72. Evaluation of Acclerate Pheno™ on Clinical and Antimicrobial Outcomes in Patients with Methicillin Susceptible Staphylococcus aureus Bloodstream Infections

Abstract Background Anti-staphylococcal beta-lactams (BL) are treatment of choice for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI) as they have superior MSSA bacteremia clearance. Based on the hypothesis that earlier initiation of anti-staphylococcal BL may improve clinical outcomes, this study compared clinical and microbiologic features of patients with MSSA BSI pre- and post-implementation of Accelerate Pheno™ (AXDX). Methods This was a case-control analysis of adult inpatients with MSSA BSI analyzed using AXDX compared to traditional laboratory methods. Cases were prospectively identified by the antimicrobial stewardship team between August and October 2020 post implementation of AXDX in July 2020. Patients were matched with historical controls (July 2018–July 2020) based on age (±4 years), gender, organism, and source of infection. The primary outcome was time to antibiotic (abx) deescalation to an anti-staphylococcal beta-lactam. Secondary outcomes included hospital length of stay (LOS), 30-day all-cause mortality and hospital readmission, and 60-day C. difficile infection. Results A total of 25 cases with MSSA BSI were identified, of which 18 (72%) were matched to historical controls. Of these patients, 12 (67%) were male with an average age of 67 years (SD ±12). Other demographics were similar between groups. The median time to species identification [21.3 hours in cases (IQR 14–31.9) vs 33.3 hours in controls (29–41.7), p=0.046] and abx susceptibilities [22.5 hours (18.8 – 42) vs 60.1 hours (46–61.9), p< 0.001] were significantly shorter in cases. The average time to abx deescalation from time to organism susceptibility was 1.7 days (±1.9) for cases compared to 2.7 days (±1.5) for controls (p = 0.129). There were no significant differences detected in hospital LOS, 30-day mortality or readmission, and 60-day C.difficile infection. Conclusion Although time to organism identification and abx susceptibilities was significantly shorter in cases, AXDX was not associated with a statistically significant reduction in time to anti-staphylococcal BL initiation nor a difference in associated clinical outcomes. A trend in shorter time to abx de-escalation was observed and warrants further investigation in a larger population. Disclosures All Authors: No reported disclosures

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254. Review of Clinical Outcomes in Patients Treated with Beta-lactam vs Non-beta-lactam Therapy for AmpC Producing Bacterial Bloodstream Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.298 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S126-S126

Author(s):

Mary L Staicu ◽

Tyler Baumeister ◽

Maryrose R Laguio-Vila

Keyword(s):

Length Of Stay ◽

Clinical Outcomes ◽

Bloodstream Infections ◽

Hospital Length ◽

Primary Objective ◽

Hospital Length Of Stay ◽

Beta Lactam ◽

Beta Lactams ◽

Fluoroquinolone Antibiotics ◽

Significant Difference

Abstract Background AmpC beta-lactamase producing organisms are traditionally treated with carbapenem or fluoroquinolone antibiotics. Recent studies, however, describe similar clinical outcomes in patients that receive cefepime or piperacillin/tazobactam. We sought to assess outcomes in patients with bloodstream infections caused by AmpC-producing organisms that received beta-lactams compared non-beta-lactam therapy. Methods Data was obtained retrospectively from the electronic health record (EHR) from January 2012 to February 2020. The primary objective was 30-day mortality from the day of first positive blood cultures with Enterobacter spp., Citrobacter spp., or Serratia spp. in patients who received non-beta-lactam therapy (carbapenem, fluoroquinolone, trimethoprim/sulfamethoxazole) to those who received beta-lactam therapy (cefepime, piperacillin/tazobactam). Secondary objectives included 30-day recurrence of bacteremia, pathogen isolated, source of bacteremia, hospital length of stay, and duration of antimicrobial therapy. Results A total of 90 patients were included, 50 in the non-beta lactam group and 40 in the beta-lactam group. Demographics were similar between groups. Thirty-day mortality was significantly higher in the beta-lactam group (20% vs 2%, p=0.009). Enterobacter spp. was the most frequently identified pathogen (67%), most commonly isolated from a urinary (31%) or intra-abdominal source (22%). The average duration of antibiotic therapy was significantly higher in the non-beta lactam group (18 vs 12 days, p=0.001). In contrast, there was no significant difference found in hospital length of stay, recurrence of bacteremia, pathogen isolated or source of bacteremia between groups. Conclusion Beta-lactam therapy for the treatment of bloodstream infections caused by Amp-C producing organisms was associated with significantly greater 30-day mortality compared to patients that received non-beta-lactam therapy. Disclosures All Authors: No reported disclosures

