OBJECTIVE: Prompt initiation of antibiotic therapy improves the survival of patients with bloodstream infections (BSI). We sought to determine if the sequence of administration of the first dose of antibiotic therapy (i.e., β-lactam or vancomycin, if both cannot be administered simultaneously) impacts early mortality for patients with BSI.

METHODS: We conducted a multicenter, observational study of patients ≥13 years with BSIs to evaluate the association of the sequence of antibiotic administration with 7-day mortality using inverse probability of treatment weighting (IPTW) incorporating propensity scores. Propensity scores were generated based on: demographics, Pitt bacteremia score, ICU status, highest lactate, highest WBC count, Charlson Comorbidity index, severe immunocompromise, administration of active empiric therapy, combination therapy, and time from emergency department arrival to first antibiotic dose.

RESULTS: Of 3,376 eligible patients, 2,685 (79.5%) received a β-lactam and 691 (20.5%) received vancomycin as their initial antibiotic. In the IPTW cohort, exposed and unexposed patients were similar on all baseline variables. Administration of a β-lactam agent prior to vancomycin protected against 7-day mortality (aOR 0.48 (95% CI: 0.33-0.69)]. Similar results were observed when evaluating 48-hour mortality (aOR 0.45 [95% CI: 0.24-0.83]). Administration of vancomycin prior to a β-lactam was not associated with improved survival in the subgroup of 524 patients with methicillin-resistant Staphylococcus aureus BSI (aOR 0.93 [95% CI: 0.33-2.63]).

CONCLUSIONS: For ill-appearing patients likely to be experiencing a BSI, prioritizing administration of a β-lactam over vancomycin may reduce early mortality, underscoring the significant impact of a relatively simple practice change on improving patient survival.

The Centers for Medicare & Medicaid Services’ Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure has appropriately established sepsis as a national priority. However, the Infectious Diseases Society of America (IDSA and five additional endorsing societies) is concerned about SEP-1’s potential to drive antibiotic overuse because it does not account for the high rate of sepsis overdiagnosis and encourages aggressive antibiotics for all patients with possible sepsis, regardless of the certainty of diagnosis or severity of illness. IDSA is also concerned that SEP-1’s complex “time zero” definition is not evidence-based and is prone to inter-observer variation. In this position paper, IDSA outlines several recommendations aimed at reducing the risk of unintended consequences of SEP-1 while maintaining focus on its evidence-based elements. IDSA’s core recommendation is to limit SEP-1 to septic shock, for which the evidence supporting the benefit of immediate antibiotics is greatest. Prompt empiric antibiotics are often appropriate for suspected sepsis without shock, but IDSA believes there is too much heterogeneity and difficulty defining this population, uncertainty about the presence of infection, and insufficient data on the necessity of immediate antibiotics to support a mandatory treatment standard for all patients in this category. IDSA believes guidance on managing possible sepsis without shock is more appropriate for guidelines that can delineate the strengths and limitations of supporting evidence and allow clinicians discretion in applying specific recommendations to individual patients. Removing sepsis without shock from SEP-1 will mitigate the risk of unnecessary antibiotic prescribing for noninfectious syndromes, simplify data abstraction, increase measure reliability, and focus attention on the population most likely to benefit from immediate empiric broad-spectrum antibiotics.

<p>The Centers for Medicare &amp; Medicaid Services' Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure has appropriately established sepsis as a national priority. However, the Infectious Diseases Society of America (IDSA and five additional endorsing societies) is concerned about SEP-1's potential to drive antibiotic overuse because it does not account for the high rate of sepsis overdiagnosis and encourages aggressive antibiotics for all patients with possible sepsis, regardless of the certainty of diagnosis or severity of illness. IDSA is also concerned that SEP-1's complex "time zero" definition is not evidence-based and is prone to inter-observer variation. In this position paper, IDSA outlines several recommendations aimed at reducing the risk of unintended consequences of SEP-1 while maintaining focus on its evidence-based elements. IDSA's core recommendation is to limit SEP-1 to septic shock, for which the evidence supporting the benefit of immediate antibiotics is greatest. Prompt empiric antibiotics are often appropriate for suspected sepsis without shock, but IDSA believes there is too much heterogeneity and difficulty defining this population, uncertainty about the presence of infection, and insufficient data on the necessity of immediate antibiotics to support a mandatory treatment standard for all patients in this category. IDSA believes guidance on managing possible sepsis without shock is more appropriate for guidelines that can delineate the strengths and limitations of supporting evidence and allow clinicians discretion in applying specific recommendations to individual patients. Removing sepsis without shock from SEP-1 will mitigate the risk of unnecessary antibiotic prescribing for noninfectious syndromes, simplify data abstraction, increase measure reliability, and focus attention on the population most likely to benefit from immediate empiric broad-spectrum antibiotics.</p>

