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We identified 1,805 gram-negative organisms in urine cultures from residents of 63 long-term care facilities (LTCFs) over 10 months. Fluoroquinolone resistance was 51% among E. coli, while 26% and 6% of Klebsiella were resistant to ceftazidime and imipenem, respectively. Resistance varied significantly by type of LTCF, LTCF size, and geographic region.
Increasing attention has been focused on the importance of antimicrobial resistance in the long-term-care facility (LTCF) population [1-3]. Antimicrobial resistance in this rapidly growing segment of the population is important because these patients often have multiple comorbidities and functional impairments that increase susceptibility to infection [4, 5]. Furthermore, LTCF residents are frequently treated empirically with broad-spectrum antibiotics, which increase selection pressure for resistance . Curbing emergence of antibiotic-resistant pathogens in the LTCF has challenges that are unique to this setting including fewer nursing resources, less availability of diagnostic testing, and morbidity associated with isolation control practices [1, 3-5].
The epidemiology of antimicrobial resistance in LTCFs remains poorly understood. Furthermore, most available data are derived from single centers. How resistance patterns differ across geographic regions, facility type (e.g., skilled nursing, assisted living), and facility bed size has not been well defined. Understanding the impact of these characteristics on resistance patterns would provide important insights to inform strategies to curb future emergence of resistance. The goals of this study were to identify the prevalence of antimicrobial resistance among urine isolates from a network of LTCFs, and to elucidate differences in resistance patterns across geographic regions, facility type, and facility size.
We conducted a cross sectional study in a network of 63 LTCFs located across three US states (New Jersey, Pennsylvania, and Delaware). All microbiologic analyses of urine cultures for these LTCFs are performed by a single laboratory (Silver Labs Inc., Cherry Hill, NJ). Species identification and antimicrobial susceptibilities were confirmed according to criteria of the Clinical and Laboratory Standards Institute (CLSI) using the Microscan Walkaway (Dade Behring Inc, West Sacramento, CA) automated susceptibility testing system . All urine cultures obtained from January 15, 2008 through November 15, 2008 were included. No repeat isolates from the same patient were included.
Initially, we assessed overall susceptibilities of all gram-negative organisms to the tested antimicrobial agents. These agents were amikacin, amoxicillin/clavulanate, ampicillin/sulbactam, aztreonam, cefazolin, cefepime, ceftazidime, ceftriaxone, gentamicin, imipenem, levofloxacin, piperacillin-tazobactam, tetracycline, tobramycin, and trimethoprim-sulfamethoxazole (TMP-SMX).
Subsequently, we focused on the three most commonly isolated organisms: Escherichia coli, Klebsiella species, and Proteus mirabilis. For these organisms, we assessed differences in the prevalence of resistance by geographic region, institution size, and institution type (i.e., skilled nursing facility (SNF) vs. assisted living facility (ALF)). Geographic location of the LTCF was assigned to one of six pre-determined geographic regions. These regions were based on counties and were divided into the following regions: Northern New Jersey, Central New Jersey, Southern New Jersey, Coastal New Jersey, Southeastern Pennsylvania, and Delaware. LTCFs were grouped into different size categories as follows: 1) <100 beds; 2) 100-150 beds; 3) 151-200 beds; and >200 beds). In analyzing difference across geographic regions and bed size, we focused only on SNFs as the majority of clinical isolates came from SNFs rather than ALFs. Differences in prevalence were assessed using an overall chi-square test . All statistical calculations were performed using STATA version 10.0 (Stata Corp, College Station TX).
Approval was obtained from the Institutional Review Board of the University of Pennsylvania.
Among residents of the 63 included facilities, there were 1,805 gram-negative organisms identified during the study period, including 1,653 isolates from SNF residents and 152 isolates from ALF residents. The three most common gram-negative organisms were E. coli (n=874), Klebsiella species (n=323); and P. mirabilis (n=285). For all organisms, there was substantial resistance to various antibiotics tested. Notably, the prevalence of levofloxacin resistance was 51% among E. coli and 29% for Klebsiella species. The prevalence of ceftazidime resistance (often used as a marker for extended-spectrum beta-lactamase (ESBL)-mediated resistance) was 26% among Klebsiella species and 12% among E. coli. Finally, 6% of Klebsiella species and 37% of Pseudomonas aeruginosa were resistant to imipenem.
