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- (-) Antibiotics (20)
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- (-) Sepsis (20)
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AHRQ Research Studies
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Research Studies is a compilation of published research articles funded by AHRQ or authored by AHRQ researchers.
Results
1 to 20 of 20 Research Studies DisplayedHechtman RK, Kipnis P, Cano J
Heterogeneity of benefit from earlier time-to-antibiotics for sepsis.
The objectives of this observational cohort study were to identify patient characteristics associated with greater benefit from shorter time-to-antibiotics. Subjects were patients hospitalized with community-onset sepsis and treated with antimicrobials within 12 hours. The findings indicated that metastatic cancer and shock were associated with the greatest benefit. The researchers concluded that shorter time-to-antibiotics for sepsis is particularly important among patients with these conditions.
AHRQ-funded; HS026725.
Citation: Hechtman RK, Kipnis P, Cano J .
Heterogeneity of benefit from earlier time-to-antibiotics for sepsis.
Am J Respir Crit Care Med 2024 Apr 1; 209(7):852-60. doi: 10.1164/rccm.202310-1800OC..
Keywords: Antibiotics, Sepsis, Medication
Donnelly JP, Seelye SM, Kipnis P
Impact of reducing time-to-antibiotics on sepsis mortality, antibiotic use, and adverse events.
Researchers estimated benefits and harms of shortened time-to-antibiotics for sepsis. Their simulation study used a cohort of over 1.5 million hospitalizations via emergency department with more than two systemic inflammatory response syndrome criteria. The results showed that impacts of faster time-to-antibiotics for sepsis varied markedly across simulated hospital types; however, even in worst-case scenarios, new antibiotic-associated adverse events were rare.
AHRQ-funded; HS026725.
Citation: Donnelly JP, Seelye SM, Kipnis P .
Impact of reducing time-to-antibiotics on sepsis mortality, antibiotic use, and adverse events.
Ann Am Thorac Soc 2024 Jan; 21(1):94-101. doi: 10.1513/AnnalsATS.202306-505OC..
Keywords: Antibiotics, Medication, Sepsis, Mortality
Pak TR, Young J, McKenna CS
Risk of misleading conclusions in observational studies of time-to-antibiotics and mortality in suspected sepsis.
Important studies indicate that every hour of sepsis that elapses until antibiotics are administered increases mortality. The researchers of this study found determined that analyses in the influential studies often adjusted for limited covariates, included patients with long delays until antibiotic administration, combined sepsis and septic shock, and used linear models presuming each hour of delay has equal impact on the sepsis and the patient. The purpose of this study was to assess the effect of the analytic decisions on the relationships between time-to-antibiotics and mortality. The researchers retrospectively identified 104,248 adults admitted from 2015-2022 to five hospitals with suspected infection. The patients included 25,990 with suspected septic shock and 23,619 with sepsis without shock. The study found that changing covariates, maximum time-to-antibiotics, and severity stratification altered the magnitude, direction, and significance of observed relationships between time-to-antibiotics and mortality. In a fully adjusted model of patients treated within 6 hours, every hour related with higher mortality for septic shock, but not sepsis without shock or suspected infection alone. Modeling every hour independently confirmed that every hour delay was related with greater mortality for septic shock, but only delays of greater than 6 hours were related with greater mortality for sepsis without shock.
AHRQ-funded; HS027170.
Citation: Pak TR, Young J, McKenna CS .
Risk of misleading conclusions in observational studies of time-to-antibiotics and mortality in suspected sepsis.
Clin Infect Dis 2023 Nov 30; 77(11):1534-43. doi: 10.1093/cid/ciad450..
Keywords: Antibiotics, Medication, Sepsis, Mortality, Quality of Care
Chiotos K, Blumenthal J, Boguniewicz J
Antibiotic indications and appropriateness in the pediatric intensive care unit: a 10-center point prevalence study.
