15 JUNE
Correspondence
Spontaneous Rupture
of the Spleen during Malaria:
A Conservative Treatment
Approach May Be
Appropriate
Sir—Spontaneous rupture of the spleen
is a rare complication of malaria. We re-
port a case of splenic rupture that was
successfully treated with a conservative
approach.
A formerly healthy 23-year-old man
was admitted to the hospital with a 2-week
history of fever, myalgia, and diarrhea,
which occurred after a stay of several
weeks in Kenya. The patient had not re-
ceived malaria prophylaxis. The initial
physical examination showed that he was
severely ill, with a body temperature of
39.8C, blood pressure of 99/41 mmHg,
Figure 1. Abdominal CT scan showing a splenic hematoma and hemoperitoneum
1858 • CID 2005:40 (15 June) • CORRESPONDENCE
and a heart rate of 126 beats/min. There
was no abdominal tenderness or rigidity,
and the spleen was not enlarged. Labo-
ratory tests revealed a WBC count of 5.4
⫻ 109 cells/L, a hemoglobin level of 128
g/L, a platelet count of 27 ⫻ 109 platelets/
L, and parasitemia (Plasmodium falcipa-
rum percentage, 2.2%). Quinine treatment
was administered intravenously.
Two days after admission to the hos-
pital, the patient became dyspneic, with a
respiratory rate of 35 breaths/min; the pa-
tient had an arterial partial pressure of ox-
ygen of 10 kPa while breathing 3 L of
oxygen/min. A chest radiograph showed
bilateral infiltrates, and the left ventricular
ejection percentage was 40%. Noninvasive
ventilation and diuretic therapy promptly
resolved these anomalies. On day 4 of hos-
pitalization, abdominal tenderness and
enlargement appeared, associated with a
drop in the hemoglobin level to 62 g/L.
Abdominal CT showed splenomegaly
(maximum spleen diameter, 23 cm), with
2 areas of rupture, a contained hematoma,
and an abundant hemoperitoneum (figure
1). Because hemodynamic parameters
were stable, a conservative treatment ap-
proach was selected. The patient was dis-
charged from the hospital 19 days after
admission, after abdominal CT demon-
strated that the perisplenic hematoma and
the hemoperitoneum had decreased. The
patient was regularly followed up for 8
months. The last CT scan, performed 1
month after admission, showed only a
small anterior splenic hypodensity. Eight
months after admission, the patient had
no abdominal symptoms, and the findings
of ultrasonography were normal.
Although spleen enlargement is a very
common feature of malaria, the incidence
of spontaneous splenic rupture is not well
known; it ranges from 0% to 2%. Using
the Medline database, we found 19 cases
reported in the literature since 1960 [1, 2].
Formation and subsequent rupture of an
initially contained hematoma is believed
to be the usual mechanism of splenic rup-
ture. In the present case, polypnea and the
use of positive-pressured noninvasive ven-
tilation may have played a role in the for-
mation of a splenic hematoma.
To our knowledge, a very limited num-
ber of cases of spontaneous splenic rup-
ture during malaria have been treated with
a nonsurgical approach [2, 3]. Splenec-
tomy has always been considered the treat-
ment of choice to control bleeding related
to splenic rupture, but the procedure leads
to loss of the immunologic function of the
spleen, resulting in an increased suscep-
tibility to infections. In the case of splenic
trauma, nonsurgical management is the
prevailing treatment approach when hem-
orrhagic shock is absent [4]. Few data are
available concerning infection-related
rupture of the spleen. However, the sig-
nificant morbidity and mortality and the
increased risk of complicated or fatal dis-
ease from future exposure to malaria that
are associated with splenectomy should
lead to the use of a conservative treatment
approach whenever possible.
Acknowledgments
Potential conflicts of interest. All authors: no
conflicts.
Frédéric M. Jacobs,1 Dominique Prat,1
Fanny Petit,2 Claude Smadja,3
and François G. Brivet1
1
Medical Intensive Care Unit and Departments
of 2Radiology and 3Surgery, Hôpital Antoine Béclère
Assistance Publique–Hôpitaux de Paris,
Clamart, France
References
1. Hamel CT, Blum J, Harder F, Kocher T. Non-
operative treatment of splenic rupture in ma-
laria tropica: review of the literature and case
report. Acta Trop 2002; 82:1–5.
