International Journal of Infectious Diseases (2006) 10, 223—230

http://intl.elsevierhealth.com/journals/ijid

The spectrum of Gram-positive bloodstream

infections in patients with hematologic
malignancies, and the in vitro activity of various
quinolones against Gram-positive bacteria isolated
from cancer patients§
Kenneth V.I. Rolston *, Davood Yadegarynia, Dimitrios P. Kontoyiannis,
Issam I. Raad, Dah H. Ho

Section of Infectious Diseases, Department of Infectious Diseases, Infection Control and Employee Health,
The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 402, Houston, TX 77030, USA

Received 9 November 2004; received in revised form 20 April 2005; accepted 5 May 2005
Corresponding Editor: Marguerite Neill, Pawtucket, USA

KEYWORDS Summary
Cancer patients; Objectives: To determine the current spectrum of Gram-positive bloodstream infections (BSI) in
Gram-positive bacteria; patients with hematologic malignancies at our institution, and to determine the in vitro activity
Quinolones of various fluoroquinolones against clinical Gram-positive isolates collected from such patients.
Methods: Institutional microbiology records from 493 consecutive episodes of Gram-positive BSI
were reviewed. The in vitro activity of six fluoroquinolones against 477 clinical isolates was
determined using an NCCLS approved, broth-dilution method.
Results: The most common Gram-positive organisms isolated from the bloodstream of patients
with hematological malignancies were coagulase-negative staphylococci (33%), Staphylococcus
aureus (15%), viridans group streptococci (10%), and the enterococci (8%). Acute leukemias were
the most common underlying malignancies, and 73% of patients were neutropenic when they
developed their BSI. The newer generation quinolones — moxifloxacin and gatifloxacin — had the
best overall in vitro activity against the Gram-positive isolates tested, and were at least 2 to 8-
fold more potent than the early generation quinolones (ofloxacin and ciprofloxacin). Of the 477
isolates tested, 405 (85%) were from patients receiving quinolone (ciprofloxacin or levofloxacin)
prophylaxis.

§
These data were presented in part at the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (Abstract # E-155),
Chicago, IL, September 14—17, 2003.
* Corresponding author. Tel.: +1 713 792 6830; fax: +1 713 745 6839.
E-mail address: krolston@mail.mdanderson.org (Kenneth V.I. Rolston).

