the two most cited published treatment trials of oseltamivir reported any drug-attributable serious adverse events. It is pregnancy category C in the United States and category B in Australia, meaning that it has been taken by a small number of women without signs of problems and in animal studies it looks safe. Dose adjustment may be needed in those with kidney problems. Mechanism of action Oseltamivir is a neuraminidase inhibitor, a competitive inhibitor of influenza's neuraminidase enzyme. The enzyme cleaves the sialic acid which is found on glycoproteins on the surface of human cells that helps new virions to exit the cell. Thus oseltamivir prevents new viral particles from being released. Resistance The vast majority of mutations conferring resistance are single amino acid residue substitutions (His274Tyr in N1) in the neuraminidase enzyme. A 2011 meta-analysis of 15 studies found a pooled incidence rate for oseltamivir resistance of 2.6%. Subgroup analyses detected higher rates among influenza A patients, especially the H1N1 subtype. It was found that a substantial number of patients might become oseltamivir-resistant as a result of oseltamivir use, and that oseltamivir resistance might be significantly associated with pneumonia. In severely immunocompromised patients there were reports of prolonged shedding of oseltamivir- (or zanamivir)-resistant virus, even after oseltamivir treatment was stopped. H1N1 flu or "Swine flu" , the World Health Organization (WHO) reported 314 samples of the prevalent 2009 pandemic H1N1 flu tested worldwide showed resistance to oseltamivir. The CDC found sporadic oseltamivir-resistant 2009 H1N1 virus infections had been identified, including with rare episodes of limited transmission, but the public health impact had been limited. Those sporadic cases of resistance were found in immunosuppressed patients during oseltamivir treatment and persons who developed illness while receiving oseltamivir chemoprophylaxis. During 2011, a new influenza A(H1N1)2009 variant with mildly reduced oseltamivir (and zanamivir) sensitivity was detected in more than 10% of community specimens in Singapore and more than 30% of samples from northern Australia. While there is concern that antiviral resistance may develop in people with haematologic malignancies due to their inability to reduce viral loads and several surveillance studies found oseltamivir-resistant pH1N1 after administration of oseltamivir in those people, , widespread transmission of oseltamivir-resistant pH1N1 has not occurred. During the 2007–08 flu season, the US CDC found 10.9% of H1N1 samples (n=1,020) to be resistant. In the 2008–09 season, the proportion of resistant H1N1 increased to 99.4%, while no other seasonal strains (H3N2,