Michael Z. David

Background: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia has historically been associated with worse outcomes than methicillin-susceptible S. aureus (MSSA), but MRSA epidemiology has evolved and contemporary data are mixed. We evaluated whether methicillin resistance is independently associated with S. aureus bacteremia (SAB) outcomes. Methods: We conducted a retrospective cohort study of adults with a first-episode SAB at two academic hospitals from January 17, 2023 to January 16, 2024. The primary outcome of in-hospital mortality/hospice discharge was compared between MRSA and MSSA. Secondary outcomes included intensive care unit (ICU) admission, 7-day readmission, metastatic complications, infective endocarditis, and recurrent bacteremia. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs), with propensity score matching as sensitivity analysis. Results: Among 329 patients with SAB, 140 (42.6%) had MRSA and 189 (57.4%) had MSSA. Compared with MSSA, MRSA was associated with younger age, lower body mass index, higher injection drug use prevalence, more skin and soft tissue sources, and lower illness severity. After covariate adjustment, methicillin resistance was not associated with mortality/hospice discharge (aOR 1.03, 95% CI 0.49–2.12), ICU admission (aOR 1.09, 95% CI 0.61–1.94), 7-day readmission (aOR 1.51, 95% CI 0.51–4.67), metastatic complications (aOR 0.98, 95% CI 0.47–2.05), infective endocarditis (aOR 1.02, 95% CI 0.42–2.45), or recurrent bacteremia (aOR 2.43, 95% CI 0.92–6.76). Findings were consistent in propensity-matched analyses. Conclusions: In this contemporary academic cohort, methicillin resistance was associated with distinct patient characteristics but not worse short-term outcomes. Host factors, illness severity, and infection source may be more important prognostic determinants.

Staphylococcus aureus is a leading cause of severe infections in neonatal intensive care units (NICUs). We present results of precision surveillance of S. aureus carriage and invasive infection in a cohort study of high-risk infants in the NICU with the goal of identifying novel strategies for prevention and control. Using whole genome sequence guided epidemiology over a 3-year timeframe, we identify spatial and temporal links for transmission between babies, suggesting shared spaces, caregivers, and physical proximity as major risks for transmission in the NICU. Moreover, environmental surveillance reveals potential environmental reservoirs of S. aureus. Remarkably, specific clusters of S. aureus strains that are associated with invasive infection are also detected in more infants over time during routine surveillance, suggesting a strong link between the rate of dissemination and disease in this vulnerable population. Overall, our findings demonstrate a strong association amongst colonization, transmission, persistence, and the development of invasive infections, underscoring the importance of targeted measures to prevent S. aureus infections in the NICU setting.

Background: Differentiation of a relapse from a new infection is challenging in patients with a recurrent bone or joint infection (BJI). We compared clinical, microbiological, and genomic definitions of relapse among patients with methicillin-resistant Staphylococcus aureus (MRSA) BJI. Methods: All MRSA isolates obtained from BJIs between July 2018 and December 2022 from patients with at least 2 episodes of BJI from 2 U.S. hospitals underwent whole-genome sequencing. Distinct intrasubject lineages (ISLs) were defined as MRSA genomes from the same individual differing by 1 ISL. Multilocus sequence type (ST) 8 was the most common (n = 147, 55.7%). In multivariable analysis, female sex and antibiotic susceptibility differences in MRSA strains were associated with >1 ISL. Compared with the genomic definition of relapse (same ISL), the level of agreement was poor (Cohen's kappa = −0.16) for the clinical definition, fair for the microbiological definition (Cohen's kappa = 0.29), and substantial for the MLST definition (Cohen's kappa = 0.63). Conclusions: Clinical and microbiological criteria were not accurate in distinguishing a relapse of BJI from a new infection.

Background: Recurrence of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a high risk complication for patients. Distinguishing persistent lineages from new infections is not standardized across clinical studies. Methods: We investigated factors contributing to recurrence of MRSA bacteremia among subjects in Philadelphia, Pennsylvania. Subject demographics and clinical history were collected and paired with whole-genome sequences of infection isolates. Recurrent bacteremia episodes were recorded and defined as relapse infections (same lineage) or new infections by genomic criteria, where a relapse contained isolates ≤ 25 single nucleotide polymorphisms (SNP) different, and by clinical criteria. All isolates were assessed for pairwise SNP distances, common mutations, and signatures of within-host adaptation using the McDonald-Kreitman test. Clusters of transmission between relapse-associated isolates and other subject lineages were identified. Results: Among 411 sequential subjects with MRSA bacteremia, 32 experienced recurrent bacteremia episodes, with 24 subjects having exclusively relapse infections, 6 with infections exclusively from a new strain, and 2 patients with both relapse and new infections. No concordance between a genomic and a clinical definition of relapse was evident (Cohen κ = 0.18; confidence interval, −0.41). Recurrence-associated lineages exhibited signatures of positive selection (G test, < 0.01). Genes with SNPs occurring in multiple relapse lineages have roles in antibiotic resistance and virulence, including 5 lineages with mutations in mprF and 3 lineages with mutations in rpoB, which corresponded with evolved phenotypic changes in daptomycin and rifampin resistance. Conclusions: Recurrent infections have a diverse strain background. Relapses can be readily distinguished from newly acquired infections using genomic sequencing but not clinical criteria.

