Relationship Between Rates of Antimicrobial Consumption and the Incidence of Antimicrobial

Resistance in Staphylococcus aureus and Pseudomonas aeruginosa Isolates From 47 French

Hospitals
Author(s): A.M.Rogues , MD, PhD; C.Dumartin , DPharm; B.Amado; A.G.Venier , MD;
N.Marty , MD, PhD; P.Parneix , MD; J.P.Gachie , MD, MPH
Source: Infection Control and Hospital Epidemiology, Vol. 28, No. 12 (December 2007), pp.
1389-1395
Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiology
of America
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infection control and hospital epidemiology december 2007, vol. 28, no. 12
or i g i na l a rt i c l e
Relationship Between Rates of Antimicrobial Consumption and
the Incidence of Antimicrobial Resistance in Staphylococcus aureus
and Pseudomonas aeruginosa Isolates From 47 French Hospitals
A. M. Rogues, MD, PhD; C. Dumartin, DPharm; B. Amadeo; A. G. Venier, MD;
N. Marty, MD, PhD; P. Parneix, MD; J. P. Gachie, MD, MPH
objective. To investigate relationships between rates of antimicrobial consumption and the incidence of antimicrobial resistance in
Staphylococcus aureus and Pseudomonas aeruginosa isolates from hospitals.
methods. We conducted an observational study that used retrospective data from 2002 and linear regression to model relationships.
Hospitals were asked to collect data on consecutive S. aureus and P. aeruginosa isolates, consumption rates for antibiotics (ie, anti-infectives
for systemic use as dened by Anatomical Therapeutic Chemical class J01), and hospital characteristics, including infection control policies.
Rates of methicillin resistance in S. aureus and rates of ceftazidime and ciprooxacin resistance in P. aeruginosa were expressed as the
percentage of isolates that were nonsusceptible (ie, either resistant or intermediately susceptible) and as the incidence of nonsuceptible
isolates (ie, the number of nonsuceptible isolates recovered per 1,000 patient-days). The rate of antimicrobial consumption was expressed
as the number of dened daily doses per 1,000 patient-days.
setting. Data were obtained from 47 French hospitals, and a total of 12,188 S. aureus isolates and 6,370 P. aeruginosa isolates were
tested.
results. In the multivariate analysis, fewer antimicrobials showed a signicant association between the consumption rate and the
percentage of isolates that were resistant than an association between the consumption rate and the incidence of resistance. The overall
rate of antibiotic consumption, not including the antibiotics used to treat methicillin-resistant S. aureus infection, explained 13% of the
variance between hospitals in the incidence of methicillin resistance among S. aureus isolates. The incidence of methicillin resistance in S.
aureus isolates increased with the use of ciprooxacin and levooxacin and with the percentage of the hospitals beds located in intensive
care units (adjusted multivariate coefcient of determination [aR
2
], 0.30). For P. aeruginosa, the incidence of ceftazidime resistance was
greater in hospitals with higher consumption rates for ceftazidime, levooxacin, and gentamicin (aR
2
, 0.37). The incidence of ciprooxacin
resistance increased with the use of uoroquinolones and with the percentage of a hospitals beds located in intensive care ( aR
2
, 0.28).
conclusions. A statistically signicant relationship existed between the rate of uoroquinolone use and the rate of antimicrobial
resistance among S. aureus and P. aeruginosa isolates. The incidence of resistant isolates showed a stronger association with the rate of
antimicrobial use than did the percentage of isolates with resistance.
Infect Control Hosp Epidemiol 2007; 28:1389-1395
From the Unite INSERM 657Pharmacoepidemiologie et evaluation de limpact des produits de sante sur les populations, IFR Sante Publique Universite
Victor Segalen (A.-M.R., J.P.G.), the Centre de Coordination de la Lutte contre les Infections Nosocomiales du Sud-Ouest, CHU Groupe hospitalier Pellegrin
(C.D., B.A., A.G.V., P.P.), the Service dHygie`ne Hospitalie`re, CHU Groupe hospitalier Pellegrin, Bordeaux (A.M.R., J.P.G.), the Service de Microbiologie,
Ho pital Purpan, Toulouse (N.M.), France.
