Clinical Experience with Single Agent and Combination
Regimens in the Management of Infection in the
Febrile Neutropenic Patient
Reuben Ramphal, MD, Gainesville, Florida, Rasim Gucalp, MD, Bronx, New York, Coleman Rotstein, MD,
Michael Cimino, MS, RPh, &ffalo, New York, David Oblon, MD, Gainesville, Florida
Choice of antibiotic therapy for the management
of infection in the neutropenic
patient continues
to challenge the clinician. The shift toward grampositive organisms and the continuing need to
provide gram-negative
coverage demands the
use of an agent or agents that provide coverage
for the spectrum of potential infecting
organisms. Cefepime is an extended-spectrum
fourth-generation
cephalosporin
that has good
activity against gram-positive
and gram-negative
organisms: in addition, it resists degradation
by
Bush group 1 p-lactamases.
These properties
make this agent a promising candidate for
empiric therapy with febrile neutropenic
patients. Data presented in this article are from
febrile neutropenic
cancer patients enrolled into
two randomized,
prospective, nonblinded
comparative
U.S. clinical trials. Patients were
randomized to receive cefepime (2 g thrice
daily) or a comparator
regimen of either
ceftazidime
(2 g thrice daily) or
piperacillin
+ gentamicin
(3 g every 4
hours + 1.5 mg/kg every 8 hours). When
indicated, vancomycin was added to the
regimen. A total of 109 febrile episodes were
treated with cefepime and 107 episodes were
treated with the comparator
regimens.
Neutropenia
(5500 PMNs/mm3)
persisted for
210 days in >40% of episodes and severe
neutropenia (5100 PMNs/mm3)
in >25%. More
than 40% of the total number of episodes were
documented
bacterial infections. These
characteristics
did not differ among treatment
groups. Duration of therapy was similar in both
groups (median: cefepime, 9 days: comparators,
11 days). In >40% of episodes, patients
received study therapy without addition of other
From the Department of Medicine, University of Florida College of Medicine, Gainesville, Florida (R.R.,D.O.); Department of Clinical Oncology,
Montefiore Medical Center, Bronx, New York (R.G.); Departments of Medicine and Pharmacy, Roswell Park Cancer Institute, State University of
New York, Buffalo, New York tC.R.,M.C.).
Reouests for reorints should be addressed to Reuben Ramphal. MD.
Department of Medicine, University of Florida College of Medjcine, PO
Box 100277, Gainesville, Florida 32610-0277.
01996 by Excerpta
All rights reserved.
Medica.
Inc.
antibacterials
(cefepime, 46%; comparators,
41%). Vancomycin was added in almost half of
all the episodes (cefepime, 45%; comparators,
53%). Patients became afebrile by the fourth
day of study therapy in approximately
60% of
episodes (cefepime, 58%; comparators,
60%).
In approximately
75% of the episodes, patients
had a satisfactory response at the end of
therapy (cefepime, 74%; comparators,
76%);
and following approximately
90% of episodes,
patients survived for ~30 days (cefepime, 90%;
comparators,
92%). Eradication rates were
similar for all pathogens for cefepime and
comparator
agents. There were similar numbers
of superinfecting
organisms in each treatment
arm; most involved gram-positive
organisms.
These multiple measures of efficacy suggest that
initial empiric cefepime monotherapy
is
comparable
to the pooled experience with
standard therapies and that antibacterial
modifications
occur with similar frequency for
cefepime compared with standard empiric
regimens. Am J Med 1996;1OO(suppl6A)
83S89s.
I
nfection is a leading cause of death in neutropenic
cancer patients. However, prompt empiric antibiotic therapy can significantly reduce patient morbidity and mortality. Several antibiotic regimens have
been suggested by the Infectious Diseases Society of
America for empiric treatment of fever in neutropenic cancer patients.’ Among the regimens are a
combination of an antipseudomonal
p-lactam and an
aminoglycoside,
a double /G&am
combination, an
antipseudomonal
p-lactam plus an aminoglycoside
plus vancomycin,
or a single broad-spectrum
p-lactam agent with antipseudomonal
activity. On the basis of clinical experience and/or numbers of published studies, some antibiotic regimens have wider
acceptance than others, but there is no unequivocal
evidence that one regimen is superior to another.
