A Case‐Control Study to Detect Modifiable Risk Factors for Colonization With Vancomycin‐Resistant Enterococci • Author(s): Mark Loeb , MD, MSc; Suzette Salama , PhD; Maxine Armstrong‐Evans , RN; GinaCapretta; Jan Olde , RN, CICSource: Infection Control and Hospital Epidemiology, Vol. 20, No. 11 (November 1999), pp.760-763Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiologyof AmericaStable URL: http://www.jstor.org/stable/10.1086/501580 .

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760 INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY November 1999

A Case-Control Study to DetectModifiable Risk Factors for ColonizationWith Vancomycin-Resistant Enterococci

Mark Loeb, MD, MSc; Suzette Salama, PhD; MaxineArmstrong-Evans, RN; Gina Capretta; Jan Olde, RN,CIC

ABSTRACTA case-control study was conducted to determine the modi-

fiable risk factors associated with vancomycin-resistantEnterococcus (VRE) colonization during a hospital outbreak.Cephalosporin use was identified as the only independent risk fac-tor (odds ratio, 13.8; 95% confidence interval, 2.5-76.3; P=.01).Nursing work-load intensity was not associated with VRE coloniza-tion in this study (Infect Control Hosp Epidemiol 1999;20:760-763).

Over the past decade, vancomycin-resistant entero-cocci (VRE) have emerged as important nosocomialpathogens.1,2 Risk factors for the acquisition of VRE includeprior exposure to antibiotics, prolonged hospitalization,proximity to a colonized patient, exposure to contaminatedmedical equipment, and severity of illness.2 Identifying

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Vol. 20 No. 11 CONCISE COMMUNICATIONS 761

modifiable risk factors may lead to interventions that helpreduce rates of VRE colonization, as has been demonstrat-ed by restricting the use of antibiotics.3

The impact of nursing work load on nosocomial acqui-sition of multiresistant organisms such as VRE has neverbeen evaluated systematically. In many hospitals, restruc-turing has led to reductions in nurse staffing levels, oftenleaving nurses with an increased work load. Concern fre-quently is raised about “cutting corners” and the effect thismay have on compliance with infection control precautions.Having an increased work load may compromise nurses’ability to maintain appropriate infection control practicesand may contribute to nosocomial transmission of multire-sistant organisms such as VRE. Staffing strategies thatdeploy more nurses may be needed to prevent transmis-sion of multiresistant bacteria. Few studies, however, haveexamined the role of nurse staffing in the transmission ofnosocomial pathogens.4-6

Following an outbreak of VRE at the Henderson hos-pital, we conducted a case-control study to determinewhether potentially modifiable risk factors such as antibiot-ic use and nursing work-load intensity were associated withVRE colonization.

METHODS

The Henderson site of the Hamilton Health SciencesCorporation is a 300-bed tertiary-care facility with two med-ical wards (A and B), one hematology ward, one oncologyward, two surgical wards, one rehabilitation ward, onemedical-surgical intensive care unit (ICU), and one cardiac-care unit. Routine surveillance for VRE included testingclinical isolates of enterococci for vancomycin resistance,screening contacts, and doing prevalence surveys. A clus-ter of eight nosocomial VRE cases in the first 2 weeks ofApril 1998 led to an outbreak investigation. The incidencedensity of nosocomial VRE colonization increased from 0per 1,000 patient-days in January 1998 to 1.34 cases per1,000 patient-days in April 1998. The outbreak period wasdefined as February 28 to April 30, 1998. Infection controlinterventions, which included placing all VRE-colonizedpatients in isolation, cohorting cases, using dedicatedequipment in isolation rooms, and enhanced environmentalcleaning, led to successful control of the outbreak, suchthat in May 1998 no further transmission of VRE wasdetected.

Case-Control StudyCase-patients were defined as individuals who

acquired VRE nosocomially during the outbreak period,detected from either clinical specimens or surveillance cul-tures, using either rectal swabs or stool specimens.Surveillance for VRE during the outbreak period was per-formed by screening all clinical enterococcal isolates forvancomycin resistance, obtaining rectal swabs on admis-sion from all individuals admitted to the hospital, perform-ing weekly point-prevalence surveys on all patient-careunits by obtaining rectal swabs, and screening contacts ofindividuals colonized with VRE.

To be categorized as having had nosocomial acquisi-tion, case-patients must have had at least one negative swab1 week preceding the positive specimen. Patients in whomVRE was detected within 48 hours of admission wereexcluded from the study.

Control-patients were randomly selected inpatientspresent on the wards or units where VRE was detected dur-ing the outbreak period who did not acquire VRE. To be eli-gible to be selected as a control, patients must have had atleast two negative rectal swabs taken at least 1 week apart.Three control-patients were selected for every case-patient.

