Infectious Events In Patients Research Articles

Infectious events in patients with alopecia areata treated with JAK inhibitors: low burden and minimal impact on persistence in treatment

ABSTRACT Background Alopecia areata (AA) is a non-scarring disorder characterized by hair loss that greatly affects patients’ quality of life and has a chronic, recurring course. This disease is marked by an inflammatory process, mainly on an autoimmune basis primarily regulated by Janus kinase (JAK). Research design and methods We conducted a retrospective study evaluating the safety of JAKi in a real-world setting in 91 AA patients, with a specific focus on the assessment of infectious events. Results Overall, 34 infectious events were observed in 28 patients (30.8%), among them 17 patients (60.7%) suspended treatment with JAKi until the infection was clinically resolved. Only in one case the infectious event led to a permanent discontinuation of the treatment. The data we observed in the study are consistent with results reported in clinical trials. Conclusion It can be stated that, during treatment with JAKi in AA patients, infectious events may occur, but in most cases these events are easily manageable and do not result in permanent discontinuation of the drug.

CD73 as a T cell dysfunction marker predicting cardiovascular and infection events in patients undergoing hemodialysis

BackgroundT cell dysfunction observed in patients undergoing hemodialysis (HD) has been linked to an extremely high morbidity of cardiovascular events (CVEs) and infections. The cell-surface 5′-nucleotidase CD73 sets the balance between pro-inflammatory nucleotides and anti-inflammatory adenosine. MethodsA total of 395 patients who had been receiving HD for at least six months were evaluated for proportions of CD73+ cells in both the CD4+ T cell and CD8+ T cell compartment and followed for one year to document CVEs and infections. Differences in the proportions of CD73-expressingT cells between healthy controls and patients undergoing HD were compared. The relationship between CD73+ T cells and clinical outcomes was analyzed using the Kaplan–Meier curve and Cox regression. ResultsHD was significantly related to a lower fraction of CD4+CD73+ T cells. In patients on HD, lower proportions of CD4+ CD73+T cells and CD8+ CD73+T cells were both associated with systemic inflammation and T cell terminal differentiation. More importantly, a lower CD4+CD73+T cell ratio independently predicted CVEs and infection in these patients. ConclusionWe identified CD73 as a T cell dysfunction marker predicting cardiovascular and infection events in patients undergoing HD, which provides a potential target in future studies of uremia-related immune dysfunction.

Long-Term Proton Pump Inhibitor Therapy Increases the Risk of Infection in Patients with Incident Hemodialysis

Background: Infection is one of the most common causes of death in patients with chronic kidney disease (CKD). Proton pump inhibitors (PPIs) are not only widely used in patients with CKD but also represent a known risk factor for infection in the general population. Here, we investigated associations between PPIs and infection events in patients with incident hemodialysis. Methods: We analyzed data from 485 consecutive patients with CKD who started hemodialysis at our hospital between January 2013 and December 2019. We analyzed associations between infection events and long-term (≥6 months) PPI use before and after propensity score-matched analysis. Results: Of the 485 patients, PPIs were administered to 177 patients (36.5%). During 24 months of follow-up, infection events occurred in 53 patients (29.9%) with PPIs and 40 patients (13.0%) without PPIs (p < 0.001). Patients with PPIs had a significantly higher cumulative incidence rate of infection events than those without PPIs (hazard ratio [HR] 2.13, 95% confidence interval [CI]: 1.36–3.32; p < 0.001). Even after propensity score-matched analysis (132 patients matched in each), the rate of infection events was higher for patients with PPIs (28.8% vs. 12.1%, HR 2.88, 95% CI: 1.61–5.16; p < 0.001). Similar results were obtained for severe infection events in both unmatched (14.1% vs. 4.5%, HR 2.97, 95% CI: 1.47–6.00; p = 0.002) and propensity score-matched analyses (14.4% vs. 3.8%, HR 4.54, 95% CI: 1.85–11.13; p < 0.001). Conclusions: In patients with incident hemodialysis, long-term PPI use increases the risk of infection. Clinicians should be wary of unnecessarily prolonging PPI therapy.

The ISAQ Score Does Not Predict Adrenal Crisis in Patients with Primary Adrenal Insufficiency.

