Characterization of predictors of ESBL-producing enterobacteriaceae in urine cultures of emergency department patients.

STUDY OBJECTIVE: With increasing prevalence of extended-spectrum beta-lactamase-producing enterobacteriaceae (ESBLE), more reliable identification of predictors for ESBLE urinary tract infection (UTI) in the emergency department (ED) is needed. Our objective was to evaluate risk factors and their predictive ability for ED patients with ESBLE UTI. METHODS: This was a retrospective case-control study at an urban academic medical center. Microbiology reports identified adult ED patients with positive urine cultures from 2015-2018. Inclusion criteria were diagnosis of UTI with monomicrobial enterobacteriaceae culture growth. Exclusions were cultures with carbapenemase-resistant enterobacteriaceae or urinary colonization. Collected variables included demographics, comorbidities, and recent medical history. Patient disposition, urine culture susceptibilities, presence of ESBLE, empiric antibiotics, and therapy modifications were collected. Patients were stratified based on ESBLE status and analyzed via descriptive statistics. The data were divided into 2 parts: the first used to identify possible predictors of ESBLE UTI and the second used to validate an additive scoring system. RESULTS: Of 466 patients, 16.3% had ESBLE urine culture growth and 83.7% did not; 39.5% of ESBLE patients required antibiotic therapy modification, as compared to 6.4% of ESBLE negative patients (odds ratio [OR] 9.5; confidence interval [CI] 8.9-10.1). Independent predictors of ESBLE UTI were IV antibiotics within 1 year (OR 5.4; CI 2.1-12.8), surgery within 90 days (OR 6.4; CI 1.5-27.8), and current refractory UTI (OR 8.5; CI 2.0-36.6). CONCLUSION: Independent predictors of ESBLE UTI in emergency department patients included IV antibiotics within 1 year, surgery within 90 days, and current refractory UTI.

Air pollution particulate matter alters antimycobacterial respiratory epithelium innate immunity.

Inhalation exposure to indoor air pollutants and cigarette smoke increases the risk of developing tuberculosis (TB). Whether exposure to ambient air pollution particulate matter (PM) alters protective human host immune responses against Mycobacterium tuberculosis has been little studied. Here, we examined the effect of PM from Iztapalapa, a municipality of Mexico City, with aerodynamic diameters below 2.5 µm (PM2.5) and 10 µm (PM10) on innate antimycobacterial immune responses in human alveolar type II epithelial cells of the A549 cell line. Exposure to PM2.5 or PM10 deregulated the ability of the A549 cells to express the antimicrobial peptides human ß-defensin 2 (HBD-2) and HBD-3 upon infection with M. tuberculosis and increased intracellular M. tuberculosis growth (as measured by CFU count). The observed modulation of antibacterial responsiveness by PM exposure was associated with the induction of senescence in PM-exposed A549 cells and was unrelated to PM-mediated loss of cell viability. Thus, the induction of senescence and downregulation of HBD-2 and HBD-3 expression in respiratory PM-exposed epithelial cells leading to enhanced M. tuberculosis growth represent mechanisms by which exposure to air pollution PM may increase the risk of M. tuberculosis infection and the development of TB.

Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A.

IL-22 has both proinflammatory and tissue-protective properties depending on the context in which it is expressed. However, the factors that influence the functional outcomes of IL-22 expression remain poorly defined. We demonstrate that after administration of a high dose of bleomycin that induces acute tissue damage and airway inflammation and is lethal to wild-type (WT) mice, Th17 cell-derived IL-22 and IL-17A are expressed in the lung. Bleomycin-induced disease was ameliorated in Il22-/- mice or after anti-IL-22 monoclonal antibody (mAb) treatment of WT mice, indicating a proinflammatory/pathological role for IL-22 in airway inflammation. However, despite increased bleomycin-induced IL-22 production, Il17a-/- mice were protected from airway inflammation, suggesting that IL-17A may regulate the expression and/or proinflammatory properties of IL-22. Consistent with this, IL-17A inhibited IL-22 production by Th17 cells, and exogenous administration of IL-22 could only promote airway inflammation in vivo by acting in synergy with IL-17A. Anti-IL-22 mAb was delivered to Il17a-/- mice and was found to exacerbate bleomycin-induced airway inflammation, indicating that IL-22 is tissue protective in the absence of IL-17A. Finally, in an in vitro culture system, IL-22 administration protected airway epithelial cells from bleomycin-induced apoptosis, and this protection was reversed after coadministration of IL-17A. These data identify that IL-17A can regulate the expression, proinflammatory properties, and tissue-protective functions of IL-22, and indicate that the presence or absence of IL-17A governs the proinflammatory versus tissue-protective properties of IL-22 in a model of airway damage and inflammation.

Chemiluminescence-based detection of gastrointestinal malignancies.

