Showing papers by "Michael Klompas published in 2018"

Difficult-to-Treat Resistance in Gram-negative Bacteremia at 173 US Hospitals: Retrospective Cohort Analysis of Prevalence, Predictors, and Outcome of Resistance to All First-line Agents.

Abstract: Background Resistance to all first-line antibiotics necessitates the use of less effective or more toxic “reserve” agents Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 active first-line antibiotic

Antibiotics for Sepsis—Finding the Equilibrium

Abstract: Sepsis is medicine’s last remaining preserve for unrestrained antibiotic prescribing. The Surviving Sepsis Campaign guidelines recommend empirical broadspectrum therapy within one hour of triage for both sepsis and septic shock.1 This recommendation, and mandates that compel it, encourage clinicians to adopt an approach of “treat first, ask questions later” for patients with any possibility of serious infection. This approach fails to account for the difficulties clinicians face with diagnosing infection, especially when patients initially present to care, and the high rate of overdiagnosis of sepsis, and thus risks promoting excess antibiotic use and causing unintended harm. The recommendation to treat quickly and aggressively may seem sensible because sepsis and septic shock are potentially deadly conditions. Delays in appropriate antimicrobial therapy have been associated with higher mortality rates, and quality improvement initiatives that encouraged earlier prescribing have reported substantial decreases in mortality. Many of the studies supporting these assertions, however, may be biased. Most of these investigations failed to account for

Infectious Diseases Society of America (IDSA) POSITION STATEMENT: Why IDSA Did Not Endorse the Surviving Sepsis Campaign Guidelines.

Abstract: IDSA did not endorse the 2016 Surviving Sepsis Campaign Guidelines despite being represented in the working group that drafted the guidelines document. Leadership from the IDSA, the Surviving Sepsis Campaign Guidelines, and the Society of Critical Care Medicine had numerous amicable discussions primarily regarding the bolded, rated guidelines recommendations. Our societies had different perspectives, however, regarding the interpretation of the major studies that informed the guidelines' recommendations, thus leading us to different conclusions and different perspectives on the recommendations. IDSA consequently elected not to endorse the guidelines. IDSA nonetheless hopes to be able to continue collaborating with the Surviving Sepsis Campaign and the Society of Critical Care Medicine to resolve our differences and to develop further strategies together to prevent sepsis and septic shock as well as reduce death and disability from these conditions both nationally and globally.

Compliance With the National SEP-1 Quality Measure and Association With Sepsis Outcomes: A Multicenter Retrospective Cohort Study.

Abstract: Objectives:Many septic patients receive care that fails the Centers for Medicare and Medicaid Services’ SEP-1 measure, but it is unclear whether this reflects meaningful lapses in care, differences in clinical characteristics, or excessive rigidity of the “all-or-nothing” measure. We compared outcom

Variability in determining sepsis time zero and bundle compliance rates for the centers for medicare and medicaid services SEP-1 measure

Abstract: We compared sepsis "time zero" and Centers for Medicare and Medicaid Services (CMS) SEP-1 pass rates among 3 abstractors in 3 hospitals. Abstractors agreed on time zero in 29 of 80 (36%) cases. Perceived pass rates ranged from 9 of 80 cases (11%) to 19 of 80 cases (23%). Variability in time zero and perceived pass rates limits the utility of SEP-1 for measuring quality.

Oral care with chlorhexidine: beware!