Data collected from patient charts included patientdemographics, underlying illness, presence of neutropenia,antibiotic use, length of stay, exposure to a VRE-colonizedroommate, and presence of a bed-bound state. For case-patients, antibiotic use was determined for up to a maxi-mum of 12 weeks prior to detection of VRE. For control-patients, antibiotics used in the interval between the firstand last negative swabs were recorded, for up to a maxi-mum of 12 weeks.

Patient-specific work-load measurements wererecorded daily by nursing staff, using the GRASP system(GRASP Systems, Inc, Ft Collins, CO).7 With this system,standardized nursing-time requirements are assigned to acomprehensive list of nursing interventions. On a dailybasis, nurses retrospectively select the interventions theyhave performed during their shift and the nursing-carerequirements (GRASP score), expressed in hours, aredetermined. The nursing time that was actually allocatedfor the shifts is also summed. The ratio of the two timeindices (work-load/utilization time) is known as the utiliza-tion rate. Expressed as a percentage, the utilization rateprovides an estimate of the intensity of nursing work loadon the ward on a daily basis. For case-patients, the meannursing work-load intensity (utilization rate) on the entireward or unit in the 2 weeks preceding colonization withVRE was determined. For control-patients, a randomlyselected 2-week interval between the first and last negativeswabs was selected and the mean nursing work-load inten-sity determined.

Laboratory MethodsFor surveillance cultures, rectal swabs were inoculat-

ed onto bile esculin enterococcal agar supplemented with 6µg/mL vancomycin (PML Microbiologicals, Mississauga,Ontario, Canada). The plates were incubated at 35ºC andexamined at 24 and 48 hours for the presence of blackcolonies. Esculin-positive colonies were subcultured to col-istin and nalidixic acid agar (PML Microbiologicals).Speciation and susceptibility testing of enterococcal iso-lates growing on brain-heart infusion agar supplementedwith 6 µg/mL vancomycin (PML Microbiologicals) wereperformed with the Vitek 120 system (software version10.3; bioMérieux Canada Inc, St Laurent, Quebec, Canada).

Statistical Analysis Data entry and analysis were performed using SAS

(version 6.04; SAS Institute, Cary, NC). Univariate analysis

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762 INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY November 1999

of risk factors for VRE colonization was performed. A logis-tic regression model was built to identify risk factors.Variables with P<.2 in univariate analysis were entered ascandidate risk factors; the final model was selected using abackward stepwise algorithm. Variables with P<.05 wereretained in the final model. To minimize potential con-founding by location-specific factors, patient ward or unitwas forced into the logistic regression model.

RESULTS

Of the 20 case-patients identified during the outbreakperiod, 11 acquired VRE on the two medical wards (7 onward A and 4 on ward B), 4 on the hematology ward, and 5in the ICU. Controls were distributed as follows: 15 on wardA, 9 on ward B, 28 on hematology, and 8 in the ICU. Withthe exception of 2 patients in whom VRE was detected onthe seventh day of admission but who had no previousswabs taken, all inpatients in whom VRE was detected dur-ing the outbreak period were included in the analysis. Themean age of cases was 74 (range, 38-95) years; 10 (50%)were female (Table). All isolates were vancomycin-resistantEnterococcus faecium detected from surveillance cultures,either through rectal swab or stool cultures, performed aspart of weekly prevalence surveys or contact tracing.Twelve isolates had a vanA phenotype and eight a vanBphenotype.

Results of univariate and logistic regression analysesare shown in the Table. In univariate analysis, the prior

administration of cephalosporin antibiotics (odds ratio[OR], 6.48; 95% confidence interval [CI95], 1.59-37.25];P=.01) and of metronidazole (OR, 2.96; CI95, 1.03-8.23;P=.04) was highly associated with VRE colonization. Themean utilization rate (work-load rate) on units of case-patients in the 2 weeks prior to colonization was higherthan for controls (113.5% vs 106.3%), but the difference wasnot statistically significant (OR for a 10% increase in nurs-ing work-load intensity, 1.4; CI95, 0.96-2.03; P=.07).

The following candidate variables were entered in themultivariable model: age, congestive heart failure, dia-betes, having a roommate with VRE, nursing work-loadintensity, metronidazole use, cephalosporin use, and ward.Only cephalosporin use remained significant in the finalmodel (OR, 13.8; CI95, 2.5-76.3; P=.01).

DISCUSSION

Prior administration of antibiotics has been consis-tently recognized to be an important risk factor for theacquisition of VRE. Previous case-control studies haveimplicated vancomycin, third-generation cephalosporins,and prior exposure to antibiotics with activity againstanaerobes as risk factors.8-10 In contrast, few data are avail-able on the effect of nursing work-load intensity on VREcolonization.