Chemiluminescence is an established method for the in vitro serum monitoring of human tumors. Chemiluminescence may have additional utility for the in vivo detection of tumors. During carcinogenesis, tumors change their phenotype and the proteins they express. Specifically, in carcinogenesis of the esophagus and stomach, enzymes that are normally only expressed in the small intestine brush border become ectopically expressed in precancerous and cancerous lesions. Intestinal alkaline phosphatase and lactase are among the small intestine brush border enzymes that are ectopically expressed. We have found that specific chemiluminescent substrates for alkaline phosphatase and lactase may be used for the in situ detection of intestinal alkaline phosphatase and lactase in unprocessed tissue. In this study, we demonstrate that chemiluminescent 1,2-dioxetane substrates may be used for the detection of precancerous and cancerous lesions from the esophagus and stomach.

Peripheral T-cell lymphoma presenting as sclerouveitis.

PURPOSE: To report an unusual case of ocular peripheral T-cell lymphoma presenting as sclerouveitis. METHODS: A 53-year-old woman presented with painful, unilateral sclerouveitis and was initially treated with antivirals and corticosteroids for what was presumed to be isolated ocular HSV infection with vasculitis. When she failed to improve the conjunctiva was biopsied and characterized by immunohistochemical and molecular methods. The literature regarding conjunctival T-cell lymphomas as well as lymphomas mimicking scleritis is reviewed. RESULTS: Biopsies of a scleral/conjunctival nodule from the right eye were obtained on 2 occasions, the second of which revealed the presence of intermediate to large size lymphocytes that were CD3, T-cell intracellular antigen 1 and Granzyme B positive but CD56 and Epstein Barr virus negative. Polymerase chain reaction showed clonal T-cell receptor gamma rearrangements in DNA samples isolated from biopsy tissue. Another biopsy was obtained from a mucosal lesion in the oropharynx, which was shown to contain an identical T-cell receptor gamma rearrangement. These results led to the diagnosis of peripheral T-cell lymphoma. Conjunctival T-cell lymphomas have been reported in two other patients both of which also had involvement of upper airway structures. Five other reports of lymphoma mimicking scleritis are discussed. CONCLUSIONS: Peripheral T-cell lymphoma should be considered in the differential diagnosis of patients who present with sclerouveitis of unknown etiology unresponsive to conventional therapy. If a conjunctival T-cell lymphoma is identified a systemic evaluation for lymphoma with particular attention to the upper airway is justified.

A colonization factor links Vibrio cholerae environmental survival and human infection.

Many bacteria that cause diseases must be able to survive inside and outside the host. Attachment to and colonization of abiotic or biotic surfaces is a common mechanism by which various microorganisms enhance their ability to survive in diverse environments. Vibrio cholerae is a Gram-negative aquatic bacillus that is often found in the environment attached to the chitinous exoskeletons of zooplankton. It has been suggested that attachment to zooplankton enhances environmental survival of Vibrio spp., probably by providing both an abundant source of carbon and nitrogen and protection from numerous environmental challenges. On ingestion by humans, some serogroups of V. cholerae cause the diarrhoeal disease cholera. The pathophysiology of cholera is a result of the effects of cholera toxin on intestinal epithelial cells. For sufficient quantities of cholera toxin to reach the intestinal epithelium and to produce clinical symptoms, colonization of the small bowel must occur. Because most V. cholerae do not colonize humans, but all probably require strategies for survival in the environment, we considered that colonization factors selected for in the environment may be the same as those required for intestinal colonization of humans. In support of this hypothesis, here we have identified a single protein required for efficient intestinal colonization that mediates attachment to both zooplankton and human epithelial cells by binding to a sugar present on both surfaces.

A Vibrio cholerae classical TcpA amino acid sequence induces protective antibody that binds an area hypothesized to be important for toxin-coregulated pilus structure.

Vibrio cholerae is a gram-negative bacterium that has been associated with cholera pandemics since the early 1800s. Whole-cell, killed, and live-attenuated oral cholera vaccines are in use. We and others have focused on the development of a subunit cholera vaccine that features standardized epitopes from various V. cholerae macromolecules that are known to induce protective antibody responses. TcpA protein is assembled into toxin-coregulated pilus (TCP), a type IVb pilus required for V. cholerae colonization, and thus is a strong candidate for a cholera subunit vaccine. Polypeptides (24 to 26 amino acids) in TcpA that can induce protective antibody responses have been reported, but further characterization of their amino acid targets relative to tertiary or quaternary TCP structures has not been done. We report a refinement of the TcpA sequences that can induce protective antibody. One sequence, TcpA 15 (residues 170 to 183), induces antibodies that bind linear TcpA in a Western blot as well as weakly bind soluble TcpA in solution. These antibodies bind assembled pili at high density and provide 80 to 100% protection in the infant mouse protection assay. This is in sharp contrast to other anti-TcpA peptide sera (TcpA 11, TcpA 13, and TcpA 17) that bind very strongly in Western blot and solution assays yet do not provide protection or effectively bind TCP, as evidenced by immunoelectron microscopy. The sequences of TcpA 15 that induce protective antibody were localized on a model of assembled TCP. These sequences are centered on a site that is predicted to be important for TCP structure.