Abstract: Pneumonia in hospitalized patients is usually induced by aspiration of oral pathogens into the lower respiratory system. Oral care with chlorhexidine for the prevention of pneumonia is an appealing alternative because it appears to be safe, effective, and less likely to select for antibiotic resistance than oropharyngeal or digestive decontamination [1, 2]. The evidence that chlorhexidine is safe and effective, however, may be less robust than it seems (Table 1). First, our perception that chlorhexidine oral care prevents ventilator-associated pneumonia (VAP) may be biased. While multiple meta-analyses of randomized controlled trials have reported lower VAP rates, this is not the case if one stratifies by blinding status [3]. Lower VAP rates are only present on meta-analysis of open label studies, not double-blind studies. This suggests a problem with ascertainment bias. Second, chlorhexidine can have adverse effects on the oral mucosa. Plantiga and colleagues, for example, documented erosive oral lesions, ulcerations, white/yellow plaques, and bleeding mucosa in 9.8% of patients treated with 2% oral chlorhexidine [4]. Fortunately, these lesions disappeared after stopping chlorhexidine. More disturbingly, two recent meta-analyses of randomized controlled trials and two observational studies have reported that oral chlorhexidine, paradoxically, may increase mortality risk [3, 5–7]. The mechanism leading to higher mortality rates is unclear, but it may be that some patients aspirate chlorhexidine and develop acute respiratory distress syndrome [8]. In addition, some patients may suffer allergic reactions, including anaphylaxis [9–11]. Finally, the presumption that oral care with chlorhexidine has no impact on resistance may be incorrect. Biocide and antibiotic efflux pump genes are present in bacteria and can confer resistance to chlorhexidine; widespread use of chlorhexidine may accelerate the spread of acquired resistance [12]. A recent study documented decreased susceptibility to chlorhexidine in a quarter of Escherichia coli isolates associated with pneumonia in ICU patients [13]. In an article recently published in Intensive Care Medicine, Deschepper et al. [14] add further concern that oral care with chlorhexidine may be harmful in some patients. These investigators performed a hospital-wide retrospective observational cohort analysis on the effects of chlorhexidine oral care on hospital mortality. They included 82,274 patients, of whom 11,138 (14%) received chlorhexidine. Thee results showed that oral chlorhexidine was associated with an increased risk of death (OR 2.92; 95% CI 2.62–3.26). The association was strongest in patients with the lowest baseline risk of death. The

Rethinking Ventilator Bundles.

Abstract: Critical Care Medicine www.ccmjournal.org 1201 7. Marino BS, Lipkin PH, Newburger JW, et al; American Heart Association Congenital Heart Defects Committee, Council on Cardiovascular Disease in the Young, Council on Cardiovascular Nursing, and Stroke Council: Neurodevelopmental outcomes in children with congenital heart disease: Evaluation and management: A scientific statement from the American Heart Association. Circulation 2012; 126:1143–1172 8. Wehrle FM, Kaufmann L, Benz LD, et al: Very preterm adolescents show impaired performance with increasing demands in executive function tasks. Early Hum Dev 2016; 92:37–43 9. Schiller RM, Madderom MJ, van Rosmalen J, et al: Working Memory Training Following Neonatal Critical Illness: A Randomized Controlled Trial. Crit Care Med 2018; 46:1158–1166 10. Holmes J, Gathercole SE, Dunning DL: Adaptive training leads to sustained enhancement of poor working memory in children. Dev Sci 2009; 12:F9–15 11. Beck SJ, Hanson CA, Puffenberger SS, et al: A controlled trial of working memory training for children and adolescents with ADHD. J Clin Child Adolesc Psychol 2010; 39:825–836 12. Grunewaldt KH, Løhaugen GC, Austeng D, et al: Working memory training improves cognitive function in VLBW preschoolers. Pediatrics 2013; 131:e747–e754 13. Fuentes A, Kerr EN: Maintenance effects of working memory intervention (Cogmed) in children with symptomatic epilepsy. Epilepsy Behav 2017; 67:51–59 14. Hitchcock C, Westwell MS: A cluster-randomised, controlled trial of the impact of Cogmed Working Memory Training on both academic performance and regulation of social, emotional and behavioural challenges. J Child Psychol Psychiatry 2017; 58:140–150 15. Diamond A, Lee K: Interventions shown to aid executive function development in children 4 to 12 years old. Science 2011; 333:959–964

Trends in "usual care" for septic shock.

