Health officials said on Wednesday five new cases were discovered in Gauteng, South Africa's premier economic region, which includes Johannesburg and Pretoria.
The discovery has stoked concerns that extremely drug resistant tuberculosis, or XDR-TB, may be spreading, complicating efforts to contain the deadly march of Aids.
An easily-transferred airborne respiratory disease, tuberculosis is the main direct cause of death for people with Aids in South Africa.
Officials said the strain of TB found in Gauteng this week did not immediately match the one that has killed 62 people in eastern KwaZulu-Natal province over the past month. All 62 were HIV positive.
"A preliminary report suggests they are not the same strain, but to say conclusively a laboratory has to do DNA testing that takes months," said Dr. Joe Khoali, TB adviser for the Gauteng Health Department.
"We are not sure if we're dealing with one or multiple strains," Khoali told Reuters.
The two males and three females had been admitted to isolation units in the Sizwe Hospital in Johannesburg, health officials said.
A senior official of the World Health Organisation told Reuters it was probable XDR-TB was not confined to South Africa.
Paul Nunn, coordinator of WHO's Stop TB Department said earlier this week XDR-TB could be present in other regions of Africa afflicted by HIV/Aids but which lacked the capacity to find and diagnose the illness.
"It isn't just an issue of a particular strain spreading," Nunn said. "It is an issue of (whether) there are outbreaks occurring that we don't know about. We feel it's quite possible."
Experts say XDR-TB has been seen worldwide, but the outbreak in South Africa is acute because of the high number of fatalities in an isolated area.
Nunn said a failure by South Africa to implement a robust infection control programme to properly manage the disease, coupled with a high HIV infection rate, could have led to the current outbreak.
An estimated 1 in 9 of South Africa's 45 million people carry the virus, giving the nation one of the worst HIV rates in the world. Infection rates in neighbouring countries like Lesotho, Botswana, Swaziland and Zimbabwe are also high.
The outbreak of XDR-TB has coincided with raging controversy over South African Health Minister Manto Tshabalala-Msimang's promotion of alternative Aids remedies.
The minister has enraged activists and many health experts by pushing "natural" HIV treatments such as beetroot and garlic while playing down anti-retroviral drugs.
In local media interviews this week, Tshabalala-Msimang denied she had ever held out these nutrition-based remedies as alternatives to anti-retroviral drugs.
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