Gram-negative Rod Bacteremia Research Articles

National study reveals gram negative bacteremia on contemporary pediatric AML protocol

Since bacteremia complicates childhood Acute myeloid leukemia (AML) patients, we assessed bacteremia rates in Israeli children with de-novo AML. All chemotherapy courses of patients enrolled in NOPHO-DBH-2012 AML protocol were included. Down syndrome, acute promyelocytic leukemia were excluded. Among 69 patients, seven had focal bacterial infections. Of the remaining 62, 77.4% had 1–8 bacteremias. Of 238 chemotherapy courses, 98 (41.2%) had bacteremia: 66 (67.3%) predominantly Gram-negative rods (GNR); 28 (28.6%) Gram-positive cocci. Escherichia coli; followed by Klebsiella were most common. Older age, Arab ethnicity, and presenting white blood cell count were associated with an increased risk of bacteremia in the univariable analysis, but these associations were not confirmed in the multivariable analysis. Mortality was high (9.7%), and bacteremia increased PICU utilization 7-fold half from GNR. Most isolates were sensitive to vancomycin/meropenem (94.7%), but GNR had low sensitivity to quinolones (61.8%). High mortality and morbidity of de-novo AML patients from predominantly GNR bacteremia require specific interventions but limited susceptibility to quinolones hampers prophylaxis.

It Takes a Village: Leveraging a Multidisciplinary Team and Technology for Urine Culturing Stewardship

Background: Patients without urinary tract infection (UTI) symptoms but with a positive urine culture are considered to have asymptomatic bacteriuria (ASB). This often represents colonization and treatment is not recommended or clinically beneficial. Treatment of ASB can promote antimicrobial resistance and increased rates of Clostriodies difficile infections. Many cases of ASB are incorrectly assigned as CAUTIs due to over-culturing practices. We hypothesized that a urine culture algorithm, embedded within a best practice alert (BPA) in the electronic medical record (EMR), would reduce urine culturing practices for ASB. Methods: From Feb 2022 through May 2023, a multidisciplinary team implemented an Inpatient Urine Culturing Stewardship Guideline. A BPA fired when a provider placed a urinalysis with reflex to culture (UACC) or urine culture (UC) order for patients who met criteria (Image 1). The BPA directed providers to remove the order, select the appropriate pathway from the guideline, or provide a rationale for placing the order. The intervention was piloted on three intensive care units and two progressive care units, containing both medical and surgical patients. Monthly ordering practices, CAUTI rates, and gram-negative rod (GNR) bacteremia rates from a 13-month pre-intervention baseline period were compared to a 16-month intervention period. Over the same time periods, we also assessed changes in ordering practices for comparison units which did not implement the intervention. Pre-and-post intervention cohorts were analyzed using median two sample tests and Exact Poison Method, as appropriate. Results: On intervention units there was a 41.0% reduction in the median number of UACC and UC orders per 1000 patient days from 16.31 during the baseline period to 9.62 in the intervention period (p=0.0036). Pan cultures per 1000 patient days in which one of the orders was a UACC or UC fell by 42.2% from a median of 10.20 per 1000 patient days to 5.90 (p=0.0008). The comparison units saw no significant reductions in UACC and UC orders (p=0.21) or pan cultures (p=1.0). On the intervention units, the CAUTI rate for the baseline period was 1.31 per 1000 catheter days versus 0.79 in the intervention period (IRR = 1.65; p=0.44). GNR bacteremias remained stable on the intervention units between the baseline and intervention periods (p=0.82). Conclusion: This multidisciplinary intervention, leveraging EMR clinical decision support, reduced urine and pan culturing practices while demonstrating a trend towards a reduced CAUTI rate. The prevalence of GNR bacteremias remained consistent with baseline levels, suggesting the intervention did not cause harm.

Carbapenem-resistant gram-negative rod bacteremia in the early postoperative period following liver transplantation

Carbapenem-resistant gram-negative rod bacteremia in the early postoperative period following liver transplantation

Anaerobic gram-negative rod bacteremia as a marker of gastrointestinal cancer in Japanese patients: a single-center retrospective study.

