Outpatient Oral Antibiotics Safe, Effective

LUXEMBOURG-Outpatient oral antibiotic therapy can be as effectiveand safe as outpatient parenteral therapy in the treatment offebrile neutropenia, according to the latest trial results fromM.D. Anderson Cancer Center's Ambulatory and Supportive Care OncologyResearch Program (ASCORP).

ASCORP investigator Edward Rubenstein, MD, speaking at the 7thInternational Symposium of the Multinational Association of SupportiveCare in Cancer (MASCC), stressed that the study population wascarefully selected. It consisted of clinically stable outpatientswho had good renal and hepatic function, had no comorbiditiesrequiring hospitalization, and lived within a 30-mile radius ofthe cancer center.

"Cost minimization is important, but we cannot overlook thefact that, along with the improvement in resource utilization,there are potential disadvantages of outpatient therapy,"Dr. Rubenstein cautioned. "We certainly don't want to developserious complications in the outpatient setting, so we need tochoose our patient population carefully and monitor them adequately."

In the last 7 years, he noted, some 300 to 400 patients with febrileneutropenia have been treated on an outpatient basis in ASCORP,with no infection-related deaths and no cases of septic shock.

The 179 participants in the new ASCORP trial were treated fora minimum of 4 afebrile days, either with oral ciprofloxacin (Cipro)plus amoxicillin/clavulanic acid (Augmentin) (88 patients), orwith an intravenous regimen of aztreonam (Azactam) plus clindamy-cin(91 patients).

Patients in whom fever persisted for 72 hours were consideredto be treatment failures and were crossed over to the other regimen.Those with microbiologically documented infections were treateduntil the infection resolved, cultures returned to negative, andthey were afebrile for 4 days.

The overall response rate to outpatient antibiotic therapy was87% in the IV group and 90% in the oral group, Dr. Rubensteinreported. "If we look at bacteremia, the response rate wasa little bit lower in the intravenous arm, 50% versus 77%,"he said.

"In using the selection criteria to define 'low risk,' wehave even been able to successfully treat pneumonia," hecontinued. "The response rate was 100%, which is a very importantobservation because, generally, mortality from neutropenic pneumoniacan be as high as 40%."

Better Response in Solid Tumors

In the IV and oral groups, the response rates were 76% and 73%,respectively, for gram-positive infections, and 88% and 100%,respectively, for gram-negative infections. Hospital admissionbecame necessary for seven orally treated patients and 10 intravenouslytreated patients, but all responded to alternative treatments.

Dr. Rubenstein noted that the study randomization had been stratifiedso that equal numbers of patients with leukemia and patients whohad received growth factors were included in each study arm. Analysisof the results revealed higher response rates among patients withsolid tumors. A trend suggested that growth factors may have boostedthe response rate in patients receiving oral, though not intravenous,therapy.

"The low-risk patient population can be identified early,usually within 4 to 6 hours of the onset of the febrile episode,and, in these patients, outpatient therapy is safe and effectivewith both intravenous and oral regimens," he said.

Future directions for outpatient therapy, Dr. Rubenstein predicted,need to center on developing separate risk-factor models for leukemiapatients and for patients who have undergone bone marrow transplantation.

As a possible approach for patients who do not fall into the low-riskcategory, he suggested that IV therapy and growth factors mightbe started in the hospital, with early responders then switchedover to an oral regimen.