Methicillin-resistant Staphylococcus Aureus Bacteremia Research Articles

The impact of coronavirus disease 2019 (COVID-19) on healthcare-associated infections in 2020: A summary of data reported to the National Healthcare Safety Network.

To determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on healthcare-associated infection (HAI) incidence in US hospitals, national- and state-level standardized infection ratios (SIRs) were calculated for each quarter in 2020 and compared to those from 2019. Central-line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated events (VAEs), select surgical site infections, and Clostridioides difficile and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia laboratory-identified events reported to the National Healthcare Safety Network for 2019 and 2020 by acute-care hospitals were analyzed. SIRs were calculated for each HAI and quarter by dividing the number of reported infections by the number of predicted infections, calculated using 2015 national baseline data. Percentage changes between 2019 and 2020 SIRs were calculated. Supporting analyses, such as an assessment of device utilization in 2020 compared to 2019, were also performed. Significant increases in the national SIRs for CLABSI, CAUTI, VAE, and MRSA bacteremia were observed in 2020. Changes in the SIR varied by quarter and state. The largest increase was observed for CLABSI, and significant increases in VAE incidence and ventilator utilization were seen across all 4 quarters of 2020. This report provides a national view of the increases in HAI incidence in 2020. These data highlight the need to return to conventional infection prevention and control practices and build resiliency in these programs to withstand future pandemics.

Length of stay, hospitalisation costs and in-hospital mortality of methicillin-susceptible and methicillin-resistant Staphylococcus aureus bacteremia in Japan

ObjectivesTo examine the length of stay, hospitalisation costs and case fatality of methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA) bacteremia in Japan. Study designRetrospective cohort study. Patients with a diagnosis of S. aureus bacteremia who were admitted to a tertiary care hospital (the National Centre for Global Health and Medicine [NCGM]) in Tokyo, Japan, between 1st January 2016 and 31st December 2020 were included in the study. MethodsWe combined Japan Nosocomial Infections Surveillance data and Diagnosis Procedure Combination data at NCGM from 2016 to 2020. The data were stratified into MSSA and MRSA groups. Length of stay (LoS), LoS after submission of a blood culture specimen (LoS-after), hospitalisation cost, hospitalisation costs per day and clinical outcome were compared after propensity score matching. ResultsMedian LoS was 46 (interquartile range [IQR] 28.5–64.5) days in the MSSA group and 66 (IQR 40–91) days in the MRSA group (P = 0.020). Median LoS-after was 38 (IQR 25–62.5) days and 45 (IQR 24–63) days (P = 0.691) in the MSSA and MRSA groups, respectively. Median hospitalisation cost was significantly higher in the MRSA group (26,035 [IQR 18,154–47,362] USD) than in the MSSA group (19,823 [IQR 13,764–32,042] USD) (P = 0.036), but cost per day was not (MRSA: 528.9 [IQR 374.9–647.4] USD; MSSA: 455.6 [IQR 359.2–701.7] USD; P = 0.990). Case fatality rate was higher in the MRSA group than in the MSSA group (22/60 vs 9/60, P = 0.012). ConclusionsPatients with MRSA bacteremia had longer LoS and higher costs than those with MSSA bacteremia. However, LoS-after and hospitalisation costs per day were not different. The longer LoS of patients in Japan compared with other countries might contribute to the higher disease burden of S. aureus bacteremia in Japan.

Select controversies in the management of methicillin-resistant Staphylococcus aureus bacteremia: answers and remaining questions from recent evidence.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia continues to cause significant morbidity and mortality despite advances in medical therapy. Vancomycin therapy remains the standard of care for most cases of MRSA bacteremia but has pharmacokinetic and pharmacodynamic limitations, dosing complications, and known toxicity. Welcomed clinical trials have recently addressed some of the controversies that plague this field, including optimization of vancomycin dosing and use of combination therapy. In this review, we discuss these trials and their implications for clinical care and future research.

