scholarly journals The Effect of Continuous Screening of Carbapenem-Resistant Enterobacteriaceae on Theprevention and Control of Bloodstream Infections in Patients with Hematopoietic Stemcell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5606-5606
Author(s):  
Tingting Yang ◽  
Xueping Luo ◽  
Qing Yang ◽  
Hongchao Chen ◽  
Yi Luo ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Bloodstream Infections ◽  
Risk Groups ◽  
Control Group ◽  
Intervention Period ◽  
Hematopoietic Stem ◽  
Carbapenem Resistant ◽  
And Control ◽  
Carbapenem Resistant Enterobacteriaceae ◽  
Related Mortality

Carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infections (BSIs) have become emerging cause of death in patients with hematopoietic stem cell transplantation (HSCT). Patients underwent HSCT from September 2017 to June 2018, and from July 2018 to February 2019, were assigned as single screening group and continuous screening group; patients transplanted from January 2016 to August 2017 were assigned as control group. Continuous screening significantly improved the CRE gut detection rate compared with single screening (10% vs 1.5%, p=0.001). The CRE infection rate in the pre-intervention period, single screening period and continuous screening period were 1.6%, 2% and 0, respectively; while related mortality was were 66.7%, 50% and 0, respectively. The time from the onset of symptoms of infection to use of tigecycline in survival patients with BSIs were shorter than died patients (24 hours vs 72 hours). For 11 CRE carriers with neutropenic fever, all received tigecycline therapy-based therapy (time from detection to therapy, -3 to 17 days) and did not develop BSIs. These results suggest that continuous screening can more effectively identify high-risk groups of CRE colonization and guide targeted preemptive treatment in the presence of infection symptoms, so as to reduce the incidence of BSIs and improve the prognosis of patients. Disclosures No relevant conflicts of interest to declare.

Treatment of AML Relapse After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Using Low-Dose Azacitidine (AZA).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3445-3445
Author(s):  
Alexandre Chiattone ◽  
Rima M Saliba ◽  
Borje S. Andersson ◽  
Sergio Giralt ◽  
Manish R Sharma ◽  
...  
Keyword(s):  
Low Dose ◽  
Conflicts Of Interest ◽  
Disease Free Survival ◽  
Control Group ◽  
Hematopoietic Stem ◽  
Dismal Prognosis ◽  
Baseline Characteristics ◽  
And Control

Abstract Abstract 3445 Background: Relapsing AML/MDS after HSCT has a dismal prognosis, with few patients achieving long-term control of the malignancy. AZA is a hypomethylating agent that is moderately active against AML/MDS, and may have beneficial immunomodulatory effects after HSCT. We have shown that a significant minority of patients with recurrent disease respond to this drug. Here, we present long-term follow-up after salvage treatment regimens that included AZA, to treat AML/MDS that recurred after HSCT. Patients and Methods: Twenty-three patients received low-dose AZA for recurrence. Decision to use AZA was based on clinical assessment of slow progression of disease and relatively slower disease ‘tempo' and relatively small AML bulk. AZA cohort preparative regimens for 1st HSCT were myeloablative in 12 cases, and of reduced intensity in 11 cases. AZA was used prior to or without a 2nd HSCT (n=17), or after a 2nd HSCT (n=6). Outcomes were compared to controls (n=18) that relapsed ≥ 8 months after HSCT, and did not receive AZA (8 months representing the median disease free survival (DFS) for AZA-treated patients). The control group included all patients that relapsed ≥ 8 months after allogeneic HSCT using myeloablative busulfan 130 mg/m2 and fludarabine 40 mg/m2 for 4 days. AZA was studied as a time dependent variable. AZA and controls had similar baseline characteristics as described in the Table, although median DFS after the first HSCT was 8 (range: 2–51) and 17 (range: 7–59) months, favoring the control group (p=0.08). AZA was administered outpatient, with good tolerance. Fatigue and nausea were commonly observed toxicities. Doses were 8 mg/m2 (n=1), 16 mg/m2 (n=3), 24 mg/m2 (n=10), 32 mg/m2 (n=5), 40 mg/m2 (n=2), and 75 mg/m2 (n=2), administered subcutaneously for 5 days, in 28–32-day cycles. Results: Median number of cycles was 4 (range, 1–44). With a median follow-up of 18 months for AZA and control patients, median survival after relapse was 17 versus 6 months, respectively for AZA and control patients. 11 (48%) AZA patients are alive, while 2 (11%) control patients are alive. Two-year overall survival (OS) for AZA and control groups was 40% and 10%, respectively. AZA and controls had similar baseline characteristics as described in the Table. Conclusion: Low-dose AZA was a well tolerated outpatient treatment that may improve survival after AML/MDS recurrence in selected cases. Major determinants of survival in this setting, however, were remission duration after HSCT, and use of a 2nd HSCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Bloodstream Infections caused by Klebsiella pneumoniae and Serratia marcescens isolates co-harboring NDM-1 and KPC-2.

