A Statewide Program to Improve Management of Suspected Urinary Tract Infection in Long-Term Care.

BACKGROUND/OBJECTIVES: Suspected urinary tract infection (UTI) is the most common indication for antibiotic use in long-term care (LTC). Due to the high prevalence of asymptomatic bacteriuria, for which antibiotics are not warranted, these antibiotics are frequently unnecessary. We implemented a collaborative quality improvement program to improve the management of suspected UTI in LTC residents by increasing awareness of current guidelines, with a focus on decreasing treatment in the absence of symptoms. DESIGN/INTERVENTION: Two separate collaboratives included workshops, webinars, and coaching calls. PARTICIPANTS: A total of 31 facilities participated in the first collaborative, with 17 submitting sufficient data for analysis and 34 in the second, with data analyzed from 25. MEASUREMENTS: Facilities reported monthly numbers of urine cultures, UTI diagnoses, Clostridioides difficile infections (CDIs), and resident days. RESULTS: When comparing the baseline period to the first collaborative period, the intercollaborative period to the second collaborative period, and the first collaborative period to the second, the incident rate ratios (95% confidence intervals) were 0.74 (0.68-0.81), 0.83 (0.73-0.94), and 0.63 (0.57-0.69), respectively, for urine culturing rate; 0.73 (0.64-0.83), 0.86 (0.70-1.05), and 0.60 (0.51-0.69), respectively, for UTI diagnosis rate; and 0.56 (0.40-0.82), 1.61 (0.71-4.14), and 0.45 (0.27-0.74), respectively, for CDI rate. CONCLUSION: The program we implemented was associated with reductions in urine cultures, UTI diagnosis, and CDI; and it suggests that this type of intervention can promote appropriate management of UTI in the LTC setting. J Am Geriatr Soc 68:62-69, 2019.

Critical role of C-terminal residues of the Alzheimer's associated ß-amyloid protein in mediating antiviral activity and modulating viral and bacterial interactions with neutrophils.

Recent studies have shown that the Alzheimer's associated ß-amyloid protein (ßA) can inhibit growth of bacteria, fungi and viruses. We reported that the 42 amino acid ßA protein inhibits replication of seasonal and pandemic strains of H3N2 and H1N1 influenza A virus (IAV) in vitro and modulates activation of neutrophils and monocytes exposed IAV. We here show that fragments composed of the N and C terminal domain of ßA42, including ßA22-42 and the 8 amino acid ßA35-42, retain viral neutralizing and viral aggregating activity, whereas fragments lacking the C-terminal amino acids 41 and 42 (e.g. ßA1-40, ßA1-34, ßA1-28, ßA22-40 or ßA33-40) have markedly diminished activities on these assays. ßA22-42 also increased viral uptake, and virus induced respiratory burst responses, by human neutrophils, while peptides lacking residues 41 and 42 did not. Similar results were obtained with regard to bacterial aggregation, or promotion of bacterial uptake by neutrophils. Published structural studies have shown that ßA1-42 has a greater propensity to form neurotoxic oligomers than ßA1-40 due to a molecular interaction between Met35 and Ala42. Our findings suggest that there is a relationship between neurotoxic and antimicrobial activities of ßA1-42. Truncated peptides containing the last 8 C-terminal amino acids of ßA1-42 retain antimicrobial and opsonizing activities likely resulting from their ability to induce viral or bacterial aggregation.

Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Zinc is essential for the regulation of immune response. T cell function declines with age. Zinc supplementation has the potential to improve the serum zinc concentrations and immunity of nursing home elderly with a low serum zinc concentration. OBJECTIVE: We aimed to determine the effect of supplementation with 30 mg Zn/d for 3 mo on serum zinc concentrations of zinc-deficient nursing home elderly. DESIGN: This was a randomized, double-blind, placebo-controlled study. Of 53 nursing home elderly (aged ≥65 y) who met eligibility criteria, 58% had a low serum zinc concentration (serum zinc <70 µg/dL); these 31 were randomly assigned to zinc (30 mg Zn/d) (n = 16) or placebo (5 mg Zn/d) (n = 15) groups. The primary outcome measure was change in serum zinc concentrations between baseline and month 3. We also explored the effects of supplementation on immune response. RESULTS: Baseline characteristics were similar in the 2 groups. The difference in the mean change in serum zinc was significantly higher, by 16%, in the zinc group than in the placebo group (P = 0.007) when baseline zinc concentrations were controlled for. In addition, controlling for baseline C-reactive protein, copper, or albumin did not change the results. However, supplementation of participants with ≤60 µg serum Zn/dL failed to increase their serum zinc to ≥70 µg/dL. Zinc supplementation also significantly increased anti-CD3/CD28 and phytohemagglutinin-stimulated T cell proliferation, and the number of peripheral T cells (P < 0.05). When proliferation was expressed per number of T cells, the significant differences between groups were lost, suggesting that the zinc-induced enhancement of T cell proliferation was mainly due to an increase in the number of T cells. CONCLUSIONS: Zinc supplementation at 30 mg/d for 3 mo is effective in increasing serum zinc concentrations in nursing home elderly; however, not all zinc-deficient elderly reached adequate concentrations. The increase in serum zinc concentration was associated with the enhancement of T cell function mainly because of an increase in the number of T cells.

Alzheimer's associated ß-amyloid protein inhibits influenza A virus and modulates viral interactions with phagocytes.

Accumulation of ß-Amyloid (ßA) is a key pathogenetic factor in Alzheimer's disease; however, the normal function of ßA is unknown. Recent studies have shown that ßA can inhibit growth of bacteria and fungi. In this paper we show that ßA also inhibits replication of seasonal and pandemic strains of H3N2 and H1N1 influenza A virus (IAV) in vitro. The 42 amino acid fragment of ßA (ßA42) had greater activity than the 40 amino acid fragment. Direct incubation of the virus with ßA42 was needed to achieve optimal inhibition. Using quantitative PCR assays ßA42 was shown to reduce viral uptake by epithelial cells after 45 minutes and to reduce supernatant virus at 24 hours post infection. ßA42 caused aggregation of IAV particles as detected by light transmission assays and electron and confocal microscopy. ßA42 did not stimulate neutrophil H2O2 production or extracellular trap formation on its own, but it increased both responses stimulated by IAV. In addition, ßA42 increased uptake of IAV by neutrophils. ßA42 reduced viral protein synthesis in monocytes and reduced IAV-induced interleukin-6 production by these cells. Hence, we demonstrate for the first time that ßA has antiviral activity and modulates viral interactions with phagocytes.

Acquisition of multidrug-resistant gram-negative bacteria: incidence and risk factors within a long-term care population.

BACKGROUND AND OBJECTIVE: An improved understanding of the transmission dynamics of multidrug-resistant (MDR) gram-negative bacteria and the mechanism of acquisition in long-term care facilities (LTCFs) could aid in the development of prevention strategies specific to LTCFs. We thus investigated the incidence of acquisition of these pathogens among an LTCF population. DESIGN: Prospective cohort study. SETTING: Three separate wards at a 600-bed LTCF in metropolitan Boston, Massachusetts, during the period October 31, 2006, through October 22, 2007. PARTICIPANTS: One hundred seventy-two LTCF residents. METHODS: A series of rectal samples were cultured to determine acquisition of MDR gram-negative bacteria, defined as absence of MDR gram-negative bacterial colonization at baseline and de novo recovery of MDR gram-negative bacteria from a follow-up culture. Molecular typing was performed to identify genetically linked strains. A nested matched case-control study was performed to identify risk factors associated with acquisition. RESULTS: Among 135 residents for whom at least 1 follow-up culture was performed, 52 (39%) acquired at least 1 MDR gram-negative organism during the study period. Thirty-two residents (62%) had not been colonized at baseline and had acquired at least 1 MDR gram-negative species at follow-up culture, and 20 residents (38%) were colonized at baseline and had acquired at least 1 MDR gram-negative species at follow-up culture. The most common coresistance pattern was resistance to extended-spectrum penicillins, ciprofloxacin, and gentamicin (57 isolates [42.5%]). Genetically related strains of MDR gram-negative bacteria were identified among multiple residents and between roommates. On conditional logistic regression analysis, antibiotic exposure during the study period was significantly associated with acquisition of MDR gram-negative bacteria (odds ratio, 5.6 [95% confidence interval, 1.1-28.7]; P = .04). CONCLUSIONS: Acquisition of MDR gram-negative bacteria occurred frequently through resident-to-resident transmission. Existing infection control interventions need to be reevaluated.

