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Background Patients with metastatic hepatocellular carcinoma (HCC) suffer symptoms of both end-stage liver disease and cancer. Palliative care (PC) enhances the quality of life via symptom control and even improves survival for some cancers. Our study characterized rates of PC utilization among metastatic HCC patients and determined factors associated with PC receipt. Methods We conducted a retrospective review of adult National Cancer Database patients diagnosed with metastatic HCC between 2004 and 2016. Chi-square tests were used to analyze two cohorts: those who received PC and those who did not. Logistic regression was performed to assess the impact of clinicodemographic factors on the likelihood of receiving PC. Results PC utilization was low at just 17%. Later year of diagnosis, insured status, and higher education level were associated with an increased likelihood of receiving PC. Treatment at academic centers or integrated network cancer programs increased the likelihood of receiving PC compared to treatment at a community center (odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.03-1.33 and OR = 1.25, 95% CI = 1.07-1.45; respectively). Hispanics were significantly less likely to received PC than non-Hispanic Whites (OR = 0.73, 95% CI = 0.64-0.82). Conclusions PC utilization among patients with metastatic HCC remains low. Targeted efforts should be enacted to increase the delivery of PC in this group.

Background The combination aztreonam/avibactam is currently under Phase 3 trials for the treatment of serious infections caused by Gram-negative bacteria including those with MBLs. Objectives To investigate the resistance mechanisms in Enterobacterales exhibiting aztreonam/avibactam MICs of ≥4 mg/L. Methods Among 8787 Enterobacterales, 17 (0.2%) isolates exhibited an aztreonam/avibactam MIC of ≥4 mg/L. Isolates were sequenced and screened for β-lactamases. Sequences of porins, penicillin-binding protein 3 (PBP3) and expression levels of AmpC and AcrA were evaluated. Results Eleven (11/4154 isolates; 0.26%) Escherichia coli, three (3/1981; 0.15%) Klebsiella pneumoniae and three (3/628; 0.5%) Enterobacter cloacae were identified. All E. coli showed either an ‘YRIK’ or ‘YRIN’ insertion in PBP3. In general, these isolates carried blaCMY and/or blaCTX-M variants, except for one isolate from Korea that also produced NDM-5 and one isolate from Turkey that produced OXA-48. Two DHA-1-producing K. pneumoniae overexpressed acrA and had a premature stop codon in either OmpK35 or OmpK36, whereas a third K. pneumoniae carried blaPER-2 and had a premature stop codon in OmpK35. All three E. cloacae expressed AmpC at levels ≥570-fold, but sequence analysis did not reveal known amino acid alterations associated with decreased avibactam binding or increased hydrolysis of β-lactams. Minor amino acid polymorphisms within OmpC, OmpF and PBP3 were noted among the E. cloacae. Conclusions A small number of isolates (0.2%) met the inclusion criteria. E. coli showed altered PBP3 as the most relevant resistance mechanism, whereas K. pneumoniae had multiple resistance mechanisms. Further investigations are needed to clarify resistance in E. cloacae.

This study investigated the activity of an oral carbapenem, tebipenem, against various molecularly characterized subsets of Escherichia coli. A total of 15.0% of E. coli isolates (360/2,035 isolates) met the MIC criteria for screening for β-lactamases. Most of those isolates (74.7% [269/360 isolates]) carried bla(CTX-M). The CTX-M distribution varied (50% to 86%) among Census Regions, as did that of plasmid AmpC genes (up to 41% among E. coli isolates from the New England Region). Tebipenem and intravenous carbapenems showed uniform activity against various E. coli subsets.