Received April 17, 2007; accepted August 3, 2007; electronically published November 1, 2007.
2007 by The Society for Healthcare Epidemiology of America. All rights reserved. 0899-823X/2007/2812-0013$15.00. DOI: 10.1086/523280
The increasing prevalence of antimicrobial-resistant organ-
isms is a major public health problem and is of particular
concern for hospitals.
1
Two problematic nosocomial patho-
gens are Staphylococcus aureus and Pseudomonas aeruginosa;
both express multidrug resistance. Different pathways and
associated factors are involved in the emergence and spread
of antimicrobial resistance in these 2 bacteria. Rates of an-
timicrobial resistance and of isolation of resistant bacteria in
hospitals are affected by various factors, including infection
control practices, usage patterns for antibiotics, local epide-
miology, and the medical and surgical procedures performed
at the hospital. Because colonization or infection with an
antimicrobial-resistant microorganism in a hospital is there-
fore the result of several factors, infection control requires a
multifaceted approach.
2
The relative roles played by cross-transmission and anti-
microbial selection pressure in the levels of bacterial resis-
tance observed in hospital settings are still to be determined.
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1390 infection control and hospital epidemiology december 2007, vol. 28, no. 12
The use of antibiotic therapy to treat individuals has an eco-
logical impact on all the patients hospitalized in the same
facility.
3,4
In most hospitals, only aggregated microbiologic
and pharmacy data are available to researchers studying this
relationship. If such aggregated data are available for many
hospitals for a dened period (eg, a single year), the corre-
lation of rates of consumption and incidences of resistance
could prove helpful for comparative purposes. Only a few
studies have taken such a collective approach.
5
The purpose of this study was to analyze and correlate
multicenter surveillance data on the incidence of antimicro-
bial resistance among S. aureus and P. aeruginosa isolates and
the rate of antibiotic consumption in hospitals. A better
knowledge of these relationships could help prioritize inter-
ventions for controlling antimicrobial resistance in the hos-
pital setting.
methods
Data Collection
An observational study design was adopted, which used a
questionnaire mailed to 96 public hospitals and 123 private
hospitals belonging to the South-West Regional Coordinating
Center for Nosocomial Infection Control. The hospitals par-
ticipated in this study voluntarily and were required to have
participated in the regional laboratory network for bacterial
resistance. Thus, the laboratories of the hospitals that par-
ticipated performed microbiological testing and interpreted
results in accordance with the same guidelines, those of the
French Society of Microbiology. Hospitals were asked to re-
port aggregated annual data for 2002. Data were collected
retrospectively from administrative, pharmacy, and labora-
tory computerized databases. If a hospital tested fewer than
10 S. aureus or P. aeruginosa isolates for susceptibility during
the year, then the hospital was excluded from the study.
Hospital Characteristics
For each hospital, administrative data were recorded: the type
and number of beds, number of patient-days (ie, periods of
more than 24 hours), and the number of admissions. This
data was collected for the whole hospital and for each hospital
ward (ie, areas where a patient stayed at least 1 night in the
hospital). The different hospital inpatient wards were classed
in groups according to the French administrative denition:
medical, surgery, intensive care, obstetric, rehabilitation,
long-term care, and psychiatry. The mean length of stay was
obtained by dividing the number of patient-days by the num-
ber of admissions. The day of admission and the day of
discharge were counted together as 1 patient-day.
In addition, the questionnaire collected information about
infection control measures implemented in the hospital.
These included the hospitals organization, use of infection
control teams, guidelines for barrier precautions, and policies
for controlling the spread of bacterial resistance, as well as
the hospitals consumption rates for disposable gowns, as well
as scrub and alcohol-based hand rub for hand disinfection.
Measurement of Antibiotic Consumption
Hospital pharmacies were requested to report the annual rate
of consumption of antibiotics for systemic use (ie, antibiotics
delivered to the various wards of the hospital for this pur-
pose), as dened by group J01 of the Anatomical Therapeutic
Chemical classication system. The use of antibiotics was
expressed in dened daily doses (DDDs) per 1,000 patient-
days for the whole hospital. The Anatomical Therapeutic
ChemicalDDD classication from the World Health Orga-
nization, 2005 version, was used.