This study aimed to investigate the ability of the immune system assessment questionnaire (ISAQ) to predict adrenal crisis (AC) and infectious events in patients with primary adrenal insufficiency (PAI). This was a prospective single-centre study over three years. Patients answered the ISAQ at baseline and were seen every 4-6 months in the endocrine outpatient clinic. At each visit previous infectious periods which required an increase in daily glucocorticoid dosage and AC were reported and documented. Seventy-five patients with PAI (53 women; 43 patients with autoimmune PAI, 20 patients with salt-wasting congenital adrenal hyperplasia and 12 patients who underwent bilateral adrenalectomy) were analysed. Due to the COVID-19 pandemic and consecutive lockdown measures, the data were analysed separately for March 2018 to March 2020 (period 1), and March 2020 to March 2021 (period 2). During period 1 the ISAQ score significantly correlated with the number of reported infectious events (r=0.351; p<0.01), but not during period 2 (r=0.059, p=0.613), in which the number of infectious events per patient-year significantly decreased (1.1±0.1 vs 0.4±0.1; p<0.001). The frequency of AC decreased from 8.8 to 2.4 per 100 patient-years between the two study periods. The ISAQ score was not different between patients with or without AC. The ISAQ score does not identify patients prone to ACs. The COVID-19 pandemic and consecutive lockdown measures significantly diminished the frequency of infectious events and ACs.

Impact of treatment with immunomodulators and tumour necrosis factor antagonists on the incidence of infectious events in patients with inflammatory bowel disease.

BackgroundCorticosteroids, immunomodulators (IM) and tumour necrosis factor antagonists (anti-TNF) are commonly used in the treatment of inflammatory bowel disease (IBD) but they also supress the defence against infectious disease. The aim of this study was to analyse the incidence of infectious events in patients with IBD and the association to concomitant medical therapy.MethodsWe performed a retrospective medical chart review of patients with IBD aged 18–65 years included in the Swedish Registry of Inflammatory Bowel Disease in the catchment area of Umeå University Hospital, Sweden. Data were collected from the period 01 January 2006, to 31 January 2019. An infectious event was defined as an outpatient prescription of antimicrobials or a positive diagnostic test for infection.ResultsDuring a period of 5,120 observation-years, we observed 1,394 events in 593 patients. The mean number of infectious events per 100 person-years was 27.2 (standard deviation [SD]: 0.46). There were no differences in mean incidence rates between patients treated with no immunosuppression (23.0 events per 100 person-years, SD: 50.4), patients treated with IM monotherapy (27.6 events per 100 person-years, SD: 49.9), patients treated with anti-TNF monotherapy (34.3 events per 100 person-years, SD: 50.1) and patients on combination therapy (22.5 events per 100-person-years, SD: 44.2). In a multivariate logistic regression, female gender (adjusted odds ratio [AOR]: 2.24; 95% confidence interval [CI]: 1.49–3.37) and combination therapy (AOR: 3.46; 95% CI: 1.52–7.85) were associated with higher risks of infection (>32 events per 100 person years). Also, patients treated with any immunosuppression treatment for 25–75% (AOR: 2.29; 95% CI: 1.21–4.34) and for >75% (AOR: 1.93; 95% CI: 1.19–3.12) of the observation period were at higher risks compared to patients treated with immunosuppression <25% of the observation period.ConclusionWe observed no significant difference in risk for infections between patients on monotherapy with IM or anti-TNF and patients with low use of immunosuppression, but there was a significant risk for combination therapy.

Epidemiology and Risk Factors for Infections in Myelodysplastic Syndromes

Background: Patients with MDS are at high risk of developing infections, which still represent the most frequent complications and the main cause of mortality and morbidity. We conducted a retrospective study with the aim of evaluating incidence, characteristics and outcome of infectious events in patients with myelodysplastic syndromes (MDS) and the risk factors associated with them.Patients and methods: 200 patients with MDS or LMMC followed by the Ancona Hematology Clinic in the last 15 years were included. In this group, we evaluated severe infectious episodes and associated risk factors, relating to patient, disease and therapy.Results: In a cohort of 200 patients, we detected 65 cases of infections of higher than third grade according to WHO. Pneumonia is the most frequent infection, especially on a bacterial basis. Risk factors that have shown significant association with infections ≥ G3 are: comorbidity (p = 0.0086), hemoglobin level (P = 0.0111), neutropenia (P = 0.0152), transfusion dependence during the course of disease (P <0.0001) and hypomethylating therapy (P = 0.0014). A subanalysis confirmed comorbidities as risk factors for the development of pneumonia (P = 0.0322) and azacitidine therapy as a risk factor for sepsis (P = 0.0038). The overall survival of the cohort is approximately 7.5 months and the predictive factors of survival are patient age (P = 0.0005), WHO disease class (P = 0.001), R-IPSS (P <0.0001) and transfusion-dependence during the course of the disease (P <0.0001). Multivariate analysis confirmed age (P = 0.0002), R-IPSS (P = 0.0043) and transfusion-dependence (P = 0.0006) as predictors of survival. Infections above grade 3 do not impact survival. Otherwise, there was a trend of reduced survival in patients who had pneumonia (P = 0.0612) or sepsis (P = 0.0927).Conclusion: Patients with MDS have a high probability of encountering an infectious problem in the course of the natural history of the disease. In one out of five cases, there are more than one infectious event. Particularly at risk of infection are patients with comorbidities, neutropenia (PMN <800 / mm³), significant transfusion needs and on therapy with hypomethylating agents. These patients should be carefully monitored for infectious complications. DisclosuresNo relevant conflicts of interest to declare.