2020 ◽  
Author(s):  
Taniela Bes ◽  
Debora Nagano ◽  
Roberta Martins ◽  
Ana Paula Marchi ◽  
Lauro Perdigão Neto ◽  
...  
Keyword(s):  
Serratia Marcescens ◽  
Low Income ◽  
Case Series ◽  
Bloodstream Infections ◽  
Surgical Patient ◽  
Hematopoietic Stem ◽  
Travel History ◽  
Molecular Tests ◽  
Carbapenem Resistant ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Carbapenem-resistant Enterobacteriaceae is a worldwide health problem, however isolates carrying both blaKPC-2 and blaNDM-1 are unusual. Here we describe microbiological and clinical characteristics of five cases of bloodstream infection (BSI) caused by carbapenem-resistant Klebsiella pneumoniae and Serratia marcescens co-harboring blaKPC-2 and blaNDM-1.Of the five blood culture isolates, three from are from hematopoietic stem cell transplantation patients, one from a renal transplant patient, and one from a soft tissue surgical patient. All patients lived in low-income neighborhoods and had no travel history. Despite antibiotic treatment, four of five patients died. The phenotypic assays showed that Meropenem added with either EDTA, PA or both showed increased zone of inhibition in comparison to Meropenem alone. Molecular tests confirmed blaKPC-2 and blaNDM-1 genes, the K. pneumoniae were assigned as ST258 and ST340 by Whole Genome Sequencing.This case-series showed high mortality of BSI caused by Enterobacteria coproducing KPC-2 and NDM-1. The detection of samples co-harboring blaKPC-2 and blaNDM-1 remains unsatisfactory with phenotypic assay. Routine microbiology laboratories must be on alert for samples co-harboring these mechanisms.

scholarly journals Bloodstream Infections caused by Klebsiella pneumoniae and Serratia marcescens isolates co-harboring NDM-1 and KPC-2.

2020 ◽  
Author(s):  
Taniela Bes ◽  
Debora Nagano ◽  
Roberta Martins ◽  
Ana Paula Marchi ◽  
Lauro Perdigão Neto ◽  
...  
Keyword(s):  
Serratia Marcescens ◽  
Low Income ◽  
Renal Transplant Patient ◽  
Bloodstream Infections ◽  
Surgical Patient ◽  
Hematopoietic Stem ◽  
Travel History ◽  
Molecular Tests ◽  
Carbapenem Resistant ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Carbapenem-resistant Enterobacteriaceae is a worldwide health problem, however isolates carrying both blaKPC-2 and blaNDM-1 are unusual. Here we describe microbiological and clinical characteristics of five cases of bloodstream infection (BSI) caused by carbapenem-resistant K lebsiella pneumoniae and Serratia marcescens co-harboring blaKPC-2 and blaNDM-1.Of the five blood culture isolates, three from are from hematopoietic stem cell transplantation patients, one from a renal transplant patient, and one from a soft tissue surgical patient. All patients lived in low-income neighborhoods and had no travel history. Despite antibiotic treatment, four of five patients died. The phenotypic assays showed that Meropenem added with either EDTA, PA or both showed increased zone of inhibition in comparison to Meropenem alone. Molecular tests confirmed blaKPC-2 and blaNDM-1 genes, the K. pneumoniae were assigned as ST258 and ST340 by Whole Genome Sequencing.

scholarly journals 526. Significant Reduction of Hospital Onset Carbapenem-Resistant Enterobacteriaceae Utilizing Infection Prevention Strategies: It takes a Village!

