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245
The search for the means to understand and control the emergence and spread of antimicrobial
resistance has become a public health priority. Project ICARE (Intensive Care Antimicrobial
Resistance Epidemiology)has establishedlaboratory-basedsurveillancefor antimicrobialresistance
and antimicrobialuse at a subset of hospitals participatingin the National Nosocomial Infection
Surveillancesystem. These data illustrate that for most antimicrobial-resistantorganisms studied,
rates of resistance were highest in the intensive care unit (ICU) areas and lowest in the outpatient
areas. A notable exception was ciprofloxacin-or ofloxacin-resistantPseudomonasaeruginosa,for
which resistance rates were highest in the outpatient areas. For most of the antimicrobialagents
associatedwith this resistance,the rate of use was highest in the ICU areas, in parallelto the pattern
seen for resistance.These comparativedata on use and resistanceamong similar areas (i.e., ICU or
other inpatient areas) can be used as a benchmarkby participatinghospitals to focus their efforts at
addressingantimicrobialresistance.
mit data from one or more ICUs to the ICU componentof the accuracyof each laboratory'smethods of susceptibility
NNIS. For ICARE,hospitalsreportedadditionalmicrobiology testing in identifyingorganismsas resistant.
and pharmacydata to CDC. These data were aggregatedfor The followingorganismswere collectedfor validitytesting:
each month and stratifiedby hospital area. Hospital areas methicillin-resistantS. aureus; vancomycin-resistantentero-
includedeach ICU separately(i.e., unitsthatprovideintensive cocci; ceftazidime-, cefotaxime-, or ceftriaxone-resistant
observation,diagnosis,andtherapeuticproceduresfor critically K.pneumoniae;ciprofloxacin- or ofloxacin-resistant
Enterobacte-
ill patients), non-ICU inpatientareas (i.e., areas where the riaceae;imipenem-resistant Enterobacteriaceae; ciprofloxacin-or
patientstays at least one nightin the hospitalexcludingICUs), ofloxacin-resistantP. aeruginosa; and imipenem-resistant
and outpatientareas(i.e., unitsthatperformsame-daysurgery, P. aeruginosa.Brothmicrodilution testingwas done
susceptibility
simple diagnosticprocedures,or therapy,such as chemother- for these isolatesaccordingto NCCLSmethodsby meansof in
apy, hemodialysis, cardiac catheterization,urgent care, or house-prepared plates[10].
emergencyunits). For the isolates tested for validation,each hospital-derived
Microbiologydata. Microbiologydataincludedantimicro- MIC or disk diffusion zone size was comparedwith results
bial susceptibilitytest resultsfor all nonduplicateclinical iso- frombrothmicrodilutiontestingby use of NCCLSbreakpoint
lates processedby the laboratoryduringeach study month.A interpretations.Organismsdefined as causing major errors
duplicateisolate was definedas an isolate of the same species were those categorizedby the hospitalas resistantandfoundto
of bacteriawith the same antimicrobialsusceptibilitypatternin be susceptibleby validitytesting. Organismsdefinedas caus-
the same patient,whateverthe site of isolation, duringeach ing minor errorswere classified as intermediateby validity
month. To accommodatedifferencesin susceptibilitytesting testing and as susceptibleor resistantby the hospitalor clas-
panels amonghospitals,reportingof resistancewas requested sified as intermediateby the hospital and as susceptibleor
for one or more of a groupof relatedantimicrobials. resistantby validitytesting.
