Anti-infectives For Use Research Articles

Low Infection Rates With Long-Term Dupilumab Treatment in Patients Aged 6 Months to 5 Years: An Open-Label Extension Study.

To evaluate long-term infection rates in children aged 6 months to 5 years with moderate-to-severe atopic dermatitis (AD) treated with dupilumab. This was a post hoc analysis of an ongoing open-label extension (OLE) study of dupilumab. Pediatric patients aged 6 months to 5 years with moderate-to-severe AD who had previously taken part in the LIBERTY AD PRESCHOOL phase 2 and 3 clinical trials received weight-based subcutaneous dupilumab every 2 or 4 weeks. Exposure-adjusted infection rates after a median dupilumab exposure of 52 weeks are compared with data from the earlier randomized, placebo-controlled, 16-week LIBERTY AD PRESCHOOL phase 3 trial. Infection rates were overall lower in the OLE study compared with the dupilumab and placebo groups in the earlier 16-week trial, including total infections (101.0 patients/100 patient-years [PY]), nonherpetic skin infections (22.7 patients/100PY), herpetic infections (7.3 patients/100PY), and nonskin infections (92.9 patients/100PY). The frequency of severe and serious infections was low (3.1 patients/100PY), compared with 17.1 placebo-treated patients/100PY and 0 dupilumab-treated patients in the earlier 16-week trial, and no infections leading to treatment discontinuation were observed. Systemic anti-infective medication use (58.9 patients/100PY) was lower in the OLE study compared with both the dupilumab and placebo groups in the 16-week trial. Overall, reduced infection rates are observed in infants and young children with moderate-to-severe AD treated with dupilumab long-term, supporting the known safety profile of dupilumab.

An Analysis of the Use of Topical Ocular Anti-Infectives in Galicia (Spain) between 2020 and 2023.

Eye infections are a global health and economic problem that affect people of both sexes at any age. Topical application of anti-infectives is widely used in the treatment of these types of infections. However, little is known about the current status and trends of the use of topical ocular anti-infectives in Spain. In the present work, we evaluated the use of this type of drug in the Spanish autonomous community of Galicia and described the variability in its consumption between Galician provinces between 2020 and 2023. In addition, the possible existence of a deviation in consumption at a seasonal level was evaluated, as well as possible changes during the study period. A descriptive, cross-sectional and retrospective study of the use of drugs belonging to the subgroups S01A (anti-infectives) and S01C (anti-inflammatory agents and anti-infectives in combination) of the Anatomic Therapeutic Chemical Classification was carried out. This work demonstrated that the most used topical ocular anti-infective in Galicia was tobramycin and that the use of these types of drugs in our region varied according to the provinces. This study also revealed that the consumption of these medications has remained stable during the period 2020-2023, with no significant seasonal differences observed.

Treatment patterns and burden of infection in patients with chronic lymphocytic leukemia and secondary immunodeficiency: a retrospective database study

Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and secondary immunodeficiency disease (SID) are susceptible to severe, recurrent, or persistent infections. This retrospective cohort study assessed the burden of infection in patients with CLL/SLL with and without SID, and in immunoglobulin replacement therapy (IgRT)-treated and -untreated patients with CLL/SLL and SID. Anonymized data from the US Optum-Humedica database (Oct-1-2015–Mar-10-2020) were used. Eligible patients aged ≥ 18 years with a confirmed CLL/SLL diagnosis were assigned to cohorts (SID or no-SID) using an algorithm based on serum IgG levels < 5.0 g/L, hypogammaglobulinemia diagnosis codes, and ≥ 1 major infection. A further sub-categorization was made based on patients with SID who received IgRT and those who did not. During 12-month follow-up, patients with CLL/SLL and SID were significantly more likely to experience infections (70.1% vs. 30.4%), including severe bacterial infections (39.8% vs. 9.2%), and infections requiring hospitalization (27.7% vs. 5.8%) than patients without SID. The use of anti-infectives and healthcare resource utilization (HCRU) was also higher in the SID cohort versus the no-SID cohort. Overall survival was shorter in patients with SID than those without (12.3 vs. 16.9 months). In patients with CLL/SLL and SID, burden of infection and HCRU were greater in IgRT-treated patients than in no-IgRT patients, potentially highlighting the IgRT-treated cohort as a more vulnerable population. Increasing understanding of SID burden may help to improve outcomes in patients with CLL/SLL. Further research is needed to develop guidance for IgRT use and to assess the benefits of IgRT in this vulnerable population.

