Methicillin-resistant S. Aureus Bacteremia Research Articles

Integrated transcriptomic analysis reveals immune signatures distinguishing persistent versus resolving outcomes in MRSA bacteremia

IntroductionStaphylococcus aureus bacteremia (SAB) is a life-threatening infection particularly involving methicillin-resistant S. aureus (MRSA). In contrast to resolving MRSA bacteremia (RB), persistent MRSA bacteremia (PB) blood cultures remain positive despite appropriate antibiotic treatment. Host immune responses distinguishing PB vs. RB outcomes are poorly understood. Here, integrated transcriptomic, IL-10 cytokine levels, and genomic analyses sought to identify signatures differentiating PB vs. RB outcomes.MethodsWhole-blood transcriptomes of propensity-matched PB (n=28) versus RB (n=30) patients treated with vancomycin were compared in one independent training patient cohort. Gene expression (GE) modules were analyzed and prioritized relative to host IL-10 cytokine levels and DNA methyltransferase-3A (DNMT3A) genotype.ResultsDifferential expression of T and B lymphocyte gene expression early in MRSA bacteremia discriminated RB from PB outcomes. Significant increases in effector T and B cell signaling pathways correlated with RB, lower IL-10 cytokine levels and DNMT3A heterozygous A/C genotype. Importantly, a second PB and RB patient cohort analyzed in a masked manner demonstrated high predictive accuracy of differential signatures.DiscussionCollectively, the present findings indicate that human PB involves dysregulated immunity characterized by impaired T and B cell responses associated with excessive IL-10 expression in context of the DNMT3A A/A genotype. These findings reveal distinct immunologic programs in PB vs. RB outcomes, enable future studies to define mechanisms by which host and/or pathogen drive differential signatures and may accelerate prediction of PB outcomes. Such prognostic assessment of host risk could significantly enhance early anti-infective interventions to avert PB and improve patient outcomes.

1656. Evaluation of Using Oxacillin versus Vancomycin for Empiric Therapy of Late-Onset Neonatal Sepsis in NICU

Abstract Background Our Pediatric Antimicrobial Stewardship Program (PedASP) assessed methicillin-sensitive (MSSA) and methicillin-resistant S. aureus (MRSA) infections in neonatal intensive care unit (NICU) and created a NICU-specific antibiogram. Due to a rising trend of NICU MSSA infections seen in our 84-bed NICU, empiric therapy of late-onset neonatal sepsis (LONS) was modified from vancomycin to oxacillin in January 2021. We report the two-year results of using empiric oxacillin for LONS.Figure 1.Summary of S. aureus identified in LONS cases Methods We assessed MSSA versus MRSA isolated from blood and non-blood cultures in NICU between January 2019 and December 2022. Infants with weight less than 750 grams, previous MRSA infections, maternal MRSA colonization, or serious infections based on clinical judgement were advised to use empiric vancomycin. We examined the vancomycin eligibility criteria, antibiotic-pathogen mismatch rate, 30-day mortality, and frequency of peripheral intravenous (PIV) access loss after vancomycin or oxacillin administration. The cost-savings was estimated by comparing drug and lab costs associated with vancomycin and oxacillin use. Results LONS cases are summarized in Figure 1. There was no statistical difference in incidence of S. aureus bacteremia before and after protocol implementation (p=0.45). Antibiotic-pathogen mismatch rate was 0%. Cases of MRSA bacteremia increased from 0 to 3 post protocol initiation; all cases met vancomycin eligibility criteria. The 30-day mortality among MRSA infections increased from 0 to 1 case. Post protocol implementation, the PIV loss rate decreased from 4.7 to 3.3% (p=0.04), and vancomycin use decreased by 1154 doses while oxacillin use increased by 485 doses. Based on antibiotic use and 141 vancomycin levels averted, the estimated cost-savings was $140,229. Conclusion Our PedASP utilized local susceptibility data to change empiric antibiotics for LONS, reinforcing the benefit of using antibiogram to optimize antibiotic use in NICU. Implementing a NICU-specific antibiogram improved the effectiveness of antibiotic treatment and achieved significant cost savings. Disclosures All Authors: No reported disclosures

Integrated transcriptomic analysis reveals T and B cell immune signatures influencing resolving outcome in MRSA bacteremia