Gram-negative rod (GNR) bacteremia has been suggested as a clinical marker of occult cancer; however, no studies are available in this regard in the Japanese population. Here, we investigated the risk factors for gastrointestinal cancer with GNR bacteremia. Patients with GNR bacteremia admitted to St. Luke's International Hospital between January 2011 and July 2021 were included. The clinical data of patients with and without cancer, 1 year before and after GNR bacteremia diagnosis, were compared. Univariate analysis was performed using χ2 and Fisher's exact tests for categorical variables and the Mann-Whitney U test for continuous variables, while multivariable analysis was performed using logistic regression analysis, and a P of <0.05 was considered statistically significant. Of 2,296 GNR bacteremia-positive patients, 96 were associated with gastrointestinal cancer, and univariate analysis showed significant differences between the gastrointestinal cancer and comparison groups in terms of mean body mass index (BMI; 20.5 vs. 21.8 kg/m2), Enterobacterales detection (64.6% vs. 81.3%), and anaerobic GNR detection (24.0% vs. 8.5%). Thirty-five (36%) and 61 (64%) patients had upper and lower gastrointestinal cancer, respectively. There were 23 patients with anaerobic GNR bacteremia related to 24 strains (upper and lower gastrointestinal cancer, 5 and 18 cases, respectively). Multivariate analysis identified anaerobic GNR [odds ratio, 3.440; 95% confidence interval (CI): 2.085-5.675, P<0.001] as a significant risk factor for cancer. Anaerobic GNR in blood cultures may be a risk factor for gastrointestinal cancer. Therefore, it is necessary consider cancer workup, such as endoscopy, for patients with anaerobic GNR bacteremia.

Impact of restrictive urinalysis reflex to culture criteria at a large community hospital

Treatment of asymptomatic bacteriuria (ASB) is a common, but often unnecessary, practice. Our objective was to determine the impact of restrictive urinalysis reflex to culture (UARC) criteria on rate of urine cultures (UC) ordered and ASB treatment. Criteria were modified from positive leukocyte esterase, positive nitrites, or white blood cells (WBC) >10 cells to only WBC >10 cells.This pre-post study evaluated UARCs ordered in the emergency department or inpatient units. The primary outcome was the proportion of reflex UCs prevented. Secondary outcomes included the frequency of repeat UARCs and stand-alone UCs, gram-negative rod (GNR) bacteremia, and ASB treatment.In the pre-intervention, there were 4761 UARCs compared to 5420 in the post-intervention; 37.9 % and 21.4 % reflexed to UCs, a 43.5 % reduction in UCs. The rate of repeat UARCs, stand-alone UCs, and GNR bacteremia in the pre- and post-interventions were similar. ASB treatment rate was numerically lower in the post-intervention.

1211. Impact of Gram-Negative Rod Bacteremia Rapid Diagnostic Testing and Real-Time Clinical Staff Pharmacist Review

Abstract Background Although Rapid Diagnostic Testing (RDT) enables optimization of antimicrobial therapy, there is no consensus on how to integrate utilization into clinical practice. At our institution, the BIOFIRE® Blood Culture Identification 2 (BCID2) RDT was implemented in September 2021 in conjunction with real-time clinical staff pharmacist result notification and review. The objective of this study was to determine the impact of RDT plus real-time clinical staff pharmacist review on the management of gram-negative rod (GNR) bacteremia. Methods This retrospective, matched cohort study included patients with a positive blood culture for a GNR on the BCID2 panel from September 2020 to August 2021 (historical) and October 2021 to September 2022 (interventional). Exclusion criteria were polymicrobial bacteremia, discrepant RDT results from traditional culture, 24-hour mortality, and comfort care or not admitted at the time of RDT result. Patients were randomly screened to include 120 patients in each group and matched based on age, pathogen, and resistance mechanism. The primary endpoint was time from Gram stain to appropriate antibiotic therapy. Secondary endpoints included time to first pathogen-directed change in therapy, days of anti-pseudomonal therapy, length of stay (LOS), and inpatient mortality. Results The study population was predominantly female (61%) and the majority were over 70 years old (55%). Escherichia coli was isolated in 71% of patients with extended-spectrum beta-lactamase-producing organisms isolated in 8%. The median time to appropriate therapy was 0 hours for both groups, indicating patients were on appropriate therapy at the time of Gram stain result (p=0.28). There was a statistically significant decrease in time to first pathogen-directed change in therapy (40 vs. 11 hours; p&amp;lt; 0.01). There was no difference in days of anti-pseudomonal therapy, LOS, or inpatient mortality between groups. Conclusion Implementation of RDT plus real-time clinical staff pharmacist intervention did not impact time to appropriate therapy in patients with GNR bacteremia but did significantly reduce time to pathogen-directed antibiotic changes. RDT plus real-time clinical staff pharmacist intervention is a practical method of utilizing technology to improve patient care. Disclosures All Authors: No reported disclosures

Impact of Gram-Negative Rod Bacteremia Rapid Diagnostic Testing and Real-Time Clinical Pharmacist Intervention