Trends of drug expenditure in Taiwan National Health Insurance before and during COVID-19 pandemic.

The Taiwanese government adopted the National Health Insurance (NHI) system in March 1995. This study aimed to understand the difference in medication costs before (year 2019) and during the COVID-19 pandemic (2020-2021) among different hospitals for treating their patients. The NHI claims database consisting of claims of prescription drugs for inpatients (IPD) and outpatients (OPD) in Taiwan was used to determine drug expenditure in different hospitals, particularly the top 10 prescription Anatomical Therapeutic Chemical (ATC) categories. In medical centers, L01X (other antineoplastic agents) showed the highest drug expenditure, followed by L04A (immunosuppressants) and J05A (direct-acting antivirals). The drug expenditure pattern in regional hospitals was similar to that in medical centers, with L01X (other antineoplastic agents) showing the highest drug expenditure. L01X (other antineoplastic agents) also showed the highest drug expenditure in district hospitals, followed by N05A (antipsychotics) and A10B (blood glucose-lowering drugs, excluding insulin). In clinics, A10B (blood glucose-lowering drugs, excluding insulin) showed the highest drug expenditure. The total medication costs in 2021 were lower or similar to those in 2019. The use of systemic use anti-infectives decreased over time in OPDs among all hospita1 levels but increased in IPDs in medical centers and district hospitals. Furthermore, our analysis revealed that the trend in drug expenditure closely mirrored the trend in drug prescription volume for the highest annual sum cost item among the top 10 drug subgroups across different hospital levels. Our analysis found that annual drug expenditures in 2021 were lower or similar to those in 2019, suggesting that the COVID-19 pandemic has contributed to this reduction in drug expenditure.

Incorporating anti-infective drugs into peripherally inserted catheters does not reduce infection rates in neonates.

This study assesses whether peripherally inserted central venous catheters (PICC), impregnated with anti-infective drugs, reduce the rate of infections in neonates compared with unimpregnated catheters. A retrospective analysis was conducted on electronic patient records of neonates born between August 2014 and May 2020, who had PICCs inserted, either standard (S-PICC) or with anti-infective drugs (A-PICC). Catheter-related bloodstream infections (CRBSI) were diagnosed based on clinical symptoms, laboratory results, and mentioning of infection in the patient record. Data on dwell time, mechanical ventilation, insertion site, maximum C-reactive protein (CRP) concentration, and anti-infective drug use were analyzed. A total of 223 PICCs were included. The infection rates were A-PICC (18.9%) and S-PICC (12.5%), which were not significantly different (p = 0.257). A-PICCs had significantly longer dwell times than S-PICCs (median 372 vs. 219 h, p = 0.004). The time to infection was not different between the groups (p = 0.3). There were also no significant differences in maximum CRP, insertion site abnormalities, or anti-infective drug use between the groups. This retrospective study did not find a significant reduction in infection rates by using PICCs containing anti-infective drugs in neonates. Current antibiotic impregnations do not seem to be effective in preventing blood stream infections.

Lack of microbiological awareness on the ward as a key factor for inappropriate use of anti-infectives: results of a point prevalence study and user satisfaction survey in a large university hospital in Austria

PurposeAlthough diagnostic stewardship issues in clinical microbiology harbor an optimization potential for anti-infective consumption, they are only marginally addressed in antimicrobial stewardship (AMS) programs. As part of an AMS point prevalence (PPS) survey we therefore aimed to gain a more dynamic view on the microbiological awareness within therapeutic regimens. By examining whether initial microbiological sampling was performed and in which way microbiological results were incorporated into further treatment considerations we sought to find out to what extent these points determine the appropriateness of treatment regimens.MethodsPPS was performed at the University Hospital Salzburg (1524 beds) in May 2021. Relevant data was determined from the patient charts and the appropriateness of anti-infective use was assessed using predefined quality indicators. Six months after the PPS, a questionnaire was administered to clinicians to obtain information on the use of microbiological findings and their relevance in the clinic.ResultsLack of microbiological awareness in the clinical setting proved to be the key reason for an overall inadequate use of anti-infectives (35.4% of cases rated as inadequate), ahead of the aspects of dose (24.1%), empirical therapy (20.3%) and treatment duration (20.2%). This was particularly the case for broad-acting agents and was most evident in urinary tract infections, skin and soft tissue infections, and pneumonia. The results of the questionnaire indicate a discrepancy between the physicians surveyed and the routine clinical setting.ConclusionA high potential in improving the use of anti-infectives in hospitals seems to lie in a strong emphasis on microbiological diagnostic stewardship measures.

