Methicillin-resistant Staphylococcus Aureus Bacteremia Research Articles

Tensor modeling of MRSA bacteremia cytokine and transcriptional patterns reveals coordinated, outcome-associated immunological programs

Abstract Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a common and life-threatening infection that imposes up to 30% mortality even when appropriate therapy is used. Despite in vitro efficacy determined by minimum inhibitory concentration (MIC) breakpoints, antibiotics often fail to resolve these infections in vivo, resulting in persistent MRSA bacteremia. Recently, several genetic, epigenetic, and proteomic correlates of persistent outcomes have been identified. However, the extent to which single variables or their composite patterns operate as independent predictors of outcome or reflect shared underlying mechanisms of persistence is unknown. To explore this question, we employed a tensor-based integration of host transcriptional and cytokine datasets across a well-characterized cohort of patients with persistent or resolving MRSA bacteremia outcomes. This method yielded high correlative accuracy with outcomes and immunologic signatures united by transcriptomic and cytokine datasets. Results reveal that patients with persistent MRSA bacteremia exhibit signals of granulocyte dysfunction, suppressed antigen presentation, and deviated lymphocyte polarization. In contrast, patients with resolving bacteremia heterogeneously exhibit correlates of robust antigen-presenting cell trafficking and enhanced neutrophil maturation corresponding to appropriate T lymphocyte polarization and B lymphocyte response. These results suggest that transcriptional and cytokine correlates of persistent versus resolving bacteremia outcomes are complex and may not be disclosed by conventional modeling. In this respect, a tensor-based integration approach may help to reveal consensus molecular and cellular mechanisms and their biological interpretation.

Impact of Povidone Application to Nares in Addition to Chlorhexidine Bath in Critically Ill Patients on Nosocomial Bacteremia and Central Line Blood Stream Infection.

Nosocomial Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia results in a significant increase in morbidity and mortality in hospitalized patients. We aimed to analyze the impact of applying 10% povidone iodine (PI) twice daily to both nares in addition to chlorhexidine (CHG) bathing on nosocomial (MRSA) bacteremia in critically ill patients. A quality improvement study was completed with pre and post-design. The study period was from January 2018 until February 2020 and February 2021 and June 2021. The control period (from January 2018 to May 2019) consisted of CHG bathing alone, and in the intervention period, we added 10% PI to the nares of critically ill patients. Our primary outcome is rates of nosocomial MRSA bacteremia, and our secondary outcome is central line associated blood stream infection (CLABSI) and potential cost savings. There were no significant differences in rates of MRSA bacteremia in critically ill patients. Nosocomial MRSA bacteremia was significantly lower during the intervention period on medical/surgical areas (MSA). CLABSIs were significantly lower during the intervention period in critically ill patients. There were no Staphylococcus aureus CLABSIs in critical care area (CCA)during the intervention period. The intervention showed potential significant cost savings. The application of 10% povidone iodine twice a day in addition to CHG bathing resulted in a significant decrease in CLABSIs in critically ill patients and a reduction in nosocomial MRSA in the non-intervention areas. Further trials are needed to tease out individual patients who will benefit from the intervention.

Combination of Antistaphylococcal β-Lactam With Standard Therapy Compared to Standard Therapy Alone for the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia: A Post Hoc Analysis of the CAMERA2 Trial Using a Desirability of Outcome Ranking Approach.

Desirability of outcome ranking (DOOR) is an emerging approach to clinical trial outcome measurement using an ordinal scale to incorporate efficacy and safety endpoints. We applied a previously validated DOOR endpoint to a cohort of CAMERA2 trial participants with methicillin-resistant Staphylococcus aureus bacteremia (MRSAB). Participants were randomly assigned to standard therapy, or to standard therapy plus an antistaphylococcal β-lactam (combination therapy). Each participant was assigned a DOOR category, within which they were further ranked according to their hospital length of stay (LOS) and duration of intravenous antibiotic treatment. We calculated the probability and the generalized odds ratio of participants receiving combination therapy having worse outcomes than those receiving standard therapy. Participants assigned combination therapy had a 54.5% (95% confidence interval [CI], 48.9%-60.1%; P = .11) probability and a 1.2-fold odds (95% CI, .95-1.50; P = .12) of having a worse outcome than participants on standard therapy. When further ranked according to LOS and duration of antibiotic treatment, participants in the combination group had a 55.6% (95% CI, 49.5%-61.7%) and 55.3% (95% CI, 49.2%-61.4%) probability of having a worse outcome than participants in the standard treatment group, respectively. When considering both efficacy and safety, treatment of MRSAB with a combination of standard therapy and a β-lactam likely results in a worse clinical outcome than standard therapy. However, a small benefit of combination therapy cannot be excluded. Most likely the toxicity of combination therapy outweighed any benefit from faster clearance of bacteremia.