Abstract: Sepsis is the focus of hospital performance improvement initiatives and national quality measures, but controversy remains regarding the importance and optimal delivery of bundled care. Early goal-directed therapy (EGDT) was initially reported in 2001 to significantly lower mortality rates in septic shock, catalyzing the Surviving Sepsis Campaign and EGDT protocols in hospitals around the world. However, 3 subsequent large, multicenter trials conducted from 2008 to 2014 showed no benefit with EGDT versus usual care. The discrepancy may be due to changes in usual care for septic shock over the past two decades. In particular, increasing emphasis on early antibiotic and fluid administration may have made usual care and EGDT more similar over time. Understanding changes in usual care for septic shock may shed light on the importance of early antibiotic and fluid administration, on the observed declines in septic shock mortality over time, and on how best to improve the quality of sepsis care. Therefore, we examined changes in treatment patterns for septic shock in the emergency department (ED) of a large academic hospital.

A Comparison of Early, Late, and No Treatment of Intensive Care Unit Delirium With Antipsychotics: A Retrospective Cohort Study

Abstract: Objective To investigate the effect of early versus late versus no antipsychotic administration on intensive care unit (ICU) delirium. Methods This retrospective cohort study was conducted in 2 adult medical ICUs at a single tertiary care center in Boston, Massachusetts, from October 1, 2015, to May 31, 2016. The study included 322 patients stratified into those who first received antipsychotics 48 hours after first positive or unscorable CAM-ICU-m (late), and never received antipsychotics. Primary outcomes were hours alive without delirium or coma and likelihood of delirium-coma resolution. Secondary outcomes included ventilator-free hours, likelihood of extubation, and 10-day mortality. In post hoc exploratory analyses, outcomes were reanalyzed excluding comatose patients. Results Mean ± SD delirium-coma-free hours were 63 ± 87 for patients who received antipsychotics early, 66 ± 92 for those who received antipsychotics late, and 89 ± 107 for those who never received antipsychotics (P = .71). Antipsychotic exposure did not impact delirium-coma resolution. Mean ventilator-free hours were 103 ± 87 for patients who received antipsychotics early, 90 ± 83 for those who received antipsychotics late, and 89 ± 101 for patients who never received antipsychotics (P = .11). The hazard ratio (HR) for 10-day mortality among patients who received antipsychotics early was 0.68 (95% CI, 0.37-1.22) and 0.30 (95% CI, 0.10-0.88) for those who received antipsychotics late compared to those who never received antipsychotics (P = .03). After excluding comatose patients, the effect of antipsychotics on 10-day mortality was no longer observed (early HR = 0.57, 95% CI, 0.30-1.07; late HR = 0.57, 95% CI, 0.28-1.18; never HR = 1 [reference]; P = .14). Conclusion Antipsychotics were not associated with changes in delirium-coma-free hours or ventilator-free hours.

What Is the Best Treatment for Vancomycin-Resistant Enterococcal Bloodstream Infections?

Abstract: 1700 www.ccmjournal.org October 2018 • Volume 46 • Number 10 indeed safe, and even beneficial, most likely through the minimization of unnecessary and sometimes harmful intervention. Of course, it may be that a more palatable, and ultimately more sustainable, approach to this problem is for us to develop closed-loop drug delivery systems that will automatically titrate our vasopressor agents to deliver the precise blood pressure targets we set, especially since successful dose reduction can sometimes require significant clinical experience. Whichever approach we choose, it is long overdue that we finally start to unravel what blood pressure to deliver, using which agents, and when, and then start to individualize blood pressure targets in a much more sophisticated fashion in our patients. Perhaps then we shall consign excessive blood pressure goals to the past, alongside overly aggressive fluid resuscitation and high tidal volumes.

Missed Opportunities for Better Sepsis Care or Misplaced Blame? Deconstructing Patients' Encounters in the Week Before Sepsis Hospitalizations.

