Investigations to date showed that the resistant-form of swine flu was not transmitted outside of two hospital wards in Wales and North Carolina where they emerged in October and November, the WHO said in statement issued overnight.
A total of a dozen patients, all with severely suppressed immune systems due to underlying medical conditions, were infected with H1N1 viruses resistant to oseltamivir, the generic name for Roche's Tamiflu.
"Transmission of resistant virus from one patient to another is suspected in both outbreaks," the WHO said.
"No illness in staff caring for these patients has been detected, suggesting that the resistant virus does not spread easily to otherwise healthy people, especially when good measures for infection control are in place."
All 8 patients in Wales were hospitalized because of severe blood disorders, which severely weakened their immune systems, according to the United Nations agency. All are alive, including one being treated in intensive care.
In the United States three of the four patients died "but the role of H1N1 infection in contributing to these deaths is uncertain," it said.
Patients with severely compromised immune systems are especially vulnerable to the H1N1 virus, according to the WHO.
"These patients are highly susceptible to infection, particularly difficult to treat and especially likely to develop resistance," it said.
Standard Tamiflu doses and length of treatment are "unlikely to be sufficient" for these patients, according to the agency.
"Zanamivir should be considered as the treatment of choice for patients who develop prolonged influenza illness despite treatment with oseltamivir," it said.
GlaxoSmithKline and Biota make zanamivir under the brand name of Relenza, a flu drug that must be inhaled.
"Once oseltamivir resistant virus has been detected in a ward treating severely immuno-compromized patients, doctors should consider switching to zanamivir as the antiviral drug of first choice for treatment," the WHO said.
Zanamivir should also be considered for preventive treatment of other patients on the ward who have been exposed, it added.