6
The antibiotics that were
considered to be used to treat infection with methicillin-
resistant S. aureus (MRSA) were glycopeptides, fosfomycin,
rifampicin, fusidic acid, trimethoprim-sulfamethoxazole, and
synergistin.
Rates of Bacterial Resistance
Each hospital was asked to collect data on consecutive S.
aureus and P. aeruginosa isolates during the entire year of
2002. Microbiological data was pooled for each hospital. Data
included information on the number of isolates that were
resistant and the number of isolates from clinical specimens
tested for susceptibility. The total number of resistant isolates
was obtained by summing the numbers of intermediately
susceptible and resistant isolates. We focused on MRSA and
on P. aeruginosa with resistance to ceftazidime or ciproox-
acin. The rate of antimicrobial resistance was expressed in 2
ways: the proportion (ie, percentage) of isolates that were
nonsuceptible (ie, resistant or intermediately susceptible) and
the number of nonsuceptible isolates per 1,000 patient-days
(ie, incidence). Duplicate isolates were excluded; these were
dened as isolates of the same organism with the same an-
timicrobial resistance pattern that were recovered from the
same patient during the study period, regardless of the site
from which they were isolated (eg, blood, sputum, urine, or
wound).
Statistical Analysis
The outcome variables were the percentage of isolates with
resistance and the incidence of resistance for S. aureus and
P. aeruginosa. The associations between different hospital
variables and resistance rates were tested in univariate anal-
ysis with the Spearman correlation test (r) and Kruskal-Wallis
test. A multiple linear regression analysis was performed
with a backward stepwise approach to identify factors asso-
ciated with rates of resistance, after checking for hospital
characteristics and infection control policies. Because the dis-
tribution was nonnormal, the incidence of antimicrobial re-
sistance in P. aeruginosa isolates was logarithmically or square-
root transformed. Structure parameters, such as hospital type,
number of beds in the hospital, and hospital areas, were
included in the multivariate analysis as potential confounders.
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rates of antibiotic use and incidence of resistance in french hospitals 1391
table 1. Consumption Rates for the Main Classes of Antibacterials for Systemic Use in French Hospitals
Class
Dened daily doses per 1,000 patient days, median (range)
P
a
All hospitals
(N p 47)
Public hospitals
(n p 31)
Private hospitals
(n p 16)
Penicillins
Any 277.4 (12.3-513.5) 246.5 (12.2-509.6) 311.6 (152-513) .05
Combination of penicillins, including
b-lactamase inhibitors 198.9 (8.1-424.6) 177.1 (8.1-420.5) 240.8 (117.5-424.6) .005
Cephalosporins
Any 37.4 (7.8-157.6) 29.2 (7.9-88.5) 47.7 (15.9-157.6) .001
First- and second-generation cephalosporins 5.5 (0-104) 4.9 (0-17.6) 27.8 (0.3-104) .001
Ceftazidime 1.8 (0-19) 2.1 (0-16) 1.1 (0-19) .37
Fluoroquinolones
Any 59.8 (8.5-455) 59.3 (8.5-129.9) 76.8 (35.3-455) .10
Ciprooxacin 16.4 (0-163) 15.4 (0-54) 16.6 (0-163) .63
Macrolides 26.0 (0-87.5) 27.4 (1.8-76.8) 23.8 (0-87.5) .71
Aminoglycosides 11.9 (1.6-77.2) 10.9 (1.6-67.9) 16.0 (3.3-77.1) .11
Imidazoles 10.7 (0-95.9) 9.4 (0-26.7) 16.2 (3-95.7) .01
Combination of sulfonamides and trimethoprim 6.1 (0-22.6) 6.4 (0-22.6) 5.4 (0-20.3) .55
Glycopeptides 4.1 (0-27.2) 4.1 (0-27.2) 4.3 (0.4-18.4) .50
a
Wilcoxon test.