The purpose of this study was to describe indications and appropriateness of antibiotic orders in pediatric intensive care unit (PICU) patients. The study found that of 1462 patients admitted to participating PICUs, 58% had at least 1 antibiotic order, with 1277 antibiotic orders being reviewed. Common indications were empiric therapy for suspected bacterial infections without sepsis or septic shock, nonoperative prophylaxis, empiric therapy for sepsis or septic shock, community-acquired pneumonia, and post-operative prophylaxis. Appropriateness was evaluated for 985 orders for which an evidence-based heading for appropriateness could be created. Of these, 34% were categorized as inappropriate. Indications with the most orders classified as inappropriate were empiric therapy for suspected bacterial infection without sepsis or septic shock, sepsis or septic shock, CAP, ventilator-associated infections, and post-operative prophylaxis. The proportion of antibiotics classified as inappropriate differed across institutions.
AHRQ-funded; HS026393.
Citation: Chiotos K, Blumenthal J, Boguniewicz J .
Antibiotic indications and appropriateness in the pediatric intensive care unit: a 10-center point prevalence study.
Clin Infect Dis 2023 Feb 8; 76(3):e1021-e30. doi: 10.1093/cid/ciac698..
Keywords: Children/Adolescents, Intensive Care Unit (ICU), Antibiotics, Medication, Antimicrobial Stewardship, Sepsis
Smith JT, Manickam RN, Barreda F
Quantifying the breadth of antibiotic exposure in sepsis and suspected infection using spectrum scores.
The purpose of this retrospective cohort study was to apply a validated method to describe the level of antimicrobial coverage in a cohort of patients with suspected infection and sepsis. The researchers conducted the study across 21 hospitals with patients admitted to the hospital through the ED between January 1, 2012, to December 31, 2017, with suspected infection or sepsis and receiving antibiotics during hospitalization. The researchers quantified the level of antimicrobial coverage using the Spectrum Score, a numerical score from 0 to 64. Of 364,506 hospital admissions through the ED, researchers identified 43.6% with suspected infection and 56.4% with sepsis. Inpatient mortality was greater among those with sepsis (8.4%) compared to those with suspected infection (1.2%). Patients with sepsis had higher median global Spectrum Scores and additive Spectrum Scores compared to those with suspected infection. Increased Spectrum Scores were related with inpatient mortality, even after covariate adjustments. Spectrum Scores quantify the inconsistency in antibiotic level among individual patients, between suspected infection and sepsis groups, over the course of the hospitalization, and across infection sources.
AHRQ-funded; HS026725.
Citation: Smith JT, Manickam RN, Barreda F .
Quantifying the breadth of antibiotic exposure in sepsis and suspected infection using spectrum scores.
Medicine 2022 Oct 14; 101(41):e30245. doi: 10.1097/md.0000000000030245..
Keywords: Antibiotics, Sepsis, Medication
Dutta S, McEvoy DS, Rubins DM
Clinical decision support improves blood culture collection before intravenous antibiotic administration in the emergency department.
This paper discusses the outcomes of using a clinical decision support (CDS) tool that was implemented in emergency departments (EDs) for sepsis patients to remind healthcare staff to take blood cultures before administration of intravenous (IV) antibiotics. The study compared timely blood culture collection outcomes prior to IV antibiotics for 54,538 adult ED patients 1 year before and after a CDS intervention implementation in the electronic health record. The baseline phase found that 46.1% had blood cultures prior to IV antibiotics, compared to 58.8% after the intervention. The CDS improved blood culture collection rates without increasing overutilization.
AHRQ-funded; HS02717.
Citation: Dutta S, McEvoy DS, Rubins DM .
Clinical decision support improves blood culture collection before intravenous antibiotic administration in the emergency department.
J Am Med Inform Assoc 2022 Sep 12;29(10):1705-14. doi: 10.1093/jamia/ocac115..
Keywords: Clinical Decision Support (CDS), Health Information Technology (HIT), Antibiotics, Emergency Department, Medication, Sepsis
Prescott HC, Seelye S, Wang XQ
Temporal trends in antimicrobial prescribing during hospitalization for potential infection and sepsis.