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S253-S253
Author(s):  
Kinta Alexander ◽  
Sean Brown ◽  
Scott Lorin ◽  
Brian Koll ◽  
Dana Mazo ◽  
...  
Keyword(s):  
Prevention And Control ◽  
Infection Prevention ◽  
Uv Light ◽  
Stable Solution ◽  
City Hospital ◽  
Intervention Period ◽  
Hospital Leadership ◽  
Carbapenem Resistant ◽  
And Control ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Background Carbapenem-resistant Enterobacteriaceae (CRE) is a Gram-negative bacteria and is considered one of the major challenges in healthcare worldwide. CRE has a high mortality rate, and the majority produce carbapenemase enzymes, which can be easily spread to other bacteria and patients. An inner-city hospital had a substantial decrease in CRE associated infections/colonization after the implementation of a multi-disciplinary process championed by hospital leadership and Infection Prevention (IP). Methods A quasi-experimental study of patients with hospital-onset CRE-positive cultures over Thirty-eight months was conducted. The pre-intervention period was from January 2015 to July 2016 and the post intervention period was from August 2016 to February 2018. The intervention comprised of a CRE prevention and control (CPC) bundle. The bundle comprised of hand hygiene, strict contact precautions, appropriate surveillance cultures and the cleaning of a patient’s environment and equipment with bleach. Hospital leadership implemented the CPC bundle during daily huddles with IP and department leaders with real-time identification and resolution of any barriers. The diligence of cleaning and disinfection was monitored using a transparent, easily cleanable and environmentally stable solution that fluoresces when exposed to UV light. The solution was used to mark standardized high touch surfaces and shared equipment in CRE patient rooms prior to terminal cleaning. These surfaces were evaluated with a UV light and used as an opportunity to educate staff on common cleaning oversight. Results Prior to implementation of the CPC bundle, there were 24 cases of CRE with a baseline rate of 2.40. After introducing the CPC bundle, there were 8 cases of CRE with a rate of 0.83 (P = 0.006). The CPC bundle was associated with a reduction in CRE cases by 67%. Conclusion A hospital-wide approach between multiple departments is critical for the success of CRE prevention and control. This study provides further evidence that a multi-faceted approach to monitoring compliance with the CPC bundle can help reduce the transmission of CRE. This approach can decrease the burden on the healthcare system and improve patient outcomes. Disclosures All authors: No reported disclosures.

scholarly journals Role of Extracorporeal Photopheresis in Prevention of Graft-Versus-Host Disease in Patients Treated with Allogeneic Hematopoietic Stem Cell Transplantation: A Randomized Controlled Trial

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 102-102
Author(s):  
Maryan M Ali ◽  
Tobias Gedde-Dahl ◽  
Marit B Veierød ◽  
Geir E Tjønnfjord ◽  
Per Ole Iversen
Keyword(s):  
Hematological Malignancy ◽  
Intervention Group ◽  
Study Groups ◽  
Control Group ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Randomized Controlled ◽  
Gvhd Prophylaxis ◽  
One Year ◽  
And Control