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627. Molecular Epidemiology of Daptomycin-resistant Staphylococcus aureus Causing Bloodstream Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.695 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S291-S291

Author(s):

Smitha Gudipati ◽

Mary Perri ◽

Natacha Couto ◽

Erica Herc ◽

Marcus Zervos

Keyword(s):

Staphylococcus Aureus ◽

Laboratory Data ◽

Point Mutations ◽

Gene Mutations ◽

Bloodstream Infections ◽

Hospital Length ◽

Hospital Length Of Stay ◽

Methicillin Resistant ◽

Epidemiological Risk ◽

Tertiary Healthcare

Abstract Background Daptomycin (Dap) has become increasingly important to combat infections caused by Staphylococcus aureus (SA). However, reports of daptomycin nonsusceptible (DNS) SA strains have emerged over the recent years, specifically with alteration of the MprF gene. Mutations in this gene lead to an increase in lysyl-phosphatidyl glycerol production resulting in a lower susceptibility to Dap and cationic antimicrobial peptides. Point mutations in the cls2 gene have also been associated with DNS SA through similar mechanisms of action. This study describes the gene mutations involved in our patients with SA bloodstream infections (BSIs) that developed Dap resistance. Methods This is a retrospective study in a tertiary healthcare system in southeast Michigan. SA blood isolates were sequenced through a gene-by-gene approach using Ridom SeqSphere. Charts were reviewed for clinical and laboratory data. Dap minimum inhibitory concentrations (MICs) were determined by E-test. DNS was defined as an MIC > 1.0 µg/mL. Results From December 3, 2015 to May 8, 2017, 7 patients were identified with DNS SA BSI. Mean age of the patients was 59 (SD = 13.7) and 86% were male. Mean bacteremia duration was 7 days (SD = 6.3), mean hospital length of stay was 13 days (SD = 9.8), 5 isolates were methicillin-resistant SA, and 2 were methicillin-sensitive SA. When comparing molecular sequencing of all seven patients with their Dap-sensitive strains vs. resistant strains, all patients, except for patient 3, had a point mutation at different allele loci in the MprF gene (Table 1). Additionally, two patients had point mutations in the cls2 gene. When comparing all 27 strains from the seven patients, each cluster was attributed to an individual patient with the exception of cluster one that included patients 5 and 6 suggesting transmission (Figure 1). Conclusion DNS SA is infrequent; however, the present study shows that it can emerge both from methicillin-resistant and -susceptible SA most commonly when developing MprF and cls2 gene mutations as seen in our patients. Patient 3 was the exception in our analysis and likely developed DNS SA through another gene mutation. Further studies are necessary to know the frequency of each mutation with all genes associated with DNS SA, and epidemiological risk factors of transmission. Disclosures All authors: No reported disclosures

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Extended Infusion of Beta-Lactams Is Associated With Improved Outcomes in Pediatric Patients

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-26.2.187 ◽

2021 ◽

Vol 26 (2) ◽

pp. 187-193

Author(s):

Tracy N. Zembles ◽

Rachael Schortemeyer ◽

Evelyn M. Kuhn ◽

Glenn Bushee ◽

Nathan E. Thompson ◽

...