Pharmacokinetics, Tissue Distribution, and Efficacy of VIO-001 (Meropenem/Piperacillin/Tazobactam) for Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia in Immunocompetent Rabbits with Chronic Indwelling Vascular Catheters.

Methicillin-resistant Staphylococcus aureus (MRSA) infections of surgically implanted subcutaneous vascular catheters (SISVCs) cause serious morbidity in patients with chronic illnesses. Previous in vitro and murine models demonstrated the synergistic interaction of equimolar concentrations of meropenem/piperacillin/tazobactam (MPT) (VIO-001) against MRSA infection. We investigated the pharmacokinetics (PK) and efficacy of VIO-001 for the treatment of MRSA bacteremia in immunocompetent rabbits with SISVCs. In PK studies, we determined that optimal dosing to achieve a time above 4× MIC (T>4×MIC) of a duration of 3 to 3.30 h required a 1-h infusion with every-4-h (Q4h) dosing. Study groups in efficacy experiments consisted of MPT combinations of 100/150/100 mg/kg of body weight (MPT100), 200/300/200 mg/kg (MPT200), and 400/600/400 mg/kg (MPT400); vancomycin (VAN) at 15 mg/kg; and untreated controls (UC). The inoculum of MRSA isolate USA300-TCH1516 (1 × 103 organisms) was administered via the SISCV on day 1 and locked for 24 h. The 8-day therapy started at 24 h postinoculation. There was a significant reduction of MRSA in blood cultures from the SISVCs in all treatment groups, with full clearance on day 4, versus UCs (P < 0.05). Consistent with the clearance of SISVC-related infection, full eradication of MRSA was achieved in lungs, heart, liver, spleen, and kidneys at the end of the study versus UC (P < 0.01). These results strongly correlated with time-kill data, where MPT in the range of 4/6/4 μg/ml to 32/48/32 μg/ml demonstrated a significant 6-log decrease in the bacterial burden versus UC (P < 0.01). In summary, VIO-001 demonstrated a favorable PK/pharmacodynamic (PD) profile and activity against SISCV MRSA infection, bacteremia, and disseminated infection. This rabbit model provides a new system for understanding new antimicrobial agents against MRSA SISVC-related infection, and these data provide a basis for future clinical investigation.

Clinical and Microbiological Characteristics of Hospital-Acquired Methicillin-Resistant Staphylococcus aureus Bacteremia Caused by a Community-Associated PVL-Negative Strain.

BackgroundST72-SCCmecIV, a community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain in Korea, originated in the community and has been spreading in health care settings. Herein, we describe the clinical and microbiological characteristics of patients with hospital-acquired MRSA bacteremia (MRSAB) caused by community-associated strains.MethodsWe analyzed hospital-acquired MRSAB cases caused by ST72-SCCmecIV using a prospective cohort of patients with SAB in a tertiary hospital in Korea from July 2008 to December 2018. We compared the clinical and microbiological characteristics of ST72-SCCmecIV with ST5-SCCmecII, a representative hospital-associated genotype strain.ResultsOf the 1782 S. aureus bacteremia (SAB) cases, 628 (35.2%) were hospital-acquired MRSAB. Of the 628 isolates, 431 (68.6%) were ST5-SCCmecII and 152 (24.2%) were ST72-SCCmecIV. Patients with ST72-SCCmecIV were younger than those with ST5-SCCmecII and less likely to have a history of recent surgery, antibiotic treatment, nasal MRSA colonization, and central venous catheter placement. Compared with ST5-SCCmecII, ST72-SCCmecIV isolates were more likely to have vancomycin MICs ≤1.0 mg/L (P < .001). Osteoarticular infection as the site of infection (7.2% [11/152] vs 1.4% [6/431]) was more common in patients with ST72-SCCmecIV. There were no significant differences in the rate of recurrence (≤90 days), persistent bacteremia (≥7 days), or 30- and 90-day mortality rates between the 2 groups.ConclusionsOsteoarticular infections were more prevalent in ST72-SCCmecIV MRSAB. Mortality rates between the ST72-SCCmecIV and ST5-SCCmecII groups were not significantly different.

