Number Of Antibiotic Days Research Articles

Antibiotic exposure for culture-negative early-onset sepsis in late-preterm and term newborns: an international study.

Early-life antibiotic exposure is disproportionately high compared to the burden of culture-proven early-onset sepsis (CP-EOS). We assessed the contribution of culture-negative cases to the overall antibiotic exposure in the first postnatal week. We conducted a retrospective analysis across eleven countries in Europe, North America, and Australia. All late-preterm and term infants born between 2014 and 2018 who received intravenous antibiotics during the first postnatal week were classified as culture-negative cases treated for ≥5 days (CN ≥ 5d), culture-negative cases treated for <5 days (CN < 5d), or CP-EOS cases. Out of 757,979 infants, 21,703 (2.9%) received intravenous antibiotics. The number of infants classified as CN ≥ 5d, CN < 5d, and CP-EOS was 7996 (37%), 13,330 (61%), and 375 (1.7%). The incidence of CN ≥ 5d, CN < 5d, and CP-EOS was 10.6 (95% CI 10.3-10.8), 17.6 (95% CI 17.3-17.9), and 0.49 (95% CI 0.44-0.54) cases per 1000 livebirths. The median (IQR) number of antibiotic days administered for CN ≥ 5d, CN < 5d, and CP-EOS was 77 (77-78), 53 (52-53), and 5 (5-5) per 1000 livebirths. CN ≥ 5d substantially contributed to the overall antibiotic exposure, and was 21-fold more frequent than CP-EOS. Antimicrobial stewardship programs should focus on shortening antibiotic treatment for culture-negative cases. In a study of 757,979 infants born in high-income countries, we report a presumed culture-negative early-onset sepsis incidence of 10.6/1000 livebirths with an associated antibiotic exposure of 77 antibiotic days per 1000 livebirths. This study sheds light on the major contribution of presumed culture-negative early-onset sepsis to early-life antibiotic exposure. Given the diagnostic uncertainty surrounding culture-negative early-onset sepsis, the low mortality rate, and the disproportionate antibiotic exposure associated with this condition, our study emphasizes the importance of targeting culture-negative early-onset sepsis in antimicrobial stewardship programs.

The budget impact of procalcitonin-guided antibiotic stewardship compared to standard of care for patients with suspected sepsis admitted to the intensive care unit in Belgium.

In Belgium, antibiotic resistance leads to approximately 530 deaths with a €24 million financial burden annually. This study estimated the impact of procalcitonin-guided antibiotic stewardship programs to reduce antibiotic consumption versus standard of care in patients with suspected sepsis. A decision analytic tree modelled health and budget outcomes of procalcitonin-guided antibiotic stewardship programs for patients admitted to the intensive care unit (ICU). A literature search, a survey with local clinical experts, and national database searches were conducted to obtain model input parameters. The main outcomes were total budget impact per patient, reduction in number of antibiotic resistance cases, and cost per antibiotic day avoided. To evaluate the impact of parameter uncertainty on the source data, a deterministic sensitivity analysis was performed. A scenario analysis was conducted to investigate budget impact when including parameters for reduction in length of ICU stay and mechanical ventilation duration, in addition to base-case parameters. Based on model predictions, procalcitonin-guided antibiotic stewardship programs could reduce the number of antibiotic days by 66,868, resulting in €1.98 million savings towards antibiotic treatment in current clinical practice. Antibiotic resistance cases could decrease by 7.7% (6.1% vs 9.2%) in the procalcitonin-guided setting compared with standard of care. The base-case budget impact suggests an investment of €1.90 per patient. The sensitivity analysis showed uncertainty, as the main drivers can alter potential cost savings. The scenario analysis indicated a saving of €1,405 per patient, with a reduction of 1.5 days in the ICU (14.8 days vs 12.8 days), and a reduction of 22.7% (18.1-27.2%) in mechanical ventilation duration. The associated sensitivity analysis was shown to be robust in all parameters. Procalcitonin-guided antibiotic stewardship programs are associated with clinical benefits that positively influence antimicrobial resistance in Belgium. A small investment per patient to implement procalcitonin testing may lead to considerable cost savings.

Real-World Data about Commonly Used Antibiotics in Long-Term Care Homes in Australia from 2016 to 2019.

In this study, we use real-world data to explore trends in antibiotic use in a dynamic cohort of long-term care (LTC) residents. A cross-sectional retrospective analysis of pharmacy medication supply records of 3459 LTC residents was conducted from 31 May 2016 to 31 May 2019. The primary outcome was the monthly prevalence of residents with an antibiotic episode. Secondary outcomes were the type of antibiotic used and duration of use. Over the three-year study period, residents were supplied 10460 antibiotics. On average, 18.9% of residents received an antibiotic monthly. Antibiotic use decreased slightly over time with a mean of 168/1000 (95% CI 146-177) residents using at least one antibiotic per month in June 2016 to 148/1000 (95% CI 127-156) in May 2019. The total number of antibiotic days per 100 resident days remained relatively constant over the study period: 8.8 days in 2016-2017, 8.4 in 2017-2018 and 6.4 in 2018-2019. Prolonged durations exceeding 100 days were seen for a small percentage of residents. We found extensive antibiotic use, which is a recognized contributor to antimicrobial resistance development, underscoring the necessity for quality treatment guidelines in this vulnerable population.