1201-9712/$32.00 # 2005 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.ijid.2005.05.007
224
Conclusions: In patients with hematologic malignancies, Gram-positive BSI are caused by a large
number of bacterial species and many occur despite antimicrobial prophylaxis. The newer genera-
tion quinolones — moxifloxacin and gatifloxacin — have better in vitro activity against these
organisms than early generation agents (ciprofloxacin and ofloxacin).
# 2005 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Introduction
The spectrum of bacterial infections in neutropenic cancer
patients undergoes periodic changes, which have been well
documented.1,2 Currently, Gram-positive organisms are iso-
lated most often from the bloodstream of such patients, with
staphylococci being the most frequent.3,4 Other common
Gram-positive organisms isolated from this group of patients
include Enterococcus species (including vancomycin-resis-
tant isolates), viridans group streptococci (VGS), beta-hemo-
lytic streptococci, Streptococcus pneumoniae, and several
organisms that colonize human skin, such as Bacillus species
and Corynebacterium species.4—6 Organisms such as Listeria
monocytogenes and Rhodococcus equi are being isolated
more often, particularly from cancer patients with impaired
cellular immunity.7—9
Factors accounting for this increase in Gram-positive
infections include: (a) widespread use of vascular access
devices and other foreign bodies, (b) intensive chemother-
apy resulting in significant oro-intestinal mucositis, and (c)
antimicrobial prophylaxis directed primarily at enteric
Gram-negative bacilli.10 Some reports have suggested that
prophylaxis with older generation quinolones (ofloxacin,
ciprofloxacin) might actually select for, and increase the
frequency of, Gram-positive BSI.11—13 The newer generation
quinolones (gatifloxacin, moxifloxacin, garenoxacin) are
reported to have more potent activity against most
Gram-positive pathogens than older generation quino-
lones.14—16 They are also quite active against most Entero-
bacteriaceae and non-fermentative Gram-negative bacilli
with the exception of Pseudomonas aeruginosa.17 Conse-
quently, the newer generation quinolones might be more
suitable for antimicrobial prophylaxis in cancer patients at
high risk for Gram-positive BSI. Circumstances at our institu-
tion offered the opportunity to examine this question
because a large number of cancer patients at high risk
for Gram-positive BSI are seen during their cancer treat-
ment, and quinolone prophylaxis with ciprofloxacin or
levofloxacin is often given. We therefore sought to deter-
mine the current microbiologic spectrum of Gram-positive
BSI by a retrospective review of the microbiology records of
patients with hematologic malignancies, and then compared
the in vitro activity of newer quinolones against recent
Gram-positive, bloodstream isolates from similar cancer
patients.
Materials and methods
Spectrum of infection
The microbiology records of our institution were examined in
order to identify all patients who developed a Gram-positive
bloodstream infection between March 2002 and October
K.V.I. Rolston et al.
2003. As a second step all BSI in patients with solid tumors
were excluded, and only those occurring in patients with
hematologic malignancies were included. Patients from
whom Gram-positive organisms were isolated from cultures
of peripheral blood alone, or peripheral blood and blood
obtained through a central venous catheter (CVC) were
considered to have a BSI. Patients with positive CVC blood
cultures but negative peripheral blood cultures were
excluded, since many of these could represent CVC coloniza-
tion without BSI. One positive blood culture was considered
sufficient for all organisms except coagulase-negative sta-
phylococci and Corynebacterium species, for which more
than one positive blood culture (same species and same
susceptibility patterns) within a 48-hour period was
required.18
Organisms
All organisms used for in vitro testing were recent blood-
stream isolates (1997—2003) from patients with hematologic
malignancies treated at our institution and were stored in
our research laboratory ‘bug bank’. Some, but not all,
were from patients included in the first part of the study
(i.e., description of the spectrum of infection), since
all clinical isolates are not routinely banked and saved
by our clinical microbiology laboratory due to space limita-
tions and privacy guidelines. Only one isolate per patient was
used in order to avoid duplication. Most patients from whom
the isolates used for susceptibility testing were recovered
had received quinolone prophylaxis prior to the develop-
ment of BSI (405 patients — 85%; levofloxacin — 267 and
ciprofloxacin — 138).
Antimicrobial agents
All antimicrobial agents were obtained from their respective
manufacturers in the form of standard laboratory powders,
and were stored at 70 8C until use.
Susceptibility testing
We used an NCCLS approved, microtiter, broth-dilution
method.19 The final inoculum tested was 5  105 CFU/ml.
Appropriate ATCC control strains (Staphylococcus aureus
ATTCC 29213, and Enterococcus faecalis ATCC 29212) were
used in order to ensure the accuracy of our results. The
minimum inhibitory concentration (MIC) was defined as the
lowest concentration of each agent that inhibited visible
growth after 20—24 h of incubation at 35 8C. NCCLS suscept-
ibility breakpoints were used to interpret the data, when
available.
Gram-positive in patients with hematologic malignancies 225

Results Table 2 The spectrum of Gram-positive bloodstream infec-

tions in patients with hematologic malignanciesa
Spectrum of infection Organisms (n = 493) Number (%)

