Treatment of Fever in Hospitalized Patients with Low White Blood Cell Counts

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The summary below is from the full report titled "Ciprofloxacin plus Piperacillin Compared with Tobramycin plus Piperacillin as Empirical Therapy in Febrile Neutropenic Patients. A Randomized, Double-Blind Trial." It is in the 16 July 2002 issue of Annals of Internal Medicine (volume 137, pages 77-86). The authors are JE Peacock Jr, DA Herrington, JC Wade, HM Lazarus, MD Reed, JW Sinclair, DC Haverstock, SF Kowalsky, DD Hurd, DA Cushing, CP Harman, and GR Donowitz.

What is the problem and what is known about it so far?

Types of cancer, such as leukemia, and the therapies used to treat them (for example, chemotherapy and bone marrow transplants) often decrease the numbers of white blood cells in the body. White blood cells fight bacterial, fungal, and viral infections. Most patients with cancer who have few white blood cells have very weak immune systems and can't fight infections well. They get infections easily and, as a result, can die, particularly if the infections are not recognized early and treated. Fever is usually one of the earliest signs of infection. Thus, doctors prescribe powerful antibiotics whenever they detect a fever and suspect an infection in a patient with cancer whose white blood cell count is low. Doctors usually give combinations of antibiotics that work against many different types of bacteria. We do not know whether certain combinations work better and cause fewer side effects than others.

Why did the researchers do this particular study?

To compare two different combinations of antibiotic drugs for treating fever in hospitalized patients with low white blood cell counts.

Who was studied?

485 hospitalized patients with cancer and a low number of white blood cells. Most had leukemia or had received bone marrow transplants. All had fever that was presumed to have been caused by infection.

How was the study done?

Patients were randomly assigned to receive one of two combinations of antibiotic drugs (peracillin plus ciprofloxacin or piperacillin plus tobramycin). The drugs were given through a vein. The patients and their doctors did not know which drug combination the patients were receiving. The researchers compared treatment responses and adverse side effects between patients who were given the two different drug combinations. The researchers considered the patients' treatment response to be successful if they had no fever for at least 4 days, resolution of signs of infection without having to change the initial antibiotic drugs, and a negative culture from the blood or the original infection site.

What did the researchers find?

Nearly 25% of the patients in both groups had successful treatment responses. Fever resolved more quickly (approximately 1 day sooner) in patients given pipericillin plus ciprofloxacin. Four percent of the patients in each group died. Approximately 70% in each group needed additional therapy with other antibiotic or antifungal drugs. Medication-related side effects, such as diarrhea and abnormal results on kidney and liver function tests, occurred in approximately 20% to 30% of patients in both groups.

What were the limitations of the study?

Many patients in both groups needed therapy other than their originally assigned antibiotic combinations. In such instances, it is difficult to sort out how effective the original antibiotic combinations were.

What are the implications of the study?

Piperacillin plus ciprofloxacin and piperacillin plus tobramycin have similar efficacy and safety for hospitalized patients with low white blood cell counts and fever.