This study examined whether the push to administer antimicrobials to prevent sepsis has increased antimicrobial use in general. This observational cohort study of hospitalized patients at 152 hospitals in 2 health care systems during 2013 to 2018 looked at almost 1.6 million patients (81% male), admitted via the emergency department with 2 or more systemic inflammatory response syndrome (SIRS) criteria. From 2013 to 2018 first antimicrobial administration to patients with sepsis decreased by 37 minutes. At the same time, antimicrobial use within 48 hours, days of antimicrobial therapy, and receipt of broad-spectrum coverage decreased among the broader cohort of patients with systemic inflammatory response syndrome (SIRS). This may have caused a decrease in in-hospital mortality, 30-day mortality, length of hospitalization, new MDR culture positivity, and new MDR blood culture positivity over the study period among both patients with sepsis and those with SIRS. For the overall hospital population there was no evidence that increasing antimicrobial timing for sepsis was associated with increasing antimicrobial use or impaired antimicrobial stewardship.
AHRQ-funded; HS026725.
Citation: Prescott HC, Seelye S, Wang XQ .
Temporal trends in antimicrobial prescribing during hospitalization for potential infection and sepsis.
JAMA Intern Med 2022 Aug;182(8):805-13. doi: 10.1001/jamainternmed.2022.2291..
Keywords: Antimicrobial Stewardship, Antibiotics, Medication, Sepsis, Inpatient Care, Hospitals
Woods-Hill CZ, Colantuoni EA, Koontz DW
Association of diagnostic stewardship for blood cultures in critically ill children with culture rates, antibiotic use, and patient outcomes: results of the Bright STAR Collaborative.
The purpose of this AHRQ-funded prospective study was to assess the relationship between a 14-site PICU blood culture collaborative, the Bright STAR (Testing Stewardship for Antibiotic Reduction) collaborative, and culture rates, antibiotic use, and patient outcomes. The researchers collected data from each participating PICU across the United States and from the Children’s Hospital Association Pediatric Health Information System. The main outcome was blood culture rates, with secondary outcomes including: broad-spectrum antibiotic use and PICU rates of central line-associated bloodstream infection (CLABSI), Clostridioides difficile infection, readmission, length of stay, sepsis, severe sepsis/septic shock, and mortality. The study found that the blood culture rate preimplementation across the 14 PICUs was 149.4 per 1000 patient days per month, and the rate postimplementation was 100.5 for a 33% relative reduction postimplementation. For those same periods, the rate of antibiotic use decreased from 506 days per 1000 patient-days per month preimplementation to 440 days per 1000 patient-days per month postimplementation, which reflects a 13% relative reduction. Rates of CLABSI decreased from 1.8 to 1.1 per 1000 central venous line days per month, a 36% relative reduction. The variables of length of stay, readmission, sepsis, severe sepsis/septic shock, and mortality were similar before and after implementation. The researchers concluded that collaborative interventions can reduce blood culture and antibiotic use in the PICU.
AHRQ-funded; HS025642.
Citation: Woods-Hill CZ, Colantuoni EA, Koontz DW .
Association of diagnostic stewardship for blood cultures in critically ill children with culture rates, antibiotic use, and patient outcomes: results of the Bright STAR Collaborative.
JAMA Pediatr 2022 Jul;176(7):690-98. doi: 10.1001/jamapediatrics.2022.1024..
Keywords: Children/Adolescents, Sepsis, Critical Care, Antibiotics, Medication, Diagnostic Safety and Quality, Antimicrobial Stewardship
Flannery DD, Puopolo KM, Hansen NI
Antimicrobial susceptibility profiles among neonatal early-onset sepsis pathogens.
This retrospective review examined antimicrobial susceptibility of infants ≥22 weeks' gestation who were cared for in Neonatal Research Network centers April 2015-March 2017. Nonsusceptibility was defined as intermediate or resistant on treatment results. The authors identified 239 pathogens (235 bacteria, 4 fungi) in 235 EOS cases among 217,480 live-born infants. Antimicrobial susceptibility data was available for 79.1% of isolates. All 81 Gram-positive isolates with ampicillin and gentamicin were susceptible in vitro. Among Gram-negative isolates with ampicillin and gentamicin susceptibility data, 76.6% isolates were nonsusceptible to ampicillin, 8.5% nonsusceptible to gentamicin, and 7.3% isolates were nonsusceptible to both. The authors estimated that overall 8% of EOS cases were caused by isolates nonsceptible to ampicillin and gentamicin and were most likely to occur among preterm, very-low birth weight infants.
AHRQ-funded; HS027468.
Citation: Flannery DD, Puopolo KM, Hansen NI .
