Methicillin-resistant Staphylococcus Aureus Bacteremia Research Articles

Evaluation of analogs of mutacin 1140 in systemic and cutaneous methicillin-resistant Staphylococcus aureus infection models in mice.

Mutacin 1140 (Mu1140) is a potent antibiotic against Gram-positive bacteria, such as Staphylococcus aureus. The antibiotic is produced by the oral bacterium Streptococcus mutans and is a member of the epidermin family of type AI lantibiotics. The antibiotic exerts its inhibitory activity by binding to the cell wall precursor lipid II, blocking cell wall synthesis, and by disrupting bacterial membranes. In previous studies, the novel K2A and R13A analogs of Mu1140 have been identified to have superior pharmacokinetic properties compared to native Mu1140. In this study, the use of a combined formulation of the Mu1140 K2A and R13A analogs was shown to be more effective at treating MRSA bacteremia than the native Mu1140 or vancomycin. The analogs were also shown to be effective in treating an MRSA skin infection. The use of K2A and R13A analogs may provide a future alternative for treating serious Gram-positive bacterial infections. In a previous study, the Mu1140 analogs were shown to have significantly longer drug clearance times, leading to higher plasma concentrations over time. These properties warranted further testing to determine whether the analogs are effective for the treatment of systemic MRSA and acute skin infections. In this study, Mu1140 analogs were shown to be more effective than currently available treatments for systemic and skin MRSA infections. Further, the study clearly shows that the new analogs are superior to native Mu1140 for the treatment of a systemic MRSA infection. These findings support continued drug product development efforts using the K2A and R13A Mu1140 analogs, and that these analogs may ameliorate the outcome of serious bacterial infections.

Evaluating Methicillin-Resistant Staphylococcus aureus Polymerase Chain Reaction Nasal Screening as a Tool for Antimicrobial Stewardship

IntroductionInitiation of broad-spectrum empiric antibiotics is common when infection is suspected in hospitalized adults. The benefits of early utilization of effective antibiotics are well documented. However, the negative effects of inappropriate antibiotic use have led to antimicrobial stewardship mandates. Recent data demonstrate the utility of methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) nasal screening to steward anti-MRSA empiric antibiotics in pneumonia. We hypothesize that MRSA PCR nasal swabs would also be effective to rule out other MRSA infection to effectively limit unnecessary antibiotics for any infectious source. MethodsWe performed a single-center retrospective chart review of all adult patient encounters from October 2019-July 2021 with MRSA PCR nasal testing. We then reviewed all charts to evaluate for the presence of infections based on source cultures results, as the gold standard. Sensitivity, specificity, negative predictive value, and positive predictive value were calculated from 2 × 2 contingency tables. ResultsAmong all patients with MRSA nasal screening, 1189 patients had any infection. Prevalence of MRSA nasal carriage among patients screened was 12%. Prevalence of MRSA infection among all infections was 7.5%. MRSA nasal swabs demonstrated a negative predictive value of 100% for MRSA urinary tract infection, 97.9% for MRSA bacteremia, 97.8% for MRSA pneumonia, 92.1% for MRSA wound infection, and 96.6% for other MRSA infections. Overall, MRSA PCR nasal swabs had a sensitivity of 68.5%, specificity of 90.1%, positive predictive value of 23.7%, and negative predictive value of 98.5% for any infections. ConclusionsMRSA PCR nasal swabs have a high negative predictive value for all infections. Our data support the use of MRSA PCR nasal swabs to rule out MRSA infection and thereby allow early de-escalation of MRSA coverage in hospitalized patients requiring empiric antibiotics. Implementation of MRSA screening could decrease antibiotic-associated morbidity, resistance, and costs. More studies should be conducted to validate these results and support these findings.

The importance of stigma theory for clinical decisions related to diabetic foot amputations

The authors examine the unconsidered impact of social stigma theory on the shared clinical decision-making process for a patient with foot osteomyelitis and MRSA bacteremia facing the prospect of an amputation.

Vancomycin plus ceftaroline for persistent methicillin-resistant Staphylococcus aureus bacteremia.

