Hematopoietic Stem Cell Transplantation Unit Research Articles

Ethical Issues Related to New Cellular Therapies and the IMPACT on Nursing Practice

Topic Significance & Study Purpose/Background/Rationale Nursing care for hematopoietic stem cell transplantation (HSCT) patients has always presented ethical challenges throughout the care continuum. Recent research indicates HSCT nurses frequently experiencing moral distress in situation related to diminished patient care quality due to poor team communication; provider giving false hope to patient or family; following family wishes to continue life support even when not in best interest of patient; patient care suffering due to lack of provider continuity; and initiating extensive life-saving actions when it is likely to only prolong death. With the addition of new cellular therapies, HSCT nurses find themselves caring for patients with hematologic and solid tumor malignancies with advanced or progressive disease. The promise of these new therapies with possible profound adverse effects promotes nursing concerns of unrealistic or uncertain patient expectations; questionable benefit versus harm in view of adverse events which have occurred in early clinical trials; and questionable patient understanding of the efficacy of phase 1 trials. Unresolved ethical issues may also contribute to team members’ burnout, compassion fatigue, and moral distress affecting recruitment and retention of healthcare team members. Methods, Intervention, & Analysis To assist nurses managing with these additional challenges the nursing leadership teams on the HSCT, leukemia and lymphoma units requested regular nursing ethics rounds to provide clinical nurses the opportunities to openly discuss their experience and distress with difficult patient situations. Nursing ethics rounds have been conducted monthly or every other month on different units for both days and night shift nurses. Clinical nurses have discussed concerns about patient selection, patient preparation for all possible outcomes, and their participation in administering treatment with uncertain or adverse outcomes. Current literature is presented on a relevant topic and continued education units are provided. Nurses are reminded of the resources available for immediate situational assistance (ethics consult) and individual assistance (employee assistance program). Findings & Interpretation Clinical nurses have discussed concerns about patient selection, patient preparation for all possible outcomes, and their participation in administering treatment with uncertain or adverse outcomes. Current literature is presented on a relevant topic and continued education units are provided. Nurses are reminded of the resources available for immediate situational assistance (ethics consult) and individual assistance (employee assistance program). Discussion & Implications Informal feedback has been positive and nurses have expressed appreciation for the opportunity to discuss their feelings about these new challenges.

Demonstrating Efficacy of CHG Bathing Treatment for Inpatient Adult Hematopoietic Stem Cell Transplant Recipients Improves Daily Compliance Among Staff

Topic Significance & Study Purpose/Background/Rationale Daily chlorhexidine gluconate (CHG) bathing is recommended as a method to decrease blood stream infections (BSI) in intensive care units; this strategy may also be effective in hematopoietic stem cell transplant (HSCT) units. Methods, Intervention, & Analysis CHG bathing treatment was initiated in the Adult HSCT unit as standard clinical care in January 2017. Patients admitted for HSCT and recovery from January 2016 through August 2018 were reviewed. Patients transferred from outside hospitals or units were excluded. Patients were grouped by frequency of documented CHG bathing treatment: (1) no CHG (includes patients before CHG implementation and patients with no CHG even after implementation); (2) 75% of admission days. CHG treatment frequency was evaluated until discharge, transfer off unit, or BSI, whichever came first. BSI was defined as either ≥2 positive blood cultures or a single positive blood culture within 24 hours of meeting ≥1 SIRS criteria. A chi square test for trend was performed to evaluate the association between CHG frequency and BSI. Findings & Interpretation One hundred eighty-six inpatients met inclusion criteria (n=79 pre-CHG implementation, 107 post-CHG). BSI developed in 28% of patients with no CHG treatment, 20% with 75% CHG treatment (Table 1). Increased CHG treatment frequency was significantly associated with decreased BSI (p = 0.0028). Discussion & Implications In this retrospective study, CHG bathing treatment was associated with significantly reduced BSI in adult HSCT inpatients. After preliminary data were shared among staff, compliance with daily CHG treatment (>75% of admission days) has increased 7.2-fold in 2018 compared to 2017. Efforts are ongoing to increase compliance by collaborating with hospital informatics to facilitate CHG treatment reminders and improve accuracy of documentation through incorporating CHG bathing orders into the electronic medical record.

