David L. Paterson

Joseph G. McCormack

Muto

Paterson, David L.

McCormack, Joseph G.

University of Queensland eSpace

More Evidence of the Benefits of Rational Antimicrobial Use in Clinical Practice • 
Author(s): David L. Paterson , MBBS, FRACP; Joseph G. McCormack , MBBCh, FRCP, MD,
FRACP
Source: Infection Control and Hospital Epidemiology, Vol. 24, No. 9 (September 2003), pp. 642-
643
Published by: Cambridge University Press on behalf of The Society for Healthcare Epidemiology of
America
Stable URL: http://www.jstor.org/stable/10.1086/502273 .
Accessed: 21/10/2015 22:58
Your use of the JSTOR archive indicates your acceptance of the Terms & Conditions of Use, available at .
http://www.jstor.org/page/info/about/policies/terms.jsp
 .
JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of
content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms
of scholarship. For more information about JSTOR, please contact support@jstor.org.
 .
Cambridge University Press and The Society for Healthcare Epidemiology of America are collaborating with
JSTOR to digitize, preserve and extend access to Infection Control and Hospital Epidemiology.
http://www.jstor.org 
This content downloaded from 23.235.32.0 on Wed, 21 Oct 2015 22:58:10 PM
All use subject to JSTOR Terms and Conditions
642 INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY September 2003
More Evidence of the Benefits of Rational
Antimicrobial Use in Clinical Practice
David L. Paterson, MBBS, FRACP; Joseph G. McCormack, MBBCh, FRCP, MD, FRACP
Many of us work in overcrowded hospitals with over-
worked nursing staff and overstressed physicians. It is easy
to dream about moving to a brand-new hospital with won-
derfully clean wards and wonderfully inspired staff (with
perfect hand hygiene). Surely then all of our infection con-
trol problems would be over forever, or would they?
Unless physicians within the hospital modified their
patterns of antibiotic use, it is doubtful that our problems
with antibiotic-resistant bacteria would be over. Selection of
antibiotic-resistant organisms would almost certainly
occur. The extent of the subsequent problem with antibiot-
ic resistance would be determined in part by the level of
misuse of antimicrobial agents. Antibiotic management or,
as it is sometimes termed, antibiotic stewardship clearly
has an integral role in infection control. It has long been
appreciated that the use of narrower spectrum, more tar-
geted antimicrobials for as short a time as possible is asso-
ciated with a lower likelihood of the development of resis-
tance. It can be difficult to promote the importance of this
message to prescribers. They often consider the immediate
interests of their patients as being of paramount impor-
tance and do not appreciate or observe the subsequent
resistance problems that may arise.
Four articles in this issue of Infection Control and
Hospital Epidemiology provide us with further data that will
help us to promote rational antimicrobial prescribing.1-4
The article by Lodise et al. examines risk factors for
bacteremia with methicillin-resistant versus methicillin-
susceptible Staphylococcus aureus (MRSA vs MSSA).3
Importantly, these authors take the local perspective in
their assessment of risk factors for MRSA. Undoubtedly,
they have read the numerous previous articles examining
risk factors for MRSA infection. However, they realize that
if they are going to reduce vancomycin use by promoting
empiric use of antistaphylococcal beta-lactam antibiotics
in preference to vancomycin in selected patients in their
hospital, they are going to need local data to have confi-
dence in their recommendations. Risk factors for methi-
cillin resistance in Detroit may be different from risk fac-
tors for methicillin resistance in Des Moines, Dublin, or
Darwin.
Their case–control study involved 494 patients with
S. aureus bacteremia during 2½ years. Almost half of the
infections (45.5%) were caused by MRSA. Onset of bac-
teremia while in the hospital, a history of hospitalization,
and the presence of decubitus ulcers were associated with
an increased likelihood of MRSA versus MSSA infection.
However, the most significant predictive factor, with an
odds ratio of 9.2, was prior antibiotic use. This study rein-
forces an association that has been established for many
other organisms. Importantly, it also allows those advising
antibiotic choice prior to susceptibilities becoming avail-
able to make recommendations with close to 90% certainty
as to the likelihood of an organism being MRSA or MSSA.
The next step is for these authors to show that with the use
of the information from this study, vancomycin use can be