An evaluation of the antimicrobial activity of some commonly used wood species

Aims: Antibiotic resistance mechanisms in pathogenic bacteria constitute an important obstacle in the fight against infection. Controlling the spread of resistant pathogens by utilizing antimicrobial activity on their surfaces may help us in this fight. There are many plant and wood species that have been previously tested for their antibacterial and antiviral properties. In this study, walnut (Juglans regia), white mulberry (Morus alba), white oak (Quercus alba), yellow pine (Pinus sylvestris), and beech (Fagus sylvetica), which are among the wood species used in the production of products that are in constant contact with humans in daily life, such as furniture, doors, and beads, were examined in terms of an antistaphylococcal effect. Methods: Five groups of tree species and glass samples selected as a positive control were cut into 1 cm3, contaminated with Staphylococcus aureus solution with a concentration of 1*106 CFU/ml, and monitored for five days. Each day, five randomly selected samples from each group were sonicated with phosphate buffered saline. Samples taken from the sonicated solution were cultured on tryptic soy agar, and the number of bacteria per sample was calculated. One sample selected from the uncontaminated samples was incubated with 0.5 McFarland standard bacterial solution on Müller Hinton agar, and the diameter of inhibition was evaluated. The study was repeated twice. The significance level was set at 0.05. Results: The agar diffusion method showed inhibition zone only in Q. alba and M. alba. In samples contaminated with bacteria, the highest antistaphylococcal effect was found in Q. alba. This was followed by M. alba, P. sylvestris, F. sylvetica. There was no significant difference between J. regia and the positive control. Conclusion: In this study in which we wanted to emphasize the importance of the antimicrobial activity of surfaces for pathogens known to live on the surface environment, all trees except J. regia showed antistaphylococcal activity. It is thought that the procyanidins?phenethyl, benzyl, and benzyl?in the bark of the trees are effective. In previous studies, Q. alba in particular is recommended for anti-infective use due to its high inhibition effect. Antibacterial activity was also found in F. sylvetica, which is known to have antiviral activity. Antibacterial activity was not demonstrated for J. regia. In order to prevent the spread of infection in collective living areas, it is recommended that trees be selected that contain antimicrobial raw materials such as M. alba, Q. alba, P. Sylvestris, and F. sylvetica and to evaluate the use of extracts from these trees as natural and edible products to combat bacteria.

Penser le dossier patient informatisé comme un outil pour les infectiologues: une démarche nécessaire pour le futur de la discipline

This expert perspective scrutinizes our engagement with electronic patient records, a vital instrument for infectious disease specialists in both patient care and the prudent use of anti-infectives. The authors propose the potential for enhancing these tools through user-centered design and system workflow improvements, along with the implementation of best practices gleaned from the scientific management of information systems. Such transformations could be expedited with the coordinated participation of the discipline professionals to assist in articulating needs and conducting evaluations in active partnership with the creators of these technologies. Concluding, the article presents a series of contemplations on possible advancements of new generations of electronic patient record components, particularly beneficial for infectious disease practice. These include tools specifically dedicated to the management of anti-infective treatments, the reporting of microbiological results, the synthesis of infectious disease medical data, vaccination management, epidemic management, and prevention of infectious risk.

Antibiotic stewardship

The spread of antimicrobial resistance (AMR) is one of the greatest threats to global health and causes very many deaths. Also in the context of sepsis-the severest complication of certain infectious diseases-does AMR play arole. Wise use of anti-infectives and application of antibiotic stewardship (AMS) principles can reduce the spread of AMR and improve the quality of management of patients with infectious diseases. Correct use of anti-infective agents includes the correct diagnostic approach and documentation of the (suspected) diagnosis, guideline-conform diagnostic workup and treatment selection, re-evaluation and tailoring during the course of treatment, afocus on treatment de-escalation depending on clinical response and microbiology results, dose optimization, and, if possible, conversion to oral therapy, and early termination of treatment if the suspected diagnosis is not confirmed. Particularly adherence to the guideline-conform treatment duration can reduce unnecessary use of anti-infectives. Prevention of infections via adherence to vaccination recommendations also contributes to areduction in the use of anti-infectives. Interdisciplinary collaboration with infectious diseases and AMS specialists, as recommended for sepsis, also improves treatment quality and patient outcomes. Particularly for complex infections such as endocarditis cases should be discussed in multidisciplinary teams including specialists in infectious diseases. In this manner, decisive steps against the spread of AMR and towards maintenance of the efficacy of available anti-infective drugs can be taken.