Infectious events in patients with severe COVID-19: results of a cohort of patients with high prevalence of underlying immune defect

BackgroundEmpirical antibiotic has been considered in severe COVID-19 although little data are available regarding concomitant infections. This study aims to assess the frequency of infections, community and hospital-acquired infections, and risk factors for infections and mortality during severe COVID-19.MethodsRetrospective single-center study including consecutive patients admitted to the intensive care unit (ICU) for severe COVID-19. Competing-risk analyses were used to assess cumulative risk of infections. Time-dependent Cox and fine and gray models were used to assess risk factors for infections and mortality. Propensity score matching was performed to estimate the effect of dexamethasone.ResultsWe included 100 patients including 34 patients with underlying malignancies or organ transplantation. First infectious event was bacterial for 35 patients, and fungal for one. Cumulative incidence of infectious events was 27% [18–35] at 10 ICU-days. Prevalence of community-acquired infections was 7% [2.8–13.9]. Incidence density of hospital-acquired infections was 125 [91–200] events per 1000 ICU-days. Risk factors independently associated with hospital-acquired infections included MV. Patient’s severity and underlying malignancy were associated with mortality. Dexamethasone was associated with increased infections (36% [20–53] vs. 12% [4–20] cumulative incidence at day-10; p = 0.01). After matching, dexamethasone was associated with hospital-acquired infections (35% [18–52] vs. 13% [1–25] at 10 days, respectively, p = 0.03), except in the subset of patients requiring MV, and had no influence on mortality.ConclusionsIn this population of COVID-19 patients with high prevalence of underlying immune defect, a high risk of infections was noted. MV and use of steroids were independently associated with infection rate.

Incidence of Infectious Events in Patients with Inflammatory Bowel Disease. The Impact of Treatment with Immunomodulators and Biologics

Incidence of Infectious Events in Patients with Inflammatory Bowel Disease. The Impact of Treatment with Immunomodulators and Biologics

UM171-Expanded Cord Blood Transplants Support Robust T-Cell Reconstitution with Low Rates of Severe Infections

