Fluoroquinolone Prophylaxis Research Articles

1773. Evaluation of Fluoroquinolone Prophylaxis in Preventing Bacterial Infection in Neutropenic Afebrile Patients Without Leukemias or HSCT: A Systematic Review

Abstract Background Per 2010 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer, routine use of fluoroquinolone (FQ) chemoprophylaxis in low-risk populations (defined as those with solid tumors or lymphoma undergoing chemotherapy) is not recommended to prevent febrile neutropenic episodes as it was not found to impact all-cause mortality. Since these guidelines were published, there have been additional randomized trials (RCTs) of FQ chemoprophylaxis in patients with cancer. Our objective was to assess the efficacy of FQ vs placebo in preventing probable or confirmed bacterial infection in patients with cancer who did not have leukemias or hematopoietic stem cell transplant (HSCT). Secondary outcomes of interest included febrile episodes, mortality, and adverse effects of antibiotic use. Methods Medline via PubMed, The Cochrane Central Register of Controlled Trials, and SCOPUS from inception through 2/17/2022 were searched. We included RCTs in English comparing FQ to placebo in preventing neutropenic fever and bacterial infections in patients with cancer who did not have leukemias or HSCT. Results We included 5 RCTs (N= 3158). The rates of probable or confirmed bacterial infection in patients with cancer revealed 541/1562 (34.6%) infections in the FQ group and 679/1560 (43.5%) in the placebo group (OR: 0.68, 95% CI:0.59,0.79, I2 = 57%, p=0.002). In evaluating development of febrile episodes, 300/1566 (19.2%) events were noted in the FQ group and 407/1555 (26.2%) in the placebo group (OR: 0.58, 95% CI:0.41,0.83, I2 = 0%, p< 0.001). Mortality events in the FQ group were 113/1597(7.1%) and 124/1508 (8.2%) in the placebo group (OR: 0.76, 95% CI:0.53,1.1, I2 = 7%, p=0.15). Adverse events associated with antibiotic use in the studies were more frequent in the FQ group. Figure 1Forest Plot of Mortality in included studiesFigure 2Results on Development of Fevers in included studies.Figure 3Forest plot of Probable or Proven Infection in included studies. Conclusion Although evidence does not show that FQ prophylaxis provides mortality benefit, it did show a decrease in development of bacterial infections and febrile episodes. This suggests that treatment may still provide clinical benefit to this population of patients, but must be weighed against risks and consequences of long-term antibiotic use, which were not reported by the included studies. Disclosures All Authors: No reported disclosures.

Chimeric Antigen Receptor T Cells: Toxicity and Management Considerations

Chimeric Antigen Receptor T Cells: Toxicity and Management Considerations

1992. Risk of Infective Endocarditis in Streptococcal mitis Bloodstream Infections Among Patients with Neutropenia from Hematologic Malignancies

Abstract Background Streptococcus mitis is a common colonizer of the human oral and gastrointestinal tract. Patients with neutropenia due to hematologic malignancy (HM), particularly those prescribed fluoroquinolone prophylaxis are at increased risk of a S. mitis bloodstream infection (BSI). Risk of infective endocarditis (IE) in this patient population remains unclear. Methods This was a multicenter, retrospective study of neutropenic (ANC < 500 K/uL) patients with HM from November 2016 - February 2022. Patients were included if they had S. mitis isolated in at least 1 blood culture bottle. The primary outcome was number of patients who developed IE based on cardiac imaging. Secondary outcomes included number of patients who underwent IE workup via cardiac imaging and BSI recurrence within 12 weeks. Results Among 171 patients who met the inclusion criteria, 101 (59%) were male and median age was 60 years old (range 19-86). Patient demographics, microbiologic information and outcomes are shown in Table 1. All patients in the cohort had native cardiac valves. Acute leukemia/myelodysplastic syndrome was the most common HM (n=129, 75%), followed by lymphoma (n=27, 16%), multiple myeloma (n=10, 6%) and chronic leukemia (n=5, 3%). Most patients had a transthoracic echocardiogram (TTE) (n=97, 56.7%) within 7 days of BSI. Of these patients, 1 had suspected valvular vegetations on TTE, but transesophageal echocardiogram (TEE) was negative. Two patients had negative TTEs, but there was a high clinical suspicion, so cardiac computed tomography was performed and showed no valvular vegetations. Despite negative cardiac imaging, 1 patient completed 6 weeks of empiric treatment for IE based on radiographic findings in the torso suggesting visceral infarcts. One patient had S. mitis BSI recurrence within 12 weeks of first positive culture. Median duration of antimicrobial therapy for BSI was 15 days (range 8-43). Conclusion IE is uncommon in neutropenic HM patients with native cardiac valves and S. mitis BSI. In this cohort where approximately half had a TTE after bacteremia and median duration of BSI therapy was 15 days, recurrent BSI was rare, suggesting that IE cases were not underdiagnosed in those without cardiac imaging. Cardiac imaging such as TTE to rule out IE may not be necessary for all patients in this population. Disclosures Ramy H. Elshaboury, PharmD, Eli Lilly: Honoraria|Gilead Sciences: Grant/Research Support David W. Kubiak, PharmD, BCPS, BCIDP, FIDSA, Astellas Pharma, Inc.: Advisor/Consultant|AVIR Pharma Inc: Advisor/Consultant|Cidara Therapeutics: Advisor/Consultant Sarah P. Hammond, MD, F2G: Advisor/Consultant|F2G: Grant/Research Support|GSK: Grant/Research Support|Scynexis: Grant/Research Support.