<p><strong>BACKGROUND: </strong>Perceived patient demand for antibiotics drives unnecessary antibiotic prescribing in outpatient settings, but little is known about how clinicians experience this demand or how this perceived demand shapes their decision-making.</p>

<p><strong>OBJECTIVE: </strong>To identify how clinicians perceive patient demand for antibiotics and the way these perceptions stimulate unnecessary prescribing.</p>

<p><strong>METHODS: </strong>Qualitative study using semi-structured interviews with clinicians in outpatient settings who prescribe antibiotics. Interviews were analyzed using conventional and directed content analysis.</p>

<p><strong>RESULTS: </strong>Interviews were conducted with 25 clinicians from nine practices across three states. Patient demand was the most common reason respondents provided for why they prescribed non-indicated antibiotics. Three related factors motivated clinically unnecessary antibiotic use in the face of perceived patient demand: (i) clinicians want their patients to regard clinical visits as valuable and believe that an antibiotic prescription demonstrates value; (ii) clinicians want to avoid negative repercussions of denying antibiotics, including reduced income, damage to their reputation, emotional exhaustion, and degraded relationships with patients; (iii) clinicians believed that certain patients are impossible to satisfy without an antibiotic prescription and felt that efforts to refuse antibiotics to such patients wastes time and invites the aforementioned negative repercussions. Clinicians in urgent care settings were especially likely to describe being motivated by these factors.</p>

<p><strong>CONCLUSION: </strong>Interventions to improve antibiotic use in the outpatient setting must address clinicians' concerns about providing value for their patients, fear of negative repercussions from denying antibiotics, and the approach to inconvincible patients.</p>

<p><strong>BACKGROUND: </strong>In 2010, the Clinical and Laboratory Standards Institute (CLSI) revised and lowered the ceftriaxone minimum inhibitory concentration breakpoints for Enterobacteriaceae and removed the requisite extended spectrum β-lactamase phenotypic testing for organisms with elevated minimum inhibitory concentrations. The impact that these recommendations have on clinical outcomes of children have not been previously evaluated.</p>

<p><strong>METHODS: </strong>We conducted a retrospective study to compare clinical outcomes between children treated with ceftriaxone and those treated with broader spectrum β-lactams for Enterobacteriaceae bacteremia with reduced susceptibility (minimum inhibitory concentrations 4-8 µg/mL) to ceftriaxone according to the new CLSI interpretive criteria. Mortality and microbiological relapse were evaluated using a multivariable logistic regression model.</p>

<p><strong>RESULTS: </strong>There were a total of 783 unique children with Enterobacteriaceae bacteremia during the study period. Using the CLSI breakpoints before 2010, 76 children would have had clinical isolates resistant to ceftriaxone. With the revised breakpoints, 229 Enterobacteriaceae isolates would no longer be susceptible to ceftriaxone (&gt;300% increase). Of the 136 children who met eligibility criteria, 63 children received ceftriaxone and 73 children received broader spectrum β-lactams. There was no difference in 30-day mortality (odds ratio 0.81, 95% confidence interval: 0.31-2.59) or microbiological relapse (odds ratio 0.97, 95% confidence interval: 0.36-2.66) between the groups.</p>

<p><strong>CONCLUSIONS: </strong>Our findings do not support the proposed clinical benefit of more conservative CLSI breakpoints. The revised breakpoints promote increased broad-spectrum β-lactam use. The need for lowered ceftriaxone breakpoints against Enterobacteriaceae in children needs to be reevaluated in larger prospective studies.</p>