Despite their recommended
use, there are problems with all of the regimens in neutropenic cancer
patients. These problems result from changes in microbial-host
interactions;
the increasing intensity of
anticancer chemotherapy;
invasive procedures,
inOOo2-9343/96,‘$15.00
PII SOOO2-9343(96)00113-l
6A-63s
SYMPOSIUM ON ANTlWlCROBiAL
THERAPY/RAMPHAL
ET AL
chiding long-standing central lines; and the use of
repeated and prolonged antibiotic regimens. These
changes have resulted in a decrease in the incidence
of gram-negative bacteremia, while the incidence of
staphylococcal and streptococcal bacteremia has increased.’ Also, resistant enteric gram-negative bacteria have emerged,3 and the majority of treatment
failures have resulted from superinfection by staphylococci, Pseudomonas spp., and fungal pathogens.4
Some specific susceptibility problems related to
these changes are (1) infections caused by grampositive bacteria that are relatively or completely resistant to existing cephalosporins4 ; (2) gram-negative bacteria, such as Enterobacter species, that
produce Bush group 1 P-lactamases, rendering them
resistant to current cephalosporins and antipseudomonal cephalosporins3; (3) gram-negative organisms that produce mutant /3-lactamases capable of
degrading extended-spectrum cephalosporins5; and
(4) gram-negative organisms, such as Pseudomonas
species or Stenotrophomonas maltophilia (formerly
Xanthomonas maltophilia), that are resistant to one
or more regimens4
Thus, selection of effective antibiotic therapy in
neutropenic cancer patients is a dynamic and changing process. New antimicrobial agents for empiric
treatment of fever in neutropenic patients must be
at least equal in spectrum and potency to existing
agents. In addition, new agents should be active
against resistant organisms that have become important pathogens.
Cefepime, a fourth-generation cephalosporin, has
shown good results as monotherapy in immunocompromised and neutropenic mice for infections
caused by Enterobacteriaceae and Pseudomonas
aeruginosa.6 In vitro studies of cefepime have
shown its gram-positive activity to be similar to that
of cefotaxime, providing good to excellent coverage
of many gram-positive organisms, including most
strains of methicillin-susceptible Staphylococcus
aureus, n-hemolytic streptococci, and some Staphylococcus epidermidis strains.7 Cefepime also has good
antipseudomonal activity, a property that is essential
for antibiotics used in this patient population.7 In
murine models of infection, bacterial resistance was
shown to be less likely to develop with cefepime
than ceftazidime.8 Cefepime is less likely to be degraded by the Bush group 1 p-lactamases produced
by Enterobacter species and other bacteria,’ and it
is relatively resistant to many TEM enzymes, including extended-spectrum TEM enzymes.g1’0
Cefepime has been evaluated for the treatment of
a variety of infections (reported in this supplement),
and it appears to have many properties desirable for
empiric therapy in febrile, neutropenic cancer patients. Eggimen et al” reported on the efficacy and
6A-64s
June
24,
1996
The American
Journal
of Medlcinee
Volume
100
safety of cefepime as monotherapy in the management of 108 febrile episodes in 84 granuIocytopenic
cancer patients. Cefepime (2 g every 8 hours) was
given for a minimum of 7 days or until resolution of
infection. Of the 91 evaluable episodes, 71% (65/91)
of the infections resolved, including 44% (8/18) of
documented gram-positive infections and 86% (6/7)
of gram-negative infections. The authors concluded
that cefepime monotherapy was well tolerated and
effective for the treatment of fever in the granulocytopenic cancer patient. In this article, comparative
clinical
trials
of cefepime for empiric therapy for febrile episodes in neutropenic cancer patients are reviewed.