Keyword(s):

Bone Marrow ◽

Clinical Outcomes ◽

Bone Marrow Transplant ◽

Marrow Transplant ◽

Hospital Length ◽

Hospital Length Of Stay ◽

Beta Lactam ◽

Beta Lactams ◽

Transplant Patients ◽

Extended Infusion

OBJECTIVE The pharmacokinetics of beta-lactam antibiotics favor administration via an extended infusion. Although literature supporting extended infusion beta-lactams exists in adults, few data are available to guide the practice in pediatrics. The purpose of this study was to compare clinical outcomes between extended and standard infusions in children. METHODS This retrospective chart analysis included hospitalized patients 0 to 18 years old who received at least 72 hours of cefepime, piperacillin-tazobactam, or meropenem between October 1, 2017, and March 31, 2019. Clinical outcomes of care included hospital length of stay, readmission within 30 days, and all-cause mortality. RESULTS A total of 551 patients (258 extended infusion, 293 standard infusion) met criteria for evaluation. Clinical outcomes among the entire population were similar. A subanalysis of select populations demonstrated decreased mortality in critical care patients (2.1% vs 19.6%, p = 0.006) and decreased 30-day readmission rates in bone marrow transplant patients (0% vs 50%, p = 0.012) who received the extended infusion compared with a standard infusion. CONCLUSIONS Outcomes were similar between extended and standard infusions in children. Subgroup analyses suggest a possible mortality benefit in the critically ill and decreased readmission rate in bone marrow transplant patients.

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Clinical Outcomes of Enterobacteriaceae Infections Stratified by Carbapenem MICs

Journal of Clinical Microbiology ◽

10.1128/jcm.03057-14 ◽

2014 ◽

Vol 53 (1) ◽

pp. 201-205 ◽

Cited By ~ 30

Author(s):

Twisha S. Patel ◽

Jerod L. Nagel

Keyword(s):

Clinical Outcomes ◽

Cohort Analysis ◽

Hospital Length ◽

Hospital Length Of Stay ◽

Limited Data ◽

Content Type ◽

Beta Lactamases ◽

Source Of Infection ◽

Poor Outcomes ◽

Enterobacteriaceae Infections

The Clinical and Laboratory Standards Institute (CLSI) lowered the MIC breakpoints for meropenem and imipenem from 4 mg/liter to 1 mg/liter forEnterobacteriaceaein 2010. The breakpoint change improves the probability of pharmacodynamic target attainment and eliminates the need for microbiology labs to perform confirmatory testing forKlebsiella pneumoniaecarbapenemase (KPC) production or other beta-lactamases that hydrolyze carbapenems. However, there are limited data evaluating clinical outcomes of the affected breakpoints, and it is unknown if patients infected withEnterobacteriaceaewith reduced susceptibility are more likely to have poor outcomes when treated with a carbapenem. We conducted a single-center retrospective matched-cohort analysis in adult patients withEnterobacteriaceaeinfections treated with meropenem, imipenem, or doripenem. Patients withEnterobacteriaceaeinfection with a carbapenem MIC of 2 to 8 mg/liter were matched based on pathogen, source of infection, comorbidities, and disease severity (1:1 ratio) to those with a carbapenem MIC of ≤1 mg/liter. A total of 36 patients were included in the study. The group with carbapenem MICs of 2 to 8 mg/liter had a significantly higher 30-day mortality than the group with carbapenem MICs of ≤1 mg/liter (38.9% compared to 5.6%,P= 0.04). Total hospital length of stay (LOS) and intensive care unit (ICU) LOS were longer in the group with MICs of 2 to 8 mg/liter than in the group with MICs of ≤1 mg/liter (57.6 days compared to 34.4 days [P= 0.06] and 56.6 days compared to 21.7 days [P< 0.01], respectively). Patients infected withEnterobacteriaceaewith a carbapenem MIC of 2, 4, or 8 mg/liter had higher mortality rates and longer ICU LOS than matched cohorts with carbapenem MICs of ≤1 mg/liter, which supports CLSI's recommendation to lower susceptibility breakpoints for carbapenems.