The Impact of Coronavirus Disease 2019 (COVID-19) on Healthcare-Associated Infections.

BackgroundThe profound changes wrought by COVID-19 on routine hospital operations may have influenced performance on hospital measures, including healthcare-associated infections (HAIs). We aimed to evaluate the association between COVID-19 surges and HAI and cluster rates.MethodsIn 148 HCA Healthcare-affiliated hospitals, 3/1/2020-9/30/2020, and a subset of hospitals with microbiology and cluster data through 12/31/2020, we evaluated the association between COVID-19 surges and HAIs, hospital-onset pathogens, and cluster rates using negative binomial mixed models. To account for local variation in COVID-19 pandemic surge timing, we included the number of discharges with a laboratory-confirmed COVID-19 diagnosis per staffed bed per month.ResultsCentral line-associated blood stream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia increased as COVID-19 burden increased. There were 60% (95% CI, 23-108%) more CLABSI, 43% (95% CI, 8-90%) more CAUTI, and 44% (95% CI, 10-88%) more cases of MRSA bacteremia than expected over 7 months based on predicted HAIs had there not been COVID-19 cases. Clostridioides difficile infection was not significantly associated with COVID-19 burden. Microbiology data from 81 of the hospitals corroborated the findings. Notably, rates of hospital-onset bloodstream infections and multidrug resistant organisms, including MRSA, vancomycin-resistant enterococcus and Gram-negative organisms were each significantly associated with COVID-19 surges. Finally, clusters of hospital-onset pathogens increased as the COVID-19 burden increased.ConclusionCOVID-19 surges adversely impact HAI rates and clusters of infections within hospitals, emphasizing the need for balancing COVID-related demands with routine hospital infection prevention.

27969 Good night, sleep tight, don’t let the Cimex bite

A 71-year-old male with history of peripheral neuropathy and tinea pedis presented with acute encephalopathy and respiratory failure requiring intubation, found to be secondary to pneumonia due to Proteus mirabilis. He had a prolonged hospital course complicated by collapse of the left lung and MRSA bacteremia. During the hospitalization, a nurse noted there was live colonization of eggs, larvae, and adult insects under his right great toe. Due to history of peripheral neuropathy, the patient was unable to feel the presence of these insects and did not complain of pruritus or pain.

Changing characteristics of S. aureus bacteremia caused by PVL-negative, MRSA strain over 11\xa0years

Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an important cause of infection. We conducted a longitudinal study to evaluate changes in clinical and microbiological characteristics as well as outcomes of sequence type (ST) 72 MRSA bacteremia. We reviewed adult patients enrolled in a prospective cohort with ST72 MRSA bacteremia from August 2008 to December 2018 at Asan Medical Center, Seoul, South Korea. Changes in clinical characteristics, outcomes, and microbiological characteristics of patients over time were evaluated. Generalized linear and linear regression models were used to evaluate changes. Of the 1,760 isolates, 915 (62%) were MRSA bacteremia and 292 (31.9%) were ST72 MRSA. During the study period, the relative risk (RR) of MRSA bacteremia decreased annually by 3.7%; however, among MRSA bacteremia, RR of ST72 MRSA increased annually by 8.5%. Vancomycin minimum inhibitory concentration (MIC) decreased over the study period. Metastatic infection, persistent bacteremia, and recurrence of bacteremia within 12 weeks decreased significantly. There were no significant changes in 30-d and 12-week mortality. Antibiotic susceptibility of ST72 MRSA was evaluated, and the resistance rate to erythromycin decreased significantly. ST72 MRSA incidence increased annually; its vancomycin MIC and erythromycin resistance rate decreased over the 11 years.