381. Antibiotic Spectrum Index and Risk of Clostridioides difficile Infection

Abstract Background Antibiotic therapy is a known risk factor for Clostridioides difficile infection (CDI) and evidence suggests the magnitude of risk varies by spectrum of antibiotic activity and days of therapy (DOT). We quantified the risk of hospital-associated (HA) CDI associated with antibiotic therapy considering spectrum of activity and DOT. Methods We performed a retrospective cohort study of adult (≥18 years) inpatient encounters at a 576-bed academic medical center in Portland, OR between January 2018 and February 2020. We excluded patients with hospital stays under 4 days and those known to have recurrent (CDI in the previous 12 weeks) or community-acquired (CDI diagnosis within first 3 days of hospitalization) CDI. The primary exposure of antibiotic utilization was measured using the Antibiotic Spectrum Index (ASI), where spectrum-based weights are applied to each agent and DOT over the time at risk, summed over the encounter, and divided by the number of antibiotic days. The primary outcome was HA-CDI. We estimated the independent association between aggregate ASI and HA-CDI using multivariable logistic regression. Results Among 37,629 inpatient encounters, 68% patients received at least one antibiotic. We identified 159 cases of non-recurrent HA-CDI, which corresponds to 4.8 cases per 10,000 patient-days. Compared to those without HA-CDI, those with HA-CDI had a greater median number of distinct antibiotics prescribed (4 vs 1), greater median days of antibiotic therapy (22 vs 2), a greater median time at-risk (9 vs 6 days), and greater median Elixhauser Comorbidity Index (9 vs 4) (Kruskal-Wallis p-value &amp;lt; 0.0001 for all comparisons). There were no significant differences by age or sex. Patients with HA-CDI had a greater mean ASI per antibiotic day than those without (5.2 vs 3.2, Student’s t-test p &amp;lt; 0.0001). After adjusting for time at-risk and Elixhauser Comorbidity Index, each one-unit of ASI per antibiotic day was associated with 1.29 times increased odds of developing HA-CDI (Odds Ratio = 1.29, 95% Confidence Interval: 1.21 to 1.37). Conclusion The Antibiotic Spectrum Index was strongly associated with HA-CDI. ASI may be a useful tool for quantifying the risk of CDI according to the specific antibiotic therapy received among hospitalized patients. Disclosures All Authors: No reported disclosures.

Is a shorter course of antibiotics better for children with CAP?

Results of the SCOUT-CAP randomized clinical trial published in the January 2022 issue of JAMA Pediatrics found that a short 5-day antibiotic treatment course is superior to a standard 10-day regimen for children with non-severe community-acquired pneumonia (CAP) in an outpatient setting. A short 5-day strategy reduced both antibiotic exposure and resistance while presenting a similar clinical response and antibiotic-related adverse effect profile as a standard 10-day course. According to the study, CAP is one of the most common serious infections in pediatric populations, with reports of about 1.5 million ambulatory visits by U.S. children yearly. “It’s critical that we minimize the use of unnecessary antibiotics, both to eliminate the risk of antibiotic adverse effects and slow the progression of antimicrobial resistance, a global public health threat,” said Derek Williams, MD, MPH, lead investigator of the study. Although antibiotics are not always needed, when required it is important to choose the right antibiotic, at the right dose, and only for as long as necessary to effectively treat the infection, said Williams, who is an associate professor of pediatrics at Vanderbilt University School of Medicine. The randomized, double-blind, placebo-controlled clinical trial included 380 healthy children between the ages of 6 months and roughly 6 years with non-severe CAP in 8 U.S. cities between December 2016 and December 2019. They were seen in outpatient clinics, urgent care settings, and emergency departments. Children were only included in the study if they had not experienced the following at time of enrollment based on caregiver reporting: subjective fever or temperature 38.3°C or higher in the previous 24 hours; tachypnea (50 and 40 breaths per minute for children younger than 2 years, and 2 years and older, respectively); and severe cough. Study participants were randomized 1:1 to either receive a 5-day course of matching placebo or an additional 5-day course of the originally prescribed β-lactam antibiotic—including amoxicillin, amoxicillin and clavulanate, or cefdinir—on day 6 of therapy. Dosing for amoxicillin or amoxicillin and clavulanate was 80 to 100 mg/kg a day (maximum 2,000 mg a day) based on the amoxicillin component divided twice daily, and cefdinir dosing was 12 to 16 mg/kg a day (maximum 600 mg a day) divided twice daily. The taste and appearance of the matching placebo was consistent and dosed at the same interval as the original 5-day course therapy. Study participants underwent two in-person outcome assessment visits on study days 6 to 10 and days 19 to 25, respectively. The primary composite endpoint—a ranking of each child’s clinical response, symptom resolution, and antibiotic-associated adverse effects—made up the end-of-treatment response adjusted for duration of antibiotic risk (RADAR) in an ordinal desirability of outcome ranking (DOOR). Participants were then ranked by the number of antibiotic days within each DOOR, with the hypothesis that shorter antibiotic durations were more desirable. RADAR was used to determine the more desirable outcome probability estimate for short- versus standard-course strategy. During the antibiotic resistance analysis, throat swab samples were taken from the oropharyngeal flora of 171 children between days 19 and 25 to assess antibiotic resistance. The research findings showed that a majority of children had an adequate clinical response to both strategies, with fewer than 10% of children experiencing a poor response. The research team found that the short-course strategy had a 69% probability of a more desirable RADAR outcome compared with the standard-course strategy. The antibiotic resistance analysis showed that the range of antibiotic resistance genes per prokaryotic cell (RGPC) was significantly lower in the short-course strategy compared with the standard-course strategy for total RGPC and β-lactamase RGPC, according to the study. “SCOUT-CAP is the first clinical trial to use this innovative trial design, taking into account both the response to and potential side effects of antibiotic therapy,” said C. Buddy Creech, MD, MPH, a professor of pediatrics at Vanderbilt University Medical Center, who was also part of the study. “These data are immediately applicable to frontline clinicians, and we hope it helps to shift the paradigm for childhood pneumonia toward more judicious treatment approaches, resulting in safer and more effective care,” said Williams. Future trials using this approach may allow us to optimize therapy for other infectious diseases in children and adults, said Creech.

