Erika M.C. D’Agata

Patterns of Antimicrobial Use Among Nursing Home Residents With Advanced Dementia

BACKGROUND Nursing home residents with advanced dementia are at high risk of infections and antimicrobial exposure near the end of life. Detailed studies quantifying antimicrobial prescribing practices among these residents have not been performed. METHODS A cohort of 214 residents with advanced dementia from 21 Boston-area nursing homes were followed up prospectively for 18 months or until death. We analyzed antimicrobial use, including type, indication, and quantity, by days of therapy per 1000 resident-days. RESULTS During an average of 322 days of follow-up, 142 residents (66.4%) with advanced dementia received at least 1 course of antimicrobial therapy (mean [SD] number of courses per resident, 4.0 [3.7]). The mean (SD) number of days of therapy per 1000 resident-days for the entire cohort was 53.0 (4.3). Quinolones and third-generation cephalosporins were the most commonly prescribed antimicrobials, accounting for 38.3% and 15.2%, respectively, of 540 prescribed antimicrobial therapy courses. A respiratory tract infection was the most common indication (46.7% of all antimicrobial therapy courses). Among 99 decedents, 42 (42.4%) received antimicrobials during the 2 weeks before death, of which 30 of 72 courses (41.7%) were administered via the parenteral route. The number of decedents receiving antimicrobials (P < .001), the number of antimicrobials prescribed (P = .01), and the days of therapy per 1000 resident-days (P < .001) increased significantly as subjects approached death. CONCLUSIONS Persons with advanced dementia are frequently exposed to antimicrobials, especially during the 2 weeks before death. The implications of this practice from the perspective of the individual treatment burden near the end of life and its contribution to the emergence of antimicrobial resistance in the nursing home setting need further evaluation.

Challenges in Assessing Nursing Home Residents with Advanced Dementia for Suspected Urinary Tract Infections

To describe the presentation of suspected urinary tract infections (UTIs) in nursing home (NH) residents with advanced dementia and how they align with minimum criteria to justify antimicrobial initiation.

A Mathematical Model Quantifying the Impact of Antibiotic Exposure and Other Interventions on the Endemic Prevalence of Vancomycin-Resistant Enterococci

BACKGROUND Mathematical modeling can be used to describe the interdependent and dynamic interactions that contribute to the transmission dynamics of vancomycin-resistant enterococci (VRE). A model was developed to quantify the contribution of antibiotic exposure and of other modifiable factors to the dissemination of VRE in the hospital setting. METHODS The model consists of 4 compartments: patients colonized with VRE receiving and not receiving antibiotics and uncolonized patients receiving and not receiving antibiotics. A series of differential equations describe the movement between these compartments. Baseline parameter estimates were obtained from pharmacy, infection-control, and clinical databases. RESULTS The main predictions of this model are that (1) preventing the initiation or enhancing the discontinuation of unnecessary antimicrobial therapy will have a greater impact if it is targeted to patients who are not colonized with VRE; (2) increasing the number of patients harboring VRE at the time of hospital admission substantially increases the endemic prevalence of VRE; and (3) eliminating the influx of VRE results in the eradication of this pathogen from the hospital. A decrease in the endemic prevalence of VRE also occurs with a decrease in the length of hospital stay of colonized patients, increased hand hygiene compliance, and a lower ratio of health-care workers : patients. CONCLUSION This mathematical model provides a framework to assist in targeting necessary interventions aimed at limiting the spread of VRE.

Infection Management and Multidrug-Resistant Organisms in Nursing Home Residents With Advanced Dementia