337 Dupilumab treatment is not associated with an increased overall risk of infections in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis

Abstract Patients with atopic dermatitis (AD) have an increased risk of infection, including skin infections. Previous studies in children aged 6–11 years and adolescents showed that dupilumab is not associated with an increased risk of overall infections and is associated with a lower incidence of skin infections compared with a placebo. This post-hoc analysis reports the impact of dupilumab treatment on infections, including skin infections, in children aged 6 months to 5 years with moderate-to-severe AD. In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled trial (NCT03346434, part B), children aged 6 months to 5 years with moderate-to-severe AD (Investigator’s Global Assessment score ≥3) were randomized 1 : 1 to subcutaneous dupilumab every 4 weeks (200 mg if baseline weight was ≥5 to &amp;lt;15 kg, 300 mg if weight was ≥15 to &amp;lt;30 kg) or placebo with concomitant low-potency topical corticosteroids for 16 weeks. Exposure-adjusted rates (patients with ≥1 event per 100 patient-years [nP/100 PY]) and systemic anti-infective medication use (nP/100PY) were used to compare treatment groups. 162 patients were randomized to dupilumab (n = 83) or placebo (n = 79). During the 16-week treatment period, total infections rates were numerically lower in the dupilumab-treated group (nP/100PY: 185.2) compared with the placebo-treated group (nP/100PY: 245.7). Fewer infections of skin-structure and soft tissues were reported in the dupilumab group (nP/100PY: 24.7) compared with the placebo group (nP/100PY: 40.2). Dupilumab-treated patients had significantly lower rates of non-herpetic skin infections (nP/100PY: 42.7) than placebo-treated patients (nP/100PY: 92.7; P &amp;lt; 0.05 vs. placebo). There was no significant difference in rates of herpetic skin infections between the dupilumab (nP/100PY: 20.0) and placebo groups (nP/100PY: 17.1; P = 0.817 vs. placebo). No helminthic infections were reported in either group. Systemic anti-infective medication use was significantly less frequent in the dupilumab group (nP/100PY: 104.7) compared with placebo (nP/100PY: 203.0; P &amp;lt; 0.05 vs. placebo). The overall safety of dupilumab was consistent with the known safety profile. Dupilumab treatment is associated with lower overall infections and significantly lower non-herpetic skin infections than placebo in children aged 6 months to 5 years with moderate-to-severe AD.

Trends in anti-infective use during pregnancy in France between 2010 and 2019: a nationwide population-based study.

To describe the trends in anti-infective use during pregnancy between 2010 and 2019 and determine whether they were prescribed according to drug foetal safety international classification systems. We conducted a population-based, nationwide study using the French national health data system including all pregnancies ended between 2010 and 2019. Anti-infective agents were considered according to their pharmacological group and potential harmful risk using the Australian and Swedish classification systems. Prevalence rate was estimated annually and by trimester. Average annual percent change (AAPC) and 95% confidence intervals (CIs) were calculated using Joinpoint regression. Among 7 571 035 pregnancies, 3 027 031 (40.0%) received ≥1 antibacterial. This proportion decreased significantly from 41.5% in 2010 to 36.1% in 2019 (AAPC = -1.7%, [95%CI, -2.5 to -1.0%]). Conversely, use of antiviral agents increased during the 10-year study period for anti-herpes simplex virus agents (AAPC =4.4%, [3.7-5.2%]), influenza agents (AAPC = 25.4%, [6.2-48.1%]) and for HIV-antiretroviral agents (AAPC =1.3%, [0.6-2.0%]). Use of influenza vaccine increased from 0.2% in 2010 to 4.2% in 2019 (AAPC = 49.7%, [39.3-60.9%]). Among all pregnancies, 0.9% had been exposed to a potentially harmful anti-infective agent increasing from 0.7% in 2010 to 1.2% in 2019 (AAPC =6.4%, [4.4-8.5%]). Based on >7 million pregnancies identified from French nationwide data, this study showed that antibacterials are frequently prescribed during pregnancy although their use has decreased over the past 10 years. Our results suggest that anti-infective agents are generally prescribed in accordance with recommendations, although with a potential for improvement in influenza vaccination.