Outbreak of adenovirus type 4 infection in a long-term care facility for the elderly.

An outbreak of acute respiratory disease due to human adenovirus and a resulting increase in mortality occurred in a long-term care facility for the elderly. By use of viral culture and polymerase chain reaction, not a rapid antigen test, the virus was detected. Human adenovirus infection can occur in elderly individuals, but detection by rapid antigen testing may be limited.

Multidrug-resistant gram-negative bacteria at a long-term care facility: assessment of residents, healthcare workers, and inanimate surfaces.

OBJECTIVE: To characterize the clinical and molecular epidemiology of multidrug-resistant (MDR) organisms in residents, in healthcare workers (HCWs), and on inanimate surfaces at a long-term care facility (LTCF). DESIGN: Point-prevalence study in 4 separate wards at a 600-bed urban LTCF that was conducted from October 31, 2006 through February 5, 2007. PARTICIPANTS: One hundred sixty-one LTCF residents and 13 HCWs. METHODS: Nasal and rectal samples were obtained for culture from each resident, selected environmental surfaces in private and common rooms, and the hands and clothing of HCWs in each ward. All cultures were evaluated for the presence of MDR gram-negative bacteria, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci. Clinical and demographic information were collected for each enrolled resident. Molecular typing was performed to identify epidemiologically related strains. RESULTS: A total of 37 (22.8%), 1 (0.6%), and 18 (11.1%) residents were colonized with MDR gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant S. aureus, respectively. MDR gram-negative bacteria were recovered from 3 (1.8%) of the 175 environmental samples cultured, all of which were obtained from common areas in LTCF wards. One (7.7%) of the 13 HCWs harbored MDR gram-negative bacteria. Molecular typing identified clonally related MDR gram-negative strains in LTCF residents. After multivariable analysis, length of hospital stay of at least 4 years, fecal incontinence, and antibiotic exposure for at least 8 days were independent risk factors associated with harboring MDR gram-negative bacteria among LTCF residents. CONCLUSIONS: The prevalence of MDR gram-negative bacteria is high among LTCF residents and exceeds that of vancomycin-resistant enterococci and methicillin-resistant S. aureus. Common areas in LTCFs may provide a unique opportunity for person-to-person transmission of MDR gram-negative bacteria.

Preservation of neuronal number despite age-related cortical brain atrophy in elderly subjects without Alzheimer disease.

Cerebral volume loss has long been associated with normal aging, but whether this is due to aging itself or to age-related diseases, including incipient Alzheimer disease, is uncertain. To understand the changes that occur in the aging brain, we examined the cerebral cortex of 27 normal individuals ranging in age from 56 to 103 years. None fulfilled the criteria for the neuropathologic diagnosis of Alzheimer disease or other neurodegenerative disease. Seventeen of the elderly participants had cognitive testing an average of 6.7 months prior to death. We used quantitative approaches to analyze cortical thickness, neuronal number, and density. Frontal and temporal neocortical regions had clear evidence of cortical thinning with age, but total neuronal numbers in frontal and temporal neocortical regions remained relatively constant during a 50-year age range. These data suggest that loss of neuronal and dendritic architecture, rather than loss of neurons, underlies neocortical volume loss with increasing age in the absence of Alzheimer disease.

Multidrug-resistant gram-negative bacteria in a long-term care facility: prevalence and risk factors.

