Risk Of Infection Adverse Events Research Articles

Trends in infectious adverse events after elective optical keratoplasty (PK, EK, and ALK) - Ten years' analysis from an eye bank.

To report the clinical profile and donor characteristics of post-optical keratoplasty adverse events notified at an eye bank. Between January 2013 and December 2022, 37,041 donor corneas were utilized for keratoplasty, of which 16,531 were used for penetrating keratoplasty (PK), 12,171 for endothelial keratoplasty (EK), and 1356 for anterior lamellar keratoplasty (ALK). EK included 10,956 Descemet stripping automated endothelial keratoplasty (DSAEK) and 1215 Descemet membrane endothelial keratoplasty (DMEK). The adverse events reported within the first 6 weeks of optical keratoplasty were analyzed for donor-related parameters. A total of 41 (0.11%) recipients had post-keratoplasty infections. Of these, 33 occurred after EK (29 after DSAEK, and four after DMEK), two after ALK, and six after PK. The clinical presentation was keratitis alone in 16 eyes and associated with endophthalmitis in 25 eyes. The organisms isolated were gram-negative bacteria in 26 eyes, fungus in eight eyes, gram-positive bacteria in four eyes, mixed infection in five eyes, and microbiology inconclusive in seven eyes. The majority (78%) of the gram-negative infections were due to multidrug-resistant organisms. Most (88%) donor corneas were harvested from hospital premises. The most common cause of donor mortality was trauma. The median duration of presentation from surgery was 4.46 (range: 1-30) days. The death to preservation time was 4.18 (1.5-7.65) hours. The death to utilization time was 3 (2-4.7) days. The overall risk of infectious adverse events after keratoplasty was 0.11%, ranging from 0.08% to 0.36%. Most (80.4%) of the adverse events occurred after EK. The majority (78.9%) of the adverse events were of bacterial etiology, of which gram-negative infections (68.4%) were the most common. The trends and microbiological spectrum of organisms associated with infections should be thoroughly documented in eye banks to gain insights and formulate guidelines on the management of adverse events.

2722. Risk of Infectious Adverse Events of Venetoclax Therapy in the Treatment of Hematologic Malignancies: A Systematic Review and Bayesian Meta-Analysis of Randomized Controlled Trials

Abstract Background Venetoclax is a small molecule inhibitor of BCL-2 used in the treatment of acute myelogenous leukemia and chronic lymphocytic leukemia. Recent post-marketing studies on venetoclax suggested that it may predispose to opportunistic infections (OIs). We sought to systematically review the randomized controlled trial (RCT) evidence on venetoclax to assess whether it predisposes patients to infectious adverse events (IAEs) and neutropenia. Methods We systematically reviewed the RCTs comparing venetoclax therapy to active (i.e., a regimen with additional anti-cancer agents) or placebo controls in patients with hematologic malignancies, irrespective of treatment line. Data on IAEs and neutropenia were pooled by Bayesian meta-analysis and we computed the probability of any increased risk in infectious or neutropenic complications (Risk Ratio [RR] >1). Subgroup analyses were conducted based on treatment line, use of an inactive comparator, malignancy type, and prophylaxis strategy. Additionally, we pooled the incidence rates of fatal OIs between venetoclax and comparator arms and compared them by univariate meta-regression. Results Seven RCTs were included comprising 2067 patients. In venetoclax versus comparator regimens there was a 81.1% probability of any increase in IAEs (RR=1.14, 95% Confidence Interval [95%CI]=0.76-1.66). The probabilities of venetoclax increasing the risk of grade 3-5 and fatal IAEs were 86.6% (RR=1.16, 95%CI=0.86-1.55) and 81.1% (RR=1.40, 95%CI=0.66-2.94), respectively. There was a 97.2% likelihood that venetoclax increased the risk of grade 3-5 neutropenia (RR=1.44, 95%CI=1.01-2.10). Venetoclax treatment did not increase the incidence of fatal OIs (P=0.55). Conclusion Our results suggest that venetoclax likely increases the risk of high-grade neutropenia and IAEs overall, but not fatal OIs. However, our analyses did not identify any specific IAEs that would benefit from routine anti-infective prophylaxis or pre-emptive testing. Disclosures Michael Sebag, MD, PhD, Amgen: Advisor/Consultant|BMS: Advisor/Consultant|Focus Therapeutics: Advisor/Consultant|Gilead: Advisor/Consultant|Janssen: Advisor/Consultant|Novartis: Advisor/Consultant|Pfizer: Advisor/Consultant|Sanofi: Advisor/Consultant Matthew Cheng, MD, Amplyx Pharmaceuticals: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Honoraria|Cidara Therapeutics: Grant/Research Support|GEn1E lifesciences: Advisor/Consultant|GEn1E lifesciences: Stocks/Bonds|Kanvas Biosciences, Inc.: Board Member|Kanvas Biosciences, Inc.: Pending patents|Kanvas Biosciences, Inc.: Ownership Interest|Merck: Honoraria|nomic bio: Advisor/Consultant|nomic bio: Stocks/Bonds|Pfizer: Honoraria|Scynexis Inc.: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Honoraria