2. Yagmur Y, Kara IH, Aldemir M, Buyukbayram
H, Tacyildiz IH, Keles C. Spontaneous rupture
of malarial spleen: two case reports and review
of literature. Crit Care 2000; 4:309–13.
3. Ribordy V, Schaller MD, Martinet O, Doenz F,
Liaudet L. Spontaneous rupture of the spleen
during malaria treated with transcatheter coil
embolization of the splenic artery. Intensive
Care Med 2002; 28:996.
4. Velmahos GC, Chan LS, Kamel E, et al. Non-
operative management of splenic injuries: have
we gone too far? Arch Surg 2000; 135:674–81.
Reprints or correspondence: Dr. Frédéric Jacobs, Service de
Réanimation Médicale, Hôpital Antoine Béclère, 157 rue de
la Porte de Trivaux, 92140 Clamart, France (frederic
.jabobs@abc.ap-hop-paris.fr).
Clinical Infectious Diseases 2005; 40:1858–9
 2005 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2005/4012-0025$15.00
Agranulocytosis and
Citrobacter Infection
Associated with Jamu,
a Herbal Remedy Containing
Phenylbutazone
Sir—A 75-year-old woman with osteo-
arthritis obtained jamu, a herbal tonic
from Indonesia, from a local health food
store. Her pains quickly disappeared. Her
regular regimen of medication included
zopiclone, diclofenac (which she had been
receiving for many years), and chondro-
itin/glucosamine capsules. After ingesting
8 sachets of jamu during a 6-week period,
she was admitted to the hospital with a 3-
day history of fever, sore throat, and dys-
phagia. She had cellulitis of the anterior
neck and severe pharyngitis. Flexible na-
sendoscopy revealed erythema and edema
of the glottic and supraglottic structures.
Her temperature was 38.0C. A complete
blood cell count revealed a hemoglobin
level of 11.3 g/dL, a WBC count of 0.3
⫻ 109 cells/L (neutrophil count, 0.0 ⫻ 109
neutrophils/L), and a platelet count of
71 ⫻ 109 cells/L, with an erythrocyte sed-
imentation rate of 72 mm/h. Serum vi-
tamin B12, folate, and immunoglobulin
levels were within the normal range. Bone
marrow aspirations showed plentiful meg-
CORRESPONDENCE • CID 2005:40 (15 June) • 1859
akaryocytes and erythroid precursors but
an absence of neutrophils and myeloid
precursors, which is consistent with a di-
agnosis of agranulocytosis. Treatment was
started with dexamethasone, metronida-
zole, ticarcillin-clavulanate, and gentami-
cin. Cultures of blood samples and throat
swab specimens subsequently yielded Ci-
trobacter koseri that was susceptible to ti-
carcillin-clavulanate and gentamicin. Four
doses of subcutaneous filgrastim (granu-
locyte colony-stimulating factor) were
given. The patient gradually recovered,
with the WBC count reaching a peak of
78 ⫻ 109 cells/L before returning to nor-
mal levels, and she was discharged.
The jamu was stated to contain ginger,
black pepper, sinthok bark, Massoia aro-
matica Becc., Abrus precatorius (i.e., wild
licorice), and Orthosiphon stamineus (i.e.,
Java tea). A literature search of the
PubMed database revealed a report of fatal
toxic epidermal necrosis associated with
jamu supplemented with phenylbutazone
[1]. Analysis of two 14-g sachets of the
jamu confirmed the presence of phenyl-
butazone at a concentration of 0.32%
weight-to-weight (45 mg of phenylbuta-
zone per sachet). Phenylbutazone was
detected using mass spectrometry for 7
principal transitions from its molecular
species.
A report was found that described
microbial contamination of jamu [2]. Cul-
tures of jamu yielded Klebsiella pneumon-
iae, Enterobacter sakazakii, and Clostrid-
ium species but not C. koseri. The aerobic
colony count was 8.0 ⫻ 105 colony-form-
ing units per gram.
Phenylbutazone is an effective anti-
inflammatory drug, but it was a common
cause of agranulocytosis until its use was
restricted in the United Kingdom to the
treatment of ankylosing spondylitis [3].
The prognosis for neutropenia due to
phenylbutazone use is generally good [4].