Impact of Fluoroquinolone Prophylaxis on Neutropenic Fever, Infections, and Antimicrobial Resistance in Newly Diagnosed AML Patients.

Fluoroquinolone prophylaxis is recommended during induction chemotherapy for patients with acute myeloid leukemia (AML) to reduce risk of neutropenic fever and systemic bacterial infections. We evaluated the effectiveness of primary fluoroquinolone prophylaxis in an area with high fluoroquinolone resistance. We performed a retrospective chart review of newly diagnosed adult AML patients who received frontline therapy at Mount Sinai Hospital in New York, NY, between 2012 and 2019. Primary outcome was development of neutropenic fever. Secondary outcomes were development of systemic bacterial infections and infections with multidrug-resistant organisms and Clostridioides difficile. Infectious outcomes were collected through 6 months after therapy initiation. We estimated the effect of fluoroquinolone prophylaxis with a time-dependent Cox proportional hazards model. Of 121 included patients, 87 received antibiotic prophylaxis and 34 did not. There was no difference in baseline characteristics, although the prophylaxis group had longer neutropenia duration (median 30 vs. 23 days, P=.013). The prophylaxis group had a reduced risk of neutropenic fever (hazard ratio 0.59, P=.039). The prophylaxis group had fewer gram-positive (P=.043) and gram-negative (P=.049) bloodstream infections and fewer clinically documented infections during frontline therapy (P=.005) and follow-up (P=.026). There was no difference in incidence of C. difficile or infection with fluoroquinolone-resistant or multidrug-resistant organisms. There was no mortality difference between groups. In an area with high fluoroquinolone resistance, primary fluoroquinolone prophylaxis in newly diagnosed AML patients reduced the risk of neutropenic fever and systemic bacterial infections without increased antimicrobial resistance. Prospective, randomized studies are needed to confirm these observations.

Topical Antibiotic Prophylaxis and Intravitreal Injections: Impact on the Incidence of Acute Endophthalmitis-A Nationwide Study in France from 2009 to 2018.

Background: The dramatic increase in intravitreal injections (IVTs) has been accompanied by a greater need for safer procedures. The ongoing debate about topical antibiotic prophylaxis after IVTs emphasizes the importance of large-scale studies. We aimed to study the role of topical antibiotic prophylaxis in reducing the risk of acute endophthalmitis after IVTs. Methods: Population-based cohort study, in France, from 2009 to 2018, including all French patients receiving IVTs of corticosteroids or anti-VEGF agents. Results: A total of 5,291,420 IVTs were performed on 605,434 patients. The rate of topical antibiotic prophylaxis after IVTs progressively decreased during the study period, with a sharp drop in 2014 (from 84.6% in 2009 to 27.4% in 2018). Acute endophthalmitis occurred in 1274 cases (incidence rate = 0.0241%). Although antibiotic prophylaxis did not alter the risk of endophthalmitis (p = 0.06), univariate analysis showed an increased risk after fluoroquinolone and aminoglycoside prophylaxis. This increased risk was not found in multivariate analysis. However, we observed an increased risk related to the use of fixed combinations of fluoroquinolones and aminoglycosides with corticosteroids (IRR = 1.89; 95% CI = 1.57–2.27%, antibiotics combined with corticosteroids). Conclusion: These results are consistent with the literature. Endophthalmitis rates after IVTs did not decrease with topical antibiotic prophylaxis. The use of a combination of antibiotics and corticosteroids doubles the risk of endophthalmitis and should be avoided. Avoiding antibiotic prophylaxis would reduce the costs and the potential risks of antibiotic resistance.

Impact of Discontinuing Levofloxacin Prophylaxis on Bloodstream Infections in Neutropenic Hematopoietic Stem Cell Transplantation Patients.

