SAN DIEGO, CaliforniaResearchers at the Jones Group/JMI
Laboratories, North Liberty, Iowa, have confirmed that Gram-positive
pathogens predominate in neutropenic cancer patients with infections. The
study also found that these organisms are no more likely to be resistant to
available drugs in the cancer population than in the general population. They
presented the results of the first year of the study in two poster
presentations at the 43rd Annual Inter-science Conference on Antimicrobial
Agents and Chemotherapy (ICAAC abstracts C2-290 and C2-296).
The 3-year longitudinal surveillance study, known as the
Chemotherapy Alliance for Neutropenics and Control of Emerging Resistance
(CANCER) Program, was founded in 2001 to monitor resistance in antimicrobial
and antifungal therapies used for oncology patients. Thirty-two oncology
centers, hospitals, and clinics from the United States and Canada submitted
2,042 isolates (1,992 bacterial and 50 yeast) to JMI Laboratories for testing
against 41 antimicrobial agents. The study is being funded by the Wyeth
According to Jeff Kirby, a medical technologist with JMI
Laboratories, during the last 2 decades, a significant change has occurred in
the prevalence of bacterial organisms in oncology patients with neutropenia.
Where once Gram-negative pathogens dominated, Gram-positives are now in the
majority. "One reason is that when Gram-negatives are prevalent,
pharmaceutical companies will target those and produce drugs that are
effective," Mr. Kirby said. "As the Gram-negatives are killed effectively,
there is a rise on the other side."
In this first year of the study, researchers found that 53%
of the bacterial isolates submitted were Gram-positive organisms. The top
five pathogens overall were Staphylococcus aureus (18.1%),
Escherichia coli (14.3%), coagulase-negative staphylococci (14.1%),
Enterococcus spp (9.9%), and Klebsiella spp (9.6%). The top five
Gram-positive pathogens were S aureus (18.1%), coagulase-negative
staphylococci (14.1%), Enterococcus spp (9.9%), Streptococcus
viridans (3.5%), and Streptococcus pneumoniae (2.6%).
"The critical question is, are the drugs we use to treat
Gram-positive isolates as effective today as they were previously, and will
they be effective in the future?" said Alan Mutnick, PharmD, director of
pharmacology, The Jones Group/JMI Laboratories.
Given the reports of problems with vancomycin resistance,
researchers were pleasantly surprised with the first-year results, Dr.
Mutnick said. "Vancomycin, the old drug, along with quinupristin/dalfopristin
[Synercid], a relatively new drug, and linezolid [Zyvox], the newest drug,
all had excellent activity against the Gram-positive isolates," he said.
Dr. Mutnick hopes that the study may help dispel some of the
myths about vancomycin as a "lost drug" that isn’t useful anymore. "Sometimes
old drugs still do work," he said. "Also, we need to take care to use the
newer agents in the most effective fashion. Otherwise, today’s new agents
will become tomorrow’s resistance problems."
Linezolid displayed the broadest coverage99.5% to 100%
susceptibilityagainst the top five Gram-positive pathogens, with no
resistance. Linezolid was the only agent with satisfactory coverage against
all species of Enterococcus.
Vancomycin and quinupristin/dalfo-pristin paralleled
linezolid’s activity against most Gram-positive isolates, with
susceptibilities ranging from 98.9% to 100% against S aureus,
coagulase-negative staphylococci, S viridans, and S pneumoniae,
and no resistant isolates among those pathogens.
Garenoxacin, Bristol-Myers Squibb’s investigational
desfluoroquinolone, compared favorably to gatifloxacin (Tequin), with
Gram-positive susceptibility rates of 81% to 90% vs 78% for gatifloxacin.
"The results of this first-year, benchmark study for the
CANCER Program was that the Gram-positive pathogens were not more resistant
in cancer patients, as compared with other hospital patient populations," Mr.
Kirby concluded. "They were actually very susceptible."