MATERIALS
AND METHODS
Adult patients who underwent cancer chemotherapy or bone marrow transplantation for the treatment of malignancies were enrolled in two prospective, nonblinded, randomized, comparative, clinical
U.S. trials. One trial compared cefepime monotherapy with ceftazidime monotherapy; the second trial
compared cefepime monotherapy with piperacillm
plus gentamicin. Patients were eligible for em-ollment if they were febrile (temperature ~38” C on
two occasions within a 24-hour period or 238.3’ C
on one occasion) and had an absolute neutrophil
count ~l,000/mm3 or the count was anticipated to
fall below this level. Informed consent was obtained
from all patients. Subjects were excluded on the basis of any one of the following: age t16 years, allergy to penicillin or cephalosporin, pregnancy, renal
dysfunction (creatinine ~2.0 mg/dL) , aplastic anemia, chronic myelogenous leukemia in blast crisis,
central nervous system infection, or intravenous antibiotic therapy in the previous 4 days. Oral antibiotics were not to be administered concurrently.
Cultures were obtained from blood and other potentially infected sites before, during, and. after therapy to assess efficacy. Antibiotic susceptibilities
were performed by broth dilution or disk diffusion
methods. Susceptibility was determined using the established breakpoints for all study drugs. Patients
were monitored for evidence of toxicity with routine
serum chemistries plus prothrombin and partial
thromboplastin times.
Antibiotic
Therapy
Patients received cefepime 2 g every 8 hours, ceftazidime 2 g every 8 hours, or piperacillin 3 g every
4 hours plus gentamicin 1.5 mg/kg every 8 hours as
empiric therapy. In the piperacillin + gentamicin
treatment group, aminoglycoside therapy was adjusted based on aminoglycoside serum levels. Antibiotic therapy was supplemented with vancomycin
(generally 1 g every 12 hours) based on specified
(suppl
6A)
SYMPOSIUM ON ANTIMICROBIAL
criteria:
therapy,
therapy
and the
clinical
persistent fever after 72-96 hours of initial
isolation of a pathogen resistant to study
(e.g., methiciIlin-resistant
staphylococci),
development of a new fever after an initial
response.
TABLE I
Characteristics
TklERAPY/RAMPHAL
ET AL
1
of Patients With Febrile Episodes
Evaluation of Response
Clinical response or outcome was evaluated at
three time points using objective criteria: ( 1) afebrile (temperature <38” C) on the fourth day of therapy; (2) afebrile with improvement or resolution of
all other signs and symptoms of clinical infection at
termination of study therapy; and (3) survival ~30
days following termination of study therapy.
Clinical responses were stratified according to
whether initial antibacterial therapy was modified.
Discontinuation
of study drug because of an unsatisfactory response, regardless of treatment modifk
cation, was considered a treatment failure. These criteria are similar to those proposed by Pizzo et al.”
Bacteriologic eradication or persistence was documented by results of blood cultures or, when applicable, cultures from a local infection site. Symptomatic infection documented by a new pathogen
during study drug administration,
or within 2 days of
termination of study therapy, was classified as a superinfection for this review.
TABLE
II
Severity and Duration of Neutropenia
Febrile episodes
5100 neutrophils/mm3
~10 days
5-9 days
s-500 neutrophils/mm3’
210 days
5-9 days
Cefepime
n
(%)
109
30
23
(26)
(21)
27
24
(251
(22)
44
24
(401
(22)
45
26
(42)
(24)
* Includes patients with 5 100 neutrophils/mm3.
TABLE
Ill
Causes of Fever
Cefepime
n
(%)
RESULTS
A total of 216 febrile episodes in 193 neutropenic
patients were treated, 109 febrile episodes with cefepime and 107 episodes with comparator drugs: ceftazidime, 50; pipercillin/gentamicin,
57. In the trial
with ceftazidime, 12 patients were enrolled more
than once with distinct febrile, neutropenic episodes
separated by several weeks.