Abstract: 644 www.ccmjournal.org April 2018 • Volume 46 • Number 4 Sepsis has been in the center of our sights for many years, but the latest report on our progress is humbling. Despite ongoing work to enhance recognition, define treatment standards, develop new therapeutics, and mandate bundled therapy, a recent analysis of sepsis burden in a large number of U.S. hospitals found that we have made little or no headway in the past few years in reducing the combined outcome of hospital death or discharge to hospice (1). Our limited success of late with improving outcomes through better hospital-based care begs the question of what more can we do to prevent sepsisrelated deaths and disabilities? A valuable new study by Liu et al (2) in this issue of Critical Care Medicine suggests a possible new direction. Liu et al (2) retrospectively evaluated 46,027 patients hospitalized with sepsis in 21 Kaiser Permanente Northern California and 114 Veterans Affairs hospitals to quantify how many were seen by a clinician in the week before they were admitted. They found that a staggering 48% saw a clinician in the 7 days before they were hospitalized. Approximately one third were assigned diagnosis codes for acute infection, and 20-40% were prescribed antibiotics, suggesting that their sepsis syndromes were already brewing at the time of their prehospitalization encounters and that their providers recognized the presence of infection. Liu et al (2) spell out the implications of their discovery: there is a potentially massive opportunity to improve patient outcomes by intervening upon infections earlier and to improve ambulatory providers’ recognition and management of early sepsis (or syndromes that are liable to evolve into sepsis) before patients present to hospital in extremis. These messages may well be true, but there are important caveats to the data by Liu et al (2) that might limit the scope of what otherwise appears to be an enormous opportunity to reduce sepsis morbidity and mortality. First, it is possible that many sepsis patients’ visits in the week before hospitalization could have been for routine care of chronic conditions without any signs or symptoms of infection. Indeed, most patients did not have infection diagnoses or receive antibiotics. The patients at greatest risk for sepsis (the elderly, the immunocompromised, patients with chronic conditions, and patients recently discharged from hospital) are also the same patients that have frequent, routine visits with their clinicians (3). The study by Liu et al (2) did not include any comparative data on whether patients’ visit frequencies in the week before sepsis were any higher than their visit frequencies during any other week of the year. Similarly, it would be interesting to compare visit frequencies in the week before sepsis hospitalization with visit frequencies in the week before nonsepsis hospitalizations to see whether sepsis in particular has premonitory encounters or if this is a nonspecific finding for all conditions. Second, many of the encounters included in the count of presepsis visits by Liu et al (2) could have been instances of very appropriate early care rather than missed opportunities. Their count included encounters on the day of hospital admission. Indeed, when Liu et al (2) plotted patients’ counts of encounters for each day in the week before sepsis admission, they found that visit rates were low and stable from days –7 to –2, rose marginally on day –1 and then increased dramatically on the day of sepsis admission itself. These visits close to the time of hospitalization and then may not necessarily represent missed opportunities for sepsis recognition but could have been quite the opposite, namely clinical encounters in which clinicians recognized that their patients were ill and rapidly referred them to a hospital. Likewise, the count of prehospital encounters included nursing home days and thus days on which nursing home clinicians recognized impending or extant sepsis and transferred their patients to hospital. We have no data *See also p. 513.

Quality measurement for Clostridium difficile infection: turning lemons into lemonade.

Abstract: W Edwards Deming is famously quoted as having said, “If you can’t measure it, you can’t manage it”. In truth, Deming’s full quotation reads, “It is wrong to suppose that if you can’t measure it, you can’t manage it—a costly myth”.1 2 In our journey to improve our hospital’s rates of Clostridium difficile , we learned first-hand the truth of Deming’s full statement—that in fact, even without the ability to measure perfectly, imperfect measures can still help us improve quality. US hospitals are currently required to report hospital-acquired C. difficile rates as a condition of participation in several Centers for Medicare and Medicaid Services (CMS) pay-for-performance programmes. CMS is seeking to shed light on this type of preventable patient harm and raising the stakes by putting financial penalties and a hospital’s public reputation at risk. However, there is a vigorous debate in the medical community over the C. difficile measurement technique used by CMS. CMS’s C. difficile rates are based on the National Healthcare Safety Network’s C. difficile ‘ LabID’ measure. This metric identifies C. difficile infections solely by positive laboratory test results, without regard to patients’ clinical signs or symptoms. This approach makes case assignments very objective (and therefore reduces ‘gaming’), but comes at the risk of misclassifying colonised patients as infected. The C. difficile tests we have only tell us whether C. difficile is present or not. They do not differentiate between colonisation and infection. This is particularly true of PCR-based testing that looks for the presence of the C. difficile toxin gene but does not determine whether the gene is producing toxin or not. The most specific test we have is the C. difficile toxin immunoassay, but even this is imperfect. The lack of specificity is the Achilles heel of the C. difficile LabID measure because …

