anti-MRSA Antibiotics Research Articles

MRSA and Skin Infections in Psoriatic Patients: Therapeutic Options and New Perspectives.

Psoriatic patients present various infectious risk factors, but there are few studies in the literature evaluating the actual impact of psoriasis in severe staphylococcal skin infections. Our narrative review of the literature suggests that psoriatic patients are at increased risk of both colonization and severe infection, during hospitalization, by S. aureus. The latter also appears to play a role in the pathogenesis of psoriasis through the production of exotoxins. Hospitalized psoriatic patients are also at increased risk of MRSA skin infections. For this reason, new molecules are needed that could both overcome bacterial resistance and inhibit exotoxin production. In our opinion, in the near future, topical quorum sensing inhibitors in combination with current anti-MRSA therapies will be able to overcome the increasing resistance and block exotoxin production. Supplementation with Vitamin E (VE) or derivatives could also enhance the effect of anti-MRSA antibiotics, considering that psoriatic patients with metabolic comorbidities show a low intake of VE and low serum levels, making VE supplementation an interesting new perspective.

Antibiotics and outcomes of CF pulmonary exacerbations in children infected with MRSA and Pseudomonas aeruginosa

Limited data exist to inform antibiotic selection among people with cystic fibrosis (CF) with airway infection by multiple CF-related microorganisms. This study aimed to determine among children with CF co-infected with methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (Pa) if the addition of anti-MRSA antibiotics to antipseudomonal antibiotic treatment for pulmonary exacerbations (PEx) would be associated with improved clinical outcomes compared with antipseudomonal antibiotics alone. Retrospective cohort study using data from the CF Foundation Patient Registry-Pediatric Health Information System linked dataset. The odds of returning to baseline lung function and having a subsequent PEx requiring intravenous antibiotics were compared between PEx treated with anti-MRSA and antipseudomonal antibiotics and those treated with antipseudomonal antibiotics alone, adjusting for confounding by indication using inverse probability of treatment weighting. 943 children with CF co-infected with MRSA and Pa contributed 2,989 PEx for analysis. Of these, 2,331 (78%) PEx were treated with both anti-MRSA and antipseudomonal antibiotics and 658 (22%) PEx were treated with antipseudomonal antibiotics alone. Compared with PEx treated with antipseudomonal antibiotics alone, the addition of anti-MRSA antibiotics to antipseudomonal antibiotic therapy was not associated with a higher odds of returning to ≥90% or ≥100% of baseline lung function or a lower odds of future PEx requiring intravenous antibiotics. Children with CF co-infected with MRSA and Pa may not benefit from the addition of anti-MRSA antibiotics for PEx treatment. Prospective studies evaluating optimal antibiotic selection strategies for PEx treatment are needed to optimize clinical outcomes following PEx treatment.

A case of septic arthritis of the elbow joint in rheumatoid arthritis diagnosed by arthroscopic synovectomy.

We report a case of methicillin-resistant Staphylococcus aureus (MRSA) septic arthritis of the elbow detected by arthroscopic synovectomy in an 81-year-old woman with rheumatoid arthritis (RA) who was initially diagnosed with a rheumatoid arthritis flare-up. The patient was administered abatacept, an antirheumatic biological agent, as the synovial fluid culture was negative. Destruction of the joint progressed despite medication, and the patient underwent arthroscopic synovectomy. MRSA was detected in the culture of the synovium that was collected intraoperatively, and septic arthritis was diagnosed. The infection subsided with anti-MRSA antibiotics, but the patient continued to experience moderate pain and limited motion. In RA patients, it might be difficult to differentiate minor findings from infection. Arthroscopic synovectomy is one of the selectable procedures that should be actively considered when infection is suspected.

Impact of MRSA polymerase chain reaction (PCR) wound swabs on antibiotic de-escalation in skin and soft tissue infections

Methicillin-resistant strains of S. aureus (MRSA) polymerase chain reaction (PCR) testing is a laboratory test that allows for rapid detection of MRSA and is available to use in skin infections via wound swab. There are limited data demonstrating the utility of MRSA PCR wound swabs on clinical outcomes in skin and soft tissue infections. This retrospective, single-center study included 652 patients to determine if the use of a MRSA PCR wound swab in skin infections results in a more rapid de-escalation in antibiotics. Patients with a MRSA PCR negative wound swab demonstrated a 1.0 (-1.5 to -0.53) day reduction of anti-MRSA antibiotic usage compared to those in the control group who did not have a MRSA PCR available (wound culture data only) (P < 0.001, unadjusted). The results of this study demonstrate that MRSA PCR wound swab assays have the potential to play a significant role in antibiotic de-escalation in the setting of skin and soft tissue infections.

