Updates

by Carol A. Kemper, MD, FACP

Adefovir Dipivoxil for Hepatitis B

Source: Marcellin P, et al. N Engl J Med. 2003;348:808-816.

Adefovir dipivoxil (AD) has potent in vitro activity against hepatitis B virus (HBV) and has been shown to reduce viremia in preliminary studies. In this large, multi-center study, 515 patients with chronic HBV infection, all of whom were positive for hepatitis B antigen, were randomly assigned to receive AD 10 mg or 30 mg or blinded placebo daily for 48 weeks.

The primary end point of the study was histologic improvement, which was determined in 329 patients for whom pretreatment liver biopsy specimens were available. Compared with 25% spontaneous histologic improvement in the placebo group, histologic improvement was observed in 53% of patients receiving a 10-mg dose of AD and 59% of patients receiving a 30-mg dose of AD (both comparisons, P < .0001). A statistically significant reduction was also observed in serum HBV DNA levels, the proportion of patients achieving undetectable HBV DNA, and normalization of alanine aminotransferase. In patients receiving either 10 or 30 mg of AD for 48 weeks, 21% and 39%, respectively, had undetectable levels of HBV DNA in serum (< 400 copies/mL), compared with none of the placebo recipients. Remarkably, 12% and 14% of patients receiving 10 and 30 mg, respectively, had seroconversion of Hbe Ag during treatment. Seven different novel substitutions were found in the reverse transcriptase gene of virus from 4 patients receiving AD and 3 receiving placebo, but virus from all 7 remained susceptible.

Adverse events were more frequent in the group receiving the higher dose of AD, although the incidence of severe events (grade 3 or 4) was similar. Drug was discontinued in only 2% of the lower dose group and 3% of the higher dose group. Renal impairment and hypophosphatemia did not appear to occur with any significant frequency; only 1 patient had a maximal increase in serum creatinine, by 1.8 mg/dL.

AD appears to be well tolerated with an efficacy profile similar to lamivudine (3TC), with no evidence to suggest the evolution of resistance during therapy.


Let’s Have a Carpet Picnic at Your House?

Source: Rice EH, et al. Emerg Infect Dis. 2003;9:1-6.

Many cases of nontyphoidal salmonellosis are believed to result from household contamination with Salmonella enterica, which increases with occupational exposure to the organisms (eg, cattle and dairy farmers, laboratory workers, and veterinarians). Rice and colleagues cultured vacuum cleaner bags from 55 households with occupants with known occupational exposure to salmonella and 24 households without known exposure.

In households with occupants with known occupational exposure to infected cattle, 8 of 26 (30.8%) vacuum bags were positive for S typhimurium. Similarly high levels of contamination were found in households of people who worked with salmonella in the field or the laboratory, where 4 of 13 (30.8%) of vacuum bags where positive. In the homes of 16 people who had been exposed to an outbreak of feline salmonellosis at the veterinary clinic at which they worked, 3 (18.8%) of the bags were positive. In contrast, only 1 of 12 (8.3%) vacuum bags from the homes of people working with livestock without known infection were positive. (The single positive culture was for serovar Dublin.)

In order to reduce household contamination, Rice et al attempted various methods of carpet cleaning. Shampooing without disinfectant resulted in a modest decrease in colony counts. Chlorhexidine added to carpet shampoo had no effect, whereas phenolic disinfectants had the greatest effect but did not totally eliminate colonization. Phenolic compounds, which are hazardous, may not be suitable for residential dwellings.

Carpet, it turns out, is a common source of household contamination with salmonella organisms, and it is nearly impossible to decontaminate. Rice et al proposed that individuals who work with potentially infected animals limit the carpets and rugs in their homes, increase the noncarpeted spaces, and remove their shoes before entering the home, as well as any potentially contaminated clothing.