LBA02-10 ASSESSING THE RISKS OF A POSITIVE URINE CULTURE IN UNCOMPLICATED RENAL COLIC PATIENTS

You have accessJournal of UrologyCME1 May 2022LBA02-10 ASSESSING THE RISKS OF A POSITIVE URINE CULTURE IN UNCOMPLICATED RENAL COLIC PATIENTS Nikhile Mookerji, Matthew Mancuso, Vardhil Gandhi, Efrem Violato, Stacey Broomfield, Tim Wollin, Trevor Schuler, and Shubha De Nikhile MookerjiNikhile Mookerji More articles by this author , Matthew MancusoMatthew Mancuso More articles by this author , Vardhil GandhiVardhil Gandhi More articles by this author , Efrem ViolatoEfrem Violato More articles by this author , Stacey BroomfieldStacey Broomfield More articles by this author , Tim WollinTim Wollin More articles by this author , Trevor SchulerTrevor Schuler More articles by this author , and Shubha DeShubha De More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002670.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Though septic stones are well recognized as a medical emergency, patients with uncomplicated renal colic (without systemic inflammatory responses or renal impairment) and positive urine cultures pose a dilemma in management considerations. Therefore, the objective of this study is to: 1) Assess the rate of ‘incidental’ positive urine cultures in patients with ureteral stones referred to our Stone Clinic. 2) Determine the risk of infectious adverse events (IAE) in patients with ureteral stones and positive urine cultures. METHODS: A retrospective chart review was performed for all Acute Stone Clinic referrals between November 10, 2019 and October 1, 2020. Urgent referrals necessitating immediate intervention were excluded. Demographics, investigations, procedures, unscheduled visits, and IAE were all documented. Descriptive statistics were used to group patients based on their urine cultures (UC). RESULTS: Over the study period 1029 patients were identified, and 35.4% (n=374) of them had urine cultures (UC) drawn at presentation. Of the 655 patients without UC, 0.6% (n=6) eventually developed sepsis and required urgent renal decompression. 87% (n=333) of UC completed at presentation were negative (no growth or mixed flora), and none of these patients went on to have an IAE. Of the 13% of urine cultures that were positive (n=39) only 2 IAEs (5.13%) were identified, 2-30 days after initial presentation. Both patients had normal acute phase reactants (WBC, CRP) and a history of recurrent UTIs. CONCLUSIONS: Approximately one third of patients referred to our Acute Stone clinic had UC at presentation, with an overall delayed IAE rate of 0.7%. Of those with positive urine cultures, only 5% experienced an IAE, suggesting conservative management may be a reasonable consideration in this patient population. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1045 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nikhile Mookerji More articles by this author Matthew Mancuso More articles by this author Vardhil Gandhi More articles by this author Efrem Violato More articles by this author Stacey Broomfield More articles by this author Tim Wollin More articles by this author Trevor Schuler More articles by this author Shubha De More articles by this author Expand All Advertisement PDF DownloadLoading ...

Risk of Adverse Events After Anti-TNF Treatment for Inflammatory Rheumatological Disease. A Meta-Analysis.

Background: Adalimumab, golimumab, infliximab, certolizumab, and etanercept are five anti-tumor necrosis factor (anti-TNF) medicines that have been approved for use in rheumatology. Apart from their well-established therapeutic usefulness, -it is unclear to what extent -they are linked to an increased risk of various side effects. The present meta-analysis was carried out to assess the risk of infection and other side effects after anti-TNF- α for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Methods: We searched PubMed, Cinahl (via Ebsco), Scopus, and Web of Sciences databases for trials comparing anti-TNF medications to placebo or no therapy in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis from August 2006 to August 2020. A total of 23 articles were used for meta-analysis. The Cochrane Collaboration’s risk of bias tool was used to assess the methodological quality of the included studies. In addition, a random-effects model was used to calculate the pooled odds ratio, and Forest plots were constructed to determine the risk of infections and cancer following the use of anti-TNF treatment. Results: Treatment with anti-TNFα agents resulted in an increase in the risk of serious infections (OR: 1.72, 95% CI: 1.56–1.90, p < 0.00001) and an increase in cancer risk (OR: 1.36, 95% CI: 1.20–1.53, p < 0.00001) whereas the risk of developing tuberculosis was not significantly different with anti-TNFα agents versus those without treatment with anti-TNFα agents (OR: 2.55, 95% CI: 0.40–16.23, p = 0.32) although the number of studies is limited to make a definitive conclusion. The risk of bias of the included studies was unclear to high across most domains, and there was evidence of publication bias for most outcomes. Conclusion: The present meta-analysis suggests an increased risk of infectious adverse events, including overall adverse events and cancer following anti-TNFα treatment, whereas the risk of tuberculosis was not significantly different. Although anti-TNF agents have shown promise to treat inflammatory conditions, their use should be balanced by the risk-benefit ratio as suggested by the meta-analysis.