IMPORTANCE Infection management in advanced dementia has important implications for (1) providing high-quality care to patients near the end of life and (2) minimizing the public health threat posed by the emergence of multidrug-resistant organisms (MDROs). DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 362 residents with advanced dementia and their health care proxies in 35 Boston area nursing homes for up to 12 months. MAIN OUTCOMES AND MEASURES Data were collected to characterize suspected infections, use of antimicrobial agents (antimicrobials), clinician counseling of proxies about antimicrobials, proxy preference for the goals of care, and colonization with MDROs (methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and multidrug-resistant gram-negative bacteria). Main outcomes were (1) proportion of suspected infections treated with antimicrobials that met minimum clinical criteria to initiate antimicrobial treatment based on consensus guidelines and (2) cumulative incidence of MDRO acquisition among noncolonized residents at baseline. RESULTS The cohort experienced 496 suspected infections; 72.4% were treated with antimicrobials, most commonly quinolones (39.8%) and third- or fourth-generation cephalosporins (20.6%). At baseline, 94.8% of proxies stated that comfort was the primary goal of care, and 37.8% received counseling from clinicians about antimicrobial use. Minimum clinical criteria supporting antimicrobial treatment initiation were present for 44.0% of treated episodes and were more likely when proxies were counseled about antimicrobial use (adjusted odds ratio, 1.42; 95% CI, 1.08-1.86) and when the infection source was not the urinary tract (referent). Among noncolonized residents at baseline, the cumulative incidence of MDRO acquisition at 1 year was 48%. Acquisition was associated with exposure (>1 day) to quinolones (adjusted hazard ratio [AHR], 1.89; 95% CI, 1.28-2.81) and third- or fourth-generation cephalosporins (AHR, 1.57; 95% CI, 1.04-2.40). CONCLUSIONS AND RELEVANCE Antimicrobials are prescribed for most suspected infections in advanced dementia but often in the absence of minimum clinical criteria to support their use. Colonization with MDROs is extensive in nursing homes and is associated with exposure to quinolones and third- and fourth-generation cephalosporins. A more judicious approach to infection management may reduce unnecessary treatment in these frail patients, who most often have comfort as their primary goal of care, and the public health threat of MDRO emergence.

Increased multi-drug resistance among the elderly on admission to the hospital—A 12-year surveillance study

Resistance to antimicrobials continues to increase worldwide. Data suggest that older patients are among the main reservoirs of multidrug-resistant organisms (MDROs) in the hospital. We hypothesized that older patients (≥ 65 years of age) are more likely to harbor MDRO at hospital admission. We compared rates of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and multidrug-resistant gram-negative bacteria (MDRGN) recovered from clinical cultures within the first 48 h of admission to an adult acute care hospital between the elderly (≥ 65 years old) and young per 1000 age-stratified admissions over a 12-year study period. Trends in antimicrobial resistance, sites of recovery and species for MDRGN were also characterized. An average of 7534 positive bacterial cultures were collected per year. The admission prevalence per 1000 age-stratified admissions was consistently higher among the elderly for all three MDRO under investigation. Among the elderly, the admission prevalence increased significantly for VRE (0.89 in 1998 to 3.62 in 2009 per 1000 admissions; p < 0.001) and MDRGN (1.41 in 1998 to 11.33 in 2009 per 1000 admissions; p < 0.001). Percentage resistant for all three MDRO increased as well. These data suggest that elderly patients are contributing substantially to the influx of MDRO into the hospital setting.

Antimicrobial use in outpatient hemodialysis units.

OBJECTIVE To quantify and characterize overall antimicrobial use, including appropriateness of indication, among patients receiving chronic hemodialysis. DESIGN Retrospective and prospective observational study. SETTING Two outpatient hemodialysis units. PATIENTS All patients receiving chronic hemodialysis. METHODS The rate of parenteral antimicrobial use (number of doses per 100 patient-months) was calculated retrospectively from September 2008 through July 2011. Indication and appropriateness of antimicrobial doses were characterized prospectively from August 2010 through July 2011. Inappropriate administration was defined as occasions when criteria for infection based on national guidelines were not met, failure to choose a more narrow-spectrum antimicrobial on the basis of culture data, or occasions when indications for surgical prophylaxis were not met. RESULTS Over the 35-month retrospective study period, the rate of parenteral antimicrobial use was 32.9 doses per 100 patient-months. Vancomycin was the most commonly prescribed antimicrobial, followed by cefazolin and third- or fourth-generation cephalosporins. Over the 12-month prospective study, 1,003 antimicrobial doses were prescribed. Among the 926 (92.3%) doses for which an indication for administration was available, 276 (29.8%) were classified as inappropriate. Of these, a total of 146 (52.9%) did not meet criteria for infection, 74 (26.8%) represented failure to choose a more narrow-spectrum antimicrobial, and 56 (20.3%) did not meet criteria for surgical prophylaxis. The most common inappropriately prescribed antimicrobials were vancomycin and third- or fourth- generation cephalosporins. CONCLUSIONS Parenteral antimicrobial use was extensive, and as much as one-third was categorized as inappropriate. The findings of this study provide novel information toward minimizing inappropriate antimicrobial use.

