Neuroinvasive Bacillus cereus Infection in Immunocompromised Hosts: Epidemiologic Investigation of 5 Patients With Acute Myeloid Leukemia.

Background: Bacillus cereus is a ubiquitous gram-positive rod-shaped bacterium that can cause sepsis and neuroinvasive disease in patients with acute leukemia or neutropenia. Methods: A single-center retrospective review was conducted to evaluate patients with acute leukemia, positive blood or cerebrospinal fluid test results for B cereus, and abnormal neuroradiographic findings between January 2018 and October 2022. Infection control practices were observed, environmental samples obtained, a dietary case-control study completed, and whole genome sequencing performed on environmental and clinical Bacillus isolates. Results: Five patients with B cereus neuroinvasive disease were identified. All patients had acute myeloid leukemia (AML), were receiving induction chemotherapy, and were neutropenic. Neurologic involvement included subarachnoid or intraparenchymal hemorrhage or brain abscess. All patients were treated with ciprofloxacin and survived with limited or no neurologic sequelae. B cereus was identified in 7 of 61 environmental samples and 1 of 19 dietary protein samples-these were unrelated to clinical isolates via sequencing. No point source was identified. Ciprofloxacin was added to the empiric antimicrobial regimen for patients with AML and prolonged or recurrent neutropenic fevers; no new cases were identified in the ensuing year. Conclusions: B cereus is ubiquitous in the hospital environment, at times leading to clusters with unrelated isolates. Fastidious infection control practices addressing a range of possible exposures are warranted, but their efficacy is unknown and they may not be sufficient to prevent all infections. Thus, including B cereus coverage in empiric regimens for patients with AML and persistent neutropenic fever may limit the morbidity of this pathogen.

Mycobacterium abscessus Cluster in Cardiac Surgery Patients Potentially Attributable to a Commercial Water Purification System.

BACKGROUND: Nontuberculous mycobacteria are water-avid pathogens that are associated with nosocomial infections. OBJECTIVE: To describe the analysis and mitigation of a cluster of Mycobacterium abscessus infections in cardiac surgery patients. DESIGN: Descriptive study. SETTING: Brigham and Women's Hospital, Boston, Massachusetts. PARTICIPANTS: Four cardiac surgery patients. INTERVENTION: Commonalities among cases were sought, potential sources were cultured, patient and environmental specimens were sequenced, and possible sources were abated. MEASUREMENTS: Description of the cluster, investigation, and mitigation. RESULTS: Whole-genome sequencing confirmed homology among clinical isolates. Patients were admitted during different periods to different rooms but on the same floor. There were no common operating rooms, ventilators, heater-cooler devices, or dialysis machines. Environmental cultures were notable for heavy mycobacterial growth in ice and water machines on the cluster unit but little or no growth in ice and water machines in the hospital's other 2 inpatient towers or in shower and sink faucet water in any of the hospital's 3 inpatient towers. Whole-genome sequencing confirmed the presence of a genetically identical element in ice and water machine and patient specimens. Investigation of the plumbing system revealed a commercial water purifier with charcoal filters and an ultraviolet irradiation unit leading to the ice and water machines in the cluster tower but not the hospital's other inpatient towers. Chlorine was present at normal levels in municipal source water but was undetectable downstream from the purification unit. There were no further cases after high-risk patients were switched to sterile and distilled water, ice and water machine maintenance was intensified, and the commercial purification system was decommissioned. LIMITATION: Transmission pathways were not clearly characterized. CONCLUSION: Well-intentioned efforts to modify water management systems may inadvertently increase infection risk for vulnerable patients. PRIMARY FUNDING SOURCE: National Institutes of Health.

Impact of Cancer History on Outcomes Among Hospitalized Patients with COVID-19.

