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Dietary interventions are increasingly being proposed as alternatives to surgery for common gastrointestinal conditions. Integrating aspects of cognitive psychology (e.g., behavioral nudges) into dietary interventions is becoming popular, but evidence is lacking on their effectiveness and unintended effects. We assessed the effects of including nudges in the development of a dietary intervention based on the Mediterranean diet. We conducted two-arm randomized surveys of United States adults. After a validated dietary questionnaire, participants received feedback about dietary consistency with a Mediterranean diet with (A) no nudge versus (B) one of several nudges: peer comparison, positive affect induction + peer comparison, or defaults. Participants rated their negative and positive emotions, motivation for dietary change, and interest in recipes. Responses were analyzed using baseline covariate-adjusted regression. Among 1709 participants, 56% were men and the median age was 36 y. Nudges as a class did not significantly affect the extent of negative or positive emotions, motivation, or interest. However, specific nudges had different effects: compared to no nudge, peer comparison blunted negative emotions and increased motivation, although decreased interest in recipes, while defaults increased interest in recipes but reduced motivation. In this pilot, behavioral nudges as a class of strategies did not improve participants' reactions to dietary feedback nor did they promote negative reactions. However, specific nudges may be better considered separately in their effects. Future testing should explore whether specific nudges including peer comparison and defaults improve dietary intervention effectiveness, especially in people with the specific gastrointestinal conditions of interest. • Dietary interventions are increasingly being proposed as alternatives to surgery. • We tested behavioral nudges in dietary feedback for intended and unintended effects. • Nudges as a class did not evoke negative reactions nor prove effective. • Specific nudges had different effects on participants' reactions. • Peer comparison and defaults may warrant further testing. [ABSTRACT FROM AUTHOR]

We evaluated the activity of ceftaroline against clinical isolates of ceftriaxone-nonsusceptible Streptococcus pneumoniae from United States medical centers. Streptococcus pneumoniae isolates (n = 21,750) were consecutively collected from 201 medical centers in 2008–2020 and tested for susceptibility by broth microdilution method. Among these isolates, 1,419 (6.5%) were ceftriaxone-nonsusceptible (ceftriaxone minimum inhibitory concentration [MIC], ≥2 mg/L). Other resistant subgroups analyzed included multidrug-resistant (MDR; nonsusceptibility to ≥3 classes of agents; n = 4,454) and extensively drug-resistant (XDR; nonsusceptibility to ≥5 classes; n = 1,708) isolates. Ceftriaxone susceptibility increased from 89.0% (2008–2011) to 98.1% (2018–2020). Ceftaroline was active against 99.9% of ceftriaxone-nonsusceptible isolates (MIC50/90, 0.25/0.25 mg/L) and retained potent activity against MDR (n = 4,454; MIC50/90, 0.12/0.25 mg/L; >99.9% susceptible) and XDR (n = 1,708; MIC50/90, 0.25/0.25 mg/L; 100.0% susceptible) isolates. Only one isolate had a ceftaroline MIC ≥0.5 mg/L. In summary, ceftaroline demonstrated potent and consistent activity over time (2008–2020) against a large collection of S. pneumoniae from U.S. medical centers, including ceftriaxone-nonsusceptible, MDR, and XDR isolates [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a multifactorial disease of the ocular surface characterized by loss of homeostasis of the tear film and accompanied by symptoms such as ocular discomfort and visual disturbance. DED is one of the most common reasons for seeking medical care in the United States and across the world. Despite this, there are a limited number of pharmacologic therapies for the treatment of DED in the United States and Europe. This review examines the different pivotal trials for DED medications and the impact the vehicle in each trial. In recent clinical trials, the vehicle of the active formulation of the medication is often used as the active comparator. A literature review of published dry eye clinical trials was performed to identify the pivotal clinical trials of DED medications and to compare treatment effect and further understand the impact of the vehicle on clinical trial outcomes. The pivotal clinical trials for the currently approved treatments for dry eye have widely varying study designs. The variations include differences in inclusion criteria, outcome measures and efficacy endpoints, and whether or not the use of concomitant artificial tears is allowed. These differences make it difficult for accurate comparisons to be made between DED medications. Each trial demonstrated that the vehicle alone has some beneficial effect on signs and symptoms of dry eye disease. This review discusses the varying trial designs and vehicles used in the pivotal studies for the four approved dry eye medications in the United States and Europe, as well as novel vehicles under development and clinical trial recommendations. [ABSTRACT FROM AUTHOR]

Very few antimicrobial agents remain active against Pseudomonas aeruginosa and Klebsiella pneumoniae in some geographic regions. We evaluated the in vitro activity of ceftazidime–avibactam, ceftolozane–tazobactam, and comparator agents against 6,210 P. aeruginosa and 6,041 K. pneumoniae isolates consecutively collected from 85 U.S. medical centers across 37 states in 2016–2018. Antimicrobial susceptibility was determined by reference broth microdilution method. K. pneumoniae isolates found to have elevated MICs for broad-spectrum cephalosporins were submitted to whole-genome sequencing analysis to detect resistance genes. Ceftazidime–avibactam (97.1% susceptible [S]) and ceftolozane–tazobactam (97.0%S) were the most active compounds against P. aeruginosa and retained activity against meropenem-nonsusceptible (88.5–89.0%S), piperacillin–tazobactam-nonsusceptible (86.6–87.0%S), and other resistant subsets of isolates. The most active agents against K. pneumoniae per CLSI criteria were ceftazidime–avibactam (>99.9%S), amikacin (98.4%S), and meropenem (97.1%S). Ceftolozane–tazobactam was active against 95.3% of K. pneumoniae but showed limited activity against extended-spectrum β-lactamase and carbapenemase producers (82.9% and 0.0%S, respectively). [ABSTRACT FROM AUTHOR]

