scholarly journals 803. The Impact of Bundled Interventions to Decrease Transmission of Drug-Resistant Pseudomonas aeruginosa from Wastewater Drain Sites on a Hematologic Malignancy/Hematopoietic Stem Cell Transplant Unit

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S496-S496
Author(s):  
Lauren Fontana ◽  
Morgan Hakki ◽  
Richard Zhang ◽  
William Messer ◽  
Grace Walker-Stevenson ◽  
...  

Abstract Background Wastewater drain (WWD) sites are an important reservoir for amplification, propagation and transmission of multidrug resistant organisms. We observed an increase in the incidence of carbapenem and fluoroquinolone non-susceptible (CP-NS and FQ-NS) P. aeruginosa bloodstream infections (BSI) among patients on our hematologic malignancies (HM) and hematopoietic cell transplant (HCT) unit. The incidence of CP-NS/FQ-NS P. aeruginosa BSI from 2012 through May 2021 is represented in Figure 1. We sought to determine the impact of low-cost, low-barrier interventions targeting WWD sites on the prevalence of patient and environmental P. aeruginosa colonization and incidence of BSI. Figure 1. Incidence of P. aeruginosa BSI, 2012 through May 2021 Methods Behavioral and structural interventions to limit acquisition from WWD sites were informed by an environmental analysis and rolled out in staged fashion beginning in September 2019. Pre- and post-intervention colonization surveys were performed on the unit to assess for patient and WWD site P. aeruginosa colonization. Whole genome sequencing (WGS) was performed on select isolates. A sensitivity analysis performed accounted for the unconfirmed patient isolates. BSI data was collected retrospectively. Results Characteristics of the pre- and post-intervention groups are presented in Table 1. Five of 27 (18.5%) and 1 of 26 (3.8%) patients in the pre- and post-intervention point prevalence survey, respectively, were confirmed to be colonized with P. aeruginosa (Figure 2), corresponding to a prevalence rate ratio of 0.21 (0.03,1.66). If the two indeterminate samples in the pre-intervention period were positive, the prevalence rate ratio would instead be 0.15 (0.02,1.12). The most frequent P. aeruginosa strains identified by WGS from the patients and environment were 111, 308 and 446. At least 87% of rooms were colonized with P. aeruginosa from at least one WWD site, from pre- and post-intervention periods (Table 2). Table 1. Demographic and clinical characteristics of patients in each epoch. Results are given as percent (frequency) unless otherwise noted. Chi square test was used unless otherwise noted. Figure 2. Proportion of patients colonized with P. aeruginosa Positive: Colonized with P. aeruginosa, confirmed by WGS; Unknown: Phenotype of isolate suggestive of P. aeruginosa, WGS not performed; Negative: No growth on selective agar or non-P aeruginosa identification on WGS Table 2. WWD site colonization, by phenotypic and WGS determination. Fisher’s exact test was used unless otherwise noted. Conclusion P. aeruginosa WWD colonization on our HM/HCT unit may predispose patients to colonization and BSI. The prevalence of patient colonization decreased following implementation of the interventions, despite persistent environmental colonization. We will follow the incidence of P. aeruginosa BSI to determine the long-term impact of these interventions. Disclosures All Authors: No reported disclosures

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 613
Author(s):  
Nidhi Sharma ◽  
Qiuhong Zhao ◽  
Bin Ni ◽  
Patrick Elder ◽  
Marcin Puto ◽  
...  

