Methicillin-resistant Staphylococcus Aureus Bloodstream Infections Research Articles

Spermidine Associated with Gut Microbiota Protects Against MRSA Bloodstream Infection by Promoting Macrophage M2 Polarization.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major human pathogen that causes various diseases. Extensive researches highlight the significant role of gut microbiota and its metabolites, particularly spermidine, in infectious diseases. However, the immunomodulatory mechanisms of spermidine in MRSA-induced bloodstream infection remain unclear. Here, we confirmed the protective effects of spermidine in bloodstream infection in mice. Spermidine reduced the bacterial load and expression of inflammatory factors by shifting the macrophage phenotype to an anti-inflammatory phenotype, ultimately prolonging the survival of the infected mice. The protective effect against MRSA infection may rely on the elevated expression of protein tyrosine phosphatase nonreceptor 2 (PTPN2). Collectively, these findings confirm the immunoprotective effects of spermidine via binding to PTPN2 in MRSA bloodstream infection, providing new ideas for the treatment of related infectious diseases.

Unraveling novel mutation patterns and morphological variations in two dalbavancin-resistant MRSA strains in Austria using whole genome sequencing and transmission electron microscopy

BackgroundThe increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) strains resistant to non-beta-lactam antimicrobials poses a significant challenge in treating severe MRSA bloodstream infections. This study explores resistance development and mechanisms in MRSA isolates, especially after the first dalbavancin-resistant MRSA strain in our hospital in 2016.MethodsThis study investigated 55 MRSA bloodstream isolates (02/2015–02/2021) from the University Hospital of the Medical University of Vienna, Austria. The MICs of dalbavancin, linezolid, and daptomycin were assessed. Two isolates (16–33 and 19–362) resistant to dalbavancin were analyzed via whole-genome sequencing, with morphology evaluated using transmission electron microscopy (TEM).ResultsS.aureus BSI strain 19–362 had two novel missense mutations (p.I515M and p.A606D) in the pbp2 gene. Isolate 16–33 had a 534 bp deletion in the DHH domain of GdpP and a SNV in pbp2 (p.G146R). Both strains had mutations in the rpoB gene, but at different positions. TEM revealed significantly thicker cell walls in 16–33 (p < 0.05) compared to 19–362 and dalbavancin-susceptible strains. None of the MRSA isolates showed resistance to linezolid or daptomycin.ConclusionIn light of increasing vancomycin resistance reports, continuous surveillance is essential to comprehend the molecular mechanisms of resistance in alternative MRSA treatment options. In this work, two novel missense mutations (p.I515M and p.A606D) in the pbp2 gene were newly identified as possible causes of dalbavancin resistance.

Case validation of bloodstream infections with an antibiotic-resistant organism

Background: Bloodstream infections (BSIs) are an important cause of morbidity and mortality in severely ill patients, contributing to increased length of hospital stay and higher cost of care. Alberta Health Services Infection Prevention and Control (IPC) conducts inpatient surveillance of new episodes of BSIs with methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) or carbapenemase-producing organisms (CPO) in 112 acute care facilities. A case-finding process was undertaken to verify the accuracy of BSI data entry. Methods: All positive MRSA, VRE or CPO blood cultures in 2021 were linked to the Inpatient Discharge Abstract Database (DAD) and the National Ambulatory Care Reporting System (NACRS) to identify new cases during acute care admissions. The results were then compared to surveillance records captured by infection control professionals (ICPs). Cases with unmatched culture date and/or encounter date and cases not identified by ICPs were screened by the study team with final decision made by ICPs. Results were analyzed by ARO and by % increase in number of surveillance records. Results: The laboratory linkage identified 286 new cases. Comparing to surveillance records (n = 248) captured by ICPs, 137 (57.3%) had matching collection dates and encounter dates, 85 (35.6%) had close matches on collection dates and encounter dates, 17 (7.1%) records had either matching collection dates or encounter dates, and 1 (0.4%) record did not have any matches on dates. There were 46 records identified in the laboratory data that were not in the surveillance system and 8 records that were in the surveillance system but not matched to the laboratory data. After review, 22 Surveillance records had data entry errors (1 CPO BSI, 20 MRSA BSI, and 1 VRE BSI), and there were 14 BSI records found to be missing (13 MRSA BSI, 1 VRE BSI). This represents a 6% increase in MRSA BSI and a 3% increase in VRE BSI identified in 2021 and no increase in CPO BSI. Conclusions: A laboratory validation to determine if BSIs with an ARO were missed during routine IPC surveillance identified a small proportion of missed bloodstream infections. The most common reason for the miss was admission through the emergency department with multiple blood cultures collected during a single admission. These results will be shared with the Infection Control program to facilitate correct BSI capture.

