Invasive Methicillin-resistant Staphylococcus Aureus Infections Research Articles

Impact of active surveillance and decolonization strategies for methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit.

To assess the impact of active surveillance and decolonization strategies on methicillin-resistant Staphylococcus aureus (MRSA) infection rates in a NICU. MRSA infection rates were compared before (2014-2016) and during (2017-2022) an active surveillance program. Eligible infants were decolonized with chlorohexidine gluconate (CHG) bathing and/or topical mupirocin. Successful decolonization and rates of recolonization were assessed. Fifty-two (0.57%) of 9 100 hospitalized infants had invasive MRSA infections from 2014 to 2022; infection rates declined non-significantly. During the 6-year surveillance program, the risk of infection was 16.9-times [CI95 8.4, 34.1] higher in colonized infants than uncolonized infants. Those colonized with mupirocin-susceptible MRSA were more likely successfully decolonized (aOR 9.7 [CI95 4.2, 22.5]). Of 57 infants successfully decolonized who remained hospitalized, 34 (60%) became recolonized. MRSA infection rates did not significantly decline in association with an active surveillance and decolonization program. Alternatives to mupirocin and CHG are needed to facilitate decolonization.

Methicillin-resistant Staphylococcus aureus mupirocin resistance rates in a large healthcare system

Methicillin-resistant Staphylococcus aureus (MRSA) is a common etiology of hospital-acquired infections (HAIs). One strategy to reduce HAIs due to MRSA involves a multistep decolonization process. This often involves nasal application of mupirocin 2% ointment. In our institution, when individuals meet criteria for decolonization, we recommend 5 days of treatment given twice daily. High levels of mupirocin resistance have been reported in some hospital systems, with >80% of tested isolates being resistant. To better understand our resistance levels, we selected 238 MRSA isolates from blood cultures to be tested for mupirocin resistance to correlate the presence of resistance and use of mupirocin for decolonization. We choose to assess MRSA blood isolates rather than nasal swabs given that we aim to prevent invasive MRSA infections, including blood stream infections, with decolonization. The blood cultures were collected from 11 acute-care facilities within our system from March 2021 through June 2022. High-level resistance was defined as an MIC >1,024 μg/mL according to Clinical and Laboratory Standards Institute guidelines. Of those, 7.14% showed high level resistance, and 76.47% occurred in those who were exposed to mupirocin and 23.53% occurred in those without mupirocin exposure (P = .0094). On average, those with high-level resistance had had more recent exposure to mupirocin compared to those without resistance, which was statistically significant. Also, those with high resistance, on average, received more doses of mupirocin, although this was not statistically significant. Conclusions: More recent and higher number of doses of mupirocin were associated with the development of resistance, which is consistent with what we know from pharmacodynamics of antibiotic resistance with other agents. These findings may be particularly important for those patients who have frequent hospitalizations and often require decolonization. Understanding baseline mupirocin resistance levels in an institution can assist with determining decolonization strategies.Disclosures: None

Molecular epidemiology and phenotypes of invasive methicillin-resistant vancomycin-intermediate Staphylococcus aureus in Taiwan

Patients with invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA), especially those with an elevated minimal inhibitory concentration (MIC) of vancomycin (VA), are likely to have treatment failure and poor outcomes. The aim of this study was to delineate and correlate the genotypes and phenotypes of clinical VA-intermediate S. aureus (VISA) from invasive infections in Taiwan. Between 2006 and 2010, a total of 670 non-duplicate MRSA isolates were collected from patients with invasive infections, mostly from blood, as part of a nationwide antimicrobial surveillance program named Tigecycline invitro Surveillance in Taiwan. Among them, 10 (1.5%) VISA (VA MIC=4mg/L) isolates were identified. Molecular typing with staphylococcal cassette chromosome mec (SCCmec), multilocus sequence typing, staphylococcal protein A (spa), mec-associated hypervariable region (dru), accessory gene regulator (agr), and pulse-field gel electrophoresis, and phenotypic analysis including antibiotic susceptibility testing, gene encoding Panton-Valentine leukocidin (pvl), and superantigenic toxin profiles, were analyzed. All but one isolate was defined as molecular health-care-associated MRSA: 6 as SCCmecIII-ST239-spa t037-agrI-dru7 (1 isolate) and dru14 (5 isolates), 2 as SCCmecII-ST5-spa t586-agrII-dru4, and one as SCCmecII-ST89-spa t3520-agrIII-dru7. One isolate was defined as SCCmecIV-ST59-spa t437-agrI-dru8, which was categorized as molecular community-associated MRSA. Five pulsotypes were identified; only one had a positive D-test and 3 were insusceptible to daptomycin (MIC ≧1mg/L). Five isolates possessed sea-selk-selq, among them 4 belonged to SCCmecIII-ST239-spa t037-agrI. In this study, VISA was rarely isolated from invasive MRSA infections, and most cases harbored limited genotypes and corresponding phenotypes.