We retained those variables that seemed to be statistically
associated with rates of resistance on the basis of a threshold
P value of .20. The backward stepwise selection was used with
a P value of .05 as the signicance level for removing variables
from the model. The nal model included all covariates that
were statistically signicant. Data analysis was performed us-
ing Stata software, version 7.0 (Stata).
results
Participating Hospitals
Data were obtained from 47 hospitals that volunteered to
participate. These hospitals had a combined total of 15,953
beds and a total of 4,719,281 patient-days; 18 of the hospitals
had more than 300 beds. These hospitals had a median ca-
pacity of 150 beds (range, 43-1,418 beds). The total number
of beds included 4,575 medical service beds in 44 hospitals,
3,708 surgical beds in 41 hospitals, 472 intensive care beds
in 35 hospitals, 970 obstetrics beds in 29 hospitals, 862 psy-
chiatric beds in 14 hospitals, 1,765 rehabilitation beds in 29
hospitals, and 2,979 long-term care beds in 26 hospitals. The
hospitals were classied according to the French administra-
tive denition; 31 hospitals (including 3 teaching hospitals)
were classied as public hospitals, and 16 were classied as
private hospitals.
All of these hospitals had an infection control committee,
but 6 of them had no infection control team, and only 18
(38%) of them had an infection control practitioner. Policies
for controlling the spread of bacterial resistance in the hospital
by use of contact precautions had been implemented for more
than 2 years by a majority of the hospitals (39 [84%]). The
overall antibiotic consumption rates for the hospitals varied
between 113 and 1,004 DDDs per 1,000 patient-days; the
median was 468 DDDs per 1,000 patient-days. The con-
sumption rates for the main antibiotic classes are presented
in Table 1.
Bacterial Resistance
A total of 12,188 S. aureus isolates and 6,370 P. aeruginosa
isolates were tested in the participating hospitals. The median
percentage of S. aureus isolates that were MRSA at each hos-
pital was 41%, and the incidence of resistance was 0.87 isolates
per 1,000 patient-days. The median percentage of P. aerugi-
nosa isolates that were resistant to ceftazidime at each hospital
was 17%, and the incidence of ceftazidime resistance was 0.2
isolates per 1,000 patient-days; the mean percentage of P.
aeruginosa isolates resistant to ciprooxacin at each hospital
was 34%, and the incidence of ciprooxacin resistance was
0.43 isolates per 1,000 patient-days. The incidence of resis-
tance was higher in public hospitals than in private hospitals
(Table 2).
The percentage of S. aureus isolates that were MRSA was
signicantly positively correlated with the percentage of cip-
rooxacin resistance in P. aeruginosa isolates (r, 0.34; P p
). The incidence of methicillin resistance in S. aureus was .01
signicantly positively correlated with the incidences of cip-
rooxacin resistance (r, 0.70; ) and ceftazidime re- P p.001
sistance (r, 0.51; ) in P. aeruginosa isolates. P p.001
There were statistically signicant relationships between
rates of antimicrobial resistance in S. aureus or P. aeruginosa
isolates and certain hospital characteristics. The percentage
of S. aureus isolates that were MRSA increased with the length
of hospital stay (r, 0.38; ) and with the percentage P p.008
of the hospitals beds located in the rehabilitation service (r,
0.48; ). The incidence of MRSA increased with the P p.001
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1392 infection control and hospital epidemiology december 2007, vol. 28, no. 12
table 2. Antimicrobial Resistance in Staphylococcus aureus and Pseudomonas aeruginosa Isolates in French
Hospitals
Bacteria, variable
Median value (range)
P
All hospitals
(N p 47)
Public hospitals
(n p 31)
Private hospitals
(n p 16)
S. aureus
No. of isolates tested for susceptibility 151 (14-2043) 226 (63-2043) 62 (14-342)
Percentage of isolates resistant to methicillin 41 (5-86) 44 (5-66) 35 (13-86) .08
No. of methicillin-resistant isolates recovered
per 1,000 patient-days 0.87 (0.11-2.04) 1.02 (0.16-2.04) 0.58 (0.11-1.62) .01
P. aeruginosa
No. of isolates tested for susceptibility 80 (11-1249) 106 (13-249) 40 (11-187)