Challenges in replicating secondary analysis of electronic health records data with multiple computable phenotypes: A case study on methicillin-resistant Staphylococcus aureus bacteremia infections

BackgroundReplication of prediction modeling using electronic health records (EHR) is challenging because of the necessity to compute phenotypes including study cohort, outcomes, and covariates. However, some phenotypes may not be easily replicated across EHR data sources due to a variety of reasons such as the lack of gold standard definitions and documentation variations across systems, which may lead to measurement error and potential bias. Methicillin-resistant Staphylococcus aureus (MRSA) infections are responsible for high mortality worldwide. With limited treatment options for the infection, the ability to predict MRSA outcome is of interest. However, replicating these MRSA outcome prediction models using EHR data is problematic due to the lack of well-defined computable phenotypes for many of the predictors as well as study inclusion and outcome criteria. ObjectiveIn this study, we aimed to evaluate a prediction model for 30-day mortality after MRSA bacteremia infection diagnosis with reduced vancomycin susceptibility (MRSA-RVS) considering multiple computable phenotypes using EHR data. MethodsWe used EHR data from a large academic health center in the United States to replicate the original study conducted in Taiwan. We derived multiple computable phenotypes of risk factors and predictors used in the original study, reported stratified descriptive statistics, and assessed the performance of the prediction model. ResultsIn our replication study, it was possible to (re)compute most of the original variables. Nevertheless, for certain variables, their computable phenotypes can only be approximated by proxy with structured EHR data items, especially the composite clinical indices such as the Pitt bacteremia score. Even computable phenotype for the outcome variable was subject to variation on the basis of the admission/discharge windows. The replicated prediction model exhibited only a mild discriminatory ability. ConclusionDespite the rich information in EHR data, replication of prediction models involving complex predictors is still challenging, often due to the limited availability of validated computable phenotypes. On the other hand, it is often possible to derive proxy computable phenotypes that can be further validated and calibrated.

C-reactive protein predicts persistent bacteremia caused by community-acquired methicillin-resistant Staphylococcus aureus strain.

There is limited data on persistent bacteremia (PB) caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Here, we aimed to investigate the clinical and microbiological characteristics of PB caused by the major CA-MRSA strain in Korea (ST72-SCCmecIV). All adult patients with S. aureus bacteremia were prospectively investigated from August 2008 to December 2018. Patients with ST72 MRSA bacteremia were included in the study. Patients were stratified into the PB group (defined as positive blood cultures for ≥ 3days) and short bacteremia (SB) group. A total of 291 patients were included, comprising 115 (39.5%) with PB and 176 (60.5%) with SB. Although the 30-day mortality did not differ between PB and SB, recurrent bacteremia within 12weeks was significantly more common in PB (8.7% vs 1.7%; P = 0.01). Multivariate analysis showed risk factors of PB were liver cirrhosis (adjusted odds ratio [aOR], 3.27; 95% confidence interval [CI], 1.50-7.12), infective endocarditis (aOR, 7.13; 95% CI, 1.37-37.12), bone and joint infections (aOR, 3.76; 95% CI, 1.62-8.77), C-reactive protein ≥ 10mg/dL (aOR, 2.20; 95% CI, 1.22-3.95), metastatic infection (aOR, 7.35; 95% CI, 3.53-15.29), and agr dysfunction (aOR, 2.47; 95% CI, 1.05-5.81). PB occurred in approximately 40% of bacteremia caused by ST72 MRSA with a significantly higher recurrence rate. Patients with risk factors of PB, including liver cirrhosis, high initial CRP, infective endocarditis, or bone and joint infections, might require early aggressive treatment.