A causal relationship between exposure
to phenylbutazone and agranulocytosis
cannot be established with certainty in this
case, because diclofenac has occasionally
been associated with agranulocytosis [5],
although the patient had been taking di-
clofenac without experiencing adverse ef-
fects. C. koseri is an unusual cause of
pharyngitis and cellulitis and of community-
acquired bacteremia. Culture of jamu yielded
other species of Enterobacteriaciae but did
not yield other species of Citrobacter.
The Trading Standards Officer was no-
tified of the presence of phenylbutazone
in jamu, resulting in the confiscation of
the supplier’s stock and the possibility of
prosecution. Jamu is an unregulated prep-
aration that is probably available world-
wide. It is important that a patient’s drug
history should include so-called “health
tonics.”
Acknowledgments
Potential conflicts of interest. All authors: no
conflicts.
John Paul,1 John R. Duncan,2 Peter Sharp,3
Andrew Norris,4 Mirza A. Siddiq,4
Clare Bacon,1 and John Weighill4
Departments of 1Microbiology and Infectious
Diseases, 2Haematology, 3Clinical Biochemistry
and Immunology, and 4Ear, Nose, and Throat
Surgery, Royal Sussex County Hospital,
Brighton, United Kingdom
References
1. Giam YC, Tham SN, Tan T, Lim A. Drug erup-
tions from phenylbutazone in jamu. Ann Acad
Med Singapore 1986; 15:118–21.
2. Limyati DA, Juniar BL. Jamu gendong, a kind
of traditional medicine in Indonesia; the mi-
crobial contamination of its raw materials and
end product. J Ethnopharmacol 1998; 63:
201–8.
3. ABPI compendium of data sheets and sum-
maries of product characteristics 1999–2000.
London: Datapharm, 1999.
4. Pennington D, Rush B, Castaldi P, eds. De gru-
chy’s clinical haematology in medical practice.
4th ed. Oxford, United Kingdom: Blackwell,
1980.
5. Ciucci AG. A review of spontaneously reported
adverse drug reactions with diclofenac sodium
(Voltarol). Rheumatol Rehabil 1979; Suppl 2:
116–21.
Reprints or correspondence: Dr. John Paul, Dept. of Micro-
biology and Infectious Diseases, The Royal Sussex County
Hospital, Eastern Rd., Brighton BN2 5BE, United Kingdom
(tetrix@pavilion.co.uk).
Clinical Infectious Diseases 2005; 40:1859–60
 2005 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2005/4012-0026$15.00
1860 • CID 2005:40 (15 June) • CORRESPONDENCE
Health Care–Associated
Methicillin-Resistant
Staphylococcus aureus
Is Evolving
Sir—We read with interest the very in-
formative review article about methicillin-
resistant Staphylococcus aureus (MRSA) by
Deresinski [1]. However, his claim that
community-associated MRSA (CA-MRSA)
strains had displaced health care–associ-
ated MRSA (HA-MRSA) strains in some
hospitals remains to be confirmed, al-
though it is possible that it may even-
tually prove to be prophetic.
In the article cited in support of this
assertion, Donnio et al. [2] described a
phenomenon wherein endemic multi-
drug-resistant HA-MRSA had been re-
placed by more-susceptible MRSA strains
with differing SCCmec types (in partic-
ular, SCCmec IV). However, it is not at
all clear that the multidrug-susceptible
strains described by Donnio et al. [2] had
arisen from the community, and, in fact,
there are reasons to consider otherwise.
First, the initial CA-MRSA strains iso-
lated in France were clonal (ST80-MRSA-
IV) rather than belonging to a more het-
erogeneous population [3]. Second (and
more importantly), this same phenom-
enon has also been observed in various
hospitals in Europe [4–6] and South
America [7] during the past decade, and
typing of these more-susceptible MRSA
strains has established that they were
related to epidemic HA-MRSA strains
rather than community strains. In par-
ticular, strains related to UK-EMRSA-15
(which also bears SCCmec IV) [5], UK-
EMRSA-16 (ST36-MRSA-II) [4, 6], and
Berlin clone (ST45-MRSA-IV) [6] have
been most successful in displacing en-
demic multidrug-resistant HA-MRSA. In
Singapore, we have similarly observed the
gradual displacement of the dominant
endemic multidrug-resistant strain (ST239-
MRSA-III) with multidrug-susceptibleUK-
EMRSA-15 (ST22-MRSA-IV) during the
past 2 years [8].