Abstract Staphylococcus aureus bacteremia is a potentially lethal infection particularly when involving methicillin-resistant S. aureus (MRSA). Contrary to MRSA bacteremia that resolves on its own (RB), persistent MRSA bacteremia (PB) happens when the infection persists after receiving antibiotic therapy. Host immune responses in PB vs. RB are poorly understood. Our goal was to identify proteomic, epigenetic, and transcriptomic features associated with PB and RB clinical outcomes. We examined the whole-blood transcriptomes of propensity score matched PB (n = 28) and RB (n = 30) patients. Gene expression (GE) modules were analysed by weighted gene co-expression network analysis (WGCNA) and quantified by module eigengene analysis. Enriched pathways and protein-protein interaction networks were identified. The correlation between host DNA methlytransferase-3A (DNMT3A) genotype and serum IL-10 level was examined in the identified GE modules. Upregulation of T and B cell immune response genes early during MRSA infection discriminate RB from PB patients. T and B cell signalling pathways were significantly increased in RB patients and correlated with lower serum IL-10 levels and the DNMT3A heterozygous A/C genotype. These findings indicate that patients with DNMT3A A/A genotypes have dysregulated adaptive immune responses characterized by impaired T and B cell function that increase the risk of PB outcome. These findings suggest that combining the genotype of the host with transcriptome and proteomic profiles might help determine the outcome of MRSA bacteremia. This knowledge may result in a better understanding of S. aureus pathogenesis and development of new anti-infective therapies and vaccines to improve patient outcomes. These studies were supported by in-part by the following NIH grants U01-AI124319, R01-AI068804 and R33-AI111661(to MRY) and U01-AI124319 and U19AL128913 (to EFR).

Clinical Characteristics and Outcomes of Persistent Staphylococcal Bacteremia in a Tertiary Care Hospital

Clinical outcomes of persistent staphylococcal bacteremia vary depending on the causative organism. This secondary data analysis study compared the clinical characteristics of persistent Staphylococcus aureus (S. aureus)- and coagulase-negative staphylococci (CoNS)-caused bacteremia, focusing on the methicillin-resistant status. This study used data collected from patients who underwent blood cultures between January 2012 and December 2021 at Tohoku University Hospital, Japan. Patients with persistent staphylococcal bacteremia were divided into groups based on the pathogen and methicillin-resistant status, and their characteristics were analyzed. The primary outcomes were early (30-day), late (30-90 days), and 90-day mortality rates. The early, late, and 90-day mortality rates were similar between the persistent CoNS and S. aureus bacteremia groups. Patients with persistent methicillin-resistant S. aureus (MRSA) bacteremia tended to have higher early, late, and 90-day mortality rates than those with persistent methicillin-susceptible S. aureus bacteremia (not statistically significant). No differences were observed between the methicillin-resistant and-susceptible CoNS groups. In patients with persistent CoNS bacteremia, mortality tended to increase, especially in debilitated or immunocompromised patients with distant metastases, underscoring the importance of infection source control. Mortality tended to be high in patients with persistent MRSA bacteremia, especially when persistent bacteremia clearance was not confirmed, illustrating the need for careful therapeutic management.

