Delays In Antibiotic Administration Research Articles

Exploring factors influencing delayed first antibiotic treatment for suspected early-onset sepsis in preterm newborns: a study before quality improvement initiative

BackgroundEarly-onset sepsis (EOS) is a serious illness that affects preterm newborns, and delayed antibiotic initiation may increase the risk of adverse outcomes.PurposeThe objective of this study was to examine the present time of antibiotic administration in preterm infants with suspected EOS and the factors that contribute to delayed antibiotic initiation.MethodsIn this retrospective study in China, a total of 82 early preterm infants with suspected EOS between December 2021 and March 2023 were included. The study utilized a linear regression analytical approach to identify independent factors that contribute to delayed antibiotic administration.ResultsThe mean gestational age and birth weight of the study population were 29.1 ± 1.4 weeks and 1265.7 ± 176.8 g, respectively. The median time of initial antibiotic administration was 3.8 (3.1-5.0) hours. Linear regression revealed that severe respiratory distress syndrome (RDS) (β = 0.07, P = 0.013), penicillin skin test (PST) timing (β = 0.06, P < 0.001) and medical order timing (β = 0.04, P = 0.017) were significantly associated with the initial timing of antibiotic administration.ConclusionsThere is an evident delay in antibiotic administration in preterm infants with suspected EOS in our unit. Severe RDS, PST postponement and delayed medical orders were found to be associated with the delayed use of antibiotics, which will be helpful for quality improvement efforts in the neonatal intensive care unit (NICU).

Delays to Antibiotics in the Emergency Department and Risk of Mortality in Children With Sepsis

Pediatric consensus guidelines recommend antibiotic administration within 1 hour for septic shock and within 3 hours for sepsis without shock. Limited studies exist identifying a specific time past which delays in antibiotic administration are associated with worse outcomes. To determine a time point for antibiotic administration that is associated with increased risk of mortality among pediatric patients with sepsis. This retrospective cohort study used data from 51 US children's hospitals in the Improving Pediatric Sepsis Outcomes collaborative. Participants included patients aged 29 days to less than 18 years with sepsis recognized within 1 hour of emergency department arrival, from January 1, 2017, through December 31, 2021. Piecewise regression was used to identify the inflection point for sepsis-attributable 3-day mortality, and logistic regression was used to evaluate odds of sepsis-attributable mortality after adjustment for potential confounders. Data analysis was performed from March 2022 to February 2024. The number of minutes from emergency department arrival to antibiotic administration. The primary outcome was sepsis-attributable 3-day mortality. Sepsis-attributable 30-day mortality was a secondary outcome. A total of 19 515 cases (median [IQR] age, 6 [2-12] years) were included. The median (IQR) time to antibiotic administration was 69 (47-116) minutes. The estimated time to antibiotic administration at which 3-day sepsis-attributable mortality increased was 330 minutes. Patients who received an antibiotic in less than 330 minutes (19 164 patients) had sepsis-attributable 3-day mortality of 0.5% (93 patients) and 30-day mortality of 0.9% (163 patients). Patients who received antibiotics at 330 minutes or later (351 patients) had 3-day sepsis-attributable mortality of 1.2% (4 patients), 30-day mortality of 2.0% (7 patients), and increased adjusted odds of mortality at both 3 days (odds ratio, 3.44; 95% CI, 1.20-9.93; P = .02) and 30 days (odds ratio, 3.63; 95% CI, 1.59-8.30; P = .002) compared with those who received antibiotics within 330 minutes. In this cohort of pediatric patients with sepsis, 3-day and 30-day sepsis-attributable mortality increased with delays in antibiotic administration 330 minutes or longer from emergency department arrival. These findings are consistent with the literature demonstrating increased pediatric sepsis mortality associated with antibiotic administration delay. To guide the balance of appropriate resource allocation with time for adequate diagnostic evaluation, further research is needed into whether there are subpopulations, such as those with shock or bacteremia, that may benefit from earlier antibiotics.

Isolated injury, Charlson Comorbidity Index, and transfer from another facility are associated with delay in antibiotic administration: a retrospective study of 963 patients with open fractures.