The majority of these more-susceptible
epidemic HA-MRSA strains only arose in
the early 1990s [4], and it may be that
they have a competitive growth advantage
over some of the older multidrug-resistant
HA-MRSA strains [9] that enables their
successful integration into (and eventual
domination of) a nosocomial setting pre-
viously populated by the latter [4–8]. It
remains to be seen whether this phenom-
enon, representing an evolutionary pro-
cess among HA-MRSA, will parallel the
spread of CA-MRSA worldwide.
Interestingly enough, these more-sus-
ceptible epidemic HA-MRSA strains have
not been successful in spreading to the
community, despite their advantages over
multidrug-resistant HA-MRSA. Converse-
ly, despite their successful dissemination
in many community settings, CA-MRSA
strains have thus far failed to penetrate
the hospital setting (beyond causing iso-
lated nosocomial outbreaks) [10]. These
are not barriers that are expected to last,
however, and the overall reality is sober-
ing—that, among Staphylococcus aureus,
the development of methicillin resistance
mirrors that of penicillin resistance [11] and
that newer and fitter strains are emerging
over time.
Acknowledgments
Potential conflicts of interest. All authors: no
conflicts.
Li-Yang Hsu,1 Tse-Hsien Koh,2
and Ban-Hock Tan1
Departments of 1Internal Medicine and 2Pathology,
Singapore General Hospital, Singapore
References
1. Deresinski S. Methicillin-resistantStaphylococ-
cus aureus: an evolutionary, epidemiologic,
and therapeutic odyssey. Clin Infect Dis 2005;
40:562–73.
2. Donnio PY, Preney L, Gautier-Lerestif AL, et al.
Changes in staphylococcal cassettechromosome
type and antibiotic resistance profile in meth-
icillin-resistant Staphylococcus aureus isolates
from a French hospital over an 11 year period.
J Antimicrob Chemother 2004; 53:808–13.
3. Dufour P, Gillet Y, Bes M, et al. Community-
acquired methicillin-resistant Staphylococcus
aureus in France: emergence of a single clone
that produces Panton-Valentine leukocidin.
Clin Infect Dis 2002; 35:819–24.
4. Perez-Roth E, Lorenzo-Diaz F, Batista N, Mo-
reno A, Mendez-Alvarez S. Tracking methicil-
 lin-resistant Staphylococcus aureus clones during
a 5-year period (1998 to 2002) in a Spanish
hospital. J Clin Microbiol 2004; 42:4649–56.
5. Witte W, Enright M, Schmitz FJ, Cuny C, Braulke
C, Heuck D. Characteristics of a new epidemic
MRSA in Germany ancestral to United King-
dom EMRSA-15. Int J Med Microbiol 2001; 290:
677–82.
6. Denis O, Deplano A, Nonhoff C, et al. National
surveillance of methicillin-resistant Staphylococ-
cus aureus in Belgian hospitals indicates rapid
diversification of epidemic clones. Antimicrob
Agents Chemother 2004; 48:3625–9.
7. Melo MC, Silva-Carvalho MC, Ferreira RL, et
al. Detection and molecular characterization
of a gentamicin-susceptible, methicillin-resis-
tant Staphylococcus aureus (MRSA) clone in
Rio de Janeiro that resembles the New York/
Japan clone. J Hosp Infect 2004; 58:276–85.
8. Hsu LY, Koh TH, Singh KS, Kang ML, Kurup
A, Tan BH. Dissemination of multi-susceptible
methicillin-resistant Staphylococcus aureus in
Singapore. J Clin Microbiol [in press].
9. Laurent F, Lelièvre H, Cornu M, et al. Fitness
and competitive growth advantage of new
gentamicin-susceptible MRSA clones spread-
ing in French hospitals. J Antimicrob Che-
mother 2001; 47:277–83.
10. Saiman L, O’Keefe M, Graham PL 3rd, et al.
Hospital transmission of community-acquired
methicillin-resistant Staphylococcus aureus
among postpartum women. Clin Infect Dis
2003; 37:1313–9.
11. Chambers HF. The changing epidemiology of
Staphylococcus aureus? Emerg Infect Dis 2001;
7:178–82.