Healthcare-associated infections and antimicrobial resistance in Canadian acute care hospitals, 2018-2022.

Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) continue to contribute to excess morbidity and mortality among Canadians. This report describes epidemiologic and laboratory characteristics and trends of HAIs and AMR from 2018 to 2022 (Candida auris, 2012-2022) using surveillance and laboratory data submitted by hospitals to the Canadian Nosocomial Infection Surveillance Program (CNISP) and by provincial and territorial laboratories to the National Microbiology Laboratory. Data collected from 88 Canadian sentinel acute care hospitals between January 1, 2018, and December 31, 2022, for Clostridioides difficile infections (CDIs), carbapenemase-producing Enterobacterales (CPE) infections, methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) and vancomycin-resistant Enterococcus (VRE) BSIs. Candida auris (C. auris) surveillance was initiated in 2019 by CNISP and in 2017 (retrospectively to 2012) by the National Microbiology Laboratory. Trend analysis for case counts, rates, outcomes, molecular characterization and AMR profiles are presented. From 2018 to 2022, decreased rates per 10,000 patient days were observed for CDIs (7% decrease; 5.42-5.02) and MRSA BSIs (2.9% decrease; 1.04-1.01). Infection rates for VRE BSIs increased by 5.9% (0.34-0.36). Infection rates for CPE remained low but increased by 133% (0.06-0.14). Forty-three C. auris isolates were identified in Canada from 2012 to 2022, with the majority in Western and Central Canada (98%). From 2018 to 2022, the incidence of MRSA BSIs and CDIs decreased and VRE BSI and CPE infections increased in the Canadian acute care hospitals participating in a national sentinel network (CNISP). Few C. auris isolates were identified from 2012 to 2022. Reporting standardized surveillance data to inform the application of infection prevention and control practices in acute care hospitals is critical to help decrease the burden of HAIs and AMR in Canada.

Genomic investigation and clinical correlates of the in vitro β-lactam: NaHCO3 responsiveness phenotype among methicillin-resistant Staphylococcus aureus isolates from a randomized clinical trial.

NaHCO3 responsiveness is a novel phenotype where some methicillin-resistant Staphylococcus aureus (MRSA) isolates exhibit significantly lower minimal inhibitory concentrations (MIC) to oxacillin and/or cefazolin in the presence of NaHCO3. NaHCO3 responsiveness correlated with treatment response to β-lactams in an endocarditis animal model. We investigated whether treatment of NaHCO3-responsive strains with β-lactams was associated with faster clearance of bacteremia. The CAMERA2 trial (Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus) randomly assigned participants with MRSA bloodstream infections to standard therapy, or to standard therapy plus an anti-staphylococcal β-lactam (combination therapy). For 117 CAMERA2 MRSA isolates, we determined by broth microdilution the MIC of cefazolin and oxacillin, with and without 44 mM of NaHCO3. Isolates exhibiting ≥4-fold decrease in the MIC to cefazolin or oxacillin in the presence of NaHCO3 were considered "NaHCO3-responsive" to that agent. We compared the rate of persistent bacteremia among participants who had infections caused by NaHCO3-responsive and non-responsive strains, and that were assigned to combination treatment with a β-lactam. Thirty-one percent (36/117) and 25% (21/85) of MRSA isolates were NaHCO3-responsive to cefazolin and oxacillin, respectively. The NaHCO3-responsive phenotype was significantly associated with sequence type 93, SCCmec type IVa, and mecA alleles with substitutions in positions -7 and -38 in the regulatory region. Among participants treated with a β-lactam, there was no association between the NaHCO3-responsive phenotype and persistent bacteremia (cefazolin, P = 0.82; oxacillin, P = 0.81). In patients from a randomized clinical trial with MRSA bloodstream infection, isolates with an in vitro β-lactam-NaHCO3-responsive phenotype were associated with distinctive genetic signatures, but not with a shorter duration of bacteremia among those treated with a β-lactam.

Comparative effectiveness of daptomycin versus vancomycin among patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections: A systematic literature review and meta-analysis.