To identify factors associated with delays in administration and pharmacy and nursing preparation of antibiotics for patients with open fractures. Retrospective review. Level I trauma center. Nine hundred sixty-three adults with open fractures administered antibiotics. Delay in antibiotic administration greater than 66 minutes from arrival and significant pharmacy-related and nursing-related delay. Isolated injury, Charlson Comorbidity Index, and transfer from another facility were associated with delay in antibiotic administration greater than 66 minutes. Injury Severity Score, transfer, and trauma team activation were associated with pharmacy-related or nursing-related delay. Interventions to reduce antibiotic administration time for open fractures should focus on early identification of open fractures and standardization of antibiotic protocols to ensure timely administration even in complex or resource-scarce care situations. Prognostic level III.

Assessment of Delay in Door-to-antibiotic Administration Time after Arrival to the Hospital among Post-chemotherapy Febrile Neutropenia Patients: A Cohort Study

ntroduction: Febrile Neutropenia (FN), a common side effect of chemotherapy, is regarded as an oncologic emergency necessitating prompt treatment. A delay in door-to-antibiotic administration time is associated with poor patient outcomes. Aim: To assess the time lag in the administration of antibiotics after arrival at the hospital in patients with solid/haematological malignancy presenting with post-chemotherapy FN. Materials and Methods: This was a cohort study conducted in the Department of Medical Oncology at Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, Rajasthan, India, over a period of one year from December 2019 to November 2020 among 80 patients with solid or haematological malignancy who presented with fever and Absolute Neutrophil Count (ANC) &lt;1000/mm3 to the Outpatient Department (OPD) or the Emergency Department and were diagnosed with FN post-chemotherapy. Upon obtaining consent, these patients were enrolled, and the timing of antibiotic administration was noted for the study participants. The participants were further followed-up for the assessment of morbidity {in terms of Intensive Care Unit (ICU) admission)}, duration of hospital stay, delay in the further chemotherapy schedule, and survival status. Data was entered into MS Excel and analysed using Statistical Packages for Social Sciences (SPSS) version 16.0. Associations were established using Chi-square tests. Results: Out of a total of 80 study participants, the mean±SD age was 45.6±18.3 years, and the number of males was 43 (53.8%). Total 57 (71.25%) patients were on chemotherapy for solid organ malignancies. The median delay in door-to-antibiotic time was 120 minutes (ranging from 30 to 260 minutes). The median day of presentation with FN after chemotherapy was day 7. Delay in antibiotic administration was found to have a significant impact on the further chemotherapy schedule and doses (p=0.004). However, ICU admission rates (p=0.133), length of hospital stay (p=0.662), and mortality (p=0.201) were not significantly associated with the delay in antibiotic administration. Conclusion: The adoption of standardised algorithms and protocols for the management of FN and ensuring timely healthseeking by the patients shall help reduce the delay in Time-toantibiotic Administration (TTA).

Barriers to and facilitators of effective management of fever episodes in hospitalised Kenyan children with cancer: protocol for convergent mixed methods study

IntroductionFebrile neutropenia is an oncological emergency in children with cancer, associated with serious infections and complications. In low-resourced settings, death from infections in children with cancer is 20 times higher...

Timing of antibiotics in febrile children meeting sepsis criteria at a paediatric emergency department.

Delay in antibiotic administration in paediatric sepsis is associated with increased mortality and prolonged organ dysfunction. This pre-intervention study evaluated performance in paediatric sepsis management. Retrospective cohort study of febrile children admitted through the ED at The Children's Hospital at Westmead, Sydney, between 1 May and 31 July 2017. Participants were children aged 29 days to 60 months excluding children with simple febrile seizures, neonates and children who had received intravenous antibiotics elsewhere. We assessed the timing of antibiotic administration in children meeting local sepsis guidelines. We conducted a survey of clinicians in ED in 2018 to describe contributing factors. There were 160 febrile children admitted and 144 presentations were included in the analysis. Male 53% (n = 76); median age 20.1 months (interquartile range [IQR] 3.9-37 months). Thirty-seven (26%) febrile children met local sepsis criteria. The median time from triage to first dose of intravenous antibiotic was 109 min (IQR 62-183 min). Delay (>60 min) occurred in 26 (76%) children. Reported reasons contributing to delay included high patient load, long waiting times, difficult intravenous access, delayed prescribing, inadequate staffing and difficulty distinguishing between a viral infection and serious bacterial infection. There was frequent delay in administering antibiotics in children meeting local sepsis criteria, more commonly in young infants. Reasons contributing to delay were specific to young children along with departmental factors that will require addressing through targeted quality improvement interventions.