Abstract Introduction In many patients diagnosed with a hematological malignancy, the disease cannot be totally eradicated by conventional therapeutic approaches, and for them allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option. A major complication of allo-HSCT is graft-versus-host disease (GvHD), affecting about 50% of transplant recipients. In addition to increased risk of death and long-lasting debilitating conditions, severe GvHD also impairs health-related quality of life. High-dose systemic steroids is the first line treatment for GvHD, but treatment failure is common, and steroid-refractoriness is a major cause of non-relapse mortality after allo-HSCT. While there is no established second line GvHD-treatment, extracorporeal photophoresis (ECP) has emerged as an attractive and increasingly applied alternative, partly due to its favourable safety profile. However, the use of ECP in preventing GvHD is sparse and data are inconclusive due to lack of randomized controlled trials (RCT). We therefore conducted a RCT to study if ECP given post transplantation could prevent the development of GvHD. Methods Between June 2017 and February 2020, we enrolled 157 patients (> 18 years) diagnosed with a hematological malignancy and treated with an allo-HSCT in first remission into an intention-to-treat open RCT. Ethical and IRB approvals were granted, and the RCT was registered with Clinical Trials (ID NCT03204721). The sample size (76 in intervention group and 81 controls) was calculated based on a reduction of 25% in the total number of patients diagnosed with any form of GvHD within the first year of allo-HCST (primary end-point) as clinically relevant. The patients were stratified according to whether they received myeloablative or reduced intensity conditioning (Table 1), and they were given GvHD prophylaxis as shown in Table 1. ECP (Therakos Cellex ®, Mallinckrodt Pharm., NJ) was initiated when patients had engrafted (i.e. leukocytes > 1 x 10 9/L and platelets > 20 x 10 9/L), and, according to the study protocol, we planned for ECP on two consecutive days/week for two weeks, then weekly for four weeks to a total eight treatments for each patient in the intervention group. Chi-square test was used to test differences between the two study groups. Results Table 1 shows that patient characteristics were well balanced among the two study groups. Four patients did not receive ECP while 39 received all the eight treatments. One year after allo-HCST, the proportion of GvHD was 45/76 (59%) in the intervention group and 52/81 (64%) in the controls (p=0.52). There were no significant differences between the intervention and control group regarding development of acute (45% vs. 48%) or chronic (39% vs. 40%) GvHD. Neither did we detect any statistical differences between the two study groups regarding organ involvement or severity of the GvHD manifestations (data not shown). During the one-year observation period, 16/76 (21%) and 10/81 (12%) relapsed in the intervention and control group, respectively (p=0.14). The corresponding numbers of deaths were 12/76 (16%) and 16/81 (20%), respectively (p=0.52). Six patients in the intervention group experienced mild to moderate temporary, adverse events that could possibly be related to the ECP-procedure. Conclusion In this first RCT addressing ECP as GvHD prophylaxis in allo-HSCT for hematological malignancy, we found no significant difference in the numbers, types, organ involvement, or severity of GvHD between the intervention and the control group. Thus, our study does not support the use of ECP as an adjunct to GvHD-prophylaxis based on cyclosporine and methotrexate, mycophenolate mofetil, or sirolimus. However, ECP did not seem to be harmful in this setting. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Infection preventionist staffing levels and rates of 10 types of healthcare-associated infections: A 9-year ambidirectional observation

2022 ◽  
pp. 1-6
Author(s):  
Robert J. Clifford ◽  
Donna Newhart ◽  
Maryrose R. Laguio-Vila ◽  
Jennifer L. Gutowski ◽  
Melissa Z. Bronstein ◽  
...  
Keyword(s):  
Control Charts ◽  
Bloodstream Infections ◽  
Central Line ◽  
Healthcare Associated Infections ◽  
Full Time ◽  
Staffing Levels ◽  
Clostridioides Difficile ◽  
Carbapenem Resistant ◽  
Healthcare Associated ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Objective: To quantitatively evaluate relationships between infection preventionists (IPs) staffing levels, nursing hours, and rates of 10 types of healthcare-associated infections (HAIs). Design and setting: An ambidirectional observation in a 528-bed teaching hospital. Patients: All inpatients from July 1, 2012, to February 1, 2021. Methods: Standardized US National Health Safety Network (NHSN) definitions were used for HAIs. Staffing levels were measured in full-time equivalents (FTE) for IPs and total monthly hours worked for nurses. A time-trend analysis using control charts, t tests, Poisson tests, and regression analysis was performed using Minitab and R computing programs on rates and standardized infection ratios (SIRs) of 10 types of HAIs. An additional analysis was performed on 3 stratifications: critically low (2–3 FTE), below recommended IP levels (4–6 FTE), and at recommended IP levels (7–8 FTE). Results: The observation covered 1.6 million patient days of surveillance. IP staffing levels fluctuated from ≤2 IP FTE (critically low) to 7–8 IP FTE (recommended levels). Periods of highest catheter-associated urinary tract infection SIRs, hospital-onset Clostridioides difficile and carbapenem-resistant Enterobacteriaceae infection rates, along with 4 of 5 types of surgical site SIRs coincided with the periods of lowest IP staffing levels and the absence of certified IPs and a healthcare epidemiologist. Central-line–associated bloodstream infections increased amid lower nursing levels despite the increased presence of an IP and a hospital epidemiologist. Conclusions: Of 10 HAIs, 8 had highest incidences during periods of lowest IP staffing and experience. Some HAI rates varied inversely with levels of IP staffing and experience and others appeared to be more influenced by nursing levels or other confounders.