Background: The optimal method for implementing rapid diagnostic testing (RDT) into clinical practice has not been determined for gram-negative rod (GNR) bacteremia. At our institution, RDT was implemented in conjunction with real-time notification of results to decentralized clinical pharmacists. Objective: To determine the impact of RDT result notification plus real-time clinical pharmacist review on the management of GNR bacteremia. Methods: This retrospective, matched cohort study included patients with a positive blood culture for a GNR on the BIOFIRE® Blood Culture Identification 2 panel from September 2020 to August 2021 (historical) and October 2021 to September 2022 (interventional). Exclusion criteria were polymicrobial bacteremia, discrepant RDT results from traditional culture, 24-hour mortality, and comfort care or not admitted at the time of RDT result. Patients were matched based on age, pathogen, and resistance. The primary endpoint was time from Gram stain to appropriate antibiotic therapy. Results: This study consisted of 240 patients (n = 120 historical, n = 120 interventional). Escherichia coli was isolated in 71% of patients with extended-spectrum beta-lactamase-producing organisms isolated in 8%. There was no difference in median time to appropriate therapy (0 vs 0 hours, P = 0.28). There was a statistically significant decrease in time to first organism-directed change in therapy (40 vs 11 hours; P < 0.01). Length of stay, days of anti-pseudomonal therapy, and inpatient mortality did not differ between groups. Conclusion: Implementation of RDT plus real-time clinical pharmacist review did not significantly decrease time to appropriate therapy in patients with GNR bacteremia but significantly reduced time to organism-directed antibiotic changes.

Are hematopoietic cell transplant recipients with Gram-negative bacteremia spending more time outpatient while on intravenous antibiotics? Addressing trends over 10 years at a single center.

IntroductionThe increasing proportion of outpatient allogeneic hematopoietic cell transplants (HCTs) coupled with increased access of once‐daily broad‐spectrum antibiotics and evidence that outpatient antibiotic treatment may be safer and less costly than inpatient treatment, suggest that allogeneic HCT recipients with Gram‐negative rod bacteremia (GNRBs) are increasingly being treated in ambulatory care settings.MethodsUsing data from the first GNRB event that occurred within the first 100 days posttransplantation among allogeneic HCT recipients transplanted at a single center between 2007 and 2016, we estimated the temporal trends in GNRB incidence and treatment management of GNRBs and identified if patient or infection characteristics impacted observed trends.ResultsA total of 11% (238/2165) of the observed allogeneic HCT recipients experienced ≥1 GNRB with available resistance data and contributed antibiotic treatment time. Patients, on average, received 55.1% of their antibiotic treatment in an outpatient setting and we observed a significant decline in the proportion of treatment time spent outpatient (crude: −3.3% [95% confidence interval: −5.0, −1.6%]). We observed similar declines in the proportion of treatment time spent outpatient among patients with similar GNRB and pretransplant complexity factors but not among patients with similar posttransplant complications (p value: .165).ConclusionThese results suggest that, despite increased availability of outpatient suitable treatment options, allogeneic HCT recipients with GNRBs received less treatment in outpatient settings. However, among patients with similar posttransplant complications, the lack of significant decline suggests that treatment location decisions remained consistent for patients with similar posttransplant complications. These findings suggest the need for additional interventions targeting outpatient antibiotic treatment among allogeneic HCT recipients with GNRBs.

A rapid and inexpensive protocol to screen for third generation cephalosporin-resistant and non-fermenting Gram-negative rods directly in positive blood cultures

Third generation cephalosporins are frequently used in the first-line treatment of Gram-negative rod (GNR) bacteremia but are unsuitable in the case of extended-spectrum-beta-lactamase-producing Enterobacterales (ESBL-E) or non-fermenting GNR infections. The aim of this study was to develop and evaluate a simple and rapid two-test protocol involving oxidase and β-Lacta tests performed directly on positive blood culture broth as a preliminary screen for non-fermenting or third generation cephalosporins-resistant GNR. The diagnostic performance of this approach was evaluated on 294 bottles for the oxidase test and 267 bottles for the β-Lacta Test. The sensitivity and specificity of the oxidase test were respectively 93.1% and 100%, and the sensitivity of the β-Lacta Test for ESBL-E was 100% and the specificity 99.5%. This simple protocol, which can be implemented in all laboratories and performed in only 20 min, may be a valuable tool to optimize first-line antibiotic therapy for bacteremia.

Expanding an Economic Evaluation of the Veterans Affairs (VA) Methicillin-resistant Staphylococcus aureus (MRSA) Prevention Initiative to Include Prevention of Infections From Other Pathogens.