Reprogramming of bone marrow derived mesenchymal stromal cells to human induced pluripotent stem cells from pediatric patients with hematological diseases using a commercial mRNA kit

The potential use of patient-specific induced pluripotent stem cells (hiPSCs) in the study and treatment of hematological diseases requires the setup of efficient and safe protocols for hiPSC generation. We aimed to adopt a reprogramming method for large-scale production of integration-free patient-specific hiPSC-lines in our stem cell processing laboratory, which supports a pediatric hematopoietic stem cell transplant unit located at a tertiary care children's hospital. We describe our 5-year experience in generation of hiPSC-lines from human bone marrow-derived mesenchymal stromal cells (BM-MSCs) using synthetic mRNAs encoding reprogramming factors. We generated hiPSC-lines from pediatric patients with β-Thalassemia, Sickle Cell Anemia, Blackfan-Diamond Anemia, Severe Aplastic Anemia, DOCK8 Immunodeficiency and 1 healthy control. After optimization of the reprogramming procedure, average reprogramming efficiency of BM-MSCs was 0.29% (range 0.25–0.4). The complete reprogramming process lasted 14–16 days. Three to five hiPSC-colonies per sample were selected, expanded to 5 culture passages and then frozen. The whole procedure took an average time of 1.8 months (range 1.6–2.2). The hiPSC-lines expressed embryonic stem cell markers and exhibited pluripotency. This mRNA reprogramming method can be applicable in a hematopoietic stem cell culture lab setting and would be useful for the clinical translation of patient-specific hiPSCs.

Survey of Compliance to Infection Control Measures and Its Impact on Healthcare of Patients in a Hematopoietic Stem Cell Transplant Unit

Background:Isolation precautions are used in hospitals to interrupt the chain of transmission of nosocomial pathogens. There are several reports that isolation negatively impacts the care given to patients. Isolation protocol compliance has been reported between 40-70% in several studies.Methods:We conducted an anonymized survey of healthcare providers assessing the knowledge, practice and perceived impact of isolation precautions. The survey was conducted in a hematopietic stem cell transplant unit and a medical unit in an academic medical center. Surveys were given to nursing staff and resident physicians working on those units. Results were analyzed using chi-square test.Results:A total of 106 responses were received, 60 from nursing staff and 46 from resident doctors. Self- reported compliance to hand hygiene practices was 59.9%, this was significantly higher on leaving as compared to entering patient rooms amongst nurses (72% vs 50%, p=0.015). Overall adherence to isolation precautions was 60.3%, surprisingly nursing staff in the transplant unit had a significantly lower rate as compared to nurses in the medicine unit (44% vs 83%, p=0.025). 70.7% of respondents felt that patients on isolation precautions have to wait longer for non-emergent care. Only 56.6% of respondents felt that patients were educated about the reasons for isolation precautions; this number was significantly lower in residents as compared to nurses (41.3% vs 68.3%, p=0.005). 77.3% felt that patients in isolation are less satisfied in the care they received. 86.9% of resident physicians felt that isolation precautions helped reduce the spread of infection vs 68.5% of nurses (p=0.025). 82% of respondents expressed overall satisfaction with infection control practices.Conclusions:In our survey, we observed a low compliance of hand hygiene and isolation practices. While respondents felt that isolation adversely impacted patient satisfaction and care, they also opined that these practices help reduce the spread of infection. Surveys can be an important tool to assess knowledge and impact of infection control practices; and can be used to direct quality improvement initiatives. DisclosuresNo relevant conflicts of interest to declare.

Feeding Practices in the Hematopoietic Stem Cell Transplant Unit

Upon completion, participants will be able to identify bone marrow transplant patients on parenteral nutrition who may have been candidates for enteral nutrition instead.

Establishing Hematopoietic Stem Cell Transplant Unit in Resource Limited Setting: A Critical Analysis of Indian Council of Medical Research 2017 Guidelines.

The scope and application of hematopoietic stem cell transplantation are increasing. With advancement in science and close cooperation of health centers, HSCT units are coming up in new developing and underdeveloped countries. India hosts many HSCT units and often provides financially viable option for HSCT to foreign patients as well. Recently Indian Council of Medical Research (ICMR) issued a guideline about HSCT unit in India. This review article discusses establishment of new HSCT unit in resource limited setting. Subsequent implication of ICMR guideline has been done.