The preferred antibiotic salvage regimen for persistent methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) is unclear. We sought to evaluate the effectiveness and safety of vancomycin plus ceftaroline for persistent MRSAB. The primary outcome was time to MRSAB clearance post-ceftaroline initiation. Secondary outcomes included microbiological cure, hospital length of stay, 90-day readmission for MRSAB, 90-day all-cause mortality, MRSAB-related mortality, and incidence of antibiotic-associated adverse effects. Single-center, retrospective cohort study between January 1, 2016, and December 31, 2021. State University of New York Upstate University Hospital, a 748-bed tertiary care, academic medical center in Syracuse, NY. Adult patients were included if they had blood cultures positive for MRSA ≥72 h, received vancomycin monotherapy initially, and received vancomycin plus ceftaroline for ≥24 h. Patients were excluded if they received other anti-MRSA antibiotics, were pregnant, or were incarcerated. Of the 178 patients identified, 30 unique patients were evaluated. Patients were medically complex with a median Pitt bacteremia score of 3, 63.3% (19/30) were admitted to the intensive care unit, and 66.7% (20/30) had infective endocarditis. Vancomycin-associated acute kidney injury was observed in 10% (3/30) of patients, which resulted in dose adjustments. No patients experienced ceftaroline-associated neutropenia or Clostridioides difficile infection, but 6.7% (2/30) developed a rash attributed to ceftaroline. Median time to MRSAB clearance post-ceftaroline initiation was 2.6 days. Microbiologic cure occurred in nearly all patients 96.7% (29/30). Median hospital length of stay was 19.5 days, and 6.7% (2/30) of patients had 90-day readmission for MRSAB. 90-day all-cause mortality and MRSAB-related mortality occurred in 26.7% (8/30) and 13.3% (4/30) of patients, respectively. Vancomycin plus ceftaroline may represent an effective and well-tolerated salvage regimen option for persistent MRSAB.

Successful Outpatient Treatment and Monitoring Following Administration of Various Anti-CD19 Chimeric Antigen Receptor Therapies in B-Cell Lymphomas

Background: Chimeric Antigen Receptor (CAR) T-cell therapy is available as a salvage option for patients with relapsed/refractory B-cell lymphomas (DLBCL, FL, and MCL). Historically, most CAR T-cell therapy has been administered in the inpatient setting due to the potential need to closely monitor or treat cytokine release syndrome (CRS) and neurologic toxicity (NT). However, the introduction of rigorous outpatient monitoring programs incorporating nurse-driven education, patient/caregiver-driven after-hours reporting, and prophylactic corticosteroids may enable outpatient administration and monitoring of CAR T-cell in a large proportion of patients. Outpatient monitoring can improve quality of life for the patient as well as reduce healthcare costs. Objective: Describe clinical outcomes in a cohort of patients who received a variety of commercial CAR T-cell therapies and were subsequently monitored in the outpatient setting. Study Design: This is a retrospective analysis of 20 patients treated with outpatient CAR T-cell therapy between February 2021 and March 2022 with all patients having at least 100 days of post-infusion follow up. Additional data points included progression free survival, overall survival, HCT-CI score, prior lines of treatment, ECOG scores (before and after treatment), and incidence of cytokine release syndrome and neurological toxicity. Responses to treatment were determined based on radiographic tumor evaluation by metabolic response with PET-CT. Patients were monitored with daily RN triage visits and in the absence of complications, were seen twice weekly by an advanced practice provider (APP) or MD. Patients did not use remote monitoring devices and both patients and caregivers were encouraged to self-report any symptoms of CRS or NT to a 24 hour on-call APP/MD. Results: Of the 20 patients in the cohort, 2, 3, 14, and 1 patients received tisagenlecleucel, axicabtagene ciloleucel, lisocabtagene maraleucel, and brexucabtagene autoleucel, respectively. The median age was 69.5 (range 46-81). 60% of patients were male. 65% (13/20) of patients were treated with prophylactic dexamethasone. 55% of patients had an IPI score of 3-4. 25% (5/20) of patents had an ECOG score of 2 or greater. Median HCT-CI score was 1 and ≥2 in 9/20 (45%) patients (range 0-5). Overall, 10/20 (50%) patients were admitted in the first month of therapy (all initially for management of CRS), and no patients were admitted within the first 72 hours after infusion. The incidence of CRS was 11/20 (55%) with grade 3+ CRS of 5%. The incidence of NT was 9/20 (45%), with grade 3+ NT of 20%. Progression free survival in the cohort was 65% at 6 months and 60% at 1 year, and overall survival was 85% and 75%, respectively. 2 (10%) patients died prior to day 30 of treatment, one due to MRSA bacteremia (which developed >1 week into hospital admission), one due to progressive disease. No patients were admitted directly to the ICU. Conclusions: In a single-center cohort of patients who received CAR T-cell therapy and were subsequently monitored in the outpatient setting without remote monitoring devices, only half of the patients were admitted in the 1st month of therapy and no patients were admitted within the first 72 hours after infusion. 2 patients died in the first month of treatment for reasons unlikely to be related to outpatient monitoring. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