Ceftaroline Fosamil for the Treatment of Methicillin-Resistant Staphylococcus Aureus Bacteremia: A Real-World Comparative Clinical Outcomes Study.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia results in substantial morbidity and mortality. As current treatments often lead to unsatisfactory outcomes, evidence guiding alternative treatment options is needed. This study evaluated real-world clinical outcomes of ceftaroline fosamil for the treatment of MRSA bacteremia. This retrospective study included adults hospitalized with MRSA bacteremia between 2011 and 2019. Patients were classified according to treatment with ceftaroline fosamil (ceftaroline), vancomycin, or daptomycin: Group 1, ceftaroline; Group 2, vancomycin or daptomycin (without ceftaroline); Group 3, combination therapy with ≥ 2 of these three agents. Clinical outcomes were compared using propensity-score-adjusted odds ratios (ORs) from logistic regression models. Overall, 24,479 patients were included (Group 1, n=532; Group 2, n=21,555; Group 3, n=2392). Mean age was 59.6, 60.8, and 57.4 years in Groups 1, 2, and 3, respectively. Mean post-index treatment length of stay was 8.8, 8.8, and 8.0 days, respectively. The most frequent line of therapy was ceftaroline first-line (42.1%), vancomycin or daptomycin first-line (95.4%), and combination therapy third-line or later (67.8%) in Groups 1, 2, and 3, respectively. Compared with Group 2, Groups 1 and 3 had similar favorable clinical responses {odds ratio [OR]=1.18 [95% confidence interval (CI) 0.98-1.44], p=0.08; OR=1.20 [95% CI 0.97-1.47], p=0.09, respectively} and were less likely to switch treatment (both p<0.001). Compared with Group 2, Group 1 was more likely to undergo 30-day all-cause readmission [OR=1.38 (95% CI 1.06-1.80), p=0.02], whereas this was less likely for Group 3 [OR=0.77 (95% CI 0.58-1.00), p=0.05]. Patients receiving ceftaroline more often had favorable clinical responses than those receiving vancomycin or daptomycin monotherapy. In the absence of large-scale randomized controlled trials, these real-world data provide insights into the potential role of ceftaroline for treating MRSA bacteremia.

The 3′ UTR of vigR is required for virulence in Staphylococcus aureus and has expanded through STAR sequence repeat insertions

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are alarmingly common, and treatment is confined to last-line antibiotics. Vancomycin is the treatment of choice for MRSA bacteremia, and treatment failure is often associated with vancomycin-intermediate S.aureus isolates. The regulatory 3' UTR of the vigR mRNA contributes to vancomycin tolerance and upregulates the autolysin IsaA. Using MS2-affinity purification coupled with RNA sequencing, we find that the vigR 3' UTR also regulates dapE, a succinyl-diaminopimelate desuccinylase required for lysine and peptidoglycan synthesis, suggesting a broader role in controlling cell wall metabolism and vancomycin tolerance. Deletion of the 3' UTR increased virulence, while the isaA mutant is completely attenuated in a wax moth larvae model. Sequence and structural analyses of vigR indicated that the 3' UTR has expanded through the acquisition of Staphylococcus aureus repeat insertions that contribute sequence for the isaA interaction seed and may functionalize the 3' UTR.

Validation of a new risk stratification system-based management for methicillin-resistant Staphylococcus aureus bacteraemia: analysis of a multicentre prospective study.