Decrease in MRSA Bacteremia After Implementation of Intranasal Mupirocin Decolonization Protocol

Background: Methicillin-resistant Staphylococcus aureus (MRSA) remains a key pathogen in burn patients and is associated with increased morbidity and mortality. Disruption of skin barrier exposes these individuals to a myriad of infections. Various decolonization approaches, including chlorhexidine baths and intranasal mupirocin, have shown favorable outcomes in preventing MRSA infections in this cohort. Methods: In August 2020, a mupirocin decolonization protocol was implemented in Michigan’s largest trauma-level 1 burn intensive care unit. All patients admitted to the burn unit received daily intranasal mupirocin for the initial 5 days of hospitalization. We compared MRSA bacteremia rates per 1,000 patient days from January–July 2020 to those after August 2020. A hospital-acquired MRSA bacteremia infection was defined as a positive blood culture after hospital day 3. Patient characteristics and hospital course were collected through medical chart review. A 2-tailed t test was used for analysis. Results: We identified 5 cases of hospital-onset MRSA bacteremia and no cases of community-onset MRSA bacteremia. On average, there were 2.6 cases per 1,000 patient days before mupirocin implementation and 1.0 cases per 1,000 patient days after mupirocin implementation (P = .26) (Figure 1). In this patient cohort, the average total body surface area burned was 45.6% (range, 18%–90%), and 60% (n = 3) of patients had sputum culture positive for MRSA prior to developing bacteremia (Table 1). Also, 2 patients (40%) with MRSA bacteremia died. Notably, the patient in the postintervention cohort was admitted in July, prior to implementation. Conclusions: Implementation of a decolonization protocol with intranasal mupirocin in burn-surgery patients markedly decreased the incidence of MRSA bacteremia in this cohort. This is the first study to evaluate the use of mupirocin as a decolonizing agent in burn victims. Continued long-term surveillance is recommended, and this strategy has potential for application to other high-risk cohorts.Funding: NoDisclosures: None

Discontinuation of Contact Precautions in Patients with Nosocomial MRSA and VRE Infections During the COVID-19 Pandemic

Background: Gaps exist in the evidence supporting the benefits of contact precautions for the prevention of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The Centers for Disease Control and Prevention allow suspending contact precautions for MRSA and VRE in cases of gown shortages, as we have seen during the COVID-19 pandemic. We evaluated the impact of discontinuing isolation precautions in hospitalized patients with MRSA and VRE infection, due to gown shortage, on the rate of hospital-acquired (HA) MRSA and VRE infections. Methods: A retrospective chart review was performed on adult patients (n = 2,200) with established MRSA or VRE infection at 5 hospitals in CommonSpirit Health, Texas Division, from March 2019 to October 2020. Data including demographics, infection site, documented symptoms, and antibiotic use were stratified based on patient location (floor vs ICU). Rates of hospital-acquired MRSA and VRE infection before and after the discontinuation of isolation (implemented in March 2020) were compared. Incidence density rate was used to assess differences in the rate of MRSA and VRE infections between pre- and postintervention groups. Results: The rate of hospital-acquired (HA) MRSA infection per 10,000 patient days before the intervention (March 19–February 20) was 12.19, compared to 10.64 after the intervention (March 20–July 20) (P = .038). The rates of HA MRSA bacteremia were 1.13 and 0.93 for the pre- and postintervention groups, respectively (P = .074). The rates of HA VRE per 10,000 patient days were 3.53 and 4.44 for the pre- and postintervention groups, respectively (P = .274). The hand hygiene rates were 0.93 before the intervention and 0.97 after the intervention (P = .028). Conclusions: Discontinuing isolation from MRSA and VRE in the hospital setting did not lead to a statistically significant increase in hospital-acquired MRSA or VRE infections. In fact, rates of hospital-acquired MRSA decreased, likely secondary to improvements in hand hygiene during this period. These results support the implementation of policies for discontinuing contact isolation for hospitalized patients with documented MRSA or VRE infection, particularly during shortages of gowns.Funding: NoDisclosures: None

Use of Pulsed-Field Gel Electrophoresis to Determine the Source of Methicillin-Resistant Staphylococcus aureus Bacteremia