Impact of Infections in Patients Receiving Pembrolizumab-Based Therapies for Non-Small Cell Lung Cancer.

Background: Immune checkpoint inhibitor (ICI) therapy has significantly improved outcomes across a range of malignancies. While infections are a well-known contributor to morbidity and mortality amongst patients receiving systemic chemotherapy regimens, little is known about the impact of infections on patients receiving ICI therapy. This study aims to assess incidence, risk factors, and outcomes in patients who develop infections while on pembrolizumab-based therapies for non-small cell lung cancer (NSCLC). Methods: Patients receiving pembrolizumab for stage III/IV NSCLC from 1/1/2017-8/1/2021 across seven hospitals were identified. Incidence and type of infection were characterized. Covariates including baseline demographics, treatment information, treatment toxicities, and immunosuppressive use were collected and compared between infected and non-infected patients. Outcomes included the rate of infections, all-cause hospital admissions, median number of treatment cycles, overall survival (OS), and progression free survival (PFS). Univariable and multivariable analysis with reported odds ratio (OR) and 95% confidence intervals (CI) were utilized to evaluate infection risks. OS and PFS were analyzed by Kaplan−Meier analysis and tested by log-rank test. p-value < 0.05 was considered statistically significant. Results: There were 243 NSCLC patients that met the inclusion criteria. Of these, 111 (45.7%) had one documented infection, and 36 (14.8%) had two or more. Compared to non-infected patients, infected patients had significantly more all-cause Emergency Department (ED) [37 (33.3%) vs. 26 (19.7%), p = 0.016], hospital [87 (78.4%) vs. 53 (40.1%), p < 0.001], and ICU visits [26 (23.4%) vs. 5 (3.8%), p < 0.001], and had poorer median OS (11.53 [95% CI 6.4−16.7] vs. 21.03 [95% CI: 14.7−24.2] months, p = 0.033). On multivariable analysis, anti-infective therapy (OR 3.32, [95% CI: 1.26−8.76], p = 0.015) and ECOG of >1 (OR 5.79, [95% CI 1.72−19.47], p = 0.005) at ICI initiation conferred an increased risk for infections. At last evaluation, 74 (66.7%) infected and 70 (53.0%) non-infected patients died (p = 0.041). Conclusion: Infections occurred in nearly half of patients receiving pembrolizumab-based therapies for NSCLC. Infected patients had frequent hospitalizations, treatment delays, and poorer survival. ECOG status and anti-infective use at ICI initiation conferred a higher infection risk. Infection prevention and control strategies are needed to ameliorate the risk for infections in patients receiving ICIs.

474: RISK FACTORS FOR EARLY-ONSET MDRO INFECTIONS IN CRITICALLY ILL PATIENTS

Introduction: It is well established that multi-drug resistant organism (MDRO) infections are associated with an increase in morbidity and mortality There are limited studies regarding preemptive identification of patients who present with first onset community acquired MDRO infections. The hypothesis of this study was to identify hypothermia, leukopenia, hypotension, and advanced age as patient risk factors for first onset MDRO infections. Methods: This retrospective, case-matched, observational study at a 550-bed academic medical center evaluated inpatients from January 2019 to December 2021. Patients were included if they had a positive culture result for a gram negative bacteria within 48 hours of hospital admission and required ICU level of care. Patients were separated into two groups based upon if they grew an MDRO or not. Results: A total of 130 participants were included with 65 patients assigned to each the MDRO group and the non-MDRO group. Patients were mostly male (56%), white (58%) and 61 ±15 years. Types of infection included pneumonia (47.7%), urinary tract (32.3%), and blood (4.6%). Enterobacterales sp. were most commonly isolated in both groups n=111 (69%) followed by Pseudomonas aeruginosa n=34 (21%). Comorbid conditions were similar between both groups for organ failure, malignancy, and immunocompromised status. The non-MDRO cohort had a higher incidence of recent anti-infective use (60% vs 35.4%, p< 0.008). Pre-specified risk factors of advanced age (> 65 years), leukopenia (white blood cells count < 4,000), and hypothermia (< 36°C) were not significantly different between groups. Hypotension within the first twenty-four hours of admission was higher in the non-MDRO group (80% vs 63%, P< 0.001). Prior to admission residence other than home was an independent predictor of MDRO infection [OR:3.46 (95% CI 1.49-8.07)]. The incidence of therapeutically active empiric anti-infective regimens was significantly higher in the non-MDRO group (94% vs 32%, P< 0.001). Conclusions: Hypothermia, leukopenia, hypotension, or advanced age were not found to be predictors for MDRO infection. Patients in the non-MDRO group received appropriate antibiotic coverage more frequently than the MDRO group but also had more hypotension on admission.