In the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs), vancomycin stands as the prevalent therapeutic agent. Daptomycin remains an alternative antibiotic to treat MRSA BSIs in cases where vancomycin proves ineffective. However, studies have conflicted on whether daptomycin is more effective than vancomycin among patients with MRSA BSI. To compare the effectiveness of daptomycin and vancomycin for the prevention of mortality among adult patients with MRSA BSI. Systematic searches of databases were performed, including Embase, PubMed, Web of Science, and Cochrane Library. The Newcastle Ottawa Scale (NOS) and Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) were used to assess the quality of individual observational and randomized control studies, respectively. Pooled odd ratios were calculated using random effects models. Twenty studies were included based on a priori set inclusion and exclusion criteria. Daptomycin treatment was associated with non-significant lower mortality odds, compared to vancomycin treatment (OR = 0.81; 95% CI, 0.62, 1.06). Sub-analyses based on the time patients were switched from another anti-MRSA treatment to daptomycin demonstrated that switching to daptomycin within 3 or 5 days was significantly associated with 55% and 45% decreased odds of all-cause mortality, respectively. However, switching to daptomycin any time after five days of treatment was not significantly associated with lower odds of mortality. Stratified analysis based on vancomycin minimum inhibitory concentration (MIC) revealed that daptomycin treatment among patients infected with MRSA strains with MIC≥1 mg/L was significantly associated with 40% lower odds of mortality compared to vancomycin treatment. Compared with vancomycin, an early switch from vancomycin to daptomycin was significantly associated with lower odds of mortality. In contrast, switching to daptomycin at any time only showed a trend towards reduced mortality, with a non-significant association. Therefore, the efficacy of early daptomycin use over vancomycin against mortality among MRSA BSIs patients may add evidence to the existing literature in support of switching to daptomycin early over remaining on vancomycin. More randomized and prospective studies are needed to assess this association.

Healthcare-associated infections and antimicrobial resistance in Canadian acute care hospitals, 2017-2021.

Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) continue to contribute to excess morbidity and mortality among Canadians. This report describes epidemiologic and laboratory characteristics and trends of HAIs and AMR from 2017 to 2021 (Candida auris 2012-2021) using surveillance and laboratory data submitted by hospitals to the Canadian Nosocomial Infection Surveillance Program (CNISP) and by provincial laboratories to the National Microbiology Laboratory (NML). Data collected from 88 Canadian sentinel acute care hospitals between January 1, 2017, and December 31, 2021, for Clostridioides difficile infections (CDI), carbapenemase-producing Enterobacterales (CPE), methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) and vancomycin-resistant Enterococcus (VRE) BSIs. Candida auris (C. auris) surveillance was initiated in 2019 by CNISP and in 2012 by the NML. Case counts, rates, outcomes, molecular characterization and antimicrobial resistance profiles are presented. From 2017 to 2021, increased rates per 10,000 patient days were observed for MRSA BSIs (35%; 0.84-1.13), VRE BSIs (43%; 0.23-0.33) and CPE infections (166%, 0.03-0.08). CDI rates decreased 11% (5.68-5.05). Thirty-one C. auris isolates were identified in Canada from 2012 to 2021, with the majority from Western Canada (68%). From 2017 to 2021, the incidence of MRSA and VRE BSIs, and CPE infections increased in Canadian acute care hospitals participating in a national sentinel network (CNISP) while CDI decreased. Few C. auris isolates were identified from 2012 to 2021. Reporting standardized surveillance data and the consistent application of infection prevention and control practises in acute care hospitals are critical to help decrease the burden of HAIs and AMR in Canada.

Epidemiology and risk factors for mortality among methicillin-resistant Staphylococcus aureus bacteremic patients in Southern Brazil.

This study aimed to evaluate the epidemiology and 30-day mortality of adult patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. We retrospectively reviewed the demographic and clinical data of adult patients with S. aureus bloodstream infections (BSI), admitted to a tertiary public teaching medical center in Porto Alegre, Southern Brazil, from January 2014 to December 2019. A total of 928 patients with S. aureus BSI were identified in the study period (68.5 per 100,000 patient-years), and the proportion of MRSA isolates was 22% (19-27%). Thus, 199 patients were included in the analyses. The median age was 62 (IQR: 51-74) years, Charlson Comorbidity Index (CCI) median was 5 (IQR: 3-6), the Pitt bacteremia score (PBS) median was 1 (IQR: 1-4), and the most common site of infection was skin and soft tissue (26%). Most infections were hospital-acquired (54%), empirical anti-MRSA treatment was initiated in 34% of the cases, and in 44% vancomycin minimum inhibitory concentration was 1.5mg/L or above. Sixty-two (31.2%) patients died up to 30 days after the bacteremia episode. Patients with more comorbid conditions (higher CCI; aOR 1.222, p = 0.006) and a more severe presentation (higher PBS; aOR 1.726, p<0.001) were independently associated with mortality. Empiric antimicrobial therapy with an anti-MRSA regimen was associated with reduced mortality (aOR 0.319, p = 0.016). Our study identified significant risk factors for 30-day mortality in patients with MRSA BSI in a population with a high incidence of S. aureus bacteremia. Empiric treatment with an anti-MRSA drug was a protective factor. No significant variation in the incidence of S. aureus BSI was recorded throughout the period.