BACKGROUND: Early reports suggested increased mortality from COVID-19 in patients with cancer but lacked rigorous comparisons to patients without cancer. We investigated whether a current cancer diagnosis or cancer history is an independent risk factor for death in hospitalized patients with COVID-19. PATIENTS AND METHODS: We identified patients with a history of cancer admitted to two large hospitals between March 13, 2020, and May 10, 2020, with laboratory-confirmed COVID-19 and matched them 1:2 to patients without a history of cancer. RESULTS: Men made up 56.2% of the population, with a median age of 69 years (range, 30-96). The median time since cancer diagnosis was 35.6 months (range, 0.39-435); 80% had a solid tumor, and 20% had a hematologic malignancy. Among patients with cancer, 27.8% died or entered hospice versus 25.6% among patients without cancer. In multivariable analyses, the odds of death/hospice were similar (odds ratio [OR], 1.09; 95% confidence interval [CI], 0.65-1.82). The odds of intubation (OR, 0.46; 95% CI, 0.28-0.78), shock (OR, 0.54; 95% CI, 0.32-0.91), and intensive care unit admission (OR, 0.51; 95% CI, 0.32-0.81) were lower for patients with a history of cancer versus controls. Patients with active cancer or who had received cancer-directed therapy in the past 6 months had similar odds of death/hospice compared with cancer survivors (univariable OR, 1.31; 95% CI, 0.66-2.60; multivariable OR, 1.47; 95% CI, 0.69-3.16). CONCLUSION: Patients with a history of cancer hospitalized for COVID-19 had similar mortality to matched hospitalized patients with COVID-19 without cancer, and a lower risk of complications. In this population, patients with active cancer or recent cancer treatment had a similar risk for adverse outcomes compared with survivors of cancer. IMPLICATIONS FOR PRACTICE: This study investigated whether a current cancer diagnosis or cancer history is an independent risk factor for death or hospice admission in hospitalized patients with COVID-19. Active cancer, systemic cancer therapy, and a cancer history are not independent risk factors for death from COVID-19 among hospitalized patients, and hospitalized patients without cancer are more likely to have severe COVID-19. These findings provide reassurance to survivors of cancer and patients with cancer as to their relative risk of severe COVID-19, may encourage oncologists to provide standard anticancer therapy in patients at risk of COVID-19, and guide triage in future waves of infection.

Change the channel: CysLoop receptor antagonists from nature.

Vertebrate and invertebrate ligand-gated ion channels (LGICs) exhibit significant structural homology and often share ligands. As a result, ligands with activity against one class can be brought to bear against another, including for development as insecticides. Receptor selectivity, metabolism and distribution must then be optimized using chemical synthesis. Here we review natural products (NPs) that ligate and inhibit the Cys-loop family of LGICs, which benefit from the unique physicochemical properties of natural product space but often present a high synthetic burden. Recent advances in chemical synthesis, however, have opened practical entries into these complex structures, several of which are highlighted. © 2020 Society of Chemical Industry.

Treating the SARS-CoV-2-positive patient with cancer: A proposal for a pragmatic and transparent ethical process.

The treatment of patients with cancer who test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses unique challenges. In this commentary, the authors describe the ethical rationale and implementation details for the creation of a novel, multidisciplinary treatment prioritization committee, including physicians, frontline staff, an ethicist, and an infectious disease expert. Organizational obligations to health care workers also are discussed. The treatment prioritization committee sets a threshold of acceptable harm to patients from decreased cancer control that is justified to reduce risk to staff. The creation of an ethical, consistent, and transparent decision-making process involving such frontline stakeholders is essential as departments across the country are faced with decisions regarding the treatment of SARS-CoV-2-positive patients with cancer.

Risk of Latent Tuberculosis Reactivation After Hematopoietic cell Transplantation.

There were no cases of tuberculosis in a cohort of 2531 patients who underwent hematopoietic cell transplantation from 2010 to 2015 after 7323 person-years of follow up (95% confidence interval [CI], 0.0-0.05 cases/100 person-years), including 29 (1.15%) patients with untreated latent tuberculosis after 89 person-years of follow-up (95% CI, 0.0-4.06 cases/100 person-years).

Assessment of Quadrivalent Human Papillomavirus Vaccine Safety Using the Self-Controlled Tree-Temporal Scan Statistic Signal-Detection Method in the Sentinel System.