State of the Union: Timeliness to Antibiotics in Open Fractures.

In open fractures, early administration of systemic antibiotics has recently been recognized as a universal recommendation, with the current American College of Surgeons Trauma Center Verification recommendation for administration within one hour of facility arrival. We sought to quantify the baseline rate of timely antibiotic administration and the various factors associated with delay. Data from the National Trauma Data Bank (NTDB) were obtained for all patients treated for open fractures in 2019. 65,552 patients were included. Univariate and multivariate analyses were performed, first for patient, prehospital and hospital factors compared to rate of antibiotic administration within one hour of hospital arrival, then with a multivariate analysis of factors affecting these times. The overall rate of antibiotic administration within one hour of arrival was 47.6%. Patient factors associated with lower rates of timely antibiotics include increased age, Medicare status, and a higher number of comorbidities. Associated prehospital factors included non-work related injuries, fixed-wing air or police transport, and walk-in arrival method. Patients with lower extremity open fractures were more likely to receive antibiotics within one hour of arrival than those with upper extremity open fractures. Traumatic amputations had a higher rate of timely administration (67.3%). ACS trauma level II (52.5%) centers performed better than Level III (48.3%), Level I (45.5%) and Level IV (34.5%) centers. Multivariate analysis confirmed the findings of the univariate analysis. Despite current clinical standards, rates of adherence to rapid antibiotic administration are low. Certain patient, facility, and environmental factors are associated with delays in antibiotic administration, and can be a focus for quality improvement processes. We plan to use this data to evaluate how focus on antibiotic administration as this quality standard changes practice over time. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The association between mortality and door-to-antibiotic time: a systematic review and meta-analysis.

Previous studies evaluating the impact of antibiotic timing on mortality in sepsis have shown conflicting results. We performed a meta-analysis to evaluate the association between door-to-antibiotic time (each hour of delay) and mortality in sepsis. We searched PubMed and Embase through 10 November 2022 to identity cohort studies that evaluated the adjusted association between door-to-antibiotic time (each hour of delay) and mortality in adult patients with sepsis. The primary outcome was mortality. Analysis was based on inverse-variance weighting using a fixed-effects model. The variances were derived from the logarithms of the reported confidence intervals (CIs) for associations. We estimated the odds ratio, 95% CI, and number needed to treat for the pooled data. Fifteen cohort studies involving 106 845 patients were included in the meta-analysis. Door-to-antibiotic time (each hour of delay) was associated with increased risk of mortality (odds ratio: 1.07; 95% CI: 1.06-1.08; P < 0.0001; number needed to treat = 91), with high heterogeneity (I2 = 82.2%). The association was robust in sensitivity analyses and consistent in subgroup analyses. No publication bias was found. In adult patients with sepsis, each hour of delay in antibiotic administration is associated with increased odds of mortality. Key messages What is already known on this topic Sepsis is a common and lethal syndrome that affects millions of people worldwide. The updated 2018 Surviving Sepsis Campaign guidelines recommended initiating empirical broad-spectrum antibiotic coverage within 1 hour of identification of sepsis and septic shock. Delay in antibiotic administration may increase the risk of mortality in patients with sepsis. What this study adds This meta-analysis evaluates and quantifies the association between door-to-antibiotic time (each hour of delay) and mortality in patients with sepsis. Each hour of delay in antibiotic administration is associated with increased odds of mortality in sepsis. The number needed to treat (NNT) with delayed antibiotic administration for one additional death was 91. How this study might affect research, practice, or policy: More efforts should be made to speed up the diagnosis of sepsis or sepsis shock.