Distinguishing between complicated and uncomplicated Staphylococcus aureus bacteraemia (SAB) is therapeutically essential. However, this distinction has limitations in reflecting the heterogeneity of SAB and encouraging targeted diagnostics. Recently, a new risk stratification system for SAB metastatic infection, involving stepwise approaches to diagnosis and treatment, has been suggested. We assessed its applicability in methicillin-resistant SAB (MRSAB) patients. We retrospectively analysed data of a 3-year multicentre, prospective cohort of hospitalised patients with MRSAB. We classified the patients into three risk groups: low, indeterminate, and high, based on the new system and compared between-group management and outcomes. Of 380 patients with MRSAB, 6.3% were classified as low-, 7.6% as indeterminate-, and 86.1% as high-risk for metastatic infection. No metastatic infection occurred in the low-, 6.9% in the indeterminate-, and 19.6% in the high-risk groups (P < 0.001). After an in-depth diagnostic work-up, patients were finally diagnosed as 'without metastatic infection (6.3%)', 'with metastatic infection (17.4%)', and 'uncertain for metastatic infection (76.3%)'. 30-day mortality increased as the severity of diagnosis shifted from 'without metastatic infection' to 'uncertain for metastatic infection' and 'with metastatic infection' (P = 0.09). In multivariable analysis, independent factors associated with metastatic complications were suspicion of endocarditis in transthoracic echocardiography, clinical signs of metastatic infection, Pitt bacteraemia score ≥ 4, and persistent bacteraemia. The new risk stratification system shows promise in predicting metastatic complications and guiding work-up and management of MRSAB. However, reducing the number of cases labelled as 'high-risk' and 'uncertain for metastatic infection' remains an area for improvement.

The molecular epidemiology and clinical implication of methicillin-resistant Staphylococcus aureus (MRSA) sequence types in pediatric bacteremia: a restrospective observational study, 2016-2021.

While there is a high burden of methicillin-resistant Staphylococcus aureus (MRSA) infections among pediatric patients, studies on the molecular epidemiology of MRSA infections in Korean children since the 2010s are lacking. This study aimed to investigate the molecular genotypes and clinical characteristics of MRSA isolates from children with MRSA bacteremia at Asan Medical Center Children's Hospital from 2016 to 2021. Clinical data were retrospectively reviewed, and the molecular types of MRSA were determined using multilocus sequence typing (MLST) and Staphylococcal cassette chromosome mec (SCCmec) typing. The overall methicillin resistance rate of S. aureus bacteremia was 44.8% (77/172); 49.5% in the period 2016-2018 (period 1) and 37.3% in the period 2019-2021 (period 2) (P = 0.116). Community-acquired infections accounted for only 3.9% of cases. The predominant ST group was ST72 group (67.6%), followed by ST5 group (18.9%) and ST1 group (5.4%). The proportion of ST5 was significantly lower in period 2 compared to period 1 (P = 0.02). Compared to the ST5 and ST1 groups, the ST72 group exhibited lower overall antibiotic resistance and multidrug-resistant (MDR) rates (12.0% [6/50] in ST72 group vs. 100.0% [14/14] in ST5 group vs. 50.0% [2/4] in ST1 group; P < 0.001). In the multivariate analysis, the ST1 group was an independent risk factor for 30-day all-cause mortality (aOR, 44.12; 95% CI, 3.46-562.19). The ST72-MRSA strain remained the most frequently isolated genotype in Korean children, while the ST1 group emerged as an independent risk factor for 30-day all-cause mortality in pediatric MRSA bacteremia. Ongoing efforts to uncover the evolving epidemiology of MRSA are essential for developing effective strategies for prevention and treatment.

Daptomycin and Ceftaroline Combination Therapy in Complicated Endovascular Infections Caused by Methicillin-Resistant Staphylococcus epidermidis.

Background In complicated endovascular infections by methicillin-resistant Staphylococcus aureus (MRSA) or Staphylococcus epidermidis (MRSE), when first-line therapy with vancomycin (VAN) or daptomycin (DAP) fails, combination therapy with ceftaroline (CFT) and DAP has been shown to be a useful approach as salvage therapy for persistent MRSA bacteremia. Objectives This study aimed to describe experience with daptomycin and ceftaroline combination therapy in MRSE-complicated endovascular infections. Methods A single-center retrospective review of consecutive patients with MRSE-complicated endovascular infections treated with ≥72 hours of DAP+CFT at any time during the course of treatment, from January 1, 2016 to December 31, 2020, at Centro Hospitalar Universitário São João (CHUSJ), Porto, Portugal, was conducted. The exclusion criteria were known resistance to daptomycin or ceftaroline, total time of combination therapy <72 hours and loss to follow-up. Results We identified seven cases that matched our criteria: five endocarditis and two central venous catheter infections. Six patients switched to combination therapy due to treatment failure with first-line agents - three due to persistent bacteremiaand three due to progression of infection despite negative blood cultures. Effective surgical source control took one to four weeks to occur. Three patients died during the treatment, one from progression of the disease and two due to another infection. Conclusions We consider the DAP+CFT combination therapy to be a valid and safe therapeutic choice in complicated patients, such as those with severe infection, poor functional status, and impossibility or delay of surgical source control. However, conclusions on the role of combination therapy should be careful due to the low number of patients and the several confounding factors.