OBJECTIVES: To quantify the prevalence, risk factors, and mode of transmission associated with colonization by multidrug-resistant gram-negative bacteria (MDRGN) in the long-term care (LTC) setting. DESIGN: Cross-sectional. SETTING: Four nursing units in a 648-bed LTC facility in Boston, Massachusetts. PARTICIPANTS: Eighty-four long-term care residents. MEASUREMENTS: Nasal and rectal swabs were obtained to determine colonization with MDRGN; if present, molecular typing was performed. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) was also determined. Demographic and clinical characteristics were obtained from the medical record. Multivariable analysis was used to identify factors independently associated with MDRGN colonization. RESULTS: A total of 51%, 28%, and 4% subjects were colonized with MDRGN, MRSA, and VRE, respectively. After multivariable adjustment, advanced dementia (adjusted odds ratio (AOR)=2.9, 95% confidence interval (CI)=1.2-7.35, P=.02) and nonambulatory status (AOR=5.7, 95% CI=1.1-28.9, P=.04) were the only independent risk factors for harboring MDRGN. Molecular typing indicated person-to-person transmission. CONCLUSION: Colonization with MDRGN is common in the LTC setting. A diagnosis of advanced dementia is a major risk factor for harboring MDRGN.

Inhaled zanamivir versus rimantadine for the control of influenza in a highly vaccinated long-term care population.

BACKGROUND: Despite vaccination, influenza commonly causes morbidity and mortality in institutional settings. Influenza control with rimantadine and amantadine is limited by emergence and transmission of drug-resistant influenza A variants, ineffectiveness against influenza B, and toxicity. This study evaluated the efficacy and tolerability of zanamivir versus rimantadine for influenza outbreak control in long-term care facilities. METHODS: This double-blind, randomized, controlled study prospectively enrolled nursing home residents for 3 influenza seasons (1997 to 2000). Vaccine was offered to all subjects. Following influenza outbreak declaration, subjects were randomized to inhaled zanamivir 10 mg or standard of care (rimantadine 100 mg for influenza A or placebo for influenza B) once daily for 14 days. The proportion of randomized subjects developing symptomatic, laboratory-confirmed influenza during prophylaxis was the primary endpoint. RESULTS: Of 482 randomizations (238 zanamivir, 231 rimantadine, 13 placebo), 96% of subjects were elderly or had high-risk conditions; over 90% were vaccinated. Symptomatic, laboratory-confirmed influenza occurred in 3% of zanamivir subjects and 8% of rimantadine subjects during chemoprophylaxis (P = .038; additional protective efficacy for zanamivir over rimantadine = 61%). Since only 25 subjects were randomized during 2 influenza B outbreaks and none developed influenza, the influenza B data were excluded from further analysis. Zanamivir was well tolerated and unassociated with emergence of resistant virus; rimantadine-resistant variants were common. CONCLUSIONS: This is the first prospective, controlled study demonstrating effectiveness of chemoprophylaxis for influenza outbreak control. Zanamivir prevents symptomatic, laboratory-confirmed influenza more effectively than rimantadine, is unassociated with resistant virus, and has a favorable safety profile. Zanamivir is an appropriate alternative for influenza outbreak control among institutionalized vaccinated elderly.

Novel strategies for prevention and treatment of influenza.

Influenza viruses continue to be a major health challenge due to antigenic variation in envelope proteins and animal reservoirs for the viruses. Of particular concern is an anticipated influenza pandemic in the near future. Vaccination is currently the most effective means of reducing morbidity and mortality during influenza epidemics. In addition, neuraminidase inhibitors have substantially improved antiviral therapy for influenza. However, influenza infection in children and the elderly remain problematic. Furthermore, major innovations in prevention and therapy will be needed to deal with an influenza pandemic. This review assesses available and investigational antivirals and vaccines for influenza, emphasising novel approaches that may improve ability to cope with infection in children and the elderly or during a pandemic. Some adverse sequelae of influenza appear to relate to impairment or pathogenic activation of immune responses. Exciting recent findings in this area, with relevance to influenza treatment, are reviewed.