The self-controlled tree-temporal scan statistic-a new signal-detection method-can evaluate whether any of a wide variety of health outcomes are temporally associated with receipt of a specific vaccine, while adjusting for multiple testing. Neither health outcomes nor postvaccination potential periods of increased risk need be prespecified. Using US medical claims data in the Food and Drug Administration's Sentinel system, we employed the method to evaluate adverse events occurring after receipt of quadrivalent human papillomavirus vaccine (4vHPV). Incident outcomes recorded in emergency department or inpatient settings within 56 days after first doses of 4vHPV received by 9- through 26.9-year-olds in 2006-2014 were identified using International Classification of Diseases, Ninth Revision, diagnosis codes and analyzed by pairing the new method with a standard hierarchical classification of diagnoses. On scanning diagnoses of 1.9 million 4vHPV recipients, 2 statistically significant categories of adverse events were found: cellulitis on days 2-3 after vaccination and "other complications of surgical and medical procedures" on days 1-3 after vaccination. Cellulitis is a known adverse event. Clinically informed investigation of electronic claims records of the patients with "other complications" did not suggest any previously unknown vaccine safety problem. Considering that thousands of potential short-term adverse events and hundreds of potential risk intervals were evaluated, these findings add significantly to the growing safety record of 4vHPV.

Evaluation of the risk of venous thromboembolism after quadrivalent human papillomavirus vaccination among US females.

After the Food and Drug Administration (FDA) licensed quadrivalent human papillomavirus vaccine (HPV4) in 2006, reports suggesting a possible association with venous thromboembolism (VTE) emerged from the Vaccine Adverse Event Reporting System and the Vaccine Safety Datalink. Our objective was to determine whether HPV4 increased VTE risk. The subjects were 9-26-year-old female members of five data partners in the FDA's Mini-Sentinel pilot project receiving HPV4 during 2006-2013. The outcome was radiologically confirmed first-ever VTE among potential cases identified by diagnosis codes in administrative data during Days 1-77 after HPV4 vaccination. With a self-controlled risk interval design, we compared counts of first-ever VTE in risk intervals (Days 1-28 and Days 1-7 post-vaccination) and control intervals (Days 36-56 for Dose 1 and Days 36-63 for Doses 2 and 3). Combined hormonal contraceptive use was treated as a potential confounder. The main analyses were: (1) unadjusted for time-varying VTE risk from contraceptive use, (2) unadjusted but restricted to cases without such time-varying risk, and (3) adjusted by incorporating the modeled risk of VTE by week of contraceptive use in the analysis. Of 279 potential VTE cases identified following 1,423,399 HPV4 doses administered, 225 had obtainable charts, and 53 were confirmed first-ever VTE. All 30 with onsets in risk or control intervals had known risk factors for VTE. VTE risk was not elevated in the first 7 or 28 days following any dose of HPV in any analysis (e.g. relative risk estimate (95% CI) from both unrestricted analyses, for all-doses, 28-day risk interval: 0.7 (0.3-1.4)). Temporal scan statistics found no clustering of VTE onsets after any dose. Thus, we found no evidence of an increased risk of VTE associated with HPV4 among 9-26-year-old females. A particular strength of this evaluation was its control for both time-invariant and contraceptive-related time-varying potential confounding.

Post-licensure rapid immunization safety monitoring program (PRISM) data characterization.

BACKGROUND: The Post-Licensure Rapid Immunization Safety Monitoring (PRISM) program is the immunization safety monitoring component of FDA's Mini-Sentinel project, a program to actively monitor the safety of medical products using electronic health information. FDA sought to assess the surveillance capabilities of this large claims-based distributed database for vaccine safety surveillance by characterizing the underlying data. METHODS: We characterized data available on vaccine exposures in PRISM, estimated how much additional data was gained by matching with select state and local immunization registries, and compared vaccination coverage estimates based on PRISM data with other available data sources. We generated rates of computerized codes representing potential health outcomes relevant to vaccine safety monitoring. Standardized algorithms including ICD-9 codes, number of codes required, exclusion criteria and location of the encounter were used to obtain the background rates. RESULTS: The majority of the vaccines routinely administered to infants, children, adolescents and adults were well captured by claims data. Immunization registry data in up to seven states comprised between 5% and 9% of data for all vaccine categories with the exception of 10% for hepatitis B and 3% and 4% for rotavirus and zoster respectively. Vaccination coverage estimates based on PRISM's computerized data were similar to but lower than coverage estimates from the National Immunization Survey and Healthcare Effectiveness Data and Information Set. For the 25 health outcomes of interest studied, the rates of potential outcomes based on ICD-9 codes were generally higher than rates described in the literature, which are typically clinically confirmed cases. CONCLUSION: PRISM program's data on vaccine exposures and health outcomes appear complete enough to support robust safety monitoring.