In October 2007, Veterans Affairs (VA) launched a nationwide effort to reduce methicillin-resistant Staphylococcus aureus (MRSA) transmission called the National MRSA Prevention Initiative. Although the initiative focused on MRSA, recent evidence suggests that it also led to a significant decrease in hospital-onset (HO) gram-negative rod (GNR) bacteremia, vancomycin-resistant Enterococci (VRE), and Clostridioides difficile infections. The objective of this analysis was to evaluate the cost-effectiveness and the budget impact of the initiative taking into account MRSA, GNR, VRE, and C. difficile infections. We developed an economic model using published data on the rate of MRSA hospital-acquired infections (HAIs) and HO-GNR bacteremia in the VA from October 2007 to September 2015, estimates of the attributable cost and mortality of these infections, and the costs associated with the intervention obtained through a microcosting approach. We explored several different assumptions for the rate of infections that would have occurred if the initiative had not been implemented. Effectiveness was measured in life-years (LYs) gained. We found that during fiscal years 2008-2015, the initiative resulted in an estimated 4761-9236 fewer MRSA HAIs, 1447-2159 fewer HO-GNR bacteremia, 3083-3602 fewer C. difficile infections, and 2075-5393 fewer VRE infections. The initiative itself was estimated to cost $561 million over this 8-year period, whereas the cost savings from prevented MRSA HAIs ranged from $165 to $315 million and from prevented HO-GNR bacteremia, CRE and C. difficile infections ranged from $174 to $200 million. The incremental cost-effectiveness of the initiative ranged from $12 146 to $38 673/LY when just including MRSA HAIs and from $1354 to $4369/LY when including the additional pathogens. The overall impact on the VA's budget ranged from $67 to$195 million. An MRSA surveillance and prevention strategy in VA may have prevented a substantial number of infections from MRSA and other organisms. The net increase in cost from implementing this strategy was quite small when considering infections from all types of organisms. Including spillover effects of organism-specific prevention efforts onto other organisms can provide a more comprehensive evaluation of the costs and benefits of these interventions.

668. Rapid Identification and Antimicrobial Susceptibility Testing of Gram-Negative Rod Bacteremia: Impact on Duration of Hospital Admission

BackgroundThere are many emerging diagnostic technologies that provide rapid identification (ID) and antimicrobial susceptibility testing (AST) of blood cultures after initial microbial growth is detected. The clinical utility of having these results sooner than standard of care (SOC) ID/AST testing is less clear; one potential advantage would be shorter hospital admissions for those patients with less severe infections whose discharge planning is delayed while waiting for ID/AST results.MethodsThe Accelerate Pheno™ rapid ID/AST system (AP) was implemented in the clinical microbiology lab at two hospitals within our academic hospital system to run in parallel with our SOC ID/AST diagnostics for all blood cultures with Gram-negative rod (GNR) bacterial growth on initial Gram stain. Results of both diagnostic assays were uploaded to the medical record when available; our antimicrobial stewardship (AS) team discussed the AP results with clinical care teams during working hours. Length of stay (LOS) data was compared between a cohort with GNR bacteremia before and after the implementation of AP testing with AS review.ResultsThere were 207 patients with GNR bacteremia admitted to the hospital during the first six months after implementation of AP testing with AS review (12/2019 – 05/2020). A historical cohort of 96 patients with GNR bacteremia (admitted 01/2018 – 08/2018) with SOC testing without AS review was used for comparison. Median LOS was 5.28 and 5.84 days for the AP and SOC cohorts, respectively; the distribution in the two groups differed significantly (Mann-Whitney U = 8728.5, p = 0.0446). There was also an increase in the percent of admissions shorter than 2 days between the AP and SOC cohorts (12.5% v. 5.2%, p = 0.024) [Figure1].Figure 1 ConclusionThe use of a rapid ID/AST diagnostic technology with AS review may lead to shorter hospitalizations in select patient populations.Disclosures Kimberle Chapin, MD, genmark (Scientific Research Study Investigator)