Introduction Rapid T cell reconstitution following hematopoietic stem cell transplantation is essential for protection against infections and has been associated with lower incidence of chronic graft-vs-host disease (cGVHD), relapse and transplant-related mortality (TRM). While cord blood (CB) transplants are associated with lower rates of cGVHD and relapse, their low stem cell content results in slower immune reconstitution and higher risk of graft failure, severe infections and TRM. Recently, results of a Phase I/II trial revealed that single UM171-expanded CB transplant allowed the use of smaller CB units without compromising engraftment. We now report on T cell reconstitution and immune function in patients transplanted with UM171-expanded CB grafts. Methods We performed a retrospective analysis of 20 patients treated with UM171-expanded CB and compared it to a contemporary cohort of 12 patients treated in the same institution who received unmanipulated CB transplant with similar conditioning regimens. Of note, no patient received ATG as part of the conditioning in either cohort. We used flow cytometry and TCR sequencing to evaluate T cell reconstitution, and virus-specific ELISpot assays to evaluate T cell function in the first year post-transplantation. We also categorized infectious events as per definitions of infection severity in the BMT CTN Technical MOP Version 3.0 and report the mean cumulative count of infectious events for each cohort. Results While median T cell dose in graft was at least 2-3x lower for the cohort of patients treated with UM171-expanded CB due to the selection of smaller cords and to cell loss occurring during CD34 selection process, numbers and phenotype of T cells at 3, 6 and 12 months post-transplant were similar in patients treated with UM171-expanded or unmanipulated CB transplant. TCR sequencing analyses revealed that UM171 patients had greater T cell diversity and higher numbers of T cell clonotypes at 12 months post-transplant compared to patients who received unmanipulated CB. Younger UM171 patients (i.e. &amp;lt;40 years old) also showed a more pronounced increase in naïve T cells and recent thymic emigrants (RTE) between 3- and 12-months post-transplant compared to age-matched unmanipulated CB patients, suggesting that UM171-expansion improves thymopoiesis at least in the young patients. This also correlated with the demonstration that UM171 expands common lymphoid progenitors in vitro. ELISpot assays revealed that UM171 patients showed early virus-specific T cell reactivity, at 2- and 3-months post-transplant. Most importantly, UM171 patients had a 2-fold lower frequency of severe (i.e. grade 2-3) infections at 1 year post-transplant, even though time to engraftment of 500 neutrophils was similar between the two cohorts (17 and 20 days for the UM171-expanded and unmanipulated CB cohorts respectively, p=0.94). Conclusion Our data show that the relative T-cell paucity of the UM171 graft is rapidly compensated after transplant with no significant difference observed between the two cohorts in terms of numbers and phenotypes of T cells at 3, 6 or 12 months post-transplant. Although it is difficult to dissect the relative contribution of homeostatic expansion and de novo thymopoiesis, recipients of UM171 grafts had a greater TCR diversity at one year, which was more evident among patients younger than 40 years of age. The prompt immune reconstitution observed in UM171 patients translated into a low rate of severe (grade 2-3) infections and no infection-related mortality. These results support rapid and functional T cell reconstitution following UM171 expanded CB transplantation, which likely contributes to the absence of moderate/severe cGVHD, infection-related mortality and late TRM observed in this cohort. Figure legend: Mean cumulative counts of infectious events in patients transplanted with UM171-expanded (blue) or unmanipulated (red) CB. Mean cumulative counts are shown for all infectious events (A), bacterial (B) and viral (C) infections. Events were categorized by type and severity as per BMT CTN guidelines (Appendix 4A). Infectious events of grade 1-3 are shown in pale colors, while more severe events (grade 2-3) are shown in dark colors. Censored patients (including those who relapsed) are indicated with white circles. Figure 1 Disclosures Dumont-Lagacé: ExCellThera: Current Employment. Busque:Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria. Sauvageau:ExCellThera: Current equity holder in private company, Other: CEO, Patents &amp; Royalties. Cohen:ExCellThera: Consultancy, Other: principal investigator of an ongoing UM171 clinical trial.

Insertion site of central venous catheter correlates with catheter-related infectious events in patients undergoing intensive chemotherapy.

Patients undergoing intensive chemotherapy are usually in need for central venous catheters (CVC). Due to contradictory study results, relation of insertion site and CVC-associated complication rate in these patients is not clear. We therefore retrospectively analyzed CVC-related data of all patients undergoing intensive chemotherapy with high risk of febrile neutropenia according to NCCN criteria, who received a CVC at our bone marrow transplantation unit between May 2016 and December 2019. In total, 210 patients received 281 CVC. CVC were placed via either the subclavian-vein (SCV, n = 58; 20%) or the internal-jugular-vein (IJV, n = 223; 80%). Median duration of CVC-lifetime and neutropenic days per CVC were comparable between the two groups (IJV vs SCV: 23 days vs 21 days (p = 0.16) and 12 days vs 11 days (p = 0.65)). Both, time to CVC removal due to local inflammation and time to central line-associated bloodstream infection was significantly shorter in patients with SCV catheters (p = 0.013 and p = 0.045). CVC placed in the IJV were associated with significantly less catheter-related infectious events compared with CVC placed in the SCV. This difference was consistent across different subgroups including 88 patients undergoing allogeneic stem cell transplantation.

Real word evidence on rituximab utilization: Combining administrative and hospital-pharmacy data.