Extracorporeal Photopheresis in Lung Transplantation - New Frontiers in Infection Immunomodulation - A Case Series

<h3>Purpose</h3> Lung transplantation outcomes are limited by chronic lung allograft dysfunction (CLAD). Infection driven loss of graft function is a common cause of CLAD. Extracorporeal photopheresis (ECP) is a salvage therapy post lung transplantation with the indications broadening as experience and availability increases. The therapeutic role of ECP is yet to be explored in infection driven CLAD. <h3>Methods</h3> A retrospective audit of all lung transplant recipients at a single UK lung transplant centre who received ECP from 2017 to 2021 was performed using electronic records.5 patients with infection driven CLAD treated with ECP were identified. <h3>Results</h3> 40% were male with median(range) age 63(30-70) years. Median duration from lung transplant to ECP was 38(13-53)months and median duration of ECP was 14(10-15) months. All 5 patients were responders at 2 months (defined as less than 20 percent FEV1 fall). Median(range) FEV1 percentage change improved from -17% (-20 to+10%) one year pre-ECP to +1%(-1to+10%) one year post-ECP (Figure1). Mycophenolate mofetil was stopped for all patients on initiation of ECP. 4 patients had a reduction in length of stay in hospital (Figure 2). 3 patients were alive 1 year post ECP whilst 2 patients are still within their first year of follow up. <h3>Conclusion</h3> ECP can help to stabilize graft function in lung transplant recipients with recurrent infections. It allows for modification of conventional immunosuppression regimens and contributes to improved quality of life by decreasing the length of hospital stay and number of antibiotic days.

Short- vs Standard-Course Outpatient Antibiotic Therapy for Community-Acquired Pneumonia in Children

Childhood community-acquired pneumonia (CAP) is usually treated with 10 days of antibiotics. Shorter courses may be effective with fewer adverse effects and decreased potential for antibiotic resistance. To compare a short (5-day) vs standard (10-day) antibiotic treatment strategy for CAP in young children. Randomized double-blind placebo-controlled clinical trial in outpatient clinic, urgent care, or emergency settings in 8 US cities. A total of 380 healthy children aged 6 to 71 months with nonsevere CAP demonstrating early clinical improvement were enrolled from December 2, 2016, to December 16, 2019. Data were analyzed from January to September 2020. On day 6 of their originally prescribed therapy, participants were randomized 1:1 to receive 5 days of matching placebo or 5 additional days of the same antibiotic. The primary end point was the end-of-treatment response adjusted for duration of antibiotic risk (RADAR), a composite end point that ranks each child's clinical response, resolution of symptoms, and antibiotic-associated adverse effects in an ordinal desirability of outcome ranking (DOOR). Within each DOOR rank, participants were further ranked by the number of antibiotic days, assuming that shorter antibiotic durations were more desirable. Using RADAR, the probability of a more desirable outcome was estimated for the short- vs standard-course strategy. In a subset of children, throat swabs were collected between study days 19 and 25 to quantify antibiotic resistance genes in oropharyngeal flora. A total of 380 children (189 randomized to short course and 191 randomized to standard course) made up the study population. The mean (SD) age was 35.7 (17.2) months, and 194 participants (51%) were male. Of the included children, 8 were Asian, 99 were Black or African American, 234 were White, 32 were multiracial, and 7 were of unknown or unreported race; 33 were Hispanic or Latino, 344 were not Hispanic or Latino, and 3 were of unknown or unreported ethnicity. There were no differences between strategies in the DOOR or its individual components. Fewer than 10% of children in either strategy had an inadequate clinical response. The short-course strategy had a 69% (95% CI, 63-75) probability of a more desirable RADAR outcome compared with the standard-course strategy. A total of 171 children were included in the resistome analysis. The median (range) number of antibiotic resistance genes per prokaryotic cell (RGPC) was significantly lower in the short-course strategy compared with the standard-course strategy for total RGPC (1.17 [0.35-2.43] vs 1.33 [0.46-11.08]; P = .01) and β-lactamase RGPC (0.55 [0.18-1.24] vs 0.60 [0.21-2.45]; P = .03). In this study, among children responding to initial treatment for outpatient CAP, a 5-day antibiotic strategy was superior to a 10-day strategy. The shortened approach resulted in similar clinical response and antibiotic-associated adverse effects, while reducing antibiotic exposure and resistance. ClinicalTrials.gov Identifier: NCT02891915.