Reduced Ceftaroline Susceptibility among Invasive MRSA Infections in Children: a Clinical and Genomic Investigation.

Ceftaroline represents an attractive therapy option for methicillin-resistant Staphylococcus aureus (MRSA). Little data is available, however, regarding the frequency of reduced susceptibility (RS) to ceftaroline among pediatric MRSA infections. We screened invasive MRSA isolates at a tertiary children's hospital for ceftaroline RS. Ceftaroline RS occurred in 2.9% of isolates and only among health care associated infections. Ceftaroline RS isolates were more often clindamycin-resistant. Sequencing data indicated the predominance of the CC5 lineage among ceftaroline RS isolates.

Genotyping of methicillin-resistant Staphylococcus aureus isolates causing invasive infections using spa typing and their correlation with antimicrobial susceptibility

Correlation of antimicrobial susceptibility patterns with particular spa types could help physicians select appropriate antibiotics for the treatment of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections. The aim of this study was to investigate invasive MRSA isolates through delineating the molecular typing results and correlating them with antibiotic susceptibility testing results. A total of 670 non-duplicate mecA-positive MRSA isolates from patients with invasive infections were collected from a 5-year nationwide antimicrobial surveillance programme [Tigecycline In vitro Surveillance in Taiwan (TIST)] and 58 spa types were identified among 639 isolates (95.4%) by determining the allelic profile of the spa gene using PCR and nucleotide sequencing. Six major spa types, including spa t002 (n=103; 15.4%) and t037 (n=253, 37.8%), were classified as healthcare-associated MRSA (HA-MRSA; 53.1%), while t437 (n=151; 22.5%), t441 (n=13; 1.9%), t1081 (n=19; 2.8%) and t3525 (n=14; 2.1%) were classified as community-associated MRSA (CA-MRSA; 29.4%). Antimicrobial susceptibility was determined by agar dilution or broth microdilution for various antibiotics, and Etest was also used both for daptomycin and vancomycin. The declining trend in vancomycin minimum inhibitory concentration (MIC) was in parallel with an increasing frequency of CA-MRSA. Antibiotic susceptibility patterns were correlated with particular spa types and this correlation could help physicians select appropriate antibiotics for the treatment of invasive MRSA infections.

Oxazolidinone-containing Hybrids with Antibacterial Activity against Methicillin-resistant Staphylococcus aureus (MRSA): A Mini-review.

The increasing danger of methicillin-resistant Staphylococcus aureus (MRSA) and the limited therapeutic options for invasive MRSA infections make an urgent demand for the development of novel anti-MRSA agents. Oxazolidinone derivatives could inhibit protein synthesis by acting on the ribosomal 50S subunit of the bacteria and prevent the formation of a functional 70S initiation complex, so oxazolidinones are a novel class of antimicrobial agents with potential activity against a wide range of clinically significant multidrug-resistant Gram-positive pathogens. However, oxazolidinones such as linezolid are associated with significant adverse events, and myelosuppression represents the main unfavorable side effects. Moreover, MRSA isolates that are resistant to oxazolidinones have already emerged. Hybridization of oxazolidinone with other antibacterial pharmacophores has the potential to interact with multiple targets or to counterbalance the known side effects associated with each pharmacophore. Thus, oxazolidinone-containing hybrids are useful scaffolds for the development of novel anti-MRSA agents. This review covers the recent advances of oxazolidinonecontaining hybrids with anti-MRSA activity developed in the last decade to set up the direction for the design and development of oxazolidinone-containing hybrids with high efficiency and low toxicity.