During the study period, 493 episodes met the definition Coagulase-negative staphylococci 161 (33)
of Gram-positive BSI in patients with hematologic malignan- Staphylococcus aureus (including MRSA) b 72 (15)
cies at our institution. Patient characteristics are shown in Viridans group streptococci 48 (10)
Table 1. The median age of patients was 57 years (range Enterococcus species (including VRE) c 41 (8)
4—89 years) with a gender distribution of 301 men (61%) Micrococcus species 38 (8)
and 192 women. The most common underlying malignancies Beta-hemolytic streptococci d 37 (7)
included acute leukemias, which accounted for 49% of Corynebacterium species 31 (6)
patients, various lymphomas (23%), chronic leukemias Streptococcus pneumoniae 21 (4)
(12%), and myelomas/plasma cell disorders (12%). Bacillus species 20
The majority of patients (359 or 73%) were neutropenic Aerococcus species 18
(absolute neutrophil count 0.5  109/l) when their BSI Listeria monocytogenes 4
developed. Stomatococcus mucilaginosus 2
The spectrum of Gram-positive BSI in these patients is a
These data were from 493 consecutive episodes of blood-
shown in Table 2. Coagulase-negative staphylococci (CoNS) stream infection.
b
were the most frequently isolated organisms and accounted MRSA: methicillin-resistant Staphylococcus aureus.
c
for 33% of these episodes despite the strict definition for BSI VRE: vancomycin-resistant enterococci.
d
used. Eighty-nine percent of these isolates were methicillin- Included beta-hemolytic streptococci — groups A, B, C and G.
resistant. Staphylococcus aureus was the next most common,
causing 15% of episodes, with 44% of isolates being methi-
Susceptibility to quinolones
cillin-resistant. Viridans group streptococci (VGS) caused 10%
of episodes with Streptococcus sanguis, Streptococcus mitis,
The in vitro activities of various quinolones against Gram-
and Streptococcus milleri being the most common species.
positive bacteria are shown in Table 3. A total of 477 isolates
Fifty-six percent of VGS isolates were penicillin non-suscep-
representing 18 bacterial species were tested. Overall, moxi-
tible, with a MIC of 0.12 mg/ml. The fourth most common
floxacin and gatifloxacin were the most active quinolones
Gram-positive organisms were Enterococcus species, 29% of
against Gram-positive bacteria, followed by garenoxacin,
which (all E. faecium) were vancomycin-resistant. A wide
levofloxacin, ciprofloxacin, and ofloxacin. Aerococcus spp,
variety of other Gram-positive organisms were also isolated
Micrococcus spp, and Stomatococcus mucilaginosus are Sta-
including various beta-hemolytic streptococci, S. pneumo-
phylococcus-like, Gram-positive cocci that are being isolated
niae, Corynebacterium species, Micrococcus species, and
with increasing frequency from cancer patients. Moxifloxacin
Bacillus species. Listeria monocytogenes and Stomatococcus
and gatifloxacin inhibited all isolates belonging to these spe-
mucilaginosus were rare (<1% each).
cies at concentrations of 0.5 mg/ml to 1.0 mg/ml. Garenoxacin
and levofloxacin also had potent activity against these organ-
isms with occasional isolates having MIC values of 2.0 mg/ml or
greater. Ciprofloxacin and ofloxacin were less active, each
Table 1 Characteristics of 493 patients with hematologic inhibiting <90% of isolates at their susceptibility breakpoints
malignancies and Gram-positive bloodstream infections for staphylococci (i.e., 1.0 mg/ml for ciprofloxacin, and
2.0 mg/ml for ofloxacin). All six agents had potent activity
Characteristic Number (%) against Bacillus spp, inhibiting >90% of isolates at individual
Gender susceptibility breakpoints. All L. monocytogenes isolates were
Male 301 (61) susceptible to all six agents, with the highest MIC for any agent
Female 192 (39) being 1.0 mg/ml. Against Corynebacterium species, moxiflox-
Median age 57 years acin and gatifloxacin inhibited 90% of isolates at 2.0 mg/ml
Age range 4—89 years each, and garenoxacin had a MIC90 of 4.0 mg/ml. The other
three agents were much less active, inhibiting just over 50% of
Underlying malignancy isolates at their susceptibility breakpoints. All six agents had
Acute leukemias 239 (49) potent activity against R. equi.
Lymphomas 115 (23) Ciprofloxacin, ofloxacin and levofloxacin had poor
Chronic leukemias 61 (12) activity against the enterococci including vancomycin-sus-
Myelomas 58 (12) ceptible and vancomycin-resistant isolates. Against van-
Others a 20 (4) comcyin-susceptible E. faecalis, moxifloxacin, gatifloxacin
Quinolone prophylaxis 405 (82) and garenoxacin had moderate activity, inhibiting well
Levofloxacin 267 (66) over 70% at concentrations of 1.0 mg/ml. The activity of
Ciprofloxacin 138 (34) all six agents against vancomycin-resistant E. faecium was
Neutropenia (ANCb  0.5  109/l) 359 (73) suboptimal.
a
All six agents were active against most methicillin-sus-
Myelodysplatic syndrome, and related disorders.
b ceptible S. aureus isolates, with moxifloxacin inhibiting all
ANC: absolute neutrophil count.
isolates at 0.5 mg/ml, and ciprofloxacin, levofloxacin, gar-
226 K.V.I. Rolston et al.

