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Cautious Use of Antibiotics Old and New in
the Age of MRSA
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by David W. Sharp
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Medicine Top Ten
Papers
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Rank
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Papers
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Cites Jan-
Feb 08
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Rank
Nov-Dec 08
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1
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C.L. Ogden, et al., "Prevalence of
overweight and obesity in the United
States,1999-2004," JAMA, 295(13):
1549-55, 5 April 2006. [Ctrs. for Disease Control,
Atlanta, GA] *028RG
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156
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1
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2
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S.E. Nissen, K. Wolski, "Effect of rosiglitazone on
the risk of myocardial infarction and death from
cardiovascular causes," New Engl. J.
Med., 356(24): 2457-71, 14 June 2007. [Cleveland
Clinic, OH] *178DR
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73
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2
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3
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T. Sjoblom, et al., "The consensus coding
sequences of human breast and colorectal cancers,"
Science, 314(5797): 268-74, 13 October 2006. [11
U.S. institutions] *093TV
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48
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6
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4
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B. Escudier, et al., "Sorafenib in
advanced clear-cell renal-cell carcinoma," New
Engl. J. Med., 356(2): 125-34, 11 January 2007. [15
institutions worldwide] *124NE
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42
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†
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5
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R.J. Motzer, et al., "Sunitinib versus
interferon alfa in metastatic renal-cell
carcinoma," New Engl. J. Med., 356(2):
115-24, 11 January 2007. [10 institutions worldwide] *124NE
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41
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5
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6
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S. Volinia, et al., "A microRNA expression
signature of human solid tumors defines cancer gene
targets," PNAS, 103(7): 2257-61, 14
February 2006. [5 institutions worldwide] *013LU
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38
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†
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7
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R.A. Morgan, et al., "Cancer regression in
patients after transfer of genetically engineered
lymphocytes," Science, 314(5796): 126-9,
6 October 2006. [Natl. Cancer Inst., NIH, Bethesda, MD]
*091LU
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37
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8
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G.J. Moran, et al., "Methicillin-resistant
S. Aureus infections among patients in the
emergency department," New Engl. J. Med.,
355(7): 666-74, 17 August 2006. [U., Calif., Los Angeles;
Ctrs. Disease Control & Prevent., Atlanta, GA] *074AN
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35
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†
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9
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The Heart Outcomes Prevention Evaluation (HOPE) 2
Investigators (E. Lonn, et al.),
"Homocysteine lowering with folic acid and B
vitamins in vascular disease," New Engl. J.
Med., 354(15): 1567-77, 13 April 2006. [Writing Group:
9 institutions worldwide] *031WW
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34
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†
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10
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The DREAM Trial Investigators (H.C. Gerstein, et
al.), "Effect of rosiglitazone on the
frequency of
diabetes
in patients with impaired glucose tolerance or impaired
fasting glucose: a randomised controlled trial,"
Lancet, 368(9541): 1096-1105, 23 September 2006.
[Correspond. address: Population Health Res. Inst.,
Hamilton, Ont., Canada] *089IC
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33
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SOURCE: Thomson Scientific's
Hot Papers Database. Read the
Legend.
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Alexander Fleming, the man who discovered penicillin but failed to develop
his finding, is quoted as having said of the staphylococcus that it is "a
very clever organism. No matter what antibiotic we find, it will get
resistant to it." He got that bit right at least. The earliest resistance
problems were ascribed to penicillinase (beta-lactamase), so novel
penicillin-like molecules with structures lacking a beta-lactam ring came
on the market. One of these, introduced in 1960, was methicillin (the "h"
is optional). This drug is no longer in clinical use but the name lives on
in the well-known and widely feared term
MRSA, which stands for
methicillin-resistant Staphylococcus aureus.
The first case of resistance to this drug was recorded in 1959 in the U.K.
(Anyone interested in the history of MRSA could start with the
recent volume in the Wellcome Witnesses to Twentieth
Century Medicine series). At first few alarm bells were rung (or
heeded), but in the 21st century MRSA has become a cause of
grave concern not just to patients but also to healthcare providers,
administrators, and politicians.
For example, here in the U.K. the Department of Health was pressured into
setting a target of halving the rate of MRSA bacteremia between 2004 and
2008, and earlier this year figures in league-table form for hospital
deaths associated with MRSA attracted the usual "superbug" headlines.
As with S. aureus itself, MRSA can be carried by people who remain
symptom-free. Although it causes most concern in hospital settings, there
is another sort, community-acquired MRSA, and there are differences between
the two epidemiologically, clinically, and biologically.
For example, community-acquired MRSA is less likely to be multiply drug
resistant. Paper #8 looks at staphylococcal skin and soft-tissue infections
in 422 patients coming to emergency departments in U.S. cities. Among the
patients, 76% of had S. aureus. Of those isolates, 78% were
methicillin resistant, and on further testing almost all of them were
community associated.
Three-quarters of the patients were treated with antibiotics, usually
accompanied by incision and drainage of the lesion, but in 100 (57%) of the
175 MRSA infections for which an antibiotic was given, that treatment was
not concordant with tests for antibiotic susceptibility.
Fortunately, this does not appear to have affected the long-term outcome
for these particular patients. A message from paper #8, supported by the
accompanying editorial (M.L. Grayson, New Engl. J. Med.,
355[7]:724-7, 2008), is that when a staphylococcal infection is suspected
an antibiotic may not always be necessary. Treatment options are, says Dr.
Grayson, "weighted in favor of surgical drainage as the priority
intervention—a concept better known to clinicians before the days of
penicillin."
That MRSA is indeed linked to previous antibiotic exposure is confirmed by
a very recent meta-analysis of 76 studies in 24,230 patients, which
revealed a 1.8-fold increase in risk (E. Tacconelli, et al.,
J. Antimicrob. Chemother., 61[1]:26-38, 2008). That this
microorganism is far from being vanquished is illustrated by data from a
U.S. surveillance network of almost 300 laboratories and 380,000 isolates
of S. aureus. Of these isolates, 58% were MRSA in 2007, the good
news being that there was little change from two years earlier (G.S.
Tillotson, et al., J. Antimicrob. Chemother. E-pub April
8, 2008 [abstract accessed May 24, 2008]).
Several drugs are available for patients with MRSA and, though resistance
is sometimes reported it is not (yet) on a huge scale. One such is
daptomycin (the focus of a companion paper to #8, by V.G. Fowler, et
al., New Engl. J. Med., 355[7]:653-65, 2006).
However, the battle will not be won by pharmaceuticals alone. Simple
hygienic practices to prevent cross-contamination and cross-infection and
susceptibility testing before any antibiotic is given have vital parts to
play.
Mr. David W. Sharp, M.A. (Cambridge), formerly deputy editor of
The Lancet, is a freelance writer in Minchinhampton, U.K.
Keywords: methicillin –resistant Staphylococcus aureus, MRSA, S.
aureus, antibiotic-resistant bacteria, antibiotic resistance, bacterial
infection.
What's Hot In... : What's Hot In Medicine Menu : Cautious Use of Antibiotics Old and New in the Age of MRSA - Jul/Aug 2008
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