Most Read Articles
Roshini Claire Anthony, 02 Feb 2018

The use of weight loss medications for at least 1 year did little to improve cardiometabolic risk factors in obese adults, according to a systematic review and meta-analysis.

17 Feb 2019
In patients with type 2 diabetes (T2D), sodium-glucose cotransporter 2 (SGLT2) inhibitor monotherapy, particularly canagliflozin, exerts greater effects on weight compared with metformin and dipeptidyl peptidase 4 (DPP-4) inhibitors or gliptins, according to the results of a meta-analysis.
26 Feb 2019
Oral fluoxetine confers beneficial effects in the management of adult and adolescent amblyopia, suggests a recent study.
19 Feb 2019
Preprandial administration of metformin successfully and safely reduces postprandial plasma triglyceride levels, a new study has shown.

Novel lytic drug shows promise for S. aureus bacteraemia

Audrey Abella
15 May 2019

The addition of the first-in-class direct lytic agent exebacase (lysin CF-301) to standard-of-care (SOC) antibiotics demonstrated efficacy against Staphylococcus aureus bacteraemia (SAB), particularly difficult-to-treat methicillin-resistant SA (MRSA), compared with SOC antibiotics alone, according to the results of a phase II trial presented at ECCMID 2019.

Researchers randomized 121 adults (mean age 56 years, 68 percent male) with documented SAB (including endocarditis) 3:2 to receive SOC alone (mean, 30.5 days) or in combination with a single, 2-hour infusion of exebacase (mean SOC, 33.3 days). The microbiological intention-to-treat (mITT) cohort comprised 116 individuals. The primary endpoint was clinical response rate (CRR) at day 14, which pertains to improvement/resolution of signs and symptoms without metastatic foci or complications and no changes in antibiotic treatment or further medical intervention. [ECCMID 2019, abstract L0012]

MRSA frequency was similar between groups (38.0 percent vs 35.6 percent for exebacase + SOC vs SOC alone). The incidence of bacteraemia was as follows: uncomplicated bacteraemia (13.8 percent), complicated bacteraemia (67.2 percent), right-sided endocarditis (RSE; 6.9 percent), and left-sided endocarditis (LSE; 12.1 percent).

CRR at day 14 in the mITT cohort was numerically higher in the exebacase + SOC vs SOC alone arm (70.4 percent vs 60.0 percent; p=0.314), and significantly higher in the exebacase + SOC arm in the MRSA subgroup (74.1 percent vs 31.3 percent; p=0.010).

“A single dose of exebacase plus SOC resulted in a 42.8-percent higher CRR in the prespecified MRSA subgroup vs SOC alone,” said study author Dr Vance Fowler from Duke University Medical Centre in Durham, North Carolina, US.

Moreover, compared with SOC alone recipients, CRRs at day 14 were higher among exebacase + SOC recipients with complicated bacteraemia (78.6 percent vs 58.3 percent) and RSE (60.0 percent vs 33.3 percent). However, these should be interpreted with caution as the sample sizes were limited, noted Fowler.

The incidence of treatment-emergent adverse events (TEAEs) was balanced between study arms (88.9 percent [exebacase + SOC] vs 85.1 percent [SOC]) as were serious TEAEs (45.8 percent vs 51.1 percent). Mortality rate through test-of-cure was higher in the exebacase + SOC vs SOC arm (19.4 percent vs 14.9 percent) which, according to Fowler, could have been due to the higher LSE rates in the exebacase + SOC vs SOC arm (15.5 percent and 6.7 percent). There were no reports of hypersensitivity to or discontinuation of the study drug.

Given the suboptimal SOC for SAB and endocarditis, which could be lethal, identifying new treatment alternatives is imperative, noted Fowler. With a rapid, targeted, and species-specific mechanism of action, lysins work synergistically with traditional antibiotics and have a low propensity for resistance.

“[Our findings showed that] exebacase demonstrated clinically meaningful improvements in RR … for MRSA bacteraemia including endocarditis and was well-tolerated … [Therefore,] exebacase may represent a novel treatment possibility for SAB and endocarditis,” said Fowler, adding that the findings could support further evaluation of this new agent in a definitive phase III trial.

 

 

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Most Read Articles
Roshini Claire Anthony, 02 Feb 2018

The use of weight loss medications for at least 1 year did little to improve cardiometabolic risk factors in obese adults, according to a systematic review and meta-analysis.

17 Feb 2019
In patients with type 2 diabetes (T2D), sodium-glucose cotransporter 2 (SGLT2) inhibitor monotherapy, particularly canagliflozin, exerts greater effects on weight compared with metformin and dipeptidyl peptidase 4 (DPP-4) inhibitors or gliptins, according to the results of a meta-analysis.
26 Feb 2019
Oral fluoxetine confers beneficial effects in the management of adult and adolescent amblyopia, suggests a recent study.
19 Feb 2019
Preprandial administration of metformin successfully and safely reduces postprandial plasma triglyceride levels, a new study has shown.