High-risk Neutropenic Patients Research Articles

Seven-day antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients: toward a new paradigm.

Data on short courses of antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients are limited. The aim of the study was to describe and compare the frequency of bacteremia relapse, 30-day overall and infection-related mortality, Clostridiodes difficile infection and length of hospital stay since bacteremia among those who received antibiotic therapy for 7 or 14days. This is a multicenter, prospective, observational cohort study in adult high-risk neutropenic patients with hematologic malignancies or hematopoietic stem cell transplant and monomicrobial Enterobacterales bacteremia. They received appropriate empirical antibiotic therapy, had a clinical response within 7days, and infection source control. Clinical, epidemiological and outcomes variables were compared based on 7 or 14days of AT. Two hundred patients were included (100, 7-day antibiotic therapy; 100, 14-day antibiotic therapy). Escherichia coli was the pathogen most frequently isolated (47.5%), followed by Klebsiella sp. (40.5%). Among those patients that received 7-day vs. 14-day antibiotic course, a clinical source of bacteremia was found in 54% vs. 57% (p = 0.66), multidrug-resistant Enterobacterales isolates in 28% vs. 30% (p = 0.75), and 40% vs. 47% (p = 0.31) received combined empirical antibiotic therapy. Overall mortality was 3% vs. 1% (p = 0.62), in no case related to infection; bacteremia relapse was 7% vs. 2% (p = 0.17), and length of hospital stay since bacteremia had a median of 9days (IQR: 7-15) vs. 14days (IQR: 13-22) (p = < 0.001). These data suggest that seven-day antibiotic therapy might be adequate for patients with high-risk neutropenia and Enterobacterales bacteremia, who receive appropriate empirical therapy, with clinical response and infection source control.

Ceftazidime-Avibactam Improves Outcomes in High-Risk Neutropenic Patients with Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales Bacteremia.

Few studies have evaluated the efficacy of ceftazidime-avibactam (CA) for Klebsiella pneumoniae carbapenemase-producing Enterobacterales bacteremia (KPC-PEB) in high-risk neutropenic patients. This is a prospective multicenter observational study in high-risk neutropenic patients with multi-drug resistant Enterobacterales bacteremia. They were compared according to the resistance mechanism and definitive treatment provided: KPC-CPE treated with CA (G1), KPC-CPE treated with other antibiotics (G2), and patients with ESBL-producing Enterobacterales bacteremia who received appropriate definitive therapy (G3). Thirty-day mortality was evaluated using a logistic regression model, and survival was analyzed with Kaplan-Meier curves. A total of 238 patients were included: 18 (G1), 52 (G2), and 168 (G3). Klebsiella spp. (60.9%) and Escherichia coli (26.4%) were the Enterobacterales most frequently isolated, and 71% of the bacteremias had a clinical source. The resistance profile between G1 and G2 was colistin 35.3% vs. 36.5%, amikacin 16.7% vs. 40.4%, and tigeclycline 11.1% vs. 19.2%. The antibiotics prescribed in combination with G2 were carbapenems, colistin, amikacin, fosfomycin, tigecycline, and fluoroquinolones. Seven-day clinical response in G1 vs. G2 vs. G3 was 94.4% vs. 42.3% vs. 82.7%, respectively (p < 0.001). Thirty-day overall mortality in G1 vs. G2 vs. G3 was 22.2% vs. 53.8% vs. 11.9%, respectively (p < 0.001), and infection-related mortality was 5.5% vs. 51.9% vs. 7.7% (p < 0.001). The independent risk factors for mortality were Pitt score > 4: OR 3.63, 95% CI, 1.18-11.14 (p = 0.025) and KPC-PEB treated with other antibiotics: OR 8.85, 95% CI, 2.58-30.33 (p = 0.001), while 7-day clinical response was a protective factor for survival: OR 0.02, 95% CI, 0.01-0.08 (p < 0.001). High-risk neutropenic patients with KPC-CPE treated with CA had an outcome similar to those treated for ESBL-producing Enterobacterales, with higher 7-day clinical response and lower overall and infection-related mortality than those treated with other antibiotics. In view of these data, CA may be considered the preferred therapeutic option for KPC-PEB in high-risk neutropenic patients.