278. Comparison of Oral Cephalexin Versus Oral Levofloxacin for Treatment of Uncomplicated Enterobacterales Bacteremia

BackgroundAerobic gram-negative rods (GNR) are a common cause of bloodstream infections. While the use of oral antibiotics as step-down therapy for GNR bacteremia is generally accepted, there is debate as to which agents are best. Fluoroquinolones have high oral bioavailability but also have concerns for toxicity, while oral beta-lactams have lower achievable blood concentrations and require more frequent dosing. At Kaweah Delta Medical Center, patients are transitioned from IV antibiotics to oral levofloxacin or cephalexin. The purpose of this study is to determine if these two oral agents are comparable when used as step-down therapy for uncomplicated GNR bacteremia.MethodsThis was a single-center, retrospective study of adult patients who were admitted from May 2018 - May 2019 with a positive GNR blood culture. The primary objective was to assess treatment failure defined as a composite outcome of readmission due to recurrent bacteremia or mortality within 60-days. Secondary outcomes included subsequent Clostridioides difficile infection, emergence of resistant GNR bacteria, and hospital length of stay.ResultsA total of 82 patients met inclusion criteria. The combined median age of both treatment groups was 58.2 years (interquartile range [IQR], 46.7–73.5) and greater than 60% of patients were female. Most patients were Hispanic (45.1%) or non-Hispanic white (43.9%). The most common documented source of GNR bacteremia was the urinary tract (74.4%), and the most frequently recovered organism was Escherichia coli (78.0%). Patients were treated with IV antibiotics for a median treatment duration of 4 days (IQR, 4–5) and oral antibiotics for a median treatment duration of 10 days (IQR, 7.3–11) and 9 days (IQR, 7–11) for cephalexin and levofloxacin, respectively. The composite outcome occurred in 2 patients (4.3%) from the cephalexin group and 0 patients from the levofloxacin group (p=0.50). Positive cultures for resistant GNR were found for 3 patients in the cephalexin group. No patients developed subsequent C. difficile infections. ConclusionPatients who received cephalexin or levofloxacin did not have a significant difference in the composite primary outcome. These findings suggest that oral cephalexin is an effective step-down option to treat uncomplicated GNR bacteremia.Disclosures All Authors: No reported disclosures

271. Clinical Outcomes Treating Gram-Negative Bacteremia with Oral Beta-Lactams vs. Trimethoprim-Sulfamethoxazole or Fluoroquinolone Step-Down Therapy

BackgroundRecently, studies about gram-negative bacteremia have shown that shorter courses and early step-down therapy with oral agents have equivalent outcomes compared to longer courses with intravenous therapy. The question remains, however, as to which oral agents may be most appropriate for oral conversion therapy. At Cone Health it has been common practice to de-escalate to oral beta-lactams due to local susceptibility patterns and safety concerns with fluoroquinolones. This study retrospectively evaluated the 30-day clinical outcomes of patients treated with oral beta-lactams as step-down therapy vs. fluoroquinolones and trimethoprim-sulfamethoxazole (TMP-SMX).MethodsIn this IRB approved, retrospective review, 200 patients with gram-negative rod bacteremia were screened. Sixty-seven patients were excluded due to inpatient mortality (17), transfer to another facility (7), hospice care (6), or receipt of intravenous antibiotics only (37). The most common organism isolated was E. coli at 57% (75/133) and a majority of cases had a genitourinary source, 79/133 (59%). The primary endpoints were 30-day readmission and mortality. Secondary endpoints included total length of antibiotic therapy and length of IV therapy.ResultsOf the 133 patients included, 101 (76%) received an oral beta-lactam and 32 (24%) received either a fluoroquinolone or TMP-SMX. In the beta-lactam group 22/101 (21.8%) were re-admitted within 30-days compared to 5/32 (15.6%) in the fluoroquinolone and TMP-SMX group (p=0.412). Each group had one patient re-admitted due to recurrence of bacteremia. The majority of patients in the beta-lactam group were re-admitted for a non-infectious reason (82%). Only 1 (1%) patient in the beta-lactam group died within 30 days of discharge compared to 2 (6%) in the fluoroquinolone group (p=0.165). Average total length of therapy in the beta-lactam group was 12.8 days compared to 14 days in the fluoroquinolone and TMP-SMX group (p=0.065). Average length of IV therapy was 3 days in the beta-lactam group and 4 days in the fluoroquinolone and TMP-SMX group (p=0.99).ConclusionAt our institution, we have not noted any significant difference in 30-day bacteremia recurrence or mortality between those who receive oral beta-lactams or fluoroquinolones/TMP-SMX.Disclosures All Authors: No reported disclosures