Characteristics of Patients with Febrile
Episodes
Demographic
data by episode are shown in Table
differences among treatment groups for any of the characteristics described.
Notably, approximately
70% of patients in each
group had a hematologic
malignancy. Pretherapy
neutrophil counts of &00/mm3
cells were observed
in 95% of patients in each group. The severity of neutropenic episodes is shown in Table II. Two-thirds
of patients in each group were neutropenic (~500
neutrophils/mm3)
for 25 days and 40% for 2 10 days.
Nearly half of the patients in each group had severe
neutropenia (5 100 neutrophils/mm3)
for 25 days
and >25% for 210 days.
I. There were no important
Causes of Fever
Causes of fever were similar in the two treatment
groups; approximately
50% in each group were of
Comparator
Drugs
-(o/o)
n
10;’
i
Febrile episodes
Bacteriologically documented
infections
Septicemia
Other sites
Clinically documented infections
Fever of unknown origin
109
47
33
14
8(71
54
Comparator
Drugs
-73
(%I
10’7
(43)
(30)
(13)
(50)
44
29
15
7
56
(41)
(271
(14)
( 7)
(52)
1
unknown origin (Table III), Approximately
30% of
the febrile episodes were due to bacteremia and represented the majority of bacteriologically
documented infections. The incidence of bacteremia in
these patients is comparable to that reported in recent trials.12~‘3
Pathogens Isolated and Susceptibilities
The susceptibilities
of pretherapy isolates are
shown in Table IV. Not all pathogens were tested
against every drug. Cefepime and gentamicin were
active against 100% of gram-negative
pathogens
tested. Cefepime was somewhat more active against
gram-positive isolates than the other agents.
Treatment with Study Therapy and Use of
Concomitant Antimicrobials
Patients were treated for a median of 9 days
(range 1-81 days) with cefepime and for 11 days
(range l-44 days) with comparators.
June 24, 1996 The American Journal of Medicine@ Volume 100 kuppl
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6A-8%
SYMPOSIUM ON ANTIMICROBIAL
TABLE
THERAPY/RAMPHAL
ET AL
IV
Susceptibility of Pretherapy Isolates
Cefepime
Ceftazidime
Gram-positive isolates
Staphylococcus aureus
Coagulase-negative staphylococci
Streptococcus species
Enterococcus species
Other*
Total gram-positive isolates testedt
Susceptible
Gram-negative isolates
Escherichia co/i
Klebsiella
z/2
11/11
15/20
14/14
o/3
Enterobacter
6/l 1
lO/ll
O/l
* Includes one strain of Listeria
t All Isolates were not tested.
monocytogenes
2/2
2/2
42/51
82%
20/27
74%
1 l/18
61%
17/17
lO/lO
5/5
2/3
13/13
7/7
5/5
5/5
38/38
100%
resistant
3/7
3/5
3/3
O/l
2/3
l/l
Pseudomonas aeruginosa
Others
Total gram-negative isolates testedt
Susceptible
Piperacillin
-
l/l
l/l
4/5
3/4
28/30
93%
2s
lO/ll
91%
Gentamicin
9/9
5/9
3.13
1.12
l/2
19/25
76%
13,/l 3
7,/7
1,/l
5/5
4/4
30,‘30
100%
to cefepime.