Efficacy of an antimicrobial stewardship intervention for early adaptation of antibiotic therapy in high-risk neutropenic patients

BackgroundThe 4th European Conference on Infections in Leukemia recommends early adaptation of empirical antibiotic therapy (EAT) for febrile neutropenia in stable patients.ObjectivesTo assess the efficacy of an antimicrobial stewardship (AMS) intervention promoting early de-escalation and discontinuation of EAT in high-risk neutropenic patients.MethodsThis before-after study was conducted in the hematology department of the University Hospital of Nice, France. The AMS intervention included the development of clinical decision support algorithms, a twice-weekly face-to-face review of all antibiotic prescriptions and monthly feedback on the intervention. The primary endpoint was overall antibiotic consumption during hospital stay, expressed as days of therapy (DOT).ResultsA total of 113 admissions were included: 56 during the pre-intervention period and 57 during the intervention period. Induction chemotherapy and conditioning for allogeneic stem cell transplantation were the most frequent reasons for admission. In the intervention period, there was a significant decrease in overall antibiotic consumption (median DOT 20 vs. 28 days, p = 0.006), carbapenem consumption (median DOT 5.5 vs. 9 days, p = 0.017) and anti-resistant Gram-positive agents consumption (median DOT 8 vs. 11.5 days, p = 0.017). We found no statistical difference in the rates of intensive care unit admission (9% in each period) and 30-day mortality (5% vs. 0%, p = 0.243). Compliance with de-escalation and discontinuation strategies was significantly higher in the intervention period (77% vs. 8%, p < 0.001).ConclusionA multifaceted AMS intervention led to high compliance with early de-escalation and discontinuation of EAT and lower overall antibiotic consumption, without negatively affecting clinical outcomes.

Guidance of empirical antimicrobial therapy by surveillance cultures in high-risk neutropenic patients: a retrospective cohort study

BackgroundIn neutropenic patients, bloodstream infections (BSI) significantly contribute to morbidity and mortality. Appropriate empirical antibiotic therapy (EAT) of BSI is essential, at the same time overconsumption of very broad-spectrum antibiotics should be avoided. We investigated: (1) whether surveillance cultures can predict BSI with third-generation cephalosporin –resistant Enterobacterales and Pseudomonas aeruginosa (3GC-R), (2) the effect of inappropriate empirical antimicrobial therapy (IEAT) on clinical outcome and (3) the potential reduction of carbapenem use when using surveillance cultures to guide therapy.MethodsRetrospective study of adult patients with haematological malignancies with febrile episodes during chemotherapy-induced high-risk neutropenia in whom surveillance cultures were collected weekly. IEAT was defined as the absence of in vitro susceptibility of blood-isolates to the administered EAT. Clinical outcome (ICU admission and death) was evaluated within 30 days.ResultsA total of 673 febrile episodes occurred among 372 high-risk neutropenic patients. BSI was present in 20.1% (135/673), of which 25.9% (35/135) were due to Enterobacterales and P. aeruginosa. Of these, 17/35 were 3GC-R and 70.6% (12/17) were preceded by 3GC-R colonization. Negative predictive value of surveillance cultures for 3GC-R BSI was 99.1%. IEAT due to (3GC-R) BSI was not significantly associated with clinical outcome. Using surveillance cultures to guide EAT could potentially reduce carbapenem use by 82.8%, when compared to standard EAT with carbapenem.ConclusionsThis retrospective analysis shows that in patients with high-risk neutropenia, surveillance cultures can potentially reduce the use of carbapenems with infrequent IEAT for 3GC-R BSI and no negative impact on clinical outcome.

Safety and risk of febrile recurrence after early antibiotic discontinuation in high-risk neutropenic patients with haematological malignancies: a multicentre observational study.

Early antibiotic discontinuation according to the Fourth European Conference on Infections in Leukaemia (ECIL-4) recommendations is not systematically applied in high-risk neutropenic patients with haematological malignancies. A retrospective multicentre observational study was conducted over 2 years to evaluate the safety of early antibiotic discontinuation for fever of unknown origin (FUO) during neutropenia after induction chemotherapy or HSCT, in comparison with a historical cohort. We used Cox proportional hazards models, censored on neutropenia resolution, to analyse factors associated with febrile recurrence. Among 147 included patients in the ECIL-4 cohort, mainly diagnosed with acute leukaemia (n = 104, 71%), antibiotics were discontinued during 170 post-chemotherapy neutropenic episodes. In comparison with the historical cohort of 178 episodes of neutropenia without antibiotic discontinuation, no significant differences were observed regarding febrile recurrences [71.2% (121/170) versus 71.3% (127/178), P = 0.97], admission in ICUs [6.5% (11/170) versus 11.2% (20/178), P = 0.17], septic shock [0.6% (1/170) versus 3.9% (7/178), P = 0.07] and 30 day mortality [1.4% (2/147) versus 2.7% (4/150), P = 0.084]. In the ECIL-4 cohort, the rate of bacteraemia in case of febrile recurrence was higher [27.1% (46/170) versus 11.8% (21/178), P < 0.01] and antibiotic consumption was significantly lower (15.5 versus 19.9 days, P < 0.001). After early antibiotic discontinuation according to ECIL-4 recommendations, enterocolitis was associated with febrile recurrence [HR = 2.31 (95% CI = 1.4-3.8), P < 0.001] and stage III-IV oral mucositis with bacteraemia [HR = 2.26 (95% CI = 1.22-4.2), P = 0.01]. After an FUO episode in high-risk neutropenia, compliance with ECIL-4 recommendations for early antibiotic discontinuation appears to be safe and mucosal damage was associated with febrile recurrence and bacteraemia. Prospective interventional studies are warranted to assess this strategy in high-risk neutropenic patients.