Enhanced Engraftment of Human CD34+ Stem Cells in NOD/SCID Mice by Diprotin A Occurs by Inhibition of Recipient CD26/Dipeptidyl Peptidase-IV (DPP-IV).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3178-3178
Author(s):  
Toshinao Kawai ◽  
Uimook Choi ◽  
Po-Ching Liu ◽  
Harry L. Malech
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Xenograft Model ◽  
Scid Mice ◽  
Control Group ◽  
Hematopoietic Stem ◽  
Human Cd34 ◽  
Dpp Iv ◽  
Cell Engraftment ◽  
And Control

Abstract CD26/DPP-IV (CD26) is a membrane-anchored ectoenzyme with N terminus exopeptidase activity that cleaves X-Pro-dipeptides. Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 play a central role in trafficking of hematopoietic stem cells in the bone marrow. SDF-1 has a proline second from the N-terminus and is cleaved by CD26. Mouse hematopoietic progenitors express CD26 and a brief treatment of these cells with Diprotin A (Ile-Pro-Ile), a specific inhibitor of CD26, enhances engraftment. We examined the effect of Diprotin A treatment of peripheral blood human CD34+ stem cells (PBSC) with respect to subsequent responses to SDF-1 and with respect to engraftment in the NOD/SCID mouse xenograft model. We found that human CD34+ PBSC with colony forming potential are unlike mouse hematopoietic stem cells in that they lack the equivalent of CD26; and also are unlike mouse cells in that their response to SDF-1 and their engraftment in the NOD/SCID xenograft model are not affected by pre-treatment with Diprotin A. However, administration of Diprotin A intravenously to the NOD/SCID mouse at the time of transplant of human PBSC greatly enhances engraftment of the human PBSC, suggesting an effect primarily on the mouse stroma. Previous reports suggested that 70% of mouse lineage negative/sca-1 positive hematopoietic stem cells express CD26. However, freshly selected mobilized human CD34+ PBSC do not express detectable CD26, though after 4 days and 7 days of ex vivo culture in growth factors (SCF, flt3-ligand, TPO, IL3) 8.9% and 26.6% of cells express CD26, indicating that CD26 may only appear in later progenitors. At day 4 the cultured human PBSC were sorted by flow cytometry into CD26 positive and negative fractions. Only the CD26 negative fraction contained colony forming cells. 4 day-cultured human PBSC were exposed to Diprotin A 5mM for 15 minutes, washed and used in a filter transwell migration assay in response to SDF-1 at concentrations from 0.5 to 10 nM. There was no statistical difference between migration of Diprotin A treated and control PBSC, even in experiments with longer treatment with Diprotin A. When these human PBSC were transplanted into NOD/SCID mice there was no difference of engraftment between the Diprotin A treated group and control group. However, when 1x106 of 4 day-cultured PBSC were injected into NOD/SCID mice without or together with 2μmol of Diprotin A, there was a profound enhancement on subsequent engraftment in the group of mice injected with Diprotin A at time of transplant. At 6 weeks after transplantation the CD45+ human cell engraftment of the Diprotin A group was 6-fold increased compared to control group (49.6±8.2% vs. 8.1 ± 3.4%, p<.0001). Taken together with the colony assay, the in vitro migration studies, and lack of effect on engraftment when only the human PBSC are treated with Diprotin A, this result suggests that the enhanced engraftment of human PBSC in NOD/SCID mice is due to an action of Diprotin A on endogenous mouse CD26/DPP-IV (where the target is unknown, but possibly stromal cells). Although, further work is required to determine levels of expression of CD26/DPP-IV in human marrow stromal cells, it is possible to speculate that inhibitors of CD26/DPP-IV activity may provide a novel approach to improve stem cell engraftment in humans.