Antimicrobial susceptibility profiles among neonatal early-onset sepsis pathogens.
Pediatr Infect Dis J 2022 Mar;41(3):263-71. doi: 10.1097/inf.0000000000003380..
Keywords: Newborns/Infants, Sepsis, Antibiotics, Medication
Flannery DD, Mukhopadhyay S, Morales KH
Delivery characteristics and the risk of early-onset neonatal sepsis.
This retrospective cohort study identified term and preterm infants at lowest risk of culture-confirmed early-onset sepsis (EOS) using delivery characteristics and also determined antibiotic use among them. The study cohort included term and preterm infants born 2009 to 2014 with blood culture with or without cerebrospinal fluid culture obtained ≤72 hours after birth. Low EOS risk criteria included: cesarean delivery, without labor or membrane rupture before delivery, and no antepartum concern for intraamniotic infection or nonreassuring fetal status. Among 53,575 births, 7549 (14.1%) were evaluated and 41 (0.5%) of those infants had EOS. For 1121 evaluated infants there were low-risk delivery characteristics and none had EOS. Duration of antibiotics administered to infants born with and without low-risk characteristics was not different.
AHRQ-funded; HS027468.
Citation: Flannery DD, Mukhopadhyay S, Morales KH .
Delivery characteristics and the risk of early-onset neonatal sepsis.
Pediatrics 2022 Feb;149(2). doi: 10.1542/peds.2021-052900..
Keywords: Newborns/Infants, Sepsis, Risk, Labor and Delivery, Antibiotics, Medication
Han X, Spicer A, Carey KA
Identifying high-risk subphenotypes and associated harms from delayed antibiotic orders and delivery.
Delayed antibiotic use can cause harms including mortality in certain novel patient subphenotypes. This study’s objective was to characterize and compare patients who experienced order or delivery delays and identify those novel subphenotypes with elevated risk of harm from delays. Two tertiary care medical centers and four community-based hospitals were analyzed retrospectively from 2008 to 2017. Patient demographics, vitals, laboratory values, medical order and administration times, and in-hospital survival data were obtained from their electronic health records. Order and delivery delays for each admission was calculated. Causal forests, a machine learning method, was used to identify the high-risk subgroup. Out of 60,817 admissions included, delays occurred in 58% of patients. Each additional hour of order delay and delivery delay was associated with increased mortality. A patient subgroup was identified with higher comorbidity burden, greater organ dysfunction, and abnormal initial lactate measures that had a higher risk of death associated with delays.
AHRQ-funded; HS027910; HS026151.
Citation: Han X, Spicer A, Carey KA .
Identifying high-risk subphenotypes and associated harms from delayed antibiotic orders and delivery.
Crit Care Med 2021 Oct;49(10):1694-705. doi: 10.1097/ccm.0000000000005054..
Keywords: Antibiotics, Medication, Sepsis
Kadri SS, Lai YL, Warner S
Inappropriate empirical antibiotic therapy for bloodstream infections based on discordant in-vitro susceptibilities: a retrospective cohort analysis of prevalence, predictors, and mortality risk in US hospitals.
Researchers sought to establish the population-level burden, predictors, and mortality risk of in-vitro susceptibility-discordant empirical antibiotic therapy among patients with bloodstream infections. They found that approximately one in five patients with bloodstream infections in US hospitals received discordant empirical antibiotic therapy, receipt of which was closely associated with infection with antibiotic-resistant pathogens. Receiving discordant empirical antibiotic therapy was associated with increased odds of mortality overall, even in patients without sepsis. They concluded that early identification of bloodstream pathogens and resistance will probably improve population-level outcomes.
AHRQ-funded.
Citation: Kadri SS, Lai YL, Warner S .
Inappropriate empirical antibiotic therapy for bloodstream infections based on discordant in-vitro susceptibilities: a retrospective cohort analysis of prevalence, predictors, and mortality risk in US hospitals.
Lancet Infect Dis 2021 Feb;21(2):241-51. doi: 10.1016/s1473-3099(20)30477-1..
Keywords: Antibiotics, Medication, Sepsis, Antimicrobial Stewardship, Mortality, Risk
Tamma PD, Miller MA, Cosgrove SE
AHRQ Author: Miller MA
Recalibrating our approach to the management of sepsis: how the four moments of antibiotic decision-making can help.
