1 Department of Pathology and Molecular Medicine, McMaster University and Hamilton Regional Laboratory Program, Hamilton, Ontario, Canada.
2 Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
3 Department of Microbiology, Toronto Medical Laboratories and Mount Sinai Hospital and the University of Toronto, Toronto, Ontario, Canada.
4 Department of Microbiology, Sunnybrook and Womens College Health Sciences Centre and the University of Toronto, Toronto, Ontario, Canada.
5 Divisions of Geriatric Medicine and Infectious Diseases, Department of Internal Medicine, Veterans Affairs Health Systems, and the University of Michigan Medical School, Ann Arbor, MI.
Received for publication March 22, 2002; accepted for publication July 24, 2002.
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ABSTRACT |
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antibiotics; drug resistance, microbial; nursing homes
Abbreviations: Abbreviations: CI, confidence interval; MRSA, methicillin-resistant Staphylococcus aureus; OR, odds ratio; TMP-SMX, trimethoprim-sulfamethoxazole.
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INTRODUCTION |
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Antimicrobial-resistant bacteria can spread from person to person by handborne transmission. Therefore, knowing the effect of a long-term care facilitys infrastructure for hand hygiene, such as the availability of hand-washing sinks or the use of antibacterial soaps, may lead to interventions to help reduce the transmission of resistance to antimicrobial agents. Given recent reductions in staffing in long-term care facilities (26), it is particularly important to assess whether a reduced level of staffing is associated with an increased prevalence of antimicrobial-resistant bacteria in nursing home settings.
We conducted a study to determine antimicrobial and institutional risk factors for the isolation of antimicrobial-resistant bacteria from residents of nursing homes in Canada and the United States.
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MATERIALS AND METHODS |
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This study was approved by the ethics review board of Hamilton Health Sciences and McMaster University.
Data collection
Data about nursing home size (number of beds), admission rates, resident characteristics at the facility level (use of feeding tubes, use of urinary catheters, proportion of residents confined to a bed or wheelchair), staffing (numbers of health care aides, nurses, and physicians), and infrastructure for hand-washing (number of hand-washing sinks, type of soap used) were collected using a questionnaire sent to each study nursing home. No data on individual-level factors such as functional status, severity of illness, comorbidity, the presence of roommates, or medical devices (urinary catheters or feeding tubes) were collected. Each nursing homes infection control practitioner completed the data collection form. Since entry into the study was staggered, the data collection period began on February 1, 1998, and ended on June 30, 1999. Data were collected prospectively over a 12-month period.
The name, duration, dose, and route of all antibiotics prescribed were recorded by the nursing homes infection control practitioner or designate. All nursing homes had service provided by a community pharmacy. For verification of accuracy, records from the pharmacy affiliated with the nursing home were obtained quarterly and reviewed. Only systemic antimicrobial agents administered within the nursing home were assessed.
All clinical bacterial culture results, including the site from which the organism was obtained, the name of the bacterium, and the susceptibility results, were obtained. Since all microbiology results from requested tests are returned to the nursing homes, complete information on bacterial cultures sent was obtained. To minimize biased sampling of resistant bacteria versus sensitive bacteria, we included only cultures sent for signs of clinical infection. However, none of the participating nursing homes routinely performed surveillance culturesthat is, cultures for the purpose of detecting resistant bacteriaat the time of the study.
Both antibiotic use and susceptibility results were linked to a unique identifier for each nursing home resident which consisted of a code for the facility, the residents initials, the unit, and the room number. These data were used to analyze the relations between the following five groups of resistant bacteria and certain target antimicrobial agents: trimethoprim-sulfamethoxazole (TMP-SMX)-resistant Enterobacteriaceae and TMP-SMX; fluoroquinolone-resistant Enterobacteriaceae and fluoroquinolones; fluoroquinolone-resistant Pseudomonas aeruginosa and fluoroquinolones; methicillin-resistant Staphylococcus aureus (MRSA) and fluoroquinolones; and MRSA and penicillins. We performed manual verification to ensure that repeat isolates (the same organism and antibiogram being isolated within 2 weeks of the first isolation) were not included in the analysis.