Prevention of ventilator-associated pneumonia by noble metal coating of endotracheal tubes: a multi-center, randomized, double-blind study

BackgroundVentilator-associated pneumonia (VAP) causes increased mortality, prolonged hospital stay and increased healthcare costs. Prevention of VAP in intensive care units (ICUs) is currently based on several measures, and application of noble metal coating on medical devices has been shown to inhibit the bacterial adherence of microorganisms to the surface. The objective of this study was to evaluate the potential benefit of noble metal coating of endotracheal tubes for the prevention of VAP.MethodsThis was a multi-center, randomized, controlled, double-blind, prospective study including ventilated patients from nine ICUs from four hospital sites in Belgium. Patients were randomly intubated with identical appearing noble metal alloy (NMA) coated (NMA-coated group) or non-coated (control group) endotracheal tubes (ETT). Primary endpoint was the incidence of VAP. Secondary endpoints were the proportion of antibiotic days during ICU stay and tracheal colonization by pathogenic bacteria.ResultsIn total, 323 patients were enrolled, 168 in the NMA-coated group and 155 in the control group. During ventilation, VAP occurred in 11 patients (6.5%) in the NMA-coated group and in 18 patients (11.6%) in the control group (p = 0.11). A higher delay in VAP occurrence was observed in the NMA-coated group compared with the control group by Cox proportional hazards regression analysis (HR 0.41, 95% CI 0.19–0.88, p = 0.02). The number of antibiotic days was 58.8% of the 1,928 ICU days in the NMA-coated group and 65.4% of the 1774 ICU days in the control group (p = 0.06). Regarding tracheal colonization, bacteria occurred in 38 of 126 patients in the NMA-coated group (30.2%) and in 37 of 109 patients in the control group (33.9%) (p = 0.57).ConclusionsThis study provides preliminary evidence to support the benefit of noble metal coating in the prevention of VAP. A confirmatory study in a larger population would be valuable.Trial registration: Clinical trial number: NCT04242706 (http://www.clinicaltrials.gov)

Neonatal Early Onset Sepsis: Impact of Kaiser Calculator in an Italian Tertiary Perinatal Center.

Suspected early-onset sepsis (EOS) results in antibiotic treatment and blood withdraw of a substantial number of neonates who are uninfected. We evaluated if the EOS calculator can reduce antibiotic exposure and invasive procedures for suspected EOS in term and late preterm neonates, without any significant increase in adverse outcomes. The proportion of EOS risk in neonates ≥35 weeks gestation exposed to antibiotics, intensive monitoring and blood withdrawal was compared between a baseline period (January 2018-May 2018), when Centers for Disease Control guidelines approach was used, and a post-EOS calculator-implementation period (June 2018-December 2019). We included 4363 newborn infants with gestational age ≥35 weeks, respectively 824 in baseline period and 3539 in the EOS calculator period. Among them, 1021 (23.4%) infants presented risk factors for neonatal sepsis. There was a halving in empirical antibiotics exposure: 3% in the baseline and 1.4% in the post-EOS-implementation period, P < 0.05. Blood culture and laboratory evaluations had fallen from 30.6% to 15.4% (P < 0.05). Close monitoring of vital parameters decreased from 25.4% to 4.8% (P < 0.05). The number of antibiotic days per 100 live births decreased from 15.05 to 6.36 days (P <0.05). The incidence of culture-confirmed sepsis and clinical sepsis was very low in 2 periods. Only one infant identified at low-risk by Kaiser calculator at birth developed symptoms after 12 h from birth. We had no readmissions for EOS. Application of the EOS calculator more than halved the burden of intensive monitoring and antibiotic exposure, without compromising safety in a population with a relatively low incidence of culture-proven EOS and good access to follow-up care.

Risk Factors of Mortality for Patients Receiving Venovenous Extracorporeal Membrane Oxygenation for COVID-19 Acute Respiratory Distress Syndrome.

