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New Dual Antibiotic Effective Against Changing Hospital Flora

New Dual Antibiotic Effective Against Changing Hospital Flora

MONTREAL-The newest beta-lactam plus beta-lactamase inhibitor combination, piperacillin/tazobactam (Zosyn), when combined with amikacin, is highly effective for empiric treatment of patients with febrile granulocyto-penia, Jean A. Klastersky, MD, said at the 19th International Congress of Chemotherapy. He was speaking at a symposium sponsored by Lederle/Wyeth-Ayerst International, manufacturer of Zosyn.

In a study conducted by the International Antimicrobial Therapy Cooperative Group (IATCG) of the European Organization for Research and Treatment of Cancer (EORTC), 61% of 342 febrile episodes were successfully treated with the piperacillin/tazobactam-amikacin combination, compared with 54% of 364 episodes treated with cef-tazidime plus amikacin (P = .05), Dr. Klastersky said.

Moreover, time to defervescence was significantly shorter (P = .01) and the time to failure was significantly longer
(P = .05) with the newer antibiotic regimen (Antimicrobial Agents and Chemotherapy 39:445-452, 1995).

Noting that standard antibiotic strategies devised a decade ago were directed primarily against gram-negative organisms, Dr. Klastersky, chief of medicine, Institut Jules Bordet, Brussels, Belgium, explained that today's hospital flora are drastically different. Although not quite as lethal as some of the gram-negative strains such as Pseudomonas aeruginosa, as many as 80% of infections in neutro-penic patients are now traced to gram-positive bacteria.

Vancomycin Resistance

To ensure adequate coverage for both gram-negative and gram-positive organisms, some experts have suggested combining ceftazidime with vancomycin. Dr. Klastersky noted that this strategy works, "but there is a price to be paid in terms of the emergence of vancomycin-resistant microbes."

Stressing the importance of reserving vancomycin for treatment of methicillin-resistant gram-positive bacteria, he characterized vancomycin-containing combinations for empiric therapy as being unnecessary in most cases.

Any new antibiotic regimen for empiric therapy of febrile neutropenic patients should have improved activity against gram-positive organisms while retaining potency against dangerous infections with gram-negatives, Dr. Klastersky said. One of the primary objectives of the IATCG-EORTC study was to assess the effectiveness of the piper-acillin/tazobactam-amikacin combination for treatment of infections due to gram-positive bacteria.

When the investigators analyzed microbiologically documented infections, they noted that 161 episodes of bactere-mia were due to single organisms, most frequently, to coagulase-negative staphylococci and viridans group streptococci. Patients' responses to bacteremic infections differed according to the treatment they received: 50% of those given piperacillin/tazobactam-amikacin were successfully treated, compared with only 35% of those who received ceftazidime-amikacin (P = .05).

Dr. Klastersky reported that these results were confirmed in a separate study conducted at eight medical centers in France. In addition to better control of fever, the combination of piperacillin/tazobactam-amikacin in the multicenter French study was also associated with a lower incidence of superinfection
(P = .08), fewer days of fever during aplasia (P = .01), fewer antibiotic changes during the entire neutropenic period (P = .02), and a reduced need for van-comycin (P = .01).

Because these neutropenic patients are vulnerable to infection, especially if granulocytopenia is prolonged, the benefit of colony-stimulating factors as a complement to effective antibiotic regimens must be assessed in appropriate trials, he said, but to date there is no clear indication that the use of these factors modifies the ultimate outcome.

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