In Vitro Cytotoxicity and Clinical Correlates of MRSA Bacteremia.

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections are associated with significant morbidity and mortality. MRSA secretes a number of virulence factors and pore-forming toxins that enable tissue invasion. Prior studies have found associations between decreased toxin production and poor outcomes in invasive MRSA infection, particularly in pneumonia. In this retrospective observational cohort study of MRSA bacteremia in adult patients from 2007 to 2015, we examined whether cytotoxicity was associated with 30-day mortality. Isolates were obtained from 776 patients and screened for cytotoxicity in a human HL-60 cell model, antimicrobial susceptibility, and spa type, and clinical data were abstracted from charts. We did not find an association between low cytotoxic activity and 30-day mortality in univariate logistic regression analyses. There was a difference in distribution of the genotypes across cytotoxicity phenotypes, with spa-CC008 accounting for a larger proportion of isolates in the high cytotoxicity group. Isolates with a skin and soft tissue primary infective site had a higher median cytotoxicity. There was no association between cytotoxicity and host factors such as age or comorbidity burden. The isolates in our study came from heterogeneous primary sites of infection and were predominantly from spa-CC002 and spa-CC008 lineages, so it is possible that findings in prior studies reflect a different distribution in genotypes and clinical syndromes. Overall, in this large study of cytotoxicity of MRSA bloodstream isolates, we did not find the low cytotoxicity phenotype to be predictive of poor outcomes in MRSA bacteremia.

Continuous medical education activities; Answers to Case No. 5: Infection control for MRSA transmission

Methicillin-resistant Staphylococcus aureus (MRSA) is still recognized as one of the most important nosocomial pathogens. These isolates are usually resistant to all currently available β-lactam antibiotics (penicillins, cephalosporins and carbapenems). Vancomycin has historically been the drug of choice and sometimes the last resort for the treatment of serious MRSA infections, providing empirical coverage and definitive therapy. However, its increased use has now become questionable. Moreover, its increased use has already led to emergence of vancomycin-intermediate S. aureus (VISA) as well as vancomycin-resistant S. aureus (VRSA) in certain parts of the world. In the early 1990s, MRSA was reported to account for 20 – 25 % of S. aureus isolates in hospitalized, worldwide. By the middle of the current decade, many hospitals experienced MRSA percentages in the range of 50-70% of total S. aureus isolates from clinical cultures. Recent studies have found that an increasing proportion of hospital-onset invasive MRSA infections are caused by community strains. The clinical scenario has been more dramatic by MRSA colonization which increases the risk of infection, and infecting strains match colonizing strains in as many as 50–80% of cases. Methicillin-resistant Staphylococcus aureus may persist within the hospital environment for a long time, complicating attempts of eradication. Besides, colonization is not static, as strains have been found to evolve and even to be replaced within the same host. Poor infection control measures as well as continues and indiscriminate use of antibiotics have resulted in this huge problem of acquisition and dissemination of MRSA.

Successful Treatment of Invasive MRSA Infections in Children Using Area Under the Vancomycin Concentration-Time Curve Divided by the Minimum Inhibitory Concentration (AUC/MIC) to Measure Vancomycin Exposure