108. Impact of Accelerate Pheno System in the Management of Gram-Negative Rod Bacteremia

BackgroundEarly pathogen identification and initiation of appropriate antimicrobial therapy is key in the management of Gram-negative rods (GNR) bloodstream infection (BSI). The Accelerate Pheno System (ACC) has been shown to reduce time to GNR identification compared to traditional culture-based methods. We aimed to determine the impact of ACC on the management of GNR BSI in the setting of a well-established antimicrobial stewardship program (ASP).Table 1 MethodsACC was introduced in our institution on February 2019. Due to issues incorporating ACC, of patients with GNR BSI, 74% had ACC done and 26% had reporting through traditional methods. This allowed for the design of a retrospective cohort study (instead of a pre-post analysis) to evaluate the association of interest. We included adult patients admitted to three affiliated hospitals in Des Moines, Iowa with BSI due to Enterobacteriales from February 2019 to February 2020. Exclusion criteria were Emergency Department visit only and death within 48 hours of blood culture collection. Primary outcomes were length of hospital stay, days to therapy optimization and in-hospital mortality. Continuous variables were compared by non-parametric methods and categorical variables were compared by Chi-square and Fisher-exact test. Logistic regression models were used to calculate odds ratio for the impact of the intervention on therapy optimization.ResultsA total of 268 patients were analyzed. The median length of stay among patients who had ACC done was 5.2 days (IQR 3.6–8.7) and in those on who ACC was not done it was 5.5 (IQR 3.8–8.9) (p=0.54). No differences in in-hospital mortality were found (p=0.942).Changes in therapy and missed opportunities for optimization according to whether ACC was done are shown in Table 1. Patients who had ACC done had 99% higher odds of de-escalation within 48 hours of blood culture collection compared to patients who did not have it done (95% CI 1.01–3.92; p=0.044).ConclusionIn the context of hospitals with baseline short length of stay and a well-established ASP, performing ACC was associated with higher odds of de-escalation within 48 hours of blood culture collection but did not impact length of stay or mortality among patients hospitalized with GNR BSI.Disclosures All Authors: No reported disclosures

Intercontinental study on pre-engraftment and post-engraftment Gram-negative rods bacteremia in hematopoietic stem cell transplantation patients: Risk factors and association with mortality

We present here data on Gram-negative rods bacteremia (GNRB) rates, risk factors and associated mortality. Data on GNRB episodes were prospectively collected in 65 allo-/67 auto-HSCT centers in 24 countries (Europe, Asia, Australia). In patients with and without GNRB, we compared: demography, underlying disease, HSCT-related data, center` fluoroquinolone prophylaxis (FQP) policy and accreditation status, and involvement of infection control team (ICT). The GNRB cumulative incidence among 2818 allo-HSCT was: pre-engraftment (pre-eng-allo-HSCT), 8.4 (95% CI 7-9%), post-engraftment (post-eng-allo-HSCT), 5.8% (95%CI: 5-7%); among 3152 auto-HSCT, pre-eng-auto-HSCT, 6.6% (95%CI: 6-7%), post-eng-auto-HSCT, 0.7% (95%CI: 0.4-1.1%). GNRB, especially MDR, was associated with increased mortality. Multivariate analysis revealed the following GNRB risk factors: (a) pre-eng-allo-HSCT: south-eastern Europe center location, underlying diseases not at complete remission, and cord blood source; (b) post-eng-allo-HSCT: center location notin northwestern Europe; underlying non-malignant disease, not providing FQP and never accredited. (c) pre-eng-auto-HSCT: older age, autoimmune and malignant (vs. plasma cell) disease, and ICT absence. Benefit of FQP should be explored in prospective studies. Increased GNRB risk in auto-HSCT patients transplanted for autoimmune diseases is worrying. Infection control and being accredited are possibly protective against bacteremia. GNRB are associated with increased mortality.

Impact of Rapid Antimicrobial Susceptibility Testing in Gram-Negative Rod Bacteremia: a Quasi-experimental Study.

Clinical justification for rapid antimicrobial susceptibility testing (AST) in Gram-negative rod (GNR) bacteremia is compelling; however, evidence supporting its value is sparse. We investigated the impact of rapid AST on clinical and antimicrobial stewardship outcomes in real-world practice. We performed a before-and-after quasi-experimental study from February 2018 to July 2019 at a tertiary hospital of the 24-h/day, 7-day/week implementation of the direct Vitek 2 AST method from positive blood culture broth for GNR bacteremia with electronic isolate-specific de-escalation comments and daytime antibiotic stewardship program (ASP) intervention. The primary outcome was time to appropriate antibiotic escalation or de-escalation, and secondary outcomes included time to oral antibiotic stepdown, hospital length of stay (LOS), all-cause 30-day mortality, 7-day incidence of acute kidney injury (AKI), and 30-day incidence of Clostridioides difficile infection (CDI). A total of 671 GNR isolates were included from 643 adult patients. Among patients for whom antibiotic change occurred after rapid AST result, rapid AST was associated with a trend in decreased time to escalation or de-escalation (hazard ratio, 1.22; 95% confidence interval [CI], 0.99 to 1.51; P = 0.06), with median times of 52.3 versus 42.2 h. Secondary outcomes were similar in both groups and include median time to oral antibiotic stepdown, LOS, all-cause mortality, and incidence of AKI and CDI. Rapid AST led to improved stewardship measures but did not impact clinical patient outcomes. These results highlight that multiple variables in addition to the timing of the AST result contribute to clinical outcome and that further intervention may be required to clinically justify rapid AST implementation.