Bloodstream Infections in Hematologic Malignancy Patients With Fever and Neutropenia: Are Empirical Antibiotic Therapies in the United States Still Effective?

BackgroundRising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant.MethodsIn a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation.ResultsAmong 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with variability across centers. Cefepime and piperacillin-tazobactam were the most commonly prescribed empirical antibiotics for FN, at 62% and 23%, respectively; a GP-directed agent was empirically included in nearly half of all FN episodes within the first 24 hours. Susceptibility to fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems was 49%, 84%, 88%, and 96%, respectively, among GN isolates. Critical illness (CrI), defined as a new requirement for mechanical ventilation, vasopressor, or death within 30 days, occurred in 15% and did not correlate with fluoroquinolone prophylaxis, organism type, initial antibiotics, or adequacy of coverage. Only severity of illness at presentation, signified by a Pitt bacteremia score ≥2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall.ConclusionsIn accordance with US guidelines, cefepime or piperacillin-tazobactam remain effective agents or empirical treatment for high-risk cancer patients with FN who are stable at presentation, maintaining high GN pathogen susceptibility and yielding excellent outcomes.

Antimicrobial stewardship in high-risk febrile neutropenia patients

BackgroundThe 2011 4th European Conference on Infections in Leukemia (ECIL4) guidelines recommend antibiotics de-escalation/discontinuation in selected febrile neutropenia (FN) patients. We aimed to assess the impact of an antimicrobial stewardship (AMS) program based on these guidelines on antibiotics use and clinical outcomes in high-risk FN patients.MethodsWe conducted an observational study in the hematology department of Cochin University Hospital in Paris, France. An ECIL4-based antibiotics de-escalation and discontinuation strategy was implemented jointly by the hematologists and the AMS team. The pre-intervention (January–October 2018) and post-intervention (January-October 2019) periods were compared. We retrospectively collected clinical and microbiological data. We compiled antibiotics consumptions via hospital pharmacy data and standardized them by calculating defined daily doses per 1000 patient-days. We analyzed the two-monthly antibiotic consumption using an interrupted time series method and built a composite endpoint for clinical outcomes based on transfer to the intensive care unit (ICU) and/or hospital death.ResultsOverall, 273 hospital stays (164 patients) in the pre-intervention and 217 (148 patients) in the post-intervention periods were analyzed. Patients were mainly hospitalized for intensive chemotherapy for acute leukemia or autologous stem-cell transplant for myeloma. Patients were slightly younger in the pre-intervention compared to the post-intervention period (median age 60.4 vs 65.2 years, p = 0.049), but otherwise comparable. After implementation of the AMS program, glycopeptide and carbapenem use decreased by 85% (p = 0.03) and 72% (p = 0.04), respectively. After adjustment on confounders, the risk of transfer to the ICU/death decreased significantly after implementation of the AMS program (post-intervention period: odds-ratio = 0.29, 95% Confidence Interval: 0.15–0.53, p < 0.001).ConclusionImplementation of a multidisciplinary AMS program for high-risk neutropenic patients was associated with lower carbapenem and glycopeptide use and improved clinical outcomes.