Statistical analysis
We sought to compare antibiotic exposure among nursing home residents from whom antimicrobial-resistant bacteria were isolated with exposure among residents from whom susceptible cultures were obtained. For example, TMP-SMX use in residents with TMP-SMX-resistant Enterobacteriaceae was compared with TMP-SMX use in residents with TMP-SMX-sensitive Enterobacteriaceae. The amount of antibiotic used was calculated using defined daily dosages, where one defined daily dose is equivalent to the standard amount of antibiotic in a typical prescription (28). Both dosage and duration of antibiotic exposure were taken into account. For each resistant bacterium and target antimicrobial agent, an analysis was performed by measuring antibiotic exposure (in defined daily doses) during the 10 weeks prior to detection of the resistant bacteria in residents and comparing this with antibiotic exposure during a 10-week interval in individuals with sensitive organisms detected. In the absence of any evidence defining an optimal period for assessment of antibiotic exposures, 10 weeks was selected by the consensus opinion of five infectious diseases specialists who have research expertise in the field of resistance to antimicrobial agents. Odds ratios associated with one defined daily dose per 100 resident-days were calculated using logistic regression. These odds ratios represented the risk of nursing home residents having clinical isolates of resistant organisms as compared with antibiotic-sensitive organisms.
Using logistic regression, we constructed multivariable models for the antibiotic exposures described above. Nursing home variables, including number of occupied beds, staffing characteristics (limited to those staff providing direct resident care), hand-washing characteristics, use of intravenous medications, and rates of new admissions, admissions from acute care, and returning admissions from acute care, were considered as covariates in the multivariable models. Univariate analysis was performed first. Variables for which the likelihood ratio test had a p value of less than 0.2 were selected, and the odds ratio associated with a change of one standard deviation in the variable was calculated. Covariates with an odds ratio greater than 1.1 or less than 0.9 were retained as candidates for multivariable analysis. Using forward selection and a cutoff of p < 0.05 for retention of variables, we built multivariable models in which covariates were added to antibiotic exposure. For assessment of the effect of antimicrobial exposure when adjusted for other factors, variables for these antimicrobial exposures were forced into their respective models. Facility-level antimicrobial usethat is, usage over the 12-month study period in each study home (measured as defined daily doses per 100 resident-days)was also considered as a covariate. All data entry and analysis was performed using SAS software, versions 6.0 and 7.0 (SAS Institute, Inc., Cary, North Carolina).
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RESULTS |
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There were 9,156 residents in the study homes at baseline, 47 percent of whom were either bed-bound or confined to a wheelchair. Four percent of residents had indwelling urinary catheters, and 3 percent had feeding tubes. There was no significant difference between the proportion of residents in Canadian homes and the proportion of residents in US homes who had urinary catheters (p = 0.85) or feeding tubes (p = 0.55). The median value for the average length of stay of residents in the 50 study homes, based on data from 5 years prior to the beginning of the study, was 2.2 years. The average length of stay was 2.5 years.
Data on factors pertaining to staffing and hand-washing are shown in table 1. Infection control duties were performed by practitioners or designated staff a mean of 4.9 hours per week per 100 residents (standard deviation 6.4). Thirty-six (72 percent) homes used antibacterial soap, and in 27 (54 percent) homes, antibacterial soap was used by staff but not by residents.
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Microbiology results
Data on the clinical isolates obtained in the study homes are summarized in table 2. There were 2,478 isolates of Enterobacteriaceae, 339 isolates of P. aeruginosa, and 353 isolates of S. aureus. Of the Enterobacteriaceae isolates, 54 percent were Escherichia coli, 20 percent were Proteus mirabilis, and 12 percent were Klebsiella pneumoniae. Ninety-one percent of Enterobacteriaceae were urinary isolates; 53 percent of P. aeruginosa were urinary isolates, and 23 percent of P. aeruginosa were from wounds. Only two surveillance cultures were received (one rectal swab and one nasal swab, both for MRSA), and these were not included in the analysis. S. aureus cultures were most commonly isolated from wounds (32 percent) and urine (16 percent).