Trends in the Proportion of Time Spent Outpatient While Receiving Antibiotics for Treatment of Gram-Negative Rod Bacteremia Among Allogeneic Hematopoietic Cell Transplant Recipients

Background Gram-negative rod bacteremia (GNRB) is a leading cause of morbidity and mortality among allogeneic hematopoietic cell transplant (HCT) recipients. Historically, GNRB has been treated with inpatient intravenous antibiotic therapies. However, outpatient antibiotic delivery has been shown to lower costs, decrease complications and may reduce rates of hospital-acquired multidrug-resistant organism (MDRO) infections. Despite such advantages, there are no data assessing trends in outpatient management of GNRB among allogeneic HCT recipients nor on the impact changing resistance profiles have on such trends. We estimated the linear time-trend, shape of trend, and average proportion of treatment time spent outpatient for allogeneic HCT recipients with GNRB. Methods First 100 day post-HCT data were retrospectively examined for adult patients transplanted at a single institution between 2007 and 2017. We defined GNRB as blood culture confirmed GNR, limited our analysis to first infections, and presumed antibiotic duration lasted 14 days. We estimated the direction and magnitude of the time trend and tested for an association between calendar year and proportion of time spent outpatient using linear analysis with a continuous year variable. We accounted for a priori selected confounders (graft vs. host disease (GVHD), neutropenia, conditioning regimen, location of GNRB diagnosis, polymicrobial culture, MDRO (Stenotrophomonas maltophilia isolates or resistance to ³1 agents in ³3 categories: cephalosporins, beta-lactamase inhibitors, carbapenems, aminoglycosides, and fluoroquinolones), and age at diagnosis) using adjusted linear analysis and estimated the shape of the time-trend using a linear model with a natural spline for time. We tested if MDRO modified the outpatient temporal trend using a likelihood ratio test. Results Of the 2,165 allogeneic HCT recipients included, 252 (11.6%) experienced 1 or more GNRB with available resistance data. Twenty-four (9.5%) analyzed infections were polymicrobial and 75 (29.8%) were MDR. On average, patients received 59.2% of their antibiotic treatment in an outpatient setting. We observed a crude and adjusted per year decline in the proportion of treatment time spent outpatient (crude: -2.6% [95% CI: -1.0, -4.2%]; adjusted: -1.1% [-2.5, 0.2%]); the decline was non-linear (Figure 1). MDR, GVHD, neutropenia, and being inpatient at diagnosis were associated with a smaller proportion of treatment time spent outpatient and MDR status was found to modify the association between calendar year and proportion of time spent outpatient (p-value: 0.04; Figure 2). Conclusion The proportion of GNRB antibiotic treatment time allogeneic HCT recipients spent in the outpatient setting declined between 2007 and 2017. However, this decline was explained by severity of illness and infection complexity factors, such as MDR and GVHD.

Proposal of a clinical score to stratify the risk of multidrug-resistant gram-negative rods bacteremia in cancer patients

IntroductionMultidrug-resistant gram-negative rods (MDR GNR) represent a growing threat for patients with cancer. Our objective was to determine the characteristics of and risk factors for MDR GNR bacteremia in patients with cancer and to develop a clinical score to predict MDR GNR bacteremia. Material and MethodsMulticenter prospective study analyzing initial episodes of MDR GNR bacteremia. Risk factors were evaluated using a multiple logistic regression (forward-stepwise selection) analysis including variables with a p<0.10 in univariate analysis. Results394 episodes of GNR bacteremia were included, with 168 (42.6 %) being MDR GNR. Five variables were identified as independent risk factors: recent antibiotic use (OR=2.8, 95 % CI 1.7–4.6, p=0.001), recent intensive care unit admission (OR=2.9, 95 % CI 1.1–7.8, p=0.027), hospitalization ≥ 7 days prior to the episode of bacteremia (OR=3.5, 95 % CI 2–6.2, p=0.005), severe mucositis (OR=5.3, 95 % CI 1.8–15.6, p=0.002), and recent or previous colonization/infection with MDR GNR (OR=2.3, 95 % CI 1.2–4.3, p=0.028). Using a cut-off value of two points, the score had a sensitivity of 66.07 % (95 % CI 58.4–73.2 %), a specificity of 77.8 % (95 % CI 71.4–82.7 %), a positive predictive value of 68 % (95 % CI 61.9–73.4 %), and a negative predictive value of 75.9 % (95 % CI 71.6–79.7 %). The overall performance of the score was satisfactory (AUROC 0.78; 95 % CI 0.73-0.82). In the cases with one or none of the risk factors identified, the negative likelihood ratio was 0.18 and the post-test probability of having MDR GNR was 11.68 %. ConclusionsWith the growing incidence of MDR GNR as etiologic agents of bacteremia in cancer patients, the development of this score could be a potential tool for clinicians.