Acute graft versus host disease (aGVHD) remains a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT). Tacrolimus (TAC), a calcineurin inhibitor that prevents T-cell activation, is commonly used as a GVHD prophylaxis. However, there is variability in the serum concentrations of TAC, and little is known on the impact of early TAC levels on aGVHD. We retrospectively analyzed 673 consecutive patients undergoing allo-HSCT at the Ohio State University between 2002 and 2016. Week 1 TAC was associated with a lower risk of aGVHD II–IV at TAC level ≥10.15 ng/mL (p = 0.03) compared to the lowest quartile. The cumulative incidence of relapse at 1, 3 and 5 years was 33%, 38% and 41%, respectively. TAC levels at week 2, ≥11.55 ng/mL, were associated with an increased risk of relapse (p = 0.01) compared to the lowest quartile. Subset analysis with acute myeloid leukemia and myelodysplastic syndrome patients showed significantly reduced aGVHD with TAC level ≥10.15 ng/mL at week 1 and a higher risk of relapse associated with week 2 TAC level ≥11.55 ng/mL (p = 0.02). Hence, achieving ≥10 ng/mL during the first week of HCT may mitigate the risk of aGVHD. However, levels (>11 ng/mL) beyond the first week may be associated with suppressed graft versus tumor effect and higher relapse.


Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 273 ◽  
Author(s):  
Stanislaw Schmidt ◽  
Michael Hogardt ◽  
Asuman Demir ◽  
Frauke Röger ◽  
Thomas Lehrnbecher

Immunosuppressive drugs are administered to a number of patients; e.g., to allogeneic hematopoietic stem cell transplant recipients. Immunosuppressive drugs impair the immune system and thus increase the risk of invasive fungal disease, but may exhibit antifungal activity at the same time. We investigated the impact of various concentrations of three commonly used immunosuppressive compounds—cyclosporin A (CsA), methylprednisolone (mPRED), and mycophenolic acid (MPA)—on the growth and viability of five clinically important Aspergillus species. Methods included disc diffusion, optical density of mycelium, and viability assays such as XTT. MPA and CsA had a species-specific and dose-dependent inhibitory effect on the growth of all Aspergillus spp. tested, although growth inhibition by MPA was highest in A. niger, A. flavus and A. brasiliensis. Both agents exhibited species-specific hyphal damage, which was higher when the immunosuppressants were added to growing conidia than to mycelium. In contrast, mPRED increased the growth of A. niger, but had no major impact on the growth and viability of any of the other Aspergillus species tested. Our findings may help to better understand the interaction of drugs with Aspergillus species and ultimately may have an impact on individualizing immunosuppressive therapy.


2019 ◽  
Vol 8 (4) ◽  
pp. 342-350 ◽  
Author(s):  
William R Otto ◽  
Barbara A Pahud ◽  
Dwight E Yin

AbstractMucormycosis is a severe infection that affects a variety of patients, including immunocompromised children and neonates. Given improved survival rates from advances in the treatment of malignancies, the population at risk for mucormycosis is increasing. We conducted a systematic review of cases of mucormycosis in children in the English-language literature reported between August 2008 and June 2017 and analyzed the clinical characteristics, diagnosis, management, and outcome of those infections. The most common underlying diagnoses included neutropenia (41%), hematologic malignancy (39%), prematurity (13%), and hematopoietic stem cell transplant (11%). Sinus disease (28%) and disseminated disease (24%) were the most common presentations. Rhizopus spp were the most common organisms isolated (22%). Amphotericin B remains the backbone of treatment and was prescribed in 86% of these cases. The resulting mortality rate remains high (32%). We provide here the results of a literature review of mucormycosis in children, including its epidemiology and clinical manifestations, and describe current advances in its diagnosis and treatment.


2019 ◽  
Vol 82 (06) ◽  
pp. 559-567
Author(s):  
Christina Niedermeier ◽  
Andrea Barrera ◽  
Eva Esteban ◽  
Ivana Ivandic ◽  
Carla Sabariego

Abstract Background In Germany a new reimbursement system for psychiatric clinics was proposed in 2009 based on the § 17d KHG Psych-Entgeltsystem. The system can be voluntary implemented by clinics since 2013 but therapists are frequently afraid it might affect treatment negatively. Objectives To evaluate whether the new system has a negative impact on treatment success by analysing routinely collected data in a Bavarian clinic. Material and methods Aggregated data of 1760 patients treated in the years 2007–2016 was analysed with segmented regression analysis of interrupted time series to assess the effects of the system on treatment success, operationalized with three outcome variables. A negative change in level after a lag period was hypothesized. The robustness of results was tested by sensitivity analyses. Results The percentage of patients with treatment success tends to increase after the new system but no significant change in level was observed. The sensitivity analyses corroborate results for 2 outcomes but when the intervention point was shifted, the positive change in level for the third outcome became significant. Conclusions Our initial hypothesis is not supported. However, the sensitivity analyses disclosed uncertainties and our study has limitations, such as a short observation time post intervention. Results are not generalizable as data of a single clinic was analysed. Nevertheless, we show the importance of collecting and analysing routine data to assess the impact of policy changes on patient outcomes.