Association between the dietary regimen and infection-related complications in neutropenic high-risk patients with cancer

BackgroundMany haematology/oncology departments still provide a germ-free diet for neutropenic patients (neutropenic diet, ND) to minimise pathogen exposure, even though evidence on benefits is missing. We analysed the effects of a standard diet (SD) in neutropenic high-risk patients with cancer while focussing on infection-related outcomes. Patients and methodsBased on the Cologne Cohort of Neutropenic Patients, we conducted a propensity score–matched case-control study in haematological/oncological patients with a period of neutropenia longer than five days treated at our department between January 2004 and December 2012 (implementation of SD in January 2008). We assessed the association between an SD and selected infection-related end-points in an adjusted multivariable regression model and time-to-event analysis. ResultsIn total, 2086 neutropenic episodes (1043 per diet group) were included into analysis. The median days of neutropenia were 9 (interquartile range 7–16). The adjusted multivariable model revealed no association between the SD and severity and persistence of fever, death within 28 days, antibiotic treatment and weight loss >3 kg and a non-significant adjusted association between SD and duration of antibiotic treatment and blood stream infections. There was a significant association between SD and incidence of diarrhoea (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.45–0.68; P < 0.001), nausea (OR, 0.53; 95% CI, 0.43–0.66; P < 0.001) and weight loss >1 kg (OR, 0.93; 95% CI, 0.89–0.98; P = 0.002) with fewer events in SD than in the ND group. The hazard ratios of SD for the analysed end-points were non-significant. ConclusionIn our study, the implementation of an SD for high-risk neutropenic patients with cancer was safe regarding infection-related end-points.

Evaluation of serum procalcitonin, serum interleukin-6, and interleukin-8 as predictors of serious infection in children with febrile neutropenia and cancer.

Early diagnosis of sepsis in children with febrile neutropenia remains difficult owing to non-specific clinical and laboratory signs of infection. There is a need to assess the utility of inflammatory markers in clinical risk assessment for their ability to discriminate between low-risk and high-risk neutropenic patients since presently there is insufficient data to recommend their routine use. This is a prospective study of children on therapy admitted with febrile neutropenia and sampled for serum procalcitonin (PCT), interleukin-6 (IL-6), and interleukin-8 (IL-8) at admission. The febrile neutropenia episodes were categorized into two groups - Group I: no focus of infection and Group II: clinically/microbiologically documented infection. Statistical analyses for comparison were performed using Z-test and receiver operating curves at various cut-off levels. A total of 46 episodes of febrile neutropenia in 33 children were analyzed. In total, 76% were categorized as group I and 24% as group II. The mean value of PCT in group II was higher (28.07 ng/mL) than group I (1.03 ng/mL) though there was no significant statistical difference. At a cut-off level of 2 ng/mL for PCT, sensitivity of 63%, specificity of 91%, positive predictive values (PPV) of 70%, and negative predictive value (NPV) of 88% were observed. There was no significant difference in the IL-6 and IL-8 levels between both the groups. However, at an optimal cut-off value of 50 pg/mL, IL-6 had an NPV of 80% and at a cut-off level of 130 pg/mL, IL-8 had an NPV of 73%, however, with low sensitivity and specificity. IL-6, IL-8, and PCT can be utilized to define a group of patients with a low risk of sepsis in view of their favorable NPV. The use of these biomarkers together can facilitate early discharge from the hospital, and the use of oral antimicrobial therapy, in turn, reducing the cost of supportive therapy in a developing country.

1158. D-index as a Novel Index to Predict Invasive Fungal Disease in High-Risk Neutropenic Pediatric Cancer Patients and Hematopoietic Stem Cell Transplantation

BackgroundProlonged and profound neutropenia are risk factors for invasive fungal disease (IFD) during febrile neutropenia (FN) episodes. The D-index combines both depth and duration of neutropenia in a single assessment and has been proposed as a useful tool to exclude or predict IFD in high-risk adult patients. We assessed the D-index as a predictor of IFD in pediatric cancer patients.MethodsWe conducted a retrospective study of pediatric oncology patients with FN at UCM Comer Children’s Hospitals. IFD was stratified as possible, probable, and proven according EORTC/MSG criteria. Patients considered high risk of IFD were receiving intensive chemotherapy with expected prolonged neutropenia >7 days, including, but not limited to, AML, high-risk acute ALL, and hematopoietic stem cell transplantation (HSCT). The D1-index was equal to 2t1 + 3t2, where t1, and t2 are the number of days from the first day of neutropenia < 500mm3 and < 100/ mm3 respectively, until the development of IFD. The D2-index approximates the area over the neutrophil curve during neutropenia. A cumulative D-index (c-D-index) was also calculated using the first day of neutropenia until the date of the first clinical manifestation of IFD. We compared duration of neutropenia vs D-index vs c-D-index as a predictor of IFD using receiver operating characteristic curve (ROC)/AUC analysis.Figure 1 Figure 2 ResultsWe identified 455 FN episodes in 203 high-risk patients. 53/455 (11.6%) had IFD, 12 (2.6%) proven, 23 (5%) probable, and 18 (4%) possible. The median of D1, D2 indexes and c-D-index were significantly higher in patients developing IFD (38, 5225, 7352) compared to the non-IFD group (26, 3857, 5169) (P=.001, P=.001, and P=.01) respectively. The ROC curve of D-index and c-D-index (figure 1,2,3) showed better performance (AUC of 0.85,0.89, 0.81) respectively compared to the duration of neutropenia alone. The ROC was highest when D-index was combined with prolonged fever >5 days (AUC 0.94)Figure 3 Figure 4 ConclusionThe D-index may be a useful tool to stratify high-risk pediatric patients according to risk of IFD. The c-D-index, particularly, may be a useful tool to guide for empiric antifungal therapy and diagnostic testing. Prospective multi-center studies using these tools are required to refine the clinical approach to IFD.Disclosures All Authors: No reported disclosures