1411: sepsis surveillance using sofa versus esofa criteria based on routine ehr data

Abstract: Critical Care Medicine • Volume 46 • Number 1 (Supplement) www.ccmjournal.org Learning Objectives: Sepsis is a clinical syndrome that has physiologic, biologic and biochemical abnormalities caused by an inflammatory response to infection. Prior reports of gender, race and regional disparities indicate the importance of continued monitoring of these disparities. The goal of our study is to determine if sepsis mortality varies by gender race/ethnicity and region in the most recent data Methods: Using CDC WONDER, a data system of the Centers for Disease Control and Prevention (CDC), we examined the Multiple Causes of Death dataset for those with any mention of sepsis, ICD-10 codes A40 (Septicemia due to streptococcus) and A41 (Other Septicemia), for years 20132015, combined for ages 15 years and older in the United States. Data were stratified by gender and region for Hispanics, Non–Hispanic whites (NHW) and NonHispanic blacks (NHB). We computed annual ageadjusted death rates per 100,000 with 95% confidence interval (CI). Results: For persons aged 15 years and older, there were a total of 548,450 sepsis-associated deaths: 281,232 females and 267,218 males. Age-adjusted annual death rates were 57.4 (95% CI 57.2 -57.7) for females and 72.4 (95% CI 72.1-.72.6) for males. Among females, age adjusted death rates for NHB was 88.4(95% CI 87.5– 89.3) and for NHW 54.8 (95% CI 54.5 – 55). Among males, ageadjusted death rates for NHB was 115.1(95% CI 113.8–116.3) and for NHW 68.5 (95% CI 68.2–68.8). Among whites, the rate in Hispanics was 63.8 and 60.6 in nonHispanics. Among NHW females, those who resided in the South had the highest age-adjusted death rate, 61(95%CI 60.661.4), while the lowest was for those in the West, 49.2 (95% CI48.7–49.7). NHW males who resided in the South had the highest rate, 74.6(74.1–75.1) while the lowest was in the West, 60.7 (95% CI 60.1–61.4). NHB females who resided in the South had the highest rate, 92.2 (95% CI 9193.3) while the lowest was in the Northeast (NE), 78.4(95% CI 76.5–80.3). NHB males who resided in the South had the highest rates, 120.9 (95% CI 119.2–122.6) while the lowest was in the West, 97.4(95% CI 93.8–101). The ratios of NHB/NHW rates in females were NE 1.45, Midwest (MW) 1.74, South 1.51, and West 1.72; In males NE 1.50, MW 1.80, South 1.62 and West 1.60. Conclusions: In 2013 – 2015 sepsis-related mortality rates were higher in males than females, in NHB than NHW, and in the South than in other regions. The NHB/NHW rate ratio was highest in the MW region and lowest in the NE.

