Health care-associated methicillin-resistant Staphylococcus aureus is evolving.

Full text

Page 1

1860 • CID 2005:40 (15 June) • CORRESPONDENCE
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-
acquiredbacteremia.Cultureofjamuyielded
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 unregulatedprep-
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.
conflicts.
All authors: no
John Paul,1John R. Duncan,2Peter Sharp,3
Andrew Norris,4Mirza A. Siddiq,4
Clare Bacon,1and John Weighill4
Departments of
Diseases,
and Immunology, and
Surgery, Royal Sussex County Hospital,
Brighton, United Kingdom
1Microbiology and Infectious
2Haematology,3Clinical Biochemistry
4Ear, Nose, and Throat
References
1. Giam YC, Tham SN, Tan T, Lim A. Drugerup-
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 spontaneouslyreported
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 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2005/4012-0026$15.00
2005;40:1859–60
Health Care–Associated
Methicillin-Resistant
Staphylococcus aureus
Is Evolving
Sir—We read with interest the very in-
formative review articleaboutmethicillin-
resistant Staphylococcusaureus(MRSA)by
Deresinski [1]. However, his claim that
community-associatedMRSA(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-susceptibleMRSAstrains
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, wehavesimilarlyobservedthe
gradual displacement of the dominant
endemicmultidrug-resistantstrain(ST239-
MRSA-III)withmultidrug-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
oversomeof theoldermultidrug-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
mirrorsthatofpenicillinresistance[11]and
that newer and fitter strains are emerging
over time.
Acknowledgments
Potential conflicts of interest.
conflicts.
All authors: no
Li-Yang Hsu,1Tse-Hsien Koh,2
and Ban-Hock Tan1
Departments of
1Internal Medicine and
Singapore General Hospital, Singapore
2Pathology,
References
1. DeresinskiS.Methicillin-resistantStaphylococ-
cus aureus: an evolutionary, epidemiologic,
and therapeutic odyssey. Clin Infect Dis 2005;
40:562–73.
2. Donnio PY, Preney L, Gautier-LerestifAL,etal.
Changesinstaphylococcalcassettechromosome
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-
by guest on May 18, 2011
cid.oxfordjournals.org
Downloaded from

Page 2

CORRESPONDENCE • CID 2005:40 (15 June) • 1861
lin-resistantStaphylococcusaureusclonesduring
a 5-year period (1998 to 2002) in a Spanish
hospital. J Clin Microbiol 2004;42:4649–56.
5. WitteW,EnrightM,SchmitzFJ,CunyC,Braulke
C, Heuck D. Characteristics of a new epidemic
MRSA in Germany ancestral to United King-
domEMRSA-15.IntJMedMicrobiol2001;290:
677–82.
6. DenisO,DeplanoA,NonhoffC,etal.National
surveillanceofmethicillin-resistantStaphylococ-
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,TanBH.Disseminationofmulti-susceptible
methicillin-resistant Staphylococcus aureus in
Singapore. J Clin Microbiol [in press].
9. Laurent F, Lelie `vre H, Cornu M, et al. Fitness
and competitive growth advantage of new
gentamicin-susceptibleMRSAclonesspread-
ing in French hospitals. J Antimicrob Che-
mother 2001;47:277–83.
10. Saiman L, O’Keefe M, Graham PL 3rd, et al.
Hospitaltransmissionofcommunity-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 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2005/4012-0027$15.00
2005;40:1860–1
Abacavir Dosing with
Hepatic Dysfunction
Sir—We appreciate the topical review of
antiretroviral drug pharmacokinetics in
patientswithhepaticdysfunctionbyWyles
and Gerber [1]. The authors note that al-
cohol dehydrogenase and glucuronyl
transferase metabolize abacavir. Citingthe
absence of pharmacokinetic datafrompa-
tients with liver disease, the authors rec-
ommend no change in the dose of aba-
cavirforpatientswithhepaticdysfunction.
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 single600-
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,theareaundertheconcentration
(AUC)–time curve increased by 89% and
thehalf-lifeincreasedby58%.Inaddition,
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-
paticimpairmentandthatabacaviriscon-
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 inanopen-label,
randomized, 3-way crossover study of 25
HIV-infected subjects, ethanol inducedan
increase in the abacavir AUC of 41% and
an increase in the elimination half-life of
26% [4].
Insummary,whenusedinpatientswith
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.
ceived recent grant support from GlaxoSmith-
Kline. D.M.G.: no conflicts.
M.B.G. hasre-
David M. Graham1
and Matthew Bidwell Goetz2
1Affiliated Program in Infectious Diseases,
2Infectious Diseases Section, Department
of Medicine, David Geffen School of Medicine,
University of California at Los Angeles,
and
Los Angeles, California
References
1. Wyles DL, Gerber JG. Antiretroviraldrugphar-
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.
Pharmacokineticinteraction
(1592U89) and ethanol in human immuno-
deficiency virus-infected adults. Antimicrob
Agents Chemother 2000;44:1686–90.
of abacavir
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
This article is in the public domain, and no copyright is
claimed.. All rights reserved. 1058-4838/2005/4012-0028
2005;40:1861
Reply to Graham and Goetz
Sir—We appreciate the comments of Drs.
GrahamandGoetz[1]regardingthephar-
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 alettertotheeditor
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 bemade:(1)abacavir
by guest on May 18, 2011
cid.oxfordjournals.org
Downloaded from