Background: Venovenous extracorporeal membrane oxygenation (VV-ECMO) for select adults with severe acute respiratory distress syndrome (ARDS) cause by coronavirus disease 2019 (COVID-19) infection is a guideline-supported therapy with associated hospital survival of 62%-74%, similar to expected survival with VV-ECMO for other indications. However, ECMO is a resource-heavy intervention, and these patients often require long ECMO runs and prolonged intensive care unit (ICU) care. Identifying factors associated with mortality in VV-ECMO patients with COVID-19 infection can inform the evaluation of ECMO candidates as well as prognostication for those patients on prolonged VV-ECMO. Patients and Methods: This was a retrospective cohort study that included all patients who received either VV- or venoarteriovenous (VAV)-ECMO at one of four ECMO Centers of Excellence in the state of Minnesota between March 1, 2020 and November 1, 2020. The primary outcome was 60-day survival. Secondary outcomes were hospital complications, infectious complications, and complications from ECMO. Results: There were 46 patients who met criteria during this study period and 30 survived to 60-day follow-up (65.2%). Prior to cannulation, older patient age (55.5 in non-survivors vs. 49.1 years in survivors; p = 0.03), lower P/F ratio (62.1 vs. 76.2; p = 0.04), and higher sequential organ failure assessment (SOFA) score (8.1 vs. 6.6; p = 0.02) were identified as risk factors for mortality. After ECMO cannulation, increased mortality was associated with increased number of antibiotic days (25.9 vs. 14.5; p = 0.04), increased number of transfusions (23.9 vs. 9.9; p = 0.03), elevated white blood cell (WBC) count at post-ECMO days one through three, elevated D-dimer at post-ECMO day 21-27, and decreased platelet count from post-ECMO days 14 and onward using univariable analysis. Conclusions: Multiple markers of infection including leukocytosis, thrombocytopenia, and increased antibiotic days are associated with increased mortality in patients placed on VV-ECMO for COVID-19 infection and subsequent ARDS. Knowledge of these factors may assist with determining appropriate candidates for this limited resource as well as direct goals of care in prolonged ECMO courses.

Institution of an antibiotic stewardship programme for rationalising antibiotic usage: a quality improvement project in the NICU of a public teaching hospital in rural central India

Antibiotic misuse is the most common cause of antimicrobial resistance—a globally declared emergency. This necessitates the introduction of rational antibiotic usage management policy. The paediatrics department of a public teaching...

Adherence to Antibiotic Stewardship Program Associated with Shorter Course of Treatment and Fewer Adverse Events

Group Name: NorthShore University HealthSystemBackground: Prolonged antibiotic use has been attributed to an increased incidence of adverse drug events (ADEs). Cessation of unnecessary antibiotics would decrease length of treatment and may help prevent these adverse events. We evaluated whether an antibiotic stewardship intervention aimed at stopping unnecessary antibiotic usage would both shorten the duration of treatment and reduce ADEs. Methods: At NorthShore University HealthSystem, a 4-hospital, 832-bed system, we identified patients who were started on empiric antibiotics during a hospital admission between May 2, 2016, and June 30, 2018. Within 24 hours of antibiotic initiation, an infectious disease (ID) physician reviewed each patient chart. If the patient was unlikely to have a symptomatic bacterial infection, the ID physician left a note in the electronic medical record (EMR) recommending antibiotic cessation. Two physician reviewers retrospectively reviewed whether the treatment team accepted these recommendations and assessed potential ADEs for 30 days after the recommendation through inpatient and outpatient notes in the EMR. These ADEs were defined using previously published criteria. If the 2 reviewers disagreed on the presence of an ADE, an ID physician acted as the tie breaker. We compared the number of antibiotic days and the number of ADEs between cases in which the recommendations were followed and cases in which they were not. Results: We reviewed 168 cases: 78 (46.43%) followed recommendations and 90 (53.57%) did not. There were no significant differences in baseline patient characteristics between the 2 groups. There was a significant difference in total ADEs between the 2 groups: in 6 cases (7.69%) the recommendations were followed, and 21 (23.33%) they were not followed (P = .011). There was also a significant difference in antibiotic days between cases in which recommendations were followed (1.40 days) versus those in which they were not followed (1.99 days) (p &lt; 0.001). Conclusions: Antibiotic-associated adverse events can cause harm to patients and increase healthcare costs, particularly when used for patients who are unlikely to have a bacterial infection. An antibiotic stewardship program to identify patients in an EMR who are unlikely to benefit from antibiotic use can decrease the length of total antibiotic usage and help prevent adverse events.Funding: NoDisclosures: None

2130. Detection of Carbapenemase-Producing Organisms and Impact on Antimicrobial Utilization for Carbapenem-Resistant Enterobacteriaceae (CRE) Infections