Background: Vancomycin is the treatment of choice for invasive methicillin-resistant Staphylococcus aureus (MRSA) infections. Previous guidelines issued by the Infectious Diseases Society of America (IDSA) recommended targeting vancomycin serum trough concentrations of 15–20 mg/L; however, troughs <15 mg/L are also associated with increased odds of renal toxicity. To minimize toxicity, recently updated ASHP/IDSA/PIDS vancomycin dosing guidelines recommend the use of an area under the vancomycin concentration-time curve divided by the minimum inhibitory concentration (AUC/MIC) pharmacodynamic index to measure vancomycin exposure, with an AUC/MIC ratio >400 correlating with clinical efficacy. However, data on vancomycin therapeutic drug monitoring (TDM) in children are limited. Our institutional practice since January 2009 has been to use AUC/MIC, rather than serum trough concentrations, to guide vancomycin dosing. In this study, we describe clinical outcomes in vancomycin-treated children with invasive MRSA infections using this dosing method. Methods: We performed a retrospective chart review of children hospitalized with invasive MRSA infections between 2006 and 2019 at Rady Children’s Hospital in San Diego, California. Clinical, microbiologic, and pharmacologic data including the site of MRSA infection, clinical failure or cure, occurrence of acute kidney injury (AKI), vancomycin MIC, vancomycin AUC, and serum trough concentrations were collected. Results: In total, 61 invasive MRSA cases were reviewed: 20 were admitted January 2016 through December 2008, and 41 were admitted January 2009 through June 2019 (Figure 1). Most patients did not have medical comorbidities. The most common types of infections were primary bacteremia (34%) and osteomyelitis (32%). Of 61 children, 50 (82%) had positive clinical outcomes regardless of vancomycin dosing method. Of 20 patients, 8 (40%) admitted prior to January 2009 developed AKI, compared with 5 (12%) of 41 patients admitted after January 2009. Conclusions: In our retrospective review, most patients had clinically successful outcomes regardless of which dosing strategy was used. We found higher rates of renal toxicity in patients who were admitted prior to 2009, with TDM based on measuring peak and trough concentrations, compared with those using AUC/MIC for TDM. Our findings suggest that AUC/MIC TDM for invasive MRSA infections may be associated with lower rates of renal toxicity.Funding: NoDisclosures: None

Hochuekkito can Prevent the Colonization of Methicillin-Resistant Staphylococcus aureus in Upper Respiratory Tract of Acute Stroke Patients.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) colonization can lead to MRSA pneumonia or other infections in compromised hosts, and invasive MRSA infections lead to significant morbidity and mortality. The present observational study elucidated whether administration of hochuekkito (HET) can prevent MRSA colonization in the upper respiratory tract and support recovery in acute stroke patients. Methods: In this retrospective, observational study, 73 acute stroke patients admitted to Kenwakai Hospital between April 2007 and December 2019 who did not require emergency surgery during this period were enrolled. Conventional treatment was provided to all patients, depending on their condition, and 7.5 g/day of HET was administered to the patients who could take the medicine via nasogastric tube or orally in three divided doses for three months. Bacterial cultures from laryngeal swabs and sputum were evaluated every week. We evaluated the presence of MRSA infection or another infectious disease within 30 days of admission; modified Rankin Scale scores, which assesses the independent living skills after stroke at three months after admission; and blood biomarkers (white blood cell count, albumin levels, C-reactive protein levels, and hemoglobin levels). Results: In total, 73 patients (HET group, n = 41; non-HET group, n = 32) were enrolled in the study. MRSA detection was significantly less likely in the HET group than in the non-HET group (p = 0.0497). The incidence of infectious diseases was significantly lower in the HET group than in the non-HET group (p = 0.0096), and the modified Rankin Scale score at three months was also significantly lower in the HET group than in the non-HET group (p = 0.033). The white blood cell count, and serum C-reactive protein levels did not differ between those who were treated with HET and those who were not. However, serum albumin and hemoglobin levels improved slightly between month one and month three after admission only in those who were treated with HET. Conclusion: Our results indicate that the administration of HET may contribute to the prevention of MRSA colonization and promote rehabilitation in stroke patients.

Reduced Daptomycin Susceptibility in Clinical MRSA Isolates Showing Vancomycin MIC Creep Phenomenon