A descriptive analysis of calls to the NSW Teratogen Information Service regarding use of anti-infectives during pregnancy.

BackgroundMotherSafe is a free telephone-based counseling service for Australian consumers and health-care providers concerned about drug exposures during pregnancy and breastfeeding. Anti-infectives are the most commonly prescribed drugs for pregnant women. This study aims to provide a descriptive analysis of prospectively collected calls received by MotherSafe regarding anti-infective exposures during pregnancy between 2000 and 2020. Aggregate data were examined by type of caller, reason for call, pregnancy category and exposure type. Inductive thematic analysis of the comments recorded by MotherSafe counsellors at the time of call was undertaken.ResultsOver the study period, 25,890 calls related to exposure to anti-infectives during pregnancy (antibiotic, antiviral, and antifungal medications). Calls from patients were dominated by low-risk exposures (pregnancy category A) to drugs while calls from health care professionals related to drugs with limited human information (pregnancy category B3). Analysis of MotherSafe counsellor comments revealed over 200 instances of concerns relating to health care professional advice to the patient. Three themes emerged: incorrect or conflicting advice, poor counselling, and refusal to treat, prescribe or dispense. It is likely that these comments are biased to the negative as patients would not call MotherSafe if they were happy with HCP advice. However, the findings are concerning as they reveal an underlying lack of knowledge in some health care professionals which may have led to undertreatment of patients. This study reinforced the importance of Teratogen Information Services such as MotherSafe in providing counselling and clear communication of evidence-based information to guide decision-making, reducing potential emotional distress in pregnant women, and optimizing maternal, pregnancy and infant outcomes.

Clinical outcomes and treatment patterns of older adults with dementia-related psychosis by dementia type in the United States

BackgroundLittle is known about the incidence of clinical events and treatment patterns among older adults with dementia-related psychosis. Given that dementia-related psychosis comprises various dementia types, this study describes the incidence of clinical events and treatment patterns by dementia type after patients with dementia are diagnosed with psychosis.MethodsAdults aged ≥ 65 years with dementia and newly diagnosed with psychosis were identified in US Medicare claims during 2013–2018. Baseline characteristics were evaluated at the time of the psychosis diagnosis. After the initial psychosis diagnosis, incidence rates (IRs) of clinical events (e.g., falls/fractures, infections, healthcare utilization), mortality, and patterns of antipsychotic treatment were described for each dementia type (Alzheimer’s disease [AD], Parkinson’s disease dementia [PDD], dementia with Lewy bodies [DLB], frontotemporal dementia [FTD], vascular dementia [VD], and unspecified dementia). Daily mean cumulative counts were estimated to describe the incidence of recurrent events over time. Mortality was described using Kaplan–Meier survival curves.ResultsWe identified 484,520 patients with dementia-related psychosis: mean age, 84 years (standard deviation, 7.8); female, 66%. At the time of psychosis diagnosis, the most prevalent type of dementia was unspecified dementia (56%), followed by AD (31%), VD (12%), PDD (10%), DLB (3%), and FTD (< 1%), and most patients had scores indicating severe illness on the Charlson Comorbidity Index (71%) and frailty index (62%). Across all dementia types, IRs (per 100 person-years) were high for emergency department visits, oral anti-infective use, and urinary tract infections after the initial psychosis diagnosis. Patients with DLB had the highest incidence of most clinical outcomes. After 1 year of follow-up, the cumulative probability of death was about 30% for all dementia types, and after 5 years, was about 80% among patients with DLB, VD, AD, or PDD and about 60%-65% among patients with FTD or unspecified dementia.ConclusionsPatients with dementia-related psychosis had a high burden of comorbidities, frailty, emergency department visits, infections, and death. Specifically, after DRP diagnosis, patients with DLB and VD had the highest burden of clinical events of interest.