Pulsed-field gel electrophoresis (PFGE) has historically been considered the gold standard in fingerprinting bacterial strains in epidemiological studies and outbreak investigations; little is known regarding its use in individual clinical cases. The current study detailed two clinical cases in which PFGE helped to determine the source of their methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Patient A was found to have MRSA bacteremia after trauma in her pelvic area. MRSA was also found in her groin but not in her nostril and rectum. PFGE was performed that showed variable bands of her MRSA isolates from blood and groin, suggestive of different strains of MRSA. Her MRSA bacteremia was determined to be unrelated to her pelvic trauma. Patient B was found to have MRSA bacteremia after colonoscopy. MRSA was also found in his nostril and rectum. PFGE was performed that showed variable bands of his MRSA isolates from blood and rectum but identical bands of MRSA isolates from his blood and nostril. His MRSA bacteremia was determined to be unrelated to his colonoscopy procedure. The current study demonstrates the use of PFGE to rule out the source of bacteremia in individual clinical cases.

Clinical Outcomes With Definitive Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia With Retained Daptomycin and Ceftaroline Combination Therapy vs De-escalation to Monotherapy With Vancomycin, Daptomycin, or Ceftaroline.

BackgroundLower mortality has been observed with combination therapy compared to monotherapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia; however, there is a lack of evidence for continued combination therapy over de-escalation to monotherapy following bacteremia clearance.MethodsThis was a single-center, retrospective study evaluating patients with MRSA bacteremia hospitalized from November 1, 2011, through July 31, 2019. Patients who received three to ten days of combination therapy followed by de-escalation to monotherapy were directly compared to patients retained on combination therapy. The primary composite outcome included inpatient infection-related mortality, 60-day readmission, and 60-day bacteremia recurrence.ResultsA total of 286 patients with MRSA bacteremia were identified, with 146 patients omitted based on exclusion criteria. The study population included 66 in the combination therapy group and 74 in the monotherapy group. Study population was 51% female (n = 71) and 78% white (n = 109) with median age of 46 years (IQR 34.5–61). No significant difference was observed in the primary composite outcome (21% combination therapy group vs 24% monotherapy group; P =.66), with retained observations after controlling for confounders. Within this outcome, there was no significant difference in 60-day readmission (20% combination therapy group vs 18% monotherapy group; P =.75), bacteremia recurrence (3% combination therapy group vs 7% monotherapy group; P =.45), or inpatient infection-related mortality (2% combination therapy group vs 5% monotherapy group; P = 1.00). ConclusionsNo difference was found in the composite outcome of 60-day bacteremia recurrence, readmission, or inpatient infection-related mortality for patients with MRSA bacteremia retained on combination therapy versus those de-escalated to monotherapy.

Efficacy and Safety of Intravenous Lincosamide Therapy in Methicillin-Resistant Staphylococcus aureus Bacteremia.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia has a high case-fatality rate, but currently recommended antimicrobial therapies have many shortcomings. The efficacy and safety of lincosamide therapy for MRSA bacteremia is incompletely defined. A retrospective audit was done of the management of all adults with MRSA bacteremia at an Australian tertiary referral hospital between 1 January 2007 and 31 December 2020. A total of 176 patients were included. The case-fatality rate declined from 14/57 (25%) in the first half of the study to 12/119 (10%) in the second half (P = 0.01). Of the 172 patients receiving antibiotics, 62 (36%) received a lincosamide-predominant regimen (lincosamide monotherapy for >50% of the intravenous course). The patients receiving lincosamide-predominant intravenous therapy had lower in-hospital mortality (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.01 to 0.53; P = 0.01) and a lower incidence of renal complications (OR [95% CI], 0.34 [0.15-0.75]; P = 0.008) than patients receiving an alternative regimen. In multivariate analysis that also considered age, disease severity, comorbidity, infectious diseases consultation, source control, and the year of admission, patients receiving a lincosamide-predominant regimen were still less likely to die in the hospital than those receiving an alternative regimen (OR [95% CI], 0.05 [0.00 to 0.65]; P = 0.02). Lincosamides appear to have utility, at least as stepdown therapy, in the treatment of MRSA bacteremia, particularly in young, clinically stable patients with few comorbidities in whom endocarditis has been excluded. Prospective studies will help define their optimal role.