enoxacin, and gatifloxacin inhibiting all isolates at 1.0 mg/ vitro activity against MRSA does not necessarily imply in vivo
ml. Moxifloxacin, gatifloxacin and garenoxacin had moderate efficacy. The other agents had poor activity against MRSA.
activity against methicillin-resistant S. aureus, inhibiting Ciprofloxacin, ofloxacin, and levofloxacin were less active
between 53% and 73% of these isolates at 1.0 mg/ml. In against methicillin-susceptible Staphylococcus epidermidis

Table 3 In vitro activity of various quinolones against Gram-positive isolates from patients with hematologic malignanciesa

Organisms (No. tested) Drug MIC (mg/ml)

50% 90% Range
Aerococcus spp (10) Ciprofloxacin 0.5 8.0 0.03—16.0
Ofloxacin 0.5 8.0 0.12—16.0
Levofloxacin 0.25 1.0 0.03—2.0
Garenoxacin 0.03 0.12 0.03—0.25
Gatifloxacin 0.03 0.06 0.03—0.5
Moxifloxacin 0.03 0.12 0.03—0.5
Bacillus spp (10) Ciprofloxacin 0.03 0.5 0.03—1.0
Ofloxacin 0.06 1.0 0.06—4.0
Levofloxacin 0.12 1.0 0.03—2.0
Garenoxacin 0.03 2.0 0.03—2.0
Gatifloxacin 0.03 1.0 0.03—1.0
Moxifloxacin 0.03 0.5 0.03—2.0
Corynebacterium spp (10) Ciprofloxacin 1.0 64.0 0.03—64.0
Ofloxacin 2.0 64.0 0.025—>64.0
Levofloxacin 0.5 64.0 0.03—64.0
Garenoxacin 0.5 4.0 0.03—8.0
Gatifloxacin 0.25 2.0 0.12—16.0
Moxifloxacin 0.25 2.0 0.06—16.0
Enterococcus faecalis (VSEb) (30) Ciprofloxacin 8.0 32.0 0.25—>64.0
Ofloxacin 8.0 64.0 1.0—>64.0
Levofloxacin 8.0 32.0 0.03—>64.0
Garenoxacin 0.5 2.0 0.12—4.0
Gatifloxacin 0.5 4.0 0.03—4.0
Moxifloxacin 0.25 2.0 0.03—4.0
Enterococcus faecium (VREc) (30) Ciprofloxacin >64.0 >64.0 8.0—>64.0
Ofloxacin >64.0 >64.0 16.0—>64.0
Levofloxacin >64.0 >64.0 8.0—>64.0
Garenoxacin 32.0 64.0 8.0—64.0
Gatifloxacin 4.0 16.0 2.0—32.0
Moxifloxacin 4.0 16.0 1.0—32.0
Listeria monocytogenes (15) Ciprofloxacin 0.25 0.5 0.03—0.5
Ofloxacin 0.25 1.0 0.12—1.0
Levofloxacin 0.5 1.0 0.25—1.0
Garenoxacin 0.25 1.0 0.25—1.0
Gatifloxacin 0.03 0.12 0.03—0.25
Moxifloxacin 0.03 0.12 0.03—0.12
Micrococcus spp (30) Ciprofloxacin 0.5 4.0 0.03—16.0
Ofloxacin 0.5 4.0 0.03—16.0
Levofloxacin 1.0 1.0 0.03—8.0
Garenoxacin 0.12 0.25 0.03—0.5
Gatifloxacin 0.12 0.5 0.12—0.5
Moxifloxacin 0.25 0.5 0.25—0.5
Rhodococcus equi (10) Ciprofloxacin 0.25 0.5 0.03—1.0
Ofloxacin 0.25 1.0 0.03—2.0
Levofloxacin 0.03 0.5 0.03—1.0
Garenoxacin 0.12 0.5 0.03—1.0
Gatifloxacin 0.06 0.12 0.03—0.12
Moxifloxacin 0.06 0.06 0.03—0.12
Gram-positive in patients with hematologic malignancies 227
Table 3 (Continued )
Organisms (No. tested) Drug MIC (mg/ml)
50% 90% Range