Introduction: Infections caused by Methicillin Resistant Staphylococcus aureus (MRSA) are associated with increased morbidity, longer antimicrobial therapy, etc. First option for treating invasive MRSA infections is glycopeptide vancomycin. Daptomycin, a lipopeptide rapidly bactericidal invitro against MRSA, is an acceptable alternative. Aim: To identify MRSA isolates from clinical specimens and assess their vancomycin and daptomycin susceptibility pattern. Materials and Methods: The cross-sectional study was conducted over a period of six months (January 2019 to June 2019) on 90 clinical samples in a rural teaching hospital in Pune, Maharashtra, India, including all samples except sputum received in the Microbiology laboratory. MRSA isolates were tested for vancomycin and daptomycin susceptibility by Epsilometer (E) test Minimum Inhibitory Concentration (MIC) method. Results: Among 90 MRSA isolates, most were from pus (51) followed by Urine (23), Blood (9), followed by Miscellaneous samples (7). Data analysis was done using Statistical Package for the Social Sciences (SPSS) version 16.0 software. All MRSA isolates in this study were susceptible to daptomycin with MIC in the range of 0.25-1 μg/mL with maximum isolates (39) with MIC of 0.38 μg/mL. Vancomycin MIC creep phenomenon was observed in 68 isolates. All these isolates also showed reduced susceptibility to daptomycin. Conclusion: MRSA in hospital set up mandates strict infection control practices in place. Daptomycin can be a good therapeutic alternative to treat infections caused by MRSA keeping in mind its therapeutic limitations and prior vancomycin usage in the same patient. Empirical therapy should always be based on antibiogram pattern. Adherence to hospital antibiotic policy and constant surveillance of antimicrobial resistance is the need of the hour.

1367. Reduced Ceftaroline Susceptibility Among Invasive MRSA Isolates at a Tertiary Children’s HospitalReduced Ceftaroline Susceptibility Among Invasive MRSA Isolates at a Tertiary Children’s Hospital

BackgroundThe emergence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) in the late 1990s-early 2000s complicated the empiric management of suspected staphylococcal infection in children. Rising clindamycin resistance rates in many communities adds further to management challenges. Ceftaroline, an anti-MRSA cephalosporin, represents an attractive therapy option. Little data are available, however, regarding the frequency of reduced susceptibility (RS) to ceftaroline among MRSA isolates from a general pediatric population.MethodsIsolates were selected from an ongoing S. aureus surveillance study at Texas Children’s Hospital. Invasive MRSA isolates from 2015-2018 were included. Isolates were initially screened for ceftaroline RS with E-test; all isolates with a ceftaroline E-test MIC ≥ 1.5µg/ml underwent ceftaroline broth dilution. Ceftaroline RS was regarded as an MIC ≥ 2 µg/ml; full ceftaroline resistance was defined as an MIC ≥ 8 μg/ml. Accessory gene regulator (agr) groups were characterized by PCR.Results201 viable isolates were included. The ceftaroline MIC50 and MIC90 were 0.5 and 1 µg/ml, respectively (Figure 1). Six isolates had MIC ≥ 2 µg/ml (2.9%) with two having MIC ≥ 8 µg/ml (0.9%). All ceftaroline RS isolates were from healthcare associated infections. Ceftaroline RS isolates were more often associated with clindamycin-resistance and agr group II (Figure 2). Infections with ceftaroline RS were associated with central venous lines, recent ICU admission, preceding antibiotic exposure (specifically cephalosporins) and prior MRSA infection. One subject with MRSA CLABSI had a ceftaroline susceptible MRSA infection followed < 1 month later by a ceftaroline resistant infection (MIC =32 μg/ml); the isolates were identical by PFGE. Only 3 subjects had previously received ceftaroline, none of which subsequently developed a ceftaroline RS isolate.Figure 1. Ceftaroline MIC Distribution Figure 2. Clinical And Microbiologic Associations with Reduced Ceftaroline Susceptibility ConclusionCeftaroline RS occurs in 2.9% of invasive MRSA isolates in children and is most prominent among healthcare-associated infections. These isolates were associated with clindamycin resistance and agr group II. While ceftaroline RS is rare among invasive MRSA infections, the lack of preceding ceftaroline exposure is concerning and warrants careful surveillance.Disclosures Sheldon L. Kaplan, MD, Allergan (Research Grant or Support)Pfizer (Grant/Research Support) Jonathon C. McNeil, MD, Allergan (Research Grant or Support, Allergan provided ceftaroline powder for use in studies described in this abstract)

The Evolving Reduction of Vancomycin and Daptomycin Susceptibility in MRSA-Salvaging the Gold Standards with Combination Therapy.