To describe patterns of utilization, survival and infectious events in patients treated with rituximab at the University Hospital of Siena (UHS) to explore the feasibility of combining routinely collected administrative and hospital-pharmacy data for examining the real-world use of intravenous antineoplastic drugs. A retrospective, longitudinal cohort study was conducted using data from the Hospital Pharmacy of Siena (HPS) and the Regional Administrative Database of Tuscany (RAD). Patients aged ≥18 years with ≥1 rituximab administration recorded between January 2012 and June 2016 were identified in the HPS database. Anonymized patient-level data were linked to RAD. Rituximab utilization during the first year of treatment was described using HPS. Hospital diagnoses of adverse infectious events that occurred during the first year of follow-up and four-year survival were observed using RAD. A total of 311 new users of rituximab were identified: 264 patients received rituximab for non-Hodgkin's lymphoma (NHL) and 47 were treated for chronic lymphocytic leukemia (CLL). Among new users with one complete year of follow-up (n = 203) over 95% received rituximab as the first-line treatment, and approximately 70% of them received 5-8 doses. No patient in the CLL group received >8 administrations. Four-year survival was approximately 70% in both CLL and NHL patients. Sepsis was the most frequent infectious event observed (5.1%). HPS and RAD provided complementary information on rituximab utilization, demonstrating their potential for future pharmacoepidemiological studies on antineoplastic medications administered in the Italian hospital setting. Overall, this general description of the real-world utilization of rituximab in patients treated for NHL and CLL at UHS was in line with treatment guidelines and current knowledge on the rituximab safety profile.

P356 Infectious events in patients with inflammatory bowel disease: The impact of immunomodulators and tumour necrosis factor antagonist therapy

Abstract Background Immunomodulators (IM) and tumour necrosis factor antagonist therapy (anti-TNF) are effective treatments for inflammatory bowel disease (IBD) but has been associated with an increased risk for infectious diseases. We investigated the frequency of infectious events in patients with IBD and the association of infectious events with concomitant treatment with IM and anti-TNF therapy. Methods We performed a retrospective medical chart review of patients with IBD, 18 to 65 years of age, included in the Swedish Registry of IBD (SWIBREG) and treated in the catchment area of Umeå University Hospital, Sweden. Data were collected from the period January 1, 2006, to January 31, 2019. An infectious event was defined as an outpatient prescription of antimicrobials or a positive diagnostic test for infection. Results Among the 593 included patients (397 patients with UC and 195 patients with CD), 1398 events occurred. The proportion of events that occurred on treatment with corticosteroids, IM, anti-TNF, combination therapy (IM + anti-TNF) and without any immunosuppressive treatments was 8.3%, 35.8%, 17.7%, 10.0% and 47.4%. Of all patients, 60.4% had at least one infectious event, and 29.3% had &amp;gt;0.3 events per year. Compared with patients not receiving immunosuppressive therapy, an event rate of &amp;gt;0.3 per year was more common among those receiving immunomodulator monotherapy or combination therapy (Table), and was more common in patients with Crohn’s disease than ulcerative colitis (35.0% vs. 26.1%, p = 0.022). There were no significant differences in infectious events between patients who had received immunomodulator monotherapy and patients who had received combination therapy. Conclusion We found an increased frequency of infection associated with the use of combination therapy and immunomodulator monotherapy, but no difference between the two treatments.

Mortality risk prediction in lupus patients complicated with invasive infection in the emergency department: LUPHAS score.

Background:Infection remains a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). This study aimed to establish a clinical prediction model for the 3-month all-cause mortality of invasive infection events in patients with SLE in the emergency department.Methods:SLE patients complicated with invasive infection admitted into the emergency department were included in this study. Patient’s demographic, clinical, and laboratory characteristics on admission were retrospectively collected as baseline data and compared between the deceased and the survivors. Independent predictors were identified by multivariable logistic regression analysis. A prediction model for all-cause mortality was established and evaluated by receiver operating characteristic (ROC) curve analysis.Results:A total of 130 eligible patients were collected with a cumulative 38.5% 3-month mortality. Lymphocyte count <800/ul, urea >7.6mmol/l, maximum prednisone dose in the past ⩾60 mg/d, quick Sequential Organ Failure Assessment (qSOFA) score, and age at baseline were independent predictors for all-cause mortality (LUPHAS). In contrast, a history of hydroxychloroquine use was protective. In a combined, odds ratio-weighted LUPHAS scoring system (score 3–22), patients were categorized to three groups: low-risk (score 3–9), medium-risk (score 10–15), and high-risk (score 16–22), with mortalities of 4.9% (2/41), 45.9% (28/61), and 78.3% (18/23) respectively. ROC curve analysis indicated that a LUPHAS score could effectively predict all-cause mortality [area under the curve (AUC) = 0.86, CI 95% 0.79–0.92]. In addition, LUPHAS score performed better than the qSOFA score alone (AUC = 0.69, CI 95% 0.59–0.78), or CURB-65 score (AUC = 0.69, CI 95% 0.59–0.80) in the subgroup of lung infections (n = 108).Conclusions:Based on a large emergency cohort of lupus patients complicated with invasive infection, the LUPHAS score was established to predict the short-term all-cause mortality, which could be a promising applicable tool for risk stratification in clinical practice.