Multidrug-resistant pathogens have emerged worldwide. We have driven the hypothesis that the non-use of fluoroquinolone prophylaxis during neutropenia could reduce antibiotic resistance in Gram-negative bacteria that cause bloodstream infections (BSIs) in hematopoietic stem cell transplantation (HSCT) patients and that this change in resistance pattern could lead to an impact on BSI mortality. This is a quasi-experimental study comparing BSI incidence, resistance patterns of bacteria that cause BSI, and BSI mortality when levofloxacin prophylaxis was routine for neutropenic HSCT patients (2016–2018) to when fluoroquinolone prophylaxis was discontinued in our center (2019). Bivariate comparisons and multivariate logistic regression models were used for analyses. A total of 310 HSCTs (66 (21%) allogeneic and 244 (79%) autologous) were performed during the study period. Sixty (19%) patients had BSIs, 30 in each evaluated period. The discontinuation of levofloxacin prophylaxis was associated with an increase in BSI incidence and a decrease in the resistance rates of causative BSI bacteria and in BSI 30-day mortality. The increase in the rate of resistant bacteria causing BSI and in BSI mortality might outweigh the benefits of a decrease in BSI incidence caused by fluoroquinolone prophylaxis in neutropenic HSCT patients. We suggest that the routine use of fluoroquinolone in this context be revisited.

Long-Term Dominance of Carbapenem-Non-Susceptible Pseudomonas aeruginosa ST111 in Hematologic Malignancy Patients and Hematopoietic Cell Transplant Recipients.

An epidemiological study uncovered that fluoroquinolone (FQ) neutropenic prophylaxis in hematopoietic cell transplant and hematologic malignancy (HCT/HM) patients was associated with breakthrough Pseudomonas aeruginosa bloodstream infections (BSIs) with isolates non-susceptible to both FQs and meropenem. The molecular epidemiology of the FQ/meropenem-non-susceptible P. aeruginosa isolates causing FQ-breakthrough BSIs in the HCT/HM patients remains unclear. Through whole genome sequencing on 57 P. aeruginosa isolates from 54 patients diagnosed with HM or receiving an HCT, we found that ST111 strains predominated, accounting for 22 (38.6%) of the isolates. 17 of 33 (51.5%) FQ-breakthrough BSIs were caused by ST111 strains, of which 15 (88.2%) were meropenem non-susceptible. ST111 strains, but not other oprD-deficient, meropenem-non-susceptible clinical strains, were found to have a colonization advantage over P. aeruginosa strain PA14 in C. elegans and to outcompete PA14 in in vitro co-culture assays. Together, we found that breakthrough P. aeruginosa BSIs during FQ prophylaxis in HCT/HM patients are dominated by clonally-related FQ/meropenem non-susceptible strains, predominantly ST111 type, and that the dominance of ST111 strains may be explained by a relative fitness advantage over other clinical strains. Additional work is necessary to better understand the factors driving the dominance and persistence of these ST111 strains.

Pseudomonas aeruginosa Infections in Cancer Patients

Pseudomonas aeruginosa (P. aeruginosa) is one of the most frequent opportunistic microorganisms causing infections in oncological patients, especially those with neutropenia. Through its ability to adapt to difficult environmental conditions and high intrinsic resistance to antibiotics, it successfully adapts and survives in the hospital environment, causing sporadic infections and outbreaks. It produces a variety of virulence factors that damage host cells, evade host immune responses, and permit colonization and infections of hospitalized patients, who usually develop blood stream, respiratory, urinary tract and skin infections. The wide intrinsic and the increasing acquired resistance of P. aeruginosa to antibiotics make the treatment of infections caused by this microorganism a growing challenge. Although novel antibiotics expand the arsenal of antipseudomonal drugs, they do not show activity against all strains, e.g., MBL (metalo-β-lactamase) producers. Moreover, resistance to novel antibiotics has already emerged. Consequently, preventive methods such as limiting the transmission of resistant strains, active surveillance screening for MDR (multidrug-resistant) strains colonization, microbiological diagnostics, antimicrobial stewardship and antibiotic prophylaxis are of particular importance in cancer patients. Unfortunately, surveillance screening in the case of P. aeruginosa is not highly effective, and a fluoroquinolone prophylaxis in the era of increasing resistance to antibiotics is controversial.

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.

The CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R/R LBCL

BackgroundCD19-directed chimeric antigen receptor T-cell therapy (CAR-T) represents a promising treatment modality for an increasing number of B-cell malignancies. However, prolonged cytopenias and infections substantially contribute to the toxicity burden...