Reprints or correspondence: Dr. Li-Yang Hsu, Dept. of Internal
Medicine, Singapore General Hospital, Outram Rd., S169608,
Singapore (liyang_hsu@yahoo.com).
Clinical Infectious Diseases 2005; 40:1860–1
 2005 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2005/4012-0027$15.00
Abacavir Dosing with
Hepatic Dysfunction
Sir—We appreciate the topical review of
antiretroviral drug pharmacokinetics in
patients with hepatic dysfunction by Wyles
and Gerber [1]. The authors note that al-
cohol dehydrogenase and glucuronyl
transferase metabolize abacavir. Citing the
absence of pharmacokinetic data from pa-
tients with liver disease, the authors rec-
ommend no change in the dose of aba-
cavir for patients with hepatic dysfunction.
This recommendation, however, over-
looks a previous study of abacavir phar-
macokinetics in cirrhotic patients with
mild hepatic impairment (defined as
Child-Pugh scores of 5–6) [2]. In this
study, the pharmacokinetics of single 600-
mg doses of abacavir administered to 9
subjects with HIV infection who had re-
ceived a diagnosis of moderate cirrhosis
were compared with those of 9 controls
who were matched for age, sex, and
weight. In patients with mild hepatic dys-
function, the area under the concentration
(AUC)–time curve increased by 89% and
the half-life increased by 58%. In addition,
the half-life of inactive metabolites in-
creased by 21% to 31%. Although there
were no adverse events after a single dose,
the authors recommended a decrease of
the abacavir dose to 150 mg twice per day.
Similarly, the abacavir prescribing infor-
mation specifies that a dose of 200 mg
twice per day should be used in mild he-
patic impairment and that abacavir is con-
traindicated in moderate to severe hepatic
impairment [3].
Finally, the association between alcohol
dehydrogenase activity and liver disease is
not certain in cases of nonalcoholic liver
disease. It is relevant that in an open-label,
randomized, 3-way crossover study of 25
HIV-infected subjects, ethanol induced an
increase in the abacavir AUC of 41% and
an increase in the elimination half-life of
26% [4].
In summary, when used in patients with
mild hepatic dysfunction in the presence
of cirrhosis, a dose of 150–200 mg twice
per day should be considered, especially
for those who use alcohol. Abacavir
should be avoided in those with more se-
vere hepatic impairment.
Acknowledgments
Potential conflicts of interest. M.B.G. has re-
ceived recent grant support from GlaxoSmith-
Kline. D.M.G.: no conflicts.
David M. Graham1
and Matthew Bidwell Goetz2
1
Affiliated Program in Infectious Diseases,
and 2Infectious Diseases Section, Department
of Medicine, David Geffen School of Medicine,
University of California at Los Angeles,
Los Angeles, California
CORRESPONDENCE • CID 2005:40 (15 June) • 1861
References
1. Wyles DL, Gerber JG. Antiretroviral drug phar-
macokinetics in hepatitis with hepatic dys-
function. Clin Infect Dis 2005; 40:174–81.
2. Raffi F, Benhamou Y, Sereni D, et al. Phar-
macokinetics of, and tolerability to, a single,
oral, 600 mg dose of abacavir in HIV-positive
subjects with or without liver disease (abstract
1630). Interscience Conference on Antimicro-
bial Agents and Chemotherapy (Toronto).
2000.
3. Prescribing information for ziagen tablets and
oral solution. Research Triangle Park, North
Carolina: GalaxoSmithKline, 2004.
4. McDowell JA, Chittick GE, Stevens CP, et al.
Pharmacokinetic interaction of abacavir
(1592U89) and ethanol in human immuno-
deficiency virus-infected adults. Antimicrob
Agents Chemother 2000; 44:1686–90.
Reprints or correspondence: Dr. Matthew Bidwell Goetz, In-
fectious Diseases Section, Dept. of Medicine, David Geffen
School of Medicine at UCLA, VA Greater Los Angeles Health-
care System (111-F), 11301 Wilshire Boulevard, Los Angeles,
CA 90073 (matthew.goetz@med.va.gov).
Clinical Infectious Diseases 2005; 40:1861
This article is in the public domain, and no copyright is
claimed.. All rights reserved. 1058-4838/2005/4012-0028
Reply to Graham and Goetz
Sir—We appreciate the comments of Drs.