Antibiotic therapy was modified in more than half and 100%among cefepime and comparators, respecof the episodes in both the cefepime and comparator
tively. Cefepime eradicated 34 of 35 gram-positive
treatment groups (Table V ) . In practice, all centers organisms and 14 of 15 gram-negative organisms.
modified initial study therapy for some febrile epi- Clostridium di$icik associated with diarrhea and
sodes, and vancomycin was frequently added before Pseudomonas aeruginosa in a chest wound infecsusceptibility results for gram-positive organisms
were obtained. The median duration of vancomycin
TABLE V
therapy was 8 days (range l-77) in the cefepime
Use of Concomitant Antimicrobials
group and 9 days (range l-40) in the comparator
Cefepime Comparator Drugs
group; 45% of cefepime patients were given vancomycin, whereas 53% of patients receiving comparaNumber of febrile episodes
109
107
Monotherapy (%I
46
41
tor drugs were given vancomycin. In some cases, anAdditional
antibacterial
tibiotics other than vancomycin were added to the
therapy (%I
54
59
treatment regimen. Addition of an aminoglycoside
Vancomycin (%I
45
53
was infrequent for cefepime-treated (6%) or cefta8*
Aminoglycoside (%I
6
zidime-treated (8%) patients. Other antibacterial
33
Other antibacterials (%I
30
36
Systemic antifungals (%)
34
agents added included erythromycin, quinolones,
’
Percentage
based
on
4
of
50
epi
s
odes
tested
with
ceftazidime.
Does not
clindamycin, and metronidazole, which were used
include piperacillin/gentamicin
treatment
group.
mainly on an empiric basis late in the course of neutropenic episodes for persistent fever or for suspected anaerobic infections. Antifungak, primarily
amphotericin B, were added at about the same freTABLE VI
quency in both treatment groups.
Clinical Responses to Antibiotic Regimen
Clinical
Patients became afebrile after 4 days of treatment
in 58%and 60%of episodes in the cefepime and comparator groups, respectively (Table VI). The rates
of satisfactory clinical responses at the time study
therapy was discontinued and survival were similar
in both groups.
Bacteriologic
Eradication
Overall, the bacteriologic eradication rate with or
without modification while on study drug was 96%
6A-86s
Febrile Episodes
Response/Total (%)
Cefepime
Comparator Drugs
Response
June
24,
1996 The American
Journal
of Medicine@
Volume
Afebrile (54 days)’
Study therapy alone
With modification
End of study therapy7
Clinical response
Survived (~30 days after
therapy)
60/103 (58%)
38/45 (84%)
22/58 (38%)
63/105 (60%)
33/42 (79%)
30/63 (48%)
74/100 (74%)
98/100 (98%)
77/101 (76%)
98/K07 (92%)
* Some patients
did not receive 4 days of therapy.
t Some patients could not be assessed
for clinical responses,
violation,
premature
removal from study drugs.
100 (suppl
6A)
eg, protocol
SYMPOSIUM ON ANTIMICROBIAL
TABLE
VII
Eradication
Gram-positive
Staphylococcus aureus
Coagulase-negative
staphylococci
Streptococcus species
Other
Total (%I
Gram-negative
Escherichia coli
Klebsiella pneumoniae
Pseudomonas
of Pathogens* t
Cefepime Comparator
lO/lO
7/7
l/l
13/13
12/12
8/S
5/6
lO/lO
7/7
3/3
0
5/5
25/25 (100)
7/7
3/3
aeruginosa
2/3
l/l
l/l
14/l 5 (93)
* Excludes those coded as “unable to determine.”
+ Includes patients receiving modified therapy.
TABLE
otherapy eradicated 8 of 10 S. aureus isolates; two
isolates were eradicated by cefepime and vancomytin. Comparative therapy eradicated S. aurexs from
the single infection caused by this organism.
Superinfection occurred with similar frequency in
both treatment groups. The organisms causing superinfections were mainly gram-positive ( 11 of 14 in
the cefepime group and 12 of 19 in the comparator
group; Table VIII); however, many (except enterococci) were susceptible to cefepime and comparator drugs. There were no gram-negative superinfections in the cefepime group, and single cases of
Bacteroides fragilis and Enterobacter spp. superinfection with comparator drugs.