Human Urine Alters Methicillin-Resistant Staphylococcus aureus Virulence and Transcriptome.

Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of hospital-associated urinary tract infections (UTI), especially in catheterized individuals. Despite being rare, MRSA UTI are prone to potentially life-threatening exacerbations such as bacteremia that can be refractory to routine antibiotic therapy. To delineate the molecular mechanisms governing MRSA urinary pathogenesis, we exposed three S. aureus clinical isolates, including two MRSA strains, to human urine for 2 h and analyzed virulence characteristics and changes in gene expression. The in vitro virulence assays showed that human urine rapidly alters adherence to human bladder epithelial cells and fibronectin, hemolysis of sheep red blood cells (RBCs), and surface hydrophobicity in a staphylococcal strain-specific manner. In addition, transcriptome sequencing (RNA-Seq) analysis of uropathogenic strain MRSA-1369 revealed that 2-h-long exposure to human urine alters MRSA transcriptome by modifying expression of genes encoding enzymes catalyzing metabolic pathways, virulence factors, and transcriptional regulators. In summary, our results provide important insights into how human urine specifically and rapidly alters MRSA physiology and facilitates MRSA survival in the nutrient-limiting and hostile urinary microenvironment. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is an uncommon cause of urinary tract infections (UTI) in the general population. However, it is important to understand MRSA pathophysiology in the urinary tract because isolation of MRSA in urine samples often precedes potentially life-threatening MRSA bacteremia. In this report, we describe how exposure to human urine alters MRSA global gene expression and virulence. We hypothesize that these alterations may aid MRSA in acclimating to the nutrient-limiting, immunologically hostile conditions within the urinary tract leading to MRSA UTI.

Optimizing outcomes using vancomycin therapeutic drug monitoring in patients with MRSA bacteremia: trough concentrations or area under the curve?

BackgroundVancomycin therapeutic drug monitoring is routinely performed but the specific measure used in practice is variable. ObjectiveTo evaluate the relationship between the first measured vancomycin trough, area-under-the-curve (AUC), and failure in patients with MRSA bacteremia. MethodsThis retrospective, cohort study included adult non-neutropenic patients with MRSA bacteremia who received vancomycin. The primary outcome was treatment failure. Initial trough and AUC values were compared between the failure and success groups. Classification and regression tree analysis was used to identify thresholds associated with failure. Multivariate analysis was performed to control for identified confounders. ResultsThere were 89 patients. Failure occurred in 23 (26%). Trough and AUC values associated with failure were < 10.6 mg/L (39% vs. 13%; P = 0.006) and AUC < 410mg*h/L (40% vs. 17%; P = 0.014). Both remained significant after controlling covariates (trough < 10.6 mg/L, OR [95% CI] = 4.91 [1.6–15]; AUC<410mg*h/L, OR [95% CI] = 3.13 [1.14–8.62]). Only AUC was predictive of nephrotoxicity. ConclusionFailure was more common with troughs < 10.6 mg/L or AUC < 410 mg*h/L. Supratherapeutic AUCs, but not trough, were associated with nephrotoxicity.