BackgroundCREs are feared pathogens with resistance occurring through the production of carbapenemases. Identification of carbapenemase-producing (CP) organisms assists with proper antimicrobial selection of commonly used agents, such as ceftazidime/avibactam (CA), meropenem/vaborbactam (MV), and tigecycline (TG). AdventHealth Orlando implemented a CRE screening method based on meropenem (MER) and a confirmatory CRE PCR testing in March 2018. Prior to implementing this test, patients were deemed to have CRE infections (CREI) if the organism demonstrated resistance to any carbapenem. The objective of this study was to evaluate the impact of this testing on the utilization of anti-CRE antibiotics.MethodsThis was a retrospective pre (March 2017–February 2018)- and post (March 2018–February 2019)-implementation study examining the impact of CRE PCR testing. Outcomes included the number of antibiotic days saved, average duration of therapy (DOT), median length of stay (LOS), and change in CP-CRE prevalence. The intervention consisted of the implementation of CRE PCR testing and included inpatients > 18 years old who received either CA, MV, or TG for the treatment of a CREI.ResultsPost-implementation, 30 unique patients were identified as having a positive K. pneumoniae carbapenemase gene by PCR, indicating a CP-CRE and received CA, MV, or TG; whereas, 42 patients in the pre-implementation group had a CREI and received CA, MV, or TG. Testing to identify CP-CREs led to a 50% reduction in the number of antibiotic days for CA, MV, and TG (575 vs. 287 days, P < 0.0001). Additionally, the average DOT decreased by 2.5 days in the post-implementation group (10.5 days vs. 8 days, P = 0.18) along with a 3.5-day shorter median LOS (15 days vs. 11.5 days, P = 0.48). The CRE prevalence based on resistance only to MER is 0.27%, compared with the previously reported rate of 2.5% that included resistance to ertapenem or MER.ConclusionImplementing CRE PCR testing to identify CP-CRE organisms resulted in a significant reduction in utilization of anti-CRE agents for CREIs. Additionally, the testing algorithm allowed for accurate reporting of our local CRE prevalence. By avoiding CA, MV, or TG in patients without CP-CREs, this has the potential to optimize therapy while reducing collateral damage associated with broad-spectrum agents.Disclosures All authors: No reported disclosures.

1090. Practicing Antimicrobial Stewardship: De-escalating Empiric Antibiotics in Patients with Acute Myelogenous Leukemia and Neutropenic Fever

BackgroundIn the era of increased antibiotic resistance, minimizing the use of broad-spectrum antibiotics is essential. We sought to determine whether there was a difference in risk of recurrent fever in patients with acute myelogenous leukemia (AML) and neutropenic fever without an identifiable source in which antibacterials were de-escalated prior to neutrophil recovery compared with those that continued until recovery.MethodsWe performed a retrospective chart review of adult patients with AML undergoing induction chemotherapy at Mount Sinai Hospital in New York, NY from 2009–2017. Neutropenic fever was defined as a temperature of 100.4°F for 1 hour or single temperature of 101°F in a patient with an absolute neutrophil count (ANC) of less than 500 cells/μL. Febrile patients were treated with cefepime, piperacillin–tazobactam, or a carbapenem. De-escalation was defined as changing from one of these antibiotics to antibacterial prophylaxis such as levofloxacin, or discontinuing antibiotics. The primary outcome was recurrent neutropenic fever. Secondary outcomes were adverse events related to antibiotics, intensive care unit (ICU) transfer, and all-cause mortality.ResultsOf 390 AML patients undergoing induction chemotherapy, 135 had a neutropenic fever; of whom, 77 had no identifiable infectious source. Of those 77, 38 had antibiotics de-escalated prior to ANC recovery (“short”) and 39 had antibiotics continued until ANC recovery or discharge (“long”). Demographics were similar (Table 1). The median number of antibiotic days for the first fever was 9 in the short group and 15 in the long group (P = 0.0008) (Table 2). Risk of recurrent fever was 46% lower in the short group compared with the long group (hazard ratio 0.54, 95% CI: 0.34–0.88; P = 0.01). There was no significant difference in ICU transfer (P = 0.11) and in-hospital mortality (P = 0.36) between the short and long groups (Table 2). There were 7 adverse drug outcomes, 2 in the short group and 5 in the long group (Table 3).ConclusionAntibiotic de-escalation in AML patients with neutropenic fever with no identifiable infectious source was associated with a lower rate of recurrent fever without affecting ICU transfer, adverse drug events, and death. Physicians should consider de-escalation prior to ANC recovery in the appropriate setting. Disclosures All authors: No reported disclosures.