Endoscopy Is Not Associated with Infectious Adverse Events After Hematopoietic Cell Transplantation: A Retrospective Cohort Study.

Patients with recent hematopoietic cell transplantation (HCT) are considered high risk for gastrointestinal endoscopy due to the potential for procedural bacterial translocation. Prior studies investigating these risks do not account for the higher baseline rate of infectious complications among those who are immunocompromised. We performed a retrospective cohort study of patients with recent HCT who underwent endoscopy and their matched controls who did not undergo endoscopy. We identified patients who underwent HCT followed by upper and/or lower endoscopy at the University of Pennsylvania from 2000 to 2018. Individuals were matched 1:1 by age, sex, and type of HCT to controls who underwent HCT without subsequent endoscopy. Infectious adverse events were assessed by Sepsis-3 and Sepsis-2 criteria. Factors associated with infectious adverse events after endoscopy/index date were assessed using multivariable conditional logistic regression. We identified 149 patients who underwent HCT and endoscopy and 149 matched controls who underwent HCT without endoscopy. Sepsis-3 infectious adverse events occurred in 3.4% of patients in each group. Sepsis-2 infectious adverse events occurred in 20.1% of patients who underwent endoscopy compared to 19.5% of controls. There was no association between endoscopy and Sepsis-2 infectious adverse events in the multivariable regression analysis (adjusted odds ratio 1.65, 95% CI 0.51-5.26). When compared to controls with similar immune statuses, patients who underwent endoscopy after HCT did not have a higher risk of infectious adverse events. These results may inform clinical decision making regarding the risks and benefits of endoscopic management after HCT.

Rituximab exhibits a better safety profile when used as a first line of treatment for pemphigus vulgaris: A retrospective study

BackgroundPemphigus is an autoimmune disease that is challenging to treat and has few available therapeutic options. Recently, several studies have demonstrated that rituximab may be an efficacious first-line treatment in newest guidelines. AimTo compare the side effect profiles of rituximab administered after a course of immunosuppressant agents versus as a first-line therapy and evaluate the impact of patient characteristics and disease severity indices on occurrence of adverse effects. MethodsA retrospective cross-sectional study was conducted on 999 patients with pemphigus vulgaris who received rituximab either as a first-line treatment or after conventional adjuvant therapies. The occurrence of partial or complete remission as well as the incidence of drug-related adverse effects were evaluated and compared between the two groups. ResultsSmoking, pulmonary comorbidity, and mucocutaneous phenotype were associated with an increased risk of developing infectious complications by 12.49, 5.79, and 2.37 fold, respectively. These associations were more prominent among those who received rituximab after immunosuppressant agents. ConclusionsEarly use of rituximab benefits pemphigus patients, especially those with a mucocutaneous phenotype, pulmonary comorbidity, or history of smoking, and reduces their risk of infectious adverse events.

Ten-year experience with rituximab for induction and maintenance therapy in patients with ANCA-associated systemic vasculitis

Rituximab (RTM), a monoclonal antibody against CD20+ receptors on the membrane of B-cells, is becoming increasingly important for the induction and maintenance treatment of antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis (ANCA-SV). The challenge facing us is to optimize its efficacy, while limiting adverse events (AEs).Objective: to evaluate the efficacy and safety of RTM used for the induction and maintenance of remission in ANCA-SV on the basis of 10-year single-center experience.Patients and methods. The paper presents the authors’ own 10-year experience with RTM used for the induction and maintenance of remission in 103 patients with ANCA-SV, including granulomatosis with polyangiitis (GPA) (n=58), microscopic polyangiitis (MPA) (n=35), ANCA-positive eosinophilic granulomatosis with polyangiitis (EGPA) (n=4), and ANCA-negative EGPA (n=6). The duration of a follow-up after initiation of RTM treatment was more than a year (with the exception of death cases) and averaged 25 to 58 months in different ANCA-SV groups. The patients were monitored every 3 months. The intervals between repeated cycles were dependent on the time course of changes in clinical and laboratory parameters. The mean cumulative RTM dose exceeded 3 g; 75% of patients received repeated cycles of RMT usually at a cumulative dose of 0.5–1.0 g at a 4–12-month interval.Results and discussion. Repeated RTM cycles for ANCA-SV were highly effective; the clinical response rate was 97%, while 90–93% of patients with different types of ANCA-SV achieved complete clinical response. Despite the fact that the examined population included a high proportion of patients with a severe or refractory course of the disease; ANCA-SV patients showed 10% mortality rates during the entire follow-up period. Anti-B-cell therapy with RTM is of great importance in obtaining long-term optimal results, making it possible to improve ANCA-SV control and to minimize the cumulative dose of glucocorticoids. Since in ANCA-SV, the use of repeated cycles of RTM, including that at a reduced dose of 0.5 g, contributes to the higher efficiency of treatment and to the lower risk of relapse, it is advisable to perform long-term (≥2 years) RTM therapy, by controlling the parameters of clinical and immunological activities and the levels of circulating CD20+ B cells and serum immunoglobulins, deficiency of which can potentially increase the risk of infectious AEs. When planning RTM therapy, it is necessary to consider the specific features of the safety profile for individual nosological entities and to make a careful appropriate monitoring of ANCA-SV patients receiving RTM. The risk of late-onset neutropenia was highest in patients with all types of ANCA-SV (3–10%). Infections in patients with GPA and MPA constitute a substantial proportion (10–11%) in serious AEs. Management of EGPA patients requires alertness to the risk of infusion-related reactions, primarily bronchospasm.Conclusion. There is a need for further investigation of an anti-B-cell therapy strategy, including the efficacy and safety of RTM in ANCA-SV and for clarification of indications and optimal RTM treatment regimens.