EPIDEMIOLOGY, PREDISPOSING FACTORS AND OUTCOME OF STAPHYLOCOCCUS AUREUS BACTEREMIA IN NEUTROPENIC PATIENTS

Staphylococcus aureus is a common cause of bloodstream infection in neutropenic patients. We analyzed trends in incidence, epidemiology, predisposing factors and outcome of S. aureus bacteremia (SAB) in febrile neutropenic patients. We reviewed a database of febrile neutropenia at a single institution in Brazil in a 30-year period (January 1991 to December 2020). We divided in 3 periods: 1991-1994 (period 1), 2001-2010 (period 2) and 2011-2020 (period 3), and looked at incidence rates, risk factors and mortality. Risk factors and prognostic factors were evaluated by univariate (Fisher or Chi-square for categorical variables and Wilcoxon test for continuous variables) and multivariate (logistic regression) analysis. We diagnosed 62 (3%) episodes of SAB in 2,243 episodes of febrile neutropenia, 23 (38%) of which were caused by methicillin-resistant S. aureus (MRSA). The incidence of SAB per 1,000 days of neutropenia was 1.57, 2.53 and 1.50 in periods 1, 2 and 3, respectively (p > 0.05), and of MRSA was 0.49, 0.84 and 1.07, respectively (p > 0.05). Most infections (70%) were diagnosed in the first day of fever and the clinical presentation were skin infection (19%), catheter-related infection (14%) and pneumonia (3%). Complications like endocarditis or osteomyelitis were not observed. The only factor associated with S. aureus bacteremia by multivariate analysis was cellulitis at site of catheter exit site or tunnel on day 1 of fever (odds ratio [OR] 4.34, 95% confidence interval [CI] 2.05 – 9.16), whereas quinolone prophylaxis was protective (OR 0.37, 95% CI 0.18 - 0.74). The crude mortality of SAB was 30.6%, compared 13.8% in patients without this infection (p < 0.001). However, early mortality (within 3 days of start of empiric antibiotic therapy) was not significantly different (4.8% vs. 1.9%, p = 0.08). The mortality with MRSA was higher than with methicillin-susceptible S. aureus (47.8% vs. 13.9%, p < 0.001), but no difference was found regarding early mortality (5.0 vs 1.7%, p = 0.27). Among various predictors of death during febrile neutropenia MRSA bacteremia (but not methicillin-sensitive) was associated with an increased risk of death by multivariate analysis. The median time from febrile neutropenia to death in MRSA episodes was 19 days. The incidence of SAB over the period remained stable. Complication of SAB were not common. Although the crude mortality was higher with SAB (including MRSA), it was not associated with early deaths, thus not demanding anti-staphylococcal coverage in the first day of febrile neutropenia. MRSA bacteremia was associated with increased risk of death, with most deaths occurring after 2 weeks of febrile neutropenia.

Everybody nose: molecular and clinical characteristics of nasal colonization during active methicillin-resistant Staphylococcus aureus bloodstream infection

BackgroundHealthcare-associated infections pose a potentially fatal threat to patients worldwide and Staphylococcus aureus is one of the most common causes of healthcare-associated infections. S. aureus is a common commensal pathogen and a frequent cause of bacteremia, with studies demonstrating that nasal and blood isolates from single patients match more than 80% of the time. Here we report on a contemporary collection of colonizing isolates from those with methicillin-resistant S. aureus (MRSA) bloodstream infections to evaluate the diversity within hosts, and detail the clinical features associated with concomitant nasal colonization.MethodsSwabs of the bilateral anterior nares were obtained from patients diagnosed with MRSA bacteremia. A single colony culture from the blood and an average of 6 colonies from the nares were evaluated for MRSA growth. For the nares cultures, we typed multiple isolates for staphylococcal protein A (spa) and derived the clonal complexes. Demographic and clinical data were obtained retrospectively from the electronic medical record system and analysed using univariate and multivariable regression models.ResultsOver an 11-month period, 68 patients were diagnosed with MRSA bloodstream infection, 53 were swabbed, and 37 (70%) were colonized with MRSA in the anterior nares. We performed molecular typing on 213 nasal colonies. Spa types and clonal complexes found in the blood were also detected in the nares in 95% of the cases. We also found that 11% of patients carried more than one clone of MRSA in the nares. Male sex and history of prior hospitalization within the past 90 days increased odds for MRSA colonization.ConclusionThe molecular epidemiological landscape of colonization in the setting of invasive disease is diverse and defining the interplay between colonization and invasive disease is critical to combating invasive MRSA disease.

Staphylococcus aureus surface protein G (sasG) allelic variants: correlation between biofilm formation and their prevalence in methicillin-resistant S. aureus (MRSA) clones

Methicillin-resistant Staphylococcus aureus (MRSA) may persist for long periods due to biofilm formation. The objective of this study was to describe biofilm formation in association with the presence of S. aureus surface protein G (sasG) and its allelic variants in MRSA bacteraemia isolates from endemic (CC5, CC8, CC22) and sporadic clones in Spain (2008–2015). Crystal violet staining was used to assess biofilm formation; DNA microarray, RT-qPCR, and long-read whole genome sequencing were applied to determine the presence, expression and structure of sasG, respectively. The endemic CC5 and CC8 clones produced more biofilm than the sporadic clones; these endemic clones carried sasG allelic variant 1. Otherwise, sporadic clones, with less biofilm formation, showed either an absence of sasG (65%) or the presence of allelic variant 2 (35%). Variants 1 and 2 differed in the expression of sasG (1.56 ± 1.20 and 0.37 ± 0.32, respectively). The analysis of a large cohort of closed S. aureus genomes available on the NCBI database confirmed the distribution of the two allelic variants with low amino acid identity (68.1%) among endemic and sporadic clones. SasG variant 1 present in the major CC5 and CC8 clones was correlated with increased biofilm formation and may represent an important virulence determinant.