Co-colonization with multiple different species of multidrug-resistant gram-negative bacteria

BACKGROUND The characteristics of co-colonization with multiple different species of multidrug-resistant gram-negative bacteria (MDRGN) have not been fully elucidated. Quantifying the prevalence of co-colonization and those patients at higher risk of co-colonization may have important implications for strategies aimed at limiting the spread of MDRGN. METHODS To determine the prevalence of MDRGN colonization, rectal swabs were obtained from 212 residents residing in a 600-bed long-term care facility. Co-colonization was defined as colonization with ≥2 different MDRGN species. Co-colonized residents were compared with residents colonized with a single MDRGN species to identify factors associated with an increased risk for co-colonization. Molecular typing was performed to determine the contribution of cross transmission to the co-colonized state. RESULTS A total of 53 (25%) residents was colonized with ≥1 MDRGN. Among these, 11 (21%) were colonized with ≥2 different species of MDRGN. A global deterioration score of ≥5 representing advanced dementia and an increased requirement for assistance from health care workers was significantly associated with co-colonization (P = .05). Clonally related MDRGN strains were identified among 7 (64%) co-colonized residents. CONCLUSION The prevalence of co-colonization with ≥2 different MDRGN is substantial. Cross transmission of MDRGN is a major contributor to the co-colonized state.

Diagnostic accuracy of surveillance cultures to detect gastrointestinal colonization with multidrug-resistant gram-negative bacteria

To quantify the sensitivity of surveillance cultures for the detection of multidrug-resistant gram-negative (MDRGN) bacteria, perianal/rectal swabs were collected from patients with positive clinical cultures for MDRGN species. Surveillance cultures identified colonization with the same genetically related MDRGN species in 29 of 37 MDRGN clinical culture isolates (78%). There was a trend toward less antimicrobial exposure among patients with false-negative surveillance culture results (P = .06).

The effect of co-colonization with community-acquired and hospital-acquired methicillin-resistant Staphylococcus aureus strains on competitive exclusion.

We investigate the in-hospital transmission dynamics of two methicillin-resistant Staphylococcus aureus (MRSA) strains: hospital-acquired methicillin resistant S. aureus (HA-MRSA) and community-acquired methicillin-resistant S. aureus (CA-MRSA). Under the assumption that patients can only be colonized with one strain of MRSA at a time, global results show that competitive exclusion occurs between HA-MRSA and CA-MRSA strains; the strain with the larger basic reproduction ratio will become endemic while the other is extinguished due to competition. Because new studies suggest that patients can be concurrently colonized with multiple strains of MRSA, we extend the model to allow patients to be co-colonized with HA-MRSA and CA-MRSA. Using the extended model, we explore the effect of co-colonization on competitive exclusion by determining the invasion reproduction ratios of the boundary equilibria. In contrast to results derived from the assumption that co-colonization does not occur, the extended model rarely exhibits competitive exclusion. More commonly, both strains become endemic in the hospital. When transmission rates are assumed equal and decolonization measures act equally on all strains, competitive exclusion never occurs. Other interesting phenomena are exhibited. For example, solutions can tend toward a co-existence equilibrium, even when the basic reproduction ratio of one of the strains is less than one.

The study of pathogen resistance and antimicrobial use in dementia: Study design and methodology

Advanced dementia is characterized by the onset of infections and antimicrobial use is extensive. The extent to which this antimicrobial use is appropriate and contributes to the emergence of antimicrobial resistant bacteria is not known. The object of this report is to present the methodology established in the Study of Pathogen Resistance and Exposure to Antimicrobials in Dementia (SPREAD), and describe how challenges specific to this research were met. SPREAD is an ongoing, federally funded, 5-year prospective cohort study initiated in September 2009. Subjects include nursing home residents with advanced dementia and their proxies recruited from 31 Boston-area facilities. The recruitment and data collection protocols are described. Characteristics of participant facilities are presented and compared to those nationwide. To date, 295 resident/proxy dyads have been recruited. Baseline and selected follow-up data demonstrate successful recruitment of subjects and repeated collection of complex data documenting infections, decision-making for these infections, and antimicrobial bacteria resistance among the residents. SPREAD integrates methods in dementia, palliative care and infectious diseases research. Its successful implementation further establishes the feasibility of conducting rigorous, multi-site NH research in advanced dementia, and the described methodology serves as a detailed reference for subsequent publications emanating from the study.