Does administration of broad-spectrum antibiotics in febrile neutropenic children trigger the emergence of BMR? A French experience

Background Blood stream infections (BSI) remain a major cause of morbidity and mortality in immunocompromised children and increase the length of hospitalisation as well as the cost of treatment. The difficulty of documenting bacteremia at the onset of fever in neutropenic patients led to an early administration of broad-spectrum antibiotics, without waiting for further clinical or microbiological evidence of infection. Furthermore, gut decontamination is performed in children with a high-risk of BSI. Does this practice trigger the emergence of multidrug resistant bacteria? Methods We performed a monocentric, retrospective and descriptive study between January 2014 and December 2017, using a large cohort of pediatric patients with hematological and oncological diseases in a tertiary care pediatric center in France, the Institute of Hematology and Oncology Pediatric (IHOPe) in Lyon. This includes patients with acute leukemia, lymphoma, children who underwent hematopoietic stem cell transplantation (HSCT) (allogenic and autogenic), children with severe combined immunodeficiency syndromes as well as children suffering from solid tumors. A bacteremia was defined by a positive blood culture sample, associated with fever. For coagulase-negative staphylococci (CoNS), two distinct positive blood cultures within 48 h were mandatory. The children were divided into 4 infectious risk groups regarding their immunosuppression level. Groups 3 and 4 received non-absorbable antibiotics for gut and oral decontamination. The empirical antibacterial therapy was adjusted to the risk group, as well as a prior identified bacteria colonisation: all patients with a central venous access received vancomycin (stopped after 48 hours in the absence of bacterial identification), amikacin and a broad-spectrum penicillin. Results During these 4 years, our institution recorded more than 8000 hospitalisations distributed within 3 units: 2 conventional hospitalisation wards and the HSCT unit. Our protected unit is equipped with spacious positive air pressure rooms, for child and parent, with high-efficiency particulate air (HEPA) filters where only a clean non-sterile outfit (gown and mask) are required. We identified 350 cases of BSI, thus an overall incidence of 4,5%. Fifteen to twenty per cent of these children suffered from a second or more re-infection. The incidence of BSI was stable throughout the four years of our study. Gram-positive bacteria represented more than 50% of BSI and CoNS was the most frequent pathogen agent found. Among the others gram-positive isolates, we counted around 5 to 6 cases/year of Streptococcus and Staphylococcus aureus. Among Gram-negative bacteria, enterobacteries accounted for 14 to 20 BSI per year and Pseudomonas aeruginosa for 2 to 4 cases per year. Among the identified bacteria, only 6.5% were multidrug resistant for all our study time. Three highly resistant bacteria were identified in 2 children priorly treated in Romania and Tunisia: 2 Klebsiella pneumoniae producing Carbapenemase (KPC), 1 Enterococcus faecium resistant to glycopeptides. Interestingly, 35% of the BSI occurred in the less immunocompromised group. The other cases were evenly distributed between the 3 more severely immunocompromised groups. Conclusion Our empirical initial broad-spectrum antimicrobial coverage is well adapted to the epidemiology of our bacterial agents and shortens hospitalisations. Furthermore, it is not associated with the emergence of antibiotic resistance patterns. The microbiological spectrum of incriminated bacteria is relatively stable over time and we do not observe the emergence of multidrug resistant gram-negative bacteria as well as the absence of vancomycin-resistant enterococci (VRE) in our tertiary center.

456 - Safety of Two-Hour Intermittent Intravenous Infusions of Tacrolimus in the Allogeneic Hematopoietic Stem Cell Transplantation Unit

At our institution, tacrolimus is used as a second-line agent for the prevention and treatment of graft-versus-host-disease in the allogeneic hematopoietic stem cell transplantation (HSCT) unit aft...

The North Wind and the Sun: Pediatric Antimicrobial Stewardship Program Combining Restrictive and Persuasive Approaches in Hematology-Oncology Ward and Hematopoietic Stem Cell Transplant Unit.

