The Use of Prophylactic Antibiotics for Neutropenia

Pharmacology Watch

Antibacterial prophylaxis is generally not recommended for neutropenic patients undergoing chemotherapy. Two studies in the Sept. 8 issue of the New England Journal of Medicine may change that recommendation. The first study from Italy looked at 760 adult patients who were undergoing treatment for acute leukemia, solid tumors, or lymphoma and were at risk for chemotherapy-induced neutropenia lasting more than 7 days. Many were undergoing stem cell transplantation. Patients were randomized received either oral levofloxacin 500 mg daily or placebo from the start of chemotherapy until the resolution of neutropenia. The rate of fever present for the duration of neutropenia was reduced in the levofloxacin group (65% levofloxacin prophylaxis, 85% placebo; RR, 0.76, 95% CI; P = 0.001). The levofloxacin group also had a lower rate of microbiologically documented infections (17% absolute difference in risk; P < 0.001), bacteremia (16% absolute difference in risk; P < 0.001), and single agent gram-negative bacteremias (7% absolute difference in risk; P < 0.01), compared to the placebo group. There was no difference in mortality, and there was no difference in outcomes between patients with acute leukemia or those with solid tumors or lymphoma. Treatment was generally well-tolerated. The authors conclude that prophylactic treatment with levofloxacin is an effective and well-tolerated way of preventing febrile episodes and other relevant infection-related outcomes in patients with cancer and profound and protracted neutropenia (Levofloxacin to Prevent Bacterial Infection in Patients with Cancer and Neutropenia. N Engl J Med. 2005;353:977-987).

The second study from England looked at 1565 patients undergoing cyclic chemotherapy for solid tumors or lymphoma who were at risk for temporary, severe neutropenia. Since these patients were receiving cyclic chemotherapy, the rate of neutropenia was significantly lower than the first study. Patients were randomized to receive levofloxacin 500 mg daily or placebo for 7 days during the expected neutropenia period. During the first cycle of chemotherapy, 3.5% of patients in the levofloxacin group had a least one febrile episode, compared with 7.9% in the placebo group (P < 0.001). During the entire chemotherapy course, 10.8% of patients in the levofloxacin group had a least one febrile episode, compared with 15.2% of patients in the placebo group (P = 0 .01); the rate of probable infection was 34.2% and 41.5%, respectively (P = 0.004). Hospitalization rates were significantly higher in the placebo group, and the rate of severe infection was twice as high in the placebo group (1.0% vs 2.0% [P = 0 .15]). The death rate was same in both groups. The authors concluded that prophylactic use of levofloxacin reduces the rate of fever, probable infection, and hospitalization (Cullen M, et al. Antibacterial Prophylaxis After Chemotherapy for Solid Tumors and Lymphomas. N Engl J Med. 2005;353:988-998).

An accompanying editorial suggests that these are important studies which provide more data on prophylactic antibiotics in neutropenia that had previously been available. However, further study still needs to define which patients are at highest risk and the period of greatest risk during chemotherapy. Most importantly, the emergence of resistant organisms, which was seen in the Italian study, is a major concern. The author states "If prophylactic antimicrobial therapy is to be adopted at a cancer center, it should be accompanied by vigorous infection-control practices and careful monitoring for the emergence of resistant organisms" (Baden LR. Prophylactic Antimicrobial Agents and the Importance of Fitness. N Engl J Med. 2005:353:1052-1054).

Is It Hot In Here?

Hot flashes are common problem for women undergoing treatment for breast cancer. A new study suggests that gabapentin adjusted 900 mg per day may help alleviate symptoms. Four hundred twenty women, with breast cancer and 2 or more hot flashes per day, were randomly assigned to receive gabapentin 300 mg per day or gabapentin 900 mg/day or placebo in 3 divided doses for 8 weeks. The 900 mg per day does reduce hot flashes by 49% and 46% at 4 and 8 weeks, respectively. The 300 mg dose was not effective at a statistical level. The authors suggest that gabapentin 900 mg per day should be considered for treatment of hot flashes in women with breast cancer (Pandya KJ, et al. Gabapentin for Hot Flashes in 420 Women with Breast Cancer: A Randomised Double-Blind Placebo-Controlled Trial. Lancet. 2005;366:818-824).

Homeopathy vs Conventional Medicine

A new study suggests that homeopathy is no better than placebo in treating disease. Researchers from the University of Berne in Switzerland, reviewed over 100 clinical trials of homeopathy and conventional medicine. Eight large homeopathy trials were eventually used in a meta-analysis, along with 6 large conventional medicine trials. The odds ratio for homeopathy was 0.88 and for conventional medicine 0.58. When only the largest trials were used, the odds ratio for homeopathy was 0.96 and for conventional medicine 0.67. This suggests that the benefit from homeopathy is no better than random chance (Shang A, et al. Are the Clinical Effects of Homeopathy Placebo Effects? Comparative Study of Placebo-Controlled Trials of Homeopathy and Allopathy. Lancet. 2005; 366:726-732). An accompanying editorial states "Now doctors need to be bold and honest with their patients about homeopathy's lack of benefit. . ." (The End of Homeopathy. Lancet. 2005;366:690). Homeopathy which uses very dilute solutions to treat disease has been popular in Europe; however, this study marks a trend away from homeopathy in England. The Swiss government also recently withdrew insurance coverage for homeopathy after a 5-year trial because it did not meet efficacy and cost effectiveness criteria.

FDA Actions

The FDA has approved a new 4-component vaccine for children aged 12 months to 12 years that includes measles, mumps, rubella, and varicella viruses. The approval was based on data showing effectiveness of the vaccine was similar to that of MMR (measles, mumps, and rubella) and varicella vaccine (Varivax). The new vaccine will be marketed under the trade name ProQuad by Merck & Co.

Sanofi-Synthelabo has received approval to market an extended release formulation of zolpidem (Ambien) for the treatment of insomnia. The new preparation is a bi-layered tablet that delivers the drug in 2 stages, a quick dissolving layer to induce sleep, and a slower release layer to provide sleep continuity. Ambien CR will be marketed in a 12.5 mg dose for adults and a 6.25 mg strength for patients 65 years and older.

The Senate has approved a bill to limit over-the-counter sales of pseudoephedrine, a key ingredient in the illicit manufacturing of methamphetamine. The bill which has bipartisan support, will require decongestant medications containing pseudoephedrine to be sold behind pharmacy counters and would limit how much any individual can buy to 7.5g a month (250 30 mg tablets).The bill also encourages a computer tracking system to limit multiple purchases at different stores and pharmacies. A similar bill is working its way to the House of Representatives.

The FDA is one step closer to approving Pfizer's inhaled insulin powder after an advisory panel voted 7-2 to urge approval. The preparation, which will be marketed under the trade name Exubera, is a short-acting insulin powder that is used before meals. The drug does not replace the need for long acting insulin injections. There have been concerns that Exubera may hamper lung function in diabetics, but Pfizer has been able to show 2-year data that suggest patients experience only minimal decrease in lung capacity that is reversible if the drug is stopped.

This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5416. E-mail: