New Dual Antibiotic Effective Against Changing Hospital Flora

MONTREAL-The newest beta-lactam plus beta-lactamase inhibitorcombination, piperacillin/tazobactam (Zosyn), when combined withamikacin, is highly effective for empiric treatment of patientswith febrile granulocyto-penia, Jean A. Klastersky, MD, said atthe 19th International Congress of Chemotherapy. He was speakingat a symposium sponsored by Lederle/Wyeth-Ayerst International,manufacturer of Zosyn.

In a study conducted by the International Antimicrobial TherapyCooperative Group (IATCG) of the European Organization for Researchand Treatment of Cancer (EORTC), 61% of 342 febrile episodes weresuccessfully treated with the piperacillin/tazobactam-amikacincombination, compared with 54% of 364 episodes treated with cef-tazidimeplus 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 (AntimicrobialAgents and Chemotherapy 39:445-452, 1995).

Noting that standard antibiotic strategies devised a decade agowere directed primarily against gram-negative organisms, Dr. Klastersky,chief of medicine, Institut Jules Bordet, Brussels, Belgium, explainedthat today's hospital flora are drastically different. Althoughnot quite as lethal as some of the gram-negative strains suchas Pseudomonas aeruginosa, as many as 80% of infectionsin neutro-penic patients are now traced to gram-positive bacteria.

Vancomycin Resistance

To ensure adequate coverage for both gram-negative and gram-positiveorganisms, some experts have suggested combining ceftazidime withvancomycin. Dr. Klastersky noted that this strategy works, "butthere is a price to be paid in terms of the emergence of vancomycin-resistantmicrobes."

Stressing the importance of reserving vancomycin for treatmentof methicillin-resistant gram-positive bacteria, he characterizedvancomycin-containing combinations for empiric therapy as beingunnecessary in most cases.

Any new antibiotic regimen for empiric therapy of febrile neutropenicpatients should have improved activity against gram-positive organismswhile retaining potency against dangerous infections with gram-negatives,Dr. Klastersky said. One of the primary objectives of the IATCG-EORTCstudy was to assess the effectiveness of the piper-acillin/tazobactam-amikacincombination 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 singleorganisms, most frequently, to coagulase-negative staphylococciand viridans group streptococci. Patients' responses to bacteremicinfections differed according to the treatment they received:50% of those given piperacillin/tazobactam-amikacin were successfullytreated, compared with only 35% of those who received ceftazidime-amikacin(P = .05).

Dr. Klastersky reported that these results were confirmed in aseparate study conducted at eight medical centers in France. Inaddition to better control of fever, the combination of piperacillin/tazobactam-amikacinin the multicenter French study was also associated with a lowerincidence of superinfection
(P = .08), fewer days of fever during aplasia (P= .01), fewer antibiotic changes during the entire neutropenicperiod (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-stimulatingfactors as a complement to effective antibiotic regimens mustbe assessed in appropriate trials, he said, but to date thereis no clear indication that the use of these factors modifiesthe ultimate outcome.