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Antibiotic exposure and antibiotic resistance
The relations between the various combinations of antibiotic exposure and antibiotic resistance are shown in table 3. All effects of antibiotic exposure are given in terms of odds ratios per defined daily dose per 100 resident-days. Receipt of TMP/SMX was a significant risk factor for TMP/SMX-resistant Enterobacteriaciae in nursing home residents (adjusted odds ratio (OR) = 1.14, 95 percent confidence interval (CI): 1.06, 1.22). Similarly, exposure to fluoroquinolones was a significant risk factor for fluoroquinolone-resistant Enterobacteriaciae (adjusted OR = 1.08 (95 percent CI: 1.04, 1.11) per defined daily dose per 100 resident-days) and fluoroquinolone-resistant P. aeruginosa (adjusted OR = 1.04 (95 percent CI: 1.01, 1.07) per defined daily dose per 100 resident-days). However, increased exposure to fluoroquinolones was not a risk factor for MRSA (adjusted OR = 1.00, 95 percent CI: 0.97, 1.03), nor was exposure to penicillins (adjusted OR = 0.97, 95 percent CI: 0.85, 1.10). Since none of the individuals with aminoglycoside-resistant bacteria were exposed to aminoglycosides, estimates of association at the individual level could not be determined.
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Other factors at the level of the nursing home were associated with resistance to antimicrobial agents. An increase in the number of occupied beds in the nursing home significantly increased the risk of TMP/SMX-resistant Enterobacteriaceae (adjusted OR = 1.02, 95 percent CI: 1.00, 1.03). Use of intravenous therapy in the nursing home was strongly associated with MRSA in the penicillin model (adjusted OR = 8.55, 95 percent CI: 3.65, 20.0).
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DISCUSSION |
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Little is known about the effect of staffing on antibiotic resistance in long-term care facilities. The association demonstrated in this study between increased staffing levels and reduced rates of MRSA is important, particularly given recent reductions in staffing in long-term care facilities (29). To our knowledge, this is the first report to demonstrate such a relation in long-term care facilities. Evidence exists that even under usual conditions, infection control practices in long-term care facilities are far from ideal. For example, in one nursing home study, gloves were changed appropriately in only 16 percent of direct care provisions between residents (30). In a study conducted by Pittet et al. (31) in a teaching hospital, nonadherence to hand-washing was greatest when the intensity of patient care was high. Better adherence to hand hygiene with increased staffing might therefore be the explanation for our findings. This is also supported by our finding that greater numbers of hand-washing sinks were protective against TMP/SMX-resistant Enterobacteriaceae. These findings are consistent with those of Kaplan et al. (32), who noted an increase in compliance with hand-washing with an increased ratio of sinks to beds in an intensive care unit. Our findings suggest that adequate staffing of nursing homes along with greater emphasis on hand hygiene may be important in limiting the spread of resistance to antimicrobial agents in nursing homes.
Use of antibacterial soap in the nursing home was associated with a reduced risk of MRSA among nursing home residents. Triclosan, the active ingredient in many antibacterial soaps, can effectively inhibit MRSA (33). This agent has been used to help interrupt outbreaks of MRSA in neonatal units (34, 35). There is little epidemiologic evidence to support or refute use of these agents in health care facilities. Our findings support the use of antibacterial soaps in the long-term care setting. A difference in the use of antibacterial soap between staff and residentsthat is, the staff used antibacterial soap and the residents used regular soapwas also independently associated with a reduction in MRSA. These findings provide evidence to support the use of antibacterial soap among staff members in long-term care facilities. However, a definitive answer to the question of whether to use antibacterial soap in long-term care settings would be best derived from a randomized controlled trial.