Risk factors for antibiotic resistance in hospital-acquired and ventilator-associated pneumonia

IntroductionUnderstanding risk factors for antibiotic resistance (AR) in patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) is important to select appropriate initial antibiotics and reduce broad-spectrum antibiotic overuse. However, available evidence is limited. We aimed to identify risk factors for AR in those patients. MethodsThis prospective observational study was conducted at a tertiary-care hospital. Pathogens with AR were defined as those resistant to ampicillin-sulbactam or ceftriaxone. Risk factors for AR in patients with HAP and VAP were assessed using penalized logistic regression analysis. ResultsIn total, 557 patients with HAP and VAP were enrolled. Pathogens were isolated from 315 patients, with AR identified in 68.3% (215/315). Among antibiotic-resistant pathogens (ARPs), Pseudomonas aeruginosa was isolated most frequently, followed by methicillin-resistant Staphylococcus aureus (MRSA). Significant risk factors for AR were chronic renal diseases (adjusted odds ratio: 2.82, 95% confidence interval: 1.79–7.83), history of ARP infection/colonization within the past 1 year (2.80, 1.90–7.02), bedridden state (1.84, 1.28–3.91), tube feeding (1.58, 1.09–2.98), and peripheral or central venous catheterization (1.57, 1.06–2.96). Additionally, a risk factor for ARPs that should be treated with anti-MRSA antibiotics was prior MRSA infection/colonization history. Those for ARPs requiring dual antipseudomonal antibiotics included prior non-MRSA ARP or MRSA infection/colonization history and bedridden state. ConclusionsThe five factors we highlighted can be important criteria for identifying patients at risk of AR. Physicians should consider these potential risk factors when selecting antibiotics for initial empirical therapy in patients with HAP and VAP.

Association Between Implementation of the Severe Sepsis and Septic Shock Early Management Bundle Performance Measure and Outcomes in Patients With Suspected Sepsis in US Hospitals

In October 2015, the Centers for Medicare & Medicaid Services began requiring US hospitals to report adherence to the Severe Sepsis and Septic Shock Early Management Bundle (SEP-1). To evaluate the association of SEP-1 implementation with sepsis treatment patterns and outcomes in diverse hospitals. This retrospective cohort study with interrupted time-series analysis and logistic regression models was conducted among adults admitted to 114 hospitals from October 2013 to December 2017 with suspected sepsis (blood culture orders, ≥2 systemic inflammatory response syndrome criteria, and acute organ dysfunction) within 24 hours of hospital arrival. Data analysis was conducted from September 2020 to September 2021. SEP-1 implementation in the fourth quarter (Q4) of 2015. The primary outcome was quarterly rates of risk-adjusted short-term mortality (in-hospital death or discharge to hospice). Secondary outcomes included lactate testing and administration of anti-methicillin-resistant Staphylococcus aureus (MRSA) or antipseudomonal β-lactam antibiotics within 24 hours of hospital arrival. Generalized estimating equations with robust sandwich variances were used to fit logistic regression models to assess for changes in level or trends in these outcomes, adjusting for baseline characteristics and severity of illness. The cohort included 117 510 patients (median [IQR] age, 67 years [55-78] years; 60 530 [51.5%] men and 56 980 [48.5%] women) with suspected sepsis. Lactate testing rates increased from 55.1% (95% CI, 53.9%-56.2%) in Q4 of 2013 to 76.7% (95% CI, 75.4%-78.0%) in Q4 of 2017, with a significant level change following SEP-1 implementation (odds ratio [OR], 1.34; 95% CI, 1.04-1.74). There were increases in use of anti-MRSA antibiotics (19.8% [95% CI, 18.9%-20.7%] in Q4 of 2013 to 26.3% [95% CI, 24.9%-27.7%] in Q4 of 2017) and antipseudomonal antibiotics (27.7% [95% CI, 26.7%-28.8%] in Q4 of 2013 to 40.5% [95% CI, 38.9%-42.0%] in Q4 of 2017), but these trends preceded SEP-1 and did not change with SEP-1 implementation. Unadjusted short-term mortality rates were similar in the pre-SEP-1 period (Q4 of 2013 through Q3 of 2015) vs the post-SEP-1 period (Q1 of 2016 through Q4 of 2017) (20.3% [95% CI, 20.0%-20.6%] vs 20.4% [95% CI, 20.1%-20.7%]), and SEP-1 implementation was not associated with changes in level (OR, 0.94; 95% CI, 0.68-1.29) or trend (OR, 1.00; 95% CI, 0.97-1.04) for risk-adjusted short-term mortality rates. In this cohort study, SEP-1 implementation was associated with an immediate increase in lactate testing rates, no change in already-increasing rates of broad-spectrum antibiotic use, and no change in short-term mortality rates for patients with suspected sepsis. Other approaches to decrease sepsis mortality may be warranted.