Methicillin-resistant Staphylococcus aureus (MRSA) is associated with substantial morbidity and mortality. Vancomycin (VAN) has been used as the gold standard treatment for invasive MRSA infections for decades but, unfortunately, the reliance of VAN as the primary treatment option against these infections has led to a reduction in VAN susceptibility in MRSA isolates. Although daptomycin (DAP) is another common treatment option against invasive MRSA infections, it has been shown that the development of VAN resistance can lead to DAP nonsusceptibility. VAN or DAP backbone regimens in combination with other antibiotics has been advocated as an alternative approach to improve patient outcomes in VAN/DAP-susceptible infections, enhance outcomes in infections caused by isolates with reduced VAN/DAP susceptibility, and/or prevent the emergence of VAN/DAP resistance or further resistance. A peer-reviewed literature search was conducted using Medline, Google Scholar and PubMed databases. The primary purpose of this review is to describe the mechanisms and epidemiology of MRSA isolates with a reduction in VAN and/or DAP susceptibility, evaluate in vitro and in vivo literature describing combination therapy (CT) against MRSA isolates with reduced VAN and/or DAP susceptibility and describe studies involving the clinical outcomes of patients treated with CT against invasive MRSA infections.

Vancomycin MIC and agr dysfunction in invasive MRSA infections in southern Brazil.

In methicillin-resistant Staphylococcus aureus (MRSA) treatment, the vancomycin minimum inhibitory concentration (MIC) increase, vancomycin heteroresistance (hVISA) presence, and accessory gene regulator (agr) dysfunction are predictors of vancomycin therapy failure. This study evaluated the association between vancomycin MIC (≥ 1.0μg/mL) and agr dysfunction in invasive MRSA isolates. Vancomycin MIC, hVISA phenotype, agr group, and function were determined in 171 MRSA isolates obtained between 2014 and 2019 from hospitals in Porto Alegre, Brazil. All MRSA were susceptible to vancomycin; 16.4% of these had MIC ≥ 1.0μg/mL. Seventeen MRSA isolates expressed the hVISA phenotype; 35.3% of them had MIC of 1.5μg/mL. agr groups I (40.9%) and II (47.1%) were the most found groups for MRSA and hVISA isolates, respectively. The proportion of MRSA with vancomycin MIC ≥ 1.0μg/mL in agr group II was significantly higher than in agr groups I and III (p = 0.002). agr dysfunction was observed in 4.7% (8/171) of MRSA, especially those with vancomycin MIC ≥ 1.0μg/mL (p < 0.001). In addition, six isolates (35.3%; 6/17) with hVISA phenotype presented agr dysfunction, which was significantly higher than that in non-hVISA phenotype (p < 0.001). In conclusion, agr dysfunction in MRSA is associated with vancomycin MIC ≥ 1.0μg/mL and hVISA phenotype, which suggests that agr dysfunction might confer potential advantages on MRSA to survive in invasive infections.

Antimicrobial Nonsusceptibility Among Invasive MRSA USA300 Strains by Healthcare Exposure, Three Sites, 2005–2016

