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ObjectivesTo re-examine the use of non-carbapenems (NCBPs), specifically piperacillin/tazobactam and cefepime, for ESBL-producing Enterobacterales (ESBL-E) urinary tract infections (UTIs).PatientsRetrospective cohort study of adults hospitalized between January 2016 and June 2020 with pyuria on urinalysis, a urine culture positive for ESBL-E treated with a study antibiotic (meropenem, ertapenem, cefepime or piperacillin/tazobactam) and did not meet criteria for study exclusion.MethodsTo compare carbapenems (CBPs) with cefepime or piperacillin/tazobactam for the treatment of ESBL-E UTI. The primary outcome was clinical cure, defined as complete resolution of signs and symptoms of infection. Secondary outcomes included in-hospital mortality, recurrence within 30 days and resistance emergence within 30 days.ResultsOne-hundred and thirty-three patients were included, based on definitive therapy received; 69 (51.9%) received CBP and 64 (48.1%) received NCBP therapy. Of the total patient population, 17 (12.8%) were admitted to the ICU, 84 (63.1%) had a complicated UTI and 64 (48.1%) had pyelonephritis. There was no difference in clinical cure between the CBP and NCBP groups (95.7% versus 96.9%, P = 0.999). Additionally, no differences in secondary outcomes were observed.ConclusionsWhen compared with CBPs, cefepime and piperacillin/tazobactam resulted in similar clinical cure, in-hospital mortality, recurrence and resistance emergence in the treatment of ESBL-E UTI.

A pandemic, by definition, involves the whole world being impacted by a common threat and calls for a united response. A highly virulent pathogen, the novel coronavirus (SARS-CoV-2) has affected every facet of modern life. The virus has revealed the world’s underlying inherent inequities, such as economic and food insecurity and availability of and access to a functional healthcare system, not to mention preparedness of nations to manage a coordinated pandemic response. For these reasons, Coronavirus disease (COVID-19) represents an unprecedented challenge to economies, healthcare systems, and nations alike. The closing of international and internal borders, physical distancing, and the resulting decrease in travel and trade have led countries to become insular geographically, socially, and economically. Somewhat ironically, this necessitates an increased need for greater collaboration between countries and other stakeholders to control the transmission of SARS-CoV-2 and better manage the global crisis upon us, so as to mitigate the long-term sequelae of this pandemic.

Background Carbapenems (CBP) are considered first-line for infections caused by extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E). However, recent literature suggests that cefepime (FEP) and piperacillin-tazobactam (TZP) may produce similar outcomes vs. CBPs for the treatment of ESBL-E urinary tract infections (UTIs). The goal of this study was to determine if non-carbapenem (NCBP) therapy with FEP or TZP is as effective as CBPs for the treatment of ESBL-E UTIs. Methods This was a retrospective observational study of patients admitted to the hospital from January 1st, 2016 to June 30th, 2020 with a urine culture positive for ESBL-E. Patients were included if they received a study antibiotic (meropenem, ertapenem, TZP, or FEP). Patients were excluded if they had any of the following: absence of pyuria, prior receipt of study antibiotic, CBP-resistant organism isolated in urine culture, polymicrobial urine culture, end-stage renal disease, or concomitant gram-negative infection. The primary outcome was clinical cure defined as complete resolution of signs and symptoms of infection. Secondary outcomes included in-hospital mortality, recurrence within 30 days, and resistance within 30 days. Results A total of 133 patients were included based on definitive therapy received; 69 (52%) received CBP and 64 (48%) received NCBP therapy. Of the total patient population, 17 (13%) were admitted to the intensive care unit, 84 (63%) had a complicated UTI, and 64 (48%) had pyelonephritis. Baseline characteristics were similar between the two groups. There was no difference in clinical cure between the CBP and NCBP therapy groups (96% vs. 97%, p = 1.0). Additionally, no differences in secondary outcomes were observed. Subgroup analyses were performed in patients with specific pathogens, uncontrolled genitourinary source, complicated UTI, and pyelonephritis. These analyses did not reveal any differences in primary or secondary outcomes between the two groups. Conclusion FEP and TZP may be reasonable CBP-sparing alternatives for the treatment of ESBL-E UTIs as clinical and microbiological outcomes were similar with these NCBP agents vs. CBPs in this study population. Disclosures Venugopalan Veena, PharmD, Melinta (Other Financial or Material Support, Received a stipend for participation in a drug registry)Merck (Other Financial or Material Support, Received a stipend for participation in a drug registry)

International audience; Background: Bacterial colonization in cystic fibrosis (CF) lungs has been directly associated to the loss of CFTR function, and/or secondarily linked to repetitive cycles of chronic inflammation/infection. We hypothesized that altered molecular properties of mucins could contribute to this process.Methods: Newborn CFTR+/+ and CFTR-/- were sacrificed before and 6 h after inoculation with luminescent Pseudomonas aeruginosa into the tracheal carina. Tracheal mucosa and the bronchoalveolar lavage (BAL) fluid were collected to determine the level of mucin O-glycosylation, bacteria binding to mucins and the airways transcriptome. Disturbances in mucociliary transport were determined by ex-vivo imaging of luminescent Pseudomonas aeruginosa.Results: We provide evidence of an increased sialylation of CF airway mucins and impaired mucociliary transport that occur before the onset of inflammation. Hypersialylation of mucins was reproduced on tracheal explants from non CF animals treated with GlyH101, an inhibitor of CFTR channel activity, indicating a causal relationship between the absence of CFTR expression and the sialylation of mucins. This increased sialylation was correlated to an increased adherence of P. aeruginosa to mucins. In vivo infection of newborn CF piglets by live luminescent P. aeruginosa demonstrated an impairment of mucociliary transport of this bacterium, with no evidence of pre-existing inflammation.Conclusions: Our results document for the first time in a well-defined CF animal model modifications that affect the O-glycan chains of mucins. These alterations precede infection and inflammation of airway tissues, and provide a favorable context for microbial development in CF lung that hallmarks this disease.