Staphylococcus Aureus Bacteremia Due to Central Venous Catheter Infection: A Clinical Comparison of Infections Caused by Methicillin-Resistant and Methicillin-Susceptible Strains.

Objectives: Staphylococcus aureus bacteremia has a mortality rate of 20-40% and is mainly caused by central venous catheter (CVC) infection. We aimed to investigate differences between patients with methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) bacteremia due to CVC infection.Methods: This retrospective study, of data collected between August 2004 and March 2016 at a single Tokyo hospital, compared the clinical background characteristics, complications, and 60-day mortality rates with positive peripheral blood cultures and positive semiquantitative cultures. MRSA carrier is defined as those with a history of MRSA detection by skin, urine, or sputum culture.Results: The median ages for the 17 MRSA and 19 MSSA patients were 72 and 55 years, respectively (P < 0.01). The occurrences of baseline disease (MRSA vs. MSSA) were 59% vs. 16% (P = 0.01), respectively, while those of complications, including septic shock, were 48% vs. 16% (P = 0.07), respectively. Catheter placement duration, time from fever onset to CVC removal, and time from fever onset to antimicrobial therapy initiation were similar in both groups. Sixty-day mortality rates were 35% and 5.3% (P = 0.04) in the MRSA and MSSA groups, respectively.Conclusion: MRSA carriers and older patients were at higher risks of CVC infection than MSSA bacteremia patients. Patients with MRSA bacteremia had higher septic shock and 60-day mortality rates despite appropriate antimicrobial therapy.

Investigation of biofilm formation in methicillin-resistant Staphylococcus aureus associated with bacteraemia in a tertiary hospital.

Biofilm formation is an important physiological process in Staphylococcus aureus (S. aureus) that can cause infections in humans. In this study, the ability of 36 methicillin-resistant S. aureus (MRSA) clinical isolates to form biofilm was studied based on genotypic and phenotypic approaches. These isolates were genotyped based on the microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) and biofilm-associated genes (icaAD) via polymerase chain reactions. Phenotyping was performed based on the determination of the strength of biofilm formation of MRSA isolates in vitro. The most prevalent MSCRAMMs and biofilm-associated genes were clfA, eno, and icaD, followed by clfB. The fnbB (38.9%) and ebpS (11.1%) occurred less frequently among the MRSA isolates, while bbp and fnbA genes were absent from all isolates. The MRSA isolates were mostly moderate to strong biofilm formers, despite the heterogeneity of the MSCRAMM profiles. MRSA isolates from different infection sources (primary, catheter-related bloodstream, or secondary infections) were capable of forming strong biofilms. However, persistent bacteraemia was observed only in 19.4% of the MRSA-infected individuals. This study suggested that persistent MRSA bacteraemia in patients might not be associated with the biofilm-forming ability of the isolates.

Methicillin-Resistant Staphylococcus aureus -Associated Diarrhea in a Critically Ill Burn Patient

Described in surgical patients after antibiotic use in the 1950s and 1960s, Staphylococcus aureus ( S. aureus ) enterocolitis is a rare form of nosocomial diarrhea. However, S. aureus is not routinely tested like Clostridium difficile ( C. difficile ). We report a case of methicillin-resistant S. aureus (MRSA) enterocolitis found on stool culture in a 22-week pregnant female with a previously negative nasal MRSA culture, and a total burn surface area greater than 60%. She also developed necrotizing MRSA pneumonia and bacteremia. After starting broad-spectrum antibiotic for the necrotizing pneumonia with subsequent acute respiratory distress syndrome, the patient exhibited large voluminous diarrhea that tested positive for MRSA and negative for C. difficile in the stool culture. Similar to other reports of high-volume diarrhea, the diarrhea resolved quickly with enteral vancomycin. S. aureus should be considered along with C. difficile during the workup of nosocomial diarrhea, especially with exposure to broad-spectrum antibiotics in the critically ill patient. J Med Cases. 2021;12(7):257-261 doi: https://doi.org/10.14740/jmc3690

Bactericidal fully human single-chain fragment variable antibodies protect mice against methicillin-resistant Staphylococcus aureus bacteraemia.