Blood ◽  
2020 ◽  
Author(s):  
David P. Steensma ◽  
Kelly L Bolton

Acquired genetic mutations in hematopoietic stem or progenitor cells can lead to clonal expansion and imbalanced blood cell production. Clonal hematopoiesis is exceptionally common with human aging, confers a risk of evolution to overt hematologic malignancy, and also increases all-cause mortality and the risk of cardiovascular disease. The degree of risk depends on the specific mutation, number of mutations, mutant allele burden, and concomitant non-genetic risk factors (e.g., hypertension or cigarette smoking). People with clonal hematopoiesis may come to clinical attention in a variety of ways, including during the evaluation of a possible hematologic malignancy, as an incidental discovery during molecular analysis of a non-hematological neoplasm, after hematopoietic cell transplant, or as a result of germline testing for inherited variants. Even though the risk of clonal progression or a cardiovascular event in an individual patient may be low, the possibility of future clinical consequences may contribute to uncertainty and worry, since it is not yet known how to modify these risks. This review summarizes clinical considerations for patients with clonal hematopoiesis, including important points for hematologists to consider discussing with affected persons - individuals who may understandably be anxious about having a mutation in their blood that predisposes them to develop malignancy, but which is statistically more likely to result in a myocardial infarction or stroke. The increasing frequency with which people with clonal hematopoiesis are discovered and the need for counseling these patients is driving many institutions to create specialized clinics; we describe our own experience with forming such clinics.


2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Takuto Takahashi ◽  
Angela R. Smith ◽  
Pamala A. Jacobson ◽  
James Fisher ◽  
Nathan T. Rubin ◽  
...  

ABSTRACT Voriconazole (VCZ) is an antifungal agent with wide inter- and intrapatient pharmacokinetic (PK) variability and narrow therapeutic index. Although obesity was associated with higher VCZ trough concentrations in adults, the impact of obesity had yet to be studied in children. We characterized the PK of VCZ in obese patients by accounting for age and CYP2C19 phenotype. We conducted intensive PK studies of VCZ and VCZ N-oxide metabolite in 44 hematopoietic stem cell transplantation (HSCT) recipients aged 2 to 21 years who received prophylactic intravenous VCZ every 12 hours (q12h). Blood samples were collected at 5 and 30 minutes; at 1, 3, 6, and 9 hours after infusion completion; and immediately before the next infusion start. We estimated PK parameters with noncompartmental analysis and evaluated for an association with obesity by multiple linear regression analysis. The 44 participants included 9 (20%) with obesity. CYP2C19 metabolism phenotypes were identified as normal in 22 (50%), poor/intermediate in 13 (30%), and rapid/ultrarapid in 9 patients (21%). Obesity status significantly affects the VCZ minimum concentration of drug in serum (Cmin) (higher by 1.4 mg/liter; 95% confidence interval [CI], 0.0 to 2.8; P = 0.047) and VCZ metabolism ratio (VCZRATIO) (higher by 0.4; 95% CI, 0.0 to 0.7; P = 0.03), while no association was observed with VCZ area under the curve (AUC) (P = 0.09) after adjusting for clinical factors. A younger age and a CYP2C19 phenotype were associated with lower VCZ AUC. Obesity was associated with decreased metabolism of VCZ to its inactive N-oxide metabolite and, concurrently, increased VCZ Cmin, which is deemed clinically meaningful. Future research should aim to further characterize its effects and determine a proper dosing regimen for the obese.


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