Infectious Diseases Watch

Herpes Simplex Vaccine Trial Misses the Mark

In a study published January 5, 2012, in The New England Journal of Medicine, researchers found a new investigational herpes simplex virus (HSV) vaccine to be effective in preventing HSV-1 genital disease and infection, but not in preventing HSV-2 disease or infection.

In this National Institutes of Health and industry—sponsored double-blind trial, 8323 women aged 18 to 30 years were randomized to receive either an investigational HSV vaccine or a low-dose hepatitis A vaccine used as a control at 0, 1, and 6 months.

The HSV vaccine protected against HSV genital disease 20% of the time (95% confidence interval [CI], -929 to 50). It showed efficacy against genital disease caused by HSV-1 after 2 doses (vaccine efficacy, 58%; 95% CI, 12-80) and 3 doses (77%; 95% CI, 31-92), but not against genital disease caused by HSV-2 after 2 doses (-38%; 95% CI, -162 to 29) or 3 doses (-40%; 95% CI, -234 to 41).

The vaccine’s overall efficacy in preventing HSV infections was 22% (95% CI, 2-38), but this number was driven by efficacy against HSV-1 infections (35%; 95% CI, 13-52). It had no efficacy against HSV-2 infection (-8%; 95% CI, -59 to 26).

The results were a disappointment to researchers, as the vaccine displayed efficacy against HSV-2 in 2 smaller trials involving discordant couples. It is not clear why the vaccine was efficacious in preventing infection and genital disease from HSV-1, but not from HIV-2, the more common cause of genital herpes.

Shorter Treatment for Patients with Latent Tuberculosis

According to a study published December 8, 2011, in The New England Journal of Medicine, the use of rifapentine and isoniazid for 3 months is just as effective as the standard regimen of isoniazid for 9 months in preventing tuberculosis, and is associated with a higher completion rate.

The Centers for Disease Control and Prevention (CDC)-sponsored prospective, open-label, randomized study enrolled individuals at high risk for progressing from latent tuberculosis infection to active disease. Nearly 8000 subjects were randomized to either receive rifapentine (900 mg) and isoniazid (900 mg), on a weekly basis under direct observation for 3 months, or self-administered isoniazid (300 mg) daily for 9 months.

The results show that the 3-month combination regimen is as effective as the standard 9-month isoniazid regimen. Seven combination-therapy patients (0.19%) developed active tuberculosis, compared with 15 in the isoniazid-only group (0.43%). In the combination-therapy group, 82.1% of patients completed treatment, whereas 69.0% in the isoniazid-only group completed treatment (P <.001).

Those in the combination-therapy group had a higher rate of permanent discontinuation due to an adverse effect compared with the isoniazid-only group (4.9% and 3.7%, respectively; P = .009). Drug-related hepatotoxicity occurred less frequently in the combination-therapy group compared with the isoniazid group (0.4% and 2.7%, respectively; P <.001).

The CDC has implemented the results from this study in their treatment guidelines. Three-month combination therapy for latent tuberculosis infection is not recommended for children younger than 2 years and pregnant women due to lack of studies, nor for HIV-infected patients being treated with antiretrovirals, due to potential drug interactions.

Researchers Investigate Means of Resensitizing Bugs to Antibiotics

In a proof-of-principle study published online on November 23, 2011, in Applied and Environmental Microbiology, researchers outlined methods to reverse bacterial resistance to antibiotics.

Scientists isolated genes from streptomycin-resistant Escherichia coli and genetically engineered them to restore sensitivity to the drug. These engineered genes were then loaded into bacteriophages, which could then infect the resistant bacteria. Once inside, the mutant genes were targeted and modified to reverse streptomycin—resistance.

The resulting resensitized E coli restored the mean inhibitory concentration, the lowest concentration of drug at which no growth is seen, from 100 mcg/mL to 12.5 mcg/mL in one strain and from 200 mcg/mL to 3.125 mcg/mL in a second strain. Additionally, researchers used the same method to resensitize nalidixic acid—resistant E coli strains with similar success.

The authors of the study suggest this method can be used to restore sensitivity of other bacteria to antibiotic agents and can be applied in the treatment of hospital surfaces to increase the treatability of drug-resistant nosocomial pathogens.

The study is a promising development that could give the health care team a valuable tool in fighting drug-resistant bacterial infections. Testing with important nosocomial pathogens such as methicillin-resistant Staphylococcus aureus, vancomycinresistant Enterococcus, and Clostridium difficile, especially in realworld settings, will need to be completed before the method’s viability and application can truly be assessed. PT