Multiple Cold Abscesses of a Chest Wall with Ribs Destruction in a Hemodialysis Patient

Cold abscess of the chest wall is an uncommon disease that is mainly caused by tuberculous infection. Staphylococcal cold abscesses of the chest wall are extremely rare and usually clinically occult, frequently leading to a delay in diagnosis and consequently severe infectious complications. We report an 88-year-old woman with end-stage renal disease, who presented with an exit site infection of a cuffed tunneled dialysis catheter caused by methicillin-resistant Staphylococcus aureus (MRSA). Despite the removal of the catheter and administration of antibiotics, she developed refractory MRSA bacteremia. Computed tomography (CT) of the chest revealed septic thrombophlebitis with metastatic cold abscesses of the chest wall and ribs destruction. Although CT-guided drainage and vancomycin therapy eliminated MRSA bacteremia, the chest wall abscesses did not resolve. Patients fitted with a central venous dialysis catheter are at risk of septic thrombophlebitis with metastatic cold abscesses of the chest wall that are resistant to antibiotic therapy. Early identification is based on serial blood cultures and prompt CT scans. Surgical management coupled with antibiotic therapy can eradicate the source of infection and improve patients’ outcomes.

A Retrospective Cohort Study Comparing Dual Therapy With Ceftaroline With Vancomycin or Daptomycin Monotherapy for High-Grade or Persistent MRSA Bacteremia

Background: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a serious clinical infection associated with a high risk of mortality. Dual therapy is often used in patients with persistent bacteremia. Objective: This study aimed to compare the outcomes of vancomycin or daptomycin monotherapy with those of dual therapy with ceftaroline in high-grade or persistent MRSA bacteremia. Methods: We conducted a retrospective cohort study at a university teaching hospital between January 2014 and June 2021, involving adults initially treated with vancomycin or daptomycin. Patients were categorized into monotherapy and dual therapy groups. The primary outcome was 30-day mortality. Secondary outcomes included microbiological relapse and antibiotic-related adverse events. Results: In a group of 155 patients, 30-day mortality rates were similar between the monotherapy (23.4%) and dual therapy (22.6%) groups, with comparable microbiological relapse rates (6.5%). In inverse probability of treatment weighting analysis, we found no significant association between dual therapy and mortality (adjusted risk ratio [ARR] 1.38, 95% CI 0.64-2.41, P = 0.38) or microbiological relapse (ARR 0.95, 95% CI 0.31-2.73, P = 0.93). Dual therapy was associated with a lower risk of antibiotic-related adverse events (ARR 0.45, 95% CI 0.21-0.89, P = 0.02). Infectious diseases (ID) consultation was associated with a reduced mortality risk (ARR 0.27, 95% CI 0.07-0.95, P = 0.04). Conclusions: Dual therapy with ceftaroline did not reduce mortality risk compared with monotherapy in patients with MRSA bacteremia. However, patients with ID consultations showed a 73% reduction in mortality rates. Large-scale, prospective, and randomized controlled trials are needed to provide conclusive evidence regarding the potential benefits of dual therapy with ceftaroline for MRSA bacteremia.

Effectiveness evaluation of antibiotic use in patients with Methicillin-resistant Staphylococcus aureus (MRSA) infection: a review

Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen that become a public health problem due to its ability to be resistant to more than three classes of antibiotics. Evaluation of the effectiveness of antibiotic use in patients with MRSA is important to optimize antibiotic use and to control antibiotic resistance. This article review attempted to evaluate the effectiveness of antibiotics in patients with MRSA. This review explored the results of previous research from PubMed as a literature source and the PRISMA flow diagram as a protocol for the article selection process. Eight studies reviewed the evaluation of the effectiveness of antibiotic use in MRSA patients with various clinical conditions, such as uncomplicated wound infections, cellulitis and no wound, purulent drainage or abscess, cSSSI infections caused by MRSA, infections caused by MRSA bacteremia and nosocomial infections caused by MRSA. In conclusion, the effectiveness of antibiotics in patients with MRSA infection depends on the clinical condition of each patient. Therefore, the use of antibiotics is adjusted based on the type of infection and the efficacy of the antibiotics. Combination therapy is recommended for MRSA patients considering its life-threatening ability.