A retrospective analysis of clinical characteristics and prognostic factors for 152 cases of Staphylococcus aureus bloodstream infection

To understand the clinical characteristics of Staphylococcus aureus bloodstream infection and the main risk factors affecting clinical prognosis, providing a reference for clinical prevention and control of Staphylococcus aureus bloodstream infection. In this study, the clinical data of 152 patients with Staphylococcus aureus bloodstream infection admitted to Guangdong Provincial People's Hospital from January 2019 to December 2021 were retrospectively analyzed by reviewing the electronic medical record system, including underlying diseases, clinical characteristics, risk factors, and bacterial resistance. Statistical methods such as Chi-Squared Test and t Test were used to analyze the related risk factors that may affect the clinical characteristics and prognosis of patients with Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection, then the variables with P<0.05 in univariate analysis were included in the multivariate logistic regression model to analyze the independent risk factors of poor prognosis. The results showed among 152 patients with Staphylococcus aureus bloodstream infection, 50 patients (32.89%) were infected with MRSA. In comparison, 102 patients (67.11%) were infected with methicillin-sensitive Staphylococcus aureus (MSSA). Except for rifampicin, the resistance rate of MRSA to commonly used antibiotics was all higher than that of MSSA, and the difference was statistically significant (Chi-square values were 8.272, 11.972, 4.998, 4.776, respectively;all P-values are less than 0.05). Strains resistant to vancomycin, linezolid, and quinupristin/dalfopristin were not found. In the MRSA group, indwelling catheter and drainage tube, carbapenems, and β-lactamase inhibitor treatment were significantly higher than the MSSA group. The difference was statistically significant (P<0.05). The incidence of poor prognosis of bloodstream infection in the MRSA group was higher than that in the MSSA group (34.00% vs 13.73%), and the difference was statistically significant (χ2=8.495, P<0.05). No independent risk factors associated with poor prognosis were found in the included patients with MRSA bloodstream infection.Multivariate Logistic regression model analysis showed that solid malignant tumors (OR=13.576, 95%CI: 3.352-54.977, P<0.05), mechanical ventilation (OR=7.468, 95%CI: 1.398-39.884, P<0.05) were the most important independent risk factors for poor prognosis in patients with Staphylococcus aureus bloodstream infection. In summary, the poor prognosis rate of MRSA bloodstream infection is higher than that of MSSA. The clinical evaluation of related risk factors should be strengthened, targeted prevention and control interventions should be taken to improve the prognosis of patients with Staphylococcus aureus bloodstream infection, and the use of antibiotics should be rational and standardized, to control bacterial infection and drug resistance effectively.

Derivation and Validation of a Risk Score for Methicillin-Resistant Staphylococcus aureus Bloodstream Infection.

Compared with methicillin sensitive Staphylococcus aureus (MSSA), the prognosis of patients with methicillin resistant Staphylococcus aureus (MRSA) bloodstream infection is poor. Therefore, the construction of MRSA and MSSA identification model has certain value for the selection of antibiotics and treatment outcome control. This study aimed to derive and validate a simple risk prediction model for MRSA bloodstream infection in Chinese patients. Three hundred and thirty-five patients with Staphylococcus aureus (S. aureus) bloodstream infection were retrospectively analyzed and divided into three groups. The first group was used for the risk score derivation (n = 163), the second group was used for internal validation (n = 80), and the third group was used for external validation (n = 92). According to the odds ratio (OR) obtained from multivariate logistic regression, the risk prediction model for MRSA bloodstream infection was established, and the prediction efficiency of the model in three cohorts were evaluated. Hospital stay before BSI ≥ 7 days, hospital acquired BSI, infection source ≥ 2 sites, indwelling gastric tube before BSI and carbapenems used before BSI and after admission were independent influencing factors of MRSA in the derivation group, the above influencing factors were scored 3, 5, 4, 3, and 3, respectively. The derivation, internal and external validation groups showed adequate discrimination (the AUCs were 0.788, 0.780, and 0.742, respectively) and good calibration (H-L tests were χ2 = 3.896, p = 0.306; χ2 = 4.221, p = 0.298; and χ2 = 3.974, p = 0.352, respectively). The risk scores were further divided into very low-risk (score 0 - 3), low-risk (score 4 - 7), high-risk (score 8 - 12), and very high-risk (score ≥ 13) layers. The simple risk score model for predicting MRSA bloodstream infection has good predictive effect, high predictive accuracy, and good clinical applicability, which can help clinicians choose sensitive antibiotics and reduce the adverse prognosis of patients.