1659. Variation in Identifying Sepsis and Organ Dysfunction Using Administrative Versus Clinical Data and Impact on Hospital Outcome Comparisons

Abstract: Abstract Background Administrative claims data are commonly used for sepsis surveillance, research, and quality improvement. However, variations in diagnosis, documentation, and coding practices may confound efforts to benchmark hospital sepsis outcomes using claims data. Methods We evaluated the sensitivity of claims data for sepsis and organ dysfunction relative to clinical data from the electronic health records of 193 US hospitals. Sepsis was defined clinically using markers of presumed infection (blood cultures and antibiotic administrations) and concurrent organ dysfunction. Organ dysfunction was measured using laboratory data (acute kidney injury, thrombocytopenia, hepatic injury), vasopressor administrations (shock), or mechanical ventilation (respiratory failure). Correlations between hospitals’ sepsis incidence and mortality rates by claims (using “explicit” ICD-9-CM codes for severe sepsis or septic shock) versus clinical data were measured by the Pearson correlation coefficient (r) and relative hospital rankings using either data source were compared. All estimates were reliability-adjusted to account for random variation using hierarchical logistic regression modeling. Results The study cohort included 4.3 million adult hospitalizations in 2013 or 2014. The sensitivity of hospitals’ claims data for sepsis and organ dysfunction was low and variable: median sensitivity 30% (range 5–54%) for sepsis, 66% (range 26–84%) for acute kidney injury, 39% (range 16–60%) for thrombocytopenia, 36% (range 29–44%) for hepatic injury, and 66% (range 29–84%) for shock (Figure 1). There was only moderate correlation between claims and clinical data for hospitals’ sepsis incidence (r = 0.64) and mortality rates (r = 0.61), and relative hospital rankings for sepsis mortality differed substantially using either method (Figure 2). Of 48 (46%) hospitals, 22 ranked in the lowest sepsis mortality quartile by claims shifted to higher mortality quartiles using clinical data. Conclusion Variation in the completeness and accuracy of claims data for identifying sepsis and organ dysfunction limits their use for comparing hospital sepsis rates and outcomes. Sepsis surveillance using objective clinical data may facilitate more meaningful hospital comparisons. Disclosures All authors: No reported disclosures.

2398. Utilization Practices of Ceftazidime–Avibactam at Academic Medical Centers in the United States

Abstract: Abstract Background Ceftazidime–avibactam (CAV) was US FDA-approved for complicated intra-abdominal/urinary tract infections in 2015, and for hospital-acquired/ventilator-associated pneumonia in 2018. However, little is known about its real-world use. Methods Encounters of inpatients receiving CAV at academic hospitals in the VizientTM Clinical Resource Manager were identified (CAV encounters). CAV administered for ≤2 consecutive days during an encounter or any duration of CAV within 2 days of admission (excluding acute care hospital transfers) was considered empiric therapy. Targeted therapy was defined as ≥4 consecutive days or death within 2 days of therapy; empiric and targeted therapy cohorts were mutually inclusive. CAV-encounter characteristics, use patterns and Infectious Disease (ID) consultation were examined. Quarterly hospital uptake of CAV and % change in CAV encounter prevalence (using Poisson regression) were calculated. Results From January 2015 to December 2017, 20,590 CAV doses occurred in 2,128 encounters among 1,652 patients. Mean duration of therapy was 8 ± 7.9 days (range 1–86); overall mortality was 24%. The number of hospitals prescribing CAV increased from 5 to 92/168 and quarterly prevalence of CAV encounters increased from 5/10,000 hospitalizations in 2015q1 to 9.8 in 2017q4 (% change=2.1[0.7–3.6] %/quarter; (P = 0.004). Therapy was empiric in 904 (42%) encounters and targeted in 1,472 (69%); 63% of empiric CAV was initiated within 2 days of admission. CAV was initiated in the ICU in 862 (40.5%) encounters. Infection site was coded as respiratory in 34%, urinary in 26% and abdominal in 16% of encounters. Within 31 hospitals reporting consultant specialty, 29% of targeted therapy occurred without ID consultation. For targeted therapy encounters, CAV monotherapy occurred in 841 (57%) and combination therapy in 631 (43%) encounters, which most often included aminoglycosides, colistin or tigecycline. Mortality was 22% in the monotherapy and 25% in the combination therapy group (P = 0.08). Conclusion CAV use across US academic medical centers has increased modestly over 3 years. More than 40% of CAV prescriptions appear to be empiric and targeted therapy often occurs without ID consultation at academic centers. Disclosures All authors: No reported disclosures.