decreased while maintaining favorable outcomes from
staphylococcal bacteremias.
The long-term use of intravenous glycopeptides is
sometimes clinically indicated and essential. There has
been much concern over the long-term use of vancomycin
leading to the development of colonization and infection
with vancomycin-intermediate S. aureus (VISA). The arti-
cle by Bernard et al. in this issue is encouraging in this
regard.2 For 34 patients with MRSA osteomyelitis, intra-
venous vancomycin was given in a standard dose (20
mg/kg/d) for a mean of 34 days or a high dose (40
mg/kg/d) for a mean of 37 days. Trough vancomycin lev-
els of 10 to 15 mg/L were targeted in the patients given the
standard dose and 20 to 25 mg/L in the patients given the
high dose. Swabs from wounds, the anterior nares, and the
groin were surveyed during therapy and 2 months after the
Dr. Paterson is from the Antibiotic Management Program, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Dr. McCormack is
from the Infectious Disease Department, University of Queensland and Mater Hospitals, Raymond Terrace, South Brisbane, Australia.
Address reprint requests to Dr. Paterson, Antibiotic Management Program, University of Pittsburgh Medical Center, Suite 3A, Falk Medical
Building, 3601 5th Avenue, Pittsburgh, PA 15213.
Editorial
This content downloaded from 23.235.32.0 on Wed, 21 Oct 2015 22:58:10 PM
All use subject to JSTOR Terms and Conditions
Vol. 24  No. 9 EDITORIAL 643
cessation of therapy. No VISA or heterogeneous VISA iso-
lates were detected.
There was also a significant and sustained reduction
in MRSA colonization at these sites; the sustained effect
was more apparent with the high dose than with the stan-
dard dose. Patients received intranasal mupirocin and
applications of 4% chlorhexidine soap during the first week
of vancomycin therapy. The suggestion that higher doses of
vancomycin contributed to a sustained reduction in MRSA
colonization is intriguing. A body of literature is also
emerging describing mutant prevention concentrations (ie,
it is possible that a concentration range of antibiotics exists
in which antibiotic-resistant mutants are selected most fre-
quently).5 Maintenance of antibiotic levels above this con-
centration may reduce the opportunity for selection of
antibiotic-resistant mutants. Clearly, much more needs to
be learned about the relationship between antibiotic dosing
and antibiotic concentrations and reduction in colonization
with resistant organisms and selection of antibiotic-resis-
tant mutants.
Donskey et al. have previously demonstrated that the
use of certain antibiotics may be linked to an increased den-
sity of vancomycin-resistant enterococci (VRE) in the gas-
trointestinal tract, and subsequently an increased risk of envi-
ronmental contamination with VRE.6 This study underscored
an important link between antibiotic use and the potential for
horizontal transmission of antibiotic-resistant organisms.
Bhalla et al. have now found that antianaerobic
antibiotic therapy promotes increased density of antibiotic-
resistant gram-negative bacilli in the gastrointestinal tract.1
In their 8-month prospective study of 140 stool samples
from 37 VRE-colonized patients published in this issue,
those who received drugs with antianaerobic activity had a
significantly higher incidence and density of stool coloniza-
tion with gram-negative bacilli resistant to ceftazidime,
ciprofloxacin, or piperacillin/tazobactam. Although their
study was restricted, for practical reasons, to patients with
VRE colonization, there is no obvious reason to think that
their results could not be extrapolated to those without
VRE colonization. The same group recently showed that
there was significant overuse of antibiotics with antianaer-
obic activity.7 Studies are now needed in which it is shown
that restriction of the use of antibiotics with antianaerobic
activity is associated with a reduction in colonization with
VRE and antibiotic-resistant gram-negative bacilli.
Finally, the article by Cordero and Ayers in this issue
describes a retrospective study of 790 consecutive extreme-
ly low birth weight infants in 30 academic centers.4 Ninety-
four percent of these infants had blood cultures performed
and empiric antibiotics prescribed for suspected early-
onset sepsis. The clinical outcome was the same when
those whose blood cultures were negative received short-
term (3 days or less) or long-term (7 days or more) antimi-
crobial therapy. The authors concluded that, at least in this
group of patients, discontinuation of empiric antimicrobials