Polymorphisms in the gene that encodes the iron transport protein ferroportin 1 influence susceptibility to tuberculosis.

BACKGROUND: We studied the association between iron intake and polymorphisms in the iron transporter gene SLC40A1 and the risk of tuberculosis. METHODS: We compared iron intake, the frequency of SLC40A1 mutations, and interactions among these variables among 98 tuberculosis patients and 125 controls in Kwazulu-Natal, South Africa. RESULTS: Four SLC40A1 single-nucleotide polymorphisms (SNPs) were associated with an increased risk of tuberculosis and 1 SNP with reduced risk. We also found a gene-environment interaction for 4 nonexonic SNPs and iron intake. CONCLUSIONS: This pilot study demonstrated an association between polymorphisms in SLC40A1 and tuberculosis and provided evidence of an interaction between dietary iron and SLC40A1.

Bi-directional screening for tuberculosis and diabetes: a systematic review.

OBJECTIVE: To assess the yield of finding additional TB or diabetes mellitus (DM) cases through systematic screening and to determine the effectiveness of preventive TB therapy in people with DM. METHODS: We systematically reviewed studies that had screened for active TB or implemented preventive therapy for TB among people with DM, and those that screened for DM among patients with TB. We searched published literature through PubMed and EMBASE and included studies that reported the number of TB cases identified among people with DM; the number of DM cases identified among patients with TB, or the relative incidence of TB between people with DM who received a TB prophylaxis and those who did not. We assessed the yield of screening by estimating the prevalence of TB or DM in each study, the prevalence ratio and difference where comparison populations were available, and the number of persons to screen to detect an additional case of TB or DM. RESULTS: Twelve studies on screening for TB in people with DM and 18 studies on screening for DM in patients with TB met our inclusion criteria. Screening for TB in persons with DM demonstrated that TB prevalence in this population is high, ranging from 1.7% to 36%, and increasing with rising TB prevalence in the underlying population as well as with DM severity. Screening patients with TB for DM also yielded high prevalences of DM ranging from 1.9% to 35%. Two studies examining the role of TB preventive therapy in people with DM did not provide sufficient details for clear evidence of the effectiveness. CONCLUSION: Active screening leads to the detection of more TB and DM with varying yield. This review highlights the need for further research in screening and preventive therapy.

The syphilis reactor grid: help or hindrance for syphilis surveillance?

BACKGROUND: Health departments use reactor grids (sex, age, and serologic test for syphilis [STS] titer criteria) to determine which persons to evaluate for untreated syphilis. GOAL: The goal of the study was to assess reactor grid performance in Chicago and reactor grid use nationally in 1999 to 2000. STUDY DESIGN: We reviewed Chicago health department records to identify characteristics of persons with a reactive STS excluded from evaluation by reactor grid criteria and syphilis cases not meeting evaluation criteria. We surveyed health departments regarding reactor grid use. RESULTS: Of persons with a reactive STS, 46% did not meet criteria for health department evaluation, including 62% of men, 29% of women, and 21% with titers > or =1:8. The reactor grid would have excluded 17% of primary syphilis cases. Overall, 82% of health departments use reactor grids. CONCLUSIONS: Reactor grids are widely used and may exclude persons with infectious syphilis from health department evaluation, especially men. The impact of reactor grid use on syphilis control and surveillance in the United States should be evaluated.