Clinical Outcomes for Telavancin for Salvage Therapy in Methicillin-resistant Staphylococcus Aureus Bacteremia

Background Little evidence exists for the use of telavancin in methicillin-resistant Staphylococcus aureus (MRSA) bacteremia as salvage therapy. This study aims to evaluate the efficacy and safety of telavancin as salvage therapy in the treatment of MRSA bacteremia. Methods Electronic medical charts of patients who received telavancin for the treatment of MRSA bacteremia at an academic, tertiary care medical center in the United States between January 1, 2015, and May 31, 2019, were reviewed for clinical cure, reinfection, prior antibiotic use, source of infection, microbiological culture clearance, patient mortality, and adverse effects. The primary outcome was clinical cure. Results Thirty-eight charts were identified, and 11 met inclusion criteria for this analysis. Vancomycin or daptomycin was given for an average of 5.4 and 2.6 days, respectively, before the initiation of telavancin. The average telavancin dose used was 7.5 mg/kg. All patients achieved clinical cure, and there were no instances of 60-day mortality. Two patients experienced reinfection: 1 patient after 268 days and another after 467 days. Four patients experienced either QTc prolongation or acute renal failure. Conclusions The use of telavancin in MRSA bacteremia demonstrated microbiological cure, clinical cure, and minimal reinfection in the reviewed patient population. Telavancin may be a potential treatment option for patients with MRSA bacteremia as salvage therapy.

Current Paradigms of Combination Therapy in Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia: Does it Work, Which Combination, and For Which Patients?

The last several years have seen an emergence of literature documenting the utility of combination antimicrobial therapy, particularly in the salvage of refractory methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Recent clinical data are shaping conundrums of which regimens may be more beneficial, which can be potentially harmful, and which subset of patients stand to benefit from more aggressive treatment regimens than called for by current standards. In addition, the incorporation of combination therapy for MRSA bacteremia should be accompanied by the reminder that antimicrobial therapy does not need to be uniform for the entire duration, with an early intensive phase in high inoculum infections (eg, with combination therapy), followed by a consolidation phase (ie, monotherapy). This review and perspective consolidates the recent data on this subject and directs future goals in filling the knowledge gaps to methodically move forward towards improving patient outcomes.

Methicillin-Resistant Staphylococcus Aureus Bacteremia: Epidemiology, Clinical Characteristics, Risk Factors, and Outcomes in a Tertiary Care Center in Riyadh, Saudi Arabia.

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) has become increasingly common in hospitals worldwide. In an era of pandemics, it is important to understand all types of infectious diseases in order to control its outcome and reduce mortality rates related to it. This study aims to identify the epidemiology of MRSA bloodstream infection, risk factors, and mortality in King Abdulaziz Medical City in Riyadh.MethodsThis is a retrospective chart review study from January 2013 to June 2017. All patients with positive blood culture for MRSA at King Abdulaziz Medical City (KAMC), which is a tertiary care center in Riyadh, Saudi Arabia, were included. Data were extracted from electronic and paper medical records for patients who had a positive blood culture for MRSA. Data collected included demographics, microbiological details, risk factors, and 30-day mortality.ResultsFrom 2013 through June 2017, 633 Staphylococcus aureus bacteremia were reported in KAMC, of which 184 (29.1%) were MRSA with a mean age of 60±19 years. Almost all of our isolates were susceptible to vancomycin, linezolid, and tigecycline. The most common infectious syndrome these patients presented with was an endovascular infection which accounts for 30.4% while 19.9% presented as a case of pneumonia. The mortality within 30 days of collection of the positive blood culture was 20.65%. Male gender (OR = 2.33; 95% CI = 1.34-4.05; P-value = 0.003) and patients with history of recent hospital (OR = 2.34; 95% CI = 1.27-4.34; P-value = 0.007) or ICU (OR = 1.66; 95% CI = 1.09-2.52; P-value = 0.018) admissions were more likely to acquire MRSA.ConclusionsThe incidence of MRSA bacteremia at King Abdulaziz Medical City is high and increasing in conjunction with incidence rate posing a significantly high rate of mortality. Recent history of hospital admission, ICU admission and males were found to be significantly associated with higher rates of MRSA infection. Some modifiable risk factors that could be used to facilitate the reduction of MRSA acquisition rates is to avoid unnecessary hospital and ICU admissions.