Attention-Deficit/Hyperactivity Disorder Is Associated With Increased Rates of Childhood Infectious Diseases: A Population-Based Case-Control Study

Infectious diseases (IDs) pose a heavy burden on children. An association between pediatric attention-deficit/hyperactivity disorder (ADHD) and specific IDs has been documented. Our objective was to test the possibility that ADHD is associated with increased likelihood for pediatric IDs at large. A population-based case-control study was conducted using Electronic Medical Records (EMRs) of a national Health Maintenance Organization, Leumit Health Services (LHS). ICD-9/10 criteria were used for all diagnoses. The study population consisted of all children and adolescents (aged 5-18 years), members of LHS between January 1, 2006-June 30, 2021. Case patients met International Classification of Diseases (ICD-9/10) criteria for ADHD. Controls included randomly selected persons without ADHD (2:1 ratio), matched individually by demographic indices. The EMRs retrieved 3 exposure categories: pediatric ID, anti-infective medications use, and number of physician visits. The study was approved by the review board of Shamir Medical Center and the Research Committee of LHS. Cases patients comprised 18,756 participants, with a mean age of 8.3 ± 2.6 years and a male/female ratio of 63%:37%. Matched controls comprised 37,512 participants, with a mean age of 8.3 ± 2.6 years and a male/female ratio of 63%:37%. Demographic variables were similar between the groups. The rates of all IDs were significantly higher in participants with ADHD than in controls and were not restricted to a single body system, including acute respiratory infection (OR= 1.4, 95% CI= 1.3-1.4, p< .001), acute gastroenteritis (OR= 1.3,95% CI 1.3-1.4, p< .001), salmonellosis (OR= 2.8, 95% CI= 2.3-3.5, p< .001), and urinary tract infection (OR= 1.3, 95% CI= 1.2-1.4, p< .001). All anti-infective agents were prescribed significantly more often to children with ADHD. There were significantly higher rates of physician visits for participants with ADHD. Study findings suggest an association between ID and pediatric ADHD Health care providers should be aware of this potential association. The Health and Economic Impact of Treated and Untreated ADHD; https://www.shamir.org/; 005-18-LEU.

Outcomes for Recurrent Mantle Cell Lymphoma Post-Ibrutinib Therapy: A Retrospective Cohort Study from a Japanese Administrative Database.

IntroductionTreatment options in patients with mantle cell lymphoma (MCL) failing ibrutinib are limited, with no standard therapies defined. This study aimed to investigate real-world treatment patterns and outcomes for patients with MCL following ibrutinib.MethodsThis study utilized a de-identified hospital-based claims database (Medical Data Vision) in Japan. Eligible patients were adults who were diagnosed with MCL and had received antitumor drugs between December 2010 and July 2020. Patients were followed from the first antitumor drug treatment until the end of available data up to July 2021. Time-to-event analyses utilized the Kaplan–Meier method. Factors for receiving post-ibrutinib therapy were explored with logistic regression analysis.ResultsOf the 1386 patients who started antitumor drug therapy, 247 patients received and discontinued ibrutinib at any line of therapy. Among them, 137 patients (55.5%) received subsequent therapy. The median age at the end of ibrutinib therapy was 77 (range 42–95), and 44 patients had a dependent activity of daily living (ADL). Factors negatively associated with receiving post-ibrutinib therapy after discontinuation of ibrutinib were age ≥ 75 years (odds ratio [95% CI] 0.46 [0.26–0.80]) and emergency hospital admissions (0.37 [0.17–0.84]). Immediate post-ibrutinib therapy regimens were highly diverse, with BR (bendamustine, rituximab) only prescribed in more than 10% of patients. The median duration of post-ibrutinib therapy was 1.5 months (95% CI 1.07–2.07). The median overall survival from the end of ibrutinib therapy in patients regardless of the receipt of post-ibrutinib therapy (n = 247), in those who did not receive post-ibrutinib therapy (n = 110), and in those who received post-ibrutinib therapy (n = 137) was 5.6 months (95% CI 3.8–8.7), 2.3 months (95% CI 1.2–3.9), and 8.7 months (95% CI 5.6–13.8), respectively. The most common adverse event during post-ibrutinib therapy was infection, with the use of anti-infectives (17%).ConclusionsPatients with MCL previously treated with ibrutinib have poor ability to carry out ADL and experience very poor outcomes. New safe, effective therapies are needed.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02258-3.

Antimicrobial stewardship.