Stomatococcus mucilaginosus (10) Ciprofloxacin 0.03 16.0 0.03—32.0

Ofloxacin 0.12 32.0 0.12—64.0
Levofloxacin 0.03 8.0 0.03—8.0
Garenoxacin 0.03 0.5 0.03—2.0
Gatifloxacin 0.03 0.5 0.03—0.5
Moxifloxacin 0.03 0.5 0.03—1.0
Staphylococcus aureus (40) (Meth.-susceptible) Ciprofloxacin 0.12 1.0 0.03—1.0
Ofloxacin 0.25 2.0 0.12—4.0
Levofloxacin 0.12 1.0 0.06—1.0
Garenoxacin 0.03 0.5 0.03—1.0
Gatifloxacin 0.03 1.0 0.03—1.0
Moxifloxacin 0.03 0.5 0.03—0.5
Staphylococcus aureus (40) (Meth.-resistant) Ciprofloxacin 8.0 64.0 0.25—>64.0
Ofloxacin 16.0 >64.0 1.0—>64.0
Levofloxacin 8.0 32.0 0.12—>64.0
Garenoxacin 1.0 16.0 0.03—>64.0
Gatifloxacin 1.0 32.0 0.03—>64.0
Moxifloxacin 1.0 32.0 0.03—>64.0
Staphylococcus epidermidis (30) (Meth.-susceptible) Ciprofloxacin 0.12 4.0 0.03—64.0
Ofloxacin 1.0 4.0 0.24—>64.0
Levofloxacin 0.12 8.0 0.03—32.0
Garenoxacin 0.25 0.5 0.03—2.0
Gatifloxacin 0.06 1.0 0.03—1.0
Moxifloxacin 0.03 1.0 0.03—1.0
Staphylococcus epidermidis (30) (Meth.-resistant) Ciprofloxacin 8.0 64.0 0.12—>64.0
Ofloxacin 8.0 >64.0 2.0—>64.0
Levofloxacin 4.0 64.0 1.0—>64.0
Garenoxacin 1.0 8.0 0.5—8.0
Gatifloxacin 0.5 4.0 0.5—8.0
Moxifloxacin 1.0 4.0 0.25—8.0
Staphylococcus hemolyticus (20) Ciprofloxacin 2.0 4.0 0.06—4.0
Ofloxacin 4.0 8.0 1.0—8.0
Levofloxacin 1.0 2.0 0.06—4.0
Garenoxacin 0.06 1.0 0.06—1.0
Gatifloxacin 0.03 0.5 0.03—1.0
Moxifloxacin 0.03 0.25 0.03—0.5
Staphylococcus hominis (15) Ciprofloxacin 16.0 32.0 0.03—>64.0
Ofloxacin 16.0 64.0 4.0—>64.0
Levofloxacin 16.0 16.0 0.03—64.0
Garenoxacin 0.12 4.0 0.03—4.0
Gatifloxacin 0.25 4.0 0.06—4.0
Moxifloxacin 0.25 2.0 0.03—2.0
Streptococcus agalactiae (20) Ciprofloxacin 0.5 1.0 0.5—1.0
Ofloxacin 0.5 2.0 0.5—20
Levofloxacin 0.5 2.0 0.5—2.0
Garenoxacin 0.12 0.25 0.03—0.5
Gatifloxacin 0.06 0.5 0.03—0.5
Moxifloxacin 0.12 0.25 0.03—0.5
Streptococcus group G (17) Ciprofloxacin 0.05 1.0 0.5—2.0
Ofloxacin 1.0 2.0 0.5—4.0
Levofloxacin 0.5 2.0 0.5—2.0
Garenoxacin 0.06 0.12 0.03—0.25
Gatifloxacin 0.12 1.0 0.03—1.0
Moxifloxacin 0.12 1.0 0.03—1.0
228 K.V.I. Rolston et al.