The Japanese government's goal for the reduction of antimicrobial consumption is two-thirds of the 2013 rate by 2020. While the antimicrobial stewardship programs (ASPs) are essential in health care facilities, ASP data on pediatric hematology-oncology and hematopoietic stem cell transplant (HSCT) patients are limited. Our aim was to evaluate the impact of restrictive and persuasive ASP on immunocompromised children. The ASP for hematology-oncology and HSCT patients at Tokyo Metropolitan Children's Medical Center was assessed. Phase 1 was a postprescriptive review of carbapenem conducted between April 2010 and September 2011. Phase 2 consisted of the preauthorization of carbapenem, prospective audit with feedback, a weekly luncheon meeting among physicians, consensus on febrile neutropenia management, and implementation of viral molecular diagnostics between October 2011 and September 2015. Both phases were compared for day-of-therapy per 1,000 patient-days, cost of intravenous antimicrobial agents, average hospitalization duration, all-cause mortality, infection-related mortality at 30 days, and appropriateness of empirical treatment of bacteremia. The ASP did not differ from phase 1 to phase 2 in terms of average hospitalization length, mortality rate, or appropriateness of empirical treatment for bacteremia. Day-of-therapies of cefepime, piperacillin/tazobactam, meropenem, vancomycin, liposomal amphotericin B, and fosfluconazole decreased by 20%, 45%, 57%, 38%, 85% and 44%, respectively (P < 0.05). The total cost of antibiotic and antifungal agents decreased by 27%, for a savings of $59,905 USD annually. Restrictive and persuasive ASP in the hematology-oncology ward and the HSCT unit safely decreased the use of antibacterial and antifungal agents.

Screening for Clostridium difficile colonization on admission to a hematopoietic stem cell transplant unit may reduce hospital-acquired C difficile infection

Clostridium difficile infection rates are higher in patients undergoing hematopoietic stem cell transplants. In our study, patients undergoing hematopoietic stem cell transplants or chemotherapy were screened for C difficile colonization at admission and placed on contact precautions if they were positive. Patient's colonized with C difficile contribute to the overall burden of C difficile infection in hospitals.

Evaluation of a Stenotrophomonas maltophilia bacteremia cluster in hematopoietic stem cell transplantation recipients using whole genome sequencing

BackgroundStenotrophomonas maltophilia ubiquitously occurs in the hospital environment. This opportunistic pathogen can cause severe infections in immunocompromised hosts such as hematopoietic stem cell transplantation (HSCT) recipients. Between February and July 2016, a cluster of four patients on the HSCT unit suffered from S. maltophilia bloodstream infections (BSI).MethodsFor epidemiological investigation we retrospectively identified the colonization status of patients admitted to the ward during this time period and performed environmental monitoring of shower heads, shower outlets, washbasins and toilets in patient rooms. We tested antibiotic susceptibility of detected S. maltophilia isolates. Environmental and blood culture samples were subjected to whole genome sequence (WGS)-based typing.ResultsOf four patients with S. maltophlilia BSI, three were found to be colonized previously. In addition, retrospective investigations revealed two patients being colonized in anal swab samples but not infected. Environmental monitoring revealed one shower outlet contaminated with S. maltophilia. Antibiotic susceptibility testing of seven S. maltophlia strains resulted in two trimethoprim/sulfamethoxazole resistant and five susceptible isolates, however, not excluding an outbreak scenario. WGS-based typing did not result in any close genotypic relationship among the patients’ isolates. In contrast, one environmental isolate from a shower outlet was closely related to a single patient’s isolate.ConclusionWGS-based typing successfully refuted an outbreak of S. maltophilia on a HSCT ward but uncoverd that sanitary installations can be an actual source of S. maltophilia transmissions.

Adapting and applying the Synergy Model on an inpatient hematology unit.

A pilot project was undertaken by an inpatient hematology and hematopoietic stem cell transplant unit to determine the feasibility of adapting the Synergy Model (Curley, 2007; 1998) to this patient population. During phase one, a patient characteristic tool for measuring complexity, stability, predictability, and participation in care was developed and tested. The tool was found to have strong face validity, high internal consistency, strong construct validity, and moderate inter-rater agreement. A nurse competency assessment was also developed, along with processes for making nursing and Health Care Aid assignments, as well as staffing decisions. The results of the pilot demonstrated that the Synergy Model can be adapted to this population and that it is feasible to use the model in an acute inpatient setting.

Don't Blame the Kids! Restricting Children in a Hematopoietic Stem Cell Transplant Unit

BACKGROUND: Community respiratory viruses (CRV) can be a major issue for Hematopoietic Stem Cell Transplant recipients (HSCT). Guidelines for preventing infectious complications among HSCT recipients recommend screening visitors and healthcare workers for upper respiratory infection (URI) symptoms and if present, restrict from contact with the patient until symptoms resolve. There are no recommendations to restrict children based on age. In summer of 2013, a cluster of Parainfluenza cases was identified on the HSCT unit. Physicians and staff were concerned that children were playing a role in hospital transmission of CRV to HSCT patients. September 2013, the unit implemented restricting visitors under age twelve. Our Infection Prevention department continued to monitor hospital acquired (HA) CRV's after the practice change to determine the impact on the incidence of CRV's.