135. Association Between Implementation of the Centers for Medicare &amp; Medicaid Services Sepsis Performance Measure (SEP-1) and Outcomes in U.S. Hospitals

BackgroundIn October 2015, CMS began requiring U.S. hospitals to report compliance with the Severe Sepsis/Septic Shock Early Management Bundle (SEP-1). We evaluated the impact of SEP-1 implementation on sepsis treatment patterns and outcomes using detailed clinical data from diverse hospitals.MethodsWe conducted a quasi-experimental interrupted time-series analysis of adults admitted to 114 hospitals in the Cerner HealthFacts dataset from October 2013-December 2017 with suspected sepsis (defined by blood culture orders, SIRS criteria, and acute organ dysfunction) within 24 hours of hospital arrival. The primary outcome was quarterly short-term mortality rates (in-hospital death or discharge to hospice). Secondary outcomes included lactate testing and administration of anti-MRSA or anti-Pseudomonal beta-lactam antibiotics within 24 hours of hospital arrival. Generalized estimating equations with robust sandwich variances were used to fit logistic regression models to assess for immediate SEP-1 impact and changes in quarterly trends after October 2015, adjusting for baseline characteristics and severity-of-illness. ResultsThe cohort included 117,510 patients with suspected sepsis on admission. Lactate testing rates increased over the study period (61.9% pre-SEP-1 vs 77.9% post-SEP-1) with a significant immediate increase in risk-adjusted testing rates after SEP-1 (OR 1.34, 95% CI 1.04-1.74) (Figure 1). There was also an increase in utilization of anti-MRSA (20.6% pre vs 23.2% post-SEP-1) and anti-Pseudomonal antibiotics (30.1% vs 39.8%), %), but these trends began before SEP-1 implementation. Unadjusted short-term mortality was similar in the pre vs post-SEP-1 periods (20.3% vs 20.4%). SEP-1 was not associated with either an immediate change (OR 0.94, 95% CI 0.68-1.29] or quarterly trend change (OR 1.00, 95% CI 0.97-1.04] in risk-adjusted short-term mortality (Figure 2). Figure 1. Quarterly risk-adjusted rates of A) lactate testing, B) anti-MRSA antibiotic administration, and C) anti-Pseudomonal beta-lactam antibiotic administration within 24 hours of hospital presentation for patients with suspected sepsis before and after SEP-1 implementation in Q4 2015. All models included time (in quarters), an indicator of the post-SEP-1 implementation period (starting Q12016, to allow for evaluation of an immediate policy effect), and a two-way interaction term to assess whether SEP-1 implementation resulted in a change in trend. When data suggested no change in trend, models were also fit without this interaction term; this yielded a significant association for an immediate level change in lactate testing (OR 1.34 [95% CI 1.04-1.74]) but not antibiotic utilization. All analyses were adjusted for patient severity of illness and baseline characteristics including age, sex, race, initial vital signs (systolic blood pressure, temperature, respiratory rate, heart rate), and initial laboratory results (creatinine, platelet count, bilirubin, white blood cell count) if done within 24 hours.Figure 2. Quarterly risk-adjusted outcomes of patients with suspected sepsis before and after SEP-1 implementation in Q4 2015: A) In-hospital death or discharge to hospice, and B) In-hospital death alone. Models included time (in quarters), an indicator of the post-SEP-1 implementation period (starting Q12016, to allow for evaluation of an immediate policy effect), and a two-way interaction term to assess whether SEP-1 implementation resulted in a change in trend. Analyses were adjusted for patient severity of illness and baseline characteristics including age, sex, race, initial vital signs (systolic blood pressure, temperature, respiratory rate, heart rate), and initial laboratory results (creatinine, platelet count, bilirubin, white blood cell count) if done within 24 hours.ConclusionSEP-1 implementation was associated with an immediate increase in lactate testing rates, no significant change in already-rising rates of broad-spectrum antibiotic use, and no change in short-term mortality rates for patients with suspected sepsis in a large cohort of hospitals. Other approaches to decrease sepsis mortality may be warranted. Disclosures Chanu Rhee, MD, MPH, UpToDate (Other Financial or Material Support, Chapter Author) Sameer S. Kadri, MD, MS, FIDSA, Nothing to disclose Michael Klompas, MD, MPH, UpToDate (Other Financial or Material Support, Chapter Author)

1310. Provider and Facility Variation in Empiric Broad-Spectrum Antibiotic Use for Hospitalization Pneumonia: A Mixed Methods Study of Veterans Affairs Facilities