Increased Activity of β-Lactam Antibiotics in Combination with Carvacrol against MRSA Bacteremia and Catheter-Associated Biofilm Infections.

β-Lactam antibiotics are the mainstay for the treatment of staphylococcal infections, but their utility is greatly limited by the emergence and rapid dissemination of methicillin-resistant Staphylococcus aureus (MRSA). Herein, we evaluated the ability of the plant-derived monoterpene carvacrol to act as an antibiotic adjuvant, revitalizing the anti-MRSA activity of β-lactam antibiotics. Increased susceptibility of MRSA to β-lactam antibiotics and significant synergistic activities were observed with carvacrol-based combinations. Carvacrol significantly inhibited MRSA biofilms and reduced the production of exopolysaccharide, polysaccharide intercellular adhesin, and extracellular DNA and showed synergistic biofilm inhibition in combination with β-lactams. Transcriptome analysis revealed profound downregulation in the expression of genes involved in two-component systems and S. aureus infection. Mechanistic studies indicate that carvacrol inhibits the expression of staphylococcal accessory regulator sarA and interferes with SarA-mecA promoter binding that decreases mecA-mediated β-lactam resistance. Consistently, the in vivo experiment also supported that carvacrol restored MRSA sensitivity to β-lactam antibiotic treatments in both murine models of bacteremia and biofilm-associated infection. Our results indicated that carvacrol has a potential role as a combinatorial partner with β-lactam antibiotics to address MRSA infections.

209. Validation of a New Risk Stratification System-Based Management for Methicillin-Resistant Staphylococcus aureus Bacteremia: Analysis of a Multicenter Prospective Study

Abstract Background Distinguishing between complicated and uncomplicated Staphylococcus aureus bacteremia (SAB) is therapeutically essential. However, this distinction has limitations in reflecting the various manifestation of SAB. In the light of this, Koujizer et al. proposed a new risk stratification system for metastatic infection in SAB, which involves a stepwise approach to diagnosis and treatment. We tested this risk stratification system in methicillin-resistant SAB (MRSAB) patients. Methods We retrospectively analyzed data of a 3-year multicenter, prospective cohort of hospitalized patients with MRSAB. We classified the patients into three risk groups: low, indeterminate, and high, based on the new system and compared between-group management and outcomes, as well as microbiologic features. Results The demographic and baseline characteristics of patients are shown in Table 1. The most frequent source of MRSAB was central venous catheter-related infection (25.5%), followed by unknown origin (15.3%) and pneumonia (11.1%). Echocardiography was performed in 248 cases (65.3%). Of 380 patients with MRSAB, 6.3% were classified as low-, 7.6% as indeterminate-, and 86.1% as high-risk for metastatic infection (Figure 1). No metastatic infection occurred in the low-, 6.9% in the indeterminate-, and 17.7% in the high-risk groups (P=0.03) (Figure 2A). After an in-depth diagnostic work-up, patients were finally diagnosed as ‘without metastatic infection (6.3%)’, ‘with metastatic infection (15.8%)’, and ‘uncertain metastatic infection (77.9%)’. 30-day mortality increased markedly as the severity of diagnosis shifted from ‘without metastatic infection’ to ‘uncertain’ and ‘with metastatic infection’ (P=0.07) (Figure 2B). In multivariable analysis, independent factors associated with metastatic complications were suspicion of endocarditis in transthoracic echocardiography, clinical signs of metastatic infection, Pitt bacteremia score ≥4, and persistent bacteremia. Figure 1. Flowchart of risk stratification and final diagnosis Figure 2. Outcomes of metastatic infection and 30-day mortality. A, metastatic infection according to the risk stratification, B, 30-day mortality according to the final diagnosis Conclusion The new risk stratification system provides good discrimination in predicting metastatic complications, making it a reliable tool for guiding work-up and management of MRSAB. However, minimizing the number of ‘uncertain metastatic infection’ cases remains an area for improvement. Disclosures All Authors: No reported disclosures

174. Impact of Ceftaroline Duration after Bacteremia Clearance When Used in Combination Therapy for Persistent or High-grade MRSA Bacteremia