Management of Risks From Water and Ice From Ice Machines for the Very Immunocompromised Host: A Process Improvement Project Prompted by an Outbreak of Rapidly Growing Mycobacteria on a Pediatric Hematopoietic Stem Cell Transplant (Hsct) Unit.

BACKGROUND In 2011, pediatric hematopoietic stem cell transplant (HSCT) patients were moved from an older hospital to a new children's hospital. To minimize bacterial growth in the new hospital's water during construction, the plumbing system was flushed and disinfected before occupancy. However, 6 months after occupancy, an increased incidence of rapidly growing mycobacteria (RGM) was detected in clinical cultures. Over 10 months, 15 pediatric HSCT patients were infected, while no pediatric HSCT patients had been infected in the preceding 12 months. OBJECTIVE To determine the cause of the outbreak and to interrupt patient acquisition of RGM. METHODS Water samples were collected from water entering the hospital and from drinking water and ice machines (DWIMs) from the old and new hospitals. Total heterotrophic plate counts (HPCs, CFU/mL) of water were undertaken, and select isolates were identified as RGM. RESULTS The cause of the outbreak was increased bacterial levels in the water (including RGM) in the DWIMs in the new (2011) hospital. Tests revealed higher HPCs in drinking water and ice from the DWIMs in the new hospital than in the DWIMs in the old hospital. Ultimately, HPCs were reduced by several different interventions. CONCLUSION In response to an RGM outbreak, HSCT patients were banned from ingesting DWIM ice and water and bottled water was provided. Since this interverntion 4 years ago, no additional RGM isolates have been identified in HSCT patient cultures. Our measures to reduce HPCs to goal levels in drinking water from DWIMs were successful, but the HPCs for ice have not consistently reached the goal of <500 CFU/mL. Infect Control Hosp Epidemiol 2017;38:792-800.

Risk Factors and Outcomes Related to Pediatric Intensive Care Unit Admission after Hematopoietic Stem Cell Transplantation: A Single-Center Experience

To describe incidence, causes, and outcomes related to pediatric intensive care unit (PICU) admission for patients undergoing hematopoietic stem cell transplantation (HSCT), we investigated the risk factors predisposing to PICU admission and prognostic factors in terms of patient survival. From October 1998 to April 2015, 496 children and young adults (0 to 23 years) underwent transplantation in the HSCT unit. Among them, 70 (14.1%) were admitted to PICU. The 3-year cumulative incidence of PICU admission was 14.3%. The main causes of PICU admission were respiratory failure (36%), multiple organ failure (16%), and septic shock (13%). The overall 90-day cumulative probability of survival after PICU admission was 34.3% (95% confidence interval, 24.8% to 47.4%). In multivariate analysis, risk factors predisposing to PICU admission were allogeneic HSCT (versus autologous HSCT, P = .030) and second or third HSCT (P = .018). Characteristics significantly associated with mortality were mismatched HSCT (P = .011), relapse of underlying disease before PICU admission (P < .001), acute respiratory distress syndrome at admission (P = .012), hepatic failure at admission (P = .021), and need for invasive ventilation during PICU course (P < .001). Our data indicate which patients have a high risk for PICU admission after HSCT and for dismal outcomes after PICU stay. These findings may provide support for the clinical decision-making process on the opportunity of PICU admission for severely compromised patients after HSCT.

542 - Prevention of Central Venous Catheter-Associated Blood Infections in a Hematopoietic Stem Cell Transplantation Unit in Brazil

542 - Prevention of Central Venous Catheter-Associated Blood Infections in a Hematopoietic Stem Cell Transplantation Unit in Brazil

Is surveillance for colonization of carbapenem-resistant gram-negative bacteria important in adult bone marrow transplantation units?