BackgroundWe previously found widespread variation in the empiric use of antibiotics against methicillin-resistant Staph aureus (anti-MRSA) and Pseudomonas aeruginosa (anti-PAER) for patients hospitalized for pneumonia. To explore this variation further, we conducted (1) quantitative analyses of facility-level versus provider-level variation, and (2) qualitative interviews with emergency department providers. MethodsFor each hospitalization, we predicted the probability of anti-MRSA and anti-PAER use by fitting machine learning models from 75 patient variables. We estimated the predicted risk of anti-MRSA/anti-PAER and facility features among patients hospitalized at upper versus lower 10% facilities after controlling for patient characteristics. We plotted density curves with the variance attributed to facility and provider alone and together. We then interviewed 16 emergency department (ED) providers at 8 VA facilities using a cognitive task analysis. ResultsAmong 215,803 hospitalizations at 128 VA facilities 1/1/2006-12/31/2016, 31% received empiric anti-MRSA and 29% received empiric anti-PAER antibiotics. Hospitalizations at upper-decile facilities had a 50% and 45% adjusted probability of receiving anti-MRSA and anti-PAER antibiotics, compared to 15% and 20% in the lower-decile facilities. Facility features most predictive of anti-MRSA or anti-PAER use after adjusting for patient characteristics were complexity level (33% and 30% in high versus 15% and 20% in low complexity facilities). Variation in empiric anti-MRSA and anti-PAER use was almost completely at the facility level (Figure 1). Providers reported social influences from the opinions of other providers during decision-making and a high trust in guidelines and order sets. Consideration of pathogens was not mentioned by any providers at high-prescribing facilities.ConclusionVariation in empiric use of anti-MRSA and anti-PAER antibiotics in pneumonia clustered nearly completely at the facility level. ED providers report social influences during decision-making and a high trust in guidelines and order sets. Guidelines, order sets, and facility-level clinical champions that promote consideration of pathogens could be important strategies for de-adoption. Disclosures All Authors: No reported disclosures

187. Vancomycin Plus Ceftaroline Salvage Therapy for Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia

BackgroundThe preferred antibiotic salvage regimen for persistent methicillin-resistant Staphylococcus aureus bacteremia (pMRSAB) is unclear. Vancomycin plus ceftaroline (V/C) has demonstrated potent in vitro synergistic activity against MRSA; however, clinical data is limited. Thus, we sought to evaluate V/C salvage therapy for pMRSAB.MethodsThis was a single-center, retrospective cohort study of patients with MRSAB who received V/C salvage therapy between 1/1/2016-3/10/2021. Adult patients were included if blood cultures (BC) were positive for MRSA for ≥ 72 hours, received anti-MRSA monotherapy initially, and subsequently received V/C ≥ 24 hours. Patients were excluded if they received other anti-MRSA antibiotics within 72 hours of V/C initiation. The primary outcome was time to BC clearance following V/C initiation. Secondary outcomes included 90-day all-cause mortality, microbiological cure, 90-day MRSAB recurrence, and length of stay (LOS). Microbiological cure was defined as BC clearance.ResultsOf 178 patients identified, 20 were evaluated after inclusion and exclusion criteria were applied. Mean (SD) age and Pitt Bacteremia score were 38.5 (14.5) years and 4.2 (3.1), respectively. Most patients were male (70%), intravenous drug users (65%), and admitted to the intensive care unit (65%). The most common source was intravenous drug use (55%) and the majority had infective endocarditis (70%). All patients received infectious disease consultation and median (IQR) vancomycin AUC:MIC was 527 (454, 611). Source control, if possible, was obtained in most patients (55%). Median (IQR) time to bloodstream clearance from first positive BC and from when ceftaroline was initiated was 9.7 (8.4, 10.2) and 2.4 (1.5, 3.1) days, respectively. 90-day all-cause mortality, microbiological cure, and 90-day MRSAB recurrence occurred in 35%, 95%, and 5% of patients, respectively. Median (IQR) LOS was 25 (14.5, 32.0) days.ConclusionTo our knowledge, this is the largest cohort to evaluate V/C for pMRSAB. Patients were medically complex; however, median time to MRSAB clearance following ceftaroline initiation was < 2.5 days and microbiological cure was obtained in nearly all patients. V/C may represent a potential salvage regimen for pMRSAB.Disclosures Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member) Jeffrey Steele, Pharm.D., Paratek Pharmaceuticals (Advisor or Review Panel member)

58. Impact of Order-set Modifications and Provider Education on Broad-Spectrum Antibiotic Use in Patients Admitted with Community Acquired Pneumonia