Table 3 (Continued )
Organisms (No. tested) Drug MIC (mg/ml)
50% 90% Range

Streptococcus pyogenes (30) Ciprofloxacin 0.25 1.0 0.12—1.0

Ofloxacin 0.5 1.0 0.12—2.0
Levofloxacin 1.0 2.0 0.5—2.0
Garenoxacin 0.06 0.12 0.03—0.5
Gatifloxacin 0.03 0.25 0.03—0.5
Moxifloxacin 0.06 0.12 0.03—0.5
Streptococcus pneumoniae (30) Ciprofloxacin 1.0 4.0 0.12—4.0
Ofloxacin 1.0 4.0 0.25—4.0
Levofloxacin 0.5 2.0 0.03—2.0
Garenoxacin 0.03 0.12 0.03—0.5
Gatifloxacin 0.03 0.25 0.03—0.25
Moxifloxacin 0.03 0.25 0.03—0.25
Viridans group streptococci (50) Ciprofloxacin 2.0 8.0 0.03—8.0
Ofloxacin 2.0 16.0 0.5—32.0
Levofloxacin 1.0 2.0 0.03—4.0
Garenoxacin 0.06 1.0 0.06—2.0
Gatifloxacin 0.06 0.5 0.06—2.0
Moxifloxacin 0.06 0.12 0.06—1.0
a
NCCLS breakpoints for susceptibility were used when available. A minimum inhibitory concentration (MIC) of 1.0 mg/ml indicated
susceptibility to ciprofloxacin, and 2.0 mg/ml indicated susceptibility to ofloxacin, levofloxacin and gatifloxacin. For moxifloxacin the
NCCLS has established breakpoints only for Streptococcus pneumoniae. For the sake of comparison we used the breakpoints that apply to
gatifloxacin (a similar agent) for moxifloxacin as well. The susceptibility breakpoint (4.0 mg/ml) used in garenoxacin clinical trials was also
used in this report.26
b
VSE: vancomycin-susceptible enterococci.
c
VRE: vancomycin-resistant enterococci.

