To evaluate temporal trends in the prevalence of gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) in the southeastern United States. Secondary objective was to examine the use of novel β-lactams for GNB with DTR by both antimicrobial use (AU) and a novel metric of adjusted AU by microbiological burden (am-AU).

Retrospective, multicenter, cohort.

Ten hospitals in the southeastern United States.

GNB with DTR including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp. from 2015 to 2020 were tracked at each institution. Cumulative AU of novel β-lactams including ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, and cefiderocol in days of therapy (DOT) per 1,000 patient-days was calculated. Linear regression was utilized to examine temporal trends in the prevalence of GNB with DTR and cumulative AU of novel β-lactams.

The overall prevalence of GNB with DTR was 0.85% (1,223/143,638) with numerical increase from 0.77% to 1.00% between 2015 and 2020 (P = .06). There was a statistically significant increase in DTR Enterobacterales (0.11% to 0.28%, P = .023) and DTR Acinetobacter spp. (4.2% to 18.8%, P = .002). Cumulative AU of novel β-lactams was 1.91 ± 1.95 DOT per 1,000 patient-days. When comparing cumulative mean AU and am-AU, there was an increase from 1.91 to 2.36 DOT/1,000 patient-days, with more than half of the hospitals shifting in ranking after adjustment for microbiological burden.

The overall prevalence of GNB with DTR and the use of novel β-lactams remain low. However, the uptrend in the use of novel β-lactams after adjusting for microbiological burden suggests a higher utilization relative to the prevalence of GNB with DTR.

The mechanism of action of antidepressant drugs is not fully understood. Application of genomic methods enables the identification of biochemical pathways that are regulated by antidepressants, and this may provide novel clues to the molecular and cellular actions of these drugs. The present study examined gene expression profiles in the hippocampus of rats exposed to chronic antidepressant treatment.

Animals were treated for 12 days with the selective serotonin reuptake inhibitor paroxetine; then, hippocampal ribonucleic acid was recovered, and changes in gene expression were assessed by microarray analysis.

A total of 160 genes that showed differential expression after paroxetine exposure were identified. Using functional relevance and observed fold change as selection criteria, the expression changes in a subset of these genes were confirmed by quantitative polymerase chain reaction.

Of this subset, only two genes, cyclin D1 (Ccnd1) and hairy and enhancer of split 6 (Hes6), showed robust and consistent changes in expression. Both genes were downregulated by paroxetine, and both have been previously implicated in neurogenesis. Further investigation of these two genes may provide new insight into the mechanism of action of antidepressants.

In bulimia nervosa (BN), borderline personality disorder (BPD) and major depression (MDD) are frequently comorbid conditions. Executive function has been found to be impaired in BPD and MDD, but the impact of comorbidity on neuropsychological function has rarely been investigated.

To investigate neuropsychological function in BN with a focus on comorbid BPD and MDD.

One hundred forty-four medication-free female patients entering a study of psychological treatments for BN performed a brief battery of neuropsychological tests. Comorbid MDD and BPD were systematically identified using standard interviews. Neuropsychological test results were compared.

Forty-one subjects had comorbid BPD and 35 had comorbid MDD, while 15 had both. There was no effect of comorbid MDD, but there was a significant effect of BPD and a significant interaction between the diagnosis of MDD and BPD on executive tasks (trail making and Stroop). Thus, compared with subjects without BPD, subjects with BPD performed significantly worse on tests of executive function, while the group with both comorbidities performed even worse.

There appears to be an additive effect of BPD and MDD resulting in impaired executive neuropsychological function. Future studies on either disorder and on BN should examine and account for the effect of comorbidity.