Comparison of Fluoroquinolones and Other Antibiotic Prophylaxis Regimens for Preventing Complications in Patients Undergoing Transrectal Prostate Biopsy.

Our study aimed to compare the incidence of infective complications after transrectal ultrasound-guided prostate biopsy (TRUSBx) when adopting different antimicrobial prophylaxis regimens. A multi-institutional cohort of 1150 patients who underwent TRUSBx was retrospectively analyzed. Procedures were performed between 2017 and 2019 (before and after the EMA warning about the use of fluoroquinolones for the antibiotic prophylaxis of patient candidates to TRUSBx). The primary endpoint was the occurrence of infective complications, including sepsis and/or fever. The population was stratified according to the antibiotic prophylaxis adopted: fluoroquinolones (levofloxacin, ciprofloxacin, prulifloxacin), cephalosporins (cefixime, ceftriaxone) or trimethoprim/sulfamethoxazole. Univariable and multivariable binomial logistic regression models were used to assess the odds ratio (OR) with 95% confidence interval (CI) testing of the risk of infective complication after adjusting for each prebiopsy covariate. In total, 478 (41.6%) patients received fluoroquinolone-based prophylaxis. Among these, 443 (38.5%), 25 (2.2%) and 10 (0.9%) patients received levofloxacin prophylaxis, ciprofloxacin and prulifloxacin, respectively while 14.6% received cefixime, 20.7% received the comedication of ceftriaxone/fosfomycin and 23.1% received trimethoprim/sulfamethoxazole. The trimethoprim/sulfamethoxazole and fluoroquinolone regimens were significantly associated with a lower risk of infective complications (OR 0.15, 95% CI 0.03–0.48, p = 0.003 and OR 0.17, 95% CI 0.06–0.43, p < 0.001, respectively). The ceftriaxone/fosfomycin (OR 0.21, 95% CI 0.04–0.92, p = 0.04) and fluoroquinolone (OR 0.07, 95% CI 0.00–0.70, p = 0.048) prophylaxis were associated with a lower risk of infective sequelae. Fluoroquinolone-based prophylaxis was associated with a lower risk of infective complications after TRUSBx compared to other prophylaxis regimens although its clinical application was recently forbidden by European Medical Agency restrictions.

QTc prolongation during levofloxacin and triazole combination chemoprophylaxis: Prevalence and predisposing risk factors in a cohort of hematopoietic cell transplantation recipients.

QTc interval prolongation has been reported when combining fluoroquinolones and triazoles for chemoprophylaxis in cancer patients. Herein, we aimed to identify the prevalence and contributing factors to QTc prolongation in hematopoietic cell transplantation (HCT) recipients who received these agents during the neutropenic phase. This is a retrospective medical chart review conducted at a university hospital in Lebanon from 2017 to 2020. It included all adult HCT inpatients on antimicrobial prophylaxis with fluoroquinolones and triazoles and whose baseline ECG monitoring done prior to chemoprophylaxis administration, then on day-3 and day-6 of therapy, were available. Overall, 68 HCT recipients met our inclusion criteria, of which 22% developed QTc prolongation. Based on bivariate analysis, female gender contributed to QTc prolongation (P = 0.001). There was a trend to QTc prolongation in patients with predisposing thyroid disease (P = 0.12), grade 2 vomiting and diarrhea (P = 0.16, P = 0.46, respectively), baseline hypokalemia (P = 0.18) and hypocalcemia (P = 0.3), hypomagnesemia on day-3 (P = 0.21) and day-6 hyponatremia (P = 0.36). Patients receiving two or more drugs with a known or probable risk of QTc prolongation (other than the fluoroquinolone/ triazole combination) were more prone to experience a prolonged QTc interval (P = 0.09). None of the patients that had QTc prolongation died or developed serious arrhythmias. The prevalence of QTc prolongation was 22% among HCT recipients on fluoroquinolone and triazole prophylaxis, yet we did not identify any independent risk factors for this issue. None of the patients that had QTc interval prolongation died or developed serious arrhythmias.

Bacteremia in Hematopoietic Stem Cell Recipients Receiving Fluoroquinolone Prophylaxis: Incidence, Resistance, and Risk Factors.