In this paper, the authors describe The Four Moments of Antibiotic Decision Making. The Four Moments were conceived as part of the Agency for Healthcare Research and Quality (AHRQ) Safety Program for Improving Antibiotic Use. The Four Moments provide a pragmatic approach to the core principle of antibiotic stewardship – ensuring patients who require antibiotic therapy promptly receive regimens associated with clinical success, while protecting patients from potential harm associated with unnecessary exposure to antibiotics.
AHRQ-authored; AHRQ-funded; 233201500020I.
Citation: Tamma PD, Miller MA, Cosgrove SE .
Recalibrating our approach to the management of sepsis: how the four moments of antibiotic decision-making can help.
Ann Am Thorac Soc 2021 Feb;18(2):200-03. doi: 10.1513/AnnalsATS.202005-484IP..
Keywords: Sepsis, Antibiotics, Antimicrobial Stewardship, Medication, Shared Decision Making, Medication: Safety, Patient Safety
Rhee C, Kadri SS, Dekker JP
Prevalence of antibiotic-resistant pathogens in culture-proven sepsis and outcomes associated with inadequate and broad-spectrum empiric antibiotic use.
Broad-spectrum antibiotics are recommended for all patients with suspected sepsis to minimize the risk of undertreatment. However, little is known regarding the net prevalence of antibiotic-resistant pathogens across all patients with community-onset sepsis or the outcomes associated with unnecessarily broad empiric treatment. The purpose of this study was to elucidate the epidemiology of antibiotic-resistant pathogens and the outcomes associated with both undertreatment and overtreatment in patients with culture-positive community-onset sepsis.
AHRQ-funded; HS025008.
Citation: Rhee C, Kadri SS, Dekker JP .
Prevalence of antibiotic-resistant pathogens in culture-proven sepsis and outcomes associated with inadequate and broad-spectrum empiric antibiotic use.
JAMA Netw Open 2020 Apr;3(4):e202899. doi: 10.1001/jamanetworkopen.2020.2899.
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Keywords: Antibiotics, Medication, Sepsis, Outcomes
Goldstein E, Olesen SW, Karaca Z
AHRQ Author: Karaca Z
Levels of outpatient prescribing for four major antibiotic classes and rates of septicemia hospitalization in adults in different US states - a statistical analysis.
The authors related state-specific rates of outpatient prescribing overall for oral fluoroquinolones, penicillins, macrolides, and cephalosporins between 2011 and 2012 to state-specific rates of septicemia hospitalization in several age groups of adults. They found positive associations between the rates of prescribing for penicillins and the rates of hospitalization with septicemia in US adults aged 50-84 years and recommended further studies.
AHRQ-authored.
Citation: Goldstein E, Olesen SW, Karaca Z .
Levels of outpatient prescribing for four major antibiotic classes and rates of septicemia hospitalization in adults in different US states - a statistical analysis.
BMC Public Health 2019 Aug 19;19(1):1138. doi: 10.1186/s12889-019-7431-8..
Keywords: Healthcare Cost and Utilization Project (HCUP), Antibiotics, Antimicrobial Stewardship, Sepsis, Medication, Hospitalization
Weinberger J, Rhee C, Klompas M
A critical analysis of the literature on time-to-antibiotics in suspected sepsis.
The Surviving Sepsis Campaign recommends immediate antibiotics for all patients with suspected sepsis and septic shock, ideally within 1 hour of recognition. An accurate understanding of the precise relationship between time-to-antibiotics and mortality for patients with possible sepsis is therefore critical. In this study, the investigators elaborate on potential sources of bias and try to distill a better understanding of what the true relationship between time-to-antibiotics and mortality may be for patients with suspected sepsis or septic shock.
AHRQ-funded; HS025008.
Citation: Weinberger J, Rhee C, Klompas M .
A critical analysis of the literature on time-to-antibiotics in suspected sepsis.
J Infect Dis 2020 Jul 21;222(Suppl 2):S110-s18. doi: 10.1093/infdis/jiaa146..