The cost-effectiveness of empirical antibiotic treatments for high-risk febrile neutropenic patients: A decision analytic model.

Febrile neutropenia has a significant clinical and economic impact on cancer patients. This study evaluates the cost-effectiveness of different current empiric antibiotic treatments. A decision analytic model was constructed to compare the use of cefepime, meropenem, imipenem/cilastatin, and piperacillin/tazobactam for treatment of high-risk patients. The analysis was performed from the perspective of U.S.-based hospitals. The time horizon was defined to be a single febrile neutropenia episode. Cost-effectiveness was determined by calculating costs and deaths averted. Cost-effectiveness acceptability curves for various willingness-to-pay thresholds (WTP), were used to address the uncertainty in cost-effectiveness. The base-case analysis results showed that treatments were equally effective but differed mainly in their cost. In increasing order: treatment with imipenem/cilastatin cost $52,647, cefepime $57,270, piperacillin/tazobactam $57,277, and meropenem $63,778. In the probabilistic analysis, mean costs were $52,554 (CI: $52,242-$52,866) for imipenem/cilastatin, $57,272 (CI: $56,951-$57,593) for cefepime, $57,294 (CI: $56,978-$57,611) for piperacillin/tazobactam, and $63,690 (CI: $63,370-$64,009) for meropenem. Furthermore, with a WTP set at $0 to $50,000, imipenem/cilastatin was cost-effective in 66.2% to 66.3% of simulations compared to all other high-risk options. Imipenem/cilastatin is a cost-effective strategy and results in considerable health care cost-savings at various WTP thresholds. Cost-effectiveness analyses can be used to differentiate the treatments of febrile neutropenia in high-risk patients.

A Randomized, Double-Blind, Placebo-Controlled Trial (TAURCAT Study) of Citrate Lock Solution for Prevention of Endoluminal Central Venous Catheter Infection in Neutropenic Hematological Patients.

Infection of long-term central venous catheters (CVCs) remains a challenge in the clinical management of cancer patients. We aimed to determine whether a lock solution with taurolidine-citrate-heparin would be more effective than placebo for preventing nontunneled CVC infection in high-risk neutropenic hematologic patients. We performed a prospective, multicenter, randomized (1:1), double-blind, parallel, superiority, placebo-controlled trial involving 150 hematological patients with neutropenia carrying nontunneled CVCs who were assigned to receive CVC lock solution with taurolidine-citrate-heparin or heparin alone. The primary endpoint was bacterial colonization of the CVC hubs. Secondary endpoints were the incidence of catheter-related bloodstream infection (CRBSI), CVC removal, adverse events related to the lock solution, and the 30-day case fatality rate. CVC lock solution with taurolidine-citrate-heparin was associated with less colonization of the CVC hubs than that with placebo, with no statistically significant differences: 4.1%, versus 10.1% (relative risk [RR] = 0.41, 95% confidence interval [CI] = 0.11 to 1.52), with a cumulative incidence of 4.17 (95% CI = 0.87 to 11.70) and 10.14 (95% CI = 4.18 to 19.79), respectively. There were no significant differences regarding the secondary endpoints. Only three episodes of CRBSI occurred during the study period. No adverse events related to the administration of the lock solution occurred. In this trial involving high-risk patients carrying nontunneled CVCs, the use of taurolidine-citrate-heparin did not show a benefit over the use of placebo. Nevertheless, the safety of this prevention strategy and the trend toward less hub colonization in the taurolidine-citrate-heparin group raise the interest in assessing its efficacy in centers with higher rates of CRBSI. (This study has been registered in ISRCTN under identifier ISRCTN47102251.).