BackgroundBacteremia is a common complication in hematopoietic stem cell transplant (HSCT) recipients. Prophylactic fluoroquinolone is recommended and used in these individuals. Breakthrough infections can occur with fluoroquinolone-resistant strains. We aimed to identify the incidence, resistance, and risk factors for bacteremia in HSCT recipients receiving fluoroquinolone prophylaxis.Materials and MethodsThis retrospective study was performed on patients who received fluoroquinolone prophylaxis and underwent autologous and allogeneic HSCT between 2015 and 2019. The incidence of bacteremia, comorbidity, treatment, and invasive procedures was compared in these patients with and without bacteremia.ResultsThere were 553 patients included in the study, 68 (12.3%) had bacteremia. The incidence of bacteremia is 8.2% of autologous HSCT recipients and 18.4% of allogeneic HSCT recipients. The significant risk factors associated with bacteremia were steroid-using (odds ratio [OR]:13.83, 95% confidence interval [CI]: 2.88 - 66.40), higher Charlson Comorbidity Index (CCI)-mean (OR: 1.57, 95% CI: 1.15 - 2.16), diabetes mellitus (OR: 4.29, 95% CI: 1.11 - 16.48) in autologous HSCT, steroid-using (OR: 6.84, 95% CI: 1.44 - 32.33), longer duration of neutropenia (OR: 1.05, 95% CI: 1.01 - 1.09) using central venous catheter (OR: 7.81, 95% CI: 1.00 - 61.23) in allogeneic HSCT. Seventy-three pathogens were isolated from a total of 68 bacteremia episodes. The most commonly occurring agents were Escherichia coli, Klebsiella pneumoniae and Enterococcus spp. Resistance to fluoroquinolones was 87.2%, 70.0% and 60.0% among these strains, respectively.ConclusionHigh CCI, diabetes mellitus, use of steroids and long-term neutropenia and use of central venous catheters were significantly associated with the breakthrough bacteremia in HSCT recipients receiving fluoroquinolone prophylaxis. Fluoroquinolone prophylaxis may reduce the incidence of bacteremia but may select strains resistant to fluoroquinolone.

Omitting Ciprofloxacin Prophylaxis in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation and Its Impact on Clinical Outcomes and Microbiome Structure

Fluoroquinolone prophylaxis during allogeneic hematopoietic stem cell transplantation (allo-HSCT) reduces bloodstream infections. However, this practice affects the gut microbiome and potentially increases dysbiosis, which is closely related to transplantation outcomes, and lower gastrointestinal (GI) tract acute graft-versus-host disease (GVHD). This study assessed the impact of omitting ciprofloxacin prophylaxis on GI GVHD, clinical outcomes, and microbiome composition in patients undergoing allo-HSCT. In this single-center, retrospective study comprising recipients of allo-HSCT performed between 2018 and 2020, routine ciprofloxacin prophylaxis (the exposure variable) was stopped in December 2018. The primary outcome was acute lower GI GVHD within 100 days post-transplantation; secondary outcomes were 1-year overall survival, nonrelapse mortality, relapse, and overall acute GVHD. Outcomes were compared using univariate and multivariate analyses and Kaplan-Meier/competing-risk analyses. Sequential stool samples were collected prospectively from a subpopulation of recipients, and the microbiome composition was analyzed. Seventy-five of the 129 patients (58.1%) received prophylactic ciprofloxacin treatment. Baseline characteristics did not differ between the 2 study groups: patients with ciprofloxacin prophylaxis and those without ciprofloxacin prophylaxis. The rate of lower GI GVHD also did not differ between the 2 groups (24% versus 18.5%; P=.597). None of the secondary outcomes was significantly different between the 2 groups in univariate, multivariate, and time-to-event analyses. In addition, microbiome analysis in a subpopulation of 22 patients did not reveal any significant between-group difference in alpha or beta diversity. Omitting prophylactic ciprofloxacin during allo-HSCT did not affect microbiome composition, lower GI-GVHD rate, or other significant clinical outcomes. The use of prophylactic antibiotics in this setting should be evaluated further.

Outbreak of Pseudomonas aeruginosa Bacteremia Infections among Stem-Cell Transplant Patients Related to Change in Prophylaxis