Keywords: Sepsis, Antibiotics, Medication, Antimicrobial Stewardship, Quality Improvement, Quality of Care, Mortality
Goldstein E, MacFadden DR, Karaca Z
AHRQ Author: Karaca Z Steiner CA
Antimicrobial resistance prevalence, rates of hospitalization with septicemia and rates of mortality with sepsis in adults in different US states.
Researchers studied the relation between the prevalence of resistance to various antibiotics in different bacteria and rates of sepsis-related outcomes. They found that, among the different combinations of antibiotics/bacteria, prevalence of resistance to fluoroquinolones in E. coli had the strongest association with septicemia hospitalization rates for individuals aged over 50 years, and with sepsis mortality rates for individuals aged 18-84 years. They also found a number of positive correlations between prevalence of resistance for different combinations of antibiotics/bacteria and septicemia hospitalization/sepsis mortality rates in adults.
AHRQ-authored.
Citation: Goldstein E, MacFadden DR, Karaca Z .
Antimicrobial resistance prevalence, rates of hospitalization with septicemia and rates of mortality with sepsis in adults in different US states.
Int J Antimicrob Agents 2019 Jul;54(1):23-34. doi: 10.1016/j.ijantimicag.2019.03.004..
Keywords: Antibiotics, Antimicrobial Stewardship, Healthcare Cost and Utilization Project (HCUP), Hospitals, Hospitalization, Medication, Mortality, Sepsis
Pepper DJ, Sun J, Rhee C
Procalcitonin-guided antibiotic discontinuation and mortality in critically ill adults: a systematic review and meta-analysis.
This study is a systematic review and meta-analysis on survival outcomes of using procalcitonin (PCT)-guided antibiotic discontinuation on critically ill adults. The study quality was assessing with the Cochrane risk of bias tool, and GRADEpro was used to grade evidence. PCT-guided discontinuation was associated with decreased mortality, but there was a high risk of bias in many of the studies reviewed with a low certainty of evidence. The authors suggest properly designed studies with mortality as the primary outcome is needed to further answer this question.
AHRQ-funded; HS025008.
Citation: Pepper DJ, Sun J, Rhee C .
Procalcitonin-guided antibiotic discontinuation and mortality in critically ill adults: a systematic review and meta-analysis.
Chest 2019 Jun;155(6):1109-18. doi: 10.1016/j.chest.2018.12.029..
Keywords: Antibiotics, Critical Care, Evidence-Based Practice, Medication, Mortality, Outcomes, Sepsis
Trent SA, Havranek EP, Ginde AA
Effect of audit and feedback on physician adherence to clinical practice guidelines for pneumonia and sepsis.
This study examined the effect of feedback with blinded peer comparison on emergency physician adherence to guidelines for appropriate antibiotic administration for inpatient pneumonia and completion of the 3-hour Surviving Sepsis Bundle for patients with severe sepsis. A quasi-experiment was conducted with attending physicians randomized into 6 clusters at a single urban safety net hospital. Feedback with blinded peer comparison significantly improved guideline adherence from 52% to 65% with feedback.
AHRQ-funded; HS022400.
Citation: Trent SA, Havranek EP, Ginde AA .
Effect of audit and feedback on physician adherence to clinical practice guidelines for pneumonia and sepsis.
Am J Med Qual 2019 May/Jun;34(3):217-25. doi: 10.1177/1062860618796947..
Keywords: Antibiotics, Emergency Department, Guidelines, Infectious Diseases, Inpatient Care, Medication, Pneumonia, Provider, Provider: Physician, Sepsis
Hume PS, Varon J, Englert JA
Trends in "usual care" for septic shock.
The investigators examined changes in treatment patterns for septic shock in the emergency department (ED) of a large academic hospital. The investigators observed, from 2003 to 2013, significant reductions in time to antibiotics and fluids for patients with septic shock in the ED, underscoring the evolution of “usual care” over time. These findings may explain why early goal-directed therapy is not beneficial in the current era and may help inform ongoing deliberations regarding best practices for sepsis care.
AHRQ-funded; HS025008.
Citation: Hume PS, Varon J, Englert JA .
Trends in "usual care" for septic shock.
Infect Control Hosp Epidemiol 2018 Sep;39(9):1125-26. doi: 10.1017/ice.2018.154..
Keywords: Antibiotics, Emergency Department, Practice Patterns, Sepsis