1087. Fluoroquinolone Prophylaxis vs. No Bacterial Prophylaxis in Hospitalized Neutropenic Patients Undergoing Induction Chemotherapy for Acute Myeloid Leukemia

BackgroundDespite evidence to support outpatient anti-pseudomonal fluoroquinolone (FQ) prophylaxis in neutropenic patients, limited data exist to support this for inpatients undergoing induction chemotherapy for acute myeloid leukemia (AML). At our institution, we implemented an initiative to replace FQ prophylaxis with a conditional order for an anti-pseudomonal β-lactam to be given if a fever occurred.MethodsA retrospective chart review was conducted to analyze the outcome differences between patients receiving FQ prophylaxis (pre-intervention) and those who had a conditional order for an anti-pseudomonal β-lactam in place of FQ prophylaxis (post-intervention). Patients were included if they were ≥18 years of age and were newly diagnosed with AML undergoing induction chemotherapy. The primary outcome was 90-day all-cause mortality. Secondary outcomes included the number of patients requiring ICU admission and rate of bacteremic episodes caused by any pathogen and from a Gram-negative rod (GNR). Additionally, ciprofloxacin susceptibility of these pathogens was analyzed.ResultsThere were 35 and 26 patients in the pre- and post-intervention groups, respectively. Between pre- and post-intervention groups, there was no difference in 90-day mortality (20.0% vs. 15.4%; P = 0.745) or ICU admissions (25.7% vs. 23.1%, P = 1), respectively. The rate of any bacteremic episode was similar between the pre- and post-intervention groups (51.4% vs. 65.4%; P = 0.307), but more patients in the post-intervention group developed GNR bacteremia (17.1% vs. 46.2%; P = 0.023). In the patients with GNR bacteremia, the number of ciprofloxacin nonsusceptible isolates was higher in the pre-intervention group (100% vs. 30.7%; P = 0.011).ConclusionReplacing FQ prophylaxis with a conditional order for an anti-pseudomonal β-lactam for inpatients newly diagnosed with AML receiving induction chemotherapy is a feasible option to decrease FQ exposure. Though increased episodes of GNR bacteremia were observed, there was no difference in total bacteremic episodes or clinical outcomes, and the improved ciprofloxacin susceptibility patterns will allow for an additional treatment option in this extremely vulnerable patient population. Disclosures All authors: No reported disclosures.

178. Evaluation of Oral Antibiotic Stepdown Therapy for the Management of Gram-Negative Rod Bacteremia in a Tertiary Care Medical Center

BackgroundTreatment strategies surrounding bacteremia are constantly changing as new data emerges. Transition from intravenous (IV) to oral (PO) antibiotics in patients with Gram-negative rod bloodstream infections (GNR BSI) remains controversial. The objective of this study was to characterize clinical outcomes in patients who received early (≤72 hours) vs. late (>72 hours) stepdown therapy (ES vs. LS, respectively) for GNR BSIs.MethodsA single-center, retrospective cohort study was conducted including adults with GNR BSIs admitted to a 610-bed tertiary care academic medical center between January 1, 2016 and December 31, 2017 who were transitioned from IV to PO antibiotics. Patients with severe renal impairment, inadequate source control, prolonged antibiotic course, HIV/AIDS, and pregnancy were excluded. The primary endpoint was clinical failure and secondary endpoints were 30- and 90-day all-cause mortality, duration of bacteremia, and adverse events.Results164 patients (ES = 61; NS = 103) were included. Population median age was 63 years, 56% were male, and 19% were immunocompromised. Genitourinary source was most common (48.7%), while the most common organism isolated was Escherichia coli (52.4%). Most infections were community-acquired (70.1%) and the most common step-down therapy choice was ciprofloxacin in 75% of patients. There were no major differences in baseline demographic and clinical characteristics between groups except for the greater presence of central venous catheters (16.4% vs. 35.9%; P = 0.006) in the LS group. Overall clinical failure was 9.8% vs. 13.6% between the ES and LS groups, respectively. The LS group had a higher rate of clinical failure defined by escalation from PO to IV antibiotics (1.6% vs. 10.7%; P = 0.03). Patients who failed therapy tended to be immunocompromised and/or have an intra-abdominal source of infection. Secondary endpoints did not differ between groups.ConclusionHigher clinical failure rates in the LS group indicate that these patients may have underlying clinical characteristics not amenable to stepdown therapy. Choice of step-down therapy was not driven by the source of infection or patient acuity. Further analysis and studies are needed to determine optimal time and population for stepdown.Disclosures All authors: No reported disclosures.