TMP/SMX and fluoroquinolones, which accounted for over one third of all antibiotics prescribed in this study, were found to be independent risk factors for TMP/SMX and fluoroquinolone resistance in Enterobacteriaceae and P. aeruginosa, respectively. These findings are important, since Enterobacteriaceae cause the vast majority of urinary tract infections in residents of long-term care facilities, for which TMP/SMX is recommended as the antibiotic of choice (2). The association between fluoroquinolone exposure and Enterobacteriaceae or P. aeruginosa in nursing homes is consistent with previous reports from long-term care facilities (16, 36). Reducing inappropriate prescribing of these and other antimicrobial agents in the long-term care setting, such as for asymptomatic bacteriuria (37), may reduce the spread of antibiotic resistance in nursing homes.
The association between intravenous therapy and antibiotic-resistant bacteria (MRSA and TMP/SMX-resistant Enterobacteriaceae) was unexpected. For MRSA, this association may have been confounded by the use of vancomycin, which is used intravenously to treat MRSA infection. Individuals with MRSA infection may have been preferentially transferred from hospitals to nursing homes that administered intravenous therapy. This may have led to the spread of MRSA among residents in these homes, resulting in increased MRSA infection. Another possibility, one which relates to either MRSA or TMP/SMX-resistant Enterobacteriaceae, is that residents in nursing homes which used intravenous therapy were more debilitated and more susceptible to acquiring infection with MRSA or TMP/SMX-resistant Enterobacteriaceae.
Our findings provide evidence for the importance of infection control factors as well as antimicrobial exposure in the spread of antibiotic-resistant bacteria in nursing homes. Strengths of this study include the large number of nursing home residents and the measurement of antibiotic exposure and resistance at the individual level, inclusion of factors related to staffing and hand hygiene, and the assessment of risk factors for a number of types of bacterial resistance.
Because this study was conducted in nursing homes with 100 or more beds, the results may not be generalizable to smaller facilities. Although participating homes were significantly larger than nonparticipating homes, the average bed size (186 beds) was within the range (50199 beds) of 80 percent of nursing homes in the United States (38). Fifty percent of nursing homes in the United States have 100 or more beds. The average length of stay of residents in our study was similar to the US national average (2.5 years vs. 2.4 years). The ratio of registered nursing staff to beds among the nursing homes in our study was the same as the national average (8.8 per 100 residents) (37).
We acknowledge that the lack of covariates at the individual level (such as underlying illnesses, decubitus ulcers, urinary catheters, feeding tubes) may have led to biased estimates of the effect of antibiotic exposure on antibiotic resistance at the individual level (2325). Other exposures, such as previous hospitalization or prior receipt of antibiotics while in the hospital, may have influenced isolation of antimicrobial-resistant bacteria. Given the large number of nursing home residents in our study, obtaining data on individual-level covariates was not feasible. However, the relation between antimicrobial exposure and bacterial resistance was adjusted for nursing-home-level variables, including feeding tubes, urinary catheters, and use of intravenous therapy. Furthermore, rates of admission from acute-care hospitals as well as readmissions from hospitals were considered. Since treatment with active antibiotics may inhibit the growth of susceptible organisms, residents selected on the basis of having susceptible bacteria cultured may have been less likely to receive antibiotics than our source population of nursing home residents (39). Since obtaining all of the clinical isolates was beyond the scope of this study, molecular typing to establish the clonality of antimicrobial-resistant bacteria was not done.
In conclusion, we found in this study that increased staffing levels, use of antimicrobial soap, and an increase in hand-washing sinks are associated with a reduced risk of antimicrobial-resistant bacteria in nursing homes. Exposure to TMP-SMX and fluoroquinolones, commonly used antimicrobial agents in nursing homes, are important risk factors for resistance to antimicrobial agents.
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ACKNOWLEDGMENTS |
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NOTES |
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REFERENCES |
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