Nurse-led study on treatment delay and streamlining antibiotic therapy among haematology patients with febrile neutropenia post chemotherapy

Objective: The aim of the study is to identify gaps that exist among health professionals that may impact practices in caring effectively for patients with febrile neutropenia (FN). Background: Haematology patients with FN following chemotherapy frequently experience delays in antibiotic administration that may be linked to poorer clinical outcomes. To aid timely review and treatment, FN care pathways have been developed. However, observations of clinical practice and patient anecdotal reports have highlighted that the care pathways may not be adhered to. The impact on patient care outcomes due to treatment delays and the rate of protocol adherence to the FN management pathway is unknown due to insufficient evidence. Methods: Using the Clinical Records Integrated System (CRIS), data were collected by auditing patients’ electronic health records (EHR) from November 2017 through to November 2018. Information retrieved were screened using the inclusion and exclusion criteria. Inclusion criteria: Haematology patients with FN (temperature ≥ 38° and neutrophil count < 1.0 x109/L) post chemotherapy, and 18 years or older. Exclusion criteria: Medical oncology patients and patients who were under 17 years old. Results: The mean time for antibiotic administration from first temperature spike was 90±15 minutes for inpatients (n=48). The mean time for antibiotic administration from medical officer review was significantly lower at 48±5 minutes for outpatients (n=31). Inpatients who were given antibiotics within 60 minutes or less of their first temperature spike, their mean length of total stay in the ward was 17±1 whilst inpatients who were given antibiotics 60 minutes after their first temperature spike, the mean length of their hospital stay was slightly greater at 21±3 days. Outpatients who were given antibiotics within 60 minutes or less of their first temperature spike, their mean length of stay was 12±2 days. For outpatients given antibiotics 60 minutes after their first temperature spike, their mean length of hospital stay was slightly shorter at 9±3 days. Conclusion: The study identified antibiotic delays among inpatient population, and with correlation to increased length of hospital stay and mortality. Another key factor identified in the study was delayed medical officer review although reasons for delays are outside of the scope this study to report. What is already known: Febrile neutropenia is a serious and life-threatening illness. Delays in antibiotic administration exists among healthcare facilities. Adherence to FN treatment guidelines among healthcare settings are challenging. What this review adds: Standardised orders to allow timely administration of antibiotic therapy that may reduce morbidity and mortality. Increased education on the seriousness and outcome from delayed antibiotics to patients, families, and healthcare staff. Further studies are required to standardise the clinical pathway and make antibiotics accessible for prompt delivery.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Assessing the impact of introducing trainee advanced clinical practitioners onto an acute oncology triage unit.

Advanced clinical practitioners (ACPs) have largely been based within acute emergency areas such as emergency departments (EDs) and acute medical units. At The Royal Wolverhampton NHS Trust, ACPs are a new element within oncology services. The acute oncology triage unit sees patients who have received systemic anti-cancer therapy (SACT) presenting with a variety of side effects and symptoms including oncological emergencies, reducing the need for ED attendance. The trainee ACPs identified the neutropenic sepsis pathway as an area requiring urgent change. Through the creation of a new neutropenic sepsis screening tool, as well delivering educational sessions to nursing staff on the unit, the trainee ACPs were able to significantly improve door-to-needle times for patients as well as increasing the use of patient group directions (PGDs), thus reducing delays in antibiotic administration.

MO156: The Choice of Empiric Antimicrobial Agent and its Association with Outcomes in Kidney Transplant Recipients with Urinary Sepsis