Background: Incidence of community-associated (CA) and healthcare-associated, community-onset (HACO) USA300 methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections has remained unchanged in recent years. Traditionally considered a CA strain, USA300 is increasingly associated with healthcare settings. We examined whether antimicrobial nonsusceptibility among USA300 strains could distinguish epidemiologic class (community vs hospital), and whether divergences in susceptibility were occurring over time. Methods: We used data on invasive MRSA infections from active, population, and laboratory-based surveillance during 2005–2016 from 11 counties in 3 states. Invasive cases were defined as MRSA isolation from a normally sterile site in a surveillance area resident. Cases were considered hospital-onset (HO) if the culture was obtained &gt;3 days after hospitalization and HACO if ≥1 of the following risk factors was present: hospitalization, surgery, dialysis, or residence in a long-term care facility in the past year; or central vascular catheter ≤2 days before culture. Otherwise, cases were considered CA. Sites submitted a convenience sample of clinical MRSA isolates for molecular typing and antimicrobial susceptibility testing. Molecular typing was performed by pulsed-field gel electrophoresis until 2008, when typing was inferred using a validated algorithm based on molecular characteristics. Reference broth microdilution was performed for 8 antimicrobials and interpreted based on CLSI interpretive criteria. We compared USA300 nonsusceptibility for HO and CA isolates. For antimicrobials with &gt;5% nonsusceptibility and for which HO isolates had greater nonsusceptibility than CA isolates, we compared nonsusceptibility for HACO and CA and analyzed annual trends in nonsusceptibility within each epidemiologic class (ie, CA, HACO, and HO) using linear regression. Results: Of 17,947 MRSA cases during 2005–2016, isolates were available for 6,685 (37%), and 2,120 were USA300 (34% CA, 52% HACO, 14% HO). HO isolates had more nonsusceptibility than CA isolates to gentamicin (2.2% vs 0.6%; P = .03), levofloxacin (47.8% vs 39.7%; P = .02), rifampin (3.7 vs 1.1%; P = .01), and trimethoprim-sulfamethoxazole (3.4% vs 0.6%; P = .04). HACO isolates also had more nonsusceptibility than CA isolates to levofloxacin (50.9% vs 39.7%; P &lt; .01). Levofloxacin nonsusceptibility increased during 2005–2016 for HACO and CA isolates (P &lt; .01), but not among HO isolates (P = .36) (Fig. 1). Conclusions: Overall, nonsusceptibility across drugs cannot distinguish USA300 isolates causing HO versus CA disease. Although HO isolates had higher levofloxacin nonsusceptibility than CA and HACO isolates early on, USA300 MRSA HACO isolates now have levofloxacin nonsusceptibility most similar to that of HO isolates. Further study could help to explore whether increases in fluoroquinolone nonsusceptibility among CA and HACO cases may be contributing to the persistence of USA300 strains.Disclosures: NoneFunding: None

Methicillin-Resistant Staphylococcus aureus Prevalence Among Healthcare Workers in Contact Tracings in a Dutch Hospital

Background: In The Netherlands, the national guidelines on Methicillin-Resistant Staphylococcus aureus (MRSA) prevention and control advocate screening of healthcare workers (HCWs) after unprotected exposure to MRSA carriers. Although this strategy is largely successful, contact tracing of staff is a time-consuming and costly component. We evaluated our contact tracing policy for HCWs over the years 2010–2018. Methods: A retrospective, observational study was performed in a Dutch teaching hospital. All HCWs who had unprotected contact with an MRSA carrier were included in contact tracing. When there had been a long period of unprotected admission prior to an MRSA finding, or when the index case was an HCW, the entire (nursing) team was tested. All samples of HCWs who were tested for MRSA carriage as part of contact tracing from 2010 until 2018 were included. A pooled nose, throat, and perineum swab was collected using the eSwab medium (Copan) and inoculated on chromID MRSA agar plates (bioMérieux) after enrichment in a broth. Molecular typing was performed using multiple-locus variable number of tandem repeat analysis (MLVA). Results: In total, we included 8,849 samples (range, 677–1,448 samples per year) from 287 contact tracings (range, 26–55 contact tracings per year). Overall, 32 HCWs were colonized with MRSA (0.36%; 95% CI, 0.26%–0.51%). None of them developed a clinical infection. Moreover, 8 HCWs (0.10%; 95% CI, 0.05%–0.19%) were colonized with the same MLVA type as the index case and were detected in 6 of 287 contact tracings (2%). In 4 of 8 of these cases, a positive HCW was the index for undertaking contact tracing. In 3 of 8 cases, it was clear that the HCW who was identified in the contact tracing was the source of the outbreak and was the cause of invasive MRSA infections in patients. Notably, a different MLVA type as the index case was found in 24 HCWs (0.27%; 95% CI, 0.18%–0.40%) of whom 7 of 24 HCWs (29.2%) were intermittent carriers. Conclusions: This study revealed a sustained low MRSA prevalence among samples in contact tracing of HCWs over 9 years. Furthermore, it shows that when MRSA contact tracing is performed according to the national guideline, only 1 of 1,000 samples results in a secondary case. This is similar to the population carriage rate of MRSA in The Netherlands. More frequently, an unrelated strain is found. These findings raise questions regarding the efficacy of the current strategy to perform contact tracing after unprotected exposure.Funding: NoneDisclosures: None