Percentage of isolates resistant to ceftazidime 17 (5-57) 15 (5-50) 19 (5-57) .30
No. of ceftazidime-resistant isolates recovered
per 1,000 patient-days 0.18 (0.02-1.71) 0.18 (0.02-0.87) 0.21 (0.03-1.71) .77
Percentage of isolates resistant to ciprooxacin 34 (5-62) 37 (14-62) 31 (5-57) .11
No. of ciprooxacin-resistant isolates recovered
per 1,000 patient-days 0.43 (0.02-1.72) 0.44 (0.12-1.72) 0.41 (0.03-1.71) .38
percentage of a hospitals beds located in the rehabilitation
service (r, 0.28; ) and with the percentage of beds P p.05
located in intensive care units (r, 0.38; ). A greater P p.004
number of beds in intensive care units was associated with
higher incidences of P. aeruginosa isolates resistant to cefta-
zidime (r, 0.48; ) and to ciprooxacin (r, 0.40; P p.006
). P p.004
The hospitals with an infection control practitioner had a
lower percentage of S. aureus isolates that were MRSA, com-
pared with hospitals without an infection control practitioner
(35.5% vs 44.6% of isolates; ). The incidence of P p.001
MRSA was higher in hospitals that had implemented policies
to control the spread of bacterial resistance within the hospital
(median [range], 1.02 [0.1-2] vs 0.72 [0.2-2] resistant isolates
per 1,000 patient days; ). Similarly, the incidence of P p.04
ciprooxacin resistance in P. aeruginosa was higher in hos-
pitals that had implemented these policies (median [range],
0.5 [0.1-1.7] vs 0.32 [0.1-0.9] resistant isolates per 1,000 pa-
tient days; ). P p.02
Rate of Antibiotic Consumption and MRSA
The overall rate of antibiotic consumption, not including the
antibiotics used to treat MRSA infection, explained 13% of
the variation in the incidence of methicillin resistance in S.
aureus isolates in the hospitals (coefcient, 0.001 [95% con-
dence interval, 0.0001-0.0023]; adjusted multivariate coef-
cient of determination [aR
2
], 0.13). The percentage of S.
aureus isolates that were MRSA was positively correlated with
ciprooxacin consumption, but not with the consumption of
other antibiotics (r, 0.31; ), whereas the incidence of P p.03
MRSA correlated with the consumption of ciprooxacin ( r,
0.37; ), levooxacin (r, 0.33; ), ceftazidime P p.008 P p.02
(r, 0.36; ), and carbapenem ( r, 0.32; ). In P p.01 P p.02
the multivariate analysis, after adjustment for hospital char-
acteristics and infection control variables, the percentage of
S. aureus isolates that were MRSA increased with the use of
ciprooxacin and with the percentage of a hospitals beds
located in the rehabilitation service (aR
2
, 0.39). The incidence
of MRSA in the hospital increased with the use of ciproox-
acin and levooxacin and with the percentage of a hospitals
beds that were in intensive care units (aR
2
, 0.30).
Rate of Antibiotic Consumption and Antimicrobial-
Resistant P. aeruginosa
In the multivariate analysis, the percentage of P. aeruginosa
isolates that were antimicrobial resistant was more likely to
be signicantly associated with the incidence of resistance,
compared with the rate of antibiotic consumption. between
the rate consumption and the percentage of isolates that were
resistant than an association between the consumption rate
and the incidence of resistance. The incidence of ceftazidime-
resistant P. aeruginosa was associated with the consumption
of ceftazidime (r, 0.31; ), ciprooxacin (r, 0.35; P p.02
), levooxacin (r, 0.43; ), macrolides (r, 0.40; P p.01 P p.01
), gentamicin (r, 0.32; ), and/or rst- or P p.004 P p.02
second-generation cephalosporins (r, 0.28; ). The in- P p.05
cidence of ciprooxacin-resistant P. aeruginosa was correlated
with the consumption of uoroquinolones (r, 0.44; P p
) and ceftazidime (r, 0.44; ). Multiple linear .001 P p.001
regression analysis yielded a nal model that included the use
of ceftazidime, levooxacin, and gentamicin; rates of con-
sumption of these antimicrobials were all independently and
positively associated with the incidence of ceftazidime resis-
tance in P. aeruginosa. The nal model explained 37% of the
variance of the dependent variable (aR
2
, 0.37). The incidence
of ciprooxacin resistance in P. aeruginosa increased with the
use of uoroquinolones and the percentage of a hospitals
beds located in intensive care (aR
2
, 0.28).