Use of a baseline risk score to identify the risk of serious infectious events in patients with rheumatoid arthritis during certolizumab pegol treatment

BackgroundThe risk of serious infectious events (SIEs) is increased in patients with rheumatoid arthritis (RA). The aim of this study was to develop an age-adjusted comorbidity index (AACI) to predict, using baseline characteristics, the SIE risk in patients with RA treated with certolizumab pegol (CZP).MethodsData of CZP-treated patients with RA were pooled from the RAPID1/RAPID2 randomized controlled trials (RCT CZP) and their open-label extensions (All CZP). Predictors of the first SIE were examined using multivariate Cox models. The AACI was developed by assigning specific weights to patient age and comorbidities on the basis of relative SIE risk. SIE rates were predicted using AACI score and baseline glucocorticoid use, and they were compared with observed rates. The percentage of patients in each SIE risk group achieving low disease activity (LDA)/remission was examined at 1 year of treatment.ResultsAmong 1224 RCT CZP patients, 40 reported ≥ 1 SIE (incidence rate [IR] 5.09/100 patient-years [PY]), and 201 of 1506 All CZP patients reported ≥ 1 SIE (IR 3.66/100 PY). Age ≥ 70 years, diabetes mellitus, and chronic obstructive pulmonary disease/asthma made the greatest contributions to AACI score. SIE rates predicted using AACI and glucocorticoid use at baseline showed good agreement with observed SIE rates across low-risk and high-risk groups. At 1 year, more high-risk All CZP patients than low-risk All CZP patients reported SIEs (IR 8.4/100 PY vs. IR 3.4/100 PY). Rates of LDA/remission were similar between groups.ConclusionsAACI and glucocorticoid use were strong baseline predictors of SIE risk in CZP-treated patients with RA. Predicted SIE risk was not associated with patients’ likelihood of clinical response. This SIE risk score may provide a valuable tool for clinicians when considering the risk of infection in individual patients with RA.Trial registrationClinicalTrials.gov, NCT00152386 (registered 7 September 2005); NCT00160602 (registered 8 September 2005); NCT00175877 (registered 9 September 2005); and NCT00160641 (registered 8 September 2005).

The impact of antimicrobial prophylaxis in morbidity and infections during azacitidine treatment.

The clinical consequences of the infectious events in patients receiving azacitidine are poorly documented. Likewise, the role of primary antimicrobial prophylaxis is unknown. In this retrospective, single-center study, we compare the impact of prophylaxis on the incidence of infection and morbidity in all consecutive higher-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients, during the first 4 azacitidine cycles. Seventy-six patients, corresponding to 283 azacitidine cycles, were studied. There were infectious events in 43% of the patients. Development of infections led to more hospital admissions, increased red blood cells and platelet requirements, and a delay in subsequent cycles. Median overall survival was comparable between patients with or without infections. In the multivariate analysis, a neutrophil count below 0.5×109/L (OR 12.5 [2.6-50]) and antimicrobial prophylaxis (OR 0.1 [0.02-04]) were independent factors for the development of infection. We conclude that infectious events have a significant impact in the early clinical course of azacitidine-treated patients by increasing hospital admissions and transfusion requirements. Antimicrobial prophylaxis may prevent infections, leading to a decreased need for supportive care in these patients with poor outcome.

Prophylaxis of post-ERC infectious complications in patients with biliary obstruction by adding antimicrobial agents into ERC contrast media- a single center retrospective study