ObjectivesThe increasing prevalence of antibiotic‐resistant Staphylococcus aureus, besides the inadequate numbers of effective antibiotics, emphasises the need to find new therapeutic agents against this lethal pathogen.MethodsIn this study, to obtain antibody fragments against S. aureus, a human single‐chain fragment variable (scFv) library was enriched against living methicillin‐resistant S. aureus (MRSA) cells, grown in three different conditions, that is human peripheral blood mononuclear cells with plasma, whole blood and biofilm. The antibacterial activity of scFvs was evaluated by the growth inhibition assay in vitro. Furthermore, the therapeutic efficacy of anti‐S. aureus scFvs was appraised in a mouse model of bacteraemia.ResultsThree scFv antibodies, that is MEH63, MEH158 and MEH183, with unique sequences, were found, which exhibited significant binding to S. aureus and reduced the viability of S. aureus in in vitro inhibition assays. Based on the results, MEH63, MEH158 and MEH183, in addition to their combination, could prolong the survival rate, reduce the bacterial burden in the blood and prevent inflammation and tissue destruction in the kidneys and spleen of mice with MRSA bacteraemia compared with the vehicle group (treated with normal saline).ConclusionThe combination therapy with anti‐S. aureus scFvs and conventional antibiotics might shed light on the treatment of patients with S. aureus infections.

282. Epidemiological Evaluation of Methicillin-Resistant Staphylococcus aureus (MRSA) and Methicillin-Susceptible Staphylococcus aureus (MSSA) Bacteremia: A Comprehensive Cancer Center’s 10-Year Experience

BackgroundCoagulase-positive Staphylococcus aureus bacteremia among cancer patients carries significant morbidity and mortality. This study aims to compare the risk factors and clinical outcomes among cancer patients diagnosed with bloodstream infection (BSI) with methicillin-sensitive S. aureus (MSSA) or methicillin-resistant S. aureus (MRSA).MethodsWe performed a retrospective cohort study on all patients diagnosed with an active solid tumor or hematologic cancer with positive blood culture for S. aureus from January 2009 to May 2019. We collected data on demographics, comorbidities, malignancy type, venous access, neutropenia status, echocardiogram results, treatment (tx) duration, antibiotics usage pre/post culture, hospital LOS, infection severity, and 7-day and 30-day mortality. We used the Chi-square test to analyze categorical variables, t-test to analyze continuous variables, and the Kaplan-Meier survival curve and multivariate regression to analyze mortality.ResultsTwo hundred eighty-three cases with malignancies and S. aureus BSIs were reviewed, and 168 were identified with BSIs for MRSA or MSSA during the ten years. The mean age for MRSA cases was 73.1 (±13.7) and 70.1 (± 14.6) for MSSA; male patients were most of the sex (P < 0.01). MRSA and MSSA bacteremia presented equally in hematologic malignancies, while MSSA was observed more in skin cancer than MRSA. Cancers that obstruct GU tracts may be associated with MRSA and MSSA from urine source as both were overrepresented in patients with bladder and rectal cancer. In most patients, the CVC was promptly removed and appropriate antibiotics were given promptly within 1 hour of the positive blood culture. For patients who underwent echocardiogram, most had a negative result in both groups. There was no significant difference for seven and 30-day mortality between the two groups. The mean hospital LOS was longer for MRSA cases (10.5 ± 13.5) versus MSSA cases (4.88 ± 9.1), (P < 0.01). Figures 1 & 2. Kaplan-Meier Survival Curve Comparing 7 and 30-day Mortality of Cancer Patients with MRSA vs MSSA BSI Figure 3 & 4. Distribution of Cancer Types for MRSA (n=84) and MSSA (n=84) BSI ConclusionEndocarditis with either MRSA or MSSA BSI is not a prominent finding among cancer patients at our institution. Given the extensive usage of CVCs and devices in patients with malignancies, prompt removal and antibiotic administration are essential to reduce morbidity; even then, the LOS for MRSA BSI remains longer than MSSA BSI.Disclosures All Authors: No reported disclosures