Re-Exposure of Cord Blood (CB) to Non-Inherited Maternal HLA Antigens (NIMA) Improves Transplant Outcome in Patients (pts) with Hematologic Malignancies and May Reduce Relapse.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 661-661
Author(s):  
Jon J van Rood ◽  
Cladd E Stevens ◽  
Jacqueline Smits ◽  
Carmelita Carrier ◽  
Carol Carpenter ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Hla Antigens ◽  
Human Leukocyte ◽  
Hematologic Malignancies ◽  
Hematopoietic Stem ◽  
Leukocyte Antigens ◽  
Grade Ii ◽  
The Impact ◽  
Related Mortality

Abstract Abstract 661 CB hematopoietic stem cell transplantation (CBT) can be successful even if donor and recipient are not fully matched for human leukocyte antigens (HLA). This may result, at least in part, from tolerance-inducing events during pregnancy, but this concept has not been tested to date. Hence we analyzed the impact of fetal exposure to NIMA of the HLA-A, -B antigens or -DRB1 alleles on the outcome of 1121 pts with hematologic malignancies. All pts received single CB units provided by the NYBC, for treatment of ALL (N=451), AML (N=376), CML (N=116), MDS (N=79), other (N=99); 22% were transplanted in advanced stage. Median age was 9.7 years (range: 0.1-67); 29% of recipients were >16 years. Most pts (96%) received myeloablative cytoreduction. Sixty-two pts received fully matched grafts while 1059 received units mismatched (MM) for one or two HLA antigens. Of these, 79 (7%) had a MM antigen which was identical to a donor NIMA (Example: Pt: A1, A3; CBU: A1, A2; mother-CBU: A1, A3; A3 is NIMA). NIMA match was found in 25 recipients with one HLA MM and 54 of those with two MM. The NIMA match was identified after the transplant and was not used in unit selection. In multivariate analyses, NIMA matched transplants (NMTs), showed faster neutrophil recovery (RR=1.3, p=0.043), even for grafts with cell dose <3×107 (RR=1.6, p=0.053). There was no difference in the incidence of acute (grade II-IV) or chronic GvHD. 3-year relapse risk (cumulative incidence 22%) was reduced compared to 1 or 2 HLA MM no NIMA matched transplants, especially in pts with myelogenous malignancies given units with 1 HLA MM (RR=0.2, p=0.074). Further, 3-year transplant-related mortality was reduced (RR=0.7, p=0.034), particularly in pts ≥5 years old (RR=0.5, p=0.006), as was the 3-year overall mortality (RR= 0.7, p=0.029 and RR=0.6, p=0.015, respectively). As a result, in the NMTs, treatment failure (relapse or death) was significantly lower, particularly in pts ≥5 years (RR=0.7, p=0.019) and DFS was significantly improved (figure) and was similar to that of the 0 HLA MM group. These findings are the first indication that donor exposure to NIMA can improve post-transplant survival in unrelated CBT and might reduce relapse. We propose to include the NIMA of CB units in search algorithms. Thus, for pts lacking fully HLA matched grafts, HLA MM but NIMA matched CB units could be selected preferentially, since no adverse effects were seen. This strategy of selecting HLA MM grafts with optimal outcome effectively “expands” the current CB Inventory several-fold.Patient GroupNRR(95% Cl)p value0 MM360.5(0.3–0.8)0.0051 MM / NIMA Match180.4(0.2–0.9)0.0262 MM / NIMA Match400.8(0.5–1.2)0.3091 MM / No NIMA Match229reference group2 MM / No NIMA Match4871.1(0.9–1.3)0.365 Disclosures: No relevant conflicts of interest to declare.

