New Antibiotics Appear Effective Against Multiply Resistant Bacteria

By William T. Elliott, MD, FACP

Two new antibiotic classes appear to be effective against multiply resistant bacteria, including vancomycin-resistant enterococci and staph. The FDA recently approved Rhone-Poulenc Rorer’s two-drug combination of quinupristin and dalfopristin, both members of the new class of antibiotics known as streptogramins. The two agents work synergistically to inhibit bacterial protein synthesis. The parenteral drug combination, which was approved for the treatment of complicated skin infections as well as infections caused by vancomycin-resistant Enterococcus faecium, will be marketed under the name Synercid. Pharmacia & Upjohn is seeking approval for its own new drug, linezolid, the first of a new class of antibiotics known as oxazolidinones. Linezolid also appears to be effective against vancomycin-resistant gram-positive organisms. It is active as both an intravenous and oral preparation. The drug is in the final regulatory stages with approval expected within the next six months.

Does growth hormone benefit critically ill patients? Two recent studies from Europe raise doubts. In controlled, double-blind studies of more than 500 intensive care patients, the in-hospital mortality rate was higher for patients treated with growth hormone (N Engl J Med 1999;341:785-792), contradicting the findings of earlier American studies. In an accompanying editorial, the reasons for the negative findings are considered, including the possibility that the drug may have been given too late in the hospitalization or that it is not effective for patients with respiratory failure, the major diagnosis in the European studies. Growth hormone also causes an increase in metabolism and is pro-inflammatory, both reasons why the drug may worsen mortality in patients with inflammatory conditions.

Phen-fen may have been given a bad rap—at least with regard to the weight loss drug combination’s propensity for causing heart valve abnormalities. The combination of phentermine and fenfluramine was implicated in the development of valvular insufficiency, eventually leading to the removal of fenfluramine (and later dexfenfluramine) from the market. But several recent studies have questioned whether the echocardiograms that showed the valvular regurgitation in the original studies may have been overread. The most recent study from Harvard/Beth Israel reviewed echocardiograms in 226 patients who were treated with phen-fen as part of a clinical study in the mid-90s. The prevalence of valvular abnormalities was found to be no higher in the phen-fen treated patients than the general population (J Am Coll Cardiol 1999;34:1153-1162). This study, and others seriously question the validity of the original studies that led to the withdrawal of these drugs.

Expect an unprecedented marketing push this winter for Glaxo’s zanamivir (Relenza) (see page 20), the recently approved anti-influenza drug, and Roche’s oseltamivir (Tamiflu) whose FDA approval is expected before the flu season starts. Both will be heavily promoted directly to flu sufferers. According to the Wall Street Journal, the marketing departments of both companies plan to track flu outbreaks around the country, then descend upon affected areas with a blitz of TV, radio, and print ads directed at consumers as well as aggressive marketing to physicians. The goal is to convince consumers that the flu is now a treatable condition and, in the process, generate more than $1 billion in revenues. In order to avoid just such a scenario, the United Kingdom's national health program will probably not cover the cost of zanamivir. A national committee of experts responsible for advising the government on how it should spend the national health budget has recommended rejecting the flu drug. Managed pharmacy plans in this country are also struggling with the relatively modest benefits of the drug vs. the price tag of $44 per treatment course.

The FDA has approved raloxifene (Evista—Eli Lilly) for the treatment of postmenopausal osteoporosis. Previously, the drug had only been approved for prevention of osteoporosis. Sales of raloxifene have been below expectations, partially due to competition from Merck’s alendronate (Fosamax). Alendronate works by inhibiting bone resorption by osteoclasts, similar to the way estrogens (and drugs like raloxifene) work. In related news, a new study sponsored by Merck suggests that the effects of alendronate and hormone replacement therapy (HRT) are additive. In a multicenter, randomized trial of nearly 430 women, the combination of alendronate and HRT significantly increased bone density in the lumbar, spine, and hip, but not the femoral neck, compared to HRT alone (J Clin Endocrinol Metab 1999;84:3076-3081).

"Head lice from hell" is the way some pediatricians feel about a wave of resistant pediculosis sweeping across the country. The high treatment rate in the United States may be partially to blame for the prevalence of permethrin-resistant pediculosis. Researchers from Harvard recently tested permethrin resistance in lice from children in Idaho, Massachusetts, and Borneo (where pediculosis is often tolerated and not treated). All the lice from Borneo were immobilized by increasing doses of permethrin, but a percentage of head lice from the U.S. sites were resistant to all doses of the permethrin (Arch Pediatr Adolesc Med 1999;153:969-973). Parents are resorting to a number of home remedies including salad dressing and mayonnaise, but a better option may be coming back. Medicis’ Ovide pediculicide, which contains malathion, is being brought back after poor sales and safety concerns forced it off the market. The product kills lice and eggs, but it is flammable, needs to be left on for 8-12 hours, and has a distinct odor.

The antidepressant mirtazapine (Remeron-Organon) may have a new and unexpected use. A report in Neurology of five patients with movement disorders (Parkinsonism, action tremor, and levodopa-induced dyskinesias) who were incidentally treated with mirtazapine for depression showed marked improvement in tremor soon after the drug was started (Neurology 1999;53:1154). Two patients stopped the drug temporarily with a return of the preexisting tremor. The drug acts on both serotonergic and noradrenergic neurons, and has been touted as an antidepressant with limited sexual and gastrointestinal side effects. The authors of these case reports recommend a further study of mirtzapine for the treatment of tremors.