An Update on Treatment Options for Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia: A Systematic Review.

Since the last century, methicillin-resistant Staphylococcus aureus (MRSA) bacteremia has become a major global and public health concern not only in terms of morbidity and mortality but also the duration of hospital stay, healthcare cost, and antimicrobial choices. Especially alarming is the growing antimicrobial resistance due to their misuse and overuse, which has led the world to be exhausted of its effective antibiotic resources. In this review article, we sought to figure out the most efficacious antimicrobial agents to treat MRSA-related bloodstream infections. We compared the data from reviewing reports from 2017 to 2022 and summarized their comparative efficacy and cost-effectiveness. Although we focused on vancomycin and daptomycin, which are the current Infectious Disease Society Of America (IDSA)-recommended antibiotics for MRSA bacteremia treatment, a deep dive into the newer agents revealed better efficacy and treatment outcome in the combination of ceftaroline (β-lactam) with daptomycin compared to traditional standard monotherapy (vancomycin/daptomycin monotherapy). Also, the IDSA recommended high-dose daptomycin (8-10 mg/kg) therapy for MRSA bacteremia treatment to be more effective in cases with vancomycin-reduced susceptibility. Moreover, we did not find any trial or study describing the use of ceftaroline as a monotherapy to compare its efficacy in MRSA bacteremia with the current standard therapy. The upshot is that we need more large-scale clinical trials exploring in-depth effectiveness and adverse effects to decide on newer agents like β-lactams to use as routine therapy for MRSA bacteremia.

Abstract 15603: Simultaneous Suction Debulking of a 3 Cm Lead Vegetation in the Right Ventricle During Extraction

A 49-year-old male with a history of NICM EF 25% with dual-chamber AICD, lupus with nonbacterial endocarditis of aortic valve, IVC filter for recurrent DVT/PE presented with septic shock due to MRSA osteomyelitis and bacteremia. TTE showed 1.8 cm vegetation. The patient had idiopathic thrombocytopenic purpura, for which IVIG was administered. To avoid obligatory systemic exposure to heparin in the setting of ITP with a larger evacuation system and crossing the IVC filter with a large bore cannula, it was decided to proceed with Penumbra evacuation of lead vegetation with simultaneous laser extraction. A short 16F sheath was inserted through the right femoral vein for the procedure. A12F Medtronic Cryo Flex sheath was advanced through the IVC filter under fluoroscopy to provide steerability in the right atrium. TEE-guided Flex sheath positioned abutting the mass/vegetation. Suction only partially retrieved the mass. RA lead was removed using mechanical extraction tools via the left chest pocket. On repeat TEE evaluation, the mass/vegetation was 3 cm on the RV lead. Since we could not aspirate the mass, we used the extraction tools to peel the mass off the lead while providing simultaneous negative suction through the Penumbra cannula. The lead was successfully extracted. TEE showed no residual mass, no significant change in tricuspid regurgitation and no pericardial effusion. Mass biopsy showed calcified blood clots. The patient was discharged on IV antibiotics. Discussion: Most cases to date report using larger systems like AngioVac for extracting larger vegetations/masses with lead extraction. Aspiration tools have been shown to extract malleable masses with lesser procedural-related morbidity. Peeling and aspiration can be used concurrently to remove these masses without significant blood loss, downstream sheading and the need for systemic anticoagulation. Further technique development can benefit in removing under such challenging scenarios.