2675. Changing Epidemiology of Bloodstream Infection During Chemotherapy for Acute Leukemia: Impact of Prophylactic Fluoroquinolone Restriction and Carbapenem Saving Strategy

BackgroundFluoroquinolone prophylaxis has been widely used in high-risk neutropenic patients with hematological malignancies, which may reduce bloodstream infection (BSI) and mortality. However, concerns about antibiotic resistance also exist. The aim of this study was to assess the impact of new institutional strategy of restricting fluoroquinolone prophylaxis and saving carbapenem, applied since October 2016. Fluoroquinolone prophylaxis was adopted only in remission induction chemotherapy, and carbapenems were saved until other antibiotics prove no effectivenessMethodsWe retrospectively reviewed all consecutive intensive chemotherapy episodes for acute leukemia from April 2016 to March 2017 at the Catholic Hematology Hospital. In addition, antibiotics consumption was assessed by calculating defined daily doses (DDDs) per 100 bed-days.ResultsAmong 420 admissions during the study period, 201 and 219 admissions were identified before (period 1) and after (period 2) the strategy modification. Baseline characteristics including types of leukemia, chemotherapy, severity and duration of neutropenia were not different between the two periods.Development of febrile neutropenia (83.6% vs. 84.0%, P = 0.487), BSI (46.3% vs. 52.5%, P = 0.291), and septic shock (4.0% vs. 6.4%, P = 0.268) were not significantly different. Polymicrobial BSI increased significantly (7.1% vs. 20.0%, p = 0.012) in period 2. Quinolone resistance (97.8% vs. 43.6%, P < 0.001) and extended-spectrum β-lactamase producers (50% vs. 29.1%, P = 0.032) among Enterobacteriaceae were significantly reduced. Carbapenem-resistant Enterobacteriaceae was not isolated in period 2. Vancomycin resistance among enterococci (66.7% vs. 15%, P = 0.006) decreased. Consumption of ciprofloxacin (37.2 vs. 13.8) and carbapenem (22.3 vs. 16.8) decreased, while piperacillin/tazobactam consumption increased (5.2 vs. 13.0). BSI-related death (1.0% vs. 0.9%) was not increased.ConclusionFluoroquinolone prophylaxis restriction and carbapenem saving strategies resulted in significant reduction of resistant bacterial BSIs, without increase in febrile neutropenia, BSI, septic shock, and BSI-related death. Antibiotics stewardship program can be tried in neutropenic patients, which may improve the ultimate outcome.Disclosures All authors: No reported disclosures.

2685. Oral Third-Generation Cephalosporins vs. Levofloxacin for Antibacterial Prophylaxis in Neutropenic Patients with Hematologic Malignancies

BackgroundFluoroquinolone (FQ) prophylaxis for high-risk neutropenic patients has been shown to reduce rates of febrile neutropenia and is standard at many centers. For patients who cannot receive a FQ, oral third-generation cephalosporins (OTGCs) are often used as an alternative; however, this strategy is not well studied. We sought to compare clinically-relevant outcomes in patients receiving FQ vs. OTGC prophylaxis.MethodsThis was a retrospective cohort study of adults who were admitted to the Malignant Hematology service at the University of California, San Francisco between December 2012 and June 2018 and received >48 hours of an OTGC (cefdinir or cefpodoxime) or an FQ (levofloxacin) for neutropenic prophylaxis. For each OTGC patient, an FQ patient was randomly selected from the same admission year. Exclusion criteria were fever on admission, receipt of systemic antibiotics prior to or during the prophylaxis period, diagnosis of acute promyelocytic leukemia, and crossover. A multivariable logistic regression analysis adjusting for age, QTc, Charlson Comorbidity Index, underlying diagnosis, receipt of stem cell transplant (SCT), and duration of neutropenia was used to compare the groups with respect to a primary composite outcome of 30-day in-hospital mortality, intensive care unit (ICU) admission, and bacteremia.ResultsOf 520 patients screened, 173 (33.3%) were included in the study; 76 of these received an OTGC and 97 received an FQ. Hematologic diagnoses included multiple myeloma (38.2%), acute myeloid leukemia (29.5%), acute lymphoblastic leukemia (8.7%), B-cell lymphoma (12.7%), aplastic anemia (2.9%), and others (3.5%). During admission, 9.2% underwent allogeneic SCT and 28.3% underwent autologous SCT. Outcomes are shown in Table 1.ConclusionProphylaxis with an OTGC rather than a FQ was not associated with worse outcomes in this pragmatic evaluation of a heterogeneous group of patients with hematologic malignancies. In this multivariable model, neutropenia lasting more than 7 days was the only consistent predictor of failure across outcomes, suggesting that degree of immunosuppression is a much more significant driver of poor outcomes in this population than is prophylaxis choice. Further evaluation of the role of prophylaxis is needed. Disclosures All authors: No reported disclosures.