Xylazine, an adulterant of unregulated opioid supplies, is increasingly prevalent in the United States and associated with distinctive wounds. Xylazine-associated wounds (XAWs) are primarily noted in the extremities and are not always associated with injection drug use. XAWs are often chronic and can become superinfected, posing a great challenge to clinical care. We share multidisciplinary guidance to care for persons with XAWs: (1) substance use disorder treatment and longitudinal multidisciplinary care including addiction medicine, wound care, infectious diseases, and surgery are imperative; (2) avoid aggressive debridement; (3) administer empirical antibiotics for methicillin-resistant Staphylococcus aureus (MRSA)– and group A Streptococcus (GAS)–infected wounds, specifically oral trimethoprim-sulfamethoxazole for MRSA and oral β-lactams for GAS; (4) administer intravenous daptomycin to reduce the discomfort and challenges associated with frequent phlebotomy for vancomycin therapeutic drug monitoring; and (5) create explicit contingency antibiotic plans with potential use of linezolid, tedizolid, or dalbavancin for patient-directed hospital discharge.

Staphylococcus lugdunensis is known to be virulent, but there are few large-scale epidemiologic studies of this species to define types of infection, susceptibility patterns, and severity. S. lugdunensis isolates from any culture at four U.S. tertiary care hospitals between 1 April 2021 and 1 April 2022 were identified. For the first isolate from each subject, clinical, demographic, and outcome data were recorded. Of 291 isolates, 223 were obtained from a clinically significant infection. Of these 223 isolates, 86 (38.6%) were from monomicrobial cultures; additionally, S. lugdunensis was considered a true pathogen in 69/137 polymicrobial infections. Among 155 subjects with S. lugdunensis infections, 49.7% were female, 46.5% were black, and 41.9% were white; 51.6% of infections were community associated. The most common infection sites were skin and soft tissue (SSTI) ( n = 98, 63.2%), urinary tract ( n = 16, 10.3%), and sinusitis ( n = 14, 9%). Of nine monomicrobial bloodstream infections (BSIs), two were fatal, three involved foreign bodies, and two had infective endocarditis. Greater than half of SSTIs required an invasive procedure for cure. Among 138/291 isolates from colonization or infection, tetracycline, trimethoprim-sulfamethoxazole, oxacillin, and vancomycin susceptibility rates were 94.8% (128/135), 95.9% (94/98), 84.1% (116/138), and 100% (138/138), respectively. There were similarities in types of infection comparing S. lugdunensis in this study and prior reports on Staphylococcus aureus . SSTI was the predominant S. lugdunensis infection type; more than 50% of SSTIs required procedural intervention. Of nine BSIs, three involved a foreign body, and there were two cases of infective endocarditis. Oxacillin resistance was identified in 16% of isolates. IMPORTANCE: In recent years, Staphylococcus lugdunensis has been identified with increasing frequency as a human pathogen causing a wide variety of clinical syndromes, from soft tissue infections to fatal cases of bloodstream infection. Despite this, there are few large-scale epidemiologic studies examining this highly virulent organism. Our study adds to the growing literature on this emerging pathogen by analyzing a large case series of sequential S. lugdunensis infections at four U.S. hospitals to define its contemporary epidemiology, including the types of infections it causes, their outcomes, treatment approaches, and antimicrobial susceptibilities. These data provide valuable insights for clinicians in diagnosing and treating patients with these often debilitating infections. The findings also improve upon our understanding of the incidence of each infection syndrome and variability in antimicrobial susceptibilities of isolates to guide the design of future studies on the genomic epidemiology of this important pathogen.

Background: Recurrence of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a high risk complication for patients. Distinguishing persistent lineages from new infections is not standardized across clinical studies. Methods: We investigated factors contributing to recurrence of MRSA bacteremia among subjects in Philadelphia, Pennsylvania. Subject demographics and clinical history were collected and paired with whole-genome sequences of infection isolates. Recurrent bacteremia episodes were recorded and defined as relapse infections (same lineage) or new infections by genomic criteria, where a relapse contains isolates <=25 single nucleotide polymorphisms (SNP) different, and by clinical criteria. All isolates were assessed for pairwise SNP distances, common mutations, and signatures of within-host adaptation using the McDonald-Kreitman test. Clusters of transmission between relapse-associated isolates and other subject lineages were identified. Results: Among 411 sequential subjects with MRSA bacteremia, 32 experienced recurrent bacteremia episodes, with 24 subjects having exclusively relapse infections, six with infections exclusively from a new strain, and two patients with both relapse and new infections. No concordance between a genomic and a clinical definition of relapse was evident (Cohen’s Kappa = 0.18, CI: -0.41). Recurrence-associated lineages exhibited signatures of positive selection(G- test:mprF and 3 lineages with mutations in rpoB, which corresponded with evolved phenotypic changes in daptomycin and rifampin resistance. Conclusions: Recurrent infections have a diverse strain background. Relapses can be readily distinguished from newly acquired infections using genomic sequencing but not clinical criteria.

Staphylococcus aureus is a common cause of skin and soft-tissue infections (SSTIs) and has become the most common cause of bloodstream infections (BSIs) in recent years, but whether the strains causing these two clinical syndromes overlap has not been studied adequately. USA300/500 (clonal complex [CC] 8–sequence type [ST] 8) and USA100 (CC5-ST5) have dominated among methicillin-resistant S aureus (MRSA) strains in the United States since the early 2000s. We compared the genomes of unselected MRSA isolates from 131 SSTIs with those from 145 BSIs at a single US center in overlapping periods in 2018–2021. CC8 MRSA was more common among SSTIs, and CC5 was more common among BSIs, consistent with prior literature. Based on clustering genomes with a threshold of 15 single-nucleotide polymorphisms, we identified clusters limited to patients with SSTI and separate clusters exclusively comprising patients with BSIs. However, we also identified eight clusters that included at least one SSTI and one BSI isolate. This suggests that virulent MRSA strains are transmitted from person to person locally in the healthcare setting or the community and that single lineages are often capable of causing both SSTIs and BSIs.