A CASE OF DOCK8 DEFICIENCY TREATED WITH DUPILUMAB

<h3>Introduction</h3> Dedicator of cytokinesis 8 gene (DOCK8) deficiency is an immune disorder associated with autosomal recessive hyper-IgE syndrome, characterized by elevated IgE levels, atopic dermatitis, and predisposition to recurrent skin and lung infections. <h3>Case Description</h3> A 12-year-old male presented to Immunology clinic for DOCK8 deficiency. He was diagnosed in infancy due to diffuse papulopustular eruption positive for candidiasis and known family history. Past medical history included severe eczematous dermatitis, asthma, interstitial lung disease, food allergies, and poor growth, with cutaneous HSV and fungal infections, HSV keratitis, and MRSA bacteremia. Family history was notable for two siblings with DOCK8 deficiency, both deceased. Physical exam demonstrated severe generalized eczematous papules and plaques and intermittent coarse breath sounds. IgE ranged from 22.9–14,730 kU/L. Absolute eosinophil count fluctuated between 30–10,350 cells/mcL. Sequencing of the <i>DOCK8</i> gene revealed a novel 2 base pair deletion resulting in a frame shift mutation in exon 14 at codon 510. He was managed on weekly subcutaneous immunoglobulin replacement, prophylactic Bactrim and valacyclovir, and followed by Immunology, Dermatology, Pulmonology, and Ophthalmology. Family declined bone marrow transplantation. Due to the severity of his eczematous dermatitis, monthly dupilumab injections were initiated. Within a year, he reported significant improvement in cutaneous and respiratory symptoms, with increase in lung function from FEV1 of 32% to 63%. <h3>Discussion</h3> In patients with DOCK8 deficiency, hematopoietic stem cell transplantation is curative. For patients who are unable or unwilling to undergo or awaiting transplant, dupilumab is a treatment option for improvement of both cutaneous and respiratory manifestations.

MYCOTIC PULMONARY ARTERY ANEURYSM SECONDARY TO SEPTIC EMBOLI: A POTENTIALLY LIFE-THREATENING COMPLICATION OF INFECTIVE ENDOCARDITIS

MYCOTIC PULMONARY ARTERY ANEURYSM SECONDARY TO SEPTIC EMBOLI: A POTENTIALLY LIFE-THREATENING COMPLICATION OF INFECTIVE ENDOCARDITIS

Prevalence of MRSA Bacteremia in Liver Transplant Patients: A Systematic Review and Meta-Analysis

Prevalence of MRSA Bacteremia in Liver Transplant Patients: A Systematic Review and Meta-Analysis

Transcriptome Analyses of Prophage in Mediating Persistent Methicillin-Resistant Staphylococcus aureus Endovascular Infection.

Persistent methicillin-resistant Staphylococcus aureus (MRSA) endovascular infections represent a significant subset of S. aureus infections and correlate with exceptionally high mortality. We have recently demonstrated that the lysogenization of prophage ϕSA169 from a clinical persistent MRSA bacteremia isolate (300-169) into a clinical resolving bacteremia MRSA isolate (301-188) resulted in the acquisition of well-defined in vitro and in vivo phenotypic and genotypic profiles related to persistent outcome. However, the underlying mechanism(s) of this impact is unknown. In the current study, we explored the genetic mechanism that may contribute to the ϕSA169-correlated persistence using RNA sequencing. Transcriptomic analyses revealed that the most significant impacts of ϕSA169 were: (i) the enhancement of fatty acid biosynthesis and purine and pyrimidine metabolic pathways; (ii) the repression of galactose metabolism and phosphotransferase system (PTS); and (iii) the down-regulation of the mutual prophage genes in both 300-169 and 301-188 strains. In addition, the influence of different genetic backgrounds between 300-169 and 301-188 might also be involved in the persistent outcome. These findings may provide targets for future studies on the persistence of MRSA.

Update on Staphylococcus aureus bacteraemia.