Abstract Background Methicillin resistant Staphylococcus aureus (MRSA) bacteremia is a clinically relevant syndrome with high mortality. Combination therapy with beta-lactam antibiotics has been employed in persistent MRSA bacteremia with reported clinical success. Ceftaroline is a beta-lactam antibiotic with activity against MRSA, which has been commonly used in combination therapy for this indication. However, adequate ceftaroline duration after bacteremia clearance continues to be elucidated. Thus, we aimed to evaluate clinical outcomes of patients receiving short vs. long duration of ceftaroline after persistent or high-grade bacteremia clearance. Methods This was a single-center, retrospective cohort study conducted from January 1, 2014, to June 30, 2021. Patients were included if ≥18 years of age, with high grade or persistent MRSA bacteremia, who received combination therapy with ceftaroline. The primary outcome was 30-day mortality. Secondary outcomes included hospital length of stay, time to bacteremia clearance, antibiotic-related adverse events and microbiological relapse. Results A total of 32 patients were included (mean age: 51.5 years; 71.9% white; 61.3% male). 96.9% had high-grade MRSA bacteremia and 68.8% had persistent bacteremia. The most common bacteremia source was bone and joint infections (28.1%). 56.3% of patients received ceftaroline in combination with vancomycin; mean duration was 8 days. Multivariable analysis showed increasing the duration of combination therapy after bacteremia clearance was not associated with a lower risk of 30-day mortality after controlling for Charlson comorbidity index and Pitt bacteremia scores (OR 0.75, 95% CI 0.94-2.45; p=0.07). Similarly, no association was observed with microbiological relapse (OR 1.03, 95% CI 0.92-1.16; p=0.73), antibiotic-related adverse event (OR 0.97, 95% CI 0.78-1.10; p=0.75), time to bacteremia clearance (p=0.88) or hospital length of stay (p=0.06). Conclusion Longer durations of ceftaroline in combination therapy after bacteremia clearance was not associated with lower rates of 30-day mortality, microbiological relapse, or higher rates of antibiotic-related adverse events. Larger studies are needed to determine the appropriate duration of combination therapy. Disclosures Cecilia Thompson, PhD, D(ABMM), MLS (ASCP), Roche Diagnostics: Honoraria

2456. Methicillin-Resistant Staphylococcus aureus Bacteremia 30-Day Mortality During 2020 Compared to 2016-2019: Assessing the Impact of COVID-19

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with substantial mortality, but the effect of the COVID-19 pandemic on MRSA mortality has not been fully explored. Methods For 2016-2020, MRSA bacteremia cases among adults aged ≥ 18 years were identified through CDC Emerging Infections Program’s active laboratory- and population-based surveillance in 5 states (16 counties). Death within 30 days of initial MRSA blood culture was determined from medical record documentation or linked state vital statistics data. Cases were classified (epi class) as hospital-onset (HO), healthcare-associated community onset (HACO), or community associated (CA) (Figure 1). Thirty-day mortality was calculated by year and epi class and, for 2020, stratified by whether a SARS-CoV-2 test was positive in the 30 days preceding MRSA culture (recent COVID-19). Using multivariate logistic regression to adjust for potential confounders, the effect of recent COVID-19 on 30-day mortality was assessed. Results MRSA bacteremia 30-day mortality was 22% (2,113/9,689) during 5 surveillance years. Mortality in 2020 was higher than in 2016-2019 overall (25% vs. 21%, p&amp;lt; .01), for HO cases (43% vs 32%, p&amp;lt; .01), and for CA cases (19% vs. 13%, p&amp;lt; .01). When limited to cases without recent COVID-19, mortality in 2020 was still higher than in 2016-2019 for CA (18%, p&amp;lt; .01) but not HO (35%, p=.39). During 2020, cases with recent COVID-19 comprised 37% of HO deaths and a smaller proportion of HACO (13%) and CA (7%) deaths. Cases with recent COVID-19 had higher 30-day mortality than those without across all epi classes (Figure 2; p≤ .01 for all), with mortality highest among HO cases with recent COVID-19 (77%). After adjusting for other factors, recent COVID-19 remained a significant risk factor for 30-day mortality (adjusted odds ratio: 5.3, 95% CI: 3.6-8.0; Table).Table.Multivariate Analysis of Factors Associated with Methicillin-Resistant Staphylococcus aureus Bacteremia 30-Day Mortality, 5 Emerging Infections Program Sites, 2020 Conclusion COVID-19 emerged as a significant independent risk factor for MRSA bacteremia-associated death in 2020, and the very high mortality for HO cases with recent COVID-19 resulted in a higher mortality for HO cases overall. Conversely, the contribution of COVID-19 to the increased mortality for CA cases in 2020 appeared small, and reasons for the increase in mortality for CA cases without recent COVID-19 need additional investigation. Disclosures Ghinwa Dumyati, MD, Pfizer: Grant/Research Support

In Vivo-Acquired Resistance to Daptomycin during Methicillin-Resistant Staphylococcus aureus Bacteremia.