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Evaluation of Delirium in Critically Ill Patients Prescribed Melatonin or Ramelteon

Annals of Pharmacotherapy ◽

10.1177/10600280211002054 ◽

2021 ◽

pp. 106002802110020

Author(s):

Natasha Romero ◽

Kevin M. Dube ◽

Kenneth E. Lupi ◽

Jeremy R. DeGrado

Keyword(s):

Clinical Outcomes ◽

Critically Ill ◽

Critically Ill Patients ◽

Receptor Agonist ◽

Hospital Length ◽

Hospital Length Of Stay ◽

Melatonin Receptor ◽

Observational Cohort ◽

Impaired Sleep ◽

Retrospective Observational Cohort Study

Background: An impaired sleep-wake cycle may be one factor that affects the development of delirium in critically ill patients. Several small studies suggest that exogenous melatonin or ramelteon may decrease the incidence and/or duration of delirium. Objective: To compare the effect of prophylactic administration of melatonin, ramelteon, or no melatonin receptor agonist on the development of delirium in the intensive care unit (ICU). Methods: This was a single-center, retrospective, observational cohort study of nondelirious patients in the ICU who received melatonin, ramelteon, or no melatonin receptor agonist. The primary end point was the incidence of delirium. Secondary end points included assessments of daily level of sedation and daily utilization of antipsychotic, sedative, and opioid agents. Results: No difference was observed in the incidence of delirium among the melatonin, ramelteon, and placebo cohorts (18.7% vs 14.3% vs 13.8%; P = 0.77). A difference was observed in the rate of agitation and sedation among the 3 groups, with the greatest observed in the melatonin cohort. Additionally, there was a difference in the use of propofol, dexmedetomidine, and opioids. Overall, there was no difference in clinical outcomes, including duration of mechanical ventilation and ICU or hospital length of stay. Conclusion and Relevance: Therapy with melatonin, ramelteon, and no melatonin receptor agonist resulted in similar rates of delirium in a mixed ICU population. Despite significant differences in agitation, sedation, and medication utilization, there was no differences in the clinical outcomes evaluated.

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Medical Comorbidity in Psychiatric Inpatients: Relation to Clinical Outcomes and Hospital Length of Stay

Psychosomatics ◽

10.1176/appi.psy.43.1.24 ◽

2002 ◽

Vol 43 (1) ◽

pp. 24-30 ◽

Cited By ~ 85

Author(s):

Constantine G. Lyketsos ◽

Gary Dunn ◽

Michael J. Kaminsky ◽

William R. Breakey

Keyword(s):

Length Of Stay ◽

Clinical Outcomes ◽

Psychiatric Inpatients ◽

Hospital Length ◽

Hospital Length Of Stay ◽

Medical Comorbidity

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Prevalence and Risk Factors Associated with Vancomycin-Resistant Staphylococcus aureus Precursor Organism Colonization among Patients with Chronic Lower-Extremity Wounds in Southeastern Michigan

Infection Control and Hospital Epidemiology ◽

10.1086/671735 ◽

2013 ◽

Vol 34 (9) ◽

pp. 954-960 ◽

Cited By ~ 13

Author(s):

Pritish K. Tosh ◽

Simon Agolory ◽

Bethany L. Strong ◽

Kerrie VerLee ◽

Jennie Finks ◽

...

Keyword(s):