Abstract BACKGROUND AND AIMS Efficient antibiotic therapy remains the cornerstone of successful sepsis treatment. Urinary sepsis, which remains the most common sepsis type in kidney transplant recipients (KTRs), is characterized by high prevalence of multidrug-resistant (MDR) bacterial strains, often limiting the choice of antimicrobial agents. The primary aim of this study was to elucidate the efficiency of primary empiric antimicrobial therapy in KTRs hospitalized for urosepsis, depending on the antibiotic choice. METHOD All primary urosepsis cases in KTRs hospitalized in 2014–2019 in the Transplantation Department of the Wroclaw Medical University Hospital were included retrospectively as the study group (n = 101). A total of 100 random KTRs hospitalized for primary urinary tract infection (UTI) were set as control group. The primary endpoint was the need for antibiotic change after 3 days of completed empiric treatment (due to lacking clinical response or proven antibiotic resistance). All patients were treated according to SSC guidelines with delay in antibiotic administration of no more than 1 h after the diagnosis of sepsis. RESULTS In the urosepsis and UTI groups, the need for antibiotic change after 3 days of treatment equaled 45.6% and 11%, respectively. Patients with urosepsis and inappropriate antibiotic therapy were at increased risk of death (OR = 10.1 with P = .021), need for acute renal replacement therapy (OR = 4.73 with P = .012) and non-recovery from AKI (OR = 3.18 with P = .031). Similar but not statistically significant trend was observed in the UTI group for lacking recovery from AKI (OR = 1.64 with P = .636). In both groups, the length of hospital stay was significantly longer in patients who did not receive appropriate empiric antimicrobial drug. Following antimicrobial agents were associated with appropriate successful treatment rates in the urosepsis and UTI groups: ciprofloxacine (0% versus 63%), amoxiciline with clavulonic acid (16.7% versus 89%), piperaciline with tazobactam (57% versus 60%), cefuroxime (67% versus 100%), third generation cephalosporines (76% versus 92%) and carbapenemes (100% versus 100%). CONCLUSION A delay in successful antibiotic therapy, caused by inappropriate choice of antimicrobial agents, for the treatment of urosepsis in KTRs is associated with detrimental kidney graft outcomes. Ciprofloxacine and amoxiciline with clavulonic acid should not be used for empiric therapy of urosepsis in this patient cohort. The development of urosepsis in KTRs as compared to non-septic UTI is associated with greater risk of antibiotic resistance among causative microorganisms and increased risk of antimicrobial failure.

Coagulation factor protein abundance in the pre-septic state predicts coagulopathic activities that arise during late-stage murine sepsis.

SummaryBackgroundAlthough sepsis accounts for 1 in 5 deaths globally, few molecular therapies exist for this condition. The development of effective biomarkers and treatments for sepsis requires a more complete understanding of host responses and pathogenic mechanisms at early stages of disease to minimize host-driven pathology.MethodsAn alternative to the current symptom-based approach used to diagnose sepsis is a precise assessment of blood proteomic changes during the onset and progression of Salmonella Typhimurium (ST) murine sepsis.FindingsA distinct pattern of coagulation factor protein abundance was identified in the pre-septic state– prior to overt disease symptoms or bacteremia– that was predictive of the dysregulation of fibrinolytic and anti-coagulant activities and resultant consumptive coagulopathy during ST murine sepsis. Moreover, the changes in protein abundance observed generally have the same directionality (increased or decreased abundance) reported for human sepsis. Significant overlap of ST coagulopathic activities was observed in Gram-negative Escherichia coli– but not in Gram-positive staphylococcal or pneumococcal murine sepsis models. Treatment with matrix metalloprotease inhibitors prevented aberrant inflammatory and coagulopathic activities post-ST infection and increased survival. Antibiotic treatment regimens initiated after specific changes arise in the plasma proteome post-ST infection were predictive of an increase in disease relapse and death after cessation of antibiotic treatment.InterpretationAltered blood proteomics provides a platform to develop rapid and easy-to-perform tests to predict sepsis for early intervention via biomarker incorporation into existing blood tests prompted by patient presentation with general malaise, and to stratify Gram-negative and Gram-positive infections for appropriate treatment. Antibiotics are less effective in microbial clearance when initiated after the onset of altered blood proteomics as evidenced by increased disease relapse and death after termination of antibiotic therapy. Treatment failure is potentially due to altered bacterial / host-responses and associated increased host-driven pathology, providing insight into why delays in antibiotic administration in human sepsis are associated with increased risk for death. Delayed treatment may thus require prolonged therapy for microbial clearance despite the prevailing notion of antibiotic de-escalation and shortened courses of antibiotics to improve drug stewardship.FundingNational Institutes of Health, U.S. Army.

Factors associated with antibiotic administration delay among preterm infants with late-onset bloodstream infection

Early antibiotic administration is an important modifiable factor in reducing mortality from late-onset bloodstream infections in preterm infants. In a cohort study including 142 infants with non-coagulase negative staphylococcus bloodstream infection at two tertiary neonatal intensive care units, we identified typical practice-related factors that may be targeted to prevent delays in antibiotic administration. Collection of cerebrospinal fluid or urine sample before administering antibiotics, a longer time taken to site a peripheral intravenous catheter among those without pre-existing access, and a longer time taken to administer fluid boluses were associated with a longer than median time to antibiotic administration.