To review recently published evidence relevant to Staphylococcus aureus bacteremia (SAB). Staphylococcus aureus is the most common pathogen causing co-infections and superinfections in patients with COVID-19. Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia ratios have sharply risen during the pandemic. SAB mortality is 18% at 1 month and 27% at 3 months but has gradually decreased over the last 30 years. Recurrences and reinfections are common (9%). Standardised items to define complicated SAB, and a new cut-off defining persisting bacteremia after 2 days with positive blood cultures have been proposed. Multiple antibiotic combinations have been trialled including vancomycin or daptomycin with β-lactams, fosfomycin, or clindamycin, without significant results. In the recently published guidelines, vancomycin remains the first line of treatment for MRSA bacteremia. For the management of methicillin-susceptible Staphylococcus aureus , cefazolin less frequently causes acute kidney injury than flucloxacillin, and when susceptibility is demonstrated, de-escalation to penicillin G is suggested. Our review confirms that Staphylococcus aureus represents a special aetiology among all causes of bloodstream infections. Pending results of platform and larger trials, its distinct epidemiology and determinants mandate careful integration of clinical variables and best available evidence to optimize patient outcomes.

Current clinical practice in antibiotic treatment of Staphylococcus aureus bacteraemia: results from a survey in five European countries.

To determine clinical practice variation and identify knowledge gaps in antibiotic treatment of Staphylococcus aureus bacteraemia (SAB). A web-based survey with questions addressing antibiotic treatment of SAB was distributed through the ESGAP network among infectious disease specialists, clinical microbiologists and internists in Croatia, France, Greece, the Netherlands and the UK between July 2021 and November 2021. A total number of 1687 respondents opened the survey link, of whom 677 (40%) answered at least one question. For MSSA and MRSA bacteraemia, 98% and 94% preferred initial monotherapy, respectively. In patients with SAB and non-removable infected prosthetic material, between 80% and 90% would use rifampicin as part of the treatment. For bone and joint infections, 65%-77% of respondents would consider oral step-down therapy, but for endovascular infections only 12%-32% would. Respondents recommended widely varying treatment durations for SAB with different foci of infection. Overall, 48% stated they used 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG-PET/CT) to guide antibiotic treatment duration. Persistent bacteraemia was the only risk factor for complicated SAB that would prompt a majority to extend treatment from 2 to 4-6 weeks. This survey in five European countries shows considerable clinical practice variation between and within countries in the antibiotic management of SAB, in particular regarding oral step-down therapy, choice of oral antibiotic agents, treatment duration and use of 18F-FDG-PET/CT. Physicians use varying criteria for treatment decisions, as evidence from clinical trials is often lacking. These areas of practice variation could be used to prioritize future studies for further improvement of SAB care.

Disease burden, associated mortality and economic impact of antimicrobial resistant infections in Australia

SummaryBackgroundThe growing spread of antimicrobial resistance (AMR) is accepted as a threat to humans, animals and the environment. This threat is considered to be both country specific and global, with bacteria resistant to antibiotic treatment geographically dispersed. Despite this, we have very few Australian estimates available that use national surveillance data supplemented with measures of risk, to generate reliable and actionable measures of AMR impact. These data are essential to direct policies and programs and support equitable healthcare resource utilisation. Importantly, such data can lead to implementation of programs to improved morbidity and mortality of patients with a resistant infection.MethodsUsing data from a previous case-cohort study, we estimated the AMR-associated health and economic impact caused by five hospital-associated AMR pathogens (Enterococcus spp., E. coli, K. pneumoniae, P. aeruginosa and S. aureus) in patients with a bloodstream, urinary tract, or respiratory tract infection in Australia in 2020. We estimated disease burden based on the counterfactual scenario in which all AMR infections were replaced by no infection.We used a population-level simulation model to compute AMR-associated mortality, loss of quality-adjusted life years and costs.FindingsIn 2020, there were 1,031 AMR-associated deaths (95% uncertainty interval [UI] 294, 2,615) from the five resistant hospital-associated infections in Australia. The greatest odds of dying were from respiratory infections (ceftazidime-resistant P. aeruginosa) and bloodstream infections, both resulting in high hospital and premature death costs. MRSA bacteraemia contributed the most to hospital costs (measured as bed-days) as patients with this infection resulted in additional 12,818 (95% UI 7246, 19966) hospital bed-days and cost the hospitals an extra $24,366,741 (95%UI $13,774,548, $37,954,686) per year. However, the cost of premature death from five resistant pathogens was $438,543,052, which was by far greater than the total hospital cost ($71,988,858). We estimate a loss of 27,705 quality-adjusted life years due to the five AMR pathogens.InterpretationThese are the first Australian estimates of AMR-associated health and economic impact. Country-level estimates of AMR impact are needed to provide local evidence to better inform programs and health policies to reduce morbidity and mortality associated with infection. The burden in hospital is likely an underestimate of the impact of AMR due to community-associated infections where data are limited, and the AMR burden is high. This should now be the focus of future study in this area.FundingTMW was supported by the Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE) (grant number GNT1116530) Fellowship.