2662. Methenamine Hippurate Decreases the Incidence of Urinary Tract Infections in Adult Renal Transplant Recipients

BackgroundUrinary tract infections (UTIs) are a common complication of renal transplantation. Methenamine hippurate is a non-antibiotic alternative that reduces the frequency of UTIs in selected non-transplant patients, but which is not recommended in renal insufficiency. We conducted a retrospective study to determine the efficacy of methenamine prophylaxis in our kidney transplant population, and identify subgroups for which efficacy is greatest.MethodsRetrospective chart review of adult kidney transplant patients at Montefiore Medical Center who were prescribed methenamine during January 1, 2016–December 31, 2017, with extraction of clinical data in the year before and after prophylaxis. Variables included demographics, creatinine clearance and hemoglobin A1c levels at the time of prescription, incidence of UTIs as determined by standardized literature definitions, hospital admissions for infections, and antibiotic use.ResultsThe incidence of UTIs per 1000 patient-days decreased significantly, from 9.66 (95% CI 7.53–12.40) the year before to 3.24 (95% CI 2.00–5.24) the year after (P < 0.001). The effect was significantly more pronounced in patients who were transplanted due to diabetic nephropathy, with a decreased incidence of 13.05 (95% Cl 10.00–17.02) UTIs/1000 patient-days to 2.90 (95% Cl 1.58–5.32) in diabetics (P < 0.001), vs. 5.50 (95% Cl 3.65–8.28) UTIs/1000 patient-days to 3.81 (95% Cl 1.70–8.55) in non-diabetics (P = 0.44). The number of days of antibiotics for UTIs per 1000 days also decreased significantly for all patients, from 128.58 (95% CI 94.87–174.28) the year before to 49.78 (95% CI 31.74–78.07) the year after (P = 0.001). No significant differences in efficacy were seen based on sex or renal function. Three patients with indwelling urinary catheters or who required intermittent catheterization did not appear to benefitConclusionMethenamine prophylaxis decreases the incidence of UTIs and number of antibiotic days in adult renal transplant recipients. This effect was seen even in patients with reduced creatinine clearance. Patients with diabetes benefited the most. The small number of patients who required catheterization did not appear to benefit. Disclosures All authors: No reported disclosures.

Effects of an automatic discontinuation of antibiotics policy: A novel approach to antimicrobial stewardship

A novel automatic discontinuation policy implemented within an antimicrobial stewardship program (ASP) is described, and results of an evaluation of the policy's effects on antibiotic usage are reported. A retrospective, before-and-after study was conducted at an 800-bed, tertiary care, academic teaching hospital to evaluate selected antibiotic usage outcomes in both intensive care unit (ICU) and non-ICU adult patients targeted for ASP interventions before and after implementation of an automatic discontinuation of antibiotics policy (ADAP) authorizing the ASP team to automatically halt antibiotic therapy in cases involving inappropriate duplicate antimicrobial coverage or excess duration of therapy. The primary outcome was total days of antibiotic therapy. Secondary outcomes included excess days of therapy and rates of 30-day readmission, Clostridioides difficile infection, and multidrug-resistant infection. There were no statistically significant differences in group demographics or clinical characteristics. The most common indication for antibiotics was hospital-acquired pneumonia, and the most common reason for ASP intervention was excess duration of therapy. The mean total number of antibiotic days per patient was reduced from 7.6 days in the pre-ADAP group to 6.6 days in the post-ADAP group (p < 0.05). The mean number of excess days of antibiotics was similarly reduced, from 2.3 days to 1.5 days, after implementation of the ADAP (p < 0.05). Adoption of an ADAP-a more active approach to ASP interventions-was effective in reducing overall antibiotic usage and improving the efficiency of the ASP.

1479. Evaluating the Impact of Procalcitonin on Antibiotic Utilization in Chronic Obstructive Pulmonary Disease Exacerbations

BackgroundAntibiotic prescription rates for treating exacerbations of chronic obstructive pulmonary disease (COPD) have been reported as high as 90% in the United States. Research has shown that over 50% of COPD exacerbations are due to viral etiologies. Elevations in procalcitonin (PCT) levels can be seen in bacterial infections and can help guide the need for antimicrobial therapy. The goal of this study is to evaluate the impact of PCT on antibiotic use in patients with COPD exacerbations.MethodsWe conducted a retrospective, pre- and post-intervention study. Patients at least 18 years of age, with a diagnosis of COPD exacerbation, and had a PCT level drawn within 24 hours of admission were included. Exclusion criteria included patients presenting with severe trauma, sepsis, bacterial pneumonia, patients who required invasive mechanical ventilation, and patients with an initial admission to the ICU. The primary outcome was antimicrobial duration of therapy. Secondary outcomes included hospital length of stay (LOS), respiratory-related 30-day readmission rates, and treatment failure defined as ICU admission, requirement of invasive mechanical ventilation, or death.ResultsA total of 139 patients were evaluated with 64 and 75 patients in the pre- and post-intervention cohorts, respectively. PCT guidance was associated with a significant reduction in number of antibiotic days of therapy (7.1 days vs. 2.4 days; P < 0.001). A trend in decreasing LOS was observed but did not reach statistical significance (5.3 days vs. 4.1 days; P = 0.080) and respiratory-related 30-day readmission rates did not differ (9.4% vs. 10.7%; P = 0.801). In addition, treatment failure defined as ICU admission (3.1% vs. 0%; P = 0.210), requirement for invasive mechanical ventilation (3.1% vs. 0%; P = 0.210), and death (1.6% vs. 0%; P = 0.460) did not differ significantly between groups.ConclusionImplementation of a PCT-guided protocol for the treatment of COPD exacerbations was associated with a significant reduction in antimicrobial days of therapy. We noted a trend in decreasing LOS and no difference respiratory-related 30-day readmissions, or treatment failure. Our PCT-guided protocol has been demonstrated to safely reduce antibiotic utilization in patients with COPD exacerbations.Disclosures All authors: No reported disclosures.