isolates than against methicillin-susceptible S. aureus iso- Discussion

lates, inhibiting just over 50% at susceptibility breakpoints.
All these isolates were susceptible to the other agents.
Ciprofloxacin, ofloxacin, and levofloxacin had poor activity
against methicillin-resistant S. epidermidis. The other three
had moderate activity against these isolates, inhibiting
between 53% and 70% at 1.0 mg/ml. Gatifloxacin, moxiflox-
acin, and garenoxacin also had good-to-moderate activity
against Staphylococcus hemolyticus and Staphylococcus
hominis isolates, with very few of these organisms having
a MIC exceeding 1.0 mg/ml.
Similar trends were observed against both beta-hemolytic
streptococci and viridans group streptococci. Overall, moxi-
floxacin, gatifloxacin, and garenoxacin were more active
against all streptococci than were ciprofloxacin, ofloxacin,
or levofloxacin. These three newer quinolones inhibited all
Streptococcus agalactiae and Streptococcus pyogenes iso-
lates at 0.5 mg/ml, and all group G streptococcal isolates
at 1.0 mg/ml. The three older quinolones were 2 to 8-fold
less active. Moxifloxacin and gatifloxacin inhibited all S.
pneumoniae isolates at 0.25 mg/ml, followed by garenox-
acin at 0.5 mg/ml. Again, levofloxacin, ofloxacin and cipro-
floxacin were less active, with MIC90 values of 2.0, 4.0 and
4.0 mg/ml respectively. Using MIC90 values to rank potency of
these agents against VGS, the order was moxifloxa-
cin > gatifloxacin > garenoxacin > levofloxacin > ciproflox-
ciprofloxacin > ofloxacin. In addition to having the lowest
MIC90 (0.12 mg/ml) against VGS, moxifloxacin also inhibited
all VGS isolates at 1.0 mg/ml, whereas the other agents
were 2 to 8-fold less active.
Recent data from several cancer treatment centers/organi-
zations indicate that Gram-positive organisms are the pre-
dominant pathogens isolated from bloodstream infections in
cancer patients.2—4,20 The staphylococci (CoNS, S. aureus)
and streptococci (VGS, beta-hemolytic streptococci, S. pneu-
moniae) are isolated most often, with the enterococci,
including VRE, becoming increasingly common.3,5 Our most
recent survey of 493 consecutive episodes of Gram-positive
BSI in patients with hematological malignancies (predomi-
nantly acute leukemias) confirm these observations (Table 2).
In our study, despite our strict definition for BSI, CoNS
accounted for 33% of episodes; Streptococcus spp collectively
accounted for 21%, and S. aureus for 15% of these infections.
We have noticed a substantial increase in isolation rates of
staphylococcus-like organisms — Micrococcus spp and Aero-
coccus spp (8% and 4%, respectively). The clinical significance
(virulence) of these isolates is unclear. Less common organ-
isms include Corynebacterium spp, Bacillus spp, L. mono-
cytogenes, and S. mucilaginosus.
The reasons cited for the current predominance of Gram-
positive pathogens in patients with hematologic malignancies
include: (a) increasing usage of vascular access devices which
facilitate the entry into the bloodstream of organisms coloniz-
ing the skin, and (b) increasingly intensive chemotherapy or
chemoradiation regimens which produce substantial oral, and
gastrointestinal mucositis.10 Chemoprophylaxis using early
generation quinolones (norfloxacin, ciprofloxacin, ofloxacin)
has reduced the frequency and severity of Gram-negative
Gram-positive in patients with hematologic malignancies
infections in neutropenic patients.21,22 However, no reduction
in the risk of Gram-positive infections has been documented
when using these agents. In fact, some suggest that these
infections might actually occur more often in patients receiv-
ing prophylaxis with early generation quinolones.11—13 This has
led to the suggestion by some, that agents with more potent
Gram-positive activity be considered for prophylaxis.11
In the second part of our study, we described the in vitro
activity of several early generation and newer generation
quinolones against a large number of recent Gram-positive,
bloodstream isolates from patients with hematological
malignancies (Table 3). Our data reveal substantial differ-
ences in the activity of these agents against most Gram-
positive pathogens tested. Overall, the new generation qui-
nolones (moxifloxacin, gatifloxacin, and garenoxacin) were
at least 2 to 8-fold more active than the older agents. These
findings are consistent with data generated from isolates
collected from multiple cancer centers in the United States
and from studies of specific pathogens, such as VGS and beta-
hemolytic streptococci.11,23,24
Four hundred and five (85%) of the 477 isolates used for
susceptibility testing were from patients receiving quinolone
prophylaxis, confirming previous reports that these agents do
not reduce the frequency of Gram-positive infections.21 Of
concern are reports documenting the selection of VGS with
diminished susceptibility to levofloxacin and other quino-
lones in patients receiving levofloxacin prophylaxis.25 The
authors of these reports caution against the use of this agent
for prophylaxis in neutropenic patients.
Our data indicate that newer generation quinolones have
enhanced Gram-positive activity compared to their older
generation counterparts. They also have excellent activity
against the Enterobacteriaceae, and most nonfermentative
Gram-negative bacilli (with the exception of P. aeruginosa),
and might be better suited for prophylaxis than older genera-
tion quinolones.14,16,17 The benefits of this approach might
include a reduction in frequency of Gram-positive infections
(which are currently far more common than Gram-negative
infections) including, perhaps, infections by VGS, which are
associated with substantial morbidity and mortality.12,13 The
lack of activity against P. aeruginosa of agents such as moxi-
floxacin and gatifloxacin might be considered by some to be a
potential drawback, but previous experience with trimetho-
prim/sulfamethoxazole (which also has poor activity against P.
aeruginosa) suggest that this is not a significant issue. Another
potential drawback is the emergence of organisms resistant to
the newer generation quinolones. While we believe that clin-
ical trials evaluating the newer generation quinolones (moxi-
floxacin, gatifloxacin) for prophylaxis in neutropenic cancer
patients would be appropriate and timely, we also believe that
this approach should only apply to patients at high risk for
developing invasive Gram-positive infections, as outlined in
the guidelines published by the Infectious Diseases Society of
America.10 Routine quinolone prophylaxis in all neutropenic
patients is not recommended.
Conflict of interest: No conflict of interest to declare.
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