BackgroundFollowing updates to IDSA guidelines in 2019, Hartford HealthCare implemented changes to the community acquired pneumonia (CAP) order-set in August 2020 to reflect criteria for prescribing of broad-spectrum antimicrobial therapy. The objective of the study was to evaluate changes in broad-spectrum antibiotic days of therapy (DOT) following these order-set updates with accompanying provider education.MethodsThis was a multi-center, quasi-experimental, retrospective study of patients with CAP from 9/1/19 to 10/31/19 (pre-intervention) and 9/1/20 to 10/31/20 (post-intervention). Patients were identified using ICD-10 codes indicating lower respiratory tract infection and excluded if had a positive SARS-COV-2 PCR during admission. Data collected included demographics, labs and vitals, radiographic, microbiological, and antibiotic data. The primary outcome was change in broad-spectrum antibiotic DOT, specifically anti-pseudomonal β-lactams and anti-MRSA antibiotics. Secondary outcomes included guideline-concordance of initial antibiotics, utilization of an order-set to prescribe antibiotics, and length of stay (LOS).ResultsA total of 331 and 352 patients were included in the pre- and post-intervention groups, respectively. The overall duration of broad-spectrum therapy was a median of 2 days (IQR 0-8 days) in the pre-intervention period and 0 days (IQR 0-4 days) in the post-intervention period (p< 0.001). Patients in whom the order-set was used in the post-intervention period were more likely to have guideline-concordant regimens ([36/40] 90% vs. [190/312] 60.9%; p = 0.003). There were no differences in order set usage (10% vs. 11.3%, p = 0.642) between the pre- and post-intervention groups, respectively. Hospital LOS was lower in the post-intervention cohort (4.8 days [2.9-7.2 days] vs. 5.3 days [IQR 3.5-8.5 days], p = .002). ConclusionDespite low utilization of the order-set, education surrounding order-set changes appeared to improve antibiotic prescribing and hospital LOS in our population. Further opportunities to improve order-set use and thus further increase guideline-concordant therapy are still available. Disclosures Joseph L. Kuti, PharmD, Allergan (Speaker’s Bureau)BioMérieux (Consultant, Research Grant or Support, Speaker’s Bureau)Contrafect (Scientific Research Study Investigator)GSK (Consultant)Merck (Research Grant or Support)Paratek (Speaker’s Bureau)Roche Diagnostics (Research Grant or Support)Shionogi (Research Grant or Support)Summit (Scientific Research Study Investigator) David P. Nicolau, PharmD, Abbvie, Cepheid, Merck, Paratek, Pfizer, Wockhardt, Shionogi, Tetraphase (Other Financial or Material Support, I have been a consultant, speakers bureau member, or have received research funding from the above listed companies.)

1112. Vancomycin Nephrotoxicity Relative to Alternative Antibiotic Treatments: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BackgroundVancomycin is one of the most frequently prescribed antibiotics. Existing clinical evidence on vancomycin nephrotoxicity is limited to observational studies which are prone to confounding and bias. The purpose of this systematic review and meta-analysis is to compare acute kidney injury between vancomycin and comparator anti-methicillin resistant Staphylococcus aureus (MRSA) antibiotics using randomized controlled trial (RCT) data.MethodsPubMed and Embase were searched for RCTs comparing intravenous vancomycin to other anti-MRSA antibiotics in adult patients, published from 1990 to January 2021. Studies were included if they reported comparative data on renal outcomes. The primary outcome was change in renal function, referred to as ‘nephrotoxicity’ in this study. Studies where another known nephrotoxic medication was part of study therapy in any treatment group were excluded. Eighteen studies met the inclusion criteria, and two independent reviewers assessed the risk of bias. Data on nephrotoxicity definition, comparator drug, infection type, vancomycin dosing strategy, duration of treatment, and concurrent gram-negative coverage were extracted. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Figure 1. Flow chart of article selection.ResultsOf 1,426 studies identified, 18 encompassing 8,966 patients were included. Treatment with vancomycin was associated with significantly increased odds of nephrotoxicity (OR, 2.41; 95% CI, 1.71 to 3.40; P< 0.00001) relative to its alternatives. A subgroup analysis grouping studies by reported vancomycin dosing approach revealed a stronger association between vancomycin and nephrotoxicity in studies with fixed-dose vancomycin regimens (OR 5.31; 95% CI 1.93 to 14.56; P=0.001) relative to studies with vancomycin therapeutic drug monitoring (TDM) (OR 2.17; 95% CI 1.51 to 3.13; P< 0.0001). Figure 2. Forest plot indicating the risk of nephrotoxicity associated with vancomycin vs. comparators. Odds ratios (ORs) and 95% confidence intervals (95% CIs) are shown for each study and the pooled analysis using a random effects model and the Mantel-Haenszel method. OR>1 means that the risk of kidney injury in the vancomycin group is greater than that in the comparator group.Figure 3. Forest plot indicating a strong association between vancomycin and nephrotoxicity in studies with fixed-dose vancomycin regimens relative to studies with vancomycin therapeutic drug monitoring (TDM). Odds ratios (ORs) and 95% confidence intervals (95% CIs) are shown for each study and the pooled analysis using a random effects model and the Mantel-Haenszel method. OR>1 means that the risk of kidney injury in the vancomycin group is greater than that in the comparator group.Table 1. Summary of included studies. ConclusionThis analysis shows that intravenous vancomycin is associated with greater odds of renal toxicity relative to alternative antibiotics. This effect was not as pronounced in studies where vancomycin TDM was used potentially indicating benefit of TDM although further study is required to confirm this.Disclosures All Authors: No reported disclosures