Predictive Factors for Survival Outcomes of High-Risk Febrile Neutropenic Patients: a 3-Year Study at a Single Center in Thailand

Objective: This study aimed to identify the risk factors associated with mortality in febrile neutropenic patients.  Materials and Methods: This 3-year, single center, retrospective, observational study was conducted at Chiangrai Prachanukroh Hospital, Chiangrai Province, Thailand. The inclusion criteria consisted of a patient age of over 15 years and a diagnosis of febrile neutropenia. Results: Most of the 303 febrile neutropenic inpatients had a Multinational Association for Supportive Care in Cancer (MASCC) risk score &lt; 21. The median length of stay was 6 days (interquartile range: 4-11 days). During 30 days of admission, 24.8% of the patients succumbed. In a univariate analysis, patients receiving G-CSF, the post-chemotherapy-related group, patients with MASCC score &gt; 16, and patients admitted in private had significantly higher survival rate. In a multivariate analysis, a MASCC score ≤ 16 and non-chemotherapy-related groups were associated with an increased mortality risk. Conclusion: The 30-day survival rate of febrile neutropenic patients in Thailand is seventy-five percent. Low MASCC score and non-chemotherapy-related neutropenia are associated with a higher risk of unfavorable outcomes.

Inappropriate Empirical Antibiotic Treatment in High-risk Neutropenic Patients With Bacteremia in the Era of Multidrug Resistance.

We aimed to describe the current rates of inappropriate empirical antibiotic treatment (IEAT) in oncohematological patients with febrile neutropenia (FN) and its impact on mortality. This was a multicenter prospective study of all episodes of bloodstream infection (BSI) in high-risk FN patients (2006-2017). Episodes receiving IEAT were compared with episodes receiving appropriate empirical therapy. Adherence to Infectious Diseases Society of America (IDSA) recommendations was evaluated. Multivariate analysis was performed to identify independent risk factors for mortality in Pseudomonas aeruginosa episodes. Of 1615 episodes, including Escherichia coli (24%), coagulase-negative staphylococci (21%), and P. aeruginosa (16%), 394 (24%) received IEAT despite IDSA recommendations being followed in 87% of cases. Patients with multidrug-resistant gram-negative bacilli (MDR-GNB), accounting for 221 (14%) of all isolates, were more likely to receive IEAT (39% vs 7%, P < .001). Overall mortality was higher in patients with GNB BSI who received IEAT (36% vs 24%, P = .004); when considering individual microorganisms, only patients with infection caused by P. aeruginosa experienced a significant increase in mortality when receiving IEAT (48% vs 31%, P = .027). Independent risk factors for mortality in PA BSI (odds ratio [95% confidence interval] were IEAT (2.41 [1.19-4.91]), shock at onset (4.62 [2.49-8.56]), and pneumonia (3.01 [1.55-5.83]). IEAT is frequent in high-risk patients with FN and BSI, despite high adherence to guidelines. This inappropriate treatment primarily impacts patients with P. aeruginosa-related BSI mortality and in turn is the only modifiable factor to improve outcomes.

Inhaled Amphotericin B as Aspergillosis Prophylaxis in Hematologic Disease: An Update.

This review summarizes the literature on inhaled amphotericin B for invasive aspergillosis prophylaxis in patients with neutropenia secondary to hematologic malignancy treatment or stem cell transplant. Six trials, 2 randomized controlled and 4 with historical controls, were identified. Three inhaled amphotericin B deoxycholate trials found a reduced invasive aspergillosis incidence, 1 reaching statistical significance. Three inhaled liposomal amphotericin B trials demonstrated similar reductions with 2 finding statistical significance. Relative risk reductions for invasive aspergillosis were routinely 40-60%. Both formulations were without reported systemic or severe adverse effects. The most common adverse events were cough, bad taste, and nausea. Discontinuation rates ranged from 0-45%. The only randomized, placebo-controlled trial utilized inhaled liposomal amphotericin B reported a nearly 60% relative risk reduction.Inhaled liposomal amphotericin B 12.5 mg twice weekly is an alternative for invasive aspergillosis prophylaxis in high risk neutropenic patients with hematologic malignancies and stem cell transplant recipients when recommended azole agents are contraindicated or should not be used.