269. Clinical Characteristics and Outcomes of Persistent Staphylococcus aureus Bacteremia

Background Staphylococcus aureus bacteremia (SAB) is a leading cause of bacteremia and persistent SAB is associated with poor outcomes. We evaluated key clinical characteristics and outcomes associated with persistent SAB.MethodsWe reviewed patients enrolled in a prospective cohort of adult patients with S. aureus bacteremia at a tertiary hospital from August 2008 to December 2018. Clinical characteristics, outcomes, and microbiologic characteristics of patients with persistent bacteremia (≥ 3 d) were evaluated.ResultsOf the total 969 patients, 617 (63.7%) patients had persistent bacteremia. The median duration of bacteremia with persistent bacteremia was 5 days. The most common sources of persistent bacteremia were central venous catheter-related infection (33.4%) and bone and joint infection (14.9%). Methicillin resistant S. aureus (MRSA) isolates were analyzed in 372 (60.3%) patients and metastatic infections were 217 (35.2%) with persistent bacteremia. In the multivariate analysis, APACHE Ⅱ score (adjusted odds ratio [aOR], 1.07; 95% confidence interval [CI], 1.03–1.10), Charlson comorbidity index score (aOR, 1.14; 95% CI, 1.04–1.25), liver cirrhosis (aOR, 2.47; 95% CI, 1.44–4.23), and S. aureus pneumonia (aOR, 3.04; 95% CI, 1.29–7.18) were independently associated with 30-d mortality. In persistent MRSA bacteremia, ST5-SCCmecⅡ was 59.7% (222/372) and agr dysfunction was 64.8% (241/372). After adjusting for confounding factors, APACHE Ⅱ score (aOR, 1.08; 95% confidence interval [CI], 1.04–1.12), liver cirrhosis (aOR, 3.09; 95% CI, 1.56–6.14), and S. aureus pneumonia (aOR, 4.37; 95% CI, 1.40–13.67) were independently associated with 30-d mortality.Table 1. Demographic and Clinical characteristics of Patients With Persistent Bacteremia Table 2. Microbiologic Characteristics and Genotypes in MRSA Isolates Responsible for Persistent Bacteremia Fig 1. Duration of Staphylococcus aureus bacteremia ConclusionIn persistent bacteremia, clinical factors, including APACHE Ⅱ score, Charlson comorbidity index score, liver cirrhosis, and S. aureus pneumonia contribute to 30-d mortality.Disclosures All Authors: No reported disclosures

Do written diagnosis-treatment recommendations on microbiological test reports improve the management of Staphylococcus aureus bacteremia? A single-center, retrospective, observational study

The objective of this study was to assess the impact of microbiological test reports that provide specific written recommendations on the appropriate management of Staphylococcus aureus bacteremia (SAB). We performed a retrospective analysis of laboratory and clinical data of all SAB patients treated at one German University hospital, 2012–2015. Among 467 included patients, methicillin-resistant S. aureus (MRSA) accounted for 15.2% of all SAB cases. All-cause in-hospital mortality was 25.2%, and was significantly elevated in individuals aged >55 years, in MRSA bacteremia and if the source of infection remained unidentified. Focus identification was achieved in 71.1%, with the most prevalent foci being catheter-associated bloodstream infection (23.1%), soft tissue infection (15.4%), osteomyelitis (5.1%) and endocarditis (4.9%). Standardized written recommendations on microbiological test reports led to a significant increase of transesophageal echocardiography, additional imaging studies for focus identification and more frequent follow-up blood cultures, but no significant effect on mortality was observed.

For MRSA Bacteremia, Two Antibiotics Weren't Better Than One

Animal models and retrospective studies in humans with methicillin-resistant S. aureus (MRSA) bacteremia suggest that adding a β-lactam to daptomycin

Higher Risk for All-cause Mortality of Staphylococcus aureus Bacteremia in Patients with Non-Dialysis Dependent Chronic Kidney Disease.