Susceptible,intermediate, andresistantisolatesof selectedor- Pharmacydata. The pharmacydata included in-hospital
ganismswere stratifiedby locationin the hospitalwhere the use of selected oral and parenteralantimicrobialagents in
organismwas acquired(eachICU ward,inpatientnon-ICUunits grams.For purposeof analysis,gramsof antimicrobialswere
combined,and outpatientareas)for each month,for 12 sentinel convertedinto numberof defineddaily doses used each month
antimicrobial-resistant organisms.These included methicillin- in each hospital area. A defined daily dose is the typical
resistantcoagulase-negativestaphylococci;methicillin-resistant numberof gramsof an antimicrobialused per day for a typical
Staphylococcus aureus; vancomycin-resistant enterococci; adult(table 1) [13]. Antimicrobialuse was stratifiedby routeof
penicillin-resistant Streptococcus pneumoniae; ciprofloxacin- administrationand hospitalarea (i.e., each ICU and inpatient
or ofloxacin-resistant
Escherichiacoli; E. coli resistantto cefta- non-ICU areas combined).Because outpatientantimicrobial
zidime,cefotaxime,or ceftriaxone;
Klebsiellapneumoniaeresis- use could not be estimatedreliably from hospital pharmacy
tant to these third-generationcephalosporins;Enterobacter records,we did not collect dataaboutoutpatientantimicrobial
species resistant to these third-generationcephalosporins; use. Finally,antimicrobialswith similarspectrumsor clinical
piperacillin-resistant Pseudomonas aeruginosa; ceftazidime- indicationswere grouped(table 1).
resistantP. aeruginosa; ciprofloxacin-or ofloxacin-resistant Statisticalanalyses. Theresistancerateof eachantimicrobial-
P. aeruginosa; and imipenem-resistantP. aeruginosa. All isolates resistantorganismwas evaluatedin two ways. First,to provide
fittingthe selectedorganism-antimicrobialcombinations, whether feedbackof datato the individualhospitals,the individualresis-
for or
responsible hospital- community-acquired infectionor for tance rateswere calculatedat each institution,by hospitalarea
colonization,were reportedto ProjectICAREby participating (i.e., individuallyfor each ICU,combinedfor all non-ICUinpa-
hospitals.Hospitalsused interpretivestandardsfromthe National tient areasand for all outpatientareas).Data from each of the
Committeefor ClinicalLaboratory Standards(NCCLS)for MIC hospitalsareas were pooled over the entire study period. To
or zone diametertestingstandards to reportnumbersof suscepti- calculatea single rate for each hospitalarea, we dividedthe
ble, intermediate,or resistantorganisms[10-12]. numberof resistantisolatesby the total numberof isolatesfor
Microbiology isolates. Each ICARE hospital's microbiol- whichsusceptibility testinghadbeendone.Resistancerateswere
ogy laboratorycollectedup to 20 nonduplicateclinicalisolates calculatedfor a particular hospitalareaonly if > 10 isolateswere
of select organismsfor validationtestingat the ProjectICARE testedfor susceptibility. Second,to compareratesbetweenhospi-
laboratoryat CDC. Only isolates having MICs or zone sizes tal areas(i.e., all ICUs combined,non-ICUinpatientareas,out-
classifiedas intermediateor resistantto a specificantimicrobial patientareas),a pooledmeanresistancerateforeachcombination
agentwere sent for validation.Eachorganismsentwas accom- of antimicrobial-resistant organismswas calculatedby poolingthe
paniedby a completedreportformand antibiogramindicating data from all ICAREhospitals.This rate was the sum of all
susceptibilitytest methodand hospital-derivedresistancepat- resistantorganisms,dividedby the sumof all organismstestedfor
tern. The resultsof this validationtestingprovideda sense of susceptibility,by hospitalarea,amongall ICAREhospitals.
CID 1999;29 (August) AntimicrobialUse and Resistance 247
Table 1. Class, grouping, and defined daily dose of antimicrobial agents-Project ICARE, phase 2.
To controlfor the populationat riskfor receivingthesedrugs, bials studiedis less well definedin the pediatricpopulationand
we expresseduse as a usagedensityrate:numberof defineddaily commonlydependson weightor age.
doses per 1,000 patient-days.Use of antimicrobial agentswas Comparisons of proportions(i.e., pooledmeanresistancerates
determined at eachhospital,by hospitalarea.Thepoolednumber of all ICAREhospitals)betweenhospitalareasweredoneby use
of gramsof each antimicrobial agentused,by hospitalarea,was of the X2test. Comparisons of the medianratesof antimicrobial
dividedby the numberof gramsper defineddaily dose for the usebetweenhospitalareas(i.e.,ICUsvs. non-ICUinpatientareas)
specificantimicrobialagent,thendividedby thepoolednumberof were doneby use of the Wilcoxonranksumtest.