The aim of this study was to investigate the rate of carbapenem-resistant gram-negative bacilli (CRGNB) colonization and to analyze the risk factors associated with CRGNB colonization. This prospective study was conducted in adult patients hospitalized in hematopoietic stem cell transplantation (HSCT) units over a period of 8 months. Rectal swab samples were obtained from each participant every Monday, and patients CRGNB positive on admission were excluded. Of 185 participants, the median age was 47 years, and 59.5% were men. CRGNB colonization was detected in 21 (11.4%) patients. The most commonly isolated CRGNB were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Multivariate analysis revealed that busulfan use (11.9 times), fludarabine use (6.4 times), transfer from another hospital (7.8 times), transfer between units (9.3 times), and central venous catheterization (5.1 times) were risk factors for CRGNB colonization. During the study period, febrile neutropenia (FN) developed in 9 (56.2%) of the 21 colonized patients, and 1 patient died. Screening of patients for CRGNB colonization may have a role in preventing the spread of CRGNB. However, the empirical antimicrobial treatment for FN in patients with CRGNB colonization did not change, and their mortality rates were similar.

Promoting Hand Hygiene Compliance: PSYGIENE—a Cluster-Randomized Controlled Trial of Tailored Interventions

The German "Clean Hands Campaign" (an adaptation of the WHO "Clean Care is Safer Care" programme) to promote hand hygiene among hospital personnel at Hannover Medical School (MHH, Medizinische Hochschule Hannover), known as Aktion Saubere Hände (ASH), met with initial success. By 2013, however, compliance rates with hygienic hand disinfection in the hospital's ten intensive care units (ICUs) and two hematopoietic stem cell transplantation units (HSCTUs) had relapsed to their initial levels (physicians: 48%; nurses: 56%). The cluster- randomized controlled trial PSYGIENE was conducted to investigate whether interventions tai - lored in ways suggested by research in behavioral psychology might bring about more sustainable improvements than the ASH. The "Health Action Process Approach" (HAPA) compliance model specifies key psychological determinants of compliance. These determinants were assessed among health care workers in the ICUs and HSCTUs of the MHH by questionnaire (response rates: physicians: 71%; nurses: 63%) and by interviews of the responsible ward physicians and head nurses (100%). In 2013, 29 tailored behavior change techniques were implemented in educational training sessions and feedback discussions in the six wards that constituted the intervention arm of the trial, while ASH training sessions were provided in the control arm. The compliance rates for 2014 and 2015 (the primary outcomes of the trial) were determined by nonparticipating observation of hygienic hand disinfection, in accordance with the World Health Organization's gold standard. The two groups did not differ in their baseline compliance rates in 2013 (intervention: 54%, control: 55%, p = 0.581). The tailored interventions led to increased compliance in each of the two follow-up years (2014: 64%, p<0.001; 2015: 70%, p = 0.001), while the compliance in the control arm increased to 68% in 2014 (p<0.001) but fell back to 64% in 2015 (p = 0.007). The compliance increases from 2013-2015 and the compliance rate in 2015 were higher in the intervention arm (p<0.005). This was mainly attributable to the nurses' behavior, as the corresponding parameters for physicians did not differ significantly between the two study arms in stratified analysis. Tailored interventions based on behavioral psychology principles led to more sustainable increases in compliance with hand hygiene guidelines than ASH training sessions did. This was true among nurses, and thus also for hospital ward personnel as a whole (i.e., nurses and physicians combined). Further studies are needed to identify more target group-specific interventions that may improve compliance among physicians.

Two-Year Surveillance Study of Nosocomial Infections in Patients with Hematological Malignancies: Risk Factors for Antimicrobial Resistance and Their Impact in Mortality