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rates of antibiotic use and incidence of resistance in french hospitals 1393
di scussi on
This study was based on an ecological design, and it attempted
to correlate multicenter surveillance data on antibiotic use
with rates of antimicrobial resistance in S. aureus and P. aeru-
ginosa isolates, with the aim of interhospital comparison.
There were differences in the incidence of antimicrobial re-
sistance in the 47 hospitals. Rates of resistance were inuenced
by the distribution of the various hospital wards within the
hospital, and the rate of methicillin-resistance among S. au-
reus isolates was strongly associated with hospital type (ie,
public or private). We showed that hospitals with a high
incidence of methicillin resistance in S. aureus isolates also
had a high prevalence or incidence of antimicrobial-resistant
P. aeruginosa. This suggests that factors affecting the rates of
methicillin resistance among the S. aureus isolates in a given
hospital might also inuence antimicrobial resistance rates
for P. aeruginosa. A signicant relationship existed between
the rate of uoroquinolone use and the rates of antimicrobial
resistance in S. aureus and P. aeruginosa isolates. That rela-
tionship persisted when hospital characteristics, infection
control measures, and exposure to other antimicrobial agents
were taken into account. The incidence of resistant isolates
showed a stronger association with the rate of antimicrobial
consumption than did the percentage of isolates with resis-
tance; incidence seemed to be a more relevant indicator than
percentage for the study of these ecological relationships.
There are some potential limitations to our method that
should be considered. First, a study based on aggregated data
that uses group-level analytic methods alone does not estab-
lish a causal relationship between antibiotic exposure and
antimicrobial resistance. The analysis of aggregated data may
be limited by ecological bias, which is the failure of group-
leveleffect estimates to reect the biological effect at the level
of the individual or patient.
7
Second, in this cross-sectional
study, data were collected for only 1 year, and therefore do
not reect longer-term trends in antimicrobial use or resis-
tance. The temporal relationship between antibiotic exposure
and resistance may vary according to the time periods ex-
amined. However, some studies showed that selection for
resistant strains takes a few months in a hospital setting
less than 1 year.
8-11
Finally, in a multicenter study it is difcult
to collect information on all potential confounders, such as
the existence of an outbreak, patient case-mix, or collection
of clinical microbiology specimens, which were not stan-
dardized at our hospitals. Notwithstanding their pitfalls, eco-
logical studies play a potentially useful role in studies of in-
fectious agents because they allow for measurement of the
total effect of an exposure. This is important because the total
effect of antibiotic exposure encompasses not just the direct
effects on the individual who receives the antibiotic therapy
but also the indirect effects mediated by effects on trans-
missibility or on the likelihood of the transmission of sus-
ceptible organisms.
7
Our ndings were consistent with previous observations
that have found a relationship between antimicrobial use and
the prevalence of MRSA.
3,11-13
The rst multivariate analysis
conducted in 50 Belgian hospitals showed that the use of
ceftazidime and cefsulodin, broad-spectrum penicillins with
b-lactamase inhibitors, and/or quinolones was associated in-
dependently with a high incidence of MRSA in the hospital.
14
In 15 international hospitals, Westh et al.
15
found correlations
between the prevalence of MRSA and the therapeutic con-
sumption of b-lactam combinations, carbapenems, and, of
course, glycopeptides. They showed that hospitals with a high
prevalence of MRSA were those with low consumption of b-
lactamasesensitive antibiotics. Muller et al.
16
demonstrated
that the selective pressure caused by the use of antimicrobials
is an independent risk factor for MRSA acquisition. Fur-
thermore, when relationships between antimicrobial use and
MRSA prevalence were analyzed by time-series analysis, tem-
poral relationships were found between the monthly per-
centage of S. aureus isolates that were MRSA and previous
rates of use of macrolides, third-generation cephalosporins,
and/or uoroquinolones.
11
Several investigations offer evidence suggesting that con-
sumption of uoroquinolones may predispose patients to in-
fection or colonization with MRSA.
16-18
The excretion of high
concentrations of quinolones in the nares and skin might
eliminate normal skin ora and promote colonization by
MRSA strains that are quinolone-resistant.
19
In 2002, in
France, susceptibility to ciprooxacin was found in less than
10% of MRSA isolates.