Infective endocarditis, is there a goal beyond antibiotics and surgery?

In the vast majority of infectious diseases, the primary endpoint to evaluate an intervention relies on short terms variables and, when relevant, in-hospital mortality, or 28 days mortality. In most cases, these early targets are directly related to an intervention but could potentially fail to estimate a more global approach where other factors could modulate long-term prognosis. This problem was largely evaluated in sepsis survivors, although still largely debated, short prognosis has been related to corticoids [1], early goal-directed therapy [2], or delay in antibiotic administration [3–6].

Strengthening sepsis care at a tertiary care teaching hospital in New Delhi, India

IntroductionFailure of early identification of sepsis in the emergency department (ED) leads to significant delays in antibiotic administration which adversely affects patient outcomes.AimThe primary objective of our Quality Improvement (QI)...

What accounts for the delay in antibiotic administration in children with suspected sepsis in the emergency department?—a case control study

What accounts for the delay in antibiotic administration in children with suspected sepsis in the emergency department?—a case control study

There is no association between weekend admissions and delays in antibiotic administration for patients admitted to the emergency department with suspicion of sepsis: A retrospective cohort study.

Admission to the emergency department (ED) on weekends has been associated with an increase in mortality and poor outcomes, but the associated findings are not consistent. It has been hypothesized that this association may be due to lower adherence to standards of care.This study was conducted to evaluate whether weekend admissions to the ED increases the time to antibiotic administration in septic patients.A retrospective cohort study of adult patients who were included in the sepsis protocol at a tertiary ED between January 2015 and December 2017 was performed. The sepsis protocol was activated for all patients with suspected severe infection.A total of 831 patients with a mean age of 59 ± 21 years were evaluated, of whom 217 (26.1%) were admitted on weekends. In addition, 391 (47.1%) patients were male, and 84 (10.1%) died in the hospital. Overall, the mean sequential organ failure assessment score was 2 ± 1.9, and the mean Charlson comorbidity index was 3.7 ± 3. The time to antibiotic administration was similar between patients admitted on weekends (36.29 ± 50 minutes CI 95%) and patients admitted on weekdays (44.44 ± 69 minutes CI 95%), P = .06; U = 60174.0. Additionally, mortality was similar in both groups of patients, with a 10.3% mortality rate on weekdays and a 9.8% mortality rate on weekends, P = 821.In this cohort of patients with suspicion of sepsis in the ED, admission on weekends was not associated with increased delays in antibiotic therapy or higher mortality rates.

Delay of Antibiotic Administration Greater than 2 Hours Predicts Surgical Site Infection in Open Fractures

Delay of Antibiotic Administration Greater than 2 Hours Predicts Surgical Site Infection in Open Fractures

Predictors for delayed antibiotic administration among bacteraemic patients in the Emergency Department: Differences between medical and surgical interns.

Bloodstream infections (BSIs) have been associated with high mortality. The aim of the study was to identify predictors of early (within 3hours from triage) administration of first antibiotic dose among patients evaluated in the Emergency Department (ED) with BSI and their role in mortality. All adult patients with BSI at the ED of the Hospital of Jura, Switzerland during a 3year period (July 2014 to June 2017) were included. Among 364 BSI, the most common sites of infection were urinary tract (39.6% of BSIs), lower respiratory tract (15.4%), intra-abdominal (15.4%) and primary BSI (9.1%). One-hundred-seventy-eight patients (48.9%) received the first antibiotic dose within 3hours from triage. Multivariate analysis identified evaluation by internal medicine intern, triage scales 1 and 2, as predictors of early antibiotic administration, while, primary BSI was associated with delayed antibiotic administration. Thirty-day mortality was 12.9% (47 patients). Charlson comorbidity index, septic shock, low respiratory tract infection were independently associated with mortality, while antibiotic administration within 3hours from triage and source control within 48hours from triage were associated with survival. The majority of patients received the first antibiotic dose after 3hours Patients evaluated by surgical interns had a significant delay in administration of antibiotics as compared to those treated by medical interns.