Extended Use of Ciprofloxacin Markedly Decreases the Incidence of Severe BK Virus-Associated Hemorrhagic Cystitis In Allogeneic HSCT Recipients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2317-2317
Author(s):  
Ashley N Miller ◽  
Ashley S Glode ◽  
Kathy Hogan ◽  
Christine Schaub ◽  
Robert K Stuart ◽  
...  
Keyword(s):  
Viral Replication ◽  
Hemorrhagic Cystitis ◽  
Conditioning Regimen ◽  
Bk Virus ◽  
Control Group ◽  
Control Groups ◽  
Hematopoietic Stem ◽  
Cox Regression Analysis ◽  
Allogeneic Hsct ◽  
And Control

Abstract Abstract 2317 Introduction: The polyoma virus BK is present in the urothelial tract of the majority of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Urothelial damage by the conditioning regimen triggers early viral replication and subsequent immune mediated damage to the urothelium. Clinical manifestations of BK virus-associated hemorrhagic cystitis (BKHC), with typical onset in the first 100 days after HSCT, range from asymptomatic microscopic hematuria to massive life threatening blood loss and urinary obstruction. There is no standard prophylaxis or treatment for BKHC. The antibacterial fluoroquinolones have been shown in vitro to inhibit BK viral replication by direct inhibition of the BK encoded DNA gyrase. Therefore, we hypothesized that extended prophylaxis with the fluoroquinolone ciprofloxacin might decrease the incidence of severe BKHC after HSCT. Methods: In March 2009 we began prescribing prophylaxis for BKHC with ciprofloxacin 500 mg orally twice daily from day 0 until day 60 after transplantation in all allograft recipients (except patients allergic to ciprofloxacin). Patient and transplant variables, as well as incidence of severe BKHC, were collected retrospectively for all consecutive patients undergoing allogeneic HSCT between June 2006 and July 2010. Severe BKHC was defined as grades 3 or 4 hemorrhagic cystitis with evidence of urinary excretion of BK virus by polymerase chain reaction. We estimated the incidence of severe BKHC and the survival free of severe BKHC for patients receiving (ciprofloxacin group) or not (control group) prophylaxis. Additionally, we performed a multivariate analysis to assess the independent role of ciprofloxacin prophylaxis in preventing episodes of severe BKHC. Results: Eighty-one consecutive patients were included in the analysis, of which 33 received ciprofloxacin prophylaxis. Median age of patients was 50 years (range 19–70) and 37% were female. Overall 47% of patients received a myeloablative conditioning regimen and 60% had an alternative (not HLA-matched sibling) donor. Median follow up for patients in the ciprofloxacin and control groups were respectively 180 (range 33–504) and 515 days (range of 29–1645). There was no difference in overall survival between ciprofloxacin and control groups. Episodes of severe BKHC occurred after a median of 60 days (range 27–118) after transplantation and were less frequent in the ciprofloxacin than in the control group (2.9% vs. 22.9%, chi-square test P= 0.01). Survival free of severe BKHC was also significantly superior in the ciprofloxacin group (Log-rank test P=0.04; Figure). In a multivariate Cox-regression analysis including age, gender, intensity of the conditioning regimen, use of mesna during conditioning and alternative donor, only the use of ciprofloxacin prophylaxis was significantly associated with the endpoint survival free of severe BKHC (P=0.01). There were no complications associated with prolonged use of ciprofloxacin, in particular no increase in Clostridium difficile associated diarrhea. Conclusion: Ciprofloxacin prophylaxis appears safe and effective in reducing the incidence of severe BKHC after allogeneic HSCT. This finding requires confirmation with a prospective randomized trial. Disclosures: Off Label Use: Ciprofloxacin- prevention of BK associated hemorragic cystitis.

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