Clinical impact of and microbiological risk factors for qacA/B positivity in ICU-acquired ST5-methicillin-resistant SCCmec type II Staphylococcus aureus bacteremia

Concern about resistance to chlorhexidine has increased due to the wide use of the latter. The impact of the qacA/B and smr chlorhexidine tolerance genes on the outcome of methicillin-resistant Staphylococcus aureus (MRSA) infections is unclear. We evaluated the prevalence and clinical impact of, and microbiological risk factors for, qacA/B tolerance in MRSA bacteremia. MRSA bacteremia that occurred more than two days after intensive care unit admission between January 2009 and December 2018 was identified from a prospective cohort of S. aureus bacteremia in a tertiary-care hospital from South Korea. A total of 183 MRSA blood isolates was identified, and the major genotype found was ST5-MRSA-II (87.4%). The prevalences of qacA/B and smr were 67.2% and 3.8%, respectively. qacA/B-positive isolates were predominantly ST5-MRSA-II (96.7% [119/123]), the dominant hospital clone. In a homogenous ST5-MRSA-II background, qacA/B positivity was independently associated with septic shock (aOR, 4.85), gentamicin resistance (aOR, 74.43), and non-t002 spa type (aOR, 74.12). qacA/B positivity was found to have decreased significantly in ST5-MRSA-II in association with a decline in qacA/B-positive t2460, despite the increasing use of chlorhexidine since 2010 (P < 0.001 for trend). Continuous surveillance of the qac genes, and molecular characterization of their plasmids, are needed to understand their role in MRSA epidemiology.

Decreasing Peripheral Intravenous Catheter (PIV) Associated Methicillin-resistant Staphylococcus Aureus (MRSA) Bacteremia

<h3>Background</h3> A 210-bed community hospital experienced 13 MRSA bacteremia events from July 2017 - June 2019. Among those infections, 46.2% were associated with the use of a PIV. Review of MRSA bacteremia infections identified a lack of standardized prevention measures in patients with PIVs. <h3>Methods</h3> A multidisciplinary team was assembled consisting of Infection Prevention (IP), nursing, anesthesia, and Emergency Medical Services (EMS) to create and implement a PIV bundle. The bundle included labeling, dating, and assessing intact, clean dressings. Following bundle development, education was conducted across the hospital via skills fair with hands-on training and roving in-services to ensure 90% of affected staff were reached. IP collected pre-intervention data and bundle audit data weekly to monitor improvement. During audits, the IP performed just-in time education and feedback on bundle non-compliance. PIV-bacteremia prevention education was incorporated into orientation for new nurses. Additional education was conducted with Anesthesia and EMS providers on PIV insertion technique and infection prevention processes. <h3>Results</h3> Baseline compliance with PIV-bundle components was 13.6% and increased to 69.0% in December of 2019 when the project ended. Dressing cleanliness increased from 66.0% in the baseline period to 88.7% Current data in December 2021 indicates an overall PIV bundle compliance rate of 80.6% demonstrating sustainability in the intervention. PIV-associated MRSA bacteremia decreased from 1.04 infections/10,000 patient days to 0 infections/10,000 patient days (p = 0.008). <h3>Conclusions</h3> PIV-associated bacteremia can be a major contributor to overall MRSA bacteremia. A comprehensive PIV bundle with stakeholder engagement is an effective intervention to reduce MRSA-bacteremia. Improving PIV maintenance practices reduces MRSA bacteremia.

Persistent Methicilin-Resistant Staphylococcus aureus Bacteremia: Resetting the Clock for Optimal Management.

A positive follow-up blood culture for methicillin-resistant Staphylococcus aureus (MRSA) while on seemingly appropriate therapy is a common and ominous development. However, the definition and management of persistent MRSA bacteremia is unstandardized. In this Opinion Paper, we identify the presence of bacteremia for > 1 calendar day as a "worry point" that should trigger an intensive diagnostic evaluation to identify metastatic infection sites. Next, we define the duration of MRSA bacteremia that likely constitutes antibiotic failure and outline a potential management algorithm for such patients. Finally, we propose pragmatic clinical trial designs to test treatment strategies for persistent MRSA bacteremia.