204. Genomic comparison of blood and colonizing nasal isolates in patients hospitalized with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of health-care associated infections, particularly bloodstream infections (BSI). Concomitant colonization of the anterior nares has been shown to have implications on persistence, recurrence, and transmission events. We performed genomic comparisons between paired nasal and blood MRSA isolates obtained from the same patient to elucidate the genetic differences that may contribute to within-host invasion and virulence. Methods Patients hospitalized with MRSA bloodstream infection were swabbed in the bilateral nares. Paired blood and nasal isolates underwent DNA extraction and spa typing. Nasal and blood isolates from the same patients with matching spa types were sequenced by Illumina and PacBio respectively. For genomic analysis, PathoSPOT and Snippy were used to compare genomes of nasal and blood isolate pairs to evaluate single nucleotide polymorphisms, insertions and deletions. Results Of 121 patients with MRSA BSI, 87 patients (72%) had concomitant colonization of the anterior nares with MRSA. Spa type of t002 predominated in both blood and nasal isolates. From the 76 pairs that underwent genomic analysis, several mutated genes were identified across all pairwise comparisons, 8 of which recurred in more than one patient pair. These included genes involved in conferring antibiotic resistance, increased mutability, immune evasion, and adaptive metabolism. Conclusion In patients with MRSA BSI and concomitant MRSA nasal colonization, mutations identified by genomic analysis in blood-nasal pairs are implicated in contributing to invasion and within-host adaptability. Disclosures All Authors: No reported disclosures.

Molecular Epidemiology, Antimicrobial Susceptibility, and Clinical Features of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections over 30 Years in Barcelona, Spain (1990-2019).

Methicillin-resistant Staphylococcus aureus bloodstream infections (MRSA-BSI) are a significant cause of mortality. We analysed the evolution of the molecular and clinical epidemiology of MRSA-BSI (n = 784) in adult patients (Barcelona, 1990−2019). Isolates were tested for antimicrobial susceptibility and genotyped (PFGE), and a selection was sequenced (WGS) to characterise the pangenome and mechanisms underlying antimicrobial resistance. Increases in patient age (60 to 71 years), comorbidities (Charlson’s index > 2, 10% to 94%), community-onset healthcare-associated acquisition (9% to 60%), and 30-day mortality (28% to 36%) were observed during the 1990−1995 and 2014−2019 periods. The proportion of catheter-related BSIs fell from 57% to 20%. Current MRSA-BSIs are caused by CC5-IV and an upward trend of CC8-IV and CC22-IV clones. CC5 and CC8 had the lowest core genome proportions. Antimicrobial resistance rates fell, and only ciprofloxacin, tobramycin, and erythromycin remained high (>50%) due to GyrA/GrlA changes, the presence of aminoglycoside-modifying enzymes (AAC(6′)-Ie-APH(2″)-Ia and ANT(4′)-Ia), and mph(C)/msr(A) or erm (C) genes. Two CC22-IV strains showed daptomycin resistance (MprF substitutions). MRSA-BSI has become healthcare-associated, affecting elderly patients with comorbidities and causing high mortality rates. Clonal replacement with CC5-IV and CC8-IV clones resulted in lower antimicrobial resistance rates. The increased frequency of the successful CC22-IV, associated with daptomycin resistance, should be monitored.

Clinical characteristics of and risk factors for secondary bloodstream infection after pneumonia among patients infected with methicillin-resistant Staphylococcus aureus