Factors Associated with Development of Invasive MRSA Infection in the Neonatal Intensive Care Unit

Purpose Critically ill infants in the neonatal intensive care unit (NICU) are particularly susceptible to methicillin-resistant Staphylococcus aureus (MRSA) colonization secondary to horizontal transmission from colonized family members, healthcare workers, or presence of MRSA on hospital surfaces. MRSA colonization poses risk for subsequent infection, and thus, infants in the NICU are at increased risk of invasive MRSA infection. Methods We conducted a retrospective cohort study of patients admitted to the St. Louis Children’s Hospital (SLCH) NICU from 2009-2017 who were …

Structure-based discovery of a small-molecule inhibitor of methicillin-resistant Staphylococcus aureus virulence

The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton-Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric, and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections.

MRSA colonisation rates on a neonatal and paediatric intensive care unit.

Methicillin-resistant Staphylococcus aureus (MRSA) colonisation is a challenge in healthcare institutions worldwide. In this retrospective nation-wide study, the rates of MRSA colonisation and infection from 2012 to 2015, on the only neonatal and paediatric intensive care unit (NPICU) in the country, were determined. Mean local rates were compared to rates of MRSA colonisation reported in units in North America, Asia and Europe between 2001 and 2010. The average rate of MRSA colonisation on admission to NPICU from 2012 to 2015 was 3.71% (95% confidence interval [CI] 2.17-5.25), while the mean rate of acquired colonisation was 14.60% (95% CI 6.16-23.04). Both were significantly higher than in units abroad: 1.9% and 4.1%, respectively (P = 0.04 and P < 0.001). There were no cases of invasive MRSA infection, while the mean rate of non-invasive infection was 0.77% (95% CI 0.54-1.01). Improved adherence to infection control measures and newer molecular diagnostic techniques are needed to further decrease the acquisition of MRSA.

469. Contributions of Infections among Persons Who Inject Drugs to the Changing Incidence of Healthcare-Associated, Community-Onset Methicillin-Resistant Staphylococcus aureus Infections, 2009–2017

BackgroundRecently, overall reductions for invasive MRSA infections (isolation from a normally sterile site) have slowed. Healthcare-associated community-onset (HACO) invasive methicillin-resistant Staphylococcus aureus (MRSA) infections are those with recent healthcare exposures who develop MRSA infection outside acute care hospitals, and account for most invasive MRSA infections. HACO incidence decreased 6.6% per year during 2005–2008; the contribution of persons who inject drugs (PWID) to HACO incidence has not been reported.MethodsWe identified invasive MRSA infections using active, population- and laboratory-based surveillance data during 2009–2017 from 25 counties in 7 sites (CA, CT, GA, MD, MN, NY, TN). Cases were HACO if culture was obtained from an outpatient, or ≤3 days after hospitalization in a patient with ≥1 of the following healthcare exposures (HEs): hospitalization, surgery, dialysis, or residence in a long-term care facility (LTCF) in the past year; or central vascular catheter ≤2 days before culture. We calculated incidence (per census population) overall, for PWID cases and others, and for cases associated with each HE. For each HE, we calculated the proportion of overall incidence increase for PWID and others.ResultsHACO MRSA incidence declined overall from 2009 to 2016 but increased from 2016 to 2017 overall (8%), for both PWID (63%) and others (5%) (figure). For both PWID and non-PWID, incidence from 2016 to 2017 increased by 0.5 cases/100,000 population; 91% of the increase in PWID occurred in cases with a past year hospitalization while 78% of the increase in cases not associated with injection drug use (IDU) occurred in cases with past year LTCF residence. Past year LTCF residence was less common among PWID (16%) then among other cases (38%, P < 0.01).ConclusionAfter years of declines, HACO MRSA incidence increased equally in 2017 for cases associated with IDU and in cases unrelated to IDU. Increases in PWID-associated cases account for half the overall increase, indicating that efforts to reduce HACO MRSA should address PWID risk factors as these infections may be due to self-injection. In addition, increases not related to PWID, if sustained, would be a reversal of historic trends and require further investigation into causes. Disclosures All authors: No reported disclosures.