Pediculosis As a Possible Contributor to Community-Acquired MRSA Bacteremia and Native Mitral Valve Endocarditis

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a known cause of infective endocarditis. In this case report, we describe a patient with community-acquired MRSA bacteremia and subsequent mitral valve endocarditis. This patient was noted to be without commonly recognized risk factors for MRSA bacteremia, thus her likely source was skin colonization, with skin trauma facilitated by pediculosis infestation.

PO-702-03 THE GHOSTS OF LEADS PAST: LEAD CASTS AND RECURRENT BACTEREMIA

Lead extraction can be complex and has inherent risk. Many acute complications are related to adhesions and fibrosis developing around chronic leads during removal. However, less appreciated chronic complications include those related to consequences of lead cast(s) retained following lead removal, including but not limited to distal embolization. We report a case of a lead cast identified with 3D intra-cardiac echocardiogram (ICE) after pacemaker extraction and its suspected role in persistent bacteremia. NA A 23-year-old male with repaired Tetralogy of Fallot and complete heart block status post dual chamber pacemaker presented with pacing induced cardiomyopathy. He subsequently underwent extraction of atrial and ventricular leads and implant of a left axillary CRT-D system. Unfortunately, he developed MRSA bacteremia necessitating CRT-D extraction, temporary pacing until bacteremia cleared, and subsequent temporizing leadless pacemaker implantation. During the extraction, two large masses were identified by TEE, which were consistent with fibrin casts retained from the previous atrial and coronary sinus pacing leads. Due to the extent of the retained debris and potential risk of future infection, 3D ICE-guided removal with catheter-based aspiration systems was attempted but was unsuccessful with both the Penumbra and Angiovac systems. Of note, the extent of fibrin deposition was better appreciated on intraprocedural 3D ICE compared to cardiac CT or transesophageal echocardiogram (TEE). One cast in particularly stretched from high SVC into the coronary sinus. In follow-up, bacteremia recurred without alternative source and antibiotics were re-initiated with future plan for surgical removal if required. Lead cast formation after extraction is common and generally carries a benign clinical course when casts are small and bacteremia has cleared; however, we present a case demonstrating both the utility of 3D ICE in visualizing fibrin casts and a concerning clinical course associated with large fibrin casts and development of recurrent bacteremia.

Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP) Annual Report 2020.

From 1 January to 31 December 2020, forty-nine institutions around Australia participated in the Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP). The aims of ASSOP 2020 were to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that were antimicrobial resistant, with particular emphasis on susceptibility to methicillin; and to characterise the molecular epidemiology of the methicillin-resistant isolates. A total of 2,734 SAB episodes were reported, of which 79.7% were community-onset. Of S. aureus isolates, 17.6% were methicillin resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 14.2%, which was not significantly different from the 13.3% mortality associated with methicillin-susceptible SAB (p = 0.6). 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 35% of methicillin-resistant S. aureus (MRSA) were resistant to erythromycin, 33% to ciprofloxacin, 13% to tetracycline, 13% to gentamicin and 4% to co-trimoxazole. When applying the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, teicoplanin resistance was detected in four S. aureus isolates. Resistance was not detected for vancomycin and linezolid. Resistance to non-beta-lactam antimicrobials was largely attributable to two healthcare-associated MRSA (HA-MRSA) clones: ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). The ST22-IV [2B] (EMRSA-15) clone is the predominant HA-MRSA clone in Australia. However, 85% percent of methicillin-resistant SAB isolates were community-associated MRSA (CA-MRSA) clones. Although polyclonal, approximately 77% of CA-MRSA clones were characterised as: ST93-IV [2B] (Queensland CA-MRSA); ST5-IV [2B]; ST45-V [5C2&5]; ST1-IV [2B]; ST30-IV [2B]; ST8-IV [2B]; and ST97-IV [2B]. The CA-MRSA clones, in particular ST45-V [5C2&5], have acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and tetracycline. The multi-resistant ST45-V [5C2&5] clone accounted for 11.0% of CA-MRSA. 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 sepsis.