Background Staphylococcus aureus bacteremia (SAB) is a common and serious infection with a high mortality. Patients with chronic kidney disease (CKD) are vulnerable to SAB, but there have been few studies performed on the clinical characteristics and outcomes of SAB in CKD patients stratified by dialysis. We aimed to estimate the all-cause mortality and identify its predictors in patients with CKD.Materials and MethodsWe conducted a retrospective study on the patients with SAB hospitalized in a tertiary care center in Korea between March 2014 and December 2018. Kaplan-Meier analysis was performed to compare all-cause mortality following SAB among patients with non-dialysis dependent CKD (ND-CKD), those receiving dialysis, and those without CKD (non-CKD). The predictors of mortality among CKD patients were analyzed by Cox proportional hazards regression.ResultsAs a total, 278 SAB of 43 ND-CKD (31 males), 58 dialysis (39 males), and 177 non-CKD (112 males) patients were included. The 30-day mortality was 39.5% in ND-CKD, 27.6% in dialysis, and 7.9% in non-CKD patients. The hazard ratio of all-cause mortality following SAB in ND-CKD was 2.335 (95% confidence interval, 1.203 – 4.531; P = 0.003), compared to non-CKD patients. For methicillin-resistant S. aureus bacteremia (MRSAB), the hazard ratio of all-cause mortality in ND-CKD was 2.628 (95% CI, 1.074 – 6.435; P = 0.011), compared to dialysis patients. Appropriate antibiotics <48 h was independently related to improved survival following SAB among ND-CKD (adjusted HR, 0.304; 95% CI, 0,108 – 0.857; P = 0.024) and dialysis (adjusted HR, 0.323; 95% CI, 0,116 – 0.897; P = 0.030) patients.ConclusionND-CKD patients demonstrated poor outcome following SAB and administration of appropriate antibiotics within 48 h could reduce the risk for mortality.

Epidemiology of Community-Onset Staphylococcus aureus Bacteremia.

IntroductionStaphylococcus aureus bacteremia (SAB) is the second-most common cause of community-onset (CO) bacteremia. The incidence of methicillin-resistant S. aureus (MRSA) has recently decreased across much of the United States, and we seek to describe risk factors for CO-MRSA bacteremia, which will aid emergency providers in their choice of empiric antibiotics.MethodsThis is a retrospective cohort study of all patients with SAB at a 500-bed safety net hospital. The proportion of S. aureus isolates that were MRSA ranged from 32–35% during the study period. Variables of interest included age, comorbid medical conditions, microbiology results, antibiotic administration, duration of bacteremia, duration of hospital admission, suspected source of SAB, and Elixhauser comorbidity score. The primary outcome was to determine risk factors for CO-MRSA bacteremia as compared to methicillin-susceptible S. aureus (MSSA) bacteremia in patients admitted to the hospital through the emergency department.ResultsWe identified 135 consecutive patients with CO-SAB. In comparison to those with MSSA bacteremia, patients with MRSA bacteremia were younger (odds ratio [OR] 0.5, 95% confidence interval [CI], 0.4–0.7) with higher Elixhauser comorbidity scores (OR 1.4, 95% CI, 1.1–1.7). Additionally, these patients were more likely to have a history of MRSA infection or colonization (OR 8.9, 95% CI, 2.7–29.7) and intravenous drug use (OR 2.4, 95% CI, 1.0–5.7).ConclusionSAB continues to be prevalent in our urban community with CO-MRSA accounting for almost one-third of SAB cases. Previous MRSA colonization was the strongest risk factor for current MRSA infection in this cohort of patients with CO-SAB.

Clinical profile of patients with heteroresistant vancomycin- intermediate Staphylococcus aureus bacteraemia compared to those with methicillin-resistant Staphylococcus aureus bacteraemia at a level-1 trauma centre of India