Among the 63 included facilities, there were 44 skilled nursing facilities (SNFs) and 19 assisted living facilities (ALFs). There were many significant differences in antimicrobial susceptibilities when comparing ALFs and SNFs (Table 1).
Among the 44 SNFs, 12 facilities had <100 beds, 12 had 101-150 beds, 13 had 151-200 beds, and seven facilities had >200 beds. Among E. coli, there were significant differences in susceptibilities to the following agents (for bed sizes <100, 100-150, 151-200, and >200, respectively): aztreonam (79%, 90%, 87%, and 87%; p=0.005); cefepime (84%, 92%, 88%, and 88%; p=0.03); ceftazidime (81%, 92%, 88%, and 87%; p=0.003); and ceftriaxone (79%, 92%, 87%, and 87%; p=0.001). Among Klebsiella, there were no significant differences in susceptibilities across facilities of different sizes. Finally, among P. mirabilis, there were significant differences in susceptibilities to the following agents (for bed sizes <100, 100-150, 151-200, and >200, respectively): ampicillin-sulbactam (74%, 89%, 87%, and 92%; p=0.02); and cefazolin (74%, 91%, 88%, and 92%; p=0.02). Of note, the distribution of SNFs within a geographic region with regard to bed size was not substantively different across geographic regions.
The 44 SNFs represented six different geographic regions. The number of SNFs in each region ranged from four to 16 (median = 6.0) and the distribution by facility type and size were similar across the six regions. There were significant differences in antimicrobial susceptibilities across geographic regions (Table 2).
Among a broad range of gram-negative organisms, there is was marked resistance to multiple antibiotics. Furthermore, resistance rates varied significantly by type of facility (i.e., SNF vs. ALF), LTCF size, and geographic region. This variability in resistance may be due to various differences across facilities including patient populations, antimicrobial use patterns and infection control practices. To elucidate the reasons for the variability in prevalence of resistance, studies specifically examining institutional and individual level risk factors for resistance should be pursued. Furthermore, given the marked differences across facilities, future studies should include multiple facilities to improve the generalizability of the results.
The high levels of resistance noted in this study have important implications for future therapeutic options. Fluoroquinolones are very commonly used in the LTCF setting but the very high rates of resistance will limit their future use. The prevalence of ceftazidime resistance (often used as a marker for ESBL-producing organisms) was also noted to be very high. Future studies should more clearly elucidate the epidemiology of ESBL-mediated resistance specifically in the LTCF setting . Finally, we noted imipenem resistance among Klebsiella (~6%) which was greatest in the Northern New Jersey geographic region. Given recent increases in carbapenemase-producing Klebsiella noted in particular in the New York City region, trends in carbapenem resistance in LTCF patients must be monitored very closely .
There are several potential limitations to our study. First, we were unable to determine whether isolates represented infection versus colonization. Second, LTCFs might choose to transfer a patient with suspected infection to an acute care facility without obtaining cultures. As such patients would likely be at increased risk of a resistant infection, the result of such a practice would be to underestimate the prevalence of resistance.
We found marked resistance to multiple antibiotics among urine cultures from LTCF residents. Furthermore, resistance rates varied significantly by type of facility, facility size, and geographic region. These results show the continued decrease in antibiotic therapy options in LTCF residents and emphasize the critical need for rigorous, multi-facility, research focused on elucidating the epidemiology of resistance in the LTCF population.
This work was supported by National Institutes of Health (NIH) grants R01-AG023792 (EL) and K24AI080942 (EL). This study was also supported in part by an Agency for Healthcare Research and Quality (AHRQ) Centers for Education and Research on Therapeutics cooperative agreement (U18-HS10399).
Dr. Lautenbach has received research support from Merck, Ortho-McNeil, Cubist and AstraZeneca.
Presented in part at the 19th Annual Meeting of the Society for Healthcare Epidemiology of America (SHEA) of March 19-22, 2009 San Diego, CA.