and recurrent SSTI compared to TMP-SMX warrants further study.

Methicillin-Resistant Staphylococcus aureus: The Effects Are More Than Skin Deep.

OBJECTIVES: To assess the psychosocial effects of a methicillin-resistant Staphylococcus aureus (MRSA) diagnosis on the households of children with MRSA skin and soft tissue infection (SSTI). STUDY DESIGN: We constructed and administered an interview to the primary caregiver within the home of a child with a history of MRSA SSTI. RESULTS: Seventy-six households were enrolled. Survey responses were analyzed and grouped into 4 themes: health behavior changes, disclosure, social interactions, and knowledge/awareness. The most common theme was disclosure; 91% of participants reported sharing their child's MRSA diagnosis with someone outside of the household. Forty-two percent of respondents reported a change in the manner in which household contacts interacted as a result of the index patient's MRSA diagnosis, including isolating the index patient from other children in the household. Many households reported adopting enhanced personal hygiene behaviors and environmental cleaning routines. Thirty-eight percent of participating households reported altering how they interact with people outside of their home, largely to avoid spreading MRSA to vulnerable individuals. In addition, many participants perceived that others regarded them with caution, especially at daycare, whereas other affected households were excluded from family gatherings. CONCLUSION: Primary caregivers of children with MRSA SSTI reported changing their health behaviors, altering their interactions with people outside of their home, and feeling isolated by others in response to their child's MRSA diagnosis. The findings of our study highlight a need for community interventions and education to prevent the negative psychosocial repercussions associated with MRSA.

Comprehensive modeling reveals proximity, seasonality, and hygiene practices as key determinants of MRSA colonization in exposed households.

BACKGROUND: Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTIs). To develop interventions to prevent recurrent infections, household attributes and individual practices influencing S. aureus colonization must be discerned. METHODS: Households of healthy children with methicillin-resistant S. aureus (MRSA) SSTI (n = 150; 671 participants) were interviewed regarding health history, activities, and hygiene practices. S. aureus colonization was assessed in household members, and recovered isolates were typed by repetitive sequence-based PCR. RESULTS: The number of unique strain types in a household (median 1, range 0-7) correlated with the number of colonized individuals (p < 0.001). The MRSA infecting strain type colonized a household member in 57% of 91 households with an available infecting strain, and was the most common strain type recovered in 45% of these households. In multivariable models, household MRSA colonization burden (p < 0.001), sharing a bedroom with MRSA-colonized individuals (p = 0.03), renting dwelling (p = 0.048), and warmer seasons (p = 0.02) were associated with increased MRSA colonization. Increasing age (p = 0.02), bathing at least daily (p = 0.01), and antibacterial soap use (p = 0.03) correlated with reduced MRSA colonization. CONCLUSIONS: This study identified practices that correlate with MRSA colonization, which will inform physician counseling and multifaceted interventions among MRSA-affected households to mitigate MRSA in the community.

Topical Decolonization Does Not Eradicate the Skin Microbiota of Community-Dwelling or Hospitalized Adults.

Topical antimicrobials are often employed for decolonization and infection prevention and may alter the endogenous microbiota of the skin. The objective of this study was to compare the microbial communities and levels of richness and diversity in community-dwelling subjects and intensive care unit (ICU) patients before and after the use of topical decolonization protocols. We enrolled 15 adults at risk for Staphylococcus aureus infection. Community subjects (n = 8) underwent a 5-day decolonization protocol (twice daily intranasal mupirocin and daily dilute bleach-water baths), and ICU patients (n = 7) received daily chlorhexidine baths. Swab samples were collected from 5 anatomic sites immediately before and again after decolonization. A variety of culture media and incubation environments were used to recover bacteria and fungi; isolates were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Overall, 174 unique organisms were recovered. Unique communities of organisms were recovered from the community-dwelling and hospitalized cohorts. In the community-dwelling cohort, microbial richness and diversity did not differ significantly between collections across time points, although the number of body sites colonized with S. aureus decreased significantly over time (P = 0.004). Within the hospitalized cohort, richness and diversity decreased over time compared to those for the enrollment sampling (from enrollment to final sampling, P = 0.01 for both richness and diversity). Topical antimicrobials reduced the burden of S. aureus while preserving other components of the skin and nasal microbiota.

Antimicrobial Susceptibility Profiles of Staphylococcus aureus Isolates Recovered from Humans, Environmental Surfaces, and Companion Animals in Households of Children with Community-Onset Methicillin-Resistant S. aureus Infections.

Our objective was to determine the antibiotic susceptibility profiles of Staphylococcus aureus isolates recovered from 110 households of children with community-onset methicillin-resistant S. aureus (MRSA) infections. Cultures were obtained from household members, household objects, and dogs and cats, yielding 1,633 S. aureus isolates. The S. aureus isolates were heterogeneous, although more than half were methicillin resistant. The highest proportion of MRSA was found in bathrooms. The majority of isolates were susceptible to antibiotics prescribed in outpatient settings.

Molecular epidemiology of Staphylococcus aureus in households of children with community-associated S aureus skin and soft tissue infections.

OBJECTIVES: Although colonization traditionally is considered a risk factor for Staphylococcus aureus infection, the relationship between contemporary S aureus colonization and infection is not well characterized. We aimed to relate the presence of colonizing and disease-causing strains of S aureus within individuals and households. STUDY DESIGN: In a prospective study of 163 pediatric outpatients (cases) with community-associated S aureus skin and soft tissue infections in St Louis, infection isolates were obtained from cases and colonization cultures were obtained from cases and their household contacts (n = 562). Molecular typing by repetitive sequence-based polymerase chain reaction was used to compare infecting and colonizing isolates within each case. The infecting strain from each case was compared with S aureus strains colonizing household contacts. The colonization status of cases was followed for 12 months. RESULTS: A total of 27 distinct strain types were identified among the 1299 S aureus isolates evaluated. Between 1 and 6 distinct strain types were detected per household. A total of 110 cases (67%) were colonized at 1 or more body sites with the infecting strain. Of the 53 cases with an infecting strain that did not match a colonizing strain, 15 (28%) had 1 or more household contacts with a colonizing strain that matched the infecting strain. Intrafamilial strain-relatedness was observed in 105 families (64%). CONCLUSION: One-third of cases were colonized with a different strain type than the strain causing the skin and soft tissue infection. Fewer than one-third of cases with discordant infecting and colonizing isolates could be linked to the strain from another household contact, suggesting acquisition from sources outside the household.

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.