Classical Empiric Antifungal Therapy Vs. D-Index Guided Early Therapy Using Micafungin for Persistent Febrile Neutropenia (CEDMIC trial): A Randomized Controlled Trial from Japan FN Study Group

Classical Empiric Antifungal Therapy Vs. D-Index Guided Early Therapy Using Micafungin for Persistent Febrile Neutropenia (CEDMIC trial): A Randomized Controlled Trial from Japan FN Study Group

De-escalation and discontinuation strategies in high-risk neutropenic patients: an interrupted time series analyses of antimicrobial consumption and impact on outcome.

Febrile neutropenia (FN) is the main reason for antibiotic prescription in hematology wards where, on the other hand, antibiotic stewardship (AS) is poorly explored. The objectives of the present study were to evaluate (1) the impact of an AS intervention on antibiotic consumption and (2) the applicability and acceptance rate of the intervention and its clinical impact. A persuasive AS intervention based on European Conference on Infection in Leukaemia (ECIL) guidelines for FN was implemented in a high-risk hematology ward in a tertiary referral public university hospital. This included the creation and diffusion of flow charts on de-escalation and discontinuation of antibiotics for FN, and the introduction in the team of a doctor dedicated to the implementation of flow charts and to antibiotic prescription revision. All consecutive patients receiving antibiotics during hospitalization were included. A segmented linear regression model was performed for the evaluation of antibiotic consumption, taking into account 1-year pre-intervention period and 6-month intervention period. Overall, 137 consecutive antibiotic prescriptions were re-evaluated, 100 prescriptions were for FN. A significant reduction of the level of carbapenem consumption was observed during the intervention period (level change (estimate coefficient ± standard error) = - 135.28 ± 59.49; p = 0.04). Applicability and acceptability of flow charts were high. No differences in terms of intensive care unit transfers, bacteremia incidence, and mortality were found. A persuasive AS intervention in hematology significantly reduced carbapenem consumption without affecting outcome and was well accepted. This should encourage further applications of ECIL guidelines for FN.

Administration of taurolidine-citrate lock solution for prevention of central venous catheter infection in adult neutropenic haematological patients: a randomised, double-blinded, placebo-controlled trial (TAURCAT)

BackgroundCatheter-related bloodstream infection (CRBSI) is one of the most frequent complications in patients with cancer who have central venous catheters (CVCs) implanted and is associated with substantial morbidity and mortality. Taurolidine is a non-antibiotic agent with broad-spectrum antimicrobial activity, which has been used as a lock solution to prevent CRBSI in some settings. However, little is known about its usefulness in high-risk adult neutropenic patients with cancer. This prospective randomised clinical trial aims to test the hypothesis that taurolidine-citrate lock solution is more effective than placebo for preventing catheter infection in neutropenic haematological patients.MethodsThis study is a prospective, multicentre, randomised, double-blinded, parallel, superiority, placebo-controlled trial. Patients with haematological cancer who are expected to develop prolonged neutropenia (> 7 days) and who have a non-tunnelled CVC implanted will be randomised to receive prophylactic taurolidine-citrate-heparin solution using a lock technique (study group) or heparin alone (placebo group). The primary endpoint will be bacterial colonisation of the CVC hubs. The secondary endpoints will be the incidence of CRBSI, CVC removal, adverse events, and 30-day case-fatality rate.DiscussionThe lock technique is a preventive strategy that inhibits bacterial colonisation in the catheter hubs, which is the initial step of endoluminal catheter colonisation and the development of infection. Taurolidine is a nontoxic agent that does not develop antibiotic resistance because it acts as an antiseptic rather than an antibiotic. Taurolidine has shown controversial results in the few trials conducted in cancer patients. These studies have important limitations due to the lack of data on adult and/or high-risk neutropenic patients, the type of catheters studied (tunnelled or ports), and the lack of information regarding the intervention (e.g. dwelling of the solution, time, and periodicity of the lock technique). If our hypothesis is proven, the study could provide important solid evidence on the potential usefulness of this preventive procedure in a population at high risk of CRBSI, in whom this complication may significantly impair patient outcome.Trial registrationISRCTN, ISRCTN47102251. Registered on 9 September 2015.