Daptomycin (DAP) represents an interesting alternative to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. Different mechanisms of DAP resistance have been described; however, in vivo-acquired resistance is uncharacterized. This study described the phenotypic and genotypic evolution of MRSA strains that became resistant to DAP in two unrelated patients with bacteremia under DAP treatment, in two hospitals in the South of France. DAP MICs were determined using broth microdilution method on the pairs of isogenic (DAP-S/DAP-R) S. aureus isolated from bloodstream cultures. Whole genome sequencing was carried out using Illumina MiSeq Sequencing system. The two cases revealed DAP-R acquisition by MRSA strains within three weeks in patients treated by DAP. The isolates belonged to the widespread ST5 (patient A) and ST8 (patient B) lineages and were of spa-type t777 and t622, respectively. SNP analysis comparing each DAP-S/DAP-R pair confirmed that the isolates were isogenic. The causative mutations were identified in MprF (Multiple peptide resistance Factor) protein: L826F (Patient A) and S295L (Patient B), and in Cls protein: R228H (Patient B). These proteins encoded both proteins of the lipid biosynthetic enzymes. The resistance to DAP is particularly poorly described whereas DAP is highly prescribed to treat MRSA. Our study highlights the non-systematic cross-resistance between DAP and glycopeptides and the importance of monitoring DAP MIC in persistent MRSA bacteremia.

Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Surveillance Outcome Program (ASSOP) Bloodstream Infection Annual Report 2022.

From 1 January to 31 December 2022, fifty-five institutions across Australia participated in the Australian Staphylococcus aureus Surveillance Outcome Program (ASSOP). The aim of ASSOP 2022 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that were antimicrobial resistant, with particular emphasis on susceptibility to methicillin and on characterisation of the molecular epidemiology of the methicillin-resistant isolates. A total of 3,214 SAB episodes were reported, of which 77.5% were community-onset. Overall, 15.0% of S. aureus were methicillin resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 21.4%, which was significantly different to the 16.8% all-cause mortality associated with methicillin-susceptible SAB (p = 0.02). With the exception of the β-lactams and erythromycin, antimicrobial resistance in methicillin-susceptible S. aureus was rare. However, in addition to the β-lactams, approximately 31% of methicillin-resistant S. aureus (MRSA) were resistant to ciprofloxacin; 30% to erythromycin; 13% to tetracycline; 11% to gentamicin; and 2% to co-trimoxazole. One MRSA isolate, with a daptomycin MIC of 1.5 mg/L, harboured the A302V mprF and A23V cls2 mutations. When applying the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, teicoplanin resistance was detected in one MRSA isolate. Resistance to vancomycin or linezolid was not detected. Resistance to non-β-lactam antimicrobials was largely attributable to the healthcare-associated MRSA (HA-MRSA) clone ST22-IV [2B] (EMRSA-15), and to the community-associated MRSA (CA-MRSA) clone ST45-V [5C2&5] which has acquired resistance to multiple antimicrobials including ciprofloxacin, clindamycin, erythromycin, gentamicin, and tetracycline. The ST22-IV [2B] (EMRSA-15) clone is the predominant HA-MRSA clone in Australia. Nonetheless, 86% of methicillin-resistant SAB episodes were due to CA-MRSA clones. Although polyclonal, approximately 72% of CA-MRSA clones were characterised as ST93-IV [2B] (Queensland clone); ST5-IV [2B]; ST45-V [5C2&5]; ST1-IV [2B]; ST30-IV [2B]; ST97-IV [2B]; ST953-IV [2B]; and ST8-IV [2B]. As CA-MRSA is well established in the Australian community, it is important to monitor antimicrobial resistance patterns in community- and healthcare-associated SAB as this information will guide therapeutic practices in treating S. aureus bacteraemia.