1360. Prevalence of Bacteremia in Hospitalized Patients with Skin and Soft Tissue Infections (SSTI)

BackgroundSkin and soft tissue infections (SSTI) are common in outpatient and inpatient settings. The prevalence of positive blood cultures (BC) ranges from 2% to 52%. Because of the variations in published data, the exact prevalence of bacteremia in hospitalized patients with SSTI is unknown. Our objective is to determine the prevalence of bacteremia in hospitalized patients with SSTI.MethodsRetrospective chart review from January 2017 to December 2018. Patients older than 18 years admitted with SSTI who required BC on admission were included. Patients who met the criteria for systemic inflammatory response syndrome (SIRS)/sepsis or severe SSTI, or had an underlying immunodeficiency underwent BC collection. Patients with diabetic foot ulcer, device related SSTI, necrotizing fasciitis, and osteomyelitis were excluded. Patients were divided into 3 groups: true positive (TP) defined as a true pathogen, false positive (FP) defined as a contaminant, and true negative (TN) defined as no growth in BC. Physician assessment, microorganisms isolated, number of positive bottles/culture sets, and timing of growth were reviewed. Patients’ comorbidities, presence of SIRS, laboratory data, duration of antibiotic use, and length of stay (LOS) were compared.ResultsWe screened 583 patients and included 541 patients. The mean age was 62 ± 18.4 years, and 60% were male. 47/ 541 (8.6%) had skin abscesses. 57 patients (11%) had positive BC, of whom 32 were TP (6%), and 25 were FP (5%). 89% of patients (484) had TN BC. The organisms isolated are described in Figures 1 and 2. Patients in the FP and TN groups had prior antibiotic use, compared to TP (P< 0.05). The FP group had a longer LOS and duration of antibiotic use compared to the TN group (p< 0.05). 76% of FP had repeated BC. Beta-lactam antibiotics were mostly used, followed by anti-MRSA antibiotics (40%). We did not find risk factors to predict the likelihood of bacteremia. The outcome was not different among the 3 groups.Figure 1. Microorganisms isolated from blood cultures of patients with SSTI – True pathogens Figure 2. Microorganisms isolated from blood cultures of patients with SSTI – Isolated contaminants ConclusionThere was a low incidence of true bacteremia (6%) in hospitalized patients with SSTI. More than 90% of TP were predictable causal microorganisms, which are covered by empiric antibiotics. BC may not affect the initial treatment of SSTI. FP BC were associated with an increased LOS, longer antibiotic use, and increased healthcare cost.Disclosures All Authors: No reported disclosures

Utility of Methicillin-Resistant Staphylococcus aureus Nares Screening in Hospitalized Children with Acute Infectious Disease Syndromes.

Studies in adults support the use of a negative methicillin-resistant Staphylococcus aureus (MRSA) nares screening (MNS) to help limit empiric anti-MRSA antibiotic therapy. We aimed to evaluate the use of MNS for anti-MRSA antibiotic de-escalation in hospitalized children (<18 years). Records of patients admitted between 1 January 2015 and 31 December 2020 with a presumed infectious diagnosis who were started on anti-MRSA antibiotics, had a PCR-based MNS, and a clinical culture performed were retrospectively reviewed. A total of 95 children were included with a median age (range) of 2 (0–17) years. The top three diagnosis groups were skin and soft tissue infections (n = 38, 40%), toxin-mediated syndromes (n = 17, 17.9%), and osteoarticular infections (n = 14, 14.7%). Nasal MRSA colonization and growth of MRSA in clinical cultures was found in seven patients (7.4%) each. The specificity and the negative predictive value (NPV) of the MNS to predict a clinical MRSA infection were both 95.5%. About half (n = 55, 57.9%) had anti-MRSA antibiotics discontinued in-house. A quarter (n = 14, 25.5%) were de-escalated based on the negative MNS test alone, and another third (n = 21, 38.2%) after negative MNS test and negative culture results became available. A high NPV suggests that MNS may be useful for limiting unnecessary anti-MRSA therapy and thereby a useful antimicrobial stewardship tool for hospitalized children. Prospective studies are needed to further characterize the utility of MNS for specific infectious diagnoses.

Impact of Order-Set Modifications and Provider Education Following Guideline Updates on Broad-Spectrum Antibiotic Use in Patients Admitted With Community Acquired Pneumonia.

Purpose: Following updates to the Infectious Diseases Society of America (IDSA) practice guidelines for the Diagnosis and Treatment of Adults with Community-acquired Pneumonia in 2019, Hartford HealthCare implemented changes to the community acquired pneumonia (CAP) order-set in August 2020 to reflect criteria for the prescribing of broad-spectrum antimicrobial therapy. The objective of the study was to evaluate changes in broad-spectrum antibiotic days of therapy (DOT) following these order-set updates with accompanying provider education. Methods: This was a multi-center, quasi-experimental, retrospective study of patients with a diagnosis of CAP from September 1, 2019 to October 31, 2019 (pre-intervention) and September 1, 2020 to October 31, 2020 (post-intervention). Patients were identified using ICD-10 codes (A48.1, J10.00-J18.9) indicating lower respiratory tract infection. Data collected included demographics, labs and vitals, radiographic, microbiological, and antibiotic data. The primary outcome was change in broad-spectrum antibiotic DOT, specifically anti-pseudomonal β-lactams and anti-MRSA antibiotics. Secondary outcomes included guideline-concordance of initial antibiotics, utilization of an order-set to prescribe antibiotics, and length of stay (LOS). Results: A total of 331 and 352 patients were included in the pre- and post-intervention cohorts, respectively. There were no differences in order-set usage (10% vs 11.3%, P = .642) between the pre- and post-intervention cohort, respectively. The overall duration of broad-spectrum therapy was a median of 2 days (IQR 0-8 days) in the pre-intervention period and 0 days (IQR 0-4 days) in the post-intervention period (P < .001). Patients in whom the order-set was used in the post-intervention period were more likely to have guideline-concordant regimens ([36/40] 90% vs [190/312] 60.9%; P = .003). Hospital LOS was shorter in the post-intervention cohort (4.8 days [2.9-7.2 days] vs 5.3 days [IQR 3.5-8.5 days], P = .002). Conclusion: Implementation of an updated CAP order-set with accompanying provider education was associated with reduced use of broad-spectrum antibiotics. Opportunities to improve compliance and thus further increase guideline-concordant therapy require investigation.

Detection of Inducible Resistance to Clindamycin among Methicillin Resistant and Sensitive strains of Staphylococcus aureus from India

The resistance to MLSB antibiotics, i.e. Macrolide-Lincosamide-Streptogramin B (MLSB), is an increasing problem among Methicillin-resistant Staphylococci. The resistance to macrolides can be by efflux mechanism or via inducible or constitutive resistance. Unfortunately, routine clindamycin susceptibility testing fails to detect the inducible resistance, which commonly results in treatment failure and necessitates incorporating a simple D-test to detect such resistance. A retrospective observational study was performed on S. aureus isolates from patients. The strains were subjected to antibiotic susceptibility testing followed by detection of mecA gene by a polymerase chain reaction and, the ‘D-test’ was performed to know the inducible resistance to clindamycin. A total of 235 isolates were identified as S. aureus. Antibiotic susceptibility test indicated 190 MRSA and 45 are sensitive to MLSB (MS). Inducible clindamycin resistance was found among 48 (20.4%) isolates and constitutive resistance in 104 (44.2%). MRSA strains had higher inducible and constitutive resistance than MSSA strains (22.1%, 51.6% and 13.3%, 13.3%, respectively). Clindamycin is a commonly used antibiotic in patients with MRSA infections to spare higher-end anti-MRSA antibiotics like linezolid and vancomycin. To detect inducible clindamycin to avoid treatment failures; the study showed the importance of incorporating the D-test in routine testing.

Consumption of anti-meticillin-resistant Staphylococcus aureus antibiotics in Swiss hospitals is associated with antibiotic stewardship measures

Consumption of antibiotics active against meticillin-resistant Staphylococcus aureus (MRSA) has been described in numerous European studies. However, the underlying predictors of consumption are still poorly understood. To describe the consumption of anti-MRSA antibiotics (daptomycin, intravenous glycopeptides, linezolid) in Switzerland over time and to identify underlying predictor variables. A retrospective observational multi-centre study was conducted in 21 Swiss hospitals over a period of 11 years (2009-2019). Multiple linear regression models were built to identify regional and hospital-specific predictor variables affecting the consumption of anti-MRSA antibiotics. Consumption of anti-MRSA antibiotics increased between 2009 and 2019 from 12.7 to 24.5 defined daily doses per 1000 bed-days (+93%). In the first model presented, which includes data of the whole study period, the following variables were associated with higher anti-MRSA antibiotic consumption: number of MRSA cases (P < 0.01), year (P < 0.01), hospital type (tertiary care university hospitals vs others, P < 0.01), hospital department (intensive care unit vs others, P < 0.01) and linguistic region (French vs German and German vs Italian, P < 0.01). In a second model including data from a query on hospital policies in place in 2019, the presence of an antibiotic stewardship group (P < 0.01) and prescription restrictions (P < 0.01) were associated with consumption of anti-MRSA antibiotics. Our study shows that both the presence of an antibiotic stewardship group and the implementation of prescription restrictions, i.e. factors that can be controlled by the hospital itself, were associated with a lower consumption of anti-MRSA antibiotics.

Clinical outcomes of intervention for carbapenems and anti-methicillin-resistant Staphylococcus aureus antibiotics by an antimicrobial stewardship team

BackgroundThere are no reports on the effects of interventions, such as discontinuation and change and/or de-escalation of carbapenems and anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotics by an antimicrobial stewardship team focusing on detailed patient outcomes. This study aimed to evaluate these effects. MethodsThis retrospective cohort study was conducted at a tertiary care hospital from December 2018 to November 2019. ResultsFavorable clinical responses were obtained in 165 of 184 cases (89.7%) in the intervention-accepted group, higher than those in the not accepted group (14/19 cases, 73.7%; P = .056). All-cause 30 day mortality was lower in the accepted group than in the not accepted group (1.1% and 10.5%, respectively; P = .045). The microbiological outcomes were similar between the two groups. Duration of carbapenem and anti-MRSA antibiotic use in the accepted group was significantly lower than that in the not accepted group (median [interquartile range]: 8 days [5-13] versus 14 days [8-15], respectively, P = .026 for carbapenem; 10 days [5.3-15] vs 15.5 days [13.8-45.3], respectively, P = .014 for anti-MRSA antibiotic). ConclusionsThis is the first study to investigate the effects of interventions such as discontinuation and change and/ or de-escalation of antibiotics on detailed outcomes. Our intervention could reduce the duration of carbapenem and anti-MRSA antibiotic use without worsening clinical and microbiological outcomes.

MRSA Community-acquired Pneumonia: Non COVID-19 Related Bilateral Ground-glass Opacities

Methicillin-resistant staph aureus (MRSA) has been known to cause severe hospital-acquired infections with its multi-drug resistant nature. MRSA Infections could quickly escalate into severe sepsis resulting in death, if not recognized and treated abruptly. This pathogen uncommonly causes Community-Acquired Pneumonia (CAP), which can lead to under treatment due to delayed coverage with anti-MRSA antibiotics resulting in poor clinical outcome. We herein describe an unusual case of MRSA CAP during COVID-19 pandemic in an 80-year-old male who was unresponsive and found to be in septic shock, intubated outside the hospital setting, and then brought to intensive care unit for further management. Laboratory and radiographic studies revealed MRSA in sputum culture and extensive bilateral consolidation with bilateral ground glass opacities and pleural effusions on imaging. Our patient was successfully treated with linezolid and extubated within 48 hours with a favorable outcome. High index of suspicion and a timely coverage with anti-MRSA antibiotics would reduce mortality and lead to a better outcome in otherwise fatal infection. Keywords: MRSA; Community-acquired pneumonia; Respiratory failure; Critical care; Case report

Antibiotic resistance among major pathogens compared to hospital treatment guidelines and antibiotic use in Nordic hospitals 2010–2018

Background The Nordic countries have comparable nationwide antibiotic resistance surveillance systems and individual antibiotic stewardship programmes. The aim of this study was to assess antibiotic resistance among major pathogens in relation to practice guidelines for hospital antibiotic treatment and antibiotic use in Nordic countries 2010–2018. Methods Antibiotic resistance among invasive isolates from 2010–2018 and aggregated antibiotic use were obtained from the European Centre for Disease Prevention and Control. Hospital practice guidelines were obtained from national or regional guidelines. Results Antibiotic resistance levels among Escherichia coli and Klebsiella pneumoniae were similar in all Nordic countries in 2018 and low compared to the European mean. Guidelines for acute pyelonephritis varied; 2nd generation cephalosporin (Finland), 3rd generation cephalosporins (Sweden, Norway), ampicillin with an aminoglycoside or aminoglycoside monotherapy (Denmark, Iceland and Norway). Corresponding guidelines for sepsis of unknown origin were 2nd (Finland) or 3rd (Sweden, Norway, Iceland) generation cephalosporins, carbapenems, (Sweden) combinations of penicillin with an aminoglycoside (Norway, Denmark), or piperacillin-tazobactam (all Nordic countries). Methicillin-resistant Staphylococcus aureus rates were 0–2% and empirical treatment with anti-MRSA antibiotics was not recommended in any country. Rates of penicillin non-susceptibility among Streptococcus pneumoniae were low (<10%) except in Finland and Iceland (<15%), but benzylpenicillin was recommended for community-acquired pneumonia in all countries. Conclusion Despite similar resistance rates among Enterobacteriaceae there were differences in practice guidelines for pyelonephritis and sepsis. National surveillance of antibiotic resistance can be used for comparison and optimization of guidelines and stewardship interventions to preserve the low levels of antibiotic resistance in Nordic countries.

State of the art in cystic fibrosis pharmacology optimization of antimicrobials in the treatment of cystic fibrosis pulmonary exacerbations: III. Executive summary

Acute pulmonary exacerbationsare complications of cystic fibrosis (CF) and are associated with increased morbidity and mortality. Methicillin-resistant Staphylococcus aureus (MRSA) and Aspergillus fumigatus are organisms that have been detected in the lungs of CF patients. The focus of this review is to provide an overview of the classes of antimicrobials used for MRSA and allergic bronchopulmonary aspergillosis (ABPA), a hypersensitivity reaction caused by A. fumigatus. The current anti-MRSA antibiotics and medications for ABPA dosing recommendations are discussed. This article also reviews the findings from the MRSA utilization surveys and the pharmacokinetic and pharmacodynamic differences between CF and non-CF patients. Antimethicillin S. aureusantibiotics include ceftaroline, clindamycin, fluoroquinolone derivatives (ciprofloxacin, levofloxacin), glycopeptide derivatives (telavancin, vancomycin), linezolid, rifampin, sulfamethoxazole/trimethoprim, and tetracycline derivatives (doxycycline, minocycline, tigecycline). Medications used for ABPA include corticosteroids, amphotericin B, azole antifungals (isavuconazole, itraconazole, posaconazole, voriconazole), and a monoclonal antibody, omalizumab.