Graham and Goetz [1] regarding the phar-
macokinetics of abacavir in the presence
of hepatic dysfunction and the altered
prescribing information that was pub-
lished shortly after our article was ac-
cepted for publication. Though we were
unaware of the original data that was pre-
sented in abstract form in 2000, it should
be noted that the abacavir package insert
did not recommend any dose adjustment
for hepatic dysfunction until this most re-
cent change in August 2004 [2]. In fact,
we recently submitted a letter to the editor
that highlights the same data and altered
dosing recommendations for abacavir in
the presence of mild hepatic dysfunction
[3].
A word of caution, however, is neces-
sary. The package insert states that aba-
cavir is contraindicated in people with
moderate to severe hepatic impairment
(because of a lack of data) [2], and Gra-
ham and Goetz echo this statement, writ-
ing that “Abacavir should be avoided in
those with more severe liver disease” [1].
But 3 points need to be made: (1) abacavir
(among antiretrovirals) possesses a rather
large therapeutic index; (2) abacavir tox-
icity, particularly the hypersensitivity re-
action, does not appear to be related to
abacavir levels; and (3) if the administra-
tion of antiretrovirals to persons with he-
patic impairment were limited to only
those drugs for which adequate pharma-
cokinetic and safety data are available,
many of the currently available antiret-
rovirals would be eliminated. If you com-
bine these points with emerging data that
suggest control of HIV infection may slow
the progression of hepatitis C virus–re-
lated liver disease in coinfected individuals
[4, 5], these limitations could certainly ad-
versely impact the survival and quality of
life of persons with HIV and hepatitis C
virus infections. In our letter [3], we took
a less dogmatic approach, stating that
treatment with the drug should not be
withheld if other compelling factors sup-
port the use of abacavir in the presence
of more advanced hepatic dysfunction [3].
5. Qurishi N, Kreuzberg C, Luchters G, et al. Ef-
fect of antiretroviral therapy on liver-related
mortality in patients with HIV and hepatitis C
coinfection. Lancet 2003; 362:1708–13.
Reprints or correspondence: Dr. John G. Gerber, 4200 E. 9th
Ave., B-168, Denver, CO 80262 (john.gerber@uchsc.edu).
Clinical Infectious Diseases 2005; 40:1861–2
 2005 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2005/4012-0029$15.00
Prophylactic Use of
Moxifloxacin in Patients
Receiving Bone Marrow
Transplants Was Not
Associated with Increased
Ciprofloxacin Resistance in
Escherichia coli and
Enterococci
Sir—Quinolone use for antibacterial pro-
phylaxis in patients with febrile neutro-
penia has become widespread since 1990,
and use of fluoroquinolones, including
norfloxacin, ciprofloxacin, and levofloxa-
cin, has been associated with the emer-
gence of quinolone-resistant Escherichia
coli and viridans group streptococci [1–4].
Moxifloxacin was introduced into Na-
tional Taiwan University Hospital in 2002,
and since 2003, this agent, instead of cip-
rofloxacin, has been extensively used (at a
dosage of 400 mg q.d. for 14–21 days) for
prophylaxis of infection for patients in
the 6-bed bone marrow transplantation
(BMT) ward at the hospital. During this
time, fluoroquinolones were used only for
therapeutic purposes in patients with feb-
rile neutropenia in the 3-bed hematology/
oncology (HO) ward at the hospital.

Acknowledgments
Potential conflicts of interest. D.L.W. and
J.G.B.: no conflicts.

David L. Wyles and John G. Gerber

University of Colorado Health Sciences Center,
Denver, Colorado

References

1. Graham DM, Goetz MD. Abacavir dosing with

hepatic dysfunction (letter). Clin Infect Dis
2005; 40:1861 (in this issue).
2. Ziagen (abacavir sulfate) [package insert
(USA)]. Research Triangle Park, North Caro-
lina: GlaxoSmithKline, 2004.
3. Wyles DL, Gerber JG. Abacavir pharmacoki-
netics in hepatic dysfunction. Clin Infect Dis
2005; 40:909–10.