Abstract 12522: Non-Ischemic Papillary Muscle Rupture Due to MRSA Myocarditis

Case Presentation: A 46-year-old male with diabetes, ESRD, and recurrent MRSA bacteremia, presented with septic shock and suffered cardiac arrest. Following resuscitation EKG showed inferolateral ischemia. TTE revealed acute mitral valve regurgitation resulting from posteromedial papillary muscle rupture (PMR). An intra-aortic balloon pump was implanted for cardiogenic shock. Coronary angiography revealed right dominant circulation and thrombotic occlusion of a small caliber distal left circumflex artery (LCX). Emergent mitral valve replacement surgery was performed. Pathologic analysis of the excised muscle and leaflet showed marked acute inflammation, bacterial invasion, and myocyte necrosis, confirming non-ischemic rupture due to MRSA myocarditis. Discussion: PMR predominantly occurs after MI, complicating 0.03% of STEMI cases in the reperfusion era. Non-ischemic causes are rare. Coexistence of myocarditis, infective endocarditis (IE), and MI poses a challenge in determining etiology. Establishing causation guides whether to expedite emergent valve surgery or focus on cardiomyocyte salvage by revascularization. The posteromedial papillary muscle is most commonly involved in PMR due to single blood supply from the PDA (most commonly a branch of the RCA, and less commonly the LCX). Coronary angiography, postoperative histopathology, and culture results determined the etiology of PMR was fulminant MRSA bacteremia culminating in myocarditis. Bacterial colonization and resultant inflammation induced physical and mechanical strain leading to complete rupture. The occluded LCX was incidental, and may have been the result of septic embolization, which occurs in up to 65% of left-sided IE. Albeit rare, non-ischemic etiologies must be considered when the anatomic presentation of acute PMR on TTE is incongruent with angiography. Definitive treatment relies on surgical intervention and mechanical circulatory support is often necessary.

Peri-transplant Treatment with Ceftaroline in Kidney Transplant Recipients at Risk of Donor-derived MRSA Infections: A Case Series

The rising prevalence of MDR pathogens has a significant impact on the recipients' outcome, as this increases the risk of graft complications and makes the management of the peri-transplant phase more difficult. Among the different MDR germs, Methicillin-resistant Staphylococcus aureus (MRSA) represents one of the most frequently isolated pathogens. We report for the first time the off-label use of Ceftaroline in six kidney transplant recipients with donor peritransplantation MRSA bacteremia at the Division of Kidney Transplant Unit of Federico II University Hospital of Naples, Italy, between September and December 2022. Each patient was followed up for the next three months after transplantation, monitoring the clinical and laboratory outcome, the risk of infection, and the efficacy and safety profile of the treatment performed. In the subsequent three months of follow-up to the transplant, none of the six patients showed donor-related infections. In particular, none of the six patients showed MRSA bacteremia or other related MRSA infections. In conclusion, our real-life experience shows that Ceftaroline could represent a valid therapeutic option in the management of solid organ transplant patients with a risk of donor-derived MRSA infection. However, despite the few cases considered, this approach deserves further investigation in ad hoc studies or clinical trials due to our positive results.

Retrospective review of intermittent and continuous infusion vancomycin for methicillin-resistant Staphylococcus aureus bacteremia.

Vancomycin is commonly administered as an intermittent infusion (IIV), although vancomycin's stability at room temperature permits administration continuously over 24h (CIV). At our institution, CIV has been the preferred infusion method for over 20years due to ease of administration and simplicity of therapeutic drug monitoring. The purpose of this study was to examine the outcomes associated with IIV compared to CIV. This was a retrospective study of patients who received vancomycin for MRSA bacteremia. The primary outcomes were the time to therapeutic goal and frequency of adverse drug reactions on IIV compared to CIV. Secondary outcomes evaluated all-cause readmission, relapse, and mortality 30days after completion of therapy. Sixty-three patients were included. Significantly fewer patients were able to achieve a therapeutic goal on IIV compared to CIV (52.4% vs. 82.5%, p < 0.01). Patients on IIV took 3.6days, on average, to reach the target goal, compared to 1.9days when patients were switched to CIV (95% confidence interval, 0.48-3.04, p < 0.01). Six patients experienced adverse events on IIV, and 15 patients experienced adverse events on CIV (IIV 9.5%, CIV 23.8%, p = 0.035). One patient experienced relapse of infection, and six patients (9.5%) were readmitted 30days after completion of therapy. There were no deaths in the cohort. For MRSA bacteremia, CIV enabled patients to achieve the AUC/MIC goal significantly faster than when patients received IIV. Furthermore, patients who were unable to achieve a therapeutic trough on IIV became therapeutic once switched to CIV.