• Tebipenem pivoxil hydrobromide is a novel oral carbapenem • Tebipenem is likely to be used in the outpatient setting, including in nursing homes • Tebipenem was highly active against Enterobacterales from outpatient centers in the United States Tebipenem is a potential option for the treatment of a range of infections because of its oral dosing coupled with the safety profile of the β-lactam antimicrobial class. To evaluate tebipenem in vitro activity against a challenge set of clinical Enterobacterales collected from outpatient and community settings. 618 Enterobacterales isolates were submitted by 11 geographically dispersed U.S medical centers that processed cultures from affiliated outpatient centers in 2022. Susceptibility tests for tebipenem and comparator agents were performed by broth microdilution. Extended-spectrum-β-lactamase (ESBL)-like isolates were identified phenotypically. Multidrug-resistant isolates were non-susceptible to ≥1 agent in ≥3 antimicrobial classes. Genotypic testing (CarbaR) was conducted on select isolates. Isolates (59% Escherichia coli) were recovered from patients seen predominantly in urology/nephrology (24%), nursing home/long-term care (21%), and ambulatory/primary care (21%) clinics. Comparator agent susceptibility rates against all isolates were as follows: levofloxacin (67.5%), amoxicillin/clavulanate (73.6%), cefixime (70.4%), cefpodoxime (70%), cephalexin (61.7%), ceftriaxone (74.4%), cefazolin (63.8%), ertapenem (97.6%), meropenem (99.7%), nitrofurantoin (64.9%), and sulfamethoxazole/trimethoprim (70.9%). Overall, 90.3% (558/619) of isolates were inhibited at a tebipenem MIC of ≤0.125 mg/L (MIC 50/90 , 0.016/0.125 mg/L), including 85.7% inhibition of ESBL-phenotype isolates (n=161; MIC 50/90 , 0.03/0.25 mg/L), 86.3% of levofloxacin and sulfamethoxazole/trimethoprim co-resistant isolates (n=95; MIC 50/90 , 0.016/0.25 mg/L) and 84.3% of multidrug-resistant isolates (n = 172; MIC 50/90 , 0.03/0.25 mg/L). Carbapenemase genes were observed in 2 ESBL-phenotype isolates with a tebipenem MIC of ≥0.5 mg/L. Relative to common oral comparators, these data demonstrate excellent tebipenem in vitro activity against Enterobacterales isolated from patients receiving care in outpatient settings, including urology clinics and nursing homes. [ABSTRACT FROM AUTHOR]

Background We evaluated the antimicrobial susceptibility of Enterobacterales (ENT) and P. aeruginosa (PSA) causing bloodstream infections (BSIs) in the United States (US) hospitals. Methods A total of 3,317 ENT and 331 PSA isolates were consecutively collected (1/patient) from patients with BSI in 68 US medical centers in 2017–2018 and tested for susceptibility (S) by reference broth microdilution methods in a central laboratory as part of the International Network for Optimal Resistance Monitoring (INFORM) Program. β-Lactamase screening was performed by whole-genome sequencing on ENT with decreased S to broad-spectrum cephalosporins (ESBL phenotype). Results The most common ENT species isolated from BSI were E. coli (EC; 41.9% of ENT), K. pneumoniae (KPN; 24.4%), and E. cloacae (ECL; 8.7%), and the most active agents against ENT were ceftazidime–avibactam (CAZ-AVI; 99.9%S), amikacin (AMK; 99.6%S) and meropenem (MEM; 99.3%S). CAZ-AVI was active against all EC and KPN isolates (100.0%S). Only 2 ENT isolates (0.06%) were CAZ-AVI resistant, 2 NDM-1-producing ECL isolated in the New York City area. Ceftolozane–tazobactam (C-T) and piperacillin–tazobactam (PIP-TAZ) showed good activity against EC and KPN (92.2–98.9%S; Table), with limited activity against ECL (81.9–83.7%S). The most common ESBLs were CTX-M-type, which was observed in 93% of ESBL producers (mainly CTX-M-15 [64% of ESBL producers] and CTX-M-27 [13%]), and OXA-1/OXA-30 (42%); 42% of ESBL producers (n = 333, excluding carbapenemase producers) displayed ≥2 ESBL genes, mainly CTX-M-15 and OXA-1/OXA-30 (40% of ESBL producers). The most active agents against ESBL producers were CAZ-AVI (100.0%S), imipenem (99.4%S), and colistin (COL; 99.1%S). Only CAZ-AVI (99.4%S), AMK (96.2%S) and MEM (92.8%S) were active against >90% of multidrug-resistant (MDR) ENT. Among 19 carbapenem-resistant ENT (CRE; 0.6% of ENT), 9 produced a KPC-like, 2 an NDM-1, and 2 an NMC-A; carbapenemase genes were not found in 6 CRE isolates. COL (100.0%S), CAZ-AVI (98.5%S), AMK (98.5%S), C-T (98.1%S), and tobramycin (97.0%S) were very active against PSA. Conclusion CAZ-AVI exhibited potent in vitro activity and great spectrum against ENT (99.9%S) and PSA (98.5%) isolated from patients with BSI from US hospitals. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]