Risk Factors ◽

Staphylococcus Aureus ◽

Lower Extremity ◽

Chronic Wounds ◽

Cohort Analysis ◽

Case Control ◽

Control Analysis ◽

Vancomycin Resistant ◽

Clinical Records ◽

Case Control Analysis

Background.Of the 13 US vancomycin-resistant Staphylococcus aureus (VRSA) cases, 8 were identified in southeastern Michigan, primarily in patients with chronic lower-extremity wounds. VRSA infections develop when the vanA gene from vancomycin-resistant enterococcus (VRE) transfers to S. aureus. Incl8-like plasmids in VRE and pSK41-like plasmids in S. aureus appear to be important precursors to this transfer.Objective.Identify the prevalence of VRSA precursor organisms.Design.Prospective cohort with embedded case-control study.Participants.Southeastern Michigan adults with chronic lower-extremity wounds.Methods.Adults presenting to 3 southeastern Michigan medical centers during the period February 15 through March 4, 2011, with chronic lower-extremity wounds had wound, nares, and perirectal swab specimens cultured for S. aureus and VRE, which were tested for pSK41-like and Incl8-like plasmids by polymerase chain reaction. We interviewed participants and reviewed clinical records. Risk factors for pSK41-positive S. aureus were assessed among all study participants (cohort analysis) and among only S. aureus-colonized participants (case-control analysis).Results.Of 179 participants with wound cultures, 26% were colonized with methicillin-susceptible S. aureus, 27% were colonized with methicillin-resistant S. aureus, and 4% were colonized with VRE, although only 17% consented to perirectal culture. Six participants (3%) had pSK41-positive S. aureus, and none had Incl8-positive VRE. Having chronic wounds for over 2 years was associated with pSK41-positive S. aureus colonization in both analyses.Conclusions.Colonization with VRSA precursor organisms was rare. Having long-standing chronic wounds was a risk factor for pSK41-positive S. aureus colonization. Additional investigation into the prevalence of VRSA precursors among a larger cohort of patients is warranted.

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Evaluating the Role of Staphylococcus aureus Nasal PCR in Pediatric Head and Neck Infections

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-26.7.734 ◽

2021 ◽

Vol 26 (7) ◽

pp. 734-739

Author(s):

Chandni Patel ◽

Guru Bhoojhawon ◽

Lukasz Weiner ◽

Danelle Wilson ◽

Derek Zhorne ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Treatment Failure ◽

Head And Neck ◽

Pediatric Patients ◽

Total Duration ◽

Kidney Injury ◽

Hospital Length ◽

Hospital Length Of Stay ◽

Head And Neck Infections

OBJECTIVE Vancomycin is often empirically used in the management of head and neck infections (HNIs) in children. The objective of this study was to determine the utility of Staphylococcus aureus (SA) nasal PCR to facilitate de-escalation of vancomycin for pediatric HNIs. METHODS This was a single-center, retrospective cohort study of pediatric patients who received empiric intravenous vancomycin for a diagnosis of HNIs between January 2010 and December 2019. Subjects were excluded if they met any of the following: confirmed/suspected coinfection of another site, dialysis, immunocompromised status, admission to the NICU, alternative diagnosis that did not require antibiotics, or readmission for HNIs within 30 days of previous admission. The primary outcome was time to de-escalation of vancomycin. Total duration of antibiotics, treatment failure, hospital length of stay (LOS), and incidence of acute kidney injury (AKI) were also assessed. RESULTS Of the 575 patients identified, 124 patients received an SA nasal PCR. The median time to de-escalation was 39.5 hours in those patients compared with 53.7 hours in patients who did not have a SA nasal PCR (p = 0.002). No difference was noted in total duration of all methicillin-resistant Staphylococcus aureus antibiotics, hospital LOS, treatment failure, and AKI. CONCLUSIONS In a large cohort of pediatric patients with HNIs, those who underwent testing with an SA nasal PCR spent less time receiving intravenous vancomycin, although their LOS was not significantly reduced. Further investigation is needed to better define the role of SA nasal PCRs in determining antibiotic therapy for HNIs.

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What Is the Impact of Ambulatory Vital Sign Monitoring on Deterioration Detection and Related Clinical Outcomes in Hospitalised Patients: a Systematic Review and Meta-analysis.

10.21203/rs.3.rs-697407/v1 ◽

2021 ◽

Author(s):

Carlos Morgado Areia ◽

Christopher Biggs ◽

Mauro Santos ◽

Neal Thurley ◽

Stephen Gerry ◽

...