Background: Infections are a leading cause of morbidity and mortality in patients suffering from hematological malignancies, with resistant bacteria being a major contributor. Special precaution is needed in these patients due to immunosuppression and safety measures are warranted to reduce related complications. Surveillance studies can offer a better understanding of risk factors associated with resistant strains and mortality.Materials and Methods: All patients hospitalized in our department of hematology, hematopoietic stem cell transplantation (HSCT) and post-transplant unit during 2014 and 2015 who presented an infectious episode were included in our study. An infectious episode was defined as a clinically detected infection not necessarily associated with specific bacteria or a positive surveillance culture. A retrospective epidemiological study was conducted using clinical data and positive cultures along with information about resistance. Our goal was to explore risk factors for infections by resistant bacteria and examine the impact of resistance on mortality.Results: During the two-year period, we identified 439 infectious episodes, 55.4% deriving from the department of hematology and 44.6% from the HSCT and post-transplant unit. Hematological malignancy was diagnosed in 429 patients, with 62.2% suffering from acute leukemia. Prevalence of resistant bacteria in our study population was 37.1%, more frequently isolated in the HSCT and post-transplant unit (52.2% vs 34.7%, p=0.001). Most of them were gram-negative, with the main representative being KPC klebsiella pneumoniae (38.7%), followed by pseudomonas aeruginosa (17.2%). Gram-positive species accounted for 19% of resistant bacteria, including MRSA staphylococcus and VRE enterococcus species. During the first semester of 2014, we identified a burkholderia cepacia outbreak with a total of 13 cases, that was successfully handled and the microorganism was eradicated.Possible risk factors for the isolation of resistant bacteria were examined. Factors included in our analysis were diagnosis, department of hospitalization, transplantation, prior chemotherapy, the presence of central venous catheter (CVC) and the presence of neutropenia. In multivariate analysis, the only significant risk factor associated with isolation of resistant bacteria was the department of hospitalization (OR 2.57, CI 1.31-5.02, p= 0.006). Duration of neutropenia was not correlated with increased rates of antimicrobial resistance (p=0.91).Mortality rate was 5.2%, mostly related to infection. Of the 23 patients that died, only six deaths were attributed to refractory disease. However, from the remaining 17, we identified 7 who presented severe immunosuppression after transplantation due to graft versus host disease (GVHD). Mortality was increased in patients with isolation of a resistant strain (73.9% vs 26.1%, p=0.001) but was not related to resistant disease or in combination with GVHD (52.9% vs 50%, p= 0.9). Using multivariate analysis, significant factors predicting mortality were neutropenia, the presence of resistant bacteria and presence of CVC. Other factors included in our analysis were the department of hospitalization, transplantation, diagnosis and preceding chemotherapy. The most powerful factor was the isolation of resistant bacteria (OR 4.08, CI 1.48-11.25, p=0.006) followed by the presence of CVC (OR 3.78, CI 1.14-12.54, p=0.03).Finally, we compared the impact of resistant bacteria between 2014 and 2015 and we observed a significant reduction in 2015 (57.1% vs 33.9%, p<0.001). We assume that this reduction is the result of more robust safety measures, including isolation of contaminated patients, intensive surveillance cultures in all patients that were routinely hospitalized and personnel discipline according to the guidelines.Conclusion: From our study we can conclude that patient colonization and possibly personnel behavior play a significant role in spreading of resistant bacteria, as the department of hospitalization was the only significant factor of bacteria isolation. Our two departments are localized in different floors of the same building with different staff on each floor, which makes cross contamination difficult. Resistance has a major impact on mortality, but appropriate measures can change distribution and improve survival in patients with hematological malignancies. DisclosuresNo relevant conflicts of interest to declare.

Chlorhexidine bathing for the prevention of colonization and infection with multidrug-resistant microorganisms in a hematopoietic stem cell transplantation unit over a 9-year period: Impact on chlorhexidine susceptibility.

Health care associated infections (HAIs) are currently among the major challenges to the care of hematopoietic stem cell transplantation (HSCT) patients. The objective of the present study was to evaluate the impact of 2% chlorhexidine (CHG) bathing on the incidence of colonization and infection with vancomycin-resistant Enterococcus (VRE), multidrug-resistant (MDR) gram-negative pathogens, and to evaluate their CHG minimum inhibitory concentration (MIC) after the intervention.A quasi-experimental study with duration of 9 years was conducted. VRE colonization and infection, HAI rates, and MDR gram-negative infection were evaluated by interrupted time series analysis. The antibacterial susceptibility profile and mechanism of resistance to CHG were analyzed in both periods by the agar dilution method in the presence or absence of the efflux pump inhibitor carbonyl cyanide-m-chlorophenyl hydrazone (CCCP) and presence of efflux pumps (qacA/E, qacA, qacE, cepA, AdeA, AdeB, and AdeC) by polymerase chain reaction (PCR).The VRE colonization and infection rates were significantly reduced in the postintervention period (P = 0.001). However, gram-negative MDR rates in the unit increased in the last years of the study. The CHG MICs for VRE increased during the period of exposure to the antiseptic. A higher MIC at baseline period was observed in MDR gram-negative strains. The emergence of a monoclonal Pseudomonas aeruginosa clone was observed in the second period.Concluding, CHG bathing was efficient regarding VRE colonization and infection, whereas no similar results were found with MDR gram-negative bacteria.