Introduction: Staphylococcus aureus is the common cause of bacteraemia, skin/soft-tissue infections and pneumonia in both developed and developing countries, with many of them being caused by methicillin-resistant S. aureus (MRSA) strains. Vancomycin has been a reliable therapeutic option for MRSA infections. Vancomycin-resistant S. aureus and heterogeneous vancomycin-intermediate S. aureus (hVISA) strains have been reported to be associated with vancomycin treatment failure. The present study was performed to determine the percentage of infections due to hVISA and also to compare the clinical characteristics of patients with hVISA infections. Methods: The study was conducted at the department of microbiology of a 1600-bedded level 1 trauma centre of India. Vancomycin minimum inhibitory concentration (MIC) using Etest was performed for MRSA strains isolated from inpatients over 3 years, 2013 to 2015. Heteroresistance determination was done for strains with vancomycin MIC ≥1 μg/ml using Macro Etest method. Clinical data of all patients with MRSA and hVISA infection were compared. Results: A total of 837 S. aureus strains were collected. Of these, 371 (44.3%) were MRSA; 108 (12.9%) had vancomycin MIC ≥1 μg/ml and 32 (3.8%) strains had hVISA. Presence of hVISA infection was found to be significantly associated with the presence of prosthetic implants and surgical-site infections. These patients had prolonged duration of hospital stay and were also associated with vancomycin treatment failure. Discussion: Percentage of hVISA strains reported at our institution was 3.8%, which may be a reflection of community scenario. Mortality rate associated with hVISA bacteraemia was more than that observed with MRSA bacteraemia though not statistically significant. hVISA isolation was greater in high-bacterial–load infections such as blood and respiratory tract infections. Presence of high-bacterial-load MRSA infections for prolonged period despite adequate vancomycin treatment is an indirect clinical marker of hVISA infection.

Methicillin-resistant Staphylococcus aureus bacteremia among liver transplant recipients: epidemiology and associated risk factors for morbidity and mortality.

Bacteremia due to Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), complicates the clinical course of liver transplantation and is associated with high morbidity and mortality. Intravascular catheters had been reported to be the most frequent source of MRSA bacteremia. Among bacteremic liver recipients, 26.3%–100% of S. aureus were MRSA. Previous studies identified pre-transplant and post-transplant acquired S. aureus carriage, greater severity of liver disease, hepatocellular carcinoma and infection with immuno-modulatory viruses as predictors of S. aureus bacteremia in liver recipients. MRSA bacteremia accompanied by pneumonia and abdominal infections was related to mortality. Vancomycin, as well as daptomycin, is a first-line antibiotic for MRSA bacteremia. The purpose of this review is to better understand the characteristics of MRSA bacteremia by summarizing the epidemiology and antimicrobial resistance of S. aureus, the primary source, and related risk factors for morbidity and mortality of MRSA bacteremia. We have also explored the diagnostic, therapeutic and preventive measures for MRSA bacteremia to improve the outcomes of liver recipients.

Impact of cefazolin co-administration with vancomycin to reduce development of vancomycin-intermediate Staphylococcus aureus

ObjectiveDevelopment of antimicrobial resistance during monotherapy of complicated methicillin-resistant Staphylococcus aureus bacteremia is problematic due to cross-resistance between vancomycin (VAN) and daptomycin, the only approved agents for this condition. Our objective was to demonstrate that development of resistance under conditions of suboptimal VAN (200 mg q 12 h) exposure in S. aureus can be attenuated by addition of cefazolin (CFZ). MethodsTwo strains of S. aureus, 1 methicillin-susceptible Staphylococcus aureus (MSSA) (RN9120) and 1 methicillin-resistant S. aureus (MRSA) (JH1), were evaluated. The organisms were exposed to subtherapeutic VAN concentrations in a 1-compartment pharmacokinetic/pharmacodynamic model combined with recycling in the presence and absence of CFZ. Changes in MIC to glyco/lipopeptides and β-lactams along with susceptibility to human cathelicidin LL-37 killing were studied. Population analysis profiles (PAPs) were performed to detect changes in VAN heteroresistance. ResultsVAN MIC of both organisms increased from 1 to 4 mg/L within 144 h under subtherapeutic VAN exposure. Increase in VAN MIC was associated with increased glyco/lipopeptides MICs. Additionally, increased survival in LL-37 killing assays from 40% to >90% accompanied the increase in VAN MIC. Addition of CFZ prevented the emergence of VAN-intermediate S. aureus. PAPs demonstrated an attenuation of VAN area under the curve shift (reduced organism selection with higher MICs values) when suboptimal VAN exposure was accompanied with CFZ compared to VAN alone (MSSA 17.81 versus 36.027, MRSA −0.35 versus 17.92, respectively). Given the emerging data on the clinical benefits of β-lactam adjunctive therapy in refractory MRSA bacteremia, additional studies on a larger collection of clinical isolates are needed to establish the utility of VAN plus CFZ for treatment of MRSA bacteremia.