Although third-generation cephalosporin use was notfound to be significant, use of all cephalosporins wasstrongly associated with VRE colonization and was in fact

TABLERISK FACTORS FOR COLONIZATION WITH VANCOMYCIN-RESISTANT ENTEROCOCCI IN UNIVARIATE ANALYSIS

Proportion (%) or Mean (SD) Univariate Logistic RegressionVariable Cases Controls P OR P*

Age, y 73.9 (15.6) 69.2 (12.2) .17 .59Male gender 10/20 (50%) 28/60 (46.4%) .80Bed bound 2/17 (12%) 4/53 (8%) .63Renal failure 5/20 (25%) 11/59 (19%) .53Congestive heart failure 7/17 (41%) 10/53 (19%) .10 .31Diabetes 8/20 (40%) 11/58 (19%) .07 .64Cancer 7/17 (41%) 31/55 (56%) .41Neutropenia 3/17 (18%) 9/60 (15%) 1.00Liver disease 2/17 (12%) 6/58 (10%) 1.00Roommate with VRE 6/20 (30%) 6/60 (10%) .06 .55Nursing work-load intensity (%) 113.5 (13.2) 106.3 (15.6) .07 .82Length of stay, d 29.2 (SD 48.8) 29.8 (SD 23.2) .93Prior antibiotic therapy

All cephalosporins 17/20 (85%) 28/60 (47%) .01 13.8 .01Third-generation cephalosporins 9/20 (45%) 22/60 (37%) .50Ciprofloxacin 10/20 (50%) 27/60 (45%) .69Clindamycin 4/20 (20%) 6/60 (10%) .26Metronidazole 9/20 (45%) 13/60 (22%) .04 .95Vancomycin (IV) 3/20 (15%) 11/60 (18%) 1.00Any antibiotic 18/20 (90%) 44/60 (73%) .21

Abbreviations: IV, intravenous; OR, odds ratio; SD, standard deviation; VRE, vancomycin-resistant enterococci.* Logistic regression P, P value at which variable was either withdrawn from or retained in the model.

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Vol. 20 No. 11 CONCISE COMMUNICATIONS 763

the only factor kept in the multivariable model. This high-lights the importance of cephalosporin use as a risk factorfor VRE colonization and is particularly relevant given thatreductions in cephalosporin use, along with vancomycinand clindamycin reduction, have been shown to lead todecreased rates of VRE colonization.3,8,9

Nursing work-load intensity was not found to be sig-nificantly associated with VRE colonization. To our knowl-edge, there are no previous studies that have examined theeffect of nursing work load on transmission of VRE.Relatively few studies have examined the effect of nursingwork load on nosocomial transmission. Haley et al foundincreased rates of clustered Staphylococcus aureus in aneonatal ICU as the infant-to-nurse ratio increased.4 Soulieret al reported that nursing work load was greater for surgi-cal ICU patients who became colonized with extended-spectrum �-lactamase–producing Enterobacteriaceae whencompared to controls.6 When a protracted outbreak of cen-tral venous catheter-associated bloodstream infections in asurgical ICU was investigated by Fridkin et al, the patient-to-nurse ratio was found to be an independent risk factor.5In contrast to these studies, the majority of our cases didnot occur in an intensive-care setting, an environmentwhere, it may be hypothesized, comparatively smallerincreases in nursing work-load intensity may result intransmission because of the greater proportion of high-riskactivities.

Several possible explanations exist for why nursingwork load was not found to be a significant risk factor. It ispossible that the GRASP systems were not sensitiveenough to detect changes in nursing work load that wouldaffect nursing infection control practices. It is conceivablethat the lack of a significant association between nursingwork-load intensity and VRE transmission was due to athreshold effect, such that a certain level of nursing work-load intensity needs to be reached before compliance withactivities such as hand washing decreases.11 Since meanutilization rates on the wards were assessed, the effect of athreshold may not have been detected. Compliance withaccurate recording of the nursing interventions is a poten-tial source of bias, particularly if low compliance occurredwhen nurses were very busy. However, this would onlyhave resulted in distortion had compliance been worse forcases than controls, causing spuriously lower utilizationrates for cases. It is important to note that, although the

point estimate of the odds ratio for nursing work-load inten-sity was not statistically significant (OR for a 10% increasein nursing work-load intensity, 1.4; CI95, 0.96-2.03), theupper level of the confidence limits did not exclude a clini-cally important effect. Therefore, more studies evaluatingthe effect of nursing work-load intensity on nosocomialtransmission of VRE are needed.

From the Departments of Laboratory Medicine (Dr. Loeb, Ms.Armstrong-Evans, Ms. Capretta, Ms. Olde) and Medicine (Dr. Salama),Hamilton Health Sciences Corporation and McMaster University,Hamilton, Ontario, Canada.

Address reprint requests to Mark Loeb, MD, Department ofLaboratory Medicine, Hamilton Health Sciences Corporation(Henderson site), 711 Concession St, Hamilton, Ontario L8V 1C3Canada.

This study was supported by a grant from the Hamilton HealthSciences Foundation.

99-CC-030. Loeb M, Salama S, Armstrong-Evans M, Capretta G,Olde J. A case-control study to detect modifiable risk factors for coloniza-tion with vancomycin-resistant enterococci. Infect Control HospEpidemiol 1999;20:760-763.

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