at approximately 48 hours was feasible and safe. This situa-
tion is somewhat analogous to that observed in adult inten-
sive care practice whereby antimicrobial therapy is com-
menced for suspected ventilator-associated pneumonia. It
is clear that some of these patients will turn out to have had
pulmonary infiltrates due to pulmonary edema, pulmonary
hemorrhage, or a host of other noninfectious etiologies.
Singh et al. used a clinical scoring system that allowed safe,
early discontinuation of antibiotic therapy for patients in
whom infection was unlikely to be present.8 Antibiotic man-
agement programs are likely to be quickly discredited by
restricting the availability of antibiotics for the critically ill.
It behooves us to develop mechanisms, like those of Singh
et al., by which antibiotics are discontinued rapidly for crit-
ically ill patients shown not to have active infection.
The four studies mentioned above published in this
issue of Infection Control and Hospital Epidemiology assist
us in spreading some of the core messages of rational
antimicrobial prescribing. (1) Prior antimicrobial use is the
most significant factor in the development of resistance;
this applies particularly to broad-spectrum agents and to a
wide range of organisms. (2) The use of appropriately
dosed, narrow-spectrum, targeted antimicrobials is associ-
ated with a lower risk of development of resistance than is
the use of broad-spectrum agents and can also reduce col-
onization rates with resistant organisms. (3) Whereas the
initiation of empiric antimicrobial therapy is often indicated
when sepsis is suspected, such therapy can often be dis-
continued early without compromise to clinical outcome.
We need all the data we can get from studies such as
these to encourage and enforce the rational use of antimi-
crobial agents. Antibiotic management and measures for
preventing spread from patient to patient9 will almost cer-
tainly be needed to reduce the harm emanating from antibi-
otic resistance in the years ahead.
REFERENCES
1. Bhalla A, Pultz NJ, Ray AJ, Hoyen CK, Eckstein EC, Donskey CJ.
Antianaerobic antibiotic therapy promotes overgrowth of antibiotic-
resistant, gram-negative bacilli and vancomycin-resistant enterococci in
the stool of colonized patients. Infect Control Hosp Epidemiol
2003;24:644-649.
2. Bernard L, Vaudaux P, Vuagnat A, et al. Effect of vancomycin therapy for
osteomyelitis on colonization by methicillin-resistant Staphylococcus
aureus: lack of emergence of glycopeptide resistance. Infect Control
Hosp Epidemiol 2003;24:650-654.
3. Lodise TP Jr, McKinnon PS, Rybak M. Prediction model to identify
patients with Staphylococcus aureus bacteremia at risk for methicillin
resistance. Infect Control Hosp Epidemiol 2003;24:655-661.
4. Cordero L, Ayers LW. Duration of empiric antibiotics for suspected
early-onset sepsis in extremely low birth weight infants. Infect Control
Hosp Epidemiol 2003;24:662-666.
5. Drlica K. The mutant selection window and antimicrobial resistance. J
Antimicrob Chemother 2003;52:11-17.
6. Donskey CJ, Chowdhry TK, Hecker MT, et al. Effect of antibiotic thera-
py on the density of vancomycin-resistant enterococci in the stool of col-
onized patients. N Engl J Med 2000;343:1925-1932.
7. Hecker MT, Aron DC, Patel NP, Lehmann MK, Donskey CJ.
Unnecessary use of antimicrobials in hospitalized patients: current pat-
terns of misuse with an emphasis on the antianaerobic spectrum of
activity. Arch Intern Med 2003;163:972-978.
8. Singh N, Rogers P, Atwood CW, Wagener MM, Yu VL. Short-course
empiric antibiotic therapy for patients with pulmonary infiltrates in the
intensive care unit: a proposed solution for indiscriminate antibiotic pre-
scription. Am J Respir Crit Care Med 2000;162:505-511.
9. Muto CA, Jernigan JA, Ostrowksy BE, et al. SHEA guideline for pre-
venting nosocomial transmission of multidrug-resistant strains of
Staphylococcus aureus and Enterococcus. Infect Control Hosp Epidemiol
2003;24:362-386.
This content downloaded from 23.235.32.0 on Wed, 21 Oct 2015 22:58:10 PM
All use subject to JSTOR Terms and Conditions


More evidence of the benefits of rational antimicrobial use in clinical practice

Crossref

More Evidence of the Benefits of Rational Antimicrobial Use in Clinical Practice

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/2FEC2223395B26FC530C632DD0204DEA/S0195941700081984a.pdf/div-class-title-more-evidence-of-the-benefits-of-rational-antimicrobial-use-in-clinical-practice-div.pdf

More evidence of the benefits of rational antimicrobial use in clinical practice

Abstract

Similar works

Full text

Available Versions

University of Queensland eSpace

Crossref