Early Antibiotic Exposure and Adverse Outcomes in Preterm, Very Low Birth Weight Infants

To determine whether antibiotic use in the first 14 postnatal days in preterm, very low birth weight (birth weight of ≤1500 g) infants is associated with risk after 14 days of age for late-onset sepsis, necrotizing enterocolitis (NEC), or death after controlling for severity of illness using the Clinical Risk Index in Babies II score, and determine whether duration of antibiotic exposure was associated with risk of adverse outcomes. This retrospective cohort study included very low birth weight infants born at ≤326/7 weeks of gestation admitted to the neonatal intensive care unit from September 2010 to June 2014. Infants were excluded if they had major congenital anomalies or culture-proven sepsis, NEC, or death during the first 14 days of life. Antibiotic exposure was recorded as days of therapy and length of therapy in days. Of 374 infants, 70 (19%) had late-onset sepsis, NEC, or death after 14 days of age. The median number of antibiotic days of therapy and length of therapy were 5.5 and 3.0, respectively. In multivariate analysis after controlling for severity of illness, each antibiotic day of therapy was associated with a 1.24 times increased risk of sepsis, NEC, or death (OR, 1.24; 95% CI, 1.17-1.31). Risk was similar when length of therapy was used (OR, 1.47; 95% CI, 1.32-1.64). After controlling for severity of illness, each day of antibiotic therapy provided to preterm, very low birth weight infants in the first 2 weeks of age is associated with an increased risk of late-onset sepsis, NEC, or death.

Pegfilgrastim: More Cost Effective and Equally Efficacious Option as Compared to Filgrastim in Autologous Stem Cell Transplant.

Use of growth factor after high-dose chemotherapy (HDC) and autologous peripheral blood stem cell (PBSC) support is current standard in reducing days of neutropenia. This retrospective study aims to compare the efficacy of two standard growth factors, pegfilgrastim (PEG) and filgrastim (FIL) after HDC. We collected data on 195 consecutive adult patients who received an autotransplant (myeloma, lymphoma and others) between January 2004 and December 2014 at two tertiary care centres. The primary end point was the duration of neutropenia in terms of days to reach an ANC > 0.5 × 109/L. Filgrastim was given to 110 patients and PEG was given to 85 patients. Time to engraftment, defined as the time to reach an ANC of 0.5 × 109/L on 2 consecutive days after the day of auto-SCT, was 12.6days with FIL compared with 12.1days with PEG group (p = 0.126). When comparing the total days of severe neutropenia (WBC < 0.1 × 109/L), there were 5.5days of severe neutropenia with FIL compared with 5.8days with PEG group (p = 0.7). The duration of febrile neutropenia was an average of 5.3days with FIL and 4.6days with PEG (p = 0.029). The total number of antibiotic days was shorter for the patients who received PEG, being 11.08days with PEG and 12.1days with FIL (p = 0.184).The average cost savings per person in terms of number of days of hospitalization and number of days of total parental nutrition was 582 Rs (p = 0.512) and 6003 Rs (p = 0.018) respectively in favour of PEG arm. PEG is similar to FIL in hematological reconstitution, however it is more cost effective alternative after HDC and PBSC.

Antibiotic Exposure Prior to Respiratory Viral Infection Is Associated with Progression to Lower Respiratory Tract Disease in Allogeneic Hematopoietic Cell Transplant Recipients

Recent publications note an association between antibiotic exposure and respiratory viral infections (RVIs). Antibiotics affect microbiota and impair immune response against RVIs in mice, and low microbiome diversity is associated with pulmonary complications including viral lower respiratory tract disease (LRTD) in hematopoietic cell transplantation (HCT) recipients. In this study, we examined whether antibiotic exposure was associated with increased risk of disease progression in RVIs post-transplantation. We analyzed patients who underwent allogeneic HCT (June 2008 to February 2016) and had their first RVI due to parainfluenza virus (PIV), respiratory syncytial virus (RSV), or human metapneumovirus (MPV) during the initial 100 days post-transplantation. Antibiotic exposure in the 3 weeks before RVI onset was defined as (1) use of specific antibiotics versus none of these antibiotics and (2) number of antibiotic-days. Cox proportional hazards models were used to examine associations between antibiotic exposures and risk of viral disease progression to proven/probable/possible LRTD. Ninety HCT recipients (84 adults, 6 children) fulfilled study criteria; 33 progressed to LRTD. The number of antibiotic-days was associated with progression to LRTD after adjusting for neutropenia, steroid use, and either lymphopenia (hazard ratio, 1.41 [95% confidence interval, 1.04 to 1.92], P = .027) or monocytopenia (hazard ratio, 1.46 [95% confidence interval, 1.11 to 1.91], P = .006). Specific antibiotic classes was not associated with the outcome. Cumulative antibiotic exposure immediately before RVI onset is a risk factor for disease progression following PIV, RSV, and MPV infections post-transplantation. Larger cohort studies are needed to determine the impact of specific antibiotics or antibiotic classes on disease severity.