BackgroundPatients with biliary obstruction are at high risk to develop septic complications after endoscopic retrograde cholangiography (ERC). We evaluated the benefits of local application of antimicrobial agents into ERC contrast media in preventing post-ERC infectious complications in a high-risk study population.MethodsPatients undergoing ERC at our tertiary referral center were retrospectively included. Addition of vancomycin, gentamicin and fluconazol into ERC contrast media was evaluated in a case-control design. Outcomes comprised infectious complications within 3 days after ERC.ResultsIn total, 84 ERC cases were analyzed. Primarily indications for ERC were sclerosing cholangitis (75%) and malignant stenosis (9.5%). Microbial testing of collected bile fluid in the treatment group was positive in 91.4%. Detected organisms were sensitive to the administered antimicrobials in 93%. The use of antimicrobials in contrast media was associated with a significant decrease in post-ERC infectious complications compared to non-use (14.3% vs. 33.3%; odds ratio [OR]: 0.33, 95% confidence interval [CI]: 0.114–0.978). After adjusting for the variables acute cholangitis prior to ERC and incomplete biliary drainage, the beneficial effect of intraductal antibiotic prophylaxis was even more evident (OR = 0.153; 95% CI: 0.039–0.598, p = 0.007). Patients profiting most obviously from intraductal antimicrobials were those with secondary sclerosing cholangitis.ConclusionLocal application of a combination of antibiotic and antimycotic agents to ERC contrast media efficiently reduced post-ERC infectious events in patients with biliary obstruction. This is the first study that evaluates ERC-related infectious complications in patients with secondary sclerosing cholangitis. Our first clinical results should now be prospectively evaluated in a larger patient cohort to improve the safety of ERC, especially in patients with secondary sclerosing cholangitis.

Effectiveness of Antibacterial Prophylaxis with Non-Absorbable Polymyxin B Compared to Levofloxacin after Allogeneic Hematopoietic Stem Cell Transplantation

▪Introduction:Bacterial infection is a major cause of early mortality after hematopoietic stem cell transplantation (HSCT). Currently, fluoroquinolones are widely used as prophylaxis against bacterial infection during neutropenia in HSCT. This strategy was established based on the results of several meta-analyses which showed that fluoroquinolones improved survival outcomes in patients receiving chemotherapy including HSCT when compared to placebo or no treatment. However, there was no evidence that the sole use of fluoroquinolones decreased mortality rates compared to other antibiotics.Intestinal flora has been investigated as a possible source of systemic infection during neutropenia through bacterial translocation from the intestinal tract. Some recent reports have shown that enterobacterial flora might be associated with bacteremia or graft-versus-host disease (GVHD) in HSCT. It was also shown in early trials that non-absorbable antibiotics which target intestinal flora improve the survival rate through decreased incidence of infection events in patients with neutropenia. However, it has been not sufficiently elucidated whether fluoroquinolones are able to reduce the infection rate more effectively than non-absorbable antibiotics, particularly in HSCT.Here we retrospectively compared systemic levofloxacin (LVFX) with non-absorbable polymyxin B (PB) in allogeneic HSCT.Patients and methods:This was a retrospective cohort study. We reviewed the charts of patients who underwent allogeneic HSCT where prophylaxis against bacterial infection was given using LVFX or PB from the start of conditioning until neutrophil engraftment. The study was conducted at our institute between 2005 and 2013.Results:A total of 226 (86 patients with PB and 140 patients with LVFX) patients were analyzed. Median age was 46 years (range: 16-69) with a 52:48 female/male ratio. The percentages for disease diagnosis, disease risk, and conditioning intensity were statistically similar. In the latter part of the study, significantly more patients were given LVFX. With the recent developments in HSCT procedure, cord blood or an HLA-mismatched donor was used as a stem cell source and drug combinations other than the classical combination, i.e., calcineurin+ short-term MTX, were used as GVHD prophylaxis in the LVFX group more frequently than in PB group.Median duration until neutrophil engraftment after HSCT was 16 days (range, 8-40) in the LVFX group and 15.5 days (range, 7-47) in the PB group (P= 0.74). The duration of prophylaxis was 11 days (range, 0-27) in the LVFX group and 12 days (range, 0-31) (P= 0.41) in the PB group. The type of antibiotic was changed in 96% of patients in the LVFX group and 94% in the PB group before engraftment, which was defined as failure of prophylaxis in this study (P=0.51). There was no significant difference in the incidence of clinically documented infection between the LVFX group (13%) and the PB group (17%) (P= 0.34). Microbiologically documented infection rates were 17% in the PB group and 11% in the LVFX group. The rate of resistance of etiological bacteria to LVFX was 100% in the LVFX group and 79% in the PB group (P=0.51).No significant difference was observed between the two groups in the cumulative incidences of prophylaxis failure (P= 0.36), clinically documented infection (P= 0.26), GVHD (P=0.50) and non-relapse mortality within the first 100 days after HSCT (P= 0.62). Furthermore, there was also no significant difference in overall survival between the two groups (P=0.72). Similar results were obtained in multivariate analysis adjusted for following factors: sex, age, transplant source, disease risk, donor type, HLA disparity, intensity of conditioning, type of GVHD prophylaxis, use of TBI or ATG.Conclusion:Our results indicate that prophylaxis against bacterial infection even with PB, a topical antimicrobial agent, might be as effective as LVFX in the early phase after allogeneic HSCT, suggesting the importance of inhibiting pathogenic bacteria in the intestine to prevent systemic infection probably due to the bacterial translocation. Antibacterial prophylaxis with PB might be a feasible strategy to preserve quinolone as an option for later use.Further optimization of oral prophylaxis against bacterial infection and/or a better understanding of influence of enterobacterial flora on after-transplant immunity are required. DisclosuresNakamae:Pfizer Inc.: Research Funding. Hayashi:Pfizer Inc.: Honoraria. Kakeya:Daiichi sankyo: Honoraria, Research Funding; Pfizer Inc.: Honoraria, Research Funding. Hino:Pfizer Inc.: Research Funding.