Background:Pseudomonas aeruginosa outbreaks can originate from various sources and can cause severe complications in posttransplant patients. Antibiotic prophylaxis can decrease posttransplant infections; however, consideration must be given to P. aeruginosa coverage as we outline an outbreak among the stem-cell transplant (SCT) population. Methods: A multidisciplinary outbreak investigation was conducted to evaluate sources of contamination and changes in clinical processes. Positive blood cultures from SCT patients and environmental isolates were analyzed using whole-genome sequencing (WGS). Incidence density rates for P. aeruginosa blood cultures from January 2019 through October 2020 were calculated per 10,000 patient days and stratified by unit, specimen, and transplant type. Statistical analysis was calculated with significance at p &lt; 0.05. Results: A cluster of 8 SCT patients was identified between May and September 2020. Moreover, 10 environmental samples were positive for P. aeruginosa including drains, water sources prior to the point-of-use (POU) filter and blood-bank thaw machines. Phylogenetic analysis revealed 1 cluster of 2 patients who shared the same room, 5 patients with unique P. aeruginosa isolates, and 2 separate clusters of environmental isolates with relatedness only to each other. Review of clinical processes showed a change from fluoroquinolone prophylaxis to cephalosporin in the spring of 2020. Also, 5 P. aeruginosa bacteremia infections occurred prior to June (11.78 cases per 10,000 patient days). During the period of cephalosporin use, 8 infections were identified (58.27 cases per 10,000 patient days) (P = .006). Following the restart of fluoroquinolone, zero infections have occurred to date, as of January 28, 2021. Conclusions: Discontinuation of fluoroquinolone prophylaxis was associated with P. aeruginosa bacteremia infections in SCT patients. Use of fluoroquinolone prophylaxis in SCT patients is protective from P. aeruginosa bacteremia infections. There have been no further infections in the following 3 months after the change back to the use of fluoroquinolone. Additionally, WGS showed that most patient isolates did not have a common source, suggesting that P. aeruginosa gastrointestinal colonization may play a role in seeding these bacteremia infections.Funding: NoDisclosures: None

The Impact of Antimicrobial Prophylaxis during Induction Chemotherapy for Acute Myeloid Leukemia in the Current Era

Background:Induction chemotherapy for acute myeloid leukemia (AML) in adults is frequently associated with infectious complications that contribute to morbidity and mortality. Antimicrobial prophylaxis is often given during 7+3 induction to prevent such complications, but these regimens are not without risk: Clostridium difficile colitis and need for total parenteral nutrition (TPN), antimicrobial-associated toxicity, and drug resistance are considerations when choosing prophylaxis. In October 2015, Massachusetts General Hospital (MGH) implemented a change such that patients without active infection at diagnosis no longer received fluoroquinolone and fluconazole prophylaxis during induction chemotherapy. In this study, we evaluated infectious events among patients who received prophylaxis during AML induction therapy before this time point and among those who did not receive antibacterial or antifungal prophylaxis.Methods:We identified adults ages 18 or older with newly diagnosed AML, treated at MGH with 7 days of cytarabine and 3 days of an anthracycline (‘7+3‘) between September 2011 and June 2017. We excluded patients with APL. Patients who were febrile at diagnosis or had a suspected infection at the start of induction received broad spectrum anti-infective coverage and were excluded from this study. Forty-five consecutive eligible patients who did not receive antibacterial or antifungal prophylaxis were evaluated as well as 90 consecutive eligible patients who received ciprofloxacin and fluconazole prophylaxis prior to October 2015. The study period spanned days 1 to 60 following the beginning of induction. Bacteremia and fungemia were defined by culture data. Colitis was defined as symptoms with radiologic findings. The incidence of each infectious event in the two groups was compared using Fisher's exact test. Time to first infectious event was compared using the log rank test. Time to neutrophil recovery in patients who achieved neutrophil recovery was compared using Wilcoxon's rank sum test.Results:The two groups did not differ in median age at diagnosis (p = 0.88), ECOG performance score at diagnosis (p = 0.56), cytogenetic risk (p = 0.44), or rate of secondary AML (p = 0.55). There was a trend towards more fungemia in the group not receiving prophylaxis, but this did not reach statistical significance (9% vs 2%, p = 0.09). Of the 5 Candida organisms that grew in blood from patients who did not receive prophylaxis, 3 were sensitive to fluconazole and 2 sensitivities could not be obtained. There was no significant difference in the incidence of bacteremia (p = 0.66), but in those patients who did develop bacteremia, this complication occurred earlier if they did not receive prophylaxis (median 10 days vs 14 days from induction start, p = 0.03). There was no significant difference in multidrug resistant bacteremia (MRSA, VRE, or ESBL E. coli). In patients who did not receive prophylaxis and developed bacteremia, 53% of organisms isolated were gram-negative, half (50%) of which were susceptible to fluoroquinolones. In patients who received quinolone prophylaxis and developed bacteremia, 64% of organisms were gram-negative and all gram-negative organisms whose sensitivities were tested proved resistant to quinolones.The incidence of all colitis (36% no prophylaxis vs 23%, p = 0.15) and C. diff positive stool (11% vs 6%, p = 0.30) did not differ significantly between the groups. More patients who did not receive prophylaxis required TPN (47% vs 26%, p = 0.02). Time to neutrophil count recovery > 500/mL was longer in the group receiving prophylaxis (24 vs 22 days, p = 0.02). There was no significant difference in grade IV infection, ICU admission for infection, or rehab requirement upon discharge.Conclusions:AML patients who did not receive a fluoroquinolone and fluconazole prophylaxis during induction had infectious complications including bacteremia earlier in their treatment course than those who received prophylaxis. The incidence of colitis or C. diff positivity did not differ between the groups, but patients not receiving prophylaxis required TPN more often. A higher percentage of positive cultures were resistant organisms among those patients given prophylaxis. Further studies are needed to continue to characterize infectious outcomes and resistance patterns based on choice of prophylaxis. [Display omitted] DisclosuresFathi:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria; Juno: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Medimmune: Consultancy, Membership on an entity's Board of Directors or advisory committees. Brunner:Takeda: Research Funding; Celgene: Research Funding.