PurposeTo investigate the clinical features and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia (MP) with secondary MRSA bloodstream infections (MRSA-BSI) (termed MP-BSI) compared with MP alone and to study the incidence of MP-BSI among patients with MP. MethodsThis was a retrospective, single-center study with clinical data derived from previous medical records. The cases were divided into groups: MP alone and MP-BSI. The determination of independent risk factors for MP-BSI relied on logistic regression analysis. Additionally, the crude outcomes were compared. ResultsA total of 435 patients with MP were recruited, with 18.9% (82/435) having MP-BSI. The median age was 62 (interquartile range, 51,72) years, and 74.5% of the patients were male. Multivariate analysis revealed that immunosuppression, community-acquired MP (CA-MP), time from initial to targeted antibiotic use, high Sequential Organ Failure Assessment (SOFA) score, increased respiratory rate, and elevated γ-GT level (all p < 0.05) were independent risk factors for MP-BSI, while targeted treatment with linezolid was a protective factor. Patients with MP-BSI had a longer duration of hospitalization (median days, 27.5 vs. 19, p = 0.001), a higher 28-day mortality rate (24.4% vs. 11.0%, p = 0.001), and a higher in-hospital mortality rate (26.8% vs. 14.7%, p = 0.009) than those with MP alone. ConclusionSecondary MRSA-BSI among patients with MP is not rare. Immunosuppression, CA-MP, time from initial to targeted antibiotic use, high SOFA score, increased respiratory rate and elevated γ-GT level are all independent risk factors for MP-BSI; however, linezolid, as a targeted antibiotic, is a protective factor. Moreover, patients with MP may have worse clinical outcomes when they develop MRSA-BSI.

Molecular characterization and virulence gene profiling of methicillin-resistant Staphylococcus aureus associated with bloodstream infections in southern China.

Methicillin-resistant Staphylococcus aureus (MRSA) causes an enormous illness burden, including skin and soft tissue infections (SSTIs), pneumonia, bloodstream infections (BSI), and sepsis. BSI are associated with significant patient morbidity and mortality worldwide. However, limited information is available on MRSA-related BSI in China. This study aimed to investigate the molecular characterization of 77 MRSA isolates recovered from hospitalized patients with BSI between 2012 and 2020 at three first-class tertiary hospitals in southern China based on multilocus sequence typing (MLST), spa typing, and staphylococcal cassette chromosome mec (SCCmec) typing. Overall, 13 clonal complexes (CCs) were identified, with CC59 and CC5 being the largest clusters, indicating high genetic diversity among BSI-causing MRSA isolates. ST59 was the most prevalent MLST type (22.1%). ST5/ST764-MRSA SCCmec II was the predominant adult MRSA clone, whereas ST59-MRSA SCCmec IV was the most common pediatric MRSA clone. ST5-t2460, ST764-t1084, and ST59-t437 were the most common types of adult MRSA isolates, whereas ST59-t437 and ST59-t172 were the predominant types of children's MRSA isolates. ST59-SCCmec IV/V represented the most common clone among community acquired-MRSA isolates. ST5/ST764-SCCmec II was the most common type of hospital-associated MRSA isolate. The most prevalent toxin-encoding genes detected were hla, hld, icaA, and clfA (96.1-100%). Forty-three (100%, 43/43) isolates harbored more than 18 of the tested virulence genes in adults and eight virulence genes (23.5%, 8/34) in children. Virulence gene analysis revealed diversity among different clones: the positivity rates for the Panton-Valentine leukocidin (PVL) gene were 55.8 and 35.3% in adult and pediatric MRSA isolates, respectively; the genes seb-sei were present in all adult strains; seb-seg-sei-seo were present in all ST5, ST59, ST15, ST45, and ST22 adult strains; and seg-sei-sem-sen-seo were present in different clones, including ST15, ST45, and ST22 adult MRSA isolates and ST25, ST30, ST546, and ST72 children's MRSA isolates. Adult MRSA isolates had significantly higher antibiotic resistance rates and virulence gene prevalence than pediatric MRSA isolates. For 8 years, this study provided epidemiological data on the molecular characteristics and virulence genes in different groups of MRSA BSI in China. Our findings may provide critical information for a better understanding of MRSA BSI.

Epidemiology and infection control of Methicillin-resistant Staphylococcus aureus in a German tertiary neonatal intensive and intermediate care unit: A retrospective study (2013-2020).

In preterm and term infants who require intermediate or intensive care Methicillin-resistant Staphylococcus aureus (MRSA) infection can lead to significant morbidity. In this study MRSA colonization and infection were assessed in a mixed tertiary neonatal intensive and intermediate care unit in Germany over an 8-year period (2013–2020). We investigated patient-related factors, associated with nosocomial MRSA acquisition, and we discuss our infection control concept for MRSA. Of 3488 patients treated during the study period, 24 were MRSA positive patients, corresponding to 26 patient hospital stays. The incidence was 0.7 MRSA patients per 100 patients. The incidence density was 0.4 MRSA patient hospital stays per 1000 patient days. Twelve patients (50%) acquired MRSA in the hospital. One patient developed a hospital acquired MRSA bloodstream infection 9 days after birth (i.e., 0.03% of all patients on the ward during the study period). A total of 122 patients had to be screened to detect one MRSA positive patient. In a logistic regression model, the use of 3rd generation intravenous cephalosporin (cefotaxim) was associated with nosocomial MRSA acquisition compared with matched control patients who did not acquire MRSA. In sum, the burden of MRSA colonization and infection in the ward was low during the study period. A comprehensive infection control concept that included microbiologic colonization screening, prospective infection surveillance together with isolation and emphasis on basic hygiene measures is essential to handle MRSA in this specialized setting.