FRI0096 Impact of Chronic Kidney Disease on the Treatment and Complications of Japanese Patients with Rheumatoid Arthritis

BackgroundPatients with rheumatoid arthritis (RA) are more likely to develop chronic kidney disease (CKD) than those without it over time [1]. CKD is one of the major limiting factors for...

The association between zolpidem and infection in patients with sleep disturbance

ObjectiveRecent case reports suggest that zolpidem usage may be associated with infection events. The aim of this study was to determine the risk of infection events in patients with sleep disturbance taking zolpidem in a full 3-year follow-up study. MethodsA total of 17474 subjects with a diagnosis of sleep disturbance in 2002 and 2003 were identified, of whom 5882 had used zolpidem after recruitment. A Cox proportional hazard model was used to estimate the 3-year infection event-free rates for the patients using zolpidem and those not using zolpidem after adjusting for confounding factors. To maximize case ascertainment, only patients hospitalized for infection events were included. ResultsA total of 646 patients had had infection events, 331 (5.63%) of whom had been taking zolpidem and 315 (2.71%) had not. Zolpidem usage increased the risk of infection events. After adjustments for gender, age, co-morbidities, and other medications, patients using zolpidem with cDDD 1-28, 29-84, and >84 had hazard ratios of 1.67 (95% CI, 1.32–2.11), 1.91 (95% CI, 1.47–2.49) and 1.62 (95% CI, 1.32–1.98) respectively, compared with patients who did not use zolpidem. ConclusionsZolpidem increased the risk of infection events in sleep disturbance patients. This increased risk of infection should be explained to sleep disturbance patients, and prescriptions of zolpidem to chronic insomnia patients should be restricted.

Incidence rates of malignancies and hospitalized infectious events in patients with psoriasis with or without treatment and a general population in the U.S.A.: 2005–09

Rates of malignancies and hospitalized infectious events (HIEs) among psoriasis patients are higher than in the general population, but it is unclear if higher rates are associated with the underlying inflammatory state, treatments or both. To assess the incidence of malignancies and HIEs in a healthy US population, a psoriasis population, and four treated psoriasis populations. Using a US claims database, we identified a general population, a psoriasis cohort, and four treatment cohorts [non-biologic systemics, etanercept, other TNF blockers (adalimumab, infliximab) and phototherapy] to assess the incidence of lymphomas, nonmelanoma skin cancer (NMSC), all malignancies (excluding NMSC), and HIEs, standardized for age and sex. Among 40 987 patients with psoriasis, 11% were prescribed non-biologics, 15% etanercept, 6% other TNF blockers and 11% phototherapy. For all cancers, the psoriasis population rate (114/10 000 person-years) was 20% greater than the rate found in the general population (95/10 000 person-years). For NMSC, the psoriasis population rate (129/10 000 person-years) was 65% greater than the general population rate (78/10 000 person-years). The incidence rate for each treatment modality was lower than the overall psoriasis cohort, except for phototherapy. There was little difference in the rates of lymphomas. NMSC rates were higher among patients treated with phototherapy. HIE rates ranged from 165/10 000 person-years for the phototherapy group to 262/10 000 person-years for the other anti-TNF group. Patients with psoriasis appear to have higher rates of malignancy and HIE than the general population, with little difference in rates between the treatment methods, except for a higher rate of cancer among those receiving phototherapy.