Deaths
VIII
Pathogens Causing Superinfections
Cefepime
Coagulase-negative staphylococci
Staphylococcus aureus
Enterococci
Other gram-positive organisms
Total gram-positive organisms
Total gram-negative organisms
Clostridium diffrcile
Fungi
Total
ET AL
Superinfections
3/3
25/25 (100)
34/35 (97)
Enterobacter species
Others
Total (%I
Drugs
THERAPY/RAMPHAL
3
2
4
2
11
0
1
2
14
Comparator
Drugs
5
2
3
2
12
2
0
5
19
IX
Mortality According to Antibiotic Regimen
Comparator
Causes of Death
Cefepime
Drugs
There were no differences in the causes of death
in either group due to the primary infection or superinfection (Table IX ) . However, more patients in
the cefepime group (6 patients) did not respond to
cancer chemotherapy, had bone marrow failure, or
died from progression of metastatic disease than in
the comparator group ( 1 patient) ; the statktical significance of this was not determined. Among therapy
failures, 1 patient in the cefepime group and 2 in the
comparator group died of their original infection.
The cefephne death was due to Pseudomomw sepsis.
However, this patient received only one dose of cefepime before being switched to other agents. In the
comparator groups, one patient died of an undocumented infection and one from Corynebacterium
sepsis.
TABLE
All deaths
(during
therapy
or
530 days after therapy)
Original infection
New infection
Underlying disease
11
1
3
7
9
2
5
2
tion were not eradicated in the cefepime-treated
group. Comparator drugs eradicated all gram-positive organisms and all gram-negative organisms.
Eradication by specific pathogen is shown in Table
VII.
Gram-positive infections were frequently
treated with vancomycin in combination with study
drugs. Eradication rates were similar for all pathogens for cefeptie and comparative therapies. The
role of monotherapy was examined for S. aureus, P.
aeruginosa, and Enterobacter. The numbers of P.
aeruginosa and Enterobacte-r isolates were too small
to allow evaluation of monotherapy. Cefepime mon-
Safety
The most common adverse events were gastrointestinal disturbances and rash. In all treatment
groups, approximately 15%of patients had diarrhea,
and 10% had rash. Worsening renal function (creatinine 23.0 mg/dL) developed in 7 of 101 (7%) of
episodes treated with comparator drugs and in 2 of
106 (2%) of episodes treated with cefepime. Renal
dysfunction was particularly apparent for episodes
treated with piperacillin + gentamicin (4 of 46
tested, or 9%). Piperacillin + gentamicin therapy
was discontinued in two patients for adverse events
probably related to aminoglycoside toxicity: one
with severe renal failure requiring dialysis and the
other with partial hearing loss.
DISCUSSION
There are many approaches to empiric antibiotic
therapy for febrile neutropenic patients. Debate remains concerning the relative merits of monotherapy
with a p-la&am versus a combination of a P-lactam
June 24, 1996 The American
Journal of Medicine@ Volume 100 k~pl
6A)
6&6X
plus an aminoglycoside
in these high-risk patients.
Monotherapy may provide the advantages of lower
cost and less toxicity. Therefore, if the efficacy of
monotherapy is similar to combination therapy, use
of monotherapy is desirable.
Cefepime shares many of the features of ceftazidime, a third-generation
cephalosporin that has been
widely studied as monotherapy in neutropenic patients. Cefepime has some in vitro advantages over
the comparator drugs used in this study (e.g., its activity against gram-positive organisms and its resistance to degradation by Bush group 1 P-lactamases) .
Differences in response rates based on in vitro
activity were not anticipated in these trials because
of the protocol requirement that organisms be susceptible to cefepime and comparator drugs for a patient to be evaluable. As a sole agent, cefepime was
effective in treating S. aureus , a problematic organism; 8 of 10 isolates were eradicated with monotherapy. Too few cases of S. aureus occurred in the
comparator group to evaluate control agents. There
were also too few cases of P. aeruginosa and Enterobactw infections to compare the efficacy of cefepime with that of comparator drugs.