Quality of inpatient antimicrobial use in hematology and oncology patients.

To compare antimicrobial prescribing practices in Australian hematology and oncology patients to noncancer acute inpatients and to identify targets for stewardship interventions. Retrospective comparative analysis of a national prospectively collected database. Using data from the 2014-2018 annual Australian point-prevalence surveys of antimicrobial prescribing in hospitalized patients (ie, Hospital National Antimicrobial Prescribing Survey called Hospital NAPS), the most frequently used antimicrobials, their appropriateness, and guideline concordance were compared among hematology/bone marrow transplant (hemBMT), oncology, and noncancer inpatients in the setting of treatment of neutropenic fever and antibacterial and antifungal prophylaxis. In 454 facilities, 94,226 antibiotic prescriptions for 62,607 adult inpatients (2,230 hemBMT, 1,824 oncology, and 58,553 noncancer) were analyzed. Appropriateness was high for neutropenic fever management across groups (83.4%-90.4%); however, hemBMT patients had high rates of carbapenem use (111 of 746 prescriptions, 14.9%), and 20.2% of these prescriptions were deemed inappropriate. Logistic regression demonstrated that hemBMT patients were more likely to receive appropriate antifungal prophylaxis compared to oncology and noncancer patients (adjusted OR, 5.3; P < .001 for hemBMT compared to noncancer patients). Oncology had a low rate of antifungal prophylaxis guideline compliance (67.2%), and incorrect dosage and frequency were key factors. Compared to oncology patients, hemBMT patients were more likely to receive appropriate nonsurgical antibacterial prophylaxis (aOR, 8.4; 95% CI, 5.3-13.3; P < .001). HemBMT patients were also more likely to receive appropriate nonsurgical antibacterial prophylaxis compared to noncancer patients (OR, 3.1; 95% CI, 1.9-5.0; P < .001). However, in the Australian context, the hemBMT group had higher than expected use of fluoroquinolone prophylaxis (66 of 831 prescriptions, 8%). This study demonstrates why separate analysis of hemBMT and oncology populations is necessary to identify specific opportunities for quality improvement in each patient group.

1080. Changing Epidemiology and Long-Term Outcome of Bloodstream Infection Due to Enterococcus for Patients with Acute Leukemia: Impacts and Limitations on Strategy of Restricting Antibiotics

BackgroundGastrointestinal dysbiosis due to antibiotics and mucosal injury by intensive chemotherapy are important risk factors for Enterococcal infection in patients with acute leukemia. However, there is still disagreement about trends of incidence and outcome of bloodstream infection (BSI) due to Enterococcus species. This study aimed to identify the changes in the epidemiology of Enterococcal BSI and to estimate the long-term impact of Enterococcal BSI on outcome in an acute leukemia cohort.MethodsAll adult acute leukemia patients diagnosed with Enterococcal BSI (N = 512) between 2014 to 2018 at the Catholic Hematology Hospital were retrospectively reviewed. The incidence rate was compared with antibiotics use and multivariable models were used to estimate the impact of Enterococcal BSI on the outcome.ResultsOf 433 patients, 512 episodes of Enterococcal BSI occurred: 172 (33.6%) of 512 were vancomycin-resistant Enterococcus (VRE) and baseline characteristics were similar in comparison with vancomycin-susceptible Enterococcus (VSE) BSI. The incidence rate of VRE seemed to decrease for 6 months after a change in the strategy of restricting prophylactic use of fluoroquinolone and empirical use of carbapenem (39.2% vs 12.2%, Odds ratio [OR]=0.312, 95% confidence interval [CI], 0.116-0.843, p=0.018). However, overall Enterococcal BSI continued to increase with the rapidly increased use of unrestricted antibiotics. VRE BSI was associated with higher 100-day mortality than VSE BSI after adjusting for covariates (hazard ratio [HR]=1.477; 95% CI, 1.027-2.125, p=0.035), but there was no difference in long-term outcome at one year. In multivariable models, high-risk groups such as old age, advanced stage of disease, polymicrobial infection, high Pitt bacteremia score, and BSI complications after hematopoietic cell transplantation (HSCT) were strongly associated with worse long-term outcome (p< 0.05 for all variables).Table 1. Baseline characteristics of Enterococcal bloodstream infection (BSI) Figure 1. Incidence rate of Enterococcal BSI with changes of aggregated antibiotics utilization in acute leukemia cohort. Vertical black dash line is the time of new institutional strategy of restricting fluoroquinolone prophylaxis and use of carbapenem. Abbreviations: DDDs, defined daily doses; Q, quarter Figure 2. Multivariable analysis of risk factors for overall survival at one year. Abbreviations: HR, hazard ratio; CI, confidence interval; BSI, bloodstream infection; CR, complete remission; HSCT, hematopoietic stem cell transplantation; ALL, acute lymphocytic leukemia; VRE, vancomycin-resistant Enterococcus ConclusionThe effort to restrict the use of fluoroquinolone and carbapenem alone is insufficient to reduce Enterococcal BSI. To improve long-term outcomes, especially in high-risk patients, multidisciplinary interventions to reduce the overall use of antibiotics along with the total incidence of Enterococcal BSI are needed.Disclosures Sung-Yeon Cho, MD, Gilead (Grant/Research Support, Speaker’s Bureau)Merck Sharp & Dohme (Grant/Research Support, Speaker’s Bureau)Pfizer (Grant/Research Support, Speaker’s Bureau)