Clinical Review on the Utility of Fecal Microbiota Transplantation in Immunocompromised Patients.

Fecal microbiota transplantation (FMT) represents a promising management modality for Clostridium difficile infection (CDI). In immunocompromised patients, FMT is utilized for CDI as well as emerging non-CDI indications such as inflammatory bowel disease and graft versus host disease. PURPOSE OF REVIEW: This review aims to shed light on the safety and efficacy of FMT in immunocompromised patients, including patients suffering for human immunodeficiency virus infection, solid organ and hematopoietic stem cell transplant recipients, cancer patients, and patients on immunosuppressive therapies. RECENT FINDINGS: Though the body of evidence concerning the use of FMT in immunocompromised is growing, no clinical trials exist to date. Present literature weighs in favor of FMT in immunocompromised patients, with an acceptable adverse effect profile and minimal risk of infectious adverse events. Further large scale studies and randomized controlled trials to validate the utility of FMT in immunocompromised individuals will be a welcomed endeavor.

Contemporary Toxicity Profile of Breast Brachytherapy Versus External Beam Radiation After Lumpectomy for Breast Cancer

We compared toxicities after brachytherapy versus external beam radiation therapy (EBRT) in contemporary breast cancer patients. Using MarketScan healthcare claims, we identified 64,112 women treated from 2003 to 2012 with lumpectomy followed by radiation (brachytherapy vs EBRT). Brachytherapy was further classified by multichannel versus single-channel applicator approach. We identified the risks and predictors of 1-year infectious and noninfectious postoperative adverse events using logistic regression and temporal trends using Cochran-Armitage tests. We estimated the 5-year Kaplan-Meier cumulative incidence of radiation-associated adverse events. A total of 4522 (7.1%) patients received brachytherapy (50.2% multichannel vs 48.7% single-channel applicator). The overall risk of infectious adverse events was higher after brachytherapy than after EBRT (odds ratio [OR]=1.21; 95% confidence interval [CI] 1.09-1.34, P<.001). However, over time, the frequency of infectious adverse events after brachytherapy decreased, from 17.3% in 2003 to 11.6% in 2012, and was stable after EBRT at 9.7%. Beyond 2007, there were no longer excess infections with brachytherapy (P=.97). The overall risk of noninfectious adverse events was higher after brachytherapy than after EBRT (OR=2.27; 95% CI 2.09-2.47, P<.0001). Over time, the frequency of noninfectious adverse events detected increased: after multichannel brachytherapy, from 9.1% in 2004 to 18.9% in 2012 (Ptrend=.64); single-channel brachytherapy, from 12.8% to 29.8% (Ptrend<.001); and EBRT, from 6.1% to 10.3% (Ptrend<.0001). The risk was significantly higher with single-channel than with multichannel brachytherapy (hazard ratio=1.32; 95% CI 1.03-1.69, P=.03). Of noninfectious adverse events, 70.9% were seroma. Seroma significantly increased breast pain risk (P<.0001). Patients with underlying diabetes, cardiovascular disease, and treatment with chemotherapy had increased infectious and noninfectious adverse events. The 5-year incidences of fat necrosis, breast pain, and rib fracture were slightly higher after brachytherapy than after EBRT (13.7% vs 8.1%, 19.4% vs 16.0%, and 1.6% vs 1.3%, respectively), but the risks were not significantly different for multichannel versus single-channel applicators. Toxicities after breast brachytherapy were distinct from those after EBRT. Temporal toxicity trends may reflect changing technology and evolving practitioner experience with brachytherapy.