A patient at Perth Royal Infirmary has died after they contracted C.difficile.
Three other patients at the Tay Ward - an elderly care ward - are under observation after they also contracted the infection.
One patient is recovering from the infection and two currently still have mild symptoms.
In the case of the patient who died, C.diff was a factor in their death but not the main cause.
The first case was isolated as soon as their infection was confirmed and the others as soon as symptoms occurred.
Consultant Microbiologist Dr Gillian Orange said: " Staff have already spoken to Tay Ward patients and families to explain the situation and to reassure them of the actions we have taken on the ward. We are making sure that patients and relatives know that if they have any further questions or concerns they should speak to the senior nurses on the ward.
"We are also contacting those few patients who have been discharged from Tay Ward since Friday, 26 March to inform them of the situation and again giving them the opportunity to speak to senior nurses if they have any concerns.
"Here in Tayside, we have comprehensive infection monitoring procedures throughout our hospitals and these are able to rapidly identify any infection which then triggers a rapid response from our infection control teams. These cases of C. diff infection were detected very early which meant we were then able to reinforce all appropriate infection control measures.
"I am absolutely confident that all appropriate procedures to deal with this infection have been put in place immediately and that every effort has been made to make patients and their families aware of what is happening."
The ward has now been closed to all new admissions.
A Scottish Government spokesman said NHS Tayside had taken the necessary steps to contain the situation.
The spokesman added: "We are being kept fully informed, and our thoughts are with the families.
"Each such incident is extremely serious, and we expect NHS boards to continue to work hard to keep bringing infection rates down further. The most recent published statistics show that cases of both C.diff and MRSA in Scottish hospitals are at their lowest since records began."
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