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.

Omitting Fluoroquinolones Antibiotic Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation Does Not Increase Gram-Negative Bacteremia Rate or Transplant-Related Mortality

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely utilized as a curative treatment for malignant and non-malignant hematological conditions. Fluoroquinolone prophylaxis (FQ-P) is demonstrated to reduce the rate of blood stream infections (BSI) caused by gram-negative bacteria (GNB) during allo-HSCT and increases overall survival (OS), making this approach the standard of care. The available data show that during the transplantation period, the intestinal microbiome diversity profoundly decreases, which is associated with a significant increase in transplant-related mortality (TRM), acute graft-versus-host disease (aGVHD) related mortality and decrease in OS. FQ-P is reported to be a dominant factor in the perturbation of the gut microbiota, leading some centers to omit or modify transplant antibiotic prophylaxis regimens. The aim of the present study has been to evaluate the effects of FQ-P omission on the prevalence of gram-negative bacteria blood stream infections (GNB-BSI), GNB susceptibility to antibiotic treatment, mortality of patients with sepsis and overall TRM. This retrospective single-center study included all consecutive patients, admitted to the Rambam Department of Hematology for allo-HSCT between 01.01.2017 and 31.12.2019. The fact that at our center, FQ-P in allo-HSCT recipients was discontinued on 01.12.2018 allowed comparison of the outcomes in patients treated with and without such prophylaxis. GNB-BSI events registered within 30 days of admission were analyzed. The proportion of first-time GNB-BSI, the antibiotic susceptibility profile, day 30 and day 90 mortality among patients with GNB-BSI were compared. The assessment also included day 30 and day 90 overall TRM, mortality related to sepsis and aGVHD. During the evaluated period, 189 patients underwent allo-HSCT and were included in the analysis. FQ-P was administered to 125 patients and omitted in 64 individuals. GNB-BSI events occurred in 23 (18.4%) patients receiving FQ-P and in 17 (26.6%) patients who did not receive it (p=0.19). GNB susceptibility to FQ, piperacillin/tazobactam and meropenem increased from 38.1% to 58.8%, from 60% to 70.6% and from 85.7% to 94.1%, respectively, after FQ-P had been stopped (p=non-significant, NS). 30-day and 90-day mortality among patients with GNB-BSI did not increase in the post-FQ-P period (Table 1). Day 30 and day 90 overall TRM rates were 10.6% and 18.9%, respectively, with FQ-P versus 13.5% and 21.9%, respectively, without FQ-P (p=NS). Before FQ-P was stopped, sepsis was the cause of death in 56% of events and aGVHD in 16% and after FQ-P was stopped, the corresponding values were 46% and 23%, respectively (p=NS). FQ-P omission has not significantly increased the rate of GNB-BSI or affected the profile of GNB susceptibility to antibiotic treatment in patients undergoing allo-HSCT. Moreover, it has not significantly changed day 30 and day 90 mortality either among patients with GNB-BSI or in the entire study population. FQ-P omission in allo-HSCT recipients appears to be safe and its implementation could contribute to the preservation of intestinal microbiome diversity, potentially leading to improved post-transplant outcome. The findings of this study need to be further evaluated in large randomized trials. Disclosures No relevant conflicts of interest to declare.