20
Furthermore, exposure to subin-
hibitory concentrations of quinolones might lead to an in-
crease in the ability of MRSA to adhere to skin.
21,22
Recent
reports demonstrated that the restriction of ciprooxacin use
resulted in a reduced incidence of MRSA in the intensive care
unit, as well as in the hospital as a whole.
23,24
Two other comments could be made here. First, although
the spread of MRSA in the hospital setting is associated with
clonal dissemination, we did not nd a relationship between
rates of antimicrobial resistance and infection control prac-
tices developed in the hospital. This could not be explained
by importation of community-associated strains of MRSA
into our hospitals, because in France, although MRSA is pre-
sent in the community and in nursing homes, most MRSA
infections are still acquired in the hospital. Our ndings pro-
vide evidence for the difculties of measuring infection con-
trol practices at the hospital level. Even if hand hygiene is
the best way of preventing the transmission of microorgan-
isms in hospital settings, it is difcult to demonstrate the
association between consumption rates of alcohol-based hand
rub and appropriate adherence to infection control measures
by the staff.
25
Although many factors are associated with
MRSA acquisition, programs aiming to control or improve
antimicrobial prescribing practices could be added to infec-
tion control measures if the latter used alone were not proven
fully effective in controlling MRSA. Society for Healthcare
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1394 infection control and hospital epidemiology december 2007, vol. 28, no. 12
Epidemiology of America guidelines discuss uoroquinolone
consumption as a risk factor for MRSA acquisition and sug-
gest that uoroquinolone use should be curtailed in areas
with a high incidence of MRSA.
26
Second, limitations in analyzing the relationship between
consumption and resistance in some projects could be due
to the unit choice for analyzing resistance (ie, prevalence vs
incidence).
27,28
Schwaber et al.
29
showed that, from the public
health perspective, rates are more appropriate than propor-
tions for measuring the burden of resistance.
Case-control studies have identied uoroquinolone use
as an individual risk factor for the acquisition of multidrug-
resistant P. aeruginosa. Hospital rates of uoroquinolone use
were predictive of the incidence of uoroquinolone-resistant
P. aeruginosa.
17,30
Higher hospital-level consumption rates for
ciprooxacin, levooxacin, and moxioxacin are each asso-
ciated with an increased proportion of hospital-acquired P.
aeruginosa isolates being nonsuceptible to ciprooxacin.
31,32
In another study, a decrease in ciprooxacin susceptibility
among P. aeruginosa isolates correlated signicantly with in-
creased use of levooxacin and antipseudomonal cephalo-
sporins. However, some results should be interpreted with
caution, because the use of certain antibiotics could be both
a cause and a consequence of the emergence of resistance;
for example, higher rates of consumption of ceftazidime and
aminoglycosides in hospitals with a higher incidence of u-
oroquinolone-resistant P. aeruginosa is likely to be a result of
the high prevalence of uoroquinolone-resistant organisms
and the use of alternative drugs to treat infection with these
organisms. Use of these non-uoroquinolone drugs may not
be a cause of the increasing prevalence of uoroquinolone-
resistant P. aeruginosa.
33
In Mohr et al.
33
, as in our study, there
was no statistical relationship between the overall rate of an-
tibiotic use and the emergence of antimicrobial resistance in
P. aeruginosa, suggesting that the development of resistance
is associated with the use of individual agents, rather than
with the overall rate of antibiotic consumption.
33
Despite the limitations of this kind of ecological study, our
results were consistent with recent observations. These results
support efforts to reduce prescriptions of selected antimicro-
bial drug classes, such as uoroquinolones, in the hospital
setting. We believe that the approach used to examine anti-
microbial use and resistance in our study could be helpful
in determining how to prioritize efforts and resources be-
tween policies to regulate antibiotic use and other interven-
tions, such as infection control practices, but these factors
are difcult to measure. Further study is required to deter-
mine the key parameters of infection control practices.
acknowledgments
We are grateful to the hospitals that participated in the survey.
Potential conicts of interest. All authors report no conicts of interest
relevant to this article.
Address reprint requests to Anne-Marie Rogues, MD, PhD, Unite INSERM
657, Universite Bordeaux 2, France (anne-marie.rogues@chu-bordeaux.fr).
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