patient-daysin the correspondinghospitalarea,andmultipliedby
Results
1,000 to derive the numberof defineddaily doses per 1,000
patient-days.PediatricICUs were excludedfromthe analysisof Participating hospitals. Phase 2 hospitals were located in
antimicrobialuse, sincethe defineddailydose of mostantimicro- 18 statesandthe Districtof Columbia:15 (37%)of these were
248 Fridkinet al. CID 1999;29 (August)
Table 3. Resistance to specific antimicrobials in isolates from different hospital areas, phase 2 of Project ICARE, January 1996 to December
1997.
Inpatientareas
Antimicrobial-resistant
organism ICUs Non-ICUinpatient P value* Outpatientareas P valuet
Methicillin-resistant
coagulase-negativestaphylococci 3,307/4,411 (75.0) 7,240/11,988(60.4) <.01 3,611/8,120(44.5) <.01
[n = 82] [n = 39] [n = 35]
Staphylococcusaureus
Methicillin-resistant 1,673/4,750(35.2) 1,597/5,097(31.9) <.01 2,231/12,580 (17.7) <.01
[n = 90] [n = 40] [n = 36]
enterococci
Vancomycin-resistant 403/3,097 (13.0) 1,763/14,917(11.8) .06 206/8,285 (2.5) <.01
[n = 75] [n = 39] [n = 35]
Pseudomonasaeruginosa
Piperacillin-resistant 381/3,117 (12.2) 695/8,423 (8.3) <.01 300/5,028 (6.0) <.01
[n = 70] [n = 37] [n = 33]
P. aeruginosa
Ceftazidime-resistant 369/3,601 (10.2) 751/10,461(7.2) <.01 293/5,784 (5.1) <.01
[n = 78] [n = 39] [n = 36]
Third-generation Enterobacter
cephalosporin-resistant 491/1,966 (25.0) 971/4,351 (22.3) .02 228/2,265 (10.1) <.01
species [n = 61] [n = 40] [n = 34]
Third-generation Klebsiella
cephalosporin-resistant 69/1,887 (3.7) 262/7,030 (3.7) .98 76/5,434 (1.4) <.01
pneumoniae [n = 62] [n = 39] [n = 35]
Third-generationcephalosporin-resistant 27/3,012 (0.9) 148/19,188(0.8) .59 67/32,618 (0.2) <.01
Escherichiacoli [n = 80] [n = 39] [n = 36]
E. coli
Ofloxacin-or ciprofloxacin-resistant 37/2,794 (1.3) 249/17,836 (1.4) .63 185/28,314(0.7) <.01
[n = 77] [n = 39] [n = 35]
P. aeruginosa
Ofloxacin-or ciprofloxacin-resistant 593/3,622 (16.4) 1,817/10,312(17.6) .10 1,177/5,871(20.0) <.01
[n = 80] [n = 40] [n = 36]
Penicillin-resistant
Streptococcuspneumoniae 27/284 (9.5) 190/1,830(10.4) .65 179/1,818(9.8) .28
[n = 17] [n = 40] [n = 31]
NOTE. ICU = intensivecare unit. Data are no. of resistantisolates/totalno. of isolates tested (%) [no. of hospitalunits reportingresultsfor > 10 isolates].
* Comparisonof ICU patientareasvs. non-ICUinpatientareascombined,X2.
t Comparisonof inpatientareasvs. outpatientareas,X2.
However, there was no significant difference in use between 140- GroupI Group2 Group3
ICU and non-ICU areas for the antistaphylococcal penicillins 120- ICU> non-ICU ICU= non-ICU ICU <non-ICU
(i.e., methicillin group), first-generation cephalosporins,
second-generation cephalosporins, or aztreonam (figure 3). In WIO 100
80l
. 60
20- n
141 I I 60 A
12-
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