Sefton told PRWeek she had resigned to pursue her "dream" of going into the wine trade. She is leaving later this month after just over a year in the role and will be replaced on an interim basis by senior partner Lorranie Thelian.
Meanwhile the UK healthcare team is facing six redundancies, which are thought to impact on a number of senior, longstanding employees and will reduce its size to around 30 staff.
They are understood to have been prompted by the growing scarcity of big-money retainers, with the agency looking to develop talent with experience in project and digital work.
The redundancies are thought to be unrelated to Sefton’s departure.
A spokesman for Ketchum said that the agency was "sorry to see Amanda go" and said it was "consulting with six employees about a new staffing structure that is less top-heavy".