Aliarcobacter butzleri (formerly known as Arcobacter butzleri) is an emerging foodborne zoonotic pathogen that establishes in vitro endosymbiotic relationships with Acanthamoeba castellanii, a free-living amoeba. Previously, we described that this bacterium acts as an endocytobiont of A. castellanii, surviving for at least 10 days in absence of bacterial replication. Thus, the aim of this study was to evaluate the ability of A. butzleri to survive as a long-term endosymbiont of A. castellanii for 30 days in two models of symbiotic interaction with A. castellanii: i) endosymbiotic culture followed by gentamicin protection assay and ii) transwell co-culture assay. The results allow us to conclude that A. butzleri is capable of surviving as an endosymbiont of A. castellanii for at least 30 days, without multiplying, under controlled laboratory conditions. In addition, in the absence of nutrients and as both microorganisms remain in the same culture, separated by semi-permeable membranes, A. castellanii does not promote the survival of A. butzleri, nor does it multiply. Our findings suggest that the greater survival capacity of A. butzleri is associated with their endosymbiont status inside A. castellanii, pointing out the complexity of this type of symbiotic relationship.

Objectives To evaluate the prevalence of acquired β-lactamase genes and susceptibility profiles of carbapenem-nonsusceptible Enterobacterales (CNSE) clinical isolates collected in US hospitals during a 5-year period. Methods Isolates were susceptibility tested by reference broth microdilution methods. Results were interpreted using CLSI breakpoints. Isolates displaying nonsusceptible MICs for imipenem or meropenem were categorized as CNSE. CNSE isolates were screened for β-lactamase-encoding genes using whole-genome sequencing. New genes were cloned, expressed in an Escherichia coli background and susceptibility tested. Results A total of 450 (1.3%) isolates were CNSE. Klebsiella pneumoniae serine carbapenemase (KPC) production was the most common resistance mechanism among CNSE isolates: 281/450 (62.4%) carried blaKPC, including three new variants. OXA-48-like and metallo-β-lactamase (MBL) encoding genes were detected among seven and 12 isolates, respectively. Among MBL genes, blaNDM-1 was the most common, but blaNDM-5, blaVIM-1 and blaIMP-27 were also identified. 169 (37.6% of the CNSE) isolates did not produce carbapenemases. Ceftazidime/avibactam was the most active agent (95.0% to 100.0% susceptible) against CNSE isolates from all carbapenemase groups except MBL-producing isolates. Ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam inhibited 100.0%, 97.6% and 92.3% of the non-carbapenemase CNSE isolates, respectively. Among the three new blaKPC variants, one conferred resistance to ceftazidime/avibactam and low meropenem MIC results while the other two had profiles similar to blaKPC-2 or blaKPC-3. Conclusions A decline in carbapenemase production was noticed in US hospitals in the 5-year period analysed in this study. New β-lactam/β-lactamase inhibitor combinations tested had good activity against CNSE isolates.

Objectives The Surveillance of Tedizolid Activity and Resistance (STAR) programme monitored the tedizolid activity against Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus anginosus group. We evaluated the antimicrobial susceptibility of 47 400 unique Gram-positive clinical isolates from the STAR programme collected from USA (21 243), Europe (17 674), Asia-Pacific (4954) and Latin America (3529) medical centres (2015–19). Methods All isolates were tested for susceptibility by reference broth microdilution method. WGS and in silico analysis were performed on linezolid-non-susceptible (NS) isolates. Results Tedizolid was active against ≥99.9% of S. aureus (100.0% of MSSA and >99.9% of MRSA), E. faecalis, S. pyogenes, S. agalactiae and S. anginosus group isolates, with MIC50 values ranging from 0.12 to 0.25 mg/L and MIC90 values of 0.25 mg/L. Linezolid, vancomycin and daptomycin were also active agents against these organisms. Tedizolid inhibited all VRE and 73.1% of linezolid-NS E. faecalis isolates. Ampicillin and daptomycin retained 100.0% activity against VRE and linezolid-NS E. faecalis isolates. Linezolid-NS E. faecalis isolates carried mostly the optrA gene. G2576T alterations in the 23S rRNA were observed in one linezolid-NS S. aureus isolate and one linezolid-NS E. faecalis isolate. Conclusions No resistance trends were observed for tedizolid during the study period.