There is no generally accepted method for evaluating antibiotic therapy in febrile neutropenic patients,
although at least one set of guidelines has been published.14 The continuing propensity of these patients to
develop infection while they are neutropenic requires
that at least two types of evaluations be made. One
evaluation is the response to the initial empiric regimen (including its early modification) because, in our
experience, modification is a reality of clinical practice
with these patients. The second method assesses clinical response at the time the study drug is discontinued, because patients often respond initially, only to
develop new fevers. Using this two-step approach, the
results of these trials do not show a difference in response but suggest that patients whose therapy was
modified in the initial 4-day period were probably the
sickest. Fewer than half of those who received early
modified therapy responded by day 4, whereas approximately 80% of those who continued initial therapy
did eventually respond.
Super-infection is another means of comparing antibiotic regimens, because it may be an early indication of a weakness in a given regimen, e.g., if a
specific pathogen of superinfection
appears more
frequently in one treatment group. In these studies,
treatment groups experienced similar numbers of
bacterial super-infections; most were caused by
gram-positive pathogens. Breakthrough gram-negative infections occurred in only a few cases; none
were in the cefepime group, arguing against early
automatic aminoglycoside use. Thus, cefepime’s superinfection profile is not unusual in any respect.
6A-88s
June 24, 1996 The Amerrcan
Journal of Medicine”
Vancomycin and aminoglycoside
usage deserves
comment. There were specific criteria in the protocol for vancomycin use, but many patients received
vancomycin earlier than specified. For example, if a
gram-positive pathogen was isolated and the patient
was febrile, vancomycin was often added before susceptibility results had been reported. This suggests,
as in other studies, that vancomycin is often overused or added prematurely. Vancomycin does have
an important role in the treatment of neutropenic
patients with infections because of the increasing incidence of resistant staphylococci and other grampositive species. However, physicians are often unwilling to wait for sensitivity studies despite data
showing little or no increased morbidity in delaying
the decision to add vancomycin.‘5~1e
It has been argued that aminoglycosides should be
added to ceftazidime monotherapy for documented
gram-negative bacteremias based on the favorable fever response in a European Organization for Research
in Treatment of Cancer (EORTC) triali Documented
gram-negative infections are now much less common
than in the 1970s when combination therapy was advocated and when the spectrum of activity of P-lactam
agents was less broad. In the current trials, investigators added aminoglycosides
to the cefepime and
ceftazidime treatment groups in < 19% of patients.
Examination of all parameters of efficacy (early afebrile response, bacterial eradication, final clinical response, and survival) indicated no significant differences among the three treatment groups. These clinical
results are comparable to the 0veralI response rates obtained in other trials investigating monotherapy with
ceftazidime, 15,17and imipenem,17 in which approximately 60% and 75% of patients responded, respectively.
CONCLUSION
Clinical and bacteriologic parameters suggest that
cefepime is as efficacious as two other commonly
used regimens to treat neutropenic patients with infections and is capable of eradicating methicillin-susceptible S. aureus infection as monotherapy. Larger
comparative studies are required to evaluate the clinical significance of the in vitro advantages of cefepime. Importantly,
more data are needed on the response of problematic
gram-negative
infections
caused by Pseudomonas spp. and Enterobacter spp.
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1990;161:381-396.
2. EORTC and Natronal Cancer Institute of Canada. Vancomycin added to em
pirical combination antibiotic therapy for fever in granulocytopenic cancer patients. J infect Dis. 1991;163:951-958.
3. Johnson MP, Ramphal R. fl-Lactam-resistant
Enterobacter bacteremia in
febrile neutropenic
patients receiving
monotherapy.
J Infect Dis.
1990;162:981-983.
Volume 100 (suppl 6A)
SYMPOSIUM ON ANTIMICROBIAL
4. Liang R, Yung R, Chiu E, et al. Ceftazrdrme versus imipenemcilastatin
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June 24, 1996 The American
Journal of Medicine@ Volume 100 (suppl 6rY
6A-89s