4. Brau N, Rodriguez-Torres M, Salvatore M, et
al. Control of HIV viral load through highly
active antiretroviral therapy (HAART) slows
down liver fibrosis progression in HIV/HCV-
coinfection and makes it the same as in HCV-
monoinfection. The Puerto Rico-New York
Hepatitis C Study Group [abstract 91]. In: Pro-
gram and abstracts of the 39th European As-
sociation for the Study of Liver Disease (Berlin). Figure 1. Correlation between annual rates of resistance to ciprofloxacin in enterococci and
Geneva, Switzerland: Keyes International, 2004. Escherichia coli isolates and consumption of 3 fluoroquinolones (ciprofloxacin, levofloxacin, and
Available at: http://www.kenes.com/easl2004 moxifloxacin) from 2001 through 2003 at National Taiwan University Hospital. Isolates were recovered
Sci/program/abstracts/91.doc. Accessed on 19 from patients treated in a hematology/oncology ward (A) and a bone marrow transplantation ward
April 2004. (B). DDD, defined daily dose.

1862 • CID 2005:40 (15 June) • CORRESPONDENCE

Table 1. Relationship between fluoroquinolone consumption and ciprofloxacin resis-
tance in enterococci and Escherichia coli in the hematology/oncology ward and the
bone marrow transplantation ward of National Taiwan University Hospital, 2001–2003.
Ciprofloxacin resistance
in the H/O ward,
by pathogen
Enterococci
Fluoroquinolone
consumed r P r P
Ciprofloxacin 0.9925 .077 0.932
Levofloxacin 0.972 .149 0.748
Moxifloxacin 0.782 .427 0.395
Any 0.997 .041 0.849
NOTE. Boldfaced values are statistically significant. BMT, bone marrow transplantation; H/O, hema-
tology/oncology.
To assess the relationship between
fluoroquinolone use and drug resistance,
we evaluated the annual rates of cipro-
floxacin resistance, as determined by the
routine disk diffusion method, in E. coli
and enterococci recovered from various
clinical specimens obtained from patients
admitted to the 2 wards and the annual
consumption (defined daily dose [DDD]
per 1000 patient-days) of 3 fluoroquino-
lones from these 2 wards from 2001
through 2003. During this 3-year period,
the number of patient-days for the HO
and BMT wards was 13,330 and 1869, re-
spectively, in 2001; 13,345 and 1767, re-
spectively, in 2002; and 11,034 and 1642,
respectively, in 2003. In 2001, the total
consumption of 3 fluoroquinolones (cip-
rofloxacin, levofloxacin, and moxifloxa-
cin) in the HO ward was 213.4 DDD per
1000 patient-days (202.2 DDD per 1000
patient-days for ciprofloxacin, 11.0 DDD
per 1000 patient-days for levofloxacin, and
0 DDD per 1000 patient-days for moxi-
floxacin). In 2002, total consumption was
154.0 DDD per 1000 patient-days (144.2
DDD per 1000 patient-days for ciproflox-
acin, 5.8 DDD per 1000 patient-days for
levofloxacin, and 4.0 DDD per 1000 pa-
tient-days for moxifloxacin). In 2003, total
consumption was 289.1 DDD per 1000
patient-days (240.8 DDD per 1000 pa-
tient-days for ciprofloxacin, 23.8 DDD per
1000 patient-days for levofloxacin, and
24.5 DDD per 1000 patient-days for mox-
ifloxacin). In the BMT ward, total con-
Ciprofloxacin resistance
in the BMT ward,
by pathogen
E. coli Enterococci E. coli
r P r P
.234 ⫺0.998 .029 ⫺0.931
.461 … … … …
.740 ⫺0.901 .285 ⫺0.992
.353 ⫺0.942 .216 ⫺0.999
sumption of fluoroquinolones (ciprofloxacin
and moxifloxacin) increased dramatically
from 45.1 DDD per 1000 patient-days (45.1
DDD per 1000 patient-days for ciprofloxacin
and 0 DDD per 1000 patient-days for mox-
ifloxacin) in 2001, to 49.5 DDD per 1000
patient-days (17.4DDDper1000patient-days
for ciprofloxacin and 32.1 DDD per 1000
patient-days for moxifloxacin) in 2002,
to 336.8 DDD per 1000 patient-days
(92.6 DDD per 1000 patient-days for cip-
rofloxacin and 244.2 DDD per 1000 pa-
tient-days for moxafloxacin) in 2003 (fig-
ure 1).
