Results of a recent Phase 3 study suggest that preventative treatment with certain oral antibiotics does not significantly decrease the rate of bacterial infections among newly diagnosed multiple myeloma patients receiving initial treatment.

In the study, myeloma patients who received prophylactic (preventative) antibiotics during the first two months of chemotherapy experienced statistically similar rates of infections during those two months and for up to two years following chemotherapy as patients who did not receive antibiotics.

“Unfortunately, prophylactic antibiotics did not significantly decrease the risk of infection,” said Dr. David Vesole from the John Theurer Cancer Center and lead investigator of the study. “This was an unexpected finding.”  Dr. Vesole indicated that perhaps different antibiotics would lower the infection rate.

However, Dr. Ravi Vij from Washington University School of Medicine in St. Louis was not surprised by the results. “Multiple trials in cancer have shown limited efficacy of antibiotic prophylaxis,” he explained.

Dr. Vij, who was not involved with the study, also pointed out that the benefits of preventative antibiotics may depend on how much the myeloma treatments suppress the immune system.  Since the chemotherapy regimens used in the study are no longer commonly used in the United States, he said there are still many unanswered questions.

Based on their findings, the study investigators conclude that prophylactic antibiotics should not be mandated for all myeloma patients undergoing active treatment.

However, they acknowledged that patients who are considered high-risk for developing bacterial infections may benefit from prophylactic antibiotics. These include patients with a history of repeated infections or severely low immunoglobulin levels, and patients receiving more intense treatment regimens.

Dr. Vesole added that immobile patients and those who underwent recent surgical procedures might also be at higher risk of developing infections.

The researchers further note that the preferred choice of prophylactic antibiotics for these patients remains unknown.

“I agree with the recommendations,” said Dr. Vij.  “I already use these criteria in routine clinical practice,” he added.

Multiple myeloma results in an overproduction of ineffective antibodies and suppression of healthy antibodies.  This leads to a weakened immune system, a condition known as immunosuppression.  The treatment of multiple myeloma can also cause myelosuppression, a decrease in the ability of the bone marrow to produce the blood cells required to fight off bacterial infections.

As a result, multiple myeloma patients are prone to developing infections. On average, myeloma patients will experience between 1.5 and 4.7 bacterial infections per year. However, they are two to three times more prone to developing an infection during the first two months of treatment with chemotherapy.

For instance, a previous study found that nearly half of all myeloma patients experience at least one infection during the first two months of treatment. Another study found that up to 10 percent of myeloma patients may die from a bacterial infection within these first two months.

In this Phase 3 study, researchers investigated whether prophylactic antibiotics would decrease the rate of serious bacterial infections in newly diagnosed myeloma patients during the first two months of treatment with chemotherapy.

The study included 212 newly diagnosed myeloma patients with a median age of 64 years.  The patients were enrolled between July 1998 and January 2008.

All patients were infection-free and did not receive any antibiotics for at least seven days prior to the start of chemotherapy.

Most patients in the study were treated with chemotherapy regimens that are no longer regularly used in the U.S. as initial myeloma therapy.  For example, 30 percent of the patients were treated with the combination of vincristine (Oncovin), doxorubicin (Adriamycin), and dexamatheasone (Decadron) -- commonly known as VAD -- and sixteen percent of the patients were treated with a combination of melphalan (Alkeran) and prednisone.

Patients in the study were randomly selected to receive an antibiotic, either Cipro (ciprofloxacin) (33 percent of patients) or Bactrim (trimethoprim-sulfamethoxazole) (35 percent of patients), or no preventative antibiotic (32 percent of patients) during the first two months of chemotherapy.

The researchers found that the rates of serious to life-threatening bacterial infections within the first two months of chemotherapy were generally lower among the patients who received Cipro (13 percent) and Bactrim (7 percent) compared to the patients who did not receive preventative antibiotics (16 percent).  However, the differences in the rates of serious infection across the three patient groups were not statistically significant.

In addition, the rates of bacterial infections of any seriousness during that time were similar among patients who received Cipro (20 percent), patients who received Bactrim (23 percent), and patients who did not receive antibiotics (22 percent).

After the two months of preventative antibiotics were completed, the rate of infection continued to be similar across the groups during the following two years, in which patients continued their multiple myeloma therapy.

For more information, please see the article in the journal Leukemia (abstract).