Unsuspected Clonal Spread of Methicillin-Resistant Staphylococcus aureus Causing Bloodstream Infections in Hospitalized Adults Detected Using Whole Genome Sequencing.

Though detection of transmission clusters of methicillin-resistant Staphylococcus aureus (MRSA) infections is a priority for infection control personnel in hospitals, the transmission dynamics of MRSA among hospitalized patients with bloodstream infections (BSIs) has not been thoroughly studied. Whole genome sequencing (WGS) of MRSA isolates for surveillance is valuable for detecting outbreaks in hospitals, but the bioinformatic approaches used are diverse and difficult to compare. We combined short-read WGS with genotypic, phenotypic, and epidemiological characteristics of 106 MRSA BSI isolates collected for routine microbiological diagnosis from inpatients in 2 hospitals over 12 months. Clinical data and hospitalization history were abstracted from electronic medical records. We compared 3 genome sequence alignment strategies to assess similarity in cluster ascertainment. We conducted logistic regression to measure the probability of predicting prior hospital overlap between clustered patient isolates by the genetic distance of their isolates. While the 3 alignment approaches detected similar results, they showed some variation. A gene family-based alignment pipeline was most consistent across MRSA clonal complexes. We identified 9 unique clusters of closely related BSI isolates. Most BSIs were healthcare associated and community onset. Our logistic model showed that with 13 single-nucleotide polymorphisms, the likelihood that any 2 patients in a cluster had overlapped in a hospital was 50%. Multiple clusters of closely related MRSA isolates can be identified using WGS among strains cultured from BSI in 2 hospitals. Genomic clustering of these infections suggests that transmission resulted from a mix of community spread and healthcare exposures long before BSI diagnosis.

Assessment of an online calculator's vancomycin dosing and exposure appropriateness in persons who inject drugs with methicillin-resistant Staphylococcus aureus bloodstream infections.

While the gold standard for calculating AUC involves two steady-state concentrations, online calculators can empirically estimate AUC and other pharmacokinetic (PK) parameters. In patients with potentially altered PK, such as persons who inject drugs (PWID), the reliability of these predictions is unclear. Our objectives were to characterize the PK of vancomycin in PWID with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) and to assess the impact of these PK parameters on dosing regimens when compared to regimens generated by an online calculator. This descriptive pilot study included a retrospective chart review of 48 inpatient PWID with MRSA BSI from 30 April 2018 through 31 August 2020. Demographic and clinical data along with vancomycin dosing and serum concentrations were collected. Patient-specific PK parameters were used to calculate the AUC of each empiric regimen compared with the originally predicted AUC. The study population had a median volume of distribution of 0.74L/kg, clearance of 0.081L/kg/h, elimination rate constant of 0.110/h and half-life of 6.3h. The online calculator empirically predicted 6 subtherapeutic and 42 appropriate AUC values with its recommended empiric dosing regimens. Using the actual patient-specific PK parameters, the empiric vancomycin regimens actually resulted in 21 (43.75%) underexposures, 24 (50%) appropriate exposures and 3 (6.25%) overexposures. In PWID, empiric vancomycin dosing strategies suggested by an online calculator frequently resulted in lower-than-predicted vancomycin exposures. These findings suggest that PWID with MRSA BSI may require higher and/or more frequent vancomycin doses than those empirically recommended by the population-based methods of an online calculator.

Multicenter Cohort Study of Ceftaroline Versus Daptomycin for Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infection.

BackgroundObservational data suggest ceftaroline may be effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI), but comparative data with standard of care are limited. This analysis compares the outcomes of MRSA BSI treated with ceftaroline or daptomycin.MethodsMulticenter, retrospective, observational cohort study of adult patients with MRSA BSI from 2010 to 2017. Patients treated with ≥72 hours of ceftaroline or daptomycin were included. Those clearing BSI before study drug and those with a pneumonia source were excluded. The primary outcome was composite treatment failure, defined as 30-day mortality, BSI duration ≥7 days on study drug, and 60-day MRSA BSI recurrence. Inverse probability of treatment weighted risk difference in composite failure between daptomycin and ceftaroline groups was computed and 15% noninferiority margin applied.ResultsTwo hundred seventy patients were included; 83 ceftaroline and 187 daptomycin. Ceftaroline was noninferior to daptomycin with respect to composite failure (39% daptomycin, 32.5% ceftaroline; weighted risk difference, 7.0% [95% confidence interval, –5.0% to 19.0%]). No differences between treatment groups was observed for 30-day mortality or other secondary efficacy outcomes. Creatine phosphokinase elevation was significantly more common among daptomycin patients (5.3% vs 0%, P = .034). Rash was significantly more common among ceftaroline patients (10.8 vs 1.1%, P = .001).ConclusionsNo difference in treatment failure or mortality was observed between MRSA BSI treated with ceftaroline or daptomycin. These data support future study of ceftaroline as a primary MRSA BSI treatment and current use of ceftaroline when an alternative to vancomycin and daptomycin is required.

Predicting Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infection Incidence Rates using Canadian Nosocomial Infection Surveillance Program (CNISP)

Methicillin-Resistant Staphylococcus aureus (MRSA) is among the most prevalent nosocomial pathogens globally, causing significant morbidity, mortality, and healthcare costs. MRSA bloodstream infection (BSI) incidence rates in Canadian hospitals have significantly risen by almost 60% and have a mortality of over 20% upon Intensive Care Unit admission. MRSA is believed to be spread through healthcare workers; thus, high hand hygiene compliancy in addition to environmental cleaning are the cornerstone countermeasures to disrupting its transmission. The Public Health Agency of Canada (PHAC), in collaboration with the Canadian Nosocomial Infection Surveillance Program (CNISP), conducts national, sentinel surveillance on healthcare-associated infections like MRSA. As a Student Epidemiologist, I developed a research proposal detailing two study objectives: 1) develop a regression model to predict all incident MRSA BSI rates among acute-care hospitals in Canada using CNISP MRSA BSI incident cases from 2000 to 2019, and 2) create a compartmental (Susceptible-Infected-Recovered-Deceased) model to determine the impact of various Infection Prevention and Control (IPC) measures on the risk of healthcare-associated MRSA BSI transmission specifically. This study hopes to demonstrate that proper IPC compliance is associated with lower incident MRSA BSI rates with the goal being to produce a manuscript draft by 2021. MRSA poses a serious threat to patient safety globally and is becoming a growing national public health concern in Canada; determining which IPC strategy is most effective at disrupting MRSA transmission is essential to reducing incidence and mortality rates.

Pneumonia, urinary tract infection, bacteremia, and Clostridioides difficile infection following major head and neck free and pedicled flap surgeries

ObjectivesMedical postoperative infections (MPIs) are important causes of morbidity following major head and neck free and pedicled flap reconstruction, but the incidence, time of onset, and microbiology are not well characterized. Materials and methodsMedical records were reviewed of all head and neck flap surgeries performed 2009–2014 at an academic medical center. Postoperative pneumonia, urinary tract infection (UTI), bloodstream infection (BSI), Clostridioides difficile (CDI), and surgical site infections (SSI) were noted. Catheter-associated UTI (CAUTI), central line-associated BSI (CLABSI), and methicillin-resistant Staphylococcus aureus (MRSA) BSI were also evaluated. ResultsFollowing 715 free (540) or pedicled (175) flap surgeries, 14.1% of patients developed ≥one MPI including pneumonia (10.6%), UTI (2.1%), BSI (0.7%), and CDI (2.4%). Onset was ≤7 days in 77%. The MPI incidence in free vs pedicled flaps was similar. By multivariate analysis, age ≥65 and clindamycin perioperative prophylaxis were associated with increased MPI risk, clean class surgery with decreased risk. The incidence of CAUTI (<1.0%), CLABSI (0.1%), and hospital-onset MRSA BSI (0.1%) was low. SSI rate (7.8% overall) was higher in patients who developed pneumonia (18.4 vs 6.6, p = 0.004). MPI cultures grew gram-negative bacilli or S. aureus in 75%. The length of stay was longer in patients who developed a MPI than those who did not (17.4 vs 10.4 days, p < 0.0001). ConclusionsOne-seventh of major head and neck flap surgeries were complicated by MPIs, three-quarters of infections developed within 1 week postoperatively. Gram-negative bacilli and S. aureus were the predominant pathogens.