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.
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
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
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.