The optimal use of antimicrobials is necessary to slow resistance development and improve patient outcomes. Antimicrobial stewardship (AMS) is a bundle of interventions aimed at promoting the responsible use of antiinfectives. The ICU is an important field of activity for AMS because of high rates of antimicrobial use, high prevalence of resistant pathogens and complex pharmacology. This review discusses aims and interventions of AMS with special emphasis on the ICU. AMS-interventions can improve the quality and quantity of antimicrobial prescribing in the ICU without compromising patient outcomes. The de-escalation of empiric therapy according to microbiology results and the limitation of treatment duration are important steps to reduce resistance pressure. Owing to the complex nature of critical illness, the pharmacological optimization of antimicrobial therapy is an important goal in the ICU. AMS-objectives and strategies are also applicable to patients with sepsis. This is reflected in the most recent guidelines by the Surviving Sepsis Campaign. AMS-interventions need to be adapted to their respective setting and be mindful of local prescribing cultures and prescribers' attitudes. AMS in the ICU is effective and safe. Intensivists should be actively involved in AMS-programs and propagate responsible use of antimicrobials.

Antibiotic and antifungal use in pediatric leukemia and lymphoma patients are associated with increasing opportunistic pathogens and decreasing bacteria responsible for activities that enhance colonic defense.

Due to decreased immunity, both antibiotics and antifungals are regularly used in pediatric hematologic-cancer patients as a means to prevent severe infections and febrile neutropenia. The general effect of antibiotics on the human gut microbiome is profound, yielding decreased diversity and changes in community structure. However, the specific effect on pediatric oncology patients is not well-studied. The effect of antifungal use is even less understood, having been studied only in mouse models. Because the composition of the gut microbiome is associated with regulation of hematopoiesis, immune function and gastrointestinal integrity, changes within the patient gut can have implications for the clinical management of hematologic malignancies. The pediatric population is particularly challenging because the composition of the microbiome is age dependent, with some of the most pronounced changes occurring in the first three years of life. We investigated how antibiotic and antifungal use shapes the taxonomic composition of the stool microbiome in pediatric patients with leukemia and lymphoma, as inferred from both 16S rRNA and metagenome data. Associations with age, antibiotic use and antifungal use were investigated using multiple analysis methods. In addition, multivariable differential abundance was used to identify and assess specific taxa that were associated with multiple variables. Both antibiotics and antifungals were linked to a general decline in diversity in stool samples, which included a decrease in relative abundance in butyrate producers that play a critical role in host gut physiology (e.g., Faecalibacterium, Anaerostipes, Dorea, Blautia),. Furthermore, antifungal use was associated with a significant increase in relative abundance of opportunistic pathogens. Collectively, these findings have important implications for the treatment of leukemia and lymphoma patients. Butyrate is important for gastrointestinal integrity; it inhibits inflammation, reinforces colonic defense, mucosal immunity. and decreases oxidative stress. The routine use of broad-spectrum anti-infectives in pediatric oncology patients could simultaneously contribute to a decline in gastrointestinal integrity and colonic defense while promoting increases in opportunistic pathogens within the patient gut. Because the gut microbiome has been linked to both short-term clinical outcomes, and longer-lasting health effects, systematic characterization of the gut microbiome in pediatric patients during, and beyond, treatment is warranted.

Management of infection in immunocompromised patients

The number of immunosuppressed patients continues to increase worldwide. The main reasons are the demographic development and improved long-term survival, also for patients under immunosuppression. A major cause of hospitalization and mortality among these patients are infections. Their management, including prevention and adequate treatment, plays a crucial role in survival and quality of life, but also with regard to economic factors.Infection management in immunocompromised patients faces new challenges today. Not only the increasing number, but also new groups of patients at risk and an increasingly aging and comorbid population pose problems for the treating physicians. While cancer medicine is no longer determined solely by radiotherapy and chemotherapy, new targeted substances are playing an increasingly important role. In addition, new targeted substances complicate adequate infection prophylaxis due to potential interactions. The worldwide increase in antibiotic-resistant pathogens complicates treatment of bacterial infections, which is associated with increased mortality, especially in the immunocompromised patient population. Further, the disruption of the microbiome shows negative antibiotic-associated effects. Hence the reasonable use of anti-infectives in prophylaxis and therapy is of great importance.There are many recommendations and guidelines for clinicians regarding the management of infections in immunocompromised patients. Overlaps of infectiology, hygiene as well as hematology and oncology sometimes lead to different recommendations. This article provides an overview of the currently existing evidence and guidelines for infection management in immunosuppressed patients.