The increase in total fluoroquinolone
consumption in the BMT ward (mainly
an increase in moxifloxacin consumption)
did not result in an increase in the rate of
ciprofloxacin resistance in E. coli (51.2%
in 2001, 51.2% in 2002, and 48.6% in
2003) or in enterococci (75.0% in 2001,
80.2% in 2002, and 64.3% in 2003); on
the contrary, it was significantly associated
with a decrease in the rate of ciprofloxacin
resistance in E. coli (r p ⫺0.999; P p
.008) (figure 1A and table 1). Rates of cip-
rofloxacin resistance in E. coli (55.82% in
2001, 37.6% in 2002, and 56.6% in 2003)
and in enterococci (74.5% in 2001, 68.2%
in 2002, and 80.9% in 2003) changed in
parallel with the consumption of fluoro-
quinolones (mainly ciprofloxacin) in the
HO ward, particularly for enterococci
(r p 0.997; P p .041) (figure 1B and ta-
ble 1).
The present study found that, although
there was widespread use of moxifloxacin
among patients in the BMT ward, rates of
ciprofloxacin resistance remained rela-
tively stable in E. coli or decreased in en-
terococci. A possible explanation for this
finding is that moxifloxacin, compared
with ciprofloxacin and levofloxacin, has
less potential for selection of antibiotic-
resistant mutants because of favorable
.237
mutation protection concentration [5].
.077 This study also demonstrated that in-
.008 creased use of fluoroquinolones in the HO
ward was associated with increased cip-
rofloxacin resistance in E. coli and enter-
ococci, although this correlation did not
reach statistical significance for E. coli. This
finding was in agreement with previous
reports. However, the prevalence of quin-
olone-resistant bacteria at a hospital de-
pends on several factors, such as the ad-
equacy of infection control (to prevent
clonal spreading of drug-resistant bacte-
ria), the use of some unrelated antibiotics
(to prevent cross-resistance to other an-
tibiotics in quinolone-resistant isolates),
the characteristics of patients, and path-
ogen-specific dynamics [1, 5]. Previous
studies have demonstrated that a corre-
lation between ciprofloxacin use and the
development of drug resistance existed in
E. coli and viridans group streptococci but
not in Pseudomonas aeruginosa and staph-
ylococci [1]. Our findings extend these
findings to enterococci.
Moxifloxacin has been shown to be a
more efficient agent than ciprofloxacin in
the prophylaxis of infection in patients
with cancer who have neutropenia [6].
The observation of the low possibility of
the development of ciprofloxacin resis-
tance during prophylactic use of moxi-
floxacin favors its suitability to replace
ciprofloxacin as a prophylactic agent in
patients receiving a BMT. However, rou-
tine use of antibiotics for bacterial pro-
phylaxis is not recommended for hema-
topoietic stem cell transplant (HSCT)
candidates [7]. If physicians choose to use
a single antibiotic for antibacterial pro-
phylaxis among asymptomatic, afebrile,
neutropenic transplant recipients, routine
CORRESPONDENCE • CID 2005:40 (15 June) • 1863
reviews of hospital and HSCT ward an-
tibiotic-susceptibility profiles are neces-
sary [7, 8]. In the interim, routine use of
a fluoroquinolone as a prophylactic agent
is not recommended in the BMT ward of
National Taiwan University Hospital be-
cause of a high rate of fluoquinolone-
resistant bacteria.
patients with profound neutropenia. Antibiot
Khimioter 2004; 49:26–31.
Reprints or correspondence: Dr. Po-Ren Hsueh, Depts. of Lab-
oratory Medicine and Internal Medicine, National Taiwan Uni-
versity Hospital, 7 Chung-Shan South Rd., Taipei, Taiwan
(hsporen@ha.mc.ntu.edu.tw).
Clinical Infectious Diseases 2005; 40:1862–4
 2005 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2005/4012-0030$15.00

Acknowledgments
Potential conflicts of interest. All authors: no
conflicts.

Po-Ren Hsueh,1,2 Hsiou-Jen Cheng,3

Jih-Luh Tang,2 Min Yao,2 and Hwei-Fang Tien2
Departments of 1Laboratory Medicine, 2Internal
Medicine, and 3Pharmacy, National Taiwan
University Hospital, National Taiwan University
College of Medicine, Taipei, Taiwan

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