Keyword(s):

Systematic Review ◽

Clinical Outcomes ◽

Standard Care ◽

Meta Analysis ◽

Ambulatory Monitoring ◽

Hospital Length ◽

Hospital Length Of Stay ◽

Monitoring Systems ◽

Hospitalised Patients ◽

The Impact

Abstract Background: Timely recognition of the deteriorating inpatient remains challenging. Ambulatory monitoring systems (AMS) may augment current monitoring practices. However, there are many challenges to implementation in the hospital environment, and evidence describing the clinical impact of AMS on deterioration detection and patient outcome remains unclear. Objective: To assess the impact of vital signs monitoring on detection of deterioration and related clinical outcomes in hospitalised patients using ambulatory monitoring systems, in comparison with standard care.Methods: A systematic search was conducted in August 2020 using MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, CENTRAL and Health Technology Assessment databases, as well as grey literature. Studies comparing the use of AMS against standard care for deterioration detection and related clinical outcomes in hospitalised patients were included. Deterioration related outcomes (primary) included unplanned intensive care admissions, rapid response team or cardiac arrest activation, total and major complications rate. Other clinical outcomes (secondary) included in-hospital mortality and hospital length of stay. Exploratory outcomes included alerting system parameters and clinical trial registry information. Results: Of 8706 citations, 10 studies with different designs met the inclusion criteria, of which 7 were included in the meta-analyses. Overall study quality was moderate. The meta-analysis indicated that the AMS, when compared with standard care, was associated with a reduction in intensive care transfers (risk ratio, RR, 0.87; 95% confidence interval, CI, 0.66 to 1.15), rapid response or cardiac arrest team activation (RR, 0.84; 95% CI 0.69 to 1.01), total (RR, 0.77; 95% CI 0.44 to 1.32) and major (RR, 0.55; 95% CI 0.24 to 1.30) complications prevalence. There was also association with reduced mortality (RR, 0.48; 95% CI 0.18 to 1.29) and hospital length of stay (mean difference, MD, -0.09; 95% CI -0.43 to 0.44). However, none were statistically significant.Conclusion: This systematic review indicates that implementation of AMS may have a positive impact on early deterioration detection and associated clinical outcomes, but differing design/quality of available studies and diversity of outcomes measures limits a definite conclusion. Our narrative findings suggested that alarms should be adjusted to minimise false alerts and promote rapid clinical action in response to deterioration.PROSPERO Registration number: CRD42020188633

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Intravenous versus Oral Step-Down for the Treatment of Staphylococcus aureus Bacteremia in a Pediatric Population

Pharmacy ◽

10.3390/pharmacy10010016 ◽

2022 ◽

Vol 10 (1) ◽

pp. 16

Author(s):

Sarah Grace Gunter ◽

Mary Joyce B. Wingler ◽

David A. Cretella ◽

Jamie L. Wagner ◽

Katie E. Barber ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Length Of Stay ◽

Therapy Group ◽

Pediatric Population ◽

Hospital Length ◽

Hospital Length Of Stay ◽

Limited Data ◽

Staphylococcus Aureus Bacteremia ◽

Secondary Endpoints ◽

Step Down

Limited data are available regarding optimal antimicrobial therapy for Staphylococcus aureus bacteremia (SAB) in pediatric patients. The purpose of this study was to assess clinical characteristics and outcomes associated with intravenous (IV) versus oral step-down treatment of pediatric SAB. This study evaluated patients aged 3 months to 18 years that received at least 72 h of inpatient treatment for SAB. The primary endpoint was 30-day readmission. Secondary endpoints included hospital length of stay and inpatient mortality. One hundred and one patients were included in this study. The median age was 7.9 years. Patients who underwent oral step-down were less likely to be immunocompromised and more likely to have community-acquired SAB from osteomyelitis or skin and soft tissue infection (SSTI). More patients in the IV therapy group had a 30-day readmission (10 (25.6%) vs. 3 (5.3%), p = 0.006). Mortality was low (5 (5%)) and not statistically different between groups. Length of stay was greater in patients receiving IV therapy only (11 vs. 7 days, p = 0.001). In this study, over half of the patients received oral step-down therapy and 30-day readmission